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Sample records for crypt foci p1-6patient

  1. The ability of two cooked food mutagens to induce aberrant crypt foci in mice

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1997-01-01

    induced a higher percentage of medium or large sized aberrant crypt foci than PhIP or IQ, The interpretation of the aberrant crypt foci as precursor lesions for colon cancer in the PhIP and IQ mice is difficult because PhIP and IQ have not been reported to be colonic carcinogens, If cooked food mutagens......The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet, In the present study two food-borne initiators, 2-amino-3-methyl-imidazo [4,5-f]quinoline (IQ) and 2......-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used, To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses, Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP, Two additional groups were given...

  2. Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Erk, van M.J.; Doornbos, R.P.; Krul, C.A.M.; Woutersen, R.A.

    2004-01-01

    The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2%

  3. Effect of dietary galacto-oligosaccharides on azoxymethane-induced aberrant crypt foci and colorectal cancer in Fischer 344 rats

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Schoterman, H.C.; Bruijntjes, J.P.; Hollanders, V.M.H.; Woutersen, R.A.

    2001-01-01

    The aim of the present study was to investigate the effects of galacto-oligosaccharides (GOS, Elix'or) on the development of aberrant crypt foci (ACF) and colorectal tumours in rats treated with azoxymethane (AOM). Two groups of 102 male Fischer 344 rats were injected twice with AOM to induce

  4. Chemopreventive efficacy of Andrographis paniculata on azoxymethane-induced aberrant colon crypt foci in vivo.

    Science.gov (United States)

    Al-Henhena, Nawal; Ying, Rozaida Poh Yuen; Ismail, Salmah; Najm, Walaa; Najm, Wala; Khalifa, Shaden A M; El-Seedi, Hesham; Ameen Abdulla, Mahmood; Abdulla, Mahmood Ameen

    2014-01-01

    Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in Southeast Asia. The aim of this study was to evaluate the chemoprotective effects of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A. paniculata treated groups showed a significant reduction in the number of ACF of the treated rats. Microscopically, ACF showed remarkably elongated and stratified cells, and depletion of the submucosal glands of AOM group compared to the treated groups. Histologically, staining showed slightly elevated masses above the surrounding mucosa with oval or slit-like orifices. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) and β-catenin protein were down-regulated in the A. paniculata treated groups compared to the AOM group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly decreased, whereas superoxide dismutase (SOD) activity was increased in the treated groups compared to the AOM group. A. paniculata ethanol extract showed antioxidant and free radical scavenging activity, as elucidated by the measure of oxidative stress markers. Further, the active fractions were assessed against cell lines of CCD841 and HT29 colon cancer cells.

  5. Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.

    Science.gov (United States)

    Hong, Mee Young; Nulton, Emily; Shelechi, Mahshid; Hernández, Lisa M; Nemoseck, Tricia

    2013-01-01

    Epidemiologic evidence supports that diets rich in polyphenols promote health and may delay the onset of colon cancer. Cocoa and chocolate products have some of the highest polyphenolic concentrations compared to other polyphenolic food sources. This study tested the hypothesis that a diet including dark chocolate can protect against colon cancer by inhibiting aberrant crypt foci (ACF) formation, downregulating gene expression of inflammatory mediators, and favorably altering cell kinetics. We also investigated whether bloomed dark chocolate retains the antioxidant capacity and protects against colon cancer. Forty-eight rats received either a diet containing control (no chocolate), regular dark chocolate, or bloomed dark chocolate and were injected subcutaneously with saline or azoxymethane. Relative to control, both regular and bloomed dark chocolate diets lowered the total number of ACF (P = 0.022). Chocolate diet-fed animals downregulated transcription levels of COX-2 (P = 0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index (P = 0.001). These results suggest that a diet including dark chocolate can reduce cell proliferation and some gene expression involving inflammation, which may explain the lower number of early preneoplastic lesions. These results provide new insight on polyphenol-rich chocolate foods and colon cancer prevention.

  6. Dietary sucrose and starch affect dysplastic characteristics in carcinogen-induced aberrant crypt foci in rat colon.

    Science.gov (United States)

    Caderni, G; Lancioni, L; Luceri, C; Giannini, A; Lodovici, M; Biggeri, A; Dolara, P

    1997-03-19

    To study whether dietary carbohydrates affect dysplasia in aberrant crypt foci (ACF), rats treated with 1,2-dimethilhydrazine (DMH) were fed for three months with diets containing 46% sucrose or corn starch. The number of ACF/colon in the two dietary groups was similar (P = 0.58), but ACF were smaller in the starch than in sucrose group (P colon carcinogenesis while sucrose in the diet is detrimental, promoting the dysplasia of preneoplastic lesions like ACF.

  7. Dietary milk fat globule membrane reduces the incidence of aberrant crypt foci in Fischer-344 rats.

    Science.gov (United States)

    Snow, Dallin R; Jimenez-Flores, Rafael; Ward, Robert E; Cambell, Jesse; Young, Michael J; Nemere, Ilka; Hintze, Korry J

    2010-02-24

    Milk fat globule membrane (MFGM) is a biopolymer composed primarily of membrane proteins and lipids that surround the fat globules in milk. Although it is considered to have potential as a bioactive ingredient, few feeding studies have been conducted to measure its potential benefits. The aim of this investigation was to determine if dietary MFGM confers protection against colon carcinogenesis compared to diets containing corn oil (CO) or anhydrous milk fat (AMF). Male, weanling Fischer-344 rats were randomly assigned to one of three dietary treatments that differed only in the fat source: (1) AIN-76A diet, corn oil; (2) AIN-76A diet, AMF; and (3) AIN-76A diet, 50% MFGM, 50% AMF. Each diet contained 50 g/kg diet of fat. With the exception of the fat source, diets were formulated to be identical in macro and micro nutrient content. Animals were injected with 1,2-dimethylhydrazine once per week at weeks 3 and 4, and fed experimental diets for a total of 13 weeks. Over the course of the study dietary treatment did not affect food consumption, weight gain or body composition. After 13 weeks animals were sacrificed, colons were removed and aberrant crypt foci (ACF) were counted by microscopy. Rats fed the MFGM diet (n = 16) had significantly fewer ACF (20.9 +/- 5.7) compared to rats fed corn oil (n = 17) or AMF (n = 16) diets (31.3 +/- 9.5 and 29.8 +/- 11.4 respectively; P < 0.05). Gene expression analysis of colonic mucosa did not reveal differential expression of candidate colon cancer genes, and the sphingolipid profile of the colonic mucosa was not affected by diet. While there were notable and significant differences in plasma and red blood cell lipids, there was no relationship to the cancer protection. These results support previous findings that dietary sphingolipids are protective against colon carcinogenesis yet extend this finding to MFGM, a milk fat fraction available as a food ingredient.

  8. Influence of Different Diets on Development of DMH-Induced Aberrant Crypt Foci and Colon Tumor Incidence in Wistar Rats

    DEFF Research Database (Denmark)

    Kristiansen, E.; Thorup, I.; Meyer, Otto A.

    1995-01-01

    The present study was undertaken to investigate certain dietary factors known to affect the development of colon cancer for their ability to modulate aberrant crypt foci (ACI;). Male Wistar rats were initiated with oral noses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once...... a week for to or 20 weeks. Throughout the study the animals were fed I) semisynthetic casein-based control diet, 2) control diet with 20% lard, 3) control diet with 20% lard and 20% dietary fiber, or 4) control diet where most of the carbohydrate pool was substituted with sucrose and dextrin....... The composition of the different diets was designed to achieve equivalent intakes of essential nutrients. Animals were killed after 10, 20, and 31 weeks. The study showed a pronounced effect of dietary composition on the development of DMH-induced ACF. The diet high in sucrose and dextrin caused a statistically...

  9. Effects of high fat fish oil and high fat corn oil diets on initiation of AOM-induced colonic aberrant crypt foci in male F344 rats

    NARCIS (Netherlands)

    Dommels, Y.E.M.; Heemskerk, S.; Berg, H. van den; Alink, G.M.; Bladeren, P.J. van; Ommen, B. van

    2003-01-01

    Modulating effects of high fat fish oil (HFFO) and high fat corn oil (HFCO) diets on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male F344 rats following 8 weeks of dietary treatment. The incidence of AOM-induced ACF was significantly lower in the proximal colon of

  10. Eicosapentaenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a double-blind randomized controlled trial

    International Nuclear Information System (INIS)

    Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Maeda, Shin; Morita, Satoshi; Natsumeda, Yutaka; Nagase, Hajime; Nakajima, Atsushi; Hosono, Kunihiro; Endo, Hiroki; Takahashi, Hirokazu; Iida, Hiroshi; Uchiyama, Takashi; Ezuka, Akiko; Uchiyama, Shiori; Yamada, Eiji

    2012-01-01

    Colorectal cancer (CRC) is one of the most commonly occurring neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Eicosapentaenoic acid (EPA), the omega-3 polyunsaturated fatty acid that is widely used in the treatment of hyperlipidemia and prevention of cardiovascular disease, has recently been suggested to have a suppressive effect on tumorigenesis and cancer cell growth. In CRC chemoprevention trials, in general, the incidence of polyps or of the cancer itself is set as the study endpoint. Although the incidence rate of CRC would be the most reliable endpoint, use of this endpoint would be unsuitable for chemoprevention trials, because of the relatively low occurrence rate of CRC in the general population and the long-term observation period that it would necessitate. Moreover, there is an ethical problem in conducting long-term trials to determine whether a test drug might be effective or harmful. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are considered as a reliable surrogate biomarker of CRC. Thus, we devised a prospective randomized controlled trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of EPA against colorectal ACF formation and the safety of this drug, in patients scheduled for polypectomy. This study is a multicenter, double-blind, placebo-controlled, randomized controlled trial to be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients shall be recruited for the study and the number of ACF in the rectum counted at the baseline colonoscopy. Then, the participants shall be allocated randomly to either one of two groups, the EPA group and the placebo group. Patients in the EPA group shall receive oral 900-mg EPA capsules thrice daily (total daily

  11. Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats

    Directory of Open Access Journals (Sweden)

    Rodrigues M.A.M.

    2002-01-01

    Full Text Available Aberrant crypt foci (ACF in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks and medium-term (30 weeks assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH in the rat. Six-week-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1% methylene-blue whole-mount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5% ACF were composed of one or two crypts and 8.5% had three or more crypts, while by the 30th week 46.9% ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks assay.

  12. The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

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    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation

  13. Influence of a Dietary Fiber on Development of Dimethylhydrazine-Induced Aberrant Crypt Foci and Colon Tumor Incidence in Wistar Rats

    DEFF Research Database (Denmark)

    Thorup, I.; Meyer, Otto A.; Kristiansen, E.

    1994-01-01

    Formation of aberrant crypt foci (ACF) in archived colon tissue from animals in a previous study was examined. The animals were fed a semisynthetic casein-based diet in which the carbohydrate pool was substituted with a dietary beet fiber (Fibeta) as the only source of fiber. Oral doses...... experimental data. The present state of knowledge could indicate that ACF represent true preneoplastic lesions progressing into colon tumors or that ACF and colon tumors represent two parallel independent events as a consequence of the cancer initiation (i.e., the ACF not being preneoplastic lesions per se)....... between duration of intake of high-fiber diet and number of animals with ACF, as well as the total number of ACF and number of small A CF (1-3 crypts) per affected animal. The previously reported data showed no protective effect of the dietary fiber at any stage of the colorectal carcinogenic process...

  14. The influence of simple sugars and starch given during pre- or post-initiation on aberrant crypt foci in rat colon

    DEFF Research Database (Denmark)

    Poulsen, Morten; Mølck, Anne-Marie; Thorup, Inger

    2001-01-01

    The aim of the present study was to investigate the enhancing effect of dietary sugar on the development of aberrant crypt foci (ACF) in male F344 rats initiated with azoxymethane (AOM). The potential role of sugar as either a co-initiator or a promoter was investigated by giving diets high...... in sucrose and dextrin (61%) during either the pre-initiation, the initiation, and/or the post initiation stage of the ACF development. The colonic cell proliferation, activity of colonic phase II enzymes, and a biomarker of lipid peroxidation were additionally examined in order to obtain information...... on the specific mechanisms involved in the suggested effect of sucrose and dextrin on ACF development. The number of large sized and the total number of ACF were significantly increased by feeding sucrose and dextrin in the post-initiation period. No positive association between colonic cell proliferation and ACF...

  15. Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats

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    Lokesh Kumar Booupathy

    2016-01-01

    Full Text Available Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF. Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.

  16. Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer

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    W. Lunz

    2008-11-01

    Full Text Available We determined the effect of long-term aerobic swimming training regimens of different intensities on colonic carcinogenesis in rats. Male Wistar rats (11 weeks old were given 4 subcutaneous injections (40 mg/kg body weight each of 1,2-dimethyl-hydrazine (DMH, dissolved in 0.9% NaCl containing 1.5% EDTA, pH 6.5, at 3-day intervals and divided into three exercise groups that swam with 0% body weight (EG1, N = 11, 2% body weight (EG2, N = 11, and 4% body weight of load (EG3, N = 10, 20 min/day, 5 days/week for 35 weeks, and one sedentary control group (CG, N = 10. At sacrifice, the colon was removed and counted for tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat was weighed. The mean number of aberrant crypt foci was reduced only for EG2 compared to CG (26.21 ± 2.99 vs 36.40 ± 1.53 crypts; P < 0.05. Tumor incidence was not significantly different among groups (CG: 90%; EG1: 72.7%; EG2: 90%; EG3: 80%. Swimming training did not affect either tumor multiplicity (CG: 2.30 ± 0.58; EG1: 2.09 ± 0.44; EG2: 1.27 ± 0.19; EG3: 1.50 ± 0.48 tumors or size (CG: 1.78 ± 0.24; EG1: 1.81 ± 0.14; EG2: 1.55 ± 0.21; EG3: 2.17 ± 0.22 cm³. Intra-abdominal fat was not significantly different among groups (CG: 10.54 ± 2.73; EG1: 6.12 ± 1.15; EG2: 7.85 ± 1.24; EG3: 5.11 ± 0.74 g. Aerobic swimming training with 2% body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat.

  17. IQ (2-amino-3-methylimidazo[4,5-f ]quinoline) – induced aberrant crypt foci and colorectal tumour development in rats fed two different carbohydrate diets

    DEFF Research Database (Denmark)

    Mølck, A. M.; Meyer, Otto A.; Kristiansen, E.

    2001-01-01

    associated with enhanced development of ACF and colorectal cancer in humans. The present study was designed as an integrated part of our earlier published ACF study and follows the animals until tumour development. The aim of the study was to investigate (1) the effect of a refined carbohydrate-rich diet...... on the development of IQ-induced ACF over time and (2) possible correlation between early and late ACF and/or colorectal tumour development. The study showed that a feeding regimen with continuous doses of 0.03% IQ in the diet for 14 weeks, followed by 32 weeks without IQ was able to induce tumours in the rat colon......In most aberrant crypt foci (ACF) and colorectal tumour studies, chemical carcinogens not normally found in food have been used as initiators. In the present study the food-related compound, IQ (2-amino-3-methylimidazo[4,5-f]quinoline), has been used. A diet high in refined carbohydrates has been...

  18. Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats.

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    Qamar, Tahir Rasool; Syed, Fatima; Nasir, Muhammad; Rehman, Habib; Zahid, Muhammad Nauman; Liu, Rui Hai; Iqbal, Sanaullah

    2016-08-01

    The selectivity and beneficial effects of prebiotics are mainly dependent on composition and glycosidic linkage among monosaccharide units. This is the first study to use prebiotic galacto-oligosaccharides (GOS) that contains β-1,6 and β-1,3 glycosidic linkages and the novel combination of GOS and inulin in cancer prevention. The objective of the present study is to explore the role of novel GOS and inulin against various biomarkers of colorectal cancer (CRC) and the incidence of aberrant crypt foci (ACF) in a 1,2-dimethyl hydrazine dihydrochloride (DMH)-induced rodent model. Prebiotic treatments of combined GOS and inulin (57 mg each), as well as individual doses (GOS: 76-151 mg; inulin 114 mg), were given to DMH-treated animals for 16 weeks. Our data reveal the significant preventive effect of the GOS and inulin combination against the development of CRC. It was observed that inhibition of ACF formation (55.8%) was significantly (p ≤ 0.05) higher using the GOS and inulin combination than GOS (41.4%) and inulin (51.2%) treatments alone. This combination also rendered better results on short-chain fatty acids (SCFA) and bacterial enzymatic activities. Dose-dependent effects of prebiotic treatments were also observed on cecum and fecal bacterial enzymes and on SCFA. Thus, this study demonstrated that novel combination of GOS and inulin exhibited stronger preventive activity than their individual treatments alone, and can be a promising strategy for CRC chemoprevention.

  19. Synbiotic preparation with Lactic acid bacteria and inulin as a functional food: In vivo evaluation of microbial activities, and preneoplastic aberrant crypt foci

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    Chaiyavat CHAIYASUT

    Full Text Available Abstract Host microbiome and metabolome are associated with the incidence of colorectal cancer (CC, one of the major health problems in developed countries. The pro and prebiotic supplementation helps to improve the host health. Inulin is one such prebiotic used for the enhancement of naïve probiotic bacterial population. This paper explains the impact of inulin (PRE extracted from Jerusalem artichoke (JA, Lactobacillus plantarum HII11 (PRO, and synbiotic (SYN; inulin + L. plantarum HII11 preparation on Azoxymethane mediated CC induced rat model with respect to changes in microbial load, microbial enzymes, and preneoplastic aberrant crypt foci. The results suggested that the PRE and SYN supplementation effectively reduced the selected pathogenic bacteria (Salmonella spp., and Escherichia coli, microbial enzymes and increased the probiotic load. The intervention of SYN significantly reduced the colonic ACF in CC model. The study results revealed that the supplementation of SYN diet (inulin and L. plantarum HII11 protects the AOM-mediated colon cancer induced host.

  20. Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats

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    Elnaz Saki

    2017-01-01

    Full Text Available Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age were randomly divided into 5 groups which were (G1 induced with azoxymethane (AOM and not given GRR (positive control, (G2 induced with AOM and given 2000 mg/kg GRR, (G3 induced with AOM and given 1000 mg/kg GRR, (G4 induced with AOM and given 500 mg/kg GRR, and (G5 not induced with AOM and not given GRR crude extract (negative control. To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.

  1. Dietary aloe vera gel powder and extract inhibit azoxymethane- induced colorectal aberrant crypt foci in mice fed a high- fat diet.

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    Chihara, Takeshi; Shimpo, Kan; Kaneko, Takaaki; Beppu, Hidehiko; Higashiguchi, Takashi; Sonoda, Shigeru; Tanaka, Miyuki; Yamada, Muneo; Abe, Fumiaki

    2015-01-01

    Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

  2. Chemopreventive effects of PBI-Se, a selenium-containing analog of PBIT, on AOM-induced aberrant crypt foci in F344 rats.

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    Janakiram, Naveena B; Mohammed, Altaf; Ravillah, Durgadevi; Choi, Chang In; Zhang, Yuting; Desai, Dhimant; Amin, Shantu; Rao, Chinthalapally V

    2013-08-01

    Inducible nitric oxide synthase (iNOS) is a potential target for the treatment of inflammation and cancer. Previously, we showed that the selective iNOS inhibitor S,S'-1,4-phenylenebis(1,2-ethanediyl)bis-isothiourea (PBIT) caused significant inhibition of colon carcinogenesis induced by azoxymethane (AOM), although it did not completely abrogate NO production due to the exogenous bioavailability of NO and NO generation by eNOS in tumor tissues. To create an iNOS-targeting molecule that may have additional benefits, a novel isosteric analog of PBIT, PBI-Se, was developed, in which sulfur was replaced with selenium. Chemopreventive efficacy of PBI-Se was evaluated in an AOM-induced rat colon carcinogenesis model using aberrant crypt foci (ACF) as the endpoint. At 7 weeks of age, rats (12/group) were fed the control diet (AIN 76A) and then colonic ACF were induced with two AOM treatments. Three days later, rats were fed diets containing PBI-Se (0-20 ppm) for 8 weeks, and then ACF were evaluated histopathologically. Dietary administration of 10 or 20 ppm of PBI-Se significantly suppressed AOM-induced total colonic ACF formation (32 or 41%, pPBI-Se was dose-dependent and was half the dose of PBIT for inhibiting total ACF in rats. Both PBIT and PBI-Se induced dose-dependent apoptosis in CaCo2 cells and caused a significant decrease in the cell cycle proteins cyclin D1 (70%, pPBI-Se (2 and 4  µM) significantly decreased the LPS-induced cytokine interleukin-6 level. Incorporation of selenium into the structure of PBIT provided the agent with additional novel cytotoxic and immunologic properties. Results from the in vitro and in vivo bioassays suggest that PBI-Se could be developed further for the prevention and treatment of colon cancer.

  3. Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

    Science.gov (United States)

    Pattananandecha, Thanawat; Sirilun, Sasithorn; Duangjitcharoen, Yodsawee; Sivamaruthi, Bhagavathi Sundaram; Suwannalert, Prasit; Peerajan, Sartjin; Chaiyasut, Chaiyavat

    2016-09-01

    Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary

  4. Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-β1 and HES-1 transcripts in 1,2-dimethylhydrazine-colon carcinogenesis in mice

    International Nuclear Information System (INIS)

    Bounaama, Abdelkader; Djerdjouri, Bahia; Laroche-Clary, Audrey; Le Morvan, Valérie; Robert, Jacques

    2012-01-01

    Highlights: ► 1,2-Dimethylhydrazine (DMH) toxicity was driven by oxidative stress. ► Arginase activity correlated to aberrant crypt foci (ACF). ► Curcumin diet restored redox status and induced apoptosis of dysplastic ACF. ► Curcumin reduced arginase activity and up regulated TGF-β1 and HES-1 transcripts. -- Abstract: This study investigated the effect of short curcumin treatment, a natural antioxidant on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in mice. The incidence of aberrant crypt foci (ACF) was 100%, with 54 ± 6 per colon, 10 weeks after the first DMH injection and reached 67 ± 12 per colon after 12 weeks. A high level of undifferentiated goblet cells and a weak apoptotic activity were shown in dysplastic ACF. The morphological alterations of colonic mucosa were associated to severe oxidative stress ratio with 43% increase in malondialdehyde vs. 36% decrease in GSH. DMH also increased inducible nitric synthase (iNOS) mRNA transcripts (250%), nitrites level (240%) and arginase activity (296%), leading to nitrosative stress and cell proliferation. Curcumin treatment, starting at week 10 post-DMH injection for 14 days, reduced the number of ACF (40%), iNOS expression (25%) and arginase activity (73%), and improved redox status by approximately 46%, compared to DMH-treated mice. Moreover, curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells differentiation. Interestingly, curcumin induced a parallel increase in TGF-β1 and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective effect of curcumin was driven by the reduction of arginase activity and nitrosative stress. The up regulation of TGF-β1 and HES-1 expression by curcumin suggests for the first time, a potential interplay between these signalling pathways in the chemoprotective mechanism of curcumin.

  5. Refined carbohydrate enhancement of aberrant crypt foci (ACF) in rat colon induced by the food-borne carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1996-01-01

    ,2-dimethylhydrazine dihydrochloride (DMH) and azoxymethane (AOM), the use of a diet-related colon cancer initiator, such as the heterocyclic amine 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) formed during meat cooking, would probably give a more relevant insight into diet-related colon carcinogenesis......The aberrant crypt foci (ACF) bioassay has been used extensively to study the early effects of different dietary components on the colonic mucosa of laboratory rodents. ACF are proposed to represent preneoplastic lesions of colon cancer. Compared to the normally used initiators 1....... In the present study it is shown that a feeding regimen with continuous low IQ doses (0.03% in the diet) throughout a study period of 10 weeks has a significant effect on the induction of ACF in the colon of male F344 rats. In addition, the study illustrates that the incidence of the IQ-induced ACF can...

  6. Chemoprevention of Colonic Aberrant Crypt Foci by Novel Schiff Based Dichlorido(4-Methoxy-2-{[2-(Piperazin-4-Ium-1-Yl)Ethyl]Iminomethyl}Phenolate)Cd Complex in Azoxymethane-Induced Colorectal Cancer in Rats

    Science.gov (United States)

    Hajrezaie, Maryam; Shams, Keivan; Moghadamtousi, Soheil Zorofchian; Karimian, Hamed; Hassandarvish, Pouya; Emtyazjoo, Mozhgan; Zahedifard, Maryam; Majid, Nazia Abdul; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2015-01-01

    Schiff-based complexes as a source of cancer chemotherapeutic compounds have been subjected to the variety of anticancer studies. The in-vitro analysis confirmed the CdCl2(C14H21N3O2) complex possess cytotoxicity and apoptosis induction properties in colon cancer cells, so lead to investigate the inhibitory efficiency of the compound on colonic aberrant crypt foci (ACF). Five groups of adult male rats were used in this study: Vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of complex for 10 weeks. The rats in vehicle group were injected subcutaneously with 15 mg/kg of sterile normal saline once a week for 2 weeks and orally administered with 5% Tween-20 (5 ml/kg) for 10 weeks, other groups were injected subcutaneously with 15 mg/kg azoxymethane once a week for 2 weeks. The rats in positive groups were injected intra-peritoneally with 35 mg/kg 5-Flourouracil four times in a month. Administration of the complex suppressed total colonic ACF formation up to 73.4% (P < 0.05). The results also showed that treatment with the complex significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. PMID:26201720

  7. Optimization of visibility and quantification of aberrant crypt foci in colonic mucosa in Wistar rats Otimização da visibilidade e quantificação de focos de criptas aberrantes em mucosa cólica de ratos Wistar

    Directory of Open Access Journals (Sweden)

    Idália Maria Brasil Burlamaqui

    2010-04-01

    Full Text Available PURPOSE: Test immersion of microscopy samples in water as an aid to visualizing and quantifying aberrant crypt foci (ACF in rat colon mucosa. METHODS: Carcinogenesis was induced with azoxymethane in Wistar rats kept on a conventional diet or a hypercaloric diet containing unsaturated fat. Fifteen weeks after induction, colon samples were retrieved and fixated in a 10% formaldehyde solution. The samples were divided into segments (distal, middle, proximal and stained with 1% toluidine blue. The technique tested in the study consisted of immersing microscopy samples in distilled water in order to eliminate the problem of light reflection known from conventional microscopy. RESULTS: When samples were immersed in water during microscopy, significantly more ACF could be visualized in all colon segments than with the conventional method proposed by Bird. CONCLUSION: Immersing microscopy samples in water aids the visualization and quantification of aberrant crypt foci in rat colon mucosa fixed in formaldehyde.OBJETIVO: Otimizar a visibilização de focos de criptas aberrantes (FCA em mucosa cólica de ratos Wistar. MÉTODOS: Colo de rato Wistar, sob diferentes dietas e submetidos a iniciação de carcinogênese pelo azoximetano há 4 meses, foram previamente lavados, abertos e fixados em solução de formalina a 10% por 24 horas. Após serem corados em azul de toluidina a 1%, foram divididos em segmentos distal, médio e proximal e imersos em água destilada para quantificação de FCA. RESULTADOS: No método de imersão foi visibilizado maior quantidade de focos de criptas aberrantes em todos os segmentos cólicos, com diferença significante, quando comparado com o método de Bird. CONCLUSÃO: O método de imersão otimiza a visibilização e quantificação de focos de criptas aberrantes em mucosa cólica (ratos Wistar fixada em solução de formalina a 10%.

  8. Comparative DNA adduct formation and induction of colonic aberrant crypt foci in mice exposed to 2-amino-9H-pyrido[2,3-b]indole, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and azoxymethane

    Science.gov (United States)

    Kim, Sangyub; Guo, Jingshu; O’Sullivan, M. Gerald; Gallaher, Daniel D.; Turesky, Robert J.

    2015-01-01

    Considerable evidence suggests that environmental factors, including diet and cigarette smoke, are involved in the pathogenesis of colon cancer. Carcinogenic nitroso compounds (NOC), such as N-nitrosodimethylamine (NDMA), are present in tobacco and processed red meat, and NOC have been implicated in colon cancer. Azoxymethane (AOM), commonly used for experimental colon carcinogenesis, is an isomer of NDMA, and it produces the same DNA adducts as does NDMA. Heterocyclic aromatic amines (HAAs) formed during the combustion of tobacco and high-temperature cooking of meats are also associated with an elevated risk of colon cancer. The most abundant carcinogenic HAA formed in tobacco smoke is 2-amino-9H-pyrido[2,3-b]indole (AαC), whereas 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) is the most potent carcinogenic HAA formed during the cooking of meat and fish. However, the comparative tumor-initiating potential of AαC, MeIQ, and AOM is unknown. In this report, we evaluate the formation of DNA adducts as a measure of genotoxicity, and the induction of colonic aberrant crypt foci (ACF) and dysplastic ACF, as an early measure of carcinogenic potency of these compounds in the colon of male A/J mice. Both AαC and AOM induced a greater number of DNA adducts than MeIQ in the liver and colon. AOM induced a greater number of ACF and dysplastic ACF than either AαC or MeIQ. Conversely, based on adduct levels, MeIQ-DNA adducts were more potent than AαC- and AOM-DNA adducts at inducing ACF. Long-term feeding studies are required to relate levels of DNA adducts, induction of ACF, and colon cancer by these colon genotoxicants. PMID:26734915

  9. Crowns and Crypts

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 6. Crowns and Crypts - A Fascinating Group of Multidentate Macrocyclic Ligands. Debasis Bandyopadhyay. General Article Volume 6 Issue 6 June 2001 pp 71-79. Fulltext. Click here to view fulltext PDF. Permanent link:

  10. Using crypts as iris minutiae

    Science.gov (United States)

    Shen, Feng; Flynn, Patrick J.

    2013-05-01

    Iris recognition is one of the most reliable biometric technologies for identity recognition and verification, but it has not been used in a forensic context because the representation and matching of iris features are not straightforward for traditional iris recognition techniques. In this paper we concentrate on the iris crypt as a visible feature used to represent the characteristics of irises in a similar way to fingerprint minutiae. The matching of crypts is based on their appearances and locations. The number of matching crypt pairs found between two irises can be used for identity verification and the convenience of manual inspection makes iris crypts a potential candidate for forensic applications.

  11. Enzootic plague foci, Algeria

    Directory of Open Access Journals (Sweden)

    M.A. Malek

    2015-03-01

    Full Text Available In Algeria, PCR sequencing of pla, glpD and rpoB genes found Yersinia pestis in 18/237 (8% rodents of five species, including Apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. Multiple spacer typing confirmed a new Orientalis variant. Rodent survey should be reinforced in this country hosting reemerging plague.

  12. Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer

    Science.gov (United States)

    Welge, Weston A.; Barton, Jennifer K.

    2016-03-01

    Aberrant crypt foci (ACF) are abnormal epithelial lesions that precede development of colonic polyps. As the earliest morphological change in the development of colorectal cancer, ACF is a highly studied phenomenon. The most common method of imaging ACF is chromoendoscopy using methylene blue as a contrast agent. Narrow- band imaging is a contrast-agent-free modality for imaging the colonic crypts. Optical coherence tomography (OCT) is an attractive alternative to chromoendoscopy and narrow-band imaging because it can resolve the crypt structure at sufficiently high sampling while simultaneously providing depth-resolved data. We imaged in vivo the distal 15 mm of colon in the azoxymethane (AOM) mouse model of colorectal cancer using a commercial swept-source OCT system and a miniature endoscope designed and built in-house. We present en face images of the colonic crypts and demonstrate that different patterns in healthy and adenoma tissue can be seen. These patterns correspond to those reported in the literature. We have previously demonstrated early detection of colon adenoma using OCT by detecting minute thickening of the mucosa. By combining mucosal thickness measurement with imaging of the crypt structure, OCT can be used to correlate ACF and adenoma development in space and time. These results suggest that OCT may be a superior imaging modality for studying the connection between ACF and colorectal cancer.

  13. Aberrant crypt foci in the colo-rectal mucosa as reliable markers of tumor development

    DEFF Research Database (Denmark)

    Thorup, Inger

    connection exists between occurrence of ACF (neither qualitatively nor quantita- tively) and later development of tumors. However, the literature has shown that part of the ACF show morphologic and genetic features characteristic for the tumorigenic process and a recent investigation indicate that all ACF...

  14. PROMOTION OF TRIHALOMETHANE-INDUCED COLON, ABERRANT CRYPT FOCI (ACF) BY A HIGH FAT DIET

    Science.gov (United States)

    Abstract:Bromodichloromethane (BOCM) and tribromomethane (TBM) enhanced neoplasia in the large intestine of rats when given by corn oil gavage; BOCM in the drinking water to male rats did not induce colon tumors, but did increase liver tumors. However, TBM and a mixture o...

  15. File list: Unc.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Dig.05.AllAg.Intestinal_crypt mm9 Unclassified Digestive tract Intestinal crypt... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Dig.05.AllAg.Intestinal_crypt.bed ...

  16. Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs

    Science.gov (United States)

    Davis, Michael E; Lisowyj, Michal P; Zhou, Lin; Wisecarver, James L; Gulizia, James M; Shostrom, Valerie K; Naud, Nathalie; Corpet, Denis E; Mirvish, Sidney S

    2012-01-01

    Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17–34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5–6, with P ANC tests. Experiment 2 showed somewhat increased numbers of colonic mucin-depleted foci in the ANC-treated group. We conclude that hot-dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon. PMID:22293095

  17. The protective effects of fermented kefir milk on azoxymethane-induced aberrant crypt formation in mice colon.

    Science.gov (United States)

    Melo, Aline Freitas de Paula; Mendonça, Monique Culturato Padilha; Rosa-Castro, Raquel de Mendonça

    2018-06-01

    Kefir is a probiotic fermented milk product produced from grains with a complex composition of bacteria and yeasts that live in a symbiotic association. Anti-proliferative, anti-inflammatory, and anti-mutagenic effects are some of the health beneficial properties of kefir grains. The present study was conducted to evaluate whether regular consumption of kefir milk would be capable of preventing the development of pre-neoplastic lesions induced by azoxymethane (AOM). Aberrant crypt foci were induced in BALB-c mice via 2 subcutaneous injections of azoxymethane (15 mg/kg) and kefir was administered by daily gavage for 8 weeks (5 ml/kg). Additionally, bacterial growth was monitored in pasteurized and ultra-high temperature (UHT) treated milk to compare different fermentation conditions. Our results showed that UHT milk presented better growth of Lactobacillus acidophilus colonies. The aberrant crypt foci were attenuated by approximately 43% (height) and 20% (width) in the kefir group compared to AOM group, suggesting that kefir treatment may contribute to prevent and control the growth of intestinal neoplastic cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Cholecystosonographic findings of clonorchiasis: Floating echogenic foci

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ho Kyun [Choong Joo X-ray Clinic, Choongjoo (Korea, Republic of)

    1989-06-15

    Author analysed cholecystosonographic findings in 22 patients with clonorchiasis, suspected prospectively by ultrasound and proved subsequently by demonstration of eggs in the stools. Fifteen gallbladders had nonshadowing, fusiform, discrete echogenic foci measuring 3{approx}6 mm in the lumen. Among these, the echogenic foci floated spontaneously in three cases, while in twelve cases they floated by position change or a light blow by the transducer. In the rest of the seven gallbladders, the echogenic foci were at the dependent portion. In the in vitro study with a worm suspension in saline in a surgical glove, the same echogenic foci as those seen in the gallbladders were demonstrated. The echogenic foci were precipitated in the dependent portion but float with a light blow on the glove. Author conclude that the floating echogenic foci in the lumen of the gallbladder are due to adult worms of clonorchis sinensis.

  19. Cholecystosonographic findings of clonorchiasis: Floating echogenic foci

    International Nuclear Information System (INIS)

    Kim, Ho Kyun

    1989-01-01

    Author analysed cholecystosonographic findings in 22 patients with clonorchiasis, suspected prospectively by ultrasound and proved subsequently by demonstration of eggs in the stools. Fifteen gallbladders had nonshadowing, fusiform, discrete echogenic foci measuring 3∼6 mm in the lumen. Among these, the echogenic foci floated spontaneously in three cases, while in twelve cases they floated by position change or a light blow by the transducer. In the rest of the seven gallbladders, the echogenic foci were at the dependent portion. In the in vitro study with a worm suspension in saline in a surgical glove, the same echogenic foci as those seen in the gallbladders were demonstrated. The echogenic foci were precipitated in the dependent portion but float with a light blow on the glove. Author conclude that the floating echogenic foci in the lumen of the gallbladder are due to adult worms of clonorchis sinensis

  20. Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury.

    Science.gov (United States)

    Poindexter, Shenika V; Reddy, Vishruth K; Mittal, Mukul K; Williams, Amanda M; Washington, M Kay; Harris, Elizabeth; Mah, Amanda; Hiebert, Scott W; Singh, Kshipra; Chaturvedi, Rupesh; Wilson, Keith T; Lund, P Kay; Williams, Christopher S

    2015-03-15

    Myeloid translocation genes (MTGs) are transcriptional corepressors implicated in development, malignancy, differentiation, and stem cell function. While MTG16 loss renders mice sensitive to chemical colitis, the role of MTG16 in the small intestine is unknown. Histological examination revealed that Mtg16(-/-) mice have increased enterocyte proliferation and goblet cell deficiency. After exposure to radiation, Mtg16(-/-) mice exhibited increased crypt viability and decreased apoptosis compared with wild-type (WT) mice. Flow cytometric and immunofluorescence analysis of intestinal epithelial cells for phospho-histone H2A.X also indicated decreased DNA damage and apoptosis in Mtg16(-/-) intestines. To determine if Mtg16 deletion affected epithelial cells in a cell-autonomous fashion, intestinal crypts were isolated from Mtg16(-/-) mice. Mtg16(-/-) and WT intestinal crypts showed similar enterosphere forming efficiencies when cultured in the presence of EGF, Noggin, and R-spondin. However, when Mtg16(-/-) crypts were cultured in the presence of Wnt3a, they demonstrated higher enterosphere forming efficiencies and delayed progression to mature enteroids. Mtg16(-/-) intestinal crypts isolated from irradiated mice exhibited increased survival compared with WT intestinal crypts. Interestingly, Mtg16 expression was reduced in a stem cell-enriched population at the time of crypt regeneration. This is consistent with MTG16 negatively regulating regeneration in vivo. Taken together, our data demonstrate that MTG16 loss promotes radioresistance and impacts intestinal stem cell function, possibly due to shifting cellular response away from DNA damage-induced apoptosis and towards DNA repair after injury.

  1. Multimodality localization of epileptic foci

    Science.gov (United States)

    Desco, Manuel; Pascau, Javier; Pozo, M. A.; Santos, Andres; Reig, Santiago; Gispert, Juan D.; Garcia-Barreno, Pedro

    2001-05-01

    This paper presents a multimodality approach for the localization of epileptic foci using PET, MRI and EEG combined without the need of external markers. Mutual Information algorithm is used for MRI-PET registration. Dipole coordinates (provided by BESA software) are projected onto the MRI using a specifically developed algorithm. The four anatomical references used for electrode positioning (nasion, inion and two preauricular points) are located on the MRI using a triplanar viewer combined with a surface-rendering tool. Geometric transformation using deformation of the ideal sphere used for dipole calculations is then applied to match the patient's brain size and shape. Eight treatment-refractory epileptic patients have been studied. The combination of the anatomical information from the MRI, hipoperfusion areas in PET and dipole position and orientation helped the physician in the diagnosis of epileptic focus location. Neurosurgery was not indicated for patients where PET and dipole results were inconsistent; in two cases it was clinically indicated despite the mismatch, showing a negative follow up. The multimodality approach presented does not require external markers for dipole projection onto the MRI, this being the main difference with previous methods. The proposed method may play an important role in the indication of surgery for treatment- refractory epileptic patients.

  2. Regulatory foci and the big five

    OpenAIRE

    Bak, Waclaw

    2009-01-01

    The distinction between promotion and prevention focus (Higgins, 1997) have been employed by many researchers dealing with processes of self-regulation. Little is known however about relations between regulatory orientations and more general personality traits. The present paper reports results of the study in which regulatory foci are analyzed in the context of five factor model of personality. To measure personality traits the NEO-FFI was used. Promotion and prevention regulatory foci was a...

  3. DNA-based watermarks using the DNA-Crypt algorithm

    Science.gov (United States)

    Heider, Dominik; Barnekow, Angelika

    2007-01-01

    Background The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. Results The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. Conclusion The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms. PMID:17535434

  4. DNA-based watermarks using the DNA-Crypt algorithm

    Directory of Open Access Journals (Sweden)

    Barnekow Angelika

    2007-05-01

    Full Text Available Abstract Background The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. Results The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. Conclusion The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms.

  5. DNA-based watermarks using the DNA-Crypt algorithm.

    Science.gov (United States)

    Heider, Dominik; Barnekow, Angelika

    2007-05-29

    The aim of this paper is to demonstrate the application of watermarks based on DNA sequences to identify the unauthorized use of genetically modified organisms (GMOs) protected by patents. Predicted mutations in the genome can be corrected by the DNA-Crypt program leaving the encrypted information intact. Existing DNA cryptographic and steganographic algorithms use synthetic DNA sequences to store binary information however, although these sequences can be used for authentication, they may change the target DNA sequence when introduced into living organisms. The DNA-Crypt algorithm and image steganography are based on the same watermark-hiding principle, namely using the least significant base in case of DNA-Crypt and the least significant bit in case of the image steganography. It can be combined with binary encryption algorithms like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target DNA with several mutation correction codes such as the Hamming-code or the WDH-code. Mutations which can occur infrequently may destroy the encrypted information, however an integrated fuzzy controller decides on a set of heuristics based on three input dimensions, and recommends whether or not to use a correction code. These three input dimensions are the length of the sequence, the individual mutation rate and the stability over time, which is represented by the number of generations. In silico experiments using the Ypt7 in Saccharomyces cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the translation of mRNA into protein. The program is able to store watermarks in living organisms and can maintain the original information by correcting mutations itself. Pairwise or multiple sequence alignments show that DNA-Crypt produces few mismatches between the sequences similar to all steganographic algorithms.

  6. Association of iris crypts with acute primary angle closure.

    Science.gov (United States)

    Koh, Victor; Chua, Jacqueline; Shi, Yuan; Thakku, Sri Gowtham; Lee, Ryan; Nongpiur, Monisha E; Baskaran, Mani; Kumar, Rajesh S; Perera, Shamira; Aung, Tin; Cheng, Ching-Yu

    2017-10-01

    To determine the relationship between iris surface features and acute primary angle closure (APAC) in eyes with angle closure. Case-control study involving Asian patients diagnosed with previous APAC, primary angle closure suspect (PACS), primary angle closure (PAC) and primary angle closure glaucoma (PACG) at an eye centre in Singapore between August 2012 and January 2015. Participants underwent ophthalmic examination and digital slit-lamp iris photography. Iris surface features were graded based on crypts, furrows and colour. Fellow eyes of APAC were compared with PACS and PAC/PACG eyes with regard to their iris surface features. Occurrence of APAC. A total of 309 patients (71 APAC, 139 PACS, 47 PAC and 52 PACG) were included (mean age: 67.7±7.2 years and 36.6% male). Compared with PACS, higher crypt grade was significantly associated with lower odds of APAC (OR=0.58 for one grade higher in crypt grade; p=0.027, adjusted for age, gender, ethnicity and pupil diameter). The results remained similar when compared with PAC/PACG group (OR=0.58 for one grade higher in crypt grade; p=0.043). We did not observe any significant associations between iris furrows or colour with presence of APAC. Our study comprising Asian eyes with angle closure suggests that the presence of a higher crypt grading may be protective for APAC. As such, assessing iris surface architecture for crypts could be a new measure for risk stratification of developing APAC in eyes with angle closure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. IGF-II transgenic mice display increased aberrant colon crypt multiplicity and tumor volume after 1,2-dimethylhydrazine treatment

    Directory of Open Access Journals (Sweden)

    Oesterle Doris

    2006-01-01

    Full Text Available Abstract In colorectal cancer insulin-like growth factor II (IGF-II is frequently overexpressed. To evaluate, whether IGF-II affects different stages of tumorigenesis, we induced neoplastic alterations in the colon of wild-type and IGF-II transgenic mice using 1,2-dimethylhydrazine (DMH. Aberrant crypt foci (ACF served as markers of early lesions in the colonic mucosa, whereas adenomas and carcinomas characterized the endpoints of tumor development. DMH-treatment led initially to significantly more ACF in IGF-II transgenic than in wild-type mice. This increase in ACF was especially prominent for those consisting of ≥three aberrant crypts (AC. Nevertheless, adenomas and adenocarcinomas of the colon, present after 34 weeks in both genetic groups, were not found at different frequency. Tumor volumes, however, were significantly higher in IGF-II transgenic mice and correlated with serum IGF-II levels. Immunohistochemical staining for markers of proliferation and apoptosis revealed increased cell proliferation rates in tumors of IGF-II transgenic mice without significant affection of apoptosis. Increased proliferation was accompanied by elevated localization of β-catenin in the cytosol and cell nuclei and reduced appearance at the inner plasma membrane. In conclusion, we provide evidence that IGF-II, via activation of the β-catenin signaling cascade, promotes growth of ACF and tumors without affecting tumor numbers.

  8. File list: ALL.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Dig.10.AllAg.Intestinal_crypt mm9 All antigens Digestive tract Intestinal crypt... SRX871676,SRX871671,SRX871675,SRX871672 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Dig.10.AllAg.Intestinal_crypt.bed ...

  9. File list: Oth.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Dig.10.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.10.AllAg.Intestinal_crypt mm9 RNA polymerase Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Dig.10.AllAg.Intestinal_crypt.bed ...

  11. File list: NoD.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Dig.20.AllAg.Intestinal_crypt mm9 No description Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Dig.20.AllAg.Intestinal_crypt.bed ...

  12. File list: ALL.Dig.20.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Dig.20.AllAg.Intestinal_crypt mm9 All antigens Digestive tract Intestinal crypt... SRX871676,SRX871672,SRX871675,SRX871671 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Dig.20.AllAg.Intestinal_crypt.bed ...

  13. File list: NoD.Dig.05.AllAg.Intestinal_crypt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Dig.05.AllAg.Intestinal_crypt mm9 No description Digestive tract Intestinal cry...pt http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Dig.05.AllAg.Intestinal_crypt.bed ...

  14. The influence of dibutyryl adenosine cyclic monophosphate on cell proliferation in the epithelium of the jejunal crypts, the colonic crypts and in colonic carcinomata of rat.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1980-01-01

    1. Cell proliferation in the jejunal crypts, the colonic crypts and in dimethylhydrazine (DMH)-induced adenocarcinomata of rat colon was measured using a stathmokinetic technique. 2. Dibutryl cyclic adneosine monophosphate (dibutyryl cAMP) was found to inhibit cell proliferation in colonic crypts and in colonic adenocarcinomata. 3. Dibutryl cAMP at very high doses was found to inhibit jejunal crypt cell proliferation but at lower doses was found to accelerate jejunal crypt cell proliferation. 4. Neither bilateral adrenalectomy nor chemical sympathectomy was found to abolish the ability of dibutryl cAMP to stimulate jejunal crypt cell proliferation. 5. The present results are difficult to interpret in terms of known hormonal influences on cell proliferation in the tissues examined and of established actions, of these hormones on cyclic nucleotide metabolism in other tissues.

  15. Imaging methods for detection of infectious foci

    International Nuclear Information System (INIS)

    Couret, I.; Rossi, M.; Weinemann, P.; Moretti, J.L.

    1993-01-01

    Several tracers can be used for imaging infection. None is a worthwhile agent for all infectious foci, but each one has preferential applications, depending on its uptake mechanism by the infectious and/or inflammatory focus. Autologous leucocytes labeled in vitro with indium-111 (In-111) or with technetium-99-hexamethylpropyleneamine oxime (Tc-99m HMPAO) were applied with success in the detection of peripheral bone infection, focal vascular graft infection and inflammatory bowel disease. Labeling with In-111 is of interest in chronic bone infection, while labeling with Tc-99m HMPAO gets the advantage of a better dosimetry and imaging. The interest of in vivo labeled leucocytes with a Tc-99m labeled monoclonal antigranulocyte antibody anti-NCA 95 (BW 250/183) was proved in the same principal type of infectious foci than in vitro labeled leucocytes. Sites of chronic infection in the spine and the pelvis, whether active or healed, appear as photopenic defects on both in vitro labeled leucocytes and Tc-99m monoclonal antigranulocyte antibody (BW 250/183) scintigraphies. With gallium-67 results showed a high sensitivity with a low specificity. This tracer demonstrated good performance to delineate foci of infectious spondylitis. In-111 and Tc-99m labeled polyclonal human immunoglobulin (HIG) was applied with success in the assessment of various infectious foci, particularly in chronic sepsis. As labeled leucocytes, labeled HIG showed cold defects in infectious sepsis of the spine. Research in nuclear medicine is very active in the development of more specific tracers of infection, mainly involved in Tc-99m or In-111 labeled chemotactic peptides, antigranulocyte antibody fragments, antibiotic derivatives and interleukins. (authors). 70 refs

  16. HIV enteropathy: HAART reduces HIV-induced stem cell hyperproliferation and crypt hypertrophy to normal in jejunal mucosa.

    Science.gov (United States)

    Batman, Philip A; Kapembwa, Moses S; Belmonte, Liliana; Tudor, Gregory; Kotler, Donald P; Potten, Christopher S; Booth, Catherine; Cahn, Pedro; Griffin, George E

    2014-01-01

    To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART). Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques. Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal antibody, and the percentage of crypt cells in proliferation was calculated at each cell position along the length of the crypt (proliferation index). Data were obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV-positive patients receiving HAART and 13 control cases. Crypt length was significantly greater in test patients than in controls, but crypt length in patients receiving HAART was normal. The proliferation index was greater in test subjects than in controls in stem and transit cell compartments, and was decreased in patients treated with HAART only in the stem cell region of the crypt. Villous atrophy in HIV enteropathy is attributed to crypt hypertrophy and encroachment of crypt cells onto villi. HAART restores normal crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the crypt bases.

  17. Relationship of histochemically detectable altered hepatocyte foci to hepatic tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Peraino, C.; Staffeldt, E.F.; Carnes, B.A.; Ludeman, V.A.; Blomquist, J.A.; Vesselinovitch, S.D.

    1984-01-01

    A new experimental system was used to examine the stages of chemically induced hepatic neoplasia in the rat. The treatment protocol involved the intraperitoneal injection of a single non-necrogenic dose of carcinogen (N-nitrosodiethylamine (NDEA) or benzo(a)pyrene (BP)) into male and female rats within one day after birth, followed by dietary exposure to promoter (0.05% phenobarbital) from weaning. Rats were killed at intervals, and their livers were examined for tumors and for histochemically detectable foci of altered hepatocytes. The data showed that (1) the new treatment protocol was highly efficient in foci and tumor production; (2) growth rates and incidence levels of foci were directly related to hepatocarcinogenic effectiveness (NDEA > BP), whereas both carcinogens had similar effects on foci phenotypic properties; (3) after their formation, foci at a given level of phenotypic complexity did not become progressively more complex; (4) incidence levels of foci were sex-dependent (females > males), but growth rates of foci were the same for both sexes; (5) growth rates and growth capacities (ranges of possible growth rates) of foci were directly related to phenotypic complexity levels of foci; (6) frequencies and phenotypic complexities of foci were inversely related; the reverse was true for tumors, although 10% of the tumors were relatively simple (three markers or fewer); (7) marker frequency distribution patterns were completely different in foci and in tumors.

  18. Restorative effect of exogenous RNA on the intestinal crypts in mice after abdominal γ-irradiation

    International Nuclear Information System (INIS)

    Zeng Guiying; Han Shichen; Liu Aiping; Xie Xuejun; Zhou Yuankai

    1995-01-01

    The author's previous investigation revealed a restorative effect of exogenous nucleic acids on the intestinal crypt in mice after abdominal γ-irradiation. In the article, the factors influencing the restorative effect of exogenous RNA on the intestinal crypt in mice post-irradiation were studied. The results showed that: (a) RNAs from different sources all showed the crypt survival enhancement capability. (b) Bell-shaped curves correlating the crypt survival fraction and RNA doses were obtained, with the optimal doses for different routes of administration estimated. (c) Comparing the different routes of RNA administration, the intravenous injection seemed to be the most effective. (d) An exponential relationship between the crypt survival fraction and the post-irradiation time of RNA administration was found. The earlier the administration, the more effective it was. (e) Administration of RNA merely once within 6h after irradiation, the increases of crypt survival fraction was statistically significant when compared with that of the irradiated control

  19. Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention

    Science.gov (United States)

    Liskay, R.Michael

    2014-01-01

    Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a ‘gatekeeper’, loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention. PMID:23996931

  20. Dentigenous infectious foci ? a risk factor of infective endocarditis

    OpenAIRE

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Kr?l, Irena; S?jka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired hear...

  1. Study of metastatic foci by CT in autopsied lung cancer

    International Nuclear Information System (INIS)

    Koga, Mitsuru; Nobe, Yoshifumi; Fujii, Kyoichi.

    1983-01-01

    The authors reexamined all of the image diagnoses made during whole hospitalization in 11 lung cancer cases with autopsy. Of 39 metastatic foci observed at autopsy in the liver, kidney, pancreas, adrenal and brain, 12 had been diagnosed on transverse CT images before death. Three foci were missed at initial readings. The period from CT to autopsy was less than 3 months for 9 of 12 correctly diagnosed foci. For 13 of 27 foci undetected by CT, CT was conducted more than 3 months before death. (Chiba, N)

  2. PMEL EcoFOCI Shelikof Line 8 Data, 1981-open

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Shelikof Line 8 Data

  3. Diurnal variations in proliferation and crypt survival suggest a small target cell population in mouse colon

    International Nuclear Information System (INIS)

    Dobbin, J.; Hamilton, E.

    1986-01-01

    Male C57BLasup(t) mice of two ages, 3-5 months (young) and 14-15 months (old) were given 11 or 15Gy whole body irradiation at different times through the day. The mice were killed after 4.5 days and the number of surviving crypts per circumference of jejunum, ileum, transverse colon and descending colon were scored. These results show crypt survival in the small and large intestine of 15-month-old mice. In the ileum the maximum crypt survival was found at 04.00 h and the minimum at 08.00 h. In the jejunum and both regions of the colon the maximum crypt survival occurred at 16.00 h. The nadir of crypt survival after 15 Gy was at 04.00 h in the jejunum and at 20.00 and 24.00 h in the transverse and descending colon, respectively. In young mice, crypt survival levels were similar to those found in old animals except at 04.00 h. when survival in the jejunum and ileum fell to 0.0004+-0.0002 and 0.0007+-0.0004, respectively. The lowest crypt survival in the colon of young mice also occurred at 04.00 h and in all four tissues the greatest number of crypts survived irradiation at 24.00 h. (author)

  4. Analysis of cryptographic mechanisms used in ransomware CryptXXX v3

    Directory of Open Access Journals (Sweden)

    Michał Glet

    2016-12-01

    Full Text Available The main purpose of this paper was to analysis how malicious software is using cryptographic mechanisms. Reverse engineering were applied in order to discover mechanisms used in ransomware CryptXXX v3. At the end were given some useful advices how to improve CryptXXX.[b]Keyword:[/b] ransomware, software engineering, reverse engineering, RC4, RSA, malicious software

  5. Enhancement of radiation effect on mouse intestinal crypt survival by timing of 5-fluorouracil administration

    International Nuclear Information System (INIS)

    Ho, E.; Coffey, C.; Maruyama, Y.

    1977-01-01

    There is a marked dependence of mouse crypt survival on the sequence of combined drug-radiation treatment and on the time lapse between irradiation and drug administration. When 5-fluorouracil is administered 6 hours after irradiation or later (up to 18 hours postirradiation), crypt survival drops significantly

  6. How dysregulated colonic crypt dynamics cause stem cell overpopulation and initiate colon cancer.

    Science.gov (United States)

    Boman, Bruce M; Fields, Jeremy Z; Cavanaugh, Kenneth L; Guetter, Arthur; Runquist, Olaf A

    2008-05-01

    Based on investigation of the earliest colonic tissue alteration in familial adenomatous polyposis (FAP) patients, we present the hypothesis that initiation of colorectal cancer by adenomatous polyposis coli (APC) mutation is mediated by dysregulation of two cellular mechanisms. One involves differentiation, which normally decreases the proportion (proliferative fraction) of colonic crypt cells that can proliferate; the other is a cell cycle mechanism that simultaneously increases the probability that proliferative cells are in S phase. In normal crypts, stem cells (SC) at the crypt bottom generate rapidly proliferating cells, which undergo differentiation while migrating up the crypt. Our modeling of normal crypts suggests that these transitions are mediated by mechanisms that regulate proliferative fraction and S-phase probability. In FAP crypts, the population of rapidly proliferating cells is shifted upwards, as indicated by the labeling index (LI; i.e., crypt distribution of cells in S phase). Our analysis of FAP indicates that these transitions are delayed because the proliferative fraction and S-phase probability change more slowly as a function of crypt level. This leads to expansion of the proliferative cell population, including a subpopulation that has a low frequency of S-phase cells. We previously reported that crypt SC overpopulation explains the LI shift. Here, we determine that SCs (or cells having high stemness) are proliferative cells with a low probability of being in S phase. Thus, dysregulation of mechanisms that control proliferative fraction and S-phase probability explains how APC mutations induce SC overpopulation at the crypt bottom, shift the rapidly proliferating cell population upwards, and initiate colon tumorigenesis.

  7. Radioprotection of intestinal crypt cells by cox-inhibitors

    International Nuclear Information System (INIS)

    Bisnar, Paul O.; Dones, Rosa Angela S.A.; Serna, Paulene-Ver A.; Deocaris, Chester C.; Guttierez, Kalangitan V.; Deocaris, Custer C.

    2006-01-01

    The regulation of tissue homeostasis in the gastrointestinal epithelium after epithelial injury focuses on the prostaglandins(PGs) as its major mediators. The two cyclooxygenase isoforms, cox-1 and cox-2, catalyze synthesis of PGs. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation, and in adenomas and carcinomas. To study the effects of various commercially-available cox-inhibitors (Ketorolac: cox-1 selective; Celecoxib: cox-2 selective; and Indocid: cox-1/2 non-selective), we determine mouse crypt epithelial cell fate after genotoxic injury with whole-body gamma-ray exposure at 15 Gy. Intestinal tissues of mice treated with cox-2 inhibitors that showed invariable apoptotic event, however, have increased occurrence of regenerating cells. Our results suggest a potential application of cox-2 selective inhibitors as radioprotective agent for normal cells after radiotherapy. (Author)

  8. Stem cell self-renewal in intestinal crypt

    International Nuclear Information System (INIS)

    Simons, Benjamin D.; Clevers, Hans

    2011-01-01

    As a rapidly cycling tissue capable of fast repair and regeneration, the intestinal epithelium has emerged as a favored model system to explore the principles of adult stem cell biology. However, until recently, the identity and characteristics of the stem cell population in both the small intestine and colon has remained the subject of debate. Recent studies based on targeted lineage tracing strategies, combined with the development of an organotypic culture system, have identified the crypt base columnar cell as the intestinal stem cell, and have unveiled the strategy by which the balance between proliferation and differentiation is maintained. These results show that intestinal stem cells operate in a dynamic environment in which frequent and stochastic stem cell loss is compensated by the proliferation of neighboring stem cells. We review the basis of these experimental findings and the insights they offer into the mechanisms of homeostatic stem cell regulation.

  9. FOCIS goes south: advances in translational and clinical immunology.

    Science.gov (United States)

    Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

    2017-09-01

    FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

  10. Radiosensitivity of ileum crypt cells in hibernating, arousing, and awake ground squirrels (Citellus tridecemlineatus)

    International Nuclear Information System (INIS)

    Jaroslow, B.N.; Michael Fry, R.J.; Suhrbier, K.M.; Sallese, A.R.

    1976-01-01

    Radiosensitivity of ileal crypt cells, to 60 Co gamma radiation, was studied in ground squirrels (Citellus tridecemlineatus) during hibernation, arousal, and the euthermic state. Survival of ileal crypt cells, assayed by the microcolony technique from stained transverse sections of ileum, was greater in animals irradiated in hibernation or 1 hr after initiation of arousal from hibernation. Crypt survival returned to the level of irradiated nonhibernating controls in animals irradiated 3 to 7 hr after initiation of arousal. Over the exposure range of 1500 to 2400 R, the survival of crypt cells for euthermic controls gave a D 0 = 133 +- 12 R and for animals irradiated in hibernation it gave a D 0 = 487 +- 92 R. In animals irradiated 1 hr after initiation of arousal, when core temperature is within the range of euthermic controls, crypt survival was almost as high as in the hibernators. These results suggest that the increased resistance of ileal crypt cells in hibernating animals could be due to hypoxia, although not direct evidence for hypoxia in hibernation was established. The changes in mitotic index of ileal crypt cells during hibernation and arousal indicate an alteration in the distribution of cells in the phases of the cycle. This change in distribution may also have contributed to the increased radioresistance of hibernators

  11. Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.

    Directory of Open Access Journals (Sweden)

    Richard C van der Wath

    Full Text Available The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2-3 days in mice (3-5 days in humans and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the 'pedigree' and the 'niche' models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation.

  12. Glucose stimulates intestinal epithelial crypt proliferation by modulating cellular energy metabolism.

    Science.gov (United States)

    Zhou, Weinan; Ramachandran, Deepti; Mansouri, Abdelhak; Dailey, Megan J

    2018-04-01

    The intestinal epithelium plays an essential role in nutrient absorption, hormone release, and barrier function. Maintenance of the epithelium is driven by continuous cell renewal by stem cells located in the intestinal crypts. The amount and type of diet influence this process and result in changes in the size and cellular make-up of the tissue. The mechanism underlying the nutrient-driven changes in proliferation is not known, but may involve a shift in intracellular metabolism that allows for more nutrients to be used to manufacture new cells. We hypothesized that nutrient availability drives changes in cellular energy metabolism of small intestinal epithelial crypts that could contribute to increases in crypt proliferation. We utilized primary small intestinal epithelial crypts from C57BL/6J mice to study (1) the effect of glucose on crypt proliferation and (2) the effect of glucose on crypt metabolism using an extracellular flux analyzer for real-time metabolic measurements. We found that glucose increased both crypt proliferation and glycolysis, and the glycolytic pathway inhibitor 2-deoxy-d-glucose (2-DG) attenuated glucose-induced crypt proliferation. Glucose did not enhance glucose oxidation, but did increase the maximum mitochondrial respiratory capacity, which may contribute to glucose-induced increases in proliferation. Glucose activated Akt/HIF-1α signaling pathway, which might be at least in part responsible for glucose-induced glycolysis and cell proliferation. These results suggest that high glucose availability induces an increase in crypt proliferation by inducing an increase in glycolysis with no change in glucose oxidation. © 2017 Wiley Periodicals, Inc.

  13. Effect of an inhibitor of noradrenaline uptake, desipramine, on cell proliferation in the intestinal crypt epithelium.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1989-01-01

    The intestinal mucosa receives an adrenergic innervation for which there is no commonly accepted function. However, in recent years, cell kinetic studies have raised the possibility that this innervation may be an important regulator of crypt cell proliferation. The effects of noradrenaline released from adrenergic nerves is terminated principally by re-uptake of the amine into the nerve and this process can be inhibited by the antidepressant drug, desipramine. In this report desipramine is shown to accelerate crypt cell proliferation in intact, but not in chemically sympathectomized rats, thus adding support to the notion that regulation of crypt cell division is an important function of the sympathetic nervous system.

  14. Fluorescent foci quantitation for high-throughput analysis

    Directory of Open Access Journals (Sweden)

    Elena Ledesma-Fernández

    2015-06-01

    Full Text Available A number of cellular proteins localize to discrete foci within cells, for example DNA repair proteins, microtubule organizing centers, P bodies or kinetochores. It is often possible to measure the fluorescence emission from tagged proteins within these foci as a surrogate for the concentration of that specific protein. We wished to develop tools that would allow quantitation of fluorescence foci intensities in high-throughput studies. As proof of principle we have examined the kinetochore, a large multi-subunit complex that is critical for the accurate segregation of chromosomes during cell division. Kinetochore perturbations lead to aneuploidy, which is a hallmark of cancer cells. Hence, understanding kinetochore homeostasis and regulation are important for a global understanding of cell division and genome integrity. The 16 budding yeast kinetochores colocalize within the nucleus to form a single focus. Here we have created a set of freely-available tools to allow high-throughput quantitation of kinetochore foci fluorescence. We use this ‘FociQuant’ tool to compare methods of kinetochore quantitation and we show proof of principle that FociQuant can be used to identify changes in kinetochore protein levels in a mutant that affects kinetochore function. This analysis can be applied to any protein that forms discrete foci in cells.

  15. Dentigenous infectious foci - a risk factor of infective endocarditis.

    Science.gov (United States)

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Krol, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-02-01

    Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis.

  16. Quality of life in childhood epilepsy with lateralized epileptogenic foci.

    Science.gov (United States)

    Mathiak, Krystyna A; Luba, Małgorzata; Mathiak, Klaus; Karzel, Katarzyna; Wolańczyk, Tomasz; Szczepanik, Elzbieta; Ostaszewski, Paweł

    2010-08-17

    Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations. We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life. We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.

  17. Dentigenous infectious foci – a risk factor of infective endocarditis

    Science.gov (United States)

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Król, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Results Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Conclusions Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID:22293883

  18. Crypt cell population kinetics in mouse jejunum under continuous beta irradiation from tritiated water

    International Nuclear Information System (INIS)

    Bhatia, A.L.; Gupta, M.L.; Saharan, B.R.

    1979-01-01

    The behaviour of crypt cell population in mouse jejunum under continuous beta irradiation from tritiated water (HTO) has been studied. Adult mice were maintained on tritiated drinking water of the activity of 1.25 μCi/ml, after priming injection. The crypts were studied at 1, 5, 7, 15 and 30 days after the initiation of treatment. It is observed that there is a partial recovery in proliferative activity after the first day of the treatment. Again there is a decrease in the crypt cells on the 7th day, after which this population appears to achieve a near-steady-state level at about 8% below normal at the last interval studied. Crypt cell population and mitotic figures showed a simultaneous dip and recovery, while dead cells showed inverse relationship. (orig.) [de

  19. Radioprotective effect of dextran sulphate and aerogenic hypoxia on intestinal crypt stem cells in mice

    International Nuclear Information System (INIS)

    Vacek, A.; Bartonickova, A.; Rotkovska, D.; Konoplyanikova, O.A.; Konoplyanikov, A.G.

    1991-01-01

    A single intraperitoneal injection of dextran sulfate given 6 h before irradiation produced higher numbers of microcolonies of intestinal crypt stem cells in whole-body irradiated mice than an injection of saline in control mice. If dextran sulfate and hypoxia are combined, the radioprotective effect of hypoxia on intestinal crypt stem cells depends on the time interval between irradiation and administration of dextran sulfate. (author). 2 figs., 12 refs

  20. Quality of life in childhood epilepsy with lateralized epileptogenic foci

    OpenAIRE

    Mathiak Krystyna A; Łuba Małgorzata; Mathiak Klaus; Karzel Katarzyna; Wolańczyk Tomasz; Szczepanik Elżbieta; Ostaszewski Paweł

    2010-01-01

    Abstract Background Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. ...

  1. Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

    Directory of Open Access Journals (Sweden)

    Ann-Marie Baker

    2014-08-01

    Full Text Available Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+. Furthermore, we show that, in adenomatous crypts (APC−/−, there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.

  2. Computational models reveal a passive mechanism for cell migration in the crypt.

    Directory of Open Access Journals (Sweden)

    Sara-Jane Dunn

    Full Text Available Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.

  3. Quality of life in childhood epilepsy with lateralized epileptogenic foci

    Directory of Open Access Journals (Sweden)

    Mathiak Krystyna A

    2010-08-01

    Full Text Available Abstract Background Measuring quality of life (QOL helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Methods Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE. Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG examinations. Results We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p Conclusions We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.

  4. Increased induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats fed diets containing purified genistein of genistein-rich soya protein

    NARCIS (Netherlands)

    Gee, J.M.; Noteborn, H.P.J.M.; Polley, A.C.J.; Johnson, I.T.

    2000-01-01

    The isoflavonoid genistein inhibits mitosis and increases apoptosis in a variety of tumour cell lines in vitro, and may exert anticarcinogenic effects in vivo. To assess its effects on the colon, rats were fed a semi-synthetic control diet, or similar diets enriched with genistein (0.25 g/kg),

  5. Effect of diets fortified with tomatoes or onions with variable quercetin-glycoside content on azoxymethane-induced aberrant crypt foci in the colon of rats

    NARCIS (Netherlands)

    Femia, A.P.; Caderni, G.; Ianni, M.; Salvadori, M.; Schijlen, E.G.W.M.; Collins, G.; Bovy, A.G.; Dolara, P.

    2003-01-01

    Background: Onion and tomato are vegetables widely consumed by humans and epidemiological studies show an inverse association between vegetable consumption and colon cancer risk; however, the effect on colon cancer of diets containing high levels of vegetables like onion and tomato are not clear.

  6. Different effects of short- and long-chained fructans on large intestinal physiology and carcinogen-induced aberrant crypt foci in rats

    DEFF Research Database (Denmark)

    Poulsen, Morten; Molck, Anne-Marie; Jacobsen, Bodil Lund

    2002-01-01

    Inulin-type fructans, which are nondigestible carbohydrates, have been shown to modulate the number of induced preneoplastic lesions in the colon as well as the colonic microflora in laboratory animals. The present study was designed to investigate the effect of a short- and long-chained inulin...

  7. Block-Centric Visualization Of Histological Whole Slide Images With Application To Revealing Growth-Patterns Of Early Colorectal Adenomas And Aberrant Crypt Foci

    Directory of Open Access Journals (Sweden)

    Norman Zerbe

    2016-06-01

    The presented methods provide an efficient means to retrieve correspondences and additional spatial information from serial sections of histological slides. They also show good applicability for specimen from different origin. Alignment methods can be applied to generate block-centric visualizations such as parallel and transparent viewing of multiple stains. Moreover, the generated stack videos and 3D models demonstrate the very good accuracy of section alignment even in large series. The visualizations enable pathologists and researchers to grasp the 3D structural relationships in the tissue at a glance, providing an excellent tool to communicate more complex histomorphological findings. Interestingly, we see two kinds of tubular adenomas, which could imply multiple ways to tubular adenoma formation in FAP-patients, possibly akin to the recent observations in mice [3].

  8. DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

    Science.gov (United States)

    Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

    2018-06-08

    Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

  9. Multi-scale modeling of APC and [Formula: see text]-catenin regulation in the human colonic crypt.

    Science.gov (United States)

    Emerick, Brooks; Schleiniger, Gilberto; Boman, Bruce M

    2018-06-01

    Stem cell renewal and differentiation in the human colonic crypt are linked to the [Formula: see text]-catenin pathway. The spatial balance of Wnt factors in proliferative cells within the crypt maintain an appropriate level of cellular reproduction needed for normal crypt homeostasis. Mutational events at the gene level are responsible for deregulating the balance of Wnt factors along the crypt, causing an overpopulation of proliferative cells, a loss of structure of the crypt domain, and the initiation of colorectal carcinomas. We formulate a PDE model describing cell movement and reproduction in a static crypt domain. We consider a single cell population whose proliferative capabilities are determined by stemness, a quantity defined by intracellular levels of adenomatous polyposis coli (APC) scaffold protein and [Formula: see text]-catenin. We fit APC regulation parameters to biological data that describe normal protein gradients in the crypt. We also fit cell movement and protein flux parameters to normal crypt characteristics such as renewal time, total cell count, and proportion of proliferating cells. The model is used to investigate abnormal crypt dynamics when subjected to a diminished APC gradient, a scenario synonymous to mutations in the APC gene. We find that a 25% decrease in APC synthesis leads to a fraction of 0.88 proliferative, which is reflective of normal-appearing FAP crypts. A 50% drop in APC activity yields a fully proliferative crypt showing a doubling of the level of stemness, which characterizes the initial stages of colorectal cancer development. A sensitivity analysis of APC regulation parameters shows the perturbation of factors that is required to restore crypt dynamics to normal in the case of APC mutations.

  10. Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance.

    Science.gov (United States)

    Zhou, Xin; Ma, Xiaofei; Wang, Zhenhua; Sun, Chao; Wang, Yupei; He, Yang; Zhang, Hong

    2015-12-15

    Radiation-induced hyperproliferation of intestinal crypts is well documented, but its potential tumorigenic effects remain elusive. Here we aim to determine the genomic surveillance process during crypt hyperproliferation, and its consequential outcome after ionizing radiation. Crypt regeneration in the intestine was induced by a single dose of 12Gy abdominal irradiation. γ-H2AX, 53BP1 and DNA-PKcs were used as DNA repair surrogates to investigate the inherent ability of intestinal crypt cells to recognize and repair double-strand breaks. Ki67 staining and the 5-bromo-2'-deoxyuridine incorporation assay were used to study patterns of cell proliferation in regenerating crypts. Staining for ATM, p53, Chk1 and Chk2 was performed to study checkpoint activation and release. Apoptosis was evaluated through H&E staining and terminal deoxynucleotidyl transferase (dUTP) nick-end labeling. The ATM-p53 pathway was immediately activated after irradiation. A second wave of DSBs in crypt cells was observed in regenerating crypts, accompanied with significantly increased chromosomal bridges. The p53-related genomic surveillance pathway was not active during the regeneration phase despite DSBs and chromosomal bridges in the cells of regenerating crypts. Non-homologous end joining (NHEJ) DSBs repair was involved in the DSBs repair process, as indicated by p-DNA-PKcs staining. Intestinal crypt cells retained hyperproliferation with inactive p53-related genomic surveillance system. NHEJ was involved in the resultant genomic instability during hyperproliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance

    Directory of Open Access Journals (Sweden)

    Tomoaki Naito

    2017-10-01

    Full Text Available We identified a crypt-specific core microbiota (CSCM dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas. Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS, through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage.

  12. Lack of correlation between villus and crypt damage in irradiated mouse intestine

    International Nuclear Information System (INIS)

    Carr, K.E.; Hamlet, R.; Nias, A.H.W.; Watt, C.

    1979-01-01

    It has been observed that scanning electron microscopy is a more sensitive indicator of mucosal damage at low radiation dose levels than conventional quantitative crypt counting techniques. Three different fractionation schedules were subjected to investigation by both of these methods to try and elucidate some features of irradiation damage to the whole of the intestinal mucosa, at dose levels commonly used in clinical practice. Despite variations in the qualitative observations, there was a marked difference in two of the schedules between damage expressed as crypt counts and that described by the qualitative techniques. In the first case high crypt numbers were associated with severe mucosal damage, whereas the second schedule produced a reduced crypt count in association with low damage to the surface mucosa. A third schedule produced results in which there was a general agreement between low crypt numbers and considerable surface mucosal damage. However, observations were made of mucosal formations not previously seen on damaged mucosa; surfaces. These resembled the appearance normally associated with the gut of patients suffering from coeliac disease. Variations in the qualitative observations were seen in the schedules so that their interpretation in terms of perturbation of cellular kinetics is difficult. (author)

  13. The re-establishment of hypersensitive cells in the crypts of irradiated mouse intestine

    International Nuclear Information System (INIS)

    Ijiri, K.; Potten, C.S.

    1984-01-01

    Two doses of γ-radiation separated by various time intervals have been used to investigate when after irradiation the cell population susceptible to acute cell death is re-established. Dead cells were scored 3 or 6 h after the second dose. Within 1-2 days of small doses (0.5 Gy) the sensitive cells, recognized histologically as apoptotic cells, are re-established at the base of the crypt (around cell position 6). After higher doses (9.0 Gy) they are not re-established until about the fourth day after irradiation. Even in the enlarged regenerating crypts the sensitive cells are found at the same position at the crypt base. It has been estimated that the crypt contains five or six cells that are susceptible to low doses (0.5 Gy) (hypersensitive cells) and up to a total of only seven or eight susceptible cells that can be induced by any dose to enter the sequence of changes implicit in apoptosis. Between 4 and 10 days after an intitial irradiation of 9.0 Gy the total number of susceptible cells increased from seven to eight to about 10 to 13 per crypt. (author)

  14. Understanding the Persistence of Plague Foci in Madagascar

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-01-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar. PMID:24244760

  15. Molecular mechanisms in DM1 - a focus on foci

    DEFF Research Database (Denmark)

    Pettersson, Olof Joakim; Aagaard, Lars; Jensen, Thomas G.

    2015-01-01

    -expanded RNA remains in the nuclear compartment, while in dividing cells such as fibroblasts a considerable fraction of the mutant RNA reaches the cytoplasm, consistent with findings that both nuclear and cytoplasmic events are mis-regulated in DM1. Recent evidence suggests that the nuclear aggregates......, or ribonuclear foci, are more dynamic than previously anticipated and regulated by several proteins, including RNA helicases. In this review, we focus on the homeostasis of DMPK mRNA foci and discuss how their dynamic regulation may affect disease-causing mechanisms in DM1...

  16. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

    Science.gov (United States)

    Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

    2015-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl− and HCO3− efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3−)-loading proteins and upregulation of the basolateral membrane HCO3−-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl−/HCO3− exchange with maximized gradients, it also had increased intracellular Cl− concentration relative to wild-type. Pharmacological reduction of intracellular Cl− concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl− and HCO3− efflux, which impairs pHi regulation by Ae2. Retention of Cl− and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

  17. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    Science.gov (United States)

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. Copyright © 2016 the American Physiological Society.

  18. Characterization of Aes nuclear foci in colorectal cancer cells

    Science.gov (United States)

    Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, M. Mark

    2016-01-01

    Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling. PMID:26229111

  19. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    International Nuclear Information System (INIS)

    Horita, Nobukatsu; Tsuchiya, Kiichiro; Hayashi, Ryohei; Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro; Okamoto, Ryuichi; Nakamura, Tetsuya; Watanabe, Mamoru

    2014-01-01

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus

  20. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    Energy Technology Data Exchange (ETDEWEB)

    Horita, Nobukatsu [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Tsuchiya, Kiichiro, E-mail: kii.gast@tmd.ac.jp [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Hayashi, Ryohei [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Department of Gastroenterology and Metabolism, Hiroshima University (Japan); Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Okamoto, Ryuichi; Nakamura, Tetsuya [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan)

    2014-11-28

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus.

  1. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon.

    Science.gov (United States)

    Bettini, Sarah; Boutet-Robinet, Elisa; Cartier, Christel; Coméra, Christine; Gaultier, Eric; Dupuy, Jacques; Naud, Nathalie; Taché, Sylviane; Grysan, Patrick; Reguer, Solenn; Thieriet, Nathalie; Réfrégiers, Matthieu; Thiaudière, Dominique; Cravedi, Jean-Pierre; Carrière, Marie; Audinot, Jean-Nicolas; Pierre, Fabrice H; Guzylack-Piriou, Laurence; Houdeau, Eric

    2017-01-20

    Food-grade titanium dioxide (TiO 2 ) containing a nanoscale particle fraction (TiO 2 -NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO 2 -NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO 2 -NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO 2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO 2 -treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO 2 from dietary sources.

  2. The proliferative response of mouse intestinal crypts during fractionated irradiation of carbon beams

    International Nuclear Information System (INIS)

    Abo, M.; Abe, Y.; Mariya, Y.; Ando, K.

    2000-01-01

    Clonogenic assay of jejunal crypt during carbon beam and X-ray irradiations was performed. Fractionation with top-up dose assay revealed carbon beam irradiations caused more damage than X-ray did. To clarify this problem is urgent. (author)

  3. Quantification of crypt and stem cell evolution in the normal and neoplastic human colon

    NARCIS (Netherlands)

    Baker, Ann-Marie; Cereser, Biancastella; Melton, Samuel; Fletcher, Alexander G.; Rodriguez-Justo, Manuel; Tadrous, Paul J.; Humphries, Adam; Elia, George; McDonald, Stuart A. C.; Wright, Nicholas A.; Simons, Benjamin D.; Jansen, Marnix; Graham, Trevor A.

    2014-01-01

    Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls

  4. Crypt base columnar stem cells in small intestines of mice are radioresistant

    NARCIS (Netherlands)

    Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

    2012-01-01

    BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that

  5. The Carcinogenic Agent Azoxymethane (AOM) Enhances Early Inflammation-induced Colon Crypt Pathology

    DEFF Research Database (Denmark)

    Venning, Freja Albjerg; Claesson, Mogens Helweg; Kissow, Hannelouise

    2013-01-01

    Severe combined immunodeficiency (SCID) mice transplanted with CD4+ T cells depleted of CD25+ regulatory T cells develop colitis within 2-3 weeks after the T cell transfer. In the present study we studied the effect of the carcinogen azoxymethane (AOM) on the colon crypt pathology of normal SCID...

  6. Cracking ShadowCrypt: Exploring the Limitations of Secure I/O Systems in Internet Browsers

    Directory of Open Access Journals (Sweden)

    Freyberger Michael

    2018-04-01

    Full Text Available An important line of privacy research is investigating the design of systems for secure input and output (I/O within Internet browsers. These systems would allow for users’ information to be encrypted and decrypted by the browser, and the specific web applications will only have access to the users’ information in encrypted form. The state-of-the-art approach for a secure I/O system within Internet browsers is a system called ShadowCrypt created by UC Berkeley researchers [23]. This paper will explore the limitations of ShadowCrypt in order to provide a foundation for the general principles that must be followed when designing a secure I/O system within Internet browsers. First, we developed a comprehensive UI attack that cannot be mitigated with popular UI defenses, and tested the efficacy of the attack through a user study administered on Amazon Mechanical Turk. Only 1 of the 59 participants who were under attack successfully noticed the UI attack, which validates the stealthiness of the attack. Second, we present multiple attack vectors against Shadow-Crypt that do not rely upon UI deception. These attack vectors expose the privacy weaknesses of Shadow DOM—the key browser primitive leveraged by ShadowCrypt. Finally, we present a sketch of potential countermeasures that can enable the design of future secure I/O systems within Internet browsers.

  7. Colon stem cell and crypt dynamics exposed by cell lineage reconstruction.

    Directory of Open Access Journals (Sweden)

    Yitzhak Reizel

    2011-07-01

    Full Text Available Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.

  8. Day-to-day variability of the latitudes of the Sq foci

    International Nuclear Information System (INIS)

    Schlapp, D.M.

    1976-01-01

    Day-to-day changes in the latitudes of the Sq foci have been studied for several longitudes and at both sunspot maximum and minimum. A small but significant correlation has been found indicating a tendency for the foci to move poleward or equatorward together. There is little correlation between the strength of the electrojet and the separation of the foci; if anything, the electrojet is weaker when the foci are closer together. (author)

  9. [The results of serological studies in different foci of tropical and tertiary malaria].

    Science.gov (United States)

    Suleĭmanov, G D; Doan, Kh N; Le, T T; Chan, B; Chan, T U

    1991-01-01

    Attempt was made to determine the value of serologic indices of malaria surveys. Following uniformed methodological and technical approaches 3 foci of P. vivax and 6 foci of P. falciparum malaria were surveyed in different endemic zones of Vietnam and the USSR. It was shown that the most objective criteria for a foci classification is its serologic mean geometric titre. The latter in its turn directly depends of transmission longevity in a foci.

  10. Identifying aggressive prostate cancer foci using a DNA methylation classifier.

    Science.gov (United States)

    Mundbjerg, Kamilla; Chopra, Sameer; Alemozaffar, Mehrdad; Duymich, Christopher; Lakshminarasimhan, Ranjani; Nichols, Peter W; Aron, Manju; Siegmund, Kimberly D; Ukimura, Osamu; Aron, Monish; Stern, Mariana; Gill, Parkash; Carpten, John D; Ørntoft, Torben F; Sørensen, Karina D; Weisenberger, Daniel J; Jones, Peter A; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning

    2017-01-12

    Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Here, we have taken advantage of the multifocal propensity of PC and categorized aggressiveness of individual PC foci based on DNA methylation patterns in primary PC foci and matched lymph node metastases. In a set of 14 patients, we demonstrate that over half of the cases have multiple epigenetically distinct subclones and determine the primary subclone from which the metastatic lesion(s) originated. Furthermore, we develop an aggressiveness classifier consisting of 25 DNA methylation probes to determine aggressive and non-aggressive subclones. Upon validation of the classifier in an independent cohort, the predicted aggressive tumors are significantly associated with the presence of lymph node metastases and invasive tumor stages. Overall, this study provides molecular-based support for determining PC aggressiveness with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to focal therapy.

  11. A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt

    KAUST Repository

    Mirams, Gary R.

    2012-11-01

    The surface epithelium lining the intestinal tract renews itself rapidly by a coordinated programme of cell proliferation, migration and differentiation events that is initiated in the crypts of Lieberkühn. It is generally believed that colorectal cancer arises due to mutations that disrupt the normal cellular dynamics of the crypts. Using a spatially structured cell-based model of a colonic crypt, we investigate the likelihood that the progeny of a mutated cell will dominate, or be sloughed out of, a crypt. Our approach is to perform multiple simulations, varying the spatial location of the initial mutation, and the proliferative and adhesive properties of the mutant cells, to obtain statistical distributions for the probability of their domination. Our simulations lead us to make a number of predictions. The process of monoclonal conversion always occurs, and does not require that the cell which initially gave rise to the population remains in the crypt. Mutations occurring more than one to two cells from the base of the crypt are unlikely to become the dominant clone. The probability of a mutant clone persisting in the crypt is sensitive to dysregulation of adhesion. By comparing simulation results with those from a simple one-dimensional stochastic model of population dynamics at the base of the crypt, we infer that this sensitivity is due to direct competition between wild-type and mutant cells at the base of the crypt. We also predict that increases in the extent of the spatial domain in which the mutant cells proliferate can give rise to counter-intuitive, non-linear changes to the probability of their fixation, due to effects that cannot be captured in simpler models. © 2012 Elsevier Ltd.

  12. The Development of M Cells in Peyer’s Patches Is Restricted to Specialized Dome-Associated Crypts

    Science.gov (United States)

    Gebert, Andreas; Fassbender, Susanne; Werner, Kerstin; Weissferdt, Annikka

    1999-01-01

    It is controversial whether the membranous (M) cells of the Peyer’s patches represent a separate cell line or develop from enterocytes under the influence of lymphocytes on the domes. To answer this question, the crypts that produce the dome epithelial cells were studied and the distribution of M cells over the domes was determined in mice. The Ulex europaeus agglutinin was used to detect M cells in mouse Peyer’s patches. Confocal microscopy with lectin-gold labeling on ultrathin sections, scanning electron microscopy, and laminin immuno-histochemistry were combined to characterize the cellular composition and the structure of the dome-associated crypts and the dome epithelium. In addition, the sites of lymphocyte invasion into the dome epithelium were studied after removal of the epithelium using scanning electron microscopy. The domes of Peyer’s patches were supplied with epithelial cells that derived from two types of crypt: specialized dome-associated crypts and ordinary crypts differing not only in shape, size, and cellular composition but also in the presence of M cell precursors. When epithelial cells derived from ordinary crypts entered the domes, they formed converging radial strips devoid of M cells. In contrast to the M cells, the sites where lymphocytes invaded the dome epithelium were not arranged in radial strips, but randomly distributed over the domes. M cell development is restricted to specialized dome-associated crypts. Only dome epithelial cells that derive from these specialized crypts differentiate into M cells. It is concluded that M cells represent a separate cell line that is induced in the dome-associated crypts by still unknown, probably diffusible lymphoid factors. PMID:10329609

  13. A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt

    KAUST Repository

    Mirams, Gary R.; Fletcher, Alexander G.; Maini, Philip K.; Byrne, Helen M.

    2012-01-01

    The surface epithelium lining the intestinal tract renews itself rapidly by a coordinated programme of cell proliferation, migration and differentiation events that is initiated in the crypts of Lieberkühn. It is generally believed that colorectal

  14. Meat and cancer: haemoglobin and haemin in a low-calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats

    Science.gov (United States)

    Pierre, Fabrice; Taché, Sylviane; Petit, Claude R; Van Der Meer, Roelof; Corpet, Denis E

    2003-01-01

    High intake of red meat, but not of white meat, is associated with an increased risk of colon cancer. However, red meat does not promote cancer in rodents. Haemin, added to low-calcium diets, increases colonic proliferation, and haemoglobin, added to high-fat diets, increases the colon tumour incidence in rats, an effect possibly due to peroxyl radicals. We thus speculated that haem might be the promoting agent in meat, and that prevention strategies could use calcium and antioxidants. These hypotheses were tested in rats at the aberrant crypt foci (ACF) stage at 100 days. F344 rats (n=124) were given an injection of azoxymethane and were then randomised to 11 groups fed with low-calcium (20μmol/g) AIN76-based diets, containing 5% safflower oil. Haemin (0.25, 0.5 and 1.5μmol/g) or haemoglobin (1.5 and 3 μmol haem/g) was added to five experimental diets, compared to a control diet without haem. Three other high-haemin diets (1.5μmol/g) were supplemented with calcium (250μmol/g), antioxidant butylated hydroxyanisole and rutin (0.05% each), and olive oil, which replaced safflower oil. Faecal water was assayed for lipid peroxidation by thiobarbituric acid reactive substances (TBARs) test, and for cytolytic activity. Haemin strikingly increased the ACF size, dose-dependently, from 2.6 to 11.4 crypts/ACF (all p<0.001). The high-haemin diet also increased the number of ACF per colon (p<0.001). Promotion was associated with increased faecal water TBARs and cytotoxicity. Calcium, olive oil, and antioxidants each inhibited the haemin-induced ACF promotion, and normalised the faecal TBARs and cytotoxicity. The haemoglobin diets increased the number of ACF and faecal TBARs, but not the ACF size or the faecal cytotoxicity. In conclusion, dietary haemin is the most potent known ACF promoter. Haemoglobin is also a potent promoter of colorectal carcinogenesis. The results suggest that myoglobin in red meat could promote colon cancer. Diets high in calcium, or in oxidation

  15. Radioprotection of the intestinal crypts of mice by recombinant human interleukin-1 alpha

    International Nuclear Information System (INIS)

    Wu, S.G.; Miyamoto, T.

    1990-01-01

    Recombinant human interleukin-1 alpha (rHIL-1 alpha or IL-1) protected the intestinal crypt cells of mice against X-ray-induced damage. The survival of crypt cells measured in terms of their ability to form colonies of regenerating duodenal epithelium in situ was increased when IL-1 was given either before or after irradiation. The maximum degree of radioprotection was seen when the drug was given between 13 and 25 h before irradiation. The IL-1 dose producing maximum protection was about 6.3 micrograms/kg. This is the first report indicating that the cytokine IL-1 has a radioprotective effect in the intestine. The finding suggests that IL-1 may be of potential value in preventing radiation injury to the gut in the clinic

  16. The Effect of Combination of Radiation with 5-Fluorouracil on Mouse Jejunal Crypt Cells

    International Nuclear Information System (INIS)

    Huh, Seung Jae; Park, Charn Il

    1985-01-01

    The interaction of radiation and 5-Fluorouracil (5-FU) on mouse jejunal crypt cells was studied using the microcolony survival assay. 150mg/kg of 5-FU was injected intraperitoneally 15 minutes before irradiation and 6 hours after irradiation. Jejunal crypt cells of mouse survived more when 5-FU was given 15 minutes before irradiation than giving it 6 hours after irradiation. The mean lethal doses (Do) of each of irradiation alone group, 5-FU injection group of 15 minutes preceding irradiation, and 5-FU injection group of 6 hours post irradiation were 135, 135, and 114 rad respectively. The dose effect factor (DEF) of each of 5-FU injection groups of 15 minutes preceding irradiation and of 6 hours post irradiation were 1.13 and 1.27

  17. The effect of melatonin on mouse jejunal crypt cell survival and apoptosis

    International Nuclear Information System (INIS)

    Kang, Jin Oh; Ha, Eun Young; Baik, Hyung Hwan; Cho, Yong Ho; Hong, Seong Eon

    2000-01-01

    To evaluate protective mechanism of melatonin against radiation damage and its relationship with apoptosis in mouse jejunum. 168 mice were divided into 28 groups according to radiation dose and melatonin treatment. To analysis crypt survival, microcolony survival assay was done according to Withers and Elkind's method. To analysis apoptosis, TUNEL assay was done according to Labet-Moleur's method. Radiation protection effect of melatonin was demonstrated by crypt survival assay and its effect was stronger in high radiation dose area. Apoptosis index with 8 Gy irradiation was 18.4% in control group and 16.5% in melatonin treated group. After 18 Gy, apoptosis index was 17.2%in control group and 15.4% in melatonin treated group. Apoptosis index did not show statistically significant difference between melatonin shows clear protective effect in mouse jejunum against radiation damage but its protective effect seems not to be related with apoptosis protection effect

  18. Modifications of S-phase cell distribution in the intestinal crypts after multiple daily fractionation

    Energy Technology Data Exchange (ETDEWEB)

    Becciolini, A; Cremonini, D; Fabbrica, D; Balzi, M [Florence Univ. (Italy). Ist. di Radiologia

    1983-01-01

    The effects obtained by multiple daily fractionation (3 Gy x2 or 3 Gy x2x2) on the distribution of S-phase cells along the crypt of the small intestine were investigated. The frequency of labelled cell distribution was reduced at early intervals; then the proliferating compartment gradually extended to the villus junctions. During recovery labelled cell frequency in the lower half of the crypts returned to control levels, while labelled cells were present in the differentiating area. With lower total dose modifications were milder and, as early as 72 h before exposure, distribution was already similar to controls. Invertase activity showed an initial increase and a higher reduction during acute damage when fractionation with higher doses was used. A lack of return to normal activity was present even 11 days after exposure when, however, the characteristic circadian pattern was observed.

  19. Cdx2 modulates proliferation in normal human intestinal epithelial crypt cells

    International Nuclear Information System (INIS)

    Escaffit, Fabrice; Pare, Frederic; Gauthier, Remy; Rivard, Nathalie; Boudreau, Francois; Beaulieu, Jean-Francois

    2006-01-01

    The homeobox gene Cdx2 is involved in the regulation of the expression of intestine specific markers such as sucrase-isomaltase and lactase-phlorizin hydrolase. Previous studies performed with immortalized or transformed intestinal cell lines have provided evidence that Cdx2 can promote morphological and functional differentiation in these experimental models. However, no data exist concerning the implication of this factor in normal human intestinal cell physiology. In the present work, we have investigated the role of Cdx2 in normal human intestinal epithelial crypt (HIEC) cells that lack this transcription factor. The establishment of HIEC cells expressing Cdx2 in an inducible manner shows that forced expression of Cdx2 significantly alters the proliferation of intestinal crypt cells and stimulates dipeptidylpeptidase IV expression but is not sufficient to trigger intestinal terminal differentiation. These observations suggest that Cdx2 requires additional factors to activate the enterocyte differentiation program in normal undifferentiated cells

  20. Neutral dynamics and cell renewal of colonic crypts in homeostatic regime

    Science.gov (United States)

    Fendrik, A. J.; Romanelli, L.; Rotondo, E.

    2018-05-01

    The self renewal process in colonic crypts is the object of several studies. We present here a new compartment model with the following characteristics: (a) we distinguish different classes of cells: stem cells, six generations of transit amplifying cells and the differentiated cells; (b) in order to take into account the monoclonal character of crypts in homeostatic regimes we include symmetric divisions of the stem cells. We first consider the dynamic differential equations that describe the evolution of the mean values of the populations, but the small observed value of the total number of cells involved plus the huge dispersion of experimental data found in the literature leads us to study the stochastic discrete process. This analysis allows us to study fluctuations, the neutral drift that leads to monoclonality, and the effects of the fixation of mutant clones.

  1. Single-dose-response curves of murine gastrointestinal crypt stem cells

    International Nuclear Information System (INIS)

    Masuda, K.; Withers, H.R.; Mason, K.A.; Chen, K.Y.

    1977-01-01

    Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant

  2. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis

    DEFF Research Database (Denmark)

    Jensen, Anders; Fagö-Olsen, Helena; Sørensen, Christian Hjort

    2013-01-01

    and included species that are considered putative pathogens in periodontal diseases, i.e. Porphyromonas gingivalis, Porphyromonas endodontalis, and Tannerella forsythia. Unifrac analysis showed that recurrent tonsillitis is associated with a shift in the microbiota of the tonsillar crypts. Fusobacterium...... were almost exclusively detected in children. In contrast, Streptococcus pseudopneumoniae was present in all samples. Obligate anaerobes like Porphyromonas, Prevotella, and Fusobacterium were abundantly present in children, but the species diversity of Porphyromonas and Prevotella was larger in adults...

  3. Effects of cytotoxic chemotherapeutic agents on split-dose repair in intestinal crypt cells

    International Nuclear Information System (INIS)

    Phillips, Theodore L.; Ross, Glenda Y.

    1997-01-01

    Purpose: Many cancer chemotherapeutic agents interact with radiation to enhance the amount of radiation damage observed in both tumor and normal tissues. It is important to predict this interaction and to determine the effect of drug on sublethal damage repair. To evaluate for effects in rapid renewing normal tissues, the intestinal crypt cell in vivo assay is an excellent one to employ. These studies investigate the effect of eleven cancer chemotherapeutic drugs on split-dose repair in the intestinal crypt cell of the mouse. Methods and Materials: LAF1 male mice, age 10-12 weeks, were exposed to whole-body irradiation with orthovoltage x-rays delivered as a single dose or as equally divided doses delivered with intervals between the two exposures of 2 to 24 h. In the experimental group, the cancer chemotherapeutic agent was administered intraperitoneally 2 h before the first radiation dose. At 3.6 days after the second irradiation, the mice were sacrificed; the jejunum was removed, fixed, and sectioned for light microscopy. The number of regenerating crypts were counted and corrected to represent the number of surviving cells per circumference. Results: Of the eleven drugs tested, only carmustine eliminated split-dose repair. Cisplatin delayed repair, and methotrexate caused marked synchronization obliterating the observation of split-dose repair. Conclusions: Most cytotoxic chemotherapeutic agents do not inhibit sublethal damage repair in intestinal crypt cells when given 2 h before the first radiation exposure. Absence of the initial increase in survival seen with split-dose radiation is noted with carmustine and high-dose methotrexate

  4. AtTZF gene family localizes to cytoplasmic foci

    OpenAIRE

    Pomeranz, Marcelo; Lin, Pei-Chi; Finer, John; Jang, Jyan-Chyun

    2010-01-01

    In eukaryotes, mRNA turnover and translational repression represent important regulatory steps in gene expression. Curiously, when under cellular stresses, factors involved in these processes aggregate into cytoplasmic foci known as Processing bodies (P-bodies) and Stress Granules (SGs). In animals, CCCH Tandem Zinc Finger (TZF) proteins play important roles in mRNA decay within P-bodies. TTP, a P-body localized mammalian TZF, can bind to the 3'UTRs of mRNAs containing AU-rich elements (AREs)...

  5. Integrated prospecting in the crypt of the Basilica of Saint Nicholas in Bari, Italy

    International Nuclear Information System (INIS)

    Calia, Angela; Leucci, Giovanni; Masini, Nicola; Matera, Loredana; Persico, Raffaele; Sileo, Maria

    2012-01-01

    In this paper, we present the results of non-destructive integrated geophysical surveys (ground penetrating radar (GPR) and seismic sonic) performed in the crypt of the Basilica of St Nicholas in Bari, Italy. The aim was twofold, namely to investigate the consistency of restoration work performed in 1950 and the presence of features of archaeological interest. The GPR technique has also been exploited to characterize the subsurface water content under the crypt. In particular, the existence of buried anomalies, probably due to the restoration work, has been identified. Moreover, by means of an electromagnetic-wave velocity analysis, an estimation of the volumetric water content under the floor has been achieved. The results indicate the main causes of the deterioration and have provided significant information for the safeguard of this historical building. Furthermore, the GPR survey allowed us to identify some anomalies buried under the crypt that are probably of archaeological interest. Finally, both sonic tomography and a GPR survey have been performed on an important mosaic, and have enabled us to identify probable ‘internal’ reasons for its decay. (paper)

  6. Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

    Science.gov (United States)

    Kennedy, M F; Tutton, P J; Barkla, D H

    1985-09-01

    Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.

  7. Analysis of ionizing radiation-induced foci of DNA damage repair proteins

    International Nuclear Information System (INIS)

    Veelen, Lieneke R. van; Cervelli, Tiziana; Rakt, Mandy W.M.M. van de; Theil, Arjan F.; Essers, Jeroen; Kanaar, Roland

    2005-01-01

    Repair of DNA double-strand breaks by homologous recombination requires an extensive set of proteins. Among these proteins are Rad51 and Mre11, which are known to re-localize to sites of DNA damage into nuclear foci. Ionizing radiation-induced foci can be visualized by immuno-staining. Published data show a large variation in the number of foci-positive cells and number of foci per nucleus for specific DNA repair proteins. The experiments described here demonstrate that the time after induction of DNA damage influenced not only the number of foci-positive cells, but also the size of the individual foci. The dose of ionizing radiation influenced both the number of foci-positive cells and the number of foci per nucleus. Furthermore, ionizing radiation-induced foci formation depended on the cell cycle stage of the cells and the protein of interest that was investigated. Rad51 and Mre11 foci seemed to be mutually exclusive, though a small subset of cells did show co-localization of these proteins, which suggests a possible cooperation between the proteins at a specific moment during DNA repair

  8. MRI Evaluation of Non-Necrotic T2-Hyperintense Foci in Pediatric Diffuse Intrinsic Pontine Glioma.

    Science.gov (United States)

    Clerk-Lamalice, O; Reddick, W E; Li, X; Li, Y; Edwards, A; Glass, J O; Patay, Z

    2016-05-19

    The conventional MR imaging appearance of diffuse intrinsic pontine glioma suggests intralesional histopathologic heterogeneity, and various distinct lesion components, including T2-hypointense foci, have been described. Here we report the prevalence, conventional MR imaging semiology, and advanced MR imaging features of non-necrotic T2-hyperintense foci in diffuse intrinsic pontine glioma. Twenty-five patients with diffuse intrinsic pontine gliomas were included in this study. MR imaging was performed at 3T by using conventional and advanced MR imaging sequences. Perfusion (CBV), vascular permeability (v e , K trans ), and diffusion (ADC) metrics were calculated and used to characterize non-necrotic T2-hyperintense foci in comparison with other lesion components, namely necrotic T2-hyperintense foci, T2-hypointense foci, peritumoral edema, and normal brain stem. Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon rank sum tests. Sixteen non-necrotic T2-hyperintense foci were found in 12 tumors. In these foci, ADC values were significantly higher than those in either T2-hypointense foci (P = .002) or normal parenchyma (P = .0002), and relative CBV values were significantly lower than those in either T2-hypointense (P = .0002) or necrotic T2-hyperintense (P = .006) foci. Volume transfer coefficient values in T2-hyperintense foci were lower than those in T2-hypointense (P = .0005) or necrotic T2-hyperintense (P = .0348) foci. Non-necrotic T2-hyperintense foci are common, distinct lesion components within diffuse intrinsic pontine gliomas. Advanced MR imaging data suggest low cellularity and an early stage of angioneogenesis with leaky vessels resulting in expansion of the extracellular space. Because of the lack of biopsy validation, the underlying histoarchitectural and pathophysiologic changes remain unclear; therefore, these foci may correspond to a poorly understood biologic event in tumor evolution. © 2016 American Society of Neuroradiology.

  9. Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats.

    Science.gov (United States)

    Santarelli, Raphaëlle L; Vendeuvre, Jean-Luc; Naud, Nathalie; Taché, Sylviane; Guéraud, Françoise; Viau, Michelle; Genot, Claude; Corpet, Denis E; Pierre, Fabrice H F

    2010-07-01

    Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 x 2 x 2 x 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high-heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar nonnitrite-treated meat (P = 0.03) and with similar nonoxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make nonpromoting processed meat. 2010 AACR.

  10. Multistability in Chua's circuit with two stable node-foci

    International Nuclear Information System (INIS)

    Bao, B. C.; Wang, N.; Xu, Q.; Li, Q. D.

    2016-01-01

    Only using one-stage op-amp based negative impedance converter realization, a simplified Chua's diode with positive outer segment slope is introduced, based on which an improved Chua's circuit realization with more simpler circuit structure is designed. The improved Chua's circuit has identical mathematical model but completely different nonlinearity to the classical Chua's circuit, from which multiple attractors including coexisting point attractors, limit cycle, double-scroll chaotic attractor, or coexisting chaotic spiral attractors are numerically simulated and experimentally captured. Furthermore, with dimensionless Chua's equations, the dynamical properties of the Chua's system are studied including equilibrium and stability, phase portrait, bifurcation diagram, Lyapunov exponent spectrum, and attraction basin. The results indicate that the system has two symmetric stable nonzero node-foci in global adjusting parameter regions and exhibits the unusual and striking dynamical behavior of multiple attractors with multistability.

  11. Alterations of pH and Pi in seizure foci of temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Hubesch, B.; Sappey-Marinier, D.; Laxer, K.; Weiner, M.W.

    1989-01-01

    Previous investigations with positron-emission tomography have demonstrated that glucose uptake is diminished in seizure foci. This paper reports on P-31 MR studies performed on patients with temporal lobe epilepsy in order to determine if metabolic alterations were detectablein seizure foci. In seven of eight patients, the pH of the seizure foci was significantly higher than the pH of the control temporal lobe. In addition, the inorganic phosphate (Pi) concentration was significantly higher in the seizure foci. These metabolic changes indicate that P-31 MR spectroscopymight be useful in the investigation of epilepsy

  12. The protective effect of fermented milk kefir on radiation-induced apoptosis in colonic crypt cells of rats

    International Nuclear Information System (INIS)

    Matsuu, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio

    2003-01-01

    To evaluate the effect of fermented milk kefir on X-ray-induced apoptosis in the colon of rats, we examined the apoptotic index, the mean number of apoptotic cells detected by H and E staining per crypt in the colon, in control rats and kefir-pretreated rats drinking kefir for 12 days before irradiation. Apoptotic cells were confirmed by TUNEL staining, and active caspase-3 expression was studied by immunohistochemistry. The cell position of apoptotic cells and active caspase-3 positive cells were examined. The apoptotic index of kefir-treated rats was significantly (p<0.05) decreased 2 h after 1 Gy irradiation in comparison with control rats at crypt cell positions 1-3, 5-7, 13, and 15. Active caspase-3 expression in the kefir-treated rats was also significantly (p<0.05) reduced in comparison with control rats 2 h after 1 Gy irradiation at crypt cell positions 1-4, 13, and 15. This study indicated that kefir protects colonic crypt cells against radiation-induced apoptosis, which was most pronounced in the stem cell region of the crypt. The antiapoptotic effect of fermented milk kefir was due to the inhibition of caspase-3 activation. (author)

  13. BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation

    Science.gov (United States)

    Reddy, Vishruth K.; Short, Sarah P.; Barrett, Caitlyn W.; Mittal, Mukul K.; Keating, Cody E.; Thompson, Joshua J.; Harris, Elizabeth I.; Revetta, Frank; Bader, David M.; Brand, Thomas; Washington, M. Kay; Williams, Christopher S.

    2016-01-01

    Blood Vessel Epicardial Substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves−/− mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wildtype (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves−/− mice. To examine stem cell function after BVES deletion, we employed ex vivo 3D-enteroid cultures. Bves−/− enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar “CBC” and “+4” stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves−/− enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves−/− mice demonstrated significantly greater small intestinal crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves−/− mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage-responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis. PMID:26891025

  14. The crypt and cell size kinetics in the irradiated intestinal epithelium in mice

    International Nuclear Information System (INIS)

    Kononenko, A.M.; Gagarin, A.U.

    1975-01-01

    A study has been made of changes in the average values of the axial cross-sectional area of the crypt and of cell area in this cross-section for eight days after a single whole-body exposure of male mice to 400 rad of X-rays. A small reduction in the crypt area in the destructive period gives way to a much greater increase in the normal dimensions of the area in the regenerative period. Two very considerable waves of anomalous increase are observed in the dimensions of the cryptal cell cross-sections, the first in the destructive and the second in the regenerative period. These fluctuations in cell dimensions do not occur around but above the control level, attaining the latter level only at the minimum (4th day). The size of the cryptal cells of the intact intestinal epithelium is evidently close to the minimum needed for enterocyte proliferation. The considerable increase in crypt dimensions in the regenerative period (beginning from the 6th day) is not due to the larger number of cells (they are even somewhat fewer than normal) but rather to a substantial increase in cell dimensions. Thus, according to these data, on the 6th-8th day after irradiation the intestinal epithelium deviates strongly from the stationary state. The index I sub(v), where I is the mitotic index and v the cell volume, was used to evaluate the changes in the value of the material stream, connected with proliferation, to the intestinal epithelium per cryptal cell. A considerable increase was found in this stream (hypertrophy of proliferative cells) in the intestinal epithelium restored after irradiation. (author)

  15. Coevolved crypts and exocrine glands support mutualistic bacteria in fungus-growing ants

    DEFF Research Database (Denmark)

    Currie, Cameron R; Poulsen, Michael; Mendenhall, John

    2006-01-01

    Attine ants engage in a quadripartite symbiosis with fungi they cultivate for food, specialized garden parasites, and parasite-inhibiting bacteria. Molecular phylogenetic evidence supports an ancient host-pathogen association between the ant-cultivar mutualism and the garden parasite. Here we show...... that ants rear the antibiotic-producing bacteria in elaborate cuticular crypts, supported by unique exocrine glands, and that these structures have been highly modified across the ants' evolutionary history. This specialized structural evolution, together with the absence of these bacteria and modifications...

  16. Cracking ShadowCrypt: Exploring the Limitations of Secure I/O Systems in Internet Browsers

    OpenAIRE

    Freyberger Michael; He Warren; Akhawe Devdatta; Mazurek Michelle L.; Mittal Prateek

    2018-01-01

    An important line of privacy research is investigating the design of systems for secure input and output (I/O) within Internet browsers. These systems would allow for users’ information to be encrypted and decrypted by the browser, and the specific web applications will only have access to the users’ information in encrypted form. The state-of-the-art approach for a secure I/O system within Internet browsers is a system called ShadowCrypt created by UC Berkeley researchers [23]. This paper wi...

  17. Serotonin receptors influencing cell proliferation in the jejunal crypt epithelium and in colonic adenocarcinomas.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1986-01-01

    Serotonin has previously been shown to stimulate cell proliferation in the jejunal crypt epithelium and in colonic tumours. The original classification of serotonin receptors into D and M groups was not conductive to the understanding of these observations. The more recent classification of serotonin receptors into 5HT1 and 5HT2 groups is considered in this report. On the balance of evidence it appears that similar receptors mediate the response to serotonin in the two tissues under consideration and that these receptors resemble those of the 5HT1 group. Such receptors are usually positively linked to adenylate cyclase.

  18. Fractionation study: survival of mouse intestinal crypts to exposure of 60Co and 11 MeV electrons

    International Nuclear Information System (INIS)

    Coffey, C.W.

    1975-01-01

    The study was conducted to determine a statistical procedure for the quantification of time, dose, fraction relations for mouse intestinal crypt survival after fractionated Co-60 and 11-MeV electron irradiation. In the initial phase of the investigation CDF/1 male mice were exposed to fractionated Co-60 irradiation. A completely randomized experimental design with three factors, total time from initiation to completion of fractionation schedule, number of fractions, and total dose was utilized. The experimental animals were irradiated with a Co-60 panoramic irradiator unit at an absorbed dose rate of approximately 51 rads per minute. Two days after completion of the fractionation schedule, the experimental animals were sacrificed by cervical dislocation. Sections of intestinal jejunum were resected and routine histological preparations performed. The surviving crypts were scored with a compound microscope using a quantitative counting technique. The resulting crypt survival was observed to increase for increasing total times and fraction numbers

  19. Collaborative teacher learning across foci of collaboration : perceived activities and outcomes

    NARCIS (Netherlands)

    Doppenberg, J.J.; Brok, den P.J.; Bakx, A.W.E.A.

    2012-01-01

    This study compared teacher collaboration with differing foci, in terms of various learning activities and learning outcomes. A total of 411 teachers from 49 primary schools participated by completing a questionnaire. Foci of collaboration explained significant differences in the frequency with

  20. De Novo Formation of Insulin-Producing “Neo-β Cell Islets” from Intestinal Crypts

    Directory of Open Access Journals (Sweden)

    Yi-Ju Chen

    2014-03-01

    Full Text Available The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet β cell program, we performed an in vivo screen by expressing three β cell “reprogramming factors” in a wide spectrum of tissues. We report that transient intestinal expression of these factors—Pdx1, MafA, and Ngn3 (PMN—promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into “neoislets” below the crypt base. Neoislet cells express insulin and show ultrastructural features of β cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal “organoids” stimulates the conversion of intestinal epithelial cells into β-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells.

  1. Scap is required for sterol synthesis and crypt growth in intestinal mucosa.

    Science.gov (United States)

    McFarlane, Matthew R; Cantoria, Mary Jo; Linden, Albert G; January, Brandon A; Liang, Guosheng; Engelking, Luke J

    2015-08-01

    SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synthesis of sterols and fatty acids is reduced, but mice are otherwise healthy. To determine whether Scap loss is tolerated in the intestine, we generated a mouse model (Vil-Scap(-)) in which tamoxifen-inducible Cre-ER(T2), a fusion protein of Cre recombinase with a mutated ligand binding domain of the human estrogen receptor, ablates Scap in intestinal mucosa. After 4 days of tamoxifen, Vil-Scap(-) mice succumb with a severe enteropathy and near-complete collapse of intestinal mucosa. Organoids grown ex vivo from intestinal crypts of Vil-Scap(-) mice are readily killed when Scap is deleted by 4-hydroxytamoxifen. Death is prevented when culture medium is supplemented with cholesterol and oleate. These data show that, unlike the liver, the intestine requires Scap to sustain tissue integrity by maintaining the high levels of lipid synthesis necessary for proliferation of intestinal crypts. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  2. Phylogenetically Diverse Burkholderia Associated with Midgut Crypts of Spurge Bugs, Dicranocephalus spp. (Heteroptera: Stenocephalidae).

    Science.gov (United States)

    Kuechler, Stefan Martin; Matsuura, Yu; Dettner, Konrad; Kikuchi, Yoshitomo

    2016-06-25

    Diverse phytophagous heteropteran insects, commonly known as stinkbugs, are associated with specific gut symbiotic bacteria, which have been found in midgut cryptic spaces. Recent studies have revealed that members of the stinkbug families Coreidae and Alydidae of the superfamily Coreoidea are consistently associated with a specific group of the betaproteobacterial genus Burkholderia, called the "stinkbug-associated beneficial and environmental (SBE)" group, and horizontally acquire specific symbionts from the environment every generation. However, the symbiotic system of another coreoid family, Stenocephalidae remains undetermined. We herein investigated four species of the stenocephalid genus Dicranocephalus. Examinations via fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM) revealed the typical arrangement and ultrastructures of midgut crypts and gut symbionts. Cloning and molecular phylogenetic analyses of bacterial genes showed that the midgut crypts of all species are colonized by Burkholderia strains, which were further assigned to different subgroups of the genus Burkholderia. In addition to the SBE-group Burkholderia, a number of stenocephalid symbionts belonged to a novel clade containing B. sordidicola and B. udeis, suggesting a specific symbiont clade for the Stenocephalidae. The symbiotic systems of stenocephalid bugs may provide a unique opportunity to study the ongoing evolution of symbiont associations in the stinkbug-Burkholderia interaction.

  3. Radioprotective effects of natural β-carotene on villi and crypts in abdominally radiated mice

    International Nuclear Information System (INIS)

    Kurabe, Teruhisa; Itoh, Youko; Matsumura, Eijin; Nakamura, Atsushi; Ayakawa, Yoshio

    2002-01-01

    The protective effect of β-carotene against radiation injury to the small intestine of abdominally radiated mice (15 Gy) was examined with administration given pre-radiation, during (pre- and post-) radiation, and post-radiation. In the β-carotene group, the ratio of villus length to crypt was significantly greater in comparison with the radiation only group at 2 days after radiation. At 7 days after radiation, the ratio of necrotic cells in the crypt vs. the total was significantly lower, and the ratio of necrotic cells in the villus vs. the total was significantly greater with β-carotene administration, which indicated that β-carotene accelerated recovery from radiation injury. Each group administered β-carotene showed a significant radioprotective effect, with pre-radiation administration yielding a smaller effect than administration during radiation and post-radiation. It is concluded that pre-, during, and post-radiation administration of β-carotene protected against radiation injury of the small intestine and accelerated recovery from it. (author)

  4. Preoperative localization of epileptic foci with SPECT brain perfusion imaging, electrocorticography, surgery and pathology

    International Nuclear Information System (INIS)

    Jia Shaowei; Xu Wengui; Chen Hongyan; Weng Yongmei; Yang Pinghua

    2002-01-01

    Objective: The value of preoperative localization of epileptic foci with SPECT brain perfusion imaging was investigated. Methods: The study population consisted of 23 patients with intractable partial seizures which was difficult to control with anticonvulsant for long period. In order to preoperatively locate the epileptic foci, double SPECT brain perfusion imaging was performed during interictal and ictal stage. The foci were confirmed with electrocorticography (EcoG), surgery and pathology. Results: The author checked with EcoG the foci shown by SPECT, 23 patients had all typical spike discharge. The regions of radioactivity increase in ictal matched with the abnormal electrical activity areas that EcoG showed. The spike wave originated in the corresponding cerebrum cortex instead of hyperplastic and adherent arachnoid or tumor itself. Conclusions: SPECT brain perfusion imaging contributes to distinguishing location, size, perfusion and functioning of epileptogenic foci, and has some directive function on to making out a treatment programme at preoperation

  5. The influence of serotonin on the mitotic rate in the colonic crypt epithelium and in colonic adenocarcinoma in rats.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1978-01-01

    1. The mitotic rate in the crypts of Lieberkühn of the descending colon and in dimethylhydrazine-induced adenocarcinomata of the descending colon of rat was measured using a stathmokinetic technique. 2. Intraperitoneal injection of a small dose (10 microgram/kg) of serotonin resulted in an increase in the tumour cell mitotic rate. 3. Blockade of serotonin receptors by 2-bromolysergic acid diethylamide and depletion of tissue serotonin levels following injection of DL-6-fluorotryptophan both result in a decrease in the tumour cell mitotic rate. 4. Treatment with serotonin, 2-bromolysergic acid diethylamide and DL-6-fluorotryptophan were all without effect on the colonic crypt cell mitotic rate.

  6. Further studies on the effect of adenosine cyclic monophosphate derivatives on cell proliferation in the jejunal crypts of rat.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1982-01-01

    1. Cell proliferation in the jejunal crypt epithelium of rat was measured using a stathmokinetic technique. 2. Sodium butyrate was found to promote jejunal crypt cell proliferation. 3. N6, O2'-Dibutyryl cyclic adenosine monophosphate (cAMP), N6-monobutyryl-cAMP and N6-monobutyryl-8-bromo-cAMP were found to inhibit cell proliferation when compared to sodium butyrate treated tissues. 4. 8-Chlorophenylthio-cAMP was found to inhibit cell division when compared to untreated animals. 5. O2'-Monobutyryl cAMP and 8-bromo-cAMP were not found to inhibit cell proliferation.

  7. Differential effects of oestrogenic hormones on cell proliferation in the colonic crypt epithelium and in colonic carcinomata of rats.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1982-01-01

    A number of hormones, including some steroids, have previously been shown to influence the rate of cell division in the colonic crypt epithelium and in colonic tumours. In this report the effect of oophorectomy and of treatment with ovarian hormones on cell proliferation in these tissues is compared. Colonic tumours cell proliferation was retarded following oophorectomy and this retardation was reversed by the administration of oestradiol, but not by the administration of progesterone. Oophorectomy did not retard cell proliferation in the colonic crypts. The possible significance of these findings in relation to age-dependent variations in the sex ratio for human bowel cancer is discussed.

  8. Multiple foci of splenic tissue autotransplantation: Splenosis in diagnostic imaging

    International Nuclear Information System (INIS)

    Laskowska, K.; Burzynska-Makuch, M.; Drewa, S.; Lasek, W.; Pilecki, S.; Junik, R.

    2005-01-01

    Splenosis is usually defined as an autotransplantation of lienal tissue in the abdomen or cest following trauma to the spleen and/or splenectomy. The authors present the case of patient 15 years after a splenectomy performed because of extensive abdominal trauma. A new computed tomographic (CT) scan of the abdomen revealed multiple homogenous nodules, different in size, spread in the abdomen. Their density was characteristic of spleen. Ultrasound examination revealed only the largest tumors, located close to the liver and apparently isoechogenic to it. Static scintigraphy and SPECT were performed to prove the presence of splenosis. After treating the patient with colloid sulfide, multiple foci of increased radioisotope accumulation were identified in the abdomen, extrahepatic at the same locations as the masses visible on the CT scans, which were comparable to splenic tissue. Nodules revealed during CT or abdominal US in patients previously treated by splenectomy require further imaging with static scintigraphy of the liver and spleen in order to confirm or exclude splenosis. (author)

  9. Localisation of epileptic foci using novel imaging modalities

    Science.gov (United States)

    De Ciantis, Alessio; Lemieux, Louis

    2013-01-01

    Purpose of review This review examines recent reports on the use of advanced techniques to map the regions and networks involved during focal epileptic seizure generation in humans. Recent findings A number of imaging techniques are capable of providing new localizing information on the ictal processes and epileptogenic zone. Evaluating the clinical utility of these findings has been mainly performed through post-hoc comparison with the findings of invasive EEG and ictal single-photon emission computed tomography, using postsurgical seizure reduction as the main outcome measure. Added value has been demonstrated in MRI-negative cases. Improved understanding of the human ictiogenic processes and the focus vs. network hypothesis is likely to result from the application of multimodal techniques that combine electrophysiological, semiological, and whole-brain coverage of brain activity changes. Summary On the basis of recent research in the field of neuroimaging, several novel imaging modalities have been improved and developed to provide information about the localization of epileptic foci. PMID:23823464

  10. Multiple foci of spatial attention in multimodal working memory.

    Science.gov (United States)

    Katus, Tobias; Eimer, Martin

    2016-11-15

    The maintenance of sensory information in working memory (WM) is mediated by the attentional activation of stimulus representations that are stored in perceptual brain regions. Using event-related potentials (ERPs), we measured tactile and visual contralateral delay activity (tCDA/CDA components) in a bimodal WM task to concurrently track the attention-based maintenance of information stored in anatomically segregated (somatosensory and visual) brain areas. Participants received tactile and visual sample stimuli on both sides, and in different blocks, memorized these samples on the same side or on opposite sides. After a retention delay, memory was unpredictably tested for touch or vision. In the same side blocks, tCDA and CDA components simultaneously emerged over the same hemisphere, contralateral to the memorized tactile/visual sample set. In opposite side blocks, these two components emerged over different hemispheres, but had the same sizes and onset latencies as in the same side condition. Our results reveal distinct foci of tactile and visual spatial attention that were concurrently maintained on task-relevant stimulus representations in WM. The independence of spatially-specific biasing mechanisms for tactile and visual WM content suggests that multimodal information is stored in distributed perceptual brain areas that are activated through modality-specific processes that can operate simultaneously and largely independently of each other. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice. Increased small intestinal crypt survival, crypt lengths and prolongation of average time to death

    International Nuclear Information System (INIS)

    Ohara, Masayuki; Lu, Huimei; Shiraki, Katsutomo; Ishimura, Yoshimasa; Uesaka, Toshihiro; Katoh, Osamu; Watanabe, Hiromitsu

    2001-01-01

    The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60 Co-γ-ray irradiation at a dose rate of 2 Gy min -1 . Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min -1 , the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects. (author)

  12. Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice: increased small intestinal crypt survival, crypt lengths and prolongation of average time to death.

    Science.gov (United States)

    Ohara, M; Lu, H; Shiraki, K; Ishimura, Y; Uesaka, T; Katoh, O; Watanabe, H

    2001-12-01

    The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60Co-gamma-ray irradiation at a dose rate of 2Gy min(-1). Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min(-1), the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects.

  13. Subnuclear foci quantification using high-throughput 3D image cytometry

    Science.gov (United States)

    Wadduwage, Dushan N.; Parrish, Marcus; Choi, Heejin; Engelward, Bevin P.; Matsudaira, Paul; So, Peter T. C.

    2015-07-01

    Ionising radiation causes various types of DNA damages including double strand breaks (DSBs). DSBs are often recognized by DNA repair protein ATM which forms gamma-H2AX foci at the site of the DSBs that can be visualized using immunohistochemistry. However most of such experiments are of low throughput in terms of imaging and image analysis techniques. Most of the studies still use manual counting or classification. Hence they are limited to counting a low number of foci per cell (5 foci per nucleus) as the quantification process is extremely labour intensive. Therefore we have developed a high throughput instrumentation and computational pipeline specialized for gamma-H2AX foci quantification. A population of cells with highly clustered foci inside nuclei were imaged, in 3D with submicron resolution, using an in-house developed high throughput image cytometer. Imaging speeds as high as 800 cells/second in 3D were achieved by using HiLo wide-field depth resolved imaging and a remote z-scanning technique. Then the number of foci per cell nucleus were quantified using a 3D extended maxima transform based algorithm. Our results suggests that while most of the other 2D imaging and manual quantification studies can count only up to about 5 foci per nucleus our method is capable of counting more than 100. Moreover we show that 3D analysis is significantly superior compared to the 2D techniques.

  14. Functional morphology, biology and sexual strategy of the circumboreal, adventitious crypt-building, Crenella decussata (Bivalvia: Mytiloidea: Crenellidae)

    DEFF Research Database (Denmark)

    Morton, Brian; Dinesen, Grete E.; Ockelmann, Kurt W.

    2016-01-01

    The anatomy of Crenella decussata (Mytiloidea) is described. Individuals of this circumboreal species occupy granular crypts composed of sand grains held in place by mucus. The swollen basal region of the tubule is occupied by an individual, which connects to the sediment surface by two posterior...

  15. Influence of anthropogenic transformation of Danube–Dniester interfluve on natural foci of tularaemia

    Directory of Open Access Journals (Sweden)

    I. T. Rusev

    2011-04-01

    Full Text Available The paper is devoted to the problem of occurrence of bacteria Francisella tularensis in steppe coastal zone of the Black Sea west part in the second half of XX century. The key factor decreasing the activity of tularaemia natural foci is anthropogenic influence. Resumed activity of natural foci appeared after implementation of big irrigation and drainage construction in former USSR – building of the Danube-Dniester-Dnepr irrigation system resulted in forming new environmental conditions as well as corridors for tularaemia distribution. The practical recommendation is to implement the eco-epizootological monitoring and to collect data for developing practical management of the natural foci of disease.

  16. Saint-Quentin (Aisne, la collégiale et la crypte de la basilique

    Directory of Open Access Journals (Sweden)

    Christian Sapin

    2005-10-01

    Full Text Available La courte campagne d’intervention fin juillet 2003, dans la crypte archéologique créée vers 1955 sous le sol du sanctuaire de la collégiale de Saint-Quentin, avait pour objet une meilleure compréhension des niveaux et des structures du haut Moyen Âge apparus lors des travaux des XIXe et XXe siècles. Un nettoyage complet, un plan et des relevés de maçonnerie sans nouvelle fouille, nous ont convaincu de l’important potentiel d’informations conservées. À partir de sondages anciens, il a été pos...

  17. The effects of herbs on the radiation-induced apoptosis in intestinal crypt cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Ho; An, Mi Ra; Nah, Seung Yeol; Lee, Jong Hwan; Kim, Jae Ha; Shin, Dong Ho [Chonnam National Univ., Gwangju (Korea, Republic of); Jo, Sung Kee [KAERI, Daejeon (Korea, Republic of); Jang, Jong Sik [Sangju National Univ., Sangju (Korea, Republic of)

    2001-03-15

    This study was performed to determine the effect of several herbs on radiation-induced apoptosis in jejunal crypt cells. Longyanrou(Euphoris logana), Suanzaoren(Zizyphus vulgaris), Yuanzhi(Polygala tenuifolia), Rensan(Panax ginseng), Fuling(Poria cocos), Muxiang(Saussurea lappa), Chuanxiong(Cnidium offcinale), Baishaoyao(Paeonia lactifolia), Shengma(Cimicifuga heracleifolia), Chaihu(Bupleurum falcatum) and Dongchongxiacao(Paecilomyces japonica) reduced the frequency of radiation-induced apoptosis(p<0.05). Although the mechanisms of this effect remain to be elucidated, these results indicated that Longyanrou, Suanzaoren, Yuanzhi, Rensan, Fuling, Muxiang, Chuanxiong, Baishaoyao, Shengma, Chaihu and Dongchongxiacao might be useful inhibitors of apoptosis, especially since these are relative nontoxic natural products.

  18. RBE of the NCT beam at Petten (The Netherlands) for intestinal crypt regeneration in mice

    International Nuclear Information System (INIS)

    Gueulette, J.; Coster, B.M. de; Wambersie, A.; Stecher-Rasmussen, F.; Huiskamp, R.; Moss, R.; Morrissey, J.

    2000-01-01

    RBE of the BNCT epithermal neutron beam at Petten (The Netherlands) has been determined for intestinal crypt regeneration in mice i.e. an in vivo system. No boron was administered. This experiment is part of an IAEA programme aiming at intercomparing radiobiologically the NCT neutron beams of different facilities world-wide. Six MV photons were used as the reference radiation. For the NCT beam at Petten, irradiation times ranging between 1 and 3 hours were applied. These low dose rate irradiations (∼3 Gy/hour) were found ∼2.4 more effective than acute photon irradiations. This type of experiment - repeated at different BNCT facilities - will improve harmonisation in the radiobiological specification of NCT neutron beams and facilitate exchange of clinical information. (author)

  19. Effect of postradiation bleeding on proliferative activity of cells in small intestine crypts of rats

    Energy Technology Data Exchange (ETDEWEB)

    Petrovic, N V [Institut za Nuklearne Nauke Boris Kidric, Vinca (Yugoslavia)

    1975-12-01

    The effect of postradiation bleeding on the dynamics of duodenal crypt's cell proliferation in rats was studied. The animals, females, three months old, weighing 170 or 180 g, were exposed to radiation of 800 R (115 R/min) and immediately after irradiation were bled by cardiac puncture to 50% of total blood volume. Proliferative activity of duodenal epithelium cells was monitored for a period of five days after irradiation. For control purposes normal, irradiated and only bled animals were used. The results demonstrated that although there are no significant differences in proliferative activity of duodenal epithelium cells in irradiated and bled animals and only irradiated animals, the postradiation reparative processes in irradiated and bled animals is considerably more stable. It is considered that bleeding itself by its hypoxic activity reduced the sensitivity of epithelium to the dose of radiation used. On the other hand, bleeding removed the damaging agents which appear after total body irradiation.

  20. Biological intercomparison using gut crypt survivals for proton and carbon ions

    International Nuclear Information System (INIS)

    Uzawa, Akiko; Ando, Koichi; Furusawa, Yoshiya

    2006-01-01

    Charged particle therapy depends on biological information for the dose prescription. Relative biological effectiveness or relative biological effectiveness (RBE) for this requirement could basically be provided by experimental data. As RBE values of protons and carbon ions depend on several factors such as cell/tissue type, endpoint, dose and fractionation schedule, a single RBE value could not function as a master key to open all rooms filled with guests of different radiosensitivities. However, any biological model with accurate reproducibility is useful for comparing biological effectiveness between different facilities. We used mouse gut crypt survivals as endpoint, and compared the cell killing efficiency of proton beams at three Japanese facilities. Three Linac X-ray machines with 4 and 6 MeV were used as reference beams, and there was only a small variation (coefficient of variance <2%) in biological effectiveness among them. The RBE values of protons relative to Linac X-rays ranged from 1.0 to 1.11 at the middle of a 6-cm SOBP (spread-out Bragg peak) and from 0.96 to 1.01 at the entrance plateau. The coefficient of variance for protons ranged between 4.0 and 5.1%. The biological comparison of carbon ions showed fairly good agreement in that the difference in biological effectiveness between National Institute of Radiological Sciences (NIRS)/Heavy Ion Medical Accelerator in Chiba (HIMAC) and Gesellschaft fur Schwerionenforschung (GSI)/Heavy Ion Synchrotron (SIS) was 1% for three positions within the 6-cm SOBP. The coefficient of variance was <1.7, <0.6 and <1.6% for proximal, middle and distal SOBP, respectively. We conclude that the inter-institutional variation of biological effectiveness is smaller for carbon ions than protons, and that beam-spreading methods of carbon ions do not critically influence gut crypt survival. (author)

  1. Biological intercomparison using gut crypt survivals for proton and carbon-ion beams

    International Nuclear Information System (INIS)

    Uzawa, Akiko; Ando, Koichi; Furusawa, Yoshiya

    2007-01-01

    Charged particle therapy depends on biological information for the dose prescription. Relative biological effectiveness or RBE for this requirement could basically be provided by experimental data. As RBE values of protons and carbon ions depend on several factors such as cell/tissue type, biological endpoint, dose and fractionation schedule, a single RBE value could not deal with all different radiosensitivities. However, any biological model with accurate reproducibility is useful for comparing biological effectiveness between different facilities. We used mouse gut crypt survivals as endpoint, and compared the cell killing efficiency of proton beams at three Japanese facilities. Three Linac X-ray machines with 4 and 6 MeV were used as reference beams, and there was only a small variation (coefficient of variance<2%) in biological effectiveness among them. The RBE values of protons relative to Linac X-rays ranged from 1.0 to 1.11 at the middle of a 6-cm SOBP (spread-out Bragg peak) and from 0.96 to 1.01 at the entrance plateau. The coefficient of variance for protons ranged between 4.0 and 5.1%. The biological comparison of carbon ions showed fairly good agreement in that the difference in biological effectiveness between National Institute of Radiological Sciences (NIRS)/ Heavy Ion Medical Accelerator in Chiba (HIMAC) and Gesellschaft fur Schwerionenforschung (GSI)/Heavy Ion Synchrotron (SIS) was 1% for three positions within the 6-cm SOBP. The coefficient of variance was <1.7, <0.6 and <1.6% for proximal, middle and distal SOBP, respectively. We conclude that the inter-institutional variation of biological effectiveness is smaller for carbon ions than protons, and that beam-spreading methods of carbon ions do not critically influence gut crypt survival. (author)

  2. Molecular Mapping to Species Level of the Tonsillar Crypt Microbiota Associated with Health and Recurrent Tonsillitis

    Science.gov (United States)

    Jensen, Anders; Fagö-Olsen, Helena; Sørensen, Christian Hjort; Kilian, Mogens

    2013-01-01

    The human palatine tonsils, which belong to the central antigen handling sites of the mucosal immune system, are frequently affected by acute and recurrent infections. This study compared the microbiota of the tonsillar crypts in children and adults affected by recurrent tonsillitis with that of healthy adults and children with tonsillar hyperplasia. An in-depth 16S rRNA gene based pyrosequencing approach combined with a novel strategy that included phylogenetic analysis and detection of species-specific sequence signatures enabled identification of the major part of the microbiota to species level. A complex microbiota consisting of between 42 and 110 taxa was demonstrated in both children and adults. This included a core microbiome of 12 abundant genera found in all samples regardless of age and health status. Yet, Haemophilus influenzae, Neisseria species, and Streptococcus pneumoniae were almost exclusively detected in children. In contrast, Streptococcus pseudopneumoniae was present in all samples. Obligate anaerobes like Porphyromonas, Prevotella, and Fusobacterium were abundantly present in children, but the species diversity of Porphyromonas and Prevotella was larger in adults and included species that are considered putative pathogens in periodontal diseases, i.e. Porphyromonas gingivalis, Porphyromonas endodontalis, and Tannerella forsythia. Unifrac analysis showed that recurrent tonsillitis is associated with a shift in the microbiota of the tonsillar crypts. Fusobacterium necrophorum, Streptococcus intermedius and Prevotella melaninogenica/histicola were associated with recurrent tonsillitis in adults, whereas species traditionally associated with acute tonsillitis like pyogenic streptococci and Staphylococcus aureus were scarce. The findings suggest that recurrent tonsillitis is a polymicrobial infection in which interactions within consortia of taxa play an etiologic role. The study contributes to the human microbiome data, to the understanding of the

  3. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis.

    Directory of Open Access Journals (Sweden)

    Anders Jensen

    Full Text Available The human palatine tonsils, which belong to the central antigen handling sites of the mucosal immune system, are frequently affected by acute and recurrent infections. This study compared the microbiota of the tonsillar crypts in children and adults affected by recurrent tonsillitis with that of healthy adults and children with tonsillar hyperplasia. An in-depth 16S rRNA gene based pyrosequencing approach combined with a novel strategy that included phylogenetic analysis and detection of species-specific sequence signatures enabled identification of the major part of the microbiota to species level. A complex microbiota consisting of between 42 and 110 taxa was demonstrated in both children and adults. This included a core microbiome of 12 abundant genera found in all samples regardless of age and health status. Yet, Haemophilus influenzae, Neisseria species, and Streptococcus pneumoniae were almost exclusively detected in children. In contrast, Streptococcus pseudopneumoniae was present in all samples. Obligate anaerobes like Porphyromonas, Prevotella, and Fusobacterium were abundantly present in children, but the species diversity of Porphyromonas and Prevotella was larger in adults and included species that are considered putative pathogens in periodontal diseases, i.e. Porphyromonas gingivalis, Porphyromonas endodontalis, and Tannerella forsythia. Unifrac analysis showed that recurrent tonsillitis is associated with a shift in the microbiota of the tonsillar crypts. Fusobacterium necrophorum, Streptococcus intermedius and Prevotella melaninogenica/histicola were associated with recurrent tonsillitis in adults, whereas species traditionally associated with acute tonsillitis like pyogenic streptococci and Staphylococcus aureus were scarce. The findings suggest that recurrent tonsillitis is a polymicrobial infection in which interactions within consortia of taxa play an etiologic role. The study contributes to the human microbiome data, to the

  4. Bacterial colonization of colonic crypt mucous gel and disease activity in ulcerative colitis.

    LENUS (Irish Health Repository)

    Rowan, Fiachra

    2012-02-01

    OBJECTIVE: To optimize total bacterial 16S rRNA quantification in microdissected colonic crypts in healthy controls and patients with ulcerative colitis (UC) and to characterize the findings with disease activity. BACKGROUND: Microscopic and molecular techniques have recently converged to allow bacterial enumeration in remote anatomic locations [eg, crypt-associated mucous gel (CAMG)]. The aims of this study were to combine laser capture microdissection (LCM) and 16S rRNA-based quantitative polymerase chain reaction (qPCR) to determine total bacterial copy number in CAMG both in health and in UC and to characterize the findings with disease activity. METHODS: LCM was used to microdissect CAMG from colonic mucosal biopsies from controls (n = 20) and patients with acute (n = 10) or subacute (n = 10) UC. Pan-bacterial 16S rRNA copy number per millimeter square in samples from 6 locations across the large bowel was obtained by qPCR using Desulfovibrio desulfuricans as a reference strain. Copy numbers were correlated with the UC disease activity index (UCDAI) and the simple clinical colitis activity index (SCCAI). RESULTS: Bacterial colonization of CAMG was detectable in all groups. Copy numbers were significantly reduced in acute UC. In subacute colitis, there was a positive correlation between copy number and UCDAI and SCCAI in the ascending, transverse and sigmoid colon. CONCLUSIONS: This study describes a sensitive method of quantitatively assessing bacterial colonization of the colonic CAMG. A positive correlation was found between CAMG bacterial load and subacute disease activity in UC, whereas detectable bacterial load was reduced in acute UC.

  5. A kinetic model to study the regulation of β-catenin, APC, and Axin in the human colonic crypt.

    Science.gov (United States)

    Emerick, Brooks; Schleiniger, Gilberto; Boman, Bruce M

    2017-11-01

    The Wnt/[Formula: see text]-catenin pathway plays a crucial role in stem cell renewal and differentiation in the normal human colonic crypt. The balance between [Formula: see text]-catenin and APC along the crypt axis determines its normal functionality. The mechanism that deregulates this balance may give insight into the initiation of colorectal cancer. This is significant because the spatial dysregulation of [Formula: see text]-catenin by the mutated tumor suppressor gene/protein APC in human colonic crypts is responsible for the initiation and growth of colorectal cancer. We consider a regulatory function that promotes APC synthesis within the cell and its effect on the accumulation of the Wnt target protein, [Formula: see text]-catenin. It is evident that an APC gradient exists along the crypt axis; however, the mechanism by which APC expression is regulated within the cell is not well known. We investigate the dynamics of an APC regulatory mechanism with an increased level of Axin at the subcellular level. Model output shows an increase of APC for a diminished Wnt signal, which explains the APC gradient along the crypt. We find that the dynamic interplay between [Formula: see text]-catenin, APC, and Axin produces oscillatory behavior, which is controlled by the Wnt stimulus. In the presence of reduced functional APC, the oscillations are amplified, which suggests that the cell remains in a more proliferative state for longer periods of time. Increased Axin levels (typical of mammalian cells) reduce oscillatory behavior and minimize the levels of [Formula: see text]-catenin within the cell while raising the levels of APC.

  6. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    NARCIS (Netherlands)

    Schuurhuis, J M; Span, L. F. R.; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

    2016-01-01

    BACKGROUND: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect

  7. Concordance and discordance between PET images and foci of scalp EEG

    International Nuclear Information System (INIS)

    Iinuma, Kazuie; Haginoya, Kazuhiro; Yanai, Kazuhiko; Hatazawa, Jun; Ito, Masatoshi.

    1989-01-01

    Epileptic foci were determined by scalp EEG and positron emission tomography (PET) with fluorine 18 in 22 children with partial epilepsy (PE, n=13) and Lennoxy-Gastaut syndrome (LGS, n=9). The patients ranged in age from 6 to 18 years. The pattern of hypometabolism was classified into the following 4 categories: non-focal, localized, hemispheric, and diffuse. In the group of PE patients, 11 showed a relative agreement between the EEG foci and region of a low cerebral metabolic rate for glucose (CMRglc) determined by PET. A decreased CMRglc was matched with the EEG foci in 4 patients with LGS. A tendency of a higher relationship between the EEG foci and PET images was significant in PE than LGS. (N.K.)

  8. Description of a newly discovered Triatoma infestans (Hemiptera: Reduviidae Foci in Ibipeba, State of Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    Renato Freitas Araújo

    2014-07-01

    Full Text Available Introduction Chagas disease transmitted by the Triatoma infestans was eradicated from Brazil in 2006. However, reports of triatomine foci threaten the control of Chagas disease. The goal of this study was to determine T. infestans foci in the City of Ibipeba, State of Bahia. Methods Triatominae specimens were collected in Ibipeba and entomologic indicators were calculated using indices of domiciliary infestation, density, and colonization. Results T. infestans foci was discovery in Ibipeba, State of Bahia. Approximately 95% of the specimens were discovered inside dwellings, of which 34% were T. infestans. This species was also discovered forming a colony in tree bark in the peridomicile. Conclusions Triatoma infestans foci in peridomestic ecotopes in Ibipeba, BA, indicate increased the risk of transmission Chagas disease.

  9. A two-dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath.

    Directory of Open Access Journals (Sweden)

    Sara-Jane Dunn

    Full Text Available The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the context of the epithelial monolayer that lines the colonic crypt, test-tube shaped invaginations that punctuate the lining of the intestine and coordinate a regular turnover of cells to replenish the epithelial layer every few days. To investigate the consequence of genetic mutations that perturb the system dynamics and can lead to colorectal cancer, it must be possible to track the emerging tissue level changes that arise in the crypt. To that end, a theoretical crypt model with a realistic, deformable geometry is required. A new discrete crypt model is presented, which focuses on the interaction between cell- and tissue-level behaviour, while incorporating key subcellular components. The model contains a novel description of the role of the surrounding tissue and musculature, based upon experimental observations of the tissue structure of the crypt, which are also reported. A two-dimensional (2D cross-sectional geometry is considered, and the shape of the crypt is allowed to evolve and deform. Simulation results reveal how the shape of the crypt may contribute mechanically to the asymmetric division events typically associated with the stem cells at the base. The model predicts that epithelial cell migration may arise due to feedback between cell loss at the crypt collar and density-dependent cell division, an hypothesis which can be investigated in a wet lab. This work forms the basis for investigation of the deformation of the crypt structure that can occur due to proliferation of cells exhibiting mutant phenotypes, experiments that would not be possible in vivo or in vitro.

  10. Residual γH2AX foci as an indication of lethal DNA lesions

    Directory of Open Access Journals (Sweden)

    Banuelos C Adriana

    2010-01-01

    Full Text Available Abstract Background Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication. Methods To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci. Results For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die. Conclusion Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci.

  11. Residual γH2AX foci as an indication of lethal DNA lesions

    International Nuclear Information System (INIS)

    Banáth, Judit P; Klokov, Dmitry; MacPhail, Susan H; Banuelos, C Adriana; Olive, Peggy L

    2010-01-01

    Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication. To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine) and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci. For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die. Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci

  12. Localized air foci in the lower thorax in the patients with pneumothorax: Skip pneumothoraces

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Takeshi, E-mail: higuchi@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Takahashi, Naoya, E-mail: nandtr@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Kiguchi, Takao, E-mail: takakig@gmail.com [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Shiotani, Motoi, E-mail: Shiotani14@gmail.com [Department of Radiology, Niigata Cancer Center Hospital, 2-15-3 Chuo-ku, Kawagishicho, Niigata 951-8566 (Japan); Maeda, Haruo, E-mail: h-maeda@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan)

    2013-08-15

    Purpose: To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Materials and methods: Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1–93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ{sup 2} test. All P values <0.05 were considered significant. Results: Localized air foci in the lower thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Conclusion: Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases.

  13. Localized air foci in the lower thorax in the patients with pneumothorax: Skip pneumothoraces

    International Nuclear Information System (INIS)

    Higuchi, Takeshi; Takahashi, Naoya; Kiguchi, Takao; Shiotani, Motoi; Maeda, Haruo

    2013-01-01

    Purpose: To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Materials and methods: Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1–93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ 2 test. All P values <0.05 were considered significant. Results: Localized air foci in the lower thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Conclusion: Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases

  14. Ground-penetrating radar investigation of St. Leonard's Crypt under the Wawel Cathedral (Cracow, Poland) - COST Action TU1208

    Science.gov (United States)

    Benedetto, Andrea; Pajewski, Lara; Dimitriadis, Klisthenis; Avlonitou, Pepi; Konstantakis, Yannis; Musiela, Małgorzata; Mitka, Bartosz; Lambot, Sébastien; Żakowska, Lidia

    2016-04-01

    The Wawel ensemble, including the Royal Castle, the Wawel Cathedral and other monuments, is perched on top of the Wawel hill immediately south of the Cracow Old Town, and is by far the most important collection of buildings in Poland. St. Leonard's Crypt is located under the Wawel Cathedral of St Stanislaus BM and St Wenceslaus M. It was built in the years 1090-1117 and was the western crypt of the pre-existing Romanesque Wawel Cathedral, so-called Hermanowska. Pope John Paul II said his first Mass on the altar of St. Leonard's Crypt on November 2, 1946, one day after his priestly ordination. The interior of the crypt is divided by eight columns into three naves with vaulted ceiling and ended with one apse. The tomb of Bishop Maurus, who died in 1118, is in the middle of the crypt under the floor; an inscription "+ MAVRVS EPC MCXVIII +" indicates the burial place and was made in 1938 after the completion of archaeological works which resulted in the discovery of this tomb. Moreover, the crypt hosts the tombs of six Polish kings and heroes: Michał Korybut Wiśniowiecki (King of the Polish-Lithuanian Commonwealth), Jan III Sobieski (King of the Polish-Lithuanian Commonwealth and Commander at the Battle of Vienna), Maria Kazimiera (Queen of the Polish-Lithuanian Commonwealth and consort to Jan III Sobieski), Józef Poniatowski (Prince of Poland and Marshal of France), Tadeusz Kościuszko (Polish general, revolutionary and a Brigadier General in the American Revolutionary War) and Władysław Sikorski (Prime Minister of the Polish Government in Exile and Commander-in-Chief of the Polish Armed Forces). The adjacent six crypts and corridors host the tombs of the other Polish kings, from Sigismund the Old to Augustus II the Strong, their families and several Polish heroes. In May 2015, the COST (European COoperation in Science and Technology) Action TU1208 "Civil engineering applications of Ground Penetrating Radar" organised and offered a Training School (TS) on the

  15. β-Catenin stabilization imparts crypt progenitor phenotype to hyperproliferating colonic epithelia

    International Nuclear Information System (INIS)

    Sellin, Joseph H.; Wang Yu; Singh, Pomila; Umar, Shahid

    2009-01-01

    Utilizing the Citrobacter rodentium (CR)-induced transmissible murine colonic hyperplasia (TMCH) model, we provide mechanistic basis of changes in β-catenin/APC/CKIε leading to progression and/or regression of hyperplasia in vivo. In response to CR-induced TMCH, crypt lengths increased significantly between days 6-27 post-infection, followed by a steep decline by day 34. β-Cat 45 /total β-catenin were elevated on day 1 post-infection, preceding changes in crypt length, and persisted for 27 days before declining by day 34. Importantly, cellular CKIε and β-catenin co-immunoprecipitated and exhibited remarkable parallel changes in kinetics during hyperplasia/regression phases. β-catenin, phosphorylated at Ser33,37 and Thr41 (β-cat 33,37/41 ), was low till day 12, followed by gradual increase until day 27 before declining by day 34. GSK-3β exhibited significant Ser 9 -phosphorylation/inactivation at days 6-12 with partial recovery at days 27-34. Wild type (wt) APC (p312) levels increased at day 6 with transient proteolysis/truncation to p130 form between days 12 and 15; p312 reappeared by day 19 and returned to baseline by day 34. The kinetics of β-Cat 45 /β-catenin nuclear accumulation and acetylation (Ac-β-Cat Lys49 ) from days 6 to 27, followed by loss of phosphorylation/acetylation by day 34 was almost identical; Tcf-4 co-immunoprecipitated with β-Cat 45 /β-catenin and localized immunohistochemically to β-Cat 41/45 -positive regions leading to elevated cyclin D1 expression, during the hyperproliferative, but not regression phases of TMCH. CKIε mediated phosphorylation of β-Cat 45 , resulting in stabilization/nuclear translocation of β-Cat 45 may be critical for maintaining proliferation at days 6-27. Reversal of GSK-3β phosphorylation and APC changes may be equally critical during the regression phase from days 27 to 34

  16. Application of magnetic source imaging in localizing the epileptic foci in patients with grey matter heterotopia

    International Nuclear Information System (INIS)

    Sun Jilin; Wu Jie; Jia Xiuchuan; Li Sumin

    2011-01-01

    Objective: To evaluate the value of magnetic source imaging (MSI) in localizing the epileptic foci of patients with histologically proved grey matter heterotopia (GMH) and seizure. Methods: MSI examinations were performed on 8 patients with GMH and seizure. The location of the epileptic foci defined by MSI was compared with the results of the ECoG. After imaging examinations, all patients received operation with 13-48 months follow up to observe the effectiveness of the operation. Results: Among the 8 patients, 1 had hippocampal sclerosis, 2 had focal cortical dysplasia of type Ⅰ B and 1 had focal cortical dysplasia of type Ⅱ B. MRI showed normal findings in 2 cases, subcortical heterotopia in 4 cases, and nodular heterotopia in 2 cases with one having schizencephaly. The epileptic foci defined by MSI were at right temporal lobe in 2 cases, left frontal lobe in 2 cases, biparietal lobe in 1 case, left parietal lobe in 1 case, left temporal lobe in 1 case, and left frontal-parietal lobe in 1 case. The epileptic foci defined by MSI were completely overlaid with area of GMH in 4 cases, closely behind the area of GMH in case, and partly overlaid with area of CMH in 1 cases with size larger than that of the latter. One patient showed two epileptic foci with one located within the area of GMH and the other one 2 centimeters anterior to the area of GMH. One case's epileptic focus located 2 centimeters posteolateral to the area of GMH. The locations of the epileptic foci defined by MSI showed no difference with those defined by ECoG in all patients. According to Engel classification of treatment effect of epilepsy, 6 patients achieved Engle class Ⅰ ( seizure free after operation), and 2 patients Engel class Ⅳ (no changes in the frequency of occurrence of seizures before and after operation). Conclusion: MSI can noninvasively and precisely localize the epileptic foci before operation in patients with GMH and seizure. (authors)

  17. Duodenal crypt health following exposure to Cr(VI): Micronucleus scoring, γ-H2AX immunostaining, and synchrotron X-ray fluorescence microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Chad M.; Wolf, Jeffrey C.; Elbekai, Reem H.; Paranjpe, Madhav G.; Seiter, Jennifer M.; Chappell, Mark A.; Tappero, Ryan V.; Suh, Mina; Proctor, Deborah M.; Bichteler, Anne; Haws, Laurie C.; Harris, Mark A.

    2015-08-01

    Lifetime exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal damage and an increase in duodenal tumors in B6C3F1 mice. To assess whether these tumors could be the result of a direct mutagenic or genotoxic mode of action, we conducted a GLP-compliant 7-day drinking water study to assess crypt health along the entire length of the duodenum. Mice were exposed to water (vehicle control), 1.4, 21, or 180 ppm Cr(VI) via drinking water for 7 consecutive days. Crypt enterocytes in Swiss roll sections were scored as normal, mitotic, apoptotic, karyorrhectic, or as having micronuclei. A single oral gavage of 50 mg/kg cyclophosphamide served as a positive control for micronucleus induction. Exposure to 21 and 180 ppm Cr(VI) significantly increased the number of crypt enterocytes. Micronuclei and γ-H2AX immunostaining were not elevated in the crypts of Cr(VI)-treated mice. In contrast, treatment with cyclophosphamide significantly increased numbers of crypt micronuclei and qualitatively increased γ-H2AX immunostaining. Synchrotron-based X-ray fluorescence (XRF) microscopy revealed the presence of strong Cr fluorescence in duodenal villi, but negligible Cr fluorescence in the crypt compartment. Together, these data indicate that Cr(VI) does not adversely effect the crypt compartment where intestinal stem cells reside, and provide additional evidence that the mode of action for Cr(VI)-induced intestinal cancer in B6C3F1 mice involves chronic villous wounding resulting in compensatory crypt enterocyte hyperplasia.

  18. MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

    Energy Technology Data Exchange (ETDEWEB)

    Balakrishnan, Anita, E-mail: anita.balakrishnan@doctors.org.uk [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Liverpool L69 3GE (United Kingdom); Stearns, Adam T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 2JD (United Kingdom); Park, Peter J. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Harvard Medical School, Center for Biomedical Informatics, Boston, MA 02115 (United States); Dreyfuss, Jonathan M. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ashley, Stanley W. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Rhoads, David B. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Pediatric Endocrine Unit, MassGeneral Hospital for Children, Boston, MA 02114 (United States); Tavakkolizadeh, Ali, E-mail: atavakkoli@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States)

    2010-12-10

    Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

  19. MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

    International Nuclear Information System (INIS)

    Balakrishnan, Anita; Stearns, Adam T.; Park, Peter J.; Dreyfuss, Jonathan M.; Ashley, Stanley W.; Rhoads, David B.; Tavakkolizadeh, Ali

    2010-01-01

    Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

  20. Adrenergic factors involved in the control of crypt cell proliferation in jejunum and descending colon of mouse.

    Science.gov (United States)

    Kennedy, M F; Tutton, P J; Barkla, D H

    1983-01-01

    The mitotic rates in the crypts of Lieberkühn of the proximal jejunum and descending colon of mouse, following different treatments, were measured using a stathmokinetic technique. Regression coefficients, representing mitotic rates, were then calculated by the method of least squares. Treatment with adrenaline, isoprenaline, phenylephrine, phentolamine, and yohimbine all resulted in decreased mitotic rate of jejunal and colonic crypt cells. Chemical sympathectomy and cryosympathectomy had a similar effect, and chemical sympathectomy was followed by a supersensitivity to clonidine. Intraperitoneal injection of metaraminol, clonidine, propranolol, prazosin, labetolol and simultaneous injection of propranolol and adrenaline all resulted in an increased rate of crypt cell proliferation in both jejunum and colon. A significant increase in mitotic rate was observed in both tissues at night. The amplitude of this diurnal variation was decreased in both jejunum and colon following chemical sympathectomy. In addition, the amplitude of this variation in jejunum was decreased after treatment with yohimbine or phentolamine. The results of the study suggest that the sympathetic nervous system stimulates epithelial cell proliferation in both the small and large intestine and that this effect is mediated by an alpha 2-adrenoceptor. By contrast, stimulation of alpha 1- and beta-adrenoceptors is inhibitory to cell proliferation in these tissues.

  1. The role of the sympathetic nervous system in radiation-induced apoptosis in jejunal crypt cells of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Matsuu, Mutsumi; Shichijo; Kazuko; Nakamura, Yasuko; Ikeda, Yuji; Naito, Shinji; Ito, Masahiro; Okaichi, Kumio; Sekine, Ichiro

    2000-01-01

    To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells. (author)

  2. Mast cells in Canine parvovirus-2-associated enteritis with crypt abscess.

    Science.gov (United States)

    Woldemeskel, M W; Saliki, J T; Blas-Machado, U; Whittington, L

    2013-11-01

    The role of mast cells (MCs) in allergic reactions and parasitic infections is well established. Their involvement in host immune response against bacterial and viral infections is reported. In this study, investigation is made to determine if MCs are associated with Canine parvovirus-2 (CPV-2)-induced enteritis with crypt abscess (ECA). Mast cell count (MCC) was made on toluidine blue-stained intestinal sections from a total of 34 dogs. These included 16 dogs exhibiting ECA positive for CPV-2 and negative for Canine distemper virus and Canine coronavirus by immunohistochemistry and fluorescent antibody test, 12 dogs with inflammatory bowel disease (IBD), and 6 non-ECA/non-IBD (control) dogs. The average total MCC per high-power field in ECA (40.8 ± 2.2) and IBD (24.7 ± 2.1) was significantly higher (P .05), MCC was also higher in ECA than in IBD. The present study for the first time has documented significantly increased MCs in CPV-2-associated ECA as was previously reported for IBD, showing that MCs may also play an important role in CPV-2-associated ECA. Further studies involving more CPV-infected dogs are recommended to substantiate the findings.

  3. A comprehensive statistical classifier of foci in the cell transformation assay for carcinogenicity testing.

    Science.gov (United States)

    Callegaro, Giulia; Malkoc, Kasja; Corvi, Raffaella; Urani, Chiara; Stefanini, Federico M

    2017-12-01

    The identification of the carcinogenic risk of chemicals is currently mainly based on animal studies. The in vitro Cell Transformation Assays (CTAs) are a promising alternative to be considered in an integrated approach. CTAs measure the induction of foci of transformed cells. CTAs model key stages of the in vivo neoplastic process and are able to detect both genotoxic and some non-genotoxic compounds, being the only in vitro method able to deal with the latter. Despite their favorable features, CTAs can be further improved, especially reducing the possible subjectivity arising from the last phase of the protocol, namely visual scoring of foci using coded morphological features. By taking advantage of digital image analysis, the aim of our work is to translate morphological features into statistical descriptors of foci images, and to use them to mimic the classification performances of the visual scorer to discriminate between transformed and non-transformed foci. Here we present a classifier based on five descriptors trained on a dataset of 1364 foci, obtained with different compounds and concentrations. Our classifier showed accuracy, sensitivity and specificity equal to 0.77 and an area under the curve (AUC) of 0.84. The presented classifier outperforms a previously published model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Incidental white-matter foci on MRI in ''healthy'' subjects: evidence of subtle cognitive dysfunction

    International Nuclear Information System (INIS)

    Baum, K.A.; Schulte, C.; Girke, W.; Reischies, F.M.; Felix, R.

    1996-01-01

    The clinical significance of incidental white-matter foci seen on MRI is controversial. Mainly using a computer-assisted neuropsychological test battery, we tested the hypothesis that there is a clinical correlate of these foci. We studied 41 individuals aged 45-65 years with no history of neurological or psychiatric disorder, in whom no indication of central nervous system abnormalities was found on standardised neurological examination. A computer-assisted neuropsychological test battery, with the advantage of precise measuring of both time and deviation (e. g. in position memory tests), and rating scales for emotional dysfunction were administered; selected soft neurological signs were assessed. In 16 subjects (39 %) MRI showed high-signal foci in the white matter on spin-echo sequences. White-matter foci not adjacent to the lateral ventricles were found to be related to performance on immediate visual memory/visuoperceptual skills, visuomotor tracking/psychomotor speed and, to a lesser degree, learning capacity and abstract and conceptual reasoning skills. Subtle cognitive dysfunction would appear to be a clinical correlate of punctate white-matter foci on MRI of otherwise ''healty'' individuals. (orig.). With 1 fig., 2 tabs

  5. Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis

    Science.gov (United States)

    Jones, Mark G.; Fabre, Aurélie; Schneider, Philipp; Cinetto, Francesco; Sgalla, Giacomo; Jogai, Sanjay; Alzetani, Aiman; Marshall, Ben G.; O’Reilly, Katherine M.A.; Warner, Jane A.; Lackie, Peter M.; Davies, Donna E.; Hansell, David M.; Nicholson, Andrew G.; Sinclair, Ian; Brown, Kevin K.; Richeldi, Luca

    2016-01-01

    In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a “wave” of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 104 to 9.9 × 107 μm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3 of lung tissue to a maximum of 11.1 per mm3 of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair. PMID:27275013

  6. [An autopsy case of brain candidiasis in premature infant: morphology and intraparenchymal distribution of Candida foci].

    Science.gov (United States)

    Yamaguchi, K; Goto, N

    1993-07-01

    An autopsy case of brain candidiasis occurring in a premature infant is presented, and the morphology and intraparenchymal distribution of Candida foci are described in detail with the aid of serial sections of the affected brain. The patient was a boy, who was born after 25 weeks of gestation and died on day 15. Candida foci were composed of two infectious forms of Candida (yeasts and pseudohyphae) and various inflammatory reactions of the host. They were widely disseminated in the brain parenchyma, leptomeninges and ventricular system. In view of their morphology, they were classified into the acute and chronic inflammatory types. The acute type foci, characterized by microabscess of infiltration of neutrophils, were large and localized predominantly in the cerebral white matter, fiber tracts, central grey matter of the midbrain, reticular formation, floor of fourth ventricle and subependymal germinal layer; most of the acute type foci were found in the watershed zones where the blood supply was considered to be poorer than the other parts of the brain parenchyma. In contrast, the chronic type foci, characterized by nodular proliferation of astrocytes, were small and localized in the grey matter (the cerebral cortex, basal ganglia and brainstem nuclei) and the leptomeninges. This study suggests that Candida infection to the brain may occur by different two kinds of way correlating with the proper vasoarchitecture of brain. In addition, it is recommended to make a close examination of the maternal vagina, placenta and umbilical cord after delivery to detect the risk of Candida infection.

  7. Spatial distribution of schistosomiasis foci on Itamaracá Island, Pernambuco, Brazil

    Directory of Open Access Journals (Sweden)

    CS Barbosa

    2004-08-01

    Full Text Available Acute cases of schistosomiasis have been found on the coastal area of Pernambuco, Brazil, due to environmental disturbances and disorderly occupation of the urban areas. This study identifies and spatially marks the main foci of the snail host species, Biomphalaria glabrata on Itamaracá Island. The chaotic occupation of the beach resorts has favoured the emergence of transmission foci, thus exposing residents and tourists to the risk of infection. A database covering five years of epidemiological investigation on snails infected by Schistosoma mansoni in the island was produced with information from the geographic positioning of the foci, number of snails collected, number of snails tested positive, and their infection rate. The spatial position of the foci were recorded through the Global Positioning System (GPS, and the geographical coordinates were imported by AutoCad. The software packages ArcView and Spring were used for data processing and spatial analysis. AutoCad 2000 was used to plot the pairs of coordinates obtained from GPS. Between 1998 and 2002 5009 snails, of which 12.2% were positive for S. mansoni, were collected in Forte Beach. A total of 27 foci and areas of environmental risk were identified and spatially analyzed allowing the identification of the areas exposed to varying degrees of risk.

  8. Localized air foci in the lower thorax in the patients with pneumothorax: skip pneumothoraces.

    Science.gov (United States)

    Higuchi, Takeshi; Takahashi, Naoya; Kiguchi, Takao; Shiotani, Motoi; Maeda, Haruo

    2013-08-01

    To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1-93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ(2) test. All P values pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Identification of Chinese plague foci from long-term epidemiological data

    Science.gov (United States)

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C.

    2012-01-01

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed. PMID:22570501

  10. Magnetic resonance imaging in relation to EEG epileptic foci in tuberous sclerosis

    International Nuclear Information System (INIS)

    Tamaki, Kyoko; Okuno, Takehiko; Ito, Masatoshi; Asato, Reinin; Konishi, Junji; Mikawa, Haruki

    1990-01-01

    In 20 patients with tuberous sclerosis (TS), who were sequentially treated for epilepsy at our clinic, the high signal lesions in the cerebral cortex and subcortex detected on T2 weighted magnetic resonance imaging (MRI) were compared with the interictal EEG findings. In four cases who showed a unilateral distribution of the MRI lesions, there was a good correlation between the laterality of the affected lobes and the localization of the EEG epileptic foci. Thirteen cases with more than four affected lobes in both hemispheres also showed bilateral epileptic foci on EEG. The MRI lesions in the occipital lobes showed the best correlation with the EEG epileptic foci, while the worst correlation was seen in the frontal lobes. In addition, the cases with four or more affected lobes without laterality on MRI are more likely to show bilateral synchronization on EEG. The prognosis of epilepsy in these cases was found to be rather poor. (author)

  11. [THE PRESENT STATE OF EPIZOOTOLOGICAL MONITORING OF THE NATURAL FOCI OF INFECTIONS IN THE RUSSIAN FEDERATION].

    Science.gov (United States)

    Trankvilevsky, D V; Tsarenko, V A; Zhukov, V I

    2016-01-01

    The facilities of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare play a leading role in epizootological monitoring. The specialists (zoologists and entomologists) of Hygiene and Epidemiology Centers do basic work in the subjects of the Russian Federation. The data obtained in the participation of different ministries and departments are used to analyze the results of monitoring. The latter is one of the important steps in the management of the epidemic, process in natural focal infections. In recent years, there has been an unjustified reduction in the volume of studies in the natural foci. This negatively affects the reliability of estimates and predictions of the epidemic activity of the natural foci of infections. Ensuring the national, security of the Russian Federation, epidemiological surveillance, and control of its natural foci requires staffing and appropriate professional training in the zoological and entomological subdivisions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare.

  12. Scintigraphy in detection of latent inflammatory foci in patients with pseudarthroses

    International Nuclear Information System (INIS)

    Woy-Wojciechowski, J.; Zawadzinski, S.

    1982-01-01

    Treatment of infected pseudarthroses is one of the most difficult problems in orthopaedic surgery. Presence of latent inflammatory foci may be a serious complication after bone grafting. In 14 cases of pseudarthroses radioisotope scanning demonstrated in 5 cases presence of additional latent inflammatory foci which gave cues as to the type and extent of surgical treatment. In all these cases evaluation of the local condition by X-ray examination was insufficient. Isotope scanning was useful for a radical surgical treatment making possible complete eradication of the inflammation and reducing thus the risk of inflammation recurrence at the site of the operation performed for achieving bone union or for implanting bone graft. (author)

  13. Visualization of the dynamic multimerization of human Cytomegalovirus pp65 in punctuate nuclear foci

    International Nuclear Information System (INIS)

    Cui Zongqiang; Zhang Ke; Zhang Zhiping; Liu Yalan; Zhou Yafeng; Wei Hongping; Zhang Xian-En

    2009-01-01

    The phosphorylated protein pp65 of human Cytomegalovirus (HCMV) is the predominant virion protein and the major tegument constituent. It plays important roles in HCMV infection and virion assembly. Live cell imaging and fluorescence recovery after photobleaching (FRAP) analysis showed that HCMV pp65 accumulated dynamically in punctuate nuclear foci when transiently expressed in mammalian cells. Fluorescence resonance energy transfer (FRET) imaging disclosed that pp65 can self-interact in its localization foci. Yeast two-hybrid assay verified that pp65 is a self-associating protein, and the N-terminal amino acids 14-22 were determined to be essential for pp65 self-association. However, these amino acids were not related to pp65 localization in the specific nuclear foci. The interaction of pp65 and ppUL97 was also studied by FRET microscopy, and the result suggested that there is another signal sequence in pp65, being the ppUL97 phosphorylation site, that is responsible for localization of pp65 in nuclear foci. These results help to understand the function of pp65 in HCMV infection and virion morphogenesis.

  14. Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa

    Science.gov (United States)

    Kuroda, Masako; Hirami, Yasuhiko; Hata, Masayuki; Mandai, Michiko; Takahashi, Masayo; Kurimoto, Yasuo

    2014-01-01

    Background The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. Methods A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch’s membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). Results The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, Pretinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa. PMID:24591813

  15. TRPV1 expression on peritoneal endometriosis foci is associated with chronic pelvic pain.

    Science.gov (United States)

    Rocha, Marcelo Gondim; e Silva, Júlio César Rosa; Ribeiro da Silva, Alfredo; Candido Dos Reis, Francisco José; Nogueira, Antonio Alberto; Poli-Neto, Omero Benedicto

    2011-06-01

    To investigate the expression of capsaicin receptor (transient receptor potential vanilloid type 1 [TRPV1]) in the peritoneal endometriosis foci of women with and without chronic pelvic pain (CPP). A case-control study was conducted on 49 women with endometriosis who underwent laparoscopy, 28 of whom had CPP and 21 without CPP. Samples from peritoneum of the rectouterine excavation (2 cm2) were obtained by laparoscopy, fixed in 4% formaldehyde, and underwent immunohistochemistry analysis using rabbit anti-TRPV1 (1:400) polyclonal antibody. Image analysis revealed that the immunoreactivity for TRPV1 was more frequent in specimens (endometriosis foci) from women with CPP (n = 15 of 28, 53.6%), compared to samples from the endometriosis foci of women without CPP (n = 6 of 21, 28.6%; P = .04). There was no correlation with duration, intensity of pain, or stage of the disease (endometriosis). The present study shows that TRPV1 expression in peritoneal endometriosis foci is related to CPP in women. However, this association is not related to the endometriosis stage. In view of the immunoreactivity for TRPV1 observed here, we believe that some endometriotic lesions may provide a scenario for TRPV1 to be tonically active and this activity may contribute to the underlying pathology of CPP.

  16. DNA DSB measurements and modelling approaches based on gamma-H2AX foci time evolution

    Science.gov (United States)

    Esposito, Giuseppe; Campa, Alessandro; Antonelli, Francesca; Mariotti, Luca; Belli, Mauro; Giardullo, Paola; Simone, Giustina; Antonella Tabocchini, Maria; Ottolenghi, Andrea

    DNA double strand breaks (DSBs) induced by ionising radiation are considered the main dam-age related to the deleterious consequences in the cells. Unrepaired or mis-repaired DSBs can cause mutations or loss of chromosome regions which can eventually lead to cell death or neo-plastic transformation. Quantification of the number and complexity of DSBs induced by low doses of radiation remains a complex problem. About ten years ago Rogakou et al. proposed an immunofluorescent technique able to detect even a single DSB per cell. This approach is based on the serine 139 phosphorylation of many molecules (up to 2000) of histone H2AX (γg-H2AX) following the induction of a DSB in the DNA. DSB can be visualized as foci by immunofluores-cence by using phospho-specific antibodies, so that enumeration of foci can be used to measure DSB induction and processing. It is still not completely clear how γ-H2AX dephosphorylation takes place; however it has been related with DSB repair, in particular with the efficiency of DSB repair. In this work we analyse the H2AX phosphorylation-dephosphorylation kinetics after irradiation of primary human fibroblasts (AG1522 cell line) with radiation of differing quality, that is γ-rays and α-particles (125 keV/µm), with the aim of comparing the time evolution of γ-H2AX foci. Our results show that, after a dose of 0.5 Gy, both γ-rays and α-particles induce the maximum number of γ-H2AX foci within 30 minutes from irradiation, that this number depends on the radiation type and is consistent with the number of track traversal in α-irradiated nuclei, that the dephosphorylation kinetics are very different, being the α-induced foci rate of disappearence slower than that of γ-induced foci. In this work a modellistic approach to estimate the number of DSB induced by γ-rays detectable by using the γ-H2AX assay is presented. The competing processes of appearance and disappearance of visible foci will be modeled taking into account the

  17. Female human resource professionals’ job embeddedness in relation to commitment foci: An exploratory study

    Directory of Open Access Journals (Sweden)

    Ingrid L. Potgieter

    2018-06-01

    Full Text Available Orientation: Managers and human resource practitioners who are concerned about managing talent as a critical resource need to recognise how employees’ job embeddedness relates to their commitment foci within the organisation. By understanding this relationship, gaps can be identified and talent can be managed optimally. Research purpose: The purpose of the study was, firstly, to establish whether a significant relationship exists between job embeddedness and a set of commitment foci and, secondly, to identify the variables that contribute the most to the relationship. Motivation for the study: Organisations increasingly devote more attention to initiatives that enhance the commitment and job embeddedness of their employees in order to assist in the design of a sound talent management plan to close the talent gaps. Research approach, design and method: A quantitative approach was used in this study, utilising a cross-sectional survey design to achieve the objective of the study. Descriptive statistics, Pearson’s product-moment correlations and canonical correlation analysis were conducted. The participants were primarily black women at an early stage of their career, who were employed in the human resource management field in a professional capacity. Main findings: The results indicated that job embeddedness significantly and positively accounted for the variance in organisational and occupational commitment foci of the participants. Practical and managerial implications: Human resource practitioners and managers need to consider how the job embeddedness of employees – specifically female employees – affects their commitment foci in developing talent management plans as part of the organisational strategy. Conclusions: The findings of the study provided empirical confirmation of theoretical views on the psychological aspects that keep employees embedded in their jobs and how these aspects relate to their commitment foci.

  18. The circadian rhythm for the number and sensitivity of radiation-induced apoptosis in the crypts of mouse small intestine

    International Nuclear Information System (INIS)

    Ijiri, K.; Potten, C.S.

    1990-01-01

    Survival curves were constructed from dose-incidence curves for apoptosis in the crypts of mouse small intestine, using the number of apoptotic cells after high doses (N M ) as maximum cell population size. The mean lethal doses (D 0 ) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both D 0 and N M values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. (author)

  19. Mapping transmission foci to eliminate malaria in the People's Republic of China, 2010-2015: a retrospective analysis.

    Science.gov (United States)

    Feng, Jun; Tu, Hong; Zhang, Li; Zhang, Shaosen; Jiang, Shan; Xia, Zhigui; Zhou, Shuisen

    2018-03-07

    China has initiated the National Malaria Elimination Action Plan, which aims to eliminate malaria by 2020. However, the transmission of malaria occurs sporadically or in distinct foci, which greatly hampers progress toward elimination in China and other countries. The object of this study was to foci categorization and evaluates whether the response met the requirements issued by the nation or WHO. Residual transmissions were investigated and located with fine spatial resolution mapping from parasitological confirmed malaria cases by use of routine national surveillance data. The "1-3-7" timeframes were monitored for each focus between 2012 and 2015. Each focus was identified, and the application of appropriate measures was evaluated. A total of 5996 indigenous cases were recorded between 2010 and 2015; during this period, the number of cases declined by 99.1% (2010, n = 4262; 2015, n = 39). Most indigenous cases (92.5%) were reported in Anhui (n = 2326), Yunnan (n = 1373), Henan (n = 930), Hubei (n = 459), and Guizhou (n = 458). The temporal distribution showed that the indigenous malaria cases were clustered during the period of May to August. A total of 320 foci were carefully investigated and analyzed: 24 were active foci; 72, residual non-active foci; and 224 cleared-up foci. For the foci response evaluation, all the active foci were investigated within 7 days, while 80.2% of the residual non-active foci were responded within 7 days. In addition, reactive case detection (RACD) was carried out with 92.9% of the active foci and vector investigation carried out with 75%. For residual non-active foci, RACD was carried out with 83.2% and vector investigation with 78.2% of the foci. This study used nationwide data to categorize foci in China and evaluate the response of these areas during the control and elimination phases. Our approach stratifies future control responses by identifying those locations where the elimination of endemic

  20. Crypts, Phantoms, and Cultural Trauma: A Hauntological Approach to Recent British First World War Fiction

    Directory of Open Access Journals (Sweden)

    Anna Branach-Kallas

    2017-10-01

    Full Text Available In my article, I analyse selected British novels about the First World War published at the turn of the 20th century, from the theoretical perspectives proposed by Maria Torok and Nicolas Abraham in The Shell and the Kernel: Renewals of Psychoanalysis. Pat Barker in Toby’s Room (2012 and Sue Gee in Earth and Heaven (2000 imagine their protagonists’ difficult evolution from melancholia to mourning after the loss of brothers and/or lovers, at the front. The concepts of incorporation and illness of mourning are used to explore the complicated process of bereavement in Barker’s novel, where hauntology becomes a form of honte-ology, from the French honte, shame. In Gee’s beautifully melancholic novel, the haunting trauma of loss is subtly evoked by images of empty fields, neglected farms, urban vistas filled with spectral figures of unemployed veterans. Moreover, Earth and Heaven affects the reader so deeply because the understated pain of loss becomes movingly tangible after the accidental death of the central protagonist’s six-year-old son, which seems to “condense” the pain of war bereavements a decade after the conflict. My intention is also to demonstrate that Sebastian Faulks in Birdsong (1993, Esther Freud in Summer at Gaglow (1997 and Pat Barker in Another World (1998 approach the Great War as a phantom haunting their contemporary protagonists. The persistence of the unknown past has a profound impact on these characters and only by trying to relate to the Great War do they find answers to their existential dilemmas. This directs our attention to the incomplete processes of First World War mourning, the persistence of endless grief and the potential continuity of unresolved trauma(s in transgenerational memory. The five novels under consideration also problematise the issue of silence—the unsayable family secret and/or the collective disregard for the national past. The psychoanalytic concept of crypt illuminates the relation

  1. Regional cerebral blood flow in epileptic foci using [I-123] IMP-SPECT

    International Nuclear Information System (INIS)

    Konishi, Tohru

    1989-01-01

    Fifty-six epileptic patients, whose ages ranged from 6 months to 16 years (a mean age, 8 years and 2 months), were examined by single photon emission computed tomography (SPECT) with [I-123] N-isopropyl p-iodoamphetamine (IMP). Of these patients, 44 had partial seizures (PS) and 12 had generalized seizures (GS). SPECT revealed abnormality of regional cerebral blood flow (rCBF) in 24 PS patients (54.5%), being correlated with EEG abnormality. Among the 24 patients, 22 had a decreased rCBF and 2 others had an increased rCBF. According to the PS type, rCBF abnormality in the foci was less frequently observed for benign age-related partial epilepsy (2/9) than for the other types of partial epilepsy (22/35). Among 35 patients with the other types of partial epilepsy, SPECT showed foci in the frontal (12), central (3), parietal (4), temporal (6), and occipital (6) regions, and diffuse spike-wave or the lack of paroaxysmals (4). The EEG foci was of the left hemisphere in 12 patients, and of the right hemisphere in 18 patients. Higher incidence of rCBF abnormality was associated with the temporal, partietal, and frontal foci than with the occipital foci. There was no correlation between the incidence of rCBF abnormlaity and the frequency of seizure activities on EEG. Complex partial seizures had a tendency to be associated with rCBF abnormality. In comparing IMP uptake in evaluable 17 patients with a decreased rCBF, a mean %CBF in foci compared to that in the contralateral area was 91.9%. All of the 12 GS patients showed no focal reduction of rCBF around the cortex. Patients with tonic-clonic seizure and myoclonic seizure had almost normal IMP images. The IMP images of organic lesions were a marked reduction of rCBF. IMP-SPECT may also be suitable for evaluating the underlying organic and secondary involving disorders with epilepsy. (N.K.)

  2. Direct Measurements of Human Colon Crypt Stem Cell Niche Genetic Fidelity: The Role of Chance in Non-Darwinian Mutation Selection

    Directory of Open Access Journals (Sweden)

    Haeyoun eKang

    2013-10-01

    Full Text Available Perfect human stem cell genetic fidelity would prevent aging and cancer. However, perfection would be difficult to achieve, and aging is universal and cancers common. A hypothesis is that because mutations are inevitable over a human lifetime, downstream mechanisms have evolved to manage the deleterious effects of beneficial and lethal mutations. In the colon, a crypt stem cell architecture reduces the number of mitotic cells at risk for mutation accumulation, and multiple niche stem cells ensure that a lethal mutation within any single stem cell does not lead to crypt death. In addition, the architecture of the colon crypt stem cell niche may harness probability or chance to randomly discard many beneficial mutations that might lead to cancer. An analysis of somatic chromosome copy number alterations (CNAs reveals a lack of perfect fidelity in individual normal human crypts, with age-related increases and higher frequencies in ulcerative colitis, a proliferative, inflammatory disease. The age-related increase in somatic CNAs appears consistent with relatively normal replication error and cell division rates. Surprisingly, and similar to point mutations in cancer genomes, the types of crypt mutations were more consistent with random fixation rather than selection. In theory, a simple non-Darwinian way to nullify selection is to reduce the size of the reproducing population. Fates are more determined by chance rather than selection in very small populations, and therefore selection may be minimized within small crypt niches. The desired effect is that many beneficial mutations that might lead to cancer are randomly lost by drift rather than fixed by selection. The subdivision of the colon into multiple very small stem cell niches may trade Darwinian evolution for non-Darwinian somatic cell evolution, capitulating to aging but reducing cancer risks.

  3. Autoradiographic investigations on the question of diurnal variations of cell proliferation in the jejunal crypt epithelia of mice

    International Nuclear Information System (INIS)

    Herterich, G.C.

    1982-01-01

    In this work the question was investigated whether the proliferation activity of the crypt epithelia of the small intestine of mice is subject to diurnal variations. The results published so far to settle this question are contradictory. The flow rate at the beginning and end of the S phase was measured as a function of daytime for the jejunal crypt epithelia of mice following a double labelling with 3-H and 14-C-TdR. The quotient of the cell flow rate in and out of the S phase is supposed to be = 1 over the whole day if there are no diurnal variations. The method of measurements of the cell flow rate was chosen above all because the quotient is largely independent of the variation from animal to animal. The experiments provided dues as to the presence of deviations of the quotient of cell flow rate at the end and beginning of the S phase and of the mitotic index from the daily mean value. However, on account of the relatively large statistical variations of the values at the different daytimes it is not possible to state clearly whether the cell proliferation of the jejunal epithelium is subject to diurnal variations. Should there be such variations, then they are not large at any rate. (orig./MG) [de

  4. New foci of cutaneous leishmaniasis in central Kenya and the Rift Valley.

    Science.gov (United States)

    Sang, D K; Okelo, G B; Ndegwa, C W; Ashford, R W

    1993-01-01

    Active case detection and investigations of sandfly resting places in suspected transmission sites of cutaneous leishmaniasis in central Kenya and the Rift Valley resulted in the identification of several foci of the disease in Samburu, Isiolo, Laikipia, Nakuru and Nyandarua districts. The foci occurred in areas ranging from semi-arid lowlands at 400 m altitude to highland plateaux at 2500 m, including the floor of the Rift Valley, and were mostly inhabited by recently settled communities, nomads and migrant charcoal burners. Four species of Phlebotomus, 3 of the subgenus Larroussius (P. pedifer, P. aculeatus and P. guggisbergi) and one Paraphlebotomus (P. saevus) were collected from caves, rock crevices and tree hollows found in river valleys and in lava flows.

  5. Advances in infectious foci imaging using 99mTc radiolabelled antibiotics

    International Nuclear Information System (INIS)

    Seyedeh Fatemeh Mirshojaei

    2015-01-01

    Conventional methods of infection diagnosis, relying on experimental tests and culture of organisms from infected foci have continued to developing new technologies and automation. Nuclear medicine is a reliable diagnostic technique capable to detect infectious foci in human disease. A wide range of radiolabeled agents have been evaluated for demonstrating their ability to distinguish microbial infectious lesions. New researches continue to be made on the use of radiolabeled antibiotics which as well as being highly specific in the diagnosis of infection would be useful in monitoring of disease treatment. Here, the new approaches of infection scintigraphic imaging by radiolabeled antibiotics are thoroughly discussed in order to assess and compare their diagnostic value as targeting imaging radiopharmaceuticals. (author)

  6. Canine Uterine Leiomyoma with Epithelial Tissue Foci, Adenomyosis, and Cystic Endometrial Hyperplasia

    OpenAIRE

    Karagiannis, George S.; Pelekanis, Mihalis; Loukopoulos, Panayiotis; Ververidis, Haris N.; Kaldrymidou, Eleni

    2011-01-01

    An 11-year-old Labrador Retriever bitch with a history of intermittent, sanguineous vaginal discharge of a six-month duration was presented. During exploratory laparotomy, two well-delineated, intramural masses were identified bilaterally in the uterine horns. Histopathologic examination of the mass on the left horn showed that it was a typical leiomyoma. However, the second mass appeared with an unusual coexistence of histological lesions, involving epithelial tissue foci, mild focal adenomy...

  7. Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci

    Czech Academy of Sciences Publication Activity Database

    Jiruška, Přemysl; Prokš, J.; Otáhal, Jakub; Mareš, Pavel

    2007-01-01

    Roč. 16, č. 7 (2007), s. 627-635 ISSN 1059-1311 R&D Projects: GA ČR(CZ) GA309/03/0770; GA ČR GA304/05/2582 Institutional research plan: CEZ:AV0Z5011922 Keywords : epileptic foci * secondary bilateral synchrony * neocortex Subject RIV: ED - Physiology Impact factor: 1.815, year: 2007

  8. Imaging Features that Discriminate between Foci Induced by High- and Low-LET Radiation in Human Fibroblasts

    International Nuclear Information System (INIS)

    Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano, Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

    2006-01-01

    In this study, we investigated the formation of radiation-induced foci in normal human fibroblasts exposed to X rays or 130 keV/mum nitrogen ions using antibodies to phosphorylated protein kinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantify the immunofluorescence of radiation-induced foci. The size of radiation-induced foci increased for both proteins over a 2-h period after nitrogen-ion irradiation, while the size of radiation-induced foci did not change after exposure to low-LET radiation. The number of radiation-induced ATMp foci showed a more rapid rise and greater frequency after X-ray exposure and was resolved more rapidly such that the frequency of radiation-induced foci decreased by 90 percent compared to 60 percent after exposure to high-LET radiation 2 h after 30 cGy. In contrast, the kinetics of radiation-induced gamma-H2AX focus formation was similar for high- and low-LET radiation in that it reached a plateau early and remained constant for up to 2 h. High-resolution 3D images of radiation-induced gamma-H2AX foci and dosimetry computation suggest that multiple double-strand breaks from nitrogen ions are encompassed within large nuclear domains of 4.4 Mbp. Our work shows that the size and frequency of radiation-induced foci vary as a function of radiation quality, dose, time and protein target. Thus, even though double-strand breaks and radiation-induced foci are correlated, the dynamic nature of both contradicts their accepted equivalence for low doses of different radiation qualities

  9. A clinical study on the detection of epileptogenic foci in epileptics using computerized tomography

    International Nuclear Information System (INIS)

    Kobayashi, Eiki

    1979-01-01

    EEG findings of partial epilepsy were classified as localized abnormality in 65%, diffuse abnormality in 21% and borderline in 14% of cases. Abnormal CT findings of partial epilepsy were observed in 37% of the patients. These findings consisted of localized abnormalities in 68% and diffuse abnormalities in 32% of cases, and these were classified into 4 groups; localized or diffuse cerebral atrophy, localized low density, localized or multiple disseminated high density (calicification) and localized enhancement with contrast medium. Abnormal CT findings were more frequent in the cases of onset under 10 years of age. The incidence of CT abnormality seemed to be higher in the cases with continuous, especially continuous localized EEG abnormality, than in the cases with the other types of EEG abnormality. In the 16 cases out of 37 with CT abnormality, that is in 43% of the cases, the location of abnormal CT findings was coincident with that of their EEG foci. And epileptogenic foci were verified in 16% of all the patients. Cerebral angiography showed various and precise vascular abnormalities in 82% of these cases. And the CT abnormal group of patients was inferred to have considerable histopathological changes in the epileptogenic foci, but the group with normal CT images did not yield such significant findings. In comparison with partial epilepsy, 100 cases of generalized epilepsy were studied, and CT abnormalities were observed only in 16% of cases. Diffuse cerebral atrophy was naturally the most frequent kind of abnormal finding, and localized abnormalities were not so frequent in generalized epilepsy. (Kanao, N.)

  10. [EPIDEMIOLOGIC SITUATION BY NATURAL-FOCI INFECTIONS IN THE CRIMEA FEDERAL DISTRICT IN 2014-2015].

    Science.gov (United States)

    Popova, A-Yu; Kulichenko, A N; Maletskaya, O V; Vasilenko, N F; Shaposhnikova, L I; Kotenev, E S; Dubyansky, V M; Volynkina, A S; Lisitskaya, Ya V; Samarina, I V; Penkovskaya, N A; Evstafiev, I L; Tovpinets, N N; Tsapko, N V; Belova, O A; Agapitov, D S; Samoded, T N; Nadolny, A A; Kovalenko, I S; Yakunin, S N; Shvarsalon, N K; Zinich, L S; Tikhonov, S N; Lyamkin, G I; Zharnikova, I V; Evchenko, Yu M

    2016-01-01

    Analysis of epidemic manifestations of natural-foci infections (NFI), clarification of spectrum of their causative agents, determination of epizootic activity of natural foci in the Crimea Federal District (KFD). Epizootologic examination of 10 administrative districts of KDF was carried out. 291 pools (2705 specimens) of ixodes ticks and 283 samples of organs of small mammals were studied by PCRmethod for the presence of DNA/RNA of causative agents of a number of NFI. Morbidity by NFI in KFD was registered by 6 nosologies: Lyme borreliosis, Marseilles fever, leptospirosis; tularemia, intestine yersiniosis and tick-borne viral encephalitis, wherein, transmissive infections made up 91.6%. Circulation of causative agents of Crimea hemorrhagic fever, Q fever, group of tick-borne spotted fever, Lyme borreliosis, human granulocytic anaplasmosis, human monocytic ehrlichiosis, hemorrhagic fever with renal syndrome, West Nile fever, tularemia and leptospirosis was established. Due to activity of natural foci of NFI further monitoring of epidemiologic and epizootologic manifestations of these infections in the Crimea, including using genetic methods of analysis, is necessary for ensuring sanitary-epidemiologic welfare of KFD population.

  11. Axial diffusivity changes in the motor pathway above stroke foci and functional recovery after subcortical infarction.

    Science.gov (United States)

    Liu, Gang; Peng, Kangqiang; Dang, Chao; Tan, Shuangquan; Chen, Hongbing; Xie, Chuanmiao; Xing, Shihui; Zeng, Jinsheng

    2018-01-01

    Secondary degeneration of the fiber tract of the motor pathway below infarct foci and functional recovery after stroke have been well demonstrated, but the role of the fiber tract above stroke foci remains unclear. This study aimed to investigate diffusion changes in motor fibers above the lesion and identify predictors of motor improvement within 12 weeks after subcortical infarction. Diffusion tensor imaging and the Fugl-Meyer (FM) scale were conducted 1, 4, and 12 weeks (W) after a subcortical infarct. Proportional recovery model residuals were used to assign patients to proportional recovery and poor recovery groups. Region of interest analysis was used to assess diffusion changes in the motor pathway above and below a stroke lesion. Multivariable linear regression was employed to identify predictors of motor improvement within 12 weeks after stroke. Axial diffusivity (AD) in the underlying white matter of the ipsilesional primary motor area (PMA) and cerebral peduncle (CP) in both proportional and poor recovery groups was lower at W1 compared to the controls and values in the contralesional PMA and CP (all P motor improvement within 12 weeks after stroke in patients with proportional or poor recovery. Increases of AD in the motor pathway above stroke foci may be associated with motor recovery after subcortical infarction. Early measurement of diffusion metrics in the ipsilesional non-ischemic motor pathway has limited value in predicting future motor improvement patterns (proportional or poor recovery).

  12. The DEAD box helicase RDE-12 promotes amplification of RNAi in cytoplasmic foci in C. elegans.

    Science.gov (United States)

    Yang, Huan; Vallandingham, Jim; Shiu, Philip; Li, Hua; Hunter, Craig P; Mak, Ho Yi

    2014-04-14

    RNAi is a potent mechanism for downregulating gene expression. Conserved RNAi pathway components are found in animals, plants, fungi, and other eukaryotes. In C. elegans, the RNAi response is greatly amplified by the synthesis of abundant secondary small interfering RNAs (siRNAs). Exogenous double-stranded RNA is processed by Dicer and RDE-1/Argonaute into primary siRNA that guides target mRNA recognition. The RDE-10/RDE-11 complex and the RNA-dependent RNA polymerase RRF-1 then engage the target mRNA for secondary siRNA synthesis. However, the molecular link between primary siRNA production and secondary siRNA synthesis remains largely unknown. Furthermore, it is unclear whether the subcellular sites for target mRNA recognition and degradation coincide with sites where siRNA synthesis and amplification occur. In the C. elegans germline, cytoplasmic P granules at the nuclear pores and perinuclear Mutator foci contribute to target mRNA surveillance and siRNA amplification, respectively. We report that RDE-12, a conserved phenylalanine-glycine (FG) domain-containing DEAD box helicase, localizes in P granules and cytoplasmic foci that are enriched in RSD-6 but are excluded from the Mutator foci. Our results suggest that RDE-12 promotes secondary siRNA synthesis by orchestrating the recruitment of RDE-10 and RRF-1 to primary siRNA-targeted mRNA in distinct cytoplasmic compartments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. PCNA-dependent accumulation of CDKN1A into nuclear foci after ionizing irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rudolph, Jeanette Heede [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Jakob, Burkhard [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Fink, Daniela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Tobias, Frank [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Blattner, Christine [Karlsruhe Inst. of Technology (KIT) (Germany). Inst. of Toxicology and Genetics; Taucher-Scholz, Gisela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany)

    2012-03-26

    The cyclin-dependent kinase inhibitor CDKN1A/p21 confers cell-cycle arrest in response to DNA damage and inhibits DNA replication through its direct interaction with the proliferating cell nuclear antigen (PCNA) and cyclin/cyclin-dependent kinase complexes. Previously, we reported that in response to densely ionizing radiation CDKN1A rapidly is recruited to the sites of particle traversal, and that CDKN1A foci formation in response to heavy ions is independent of its transactivation by TP53. In this paper, we show that exposure of normal human fibroblasts to X-rays or to H2O2 also induces nuclear accumulations of CDKN1A. We find that CDKN1A foci formation in response to radiation damage is dependent on its dephosphorylation and on its direct physical interaction with PCNA. Live cell imaging analyses of ectopically expressed EGFP-CDKN1A and dsRed-PCNA show rapid recruitment of both proteins into foci after radiation damage. Detailed dynamic measurements reveal a slightly delayed recruitment of CDKN1A compared to PCNA, which is best described by bi-exponential curve fitting, taking the preceding binding of PCNA to DNA into account. Finally, we propose a regulatory role for CDKN1A in mediating PCNA function after radiation damage, and provide evidence that this role is distinct from its involvement in nucleotide excision repair and unrelated to double-strand break repair.

  14. Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle.

    Directory of Open Access Journals (Sweden)

    Wesley H Stepp

    2017-10-01

    Full Text Available We have shown previously that Sp100 (a component of the ND10 nuclear body represses transcription, replication and establishment of incoming human papillomavirus (HPV DNA in the early stages of infection. In this follow up study, we show that Sp100 does not substantially regulate viral infection in the maintenance phase, however at late stages of infection Sp100 interacts with amplifying viral genomes to repress viral processes. We find that Sp100 localizes to HPV16 replication foci generated in primary keratinocytes, to HPV31 replication foci that form in differentiated cells, and to HPV16 replication foci in CIN 1 cervical biopsies. To analyze this further, Sp100 was down regulated by siRNA treatment of differentiating HPV31 containing cells and levels of viral transcription and replication were assessed. This revealed that Sp100 represses viral transcription and replication in differentiated cells. Analysis of Sp100 binding to viral chromatin showed that Sp100 bound across the viral genome, and that binding increased at late stages of infection. Therefore, Sp100 represses the HPV life cycle at both early and late stages of infection.

  15. An APC:WNT counter-current-like mechanism regulates cell division along the colonic crypt axis: a mechanism that explains how APC mutations induce proliferative abnormalities that drive colon cancer development.

    Directory of Open Access Journals (Sweden)

    Bruce M Boman

    2013-11-01

    Full Text Available APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside. WNT signaling, in contrast, is high at the bottom (where SCs reside and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g. survivin are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric. APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly-proliferating cells during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes.

  16. An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development

    Science.gov (United States)

    Boman, Bruce M.; Fields, Jeremy Z.

    2013-01-01

    APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID:24224156

  17. AFSC/RACE/EcoFOCI - Ichthyoplankton data collected in support of FOCI assessment surveys and ecosystem observations in the Bering, Beaufort, and Chukchi Seas and the Gulf of Alaska 1972 to Present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The dataset contains records of fish eggs and larvae collected during FOCI assessment surveys. Records include all data pertinent to identify where specimens were...

  18. Protection of the Peyer's patch-associated crypt and villus epithelium against methotrexate-induced damage is based on its distinct regulation of proliferation

    NARCIS (Netherlands)

    Renes, Ingrid B.; Verburg, Melissa; Bulsing, Nathalie P.; Ferdinandusse, Sacha; Büller, Hans A.; Dekker, Jan; Einerhand, Alexandra W. C.

    2002-01-01

    The crypt and villus epithelium associated with Peyer's patches (PPs) is largely spared from methotrexate (MTX)-induced damage, compared with the non-patch (NP) epithelium. To assess the mechanism(s) preventing damage to the PP epithelium after MTX treatment, epithelial proliferation, apoptosis, and

  19. Further textile artefacts from the Royal Crypt at Prague Castle (CZ). A tablet-woven silk band and fragments of a child's funeral tunic

    Czech Academy of Sciences Publication Activity Database

    Bravermanová, M.; Březinová, Helena

    2015-01-01

    Roč. 2015, č. 57 (2015), s. 104-110 ISSN 2245-7135 R&D Projects: GA ČR(CZ) GA14-06451S Institutional support: RVO:67985912 Keywords : Royal Crypt * Anna Falcká * tablet-weaving * archaeological textile Subject RIV: AC - Archeology, Anthropology, Ethnology

  20. The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Strandsby, Anne Bystrup; Larsen, Casper Kornbech

    2011-01-01

    The colonic epithelium absorbs and secretes electrolytes and water. Ion and water absorption occurs primarily in surface cells, whereas crypt cells perform secretion. Ion transport in distal colon is regulated by aldosterone, which stimulates both Na+ absorption and K+ secretion. The electrogenic...

  1. Comparison of the dose-response relationship of radiation-induced apoptosis in the hippocampal dentate gyrus and intestinal crypt of adult mice

    International Nuclear Information System (INIS)

    Kim, J. S.; Yang, M.; Kim, J.; Lee, D.; Kim, J. C.; Shin, T.; Kim, S. H.; Moon, C.

    2012-01-01

    The present study compared the dose-response curves for the frequency of apoptosis in mouse hippocampal dentate gyrus (DG) and intestinal crypt using whole-body gamma irradiation. The incidence of gamma-ray-induced apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labelling (TUNEL) method. TUNEL-positive apoptotic nuclei in the DG and intestinal crypt were increased in a dose-dependent pattern (0-2 Gy). The dose-response curves were linear-quadratic, with a significant relationship between the appearance of apoptosis and irradiation dose. The slopes of the dose-response curves in the DG were much steeper (∼5-6-fold) than those in the intestinal crypt within the range of 0-1 Gy exposure. Hippocampal DG might be a more effective and sensitive evaluation structure than the intestinal crypt to estimate the degree of radiation exposure in damaged organs of adult mice exposed to low irradiation dose. copy; The Author 2011. Published by Oxford Univ. Press. All rights reserved. (authors)

  2. AFSC/RACE/EcoFOCI: 2010 BEST and BSIERP Study 1WE10/WE10-08

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Ecosystem & Fisheries-Oceanography Coordinated Investigations (Eco-FOCI) is an effort by National Oceanic and Atmospheric Administration (NOAA) and associated...

  3. ASSESSMENT OF EPIZOOTIC ACTIVITY AND EPIDEMIC RISK IN HEMORRHAGIC FEVER WITH RENAL SYNDROME FOREST FOCI OF PRIMORSKII KRAI

    Directory of Open Access Journals (Sweden)

    Tatyana Valerevna Kushnareva

    2016-06-01

    The obtained threshold indicators of active circulation of Amur hantavirus in population dynamics of natural host allows to predicting the periods of the increased risk of infection for people in HFRS forest foci.

  4. ASSESSMENT OF EPIZOOTIC ACTIVITY AND EPIDEMIC RISK IN HEMORRHAGIC FEVER WITH RENAL SYNDROME FOREST FOCI OF PRIMORSKY KRAI

    Directory of Open Access Journals (Sweden)

    Tatyana Valerevna Kushnareva

    2017-06-01

    The obtained threshold values of Amur hantavirus active circulation in population dynamics of the natural host allows to predict the periods of the increased risk of infection in HFRS forest foci for humans.

  5. White matter abnormalities in the anterior temporal lobe suggest the side of the seizure foci in temporal lobe epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Y.; Yagishita, A. [Tokyo Metropolitan Neurological Hospital, Department of Neuroradiology, Fuchu, Tokyo (Japan); Arai, N. [Tokyo Metropolitan Neurological Institute, Department of Clinical Neuropathology, Fuchu, Tokyo (Japan)

    2006-07-15

    White matter abnormalities in the anterior temporal lobe (WAATL) are sometimes observed on magnetic resonance (MR) images of patients with temporal lobe epilepsy (TLE). Our purpose was to determine whether WAATL could indicate if the seizure foci are ipsilateral on electroencephalograms (EEG) in TLE patients. We reviewed 112 consecutive patients with medically intractable TLE. We compared the side of seizure foci on EEG (preoperative and intraoperative) and MR images. Both loss of gray-white matter demarcation and increased signal intensity changes in the anterior white matter (positive WAATL) were observed in 54 of 112 patients (48.2%) with TLE. WAATL were present on the same side as the seizure foci on preoperative intracranial EEG with subdural electrodes (iEEG) and on intraoperative electrocorticography (ECG) in all the patients. In 47 patients, MR images showed WAATL and focal lesions that were possibly epileptogenic for TLE. In 2 of the 47 patients, the seizure foci on iEEG and ECG were contralateral to the focal lesion; in the remaining 45 patients, the seizure foci on surface EEG (sEEG) and ECG and the focal lesion were on the same side. In three patients, no focal lesions were seen but WAATL were present on the same side as the seizure foci on sEEG and ECG. In four patients, MR images showed focal lesions for which epileptogenicity was questionable, and WAATL on the same side as the seizure foci on EEG. WAATL are clinically useful because they indicate the side of the seizure foci. (orig.)

  6. White matter abnormalities in the anterior temporal lobe suggest the side of the seizure foci in temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Adachi, Y.; Yagishita, A.; Arai, N.

    2006-01-01

    White matter abnormalities in the anterior temporal lobe (WAATL) are sometimes observed on magnetic resonance (MR) images of patients with temporal lobe epilepsy (TLE). Our purpose was to determine whether WAATL could indicate if the seizure foci are ipsilateral on electroencephalograms (EEG) in TLE patients. We reviewed 112 consecutive patients with medically intractable TLE. We compared the side of seizure foci on EEG (preoperative and intraoperative) and MR images. Both loss of gray-white matter demarcation and increased signal intensity changes in the anterior white matter (positive WAATL) were observed in 54 of 112 patients (48.2%) with TLE. WAATL were present on the same side as the seizure foci on preoperative intracranial EEG with subdural electrodes (iEEG) and on intraoperative electrocorticography (ECG) in all the patients. In 47 patients, MR images showed WAATL and focal lesions that were possibly epileptogenic for TLE. In 2 of the 47 patients, the seizure foci on iEEG and ECG were contralateral to the focal lesion; in the remaining 45 patients, the seizure foci on surface EEG (sEEG) and ECG and the focal lesion were on the same side. In three patients, no focal lesions were seen but WAATL were present on the same side as the seizure foci on sEEG and ECG. In four patients, MR images showed focal lesions for which epileptogenicity was questionable, and WAATL on the same side as the seizure foci on EEG. WAATL are clinically useful because they indicate the side of the seizure foci. (orig.)

  7. Imaging Features that Discriminate between Foci Induced by High-and Low-LET Radiation in Human Fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano,Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

    2006-10-08

    In this study, we investigated the formation ofradiation-induced foci in normal human fibroblasts exposed to X rays or130 keV/mum nitrogen ions using antibodies to phosphorylated proteinkinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantifythe immunofluorescence of radiation-induced foci. The size ofradiation-induced foci increased for both proteins over a 2-h periodafter nitrogen-ion irradiation, while the size of radiation-induced focidid not change after exposure to low-LET radiation. The number ofradiation-induced ATMp foci showed a more rapid rise and greaterfrequency after X-ray exposure and was resolved more rapidly such thatthe frequency of radiation-induced foci decreased by 90 percent comparedto 60 percent after exposure to high-LET radiation 2 h after 30 cGy. Incontrast, the kinetics of radiation-induced gamma-H2AX focus formationwas similar for high- and low-LET radiation in that it reached a plateauearly and remained constant for up to 2 h. High-resolution 3D images ofradiation-induced gamma-H2AX foci and dosimetry computation suggest thatmultiple double-strand breaks from nitrogen ions are encompassed withinlarge nuclear domains of 4.4 Mbp. Our work shows that the size andfrequency of radiation-induced foci vary as a function of radiationquality, dose, time and protein target. Thus, even though double-strandbreaks and radiation-induced foci are correlated, the dynamic nature ofboth contradicts their accepted equivalence for low doses of differentradiation qualities.

  8. Quality assurance (QA) program in BNCT. RBE of 7 NCT beams for intestinal crypt regeneration in mice

    International Nuclear Information System (INIS)

    John, Gueulette; De Coster, Blanche-Marie; Wambersie, Andre; Gregoire, Vincent; Rasmussen, Finn S.; Auterinen, Iiro; Binns, Peter; Blaumann, Herman; Matsumura, Akira; Liu Hongming

    2006-01-01

    The epithermal neutron beams presently used for Neutron Capture Therapy (NCT) differ substantially in their composition (relative contribution of the different dose components to the total dose), in their dose rate (depending on the power of the reactor) as well as in their general feature (e.g. beam delivery system). Each of these elements might alter significantly the biological effectiveness of the beams. Therefore, the Relative Biological Effectiveness (RBE) of 7 NCT beams was intercompared, for a reference biological system (crypt regeneration in mice) and under well-defined irradiation conditions. This type of experiments - which should facilitate the exchange of radiobiological/clinical information - should take part of the Quality Assurance (QA) procedure of all NCT beams. (author)

  9. Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype.

    Directory of Open Access Journals (Sweden)

    Stephanie Plog

    Full Text Available The human CLCA4 (chloride channel regulator, calcium-activated modulates the intestinal phenotype of cystic fibrosis (CF patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological properties. The CLCA4b gene is a pig-specific duplication product of the CLCA4 ancestor and its protein is exclusively expressed in small and large intestinal crypt epithelial cells, a niche specifically occupied by no other porcine CLCA family member. Surprisingly, a unique deleterious mutation of the CLCA4b gene is spread among modern and ancient breeds in the pig population, but this mutation did not result in an apparent phenotype in homozygously affected animals. Electrophysiologically, neither the products of the wild type nor of the mutated CLCA4b genes were able to evoke a calcium-activated anion conductance, a consensus feature of other CLCA proteins. The apparently pig-specific duplication of the CLCA4 gene with unique expression of the CLCA4b protein variant in intestinal crypt epithelial cells where the porcine CFTR is also present raises the question of whether it may modulate the porcine CF phenotype. Moreover, the naturally occurring null variant of CLCA4b will be valuable for the understanding of CLCA protein function and their relevance in modulating the CF phenotype.

  10. Cell Adhesion Molecule CD166/ALCAM Functions Within the Crypt to Orchestrate Murine Intestinal Stem Cell HomeostasisSummary

    Directory of Open Access Journals (Sweden)

    Nicholas R. Smith

    2017-05-01

    Full Text Available Background & Aims: Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs, it remains unclear what role cell adhesion plays in shaping the regulatory niche. Previously we have shown that the cell adhesion molecule and cancer stem cell marker, CD166/ALCAM (activated leukocyte cell adhesion molecule, is highly expressed by both active-cycling Lgr5+ ISCs and adjacent Paneth cells within the crypt base, supporting the hypothesis that CD166 functions to mediate ISC maintenance and signal coordination. Methods: Here we tested this hypothesis by analyzing a CD166–/– mouse combined with immunohistochemical, flow cytometry, gene expression, and enteroid culture. Results: We found that animals lacking CD166 expression harbored fewer active-cycling Lgr5+ ISCs. Homeostasis was maintained by expansion of the transit-amplifying compartment and not by slow-cycling Bmi1+ ISC stimulation. Loss of active-cycling ISCs was coupled with deregulated Paneth cell homeostasis, manifested as increased numbers of immature Paneth progenitors due to decreased terminal differentiation, linked to defective Wnt signaling. CD166–/– Paneth cells expressed reduced Wnt3 ligand expression and depleted nuclear β-catenin. Conclusions: These data support a function for CD166 as an important cell adhesion molecule that shapes the signaling microenvironment by mediating ISC–niche cell interactions. Furthermore, loss of CD166 expression results in decreased ISC and Paneth cell homeostasis and an altered Wnt microenvironment. Keywords: Intestinal Stem Cell, Homeostasis

  11. Objective scoring of transformed foci in BALB/c 3T3 cell transformation assay by statistical image descriptors.

    Science.gov (United States)

    Urani, C; Corvi, R; Callegaro, G; Stefanini, F M

    2013-09-01

    In vitro cell transformation assays (CTAs) have been shown to model important stages of in vivo carcinogenesis and have the potential to predict carcinogenicity in humans. Advantages of CTAs are their ability of revealing both genotoxic and non-genotoxic carcinogens while reducing both experimental costs and the number of animals used. The endpoint of the CTA is foci formation, and requires classification under light microscopy based on morphology. Thus current limitations for the wide adoption of the assay partially depend on a fair degree of subjectivity in foci scoring. An objective evaluation may be obtained after separating foci from background monolayer in the digital image, and quantifying values of statistical descriptors which are selected to capture eye-scored morphological features. The aim of this study was to develop statistical descriptors to be applied to transformed foci of BALB/c 3T3, which cover foci size, multilayering and invasive cell growth into the background monolayer. Proposed descriptors were applied to a database of 407 foci images to explore the numerical features, and to illustrate open problems and potential solutions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. p53 binding protein 1 foci as a biomarker of DNA double strand breaks induced by ionizing radiation

    International Nuclear Information System (INIS)

    Ng, C.K.M.; Wong, M.Y.P.; Lam, R.K.K.; Ho, J.P.Y.; Chiu, S.K.; Yu, K.N.

    2011-01-01

    Foci of p53 binding protein 1 (53 BP1) have been used as a biomarker of DNA double-strand breaks (DSBs) in cells induced by ionizing radiations. 53 BP1 was shown to relocalize into foci shortly after irradiation, with the number of foci closely paralleling the number of DNA DSBs. However, consensus on criteria in terms of the numbers of 53 BP1 foci to define cells damaged by direct irradiation or by bystander signals has not been reached, which is partly due to the presence of 53 BP1 also in normal cells. The objective of the present work was to study the changes in the distribution of cells with different numbers of 53 BP1 foci in a cell population after low-dose ionizing irradiation (<0.1 Gy) provided by alpha particles, with a view to propose feasible criteria for defining cells damaged by direct irradiation or by bystander signals. It was proposed that the change in the percentage of cells with 1-3 foci should be used for such purposes. The underlying reasons were discussed.

  13. Age-related disease association of endogenous γ-H2AX foci in mononuclear cells derived from leukapheresis.

    Directory of Open Access Journals (Sweden)

    Shepherd H Schurman

    Full Text Available The phosphorylated form of histone H2AX (γ-H2AX forms immunohistochemically detectable foci at DNA double strand breaks. In peripheral blood mononuclear cells (PBMCs derived from leukapheresis from patients enrolled in the Baltimore Longitudinal Study of Aging, γ-H2AX foci increased in a linear fashion with regards to age, peaking at ~57 years. The relationship between the frequency of γ-H2AX foci and age-related pathologies was assessed. We found a statistically significant (p = 0.023 50% increase in foci in PBMCs derived from patients with a known history of vitamin D deficiency. In addition, there were trends toward increased γ-H2AX foci in patients with cataracts (34% increase, p<0.10 and in sleep apnea patients (44%, p<0.10. Among patients ≥57 y/o, we found a significant (p = 0.037 36% increase in the number of γ-H2AX foci/cell for patients with hypertension compared to non-hypertensive patients. Our results support a role for increased DNA damage in the morbidity of age-related diseases. γ -H2AX may be a biomarker for human morbidity in age-related diseases.

  14. [THE EPIZOOTIC AND EPIDEMIC ACTIVITY OF NATURAL TULAREMIA FOCI OF DIFFERENT LANDSCAPE EPIDEMIOLOGICAL TYPES IN 2009-2014].

    Science.gov (United States)

    Meshcheryakova, I S; Mikhailova, T V; Demidova, T N; Kormilitsyna, M I

    2016-01-01

    to assess the present state of the natural tularemia foci of different landscape epidemiological types, by using individual focal areas as an example. Epizootological monitoring and epidemiological analysis were conducted in the areas of natural tularemia foci of tundra (Wrangel Island), meadow-field (Central Federal District of the Russian Federation), flood-swamp (Arkhangelsk Region, Khanty-Mansi Autonomous District), and steppe (Mongolii) types. Small mammals (organs, blood), tularemia patients' sera, and environniental objects were examined. Molecular genetic and immune serological diagnostic assays were used. The incidence of tularemia in the past decade was analyzed using the maps for the epidemiological examinations of tularemia cases and medical reports. The natural foci of tularemia were established to continue to actively operate. There were 2913 cases of tularemia in the Russian Federation in 2001 to 2014. The flood-swamp natural foci, in which there were summer transmissive tularemia outbreaks, the largest of high occurred in Khanti-Mansiysk in 2013 when a total of 1005 people fell ill, are a special epidemic hazard. Analysis of the tularemia outbreaks suggests that there is a need for continuous epizootological monitoring of the areas of natural tularemia foci for the timely prediction and prevention of epidemic complications. It is noted that there is an unfounded reduction in the scope of preventive measures, and immunoprevention in particular, and a weaker control of the antitularemia immune status in the population residing in the area of active natural foci of tularemia.

  15. Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.

    Science.gov (United States)

    Hu, Jiaxin; Rong, Ziye; Gong, Xin; Zhou, Zhengyang; Sharma, Vivek K; Xing, Chao; Watts, Jonathan K; Corey, David R; Mootha, V Vinod

    2018-03-15

    Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has ∼2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.

  16. Identification of a developmental gene expression signature, including HOX genes, for the normal human colonic crypt stem cell niche: overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis.

    Science.gov (United States)

    Bhatlekar, Seema; Addya, Sankar; Salunek, Moreh; Orr, Christopher R; Surrey, Saul; McKenzie, Steven; Fields, Jeremy Z; Boman, Bruce M

    2014-01-15

    Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, 68 in the middle, and 131 in the top. Among genes upregulated in the bottom, ∼30% were classified as growth and/or developmental genes including several in the PI3 kinase pathway, a six-transmembrane protein STAMP1, and two homeobox (HOXA4, HOXD10) genes. qPCR and immunostaining validated that HOXA4 and HOXD10 are selectively expressed in the normal crypt bottom and are overexpressed in colon carcinomas (CRCs). Immunostaining showed that HOXA4 and HOXD10 are co-expressed with the SC markers CD166 and ALDH1 in cells at the normal crypt bottom, and the number of these co-expressing cells is increased in CRCs. Thus, our findings show that these two HOX genes are selectively expressed in colonic SCs and that HOX overexpression in CRCs parallels the SC overpopulation that occurs during CRC development. Our study suggests that developmental genes play key roles in the maintenance of normal SCs and crypt renewal, and contribute to the SC overpopulation that drives colon tumorigenesis.

  17. Foci of cyclin A2 interact with actin and RhoA in mitosis.

    Science.gov (United States)

    Loukil, Abdelhalim; Izard, Fanny; Georgieva, Mariya; Mashayekhan, Shaereh; Blanchard, Jean-Marie; Parmeggiani, Andrea; Peter, Marion

    2016-06-09

    Cyclin A2 is a key player in the regulation of the cell cycle. Its degradation in mid-mitosis depends primarily on the ubiquitin-proteasome system (UPS), while autophagy also contributes. However, a fraction of cyclin A2 persists beyond metaphase. In this work, we focus on cyclin A2-rich foci detected in mitosis by high resolution imaging and analyse their movements. We demonstrate that cyclin A2 interacts with actin and RhoA during mitosis, and that cyclin A2 depletion induces a dramatic decrease in active RhoA in mitosis. Our data suggest cyclin A2 participation in RhoA activation in late mitosis.

  18. Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

    Science.gov (United States)

    Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

    2017-12-08

    Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci

  19. A Systematic Literature Mining of Sponge City: Trends, Foci and Challenges Standing Ahead

    Directory of Open Access Journals (Sweden)

    Zongmin Li

    2018-04-01

    Full Text Available Sponge City research has been attracting extensive attention both in practical and theoretical research field, as the increased threat of flood risk and environmental safety due to urbanization. Varies names of Sponge City prevalent in different countries, which leads to disconnection of literature in the same field of Sponge City. In this paper, a systematic literature mining of Sponge City is presented. A literature analysis system is created, which includes literature export from Web of Sciences and systematic analysis via NoteExpress and CiteSpace. Based on the final document storage which contains 962 articles, general trends are identified. Literature is classified into 9 theme types. Research foci of Sponge City are detected by citation and keywords burst detection. Further, some future research directions of Sponge City are anticipated, including trans-disciplinary approaches, a comprehensive design framework, application of information technology, and case studies of Sponge City in more parts of the world. The significance of this paper lies in summarizing past research, identifying research types, foci and anticipating some future research directions.

  20. Arabidopsis TCP Transcription Factors Interact with the SUMO Conjugating Machinery in Nuclear Foci

    Directory of Open Access Journals (Sweden)

    Magdalena J. Mazur

    2017-11-01

    Full Text Available In Arabidopsis more than 400 proteins have been identified as SUMO targets, both in vivo and in vitro. Among others, transcription factors (TFs are common targets for SUMO conjugation. Here we aimed to exhaustively screen for TFs that interact with the SUMO machinery using an arrayed yeast two-hybrid library containing more than 1,100 TFs. We identified 76 interactors that foremost interact with the SUMO conjugation enzyme SCE1 and/or the SUMO E3 ligase SIZ1. These interactors belong to various TF families, which control a wide range of processes in plant development and stress signaling. Amongst these interactors, the TCP family was overrepresented with several TCPs interacting with different proteins of the SUMO conjugation cycle. For a subset of these TCPs we confirmed that the catalytic site of SCE1 is essential for this interaction. In agreement, TCP1, TCP3, TCP8, TCP14, and TCP15 were readily SUMO modified in an E. coli sumoylation assay. Strikingly, these TCP-SCE1 interactions were found to redistribute these TCPs into nuclear foci/speckles, suggesting that these TCP foci represent sites for SUMO (conjugation activity.

  1. The Performance of Ictal Brain SPECT for Localizing Epileptogenic Foci in Temporal Lobe epilepsies

    International Nuclear Information System (INIS)

    Kim, Eun Sil; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Koh, Chang Soon; Chang, Kee Hyun; Lee, Sang Kun; Chung, Chun Kee

    1995-01-01

    Anterior temporal lobectomy has become a widely used respective surgery in patients with medically intractable temporal lobe epilepsies. Prerequisites of this resection include the accurate localization of the epileptogenic focus and the determination that the proposed resection would not result in unacceptable postoperative memory or language deficits. The purpose of this study was to evaluate the performance of ictal SPECT compared to MRI findings for localization of epileptogenic foci in this group of patients. 11 patients who had been anterior temporal oral lobectomy were evaluated with ictal 99m Tc-HMPAO SPECT and MRI. MRI showed 8/11(73%) concordant lesion to the side of surgery and ictal SPECT also showed 8/11(73%) concordant hyperperfusion. In 3 cases with incorrect or nonlocalizing findings of MRI, ictal SPECT showed concordant hyperperfusion. In 2 cases confirmed by pre-resectional invasive EEG, MRI showed bilateral and contralateral lesion but ictal SPECT showed concordant hyperperfusion. 3 delayed injection of ictal SPECT showed discordant hyperperfusion. Thus, ictal SPECT was a useful method for localizing epileptogenic foci in temporal lobe epilepsies and appeared complementay to MRI.

  2. [Malaria in Guiana. II. The characteristics of different foci and antimalarial control].

    Science.gov (United States)

    Mouchet, J; Nadire-Galliot, M; Gay, F; Poman, J P; Lepelletier, L; Claustre, J; Bellony, S

    1989-01-01

    In French Guiana, the distribution of malaria in foci inhabited by quite different ethnic groups calls for specific studies. Along the Oyapock on the Brasilian border and along the Litani on the Surinam border, incidence among American Indians and Creoles ranges from 300 and 900 per thousand; Plasmodium falciparum accounts for 65% and P. vivax for 35%. Along the middle and lower Maroni on the Surinam border, the Boni and Ndjukas Negroes move freely through the frontier and since the civil strife Surinamese used to attend health centres of Guiana. Therefore it is difficult to find the sources of contamination and the incidence among French citizens; P. falciparum is the only parasite recorded in this focus. In 1987 a small outbreak mainly due to P. vivax, occurred in a Lao refugees village in the hinterland. The coastal foci harbour large communities of Haitian and Brazilian migrants. The vector is Anopheles darlingi and up to now there is no evidence that other species could be involved. The rise of malaria despite of control measures involves several factors: the house spraying is no more accepted by a large percentage of house holders and the alternative larviciding has only a limited efficacy; the houses of American Indians have no walls to be sprayed; there is a continuous introduction of parasites by migrants. It has been said that vectors have change their behaviour toward exophily but such a statement has not yet been supported by evidence. All these factors should be taken in account to improve malaria control.

  3. Characterization of tick-borne encephalitis (TBE) foci in Germany and Latvia (1997-2000).

    Science.gov (United States)

    Süss, Jochen; Schrader, Christina; Abel, Ulrich; Bormane, Antra; Duks, Arnis; Kalnina, Vaira

    2002-06-01

    Knowledge concerning the prevalence of the tick-borne encephalitis virus (TBEV) in wild living tick populations is very important for understanding the epidemiology of the disease and for immuno prophylactic strategy. In Germany high and low risk areas of TBE exist. In the years 1997-2000, 533 autochthonous clinical TBE cases were recorded, in the high-risk areas of Bavaria and Baden-Wuerttemberg 140 and 363, and in the low risk areas in Hesse (Odenwald) and Rhineland-Palatinate 22 and 8, respectively. Corresponding to these case reports we have measured the virus prevalence in free living ticks in these four risk areas and compared these findings with the situation in high-risk areas in Latvia. In the years 1997-2000, 2,797 clinical TBE cases were recorded in Latvia. For the studies in Germany, a total of 17,398 Ixodesricinus ticks (14,860 nymphs and 2,538 adults) were collected by flagging and examined for TBEV, in Latvia the corresponding numbers were 525 I. ricinus ticks (350 adults and 175 nymphs) and 281 I. persulcatus ticks (adults only). Information concerning annual and seasonal differences of the TBEV prevalence in natural TBE foci is not available in Germany. This paper is a continuation of the study (Süss et al., 1999), starting in 1997. We investigated every year, in May and September, the virus prevalence in ticks in high risk areas of Bavaria (8 foci) and Baden-Wuerttemberg (5 foci). A total of 15,400 ticks (13,100 nymphs and 2,300 adults) were examined for TBEV. The ticks were tested for the presence of TBEV-RNA using a sensitive, nested-RT-PCR. The virus prevalence in the Bavarian foci of the whole tick population ranged from 0.3 to 2.0% during these four years, in adults between 1.2 and 5.3% and in nymphs between 0.1 and 1.4%. In the high-risk areas of Baden-Wuerttemberg, in the Black Forest, the estimated virus prevalence rates of investigated ticks varied from 0.2 to 3.4%, in adults from 0 to 4.8%, and in nymphs from 0.2 to 3.4%. Using the same

  4. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication

    Science.gov (United States)

    Rafelski, Susanne M.; Keller, Lani C.; Alberts, Jonathan B.; Marshall, Wallace F.

    2011-04-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.

  5. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication

    International Nuclear Information System (INIS)

    Rafelski, Susanne M; Keller, Lani C; Marshall, Wallace F; Alberts, Jonathan B

    2011-01-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713–22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed

  6. Imaging and clinical characteristics of children with multiple foci of microsusceptibility changes in the brain on susceptibility-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Tetsu [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Aida, Noriko; Fujita, Kazutoshi; Shishikura, Ayako [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Takahara, Taro; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Miyata, Daiki [Kanagawa Children' s Medical Center, Department of Circulation Medicine, Yokohama (Japan); Inoue, Tomio [Yokohama City University, Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

    2010-10-15

    Microsusceptibility changes in the brain are well known to correspond with microbleeds or micrometal fragments in adults, but this phenomenon has not been explored well in children. To assess imaging and clinical characteristics of children with multiple foci of microsusceptibility changes using susceptibility-weighted imaging (SWI). Between 2006 and 2008, 12 children with multiple foci of microsusceptibility on SWI without corresponding abnormal signal on conventional MRI were identified and were retrospectively assessed. The locations of foci of microsusceptibility included the cerebral white matter, basal ganglia, brainstem and cerebellar white matter, without any clear systematic anatomic distribution. CT (n = 5) showed no calcification at the locations corresponding to the microsusceptibility on SWI. Conventional MR imaging showed white matter volume loss (n = 5), delayed myelination (n = 2), acute infarction (n = 1), chronic infarction (n = 1), meningitis (n = 1), slight signal abnormality in the white matter (n = 1) and no abnormal findings (n = 1). Follow-up SWI (n = 3) showed no change of the microsusceptibility foci. Interestingly, all children had a history of heart surgery under extracorporeal circulation for congenital heart disease. Multiple foci of microsusceptibility can be seen in the brain on SWI in children with congenital heart disease who underwent heart surgery with extracorporeal circulation. (orig.)

  7. The foci of DNA double strand break-recognition proteins localize with γH2AX after heat treatment

    International Nuclear Information System (INIS)

    Takahashi, Akihisa; Mori, Eiichiro; Ohnishi, Takeo

    2010-01-01

    Recently, there have been many reports concerning proteins which can recognize DNA double strand break (DSBs), and such proteins include histone H2AX phosphorylated at serine 139 (γH2AX), ataxia telangiectasia mutated (ATM) phospho-serine 1981, DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phospho-threonine 2609, Nijmegen breakage syndrome 1 (NBS1) phospho-serine 343, checkpoint kinase 2 (CHK2), phospho-threonine 68, and structural maintenance of chromosomes 1 (SMC1) phospho-serine 966. Thus, it should be possible to follow the formation of DSBs and their repair using immunohistochemical methods with multiple antibodies to detect these proteins. When normal human fibroblasts (AG1522 cells) were exposed to 3 Gy of X-rays as a control, clearly discernable foci for these proteins were detected, and these foci localized with γH2AX foci. After heat treatment at 45.5 deg C for 20 min, these proteins are partially localized with γH2AX foci. Here we show that there were slight differences in the localization pattern among these proteins, such as a disappearance from the nucleus (phospho-ATM) and translocation to the cytoplasm (phospho-NBS1) at 30 min after heat treatment, and some foci (phospho-DNA-PKcs and phospho-CHK2) appeared at 8 h after heat treatment. These results are discussed from perspectives of heat-induced denaturation of proteins and formation of DSBs. (author)

  8. Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes

    Directory of Open Access Journals (Sweden)

    Delorenzi Mauro

    2005-05-01

    Full Text Available Abstract Background The purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression. Results We have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8, the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff ≤ 0.05 of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p ≤ 0.05 along the anterior-posterior axis was observed. Conclusion All nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the

  9. The effect of 60Co γ-radiation and hydroxyurea on the in vivo chain growth of DNA in crypt cells of the small intestine of the mouse

    International Nuclear Information System (INIS)

    Johanson, K.J.; Rydberg, B.

    1977-01-01

    DNA chain growth has been studied in small intestinal crypt cells of the mouse in vivo using a sensitive method. The method was designed primarily to study radiation-induced DNA-breaks and their repair; but since there were breaks in DNA at the replicating fork, it was also possible to study DNA chain growth after a 3 H-thymidine pulse. It was found that DNA chain growth was not depressed by 200 rad of 60 Co γ-radiation. This finding supports the hypothesis that irradiation interferes mainly with the initiation of new replicons in mammalian cells affecting DNA chain growth only at higher doses. Hydroxyurea at sufficient dosage, however, depressed or even stopped DNA chain growth in mouse crypt cells in vivo. (author)

  10. ON STRUCTURED AND DIFFUSE SEISMICITY, STIFFNESS OF EARTHQUAKE FOCI, AND NONLINEARITY OF MAGNITUDE RECURRENCE GRAPHS

    Directory of Open Access Journals (Sweden)

    Evgeny G. Bugaev

    2011-01-01

    Full Text Available Geological, geophysical and seismogeological studies are now conducted in a more detail and thus provide for determining seismic sources with higher accuracy, from the first meters to first dozens of meters [Waldhauser, Schaff, 2008]. It is now possible to consider uncertainty ellipses of earthquake hypocenters, that are recorded in the updated Earthquake Catalogue, as surfaces of earthquake focus generators. In our article, it is accepted that a maximum horizontal size of an uncertainty ellipse corresponds to an area of a focus generator, and seismic events are thus classified into two groups, earthquakes with nonstiff and stiff foci. Criteria of such a classification are two limits of elastic strain and brittle strain in case of uniaxial (3⋅10–5 or omnidirectional (10–6 compression. The criteria are established from results of analyses of parameters of seismic dislocations and earthquake foci with regard to studies of surface parameters and deformation parameters of fault zones. It is recommendable that the uniaxial compression criterion shall be applied to zones of interaction between tectonic plates, and the unilateral compression criterion shall be applied to low active (interplate areas. Sample cases demonstrate the use of data sets on nonstiff and stiff foci for separate evaluation of magnitude reoccurrence curves, analyses of structured and dissipated seismicity, review of the physical nature of nonlinearity of recurrence curves and conditions of preparation of strong earthquakes. Changes of parameters of the recurrence curves with changes of data collection square areas are considered. Reviewed are changes of parameters of the recurrence curves during preparation for the Japan major earthquake of 11 March 2011 prior to and after the major shock. It is emphasized that it is important to conduct even more detailed geological and geophysical studies and to improve precision and sensitivity of local seismological monitoring networks

  11. An investigation of multi-rate sound decay under strongly non-diffuse conditions: The crypt of the Cathedral of Cadiz

    Science.gov (United States)

    Martellotta, Francesco; Álvarez-Morales, Lidia; Girón, Sara; Zamarreño, Teófilo

    2018-05-01

    Multi-rate sound decays are often found and studied in complex systems of coupled volumes where diffuse field conditions generally apply, although the openings connecting different sub-spaces are by themselves potential causes of non-diffuse behaviour. However, in presence of spaces in which curved surfaces clearly prevent diffuse field behaviour from being established, things become more complex and require more sophisticated tools (or, better, combinations of them) to be fully understood. As an example of such complexity, the crypt of the Cathedral of Cadiz is a relatively small space characterised by a central vaulted rotunda, with five radial galleries with flat and low ceiling. In addition, the crypt is connected to the main cathedral volume by means of several small openings. Acoustic measurements carried out in the crypt pointed out the existence of at least two decay processes combined, in some points, with flutter echoes. Application of conventional methods of analysis pointed out the existence of significant differences between early decay time and reverberation time, but was inconclusive in explaining the origin of the observed phenomena. The use of more robust Bayesian analysis permitted the conclusion that the late decay appearing in the crypt had a different rate than that observed in the cathedral, thus excluding the explanation based on acoustic coupling of different volumes. Finally, processing impulse responses collected by means of a B-format microphone to obtain directional intensity maps demonstrated that the late decay was originated from the rotunda where a repetitive reflection pattern appeared between the floor and the dome causing both flutter echoes and a longer reverberation time.

  12. Diagnostic accuracy of CT, US and angiography in histologically verified hepatocellular carcinoma. Report on 125 foci in 84 cases

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Hiroo; Moriyama, Noriyuki; Shima, Yasuo; Muramatsu, Yukio; Takayasu, Kenichi; Ushio, Kyosuke; Matsue, Hiroto; Sasagawa, Michizo; Yamada, Tatsuya

    1985-02-01

    Detectability of a total of 125 foci in 84 cases with HCC was evaluated. All foci were surgically resected and confirmed histologically. Tumor size >=2.1 cm in diameter:each modality has the accuracy more than 90%, 2.0>=Tumor size>=1.1 cm:CT has the accuracy of 81%, US 56% and Angio 56% respectively. 1.0 cm>=Tumor size:CT shows the accuracy of 35%, US 5% and Angio 30%. Combined with CT, US and Angio in the lesions more than 1.1 cm in diameter, over all accuracy was 100%. Whereas, in the foci less than 1.0 cm, over all accuracy was only 45%, comparing with that of intraoperative US. 57%. Therefore, it was clarified to be very difficult to detect these small lesions, and a careful survey is needed. (author).

  13. Positive Foci of Glutathione S‐Transferase Placental Form in the Liver of Rats Given Furfural by Oral Administration

    Science.gov (United States)

    Shimizu, Akio; Nakamura, Yoshiyasu; Harada, Masaoki; Ono, Tetsuo; Sato, Kiyomi; Inoue, Tohru; Kanisawa, Masayoshi

    1989-01-01

    We observed GST‐P‐positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural‐containing diet (20–30 rag/kg diet) for 15–150 days, and killed 14 days after terminating furfural feeding. Immuno‐histochemical investigation of GST‐P‐positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural‐induced cirrhosis on chemical hepatocarcino‐genesis. PMID:2507483

  14. N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice.

    Science.gov (United States)

    Amrouche-Mekkioui, Ilhem; Djerdjouri, Bahia

    2012-09-15

    The effect of N-acetylcysteine (NAC), a pharmacological antioxidant was investigated in a murine model of chronic colitis. Male NMRI mice were given 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 10 days of water, three times. Compared to control mice given water, DSS-treated mice displayed severe imbalanced redox status with decreased glutathione and catalase, but increased malondialdehyde, protein carbonyls, nitric oxide and myeloperoxidase levels, at days 35th (active colitis) and 45th (recovery period). It also resulted in mitochondrial dysfunction, mucosal ulcers, mucin-depleted crypts and epithelial cell apoptosis. Crypt abscesses and glandular hyperplasia occurred selectively in distal colon. NAC (150 mg/kg) given in drinking water for 45 days along with 3 DSS cycles improved the hallmarks of DSS-colitis. Interestingly, the moderate impact of NAC on lipids and proteins oxidation correlated with myeloperoxidase and nitric oxide levels.NAC as a mucoregulator and a thiol restoring agent is protective on oxidative crypt alterations, mucin depletion, epithelial cell hyperplasia and apoptosis. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived reactive oxygen species in mice DDS-colitis, suggesting that a long term NAC diet might be beneficial in inflammatory bowel diseases and colorectal cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1981-08-01

    Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune-deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2.

  16. Circadian rhythms in the incidence of apoptotic cells and number of clonogenic cells in intestinal crypts after radiation using normal and reversed light conditions

    International Nuclear Information System (INIS)

    Ijiri, K.; Potten, C.S.

    1988-01-01

    Variations in the number of radiation-induced morphologically dead or dying cells (apoptotic cells) in the crypts in the small intestine of the mouse have been studied throughout a 24-h period under a normal light regimen. A clear circadian rhythm was displayed in the apoptotic incidence 3 or 6 h after irradiation for each gamma-ray dose studied (range 0.14-9.0 Gy). The most prominent circadian rhythm was obtained after 0.5 Gy. Peak time of day for inducing apoptosis was 06.00-09.00 h, and the trough occurred at 18.00-21.00 h. Some mice were also transferred to a reversed light cycle, and irradiated on different days after transfer. Apoptosis induced by 0.5 Gy or 9.0 Gy, or number of surviving crypts (microcolonies) after 11.0 Gy or 13.0 Gy was examined. The transition point for reversal of circadian rhythm in apoptosis (after 0.5 Gy) occurred 7 days after transfer and the rhythm was reversed by 14 days. The rhythm for crypt survival (i.e. for clonogenic cell radiosensitivity) was disturbed on 1 day and transition point for reversal occurred 3 days after transfer. The rhythm became reversed by 7 days. (author)

  17. Relationship between increasing concentrations of two carcinogens and statistical image descriptors of foci morphology in the cell transformation assay.

    Science.gov (United States)

    Callegaro, Giulia; Corvi, Raffaella; Salovaara, Susan; Urani, Chiara; Stefanini, Federico M

    2017-06-01

    Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i.e. the step in which transformed colonies or foci are evaluated through morphological features. An objective evaluation of morphological features has been previously obtained through automated digital processing of foci images to extract the value of three statistical image descriptors. In this study a further potential of the CTA using BALB/c 3T3 cells is addressed by analysing the effect of increasing concentrations of two known carcinogens, benzo[a]pyrene and NiCl 2 , with different modes of action on foci morphology. The main result of our quantitative evaluation shows that the concentration of the considered carcinogens has an effect on foci morphology that is statistically significant for the mean of two among the three selected descriptors. Statistical significance also corresponds to visual relevance. The statistical analysis of variations in foci morphology due to concentration allowed to quantify morphological changes that can be visually appreciated but not precisely determined. Therefore, it has the potential of providing new quantitative parameters in CTAs, and of exploiting all the information encoded in foci. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. PENGGUNAAN BRUTE FORCE ATTACK DALAM PENERAPANNYA PADA CRYPT8 DAN CSA-RAINBOW TOOL UNTUK MENCARI BISS

    Directory of Open Access Journals (Sweden)

    Indra Gunawan

    2016-09-01

    Full Text Available Algoritma Brute Force merupakan suatu aritmatika untuk mencari dan mengetahui sebuah jenis sandi atau kode yang salh satunya sebuah kode acakan misalnya jenis acakan BISS (Basic Interoperable Scrambling System. Algoritma brute force yang umumnya dipakai untuk mencari kasus kode acakan seperti ini umumnya disebut Brute Force Attack.    Brute force attack menggunakan sebuah himpunan karakter atau teks yang akan dipakai untuk referensi karakter-karakter dari kode yang ingin dicari. Himpunan karakter yang dipakai akan menjadi sebuah ukuran keefektifan dari algoritma itu sendiri. Semakin banyak anggota himpunan karakter ini, tentunya persentasi kode biss untuk sebuah kode biss dapat dicari akan tinggi. Namun, semakin banyak karakter yang ada di dalam himpunan itu harus dibayar dengan waktu pengerjaan yang lebih lama. Brute Force ini sudah mulai dikembangkan untuk mencari kode. Salah satu pengembangannya adalah pengumpulan chain sebagai database dan penggunaan Crypt8 dan CSA-Rainbow Tool yang menggunakan algoritma brute force sehingga memungkinkan untuk memangkas waktu yang diperlukan Brute Force Attack.

  19. Combination of aging and dimethylhydrazine treatment causes an increase in cancer-stem cell population of rat colonic crypts.

    Science.gov (United States)

    Levi, Edi; Misra, Sandhya; Du, Jianhua; Patel, Bhaumik B; Majumdar, Adhip P N

    2009-07-31

    Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and carcinogen exposure on the status of colon CSCs in an experimental model. We used young (4-6 months) and aged (22-24 months) rats and exposed them to the carcinogen, dimethylhydroxide (DMH). We investigated the expression of colon cancer stem cell markers, CD44, CD166, EpCam, and ALDH1 as well as EGFR expression in normal colonic crypt epithelium following carcinogen treatment. Our results demonstrate that aging per se or carcinogen treatment alone causes an increase in the number of colon cancer stems cells, as evidenced by increased immunoreactive-CSC-markers positive cells in the colonic mucosa. In aged rats, carcinogen exposure results in a more pronounced increase in colon cancer stem cells. Our study shows that in aging colon the effects of carcinogens are more pronounced, and an increase in colon CSCs is one of the earliest changes preceding tumor development. Moreover, the current investigation of the use of a panel of immunohistochemical markers of colon CSC can potentially serve as a prognostic marker during screening for colon cancer.

  20. Co-workers' Justice Judgments, own Justice Judgments and Employee Commitment: A multi-foci approach

    Directory of Open Access Journals (Sweden)

    Florence Stinglhamber

    2008-06-01

    Full Text Available Using a sample of 212 employees, we conducted a study to examine whether employees use their co-workers' fairness perceptions to generate their own justice judgments and to develop their subsequent affective commitment. The conceptual framework used to investigate these linkages is social exchange theory combined with a multiple foci approach. Results of the structural equation modeling analyses revealed that co-workers' procedural justice judgments strengthened employee's own procedural justice judgments, which in turn influenced their affective commitment to the organisation. Similarly, co-workers' interactional justice judgments increased employee's own interactional justice judgments, which in turn impacted on their affective commitment to both the supervisor and the organisation. As a whole, findings suggest that coworkers' justice judgments strengthened employee's affective attachments toward the justice sources by reinforcing employee's own justice perceptions.

  1. Multistability in Chua's circuit with two stable node-foci

    Energy Technology Data Exchange (ETDEWEB)

    Bao, B. C.; Wang, N.; Xu, Q. [School of Information Science and Engineering, Changzhou University, Changzhou 213164 (China); Li, Q. D. [Research Center of Analysis and Control for Complex Systems, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China)

    2016-04-15

    Only using one-stage op-amp based negative impedance converter realization, a simplified Chua's diode with positive outer segment slope is introduced, based on which an improved Chua's circuit realization with more simpler circuit structure is designed. The improved Chua's circuit has identical mathematical model but completely different nonlinearity to the classical Chua's circuit, from which multiple attractors including coexisting point attractors, limit cycle, double-scroll chaotic attractor, or coexisting chaotic spiral attractors are numerically simulated and experimentally captured. Furthermore, with dimensionless Chua's equations, the dynamical properties of the Chua's system are studied including equilibrium and stability, phase portrait, bifurcation diagram, Lyapunov exponent spectrum, and attraction basin. The results indicate that the system has two symmetric stable nonzero node-foci in global adjusting parameter regions and exhibits the unusual and striking dynamical behavior of multiple attractors with multistability.

  2. Canine Uterine Leiomyoma with Epithelial Tissue Foci, Adenomyosis, and Cystic Endometrial Hyperplasia

    Directory of Open Access Journals (Sweden)

    George S. Karagiannis

    2011-01-01

    Full Text Available An 11-year-old Labrador Retriever bitch with a history of intermittent, sanguineous vaginal discharge of a six-month duration was presented. During exploratory laparotomy, two well-delineated, intramural masses were identified bilaterally in the uterine horns. Histopathologic examination of the mass on the left horn showed that it was a typical leiomyoma. However, the second mass appeared with an unusual coexistence of histological lesions, involving epithelial tissue foci, mild focal adenomyosis, and cystic endometrial hyperplasia. Interestingly, such combination was never encountered before in dogs. Although uterine leiomyoma is quite usual in the reproductive system of female dogs, this case resembled relevant cases of human uterine adenomyomas in morphology, and thus it was offered a similar tentative diagnosis.

  3. Prevalence of small testicular hyperechogenic foci in subgroups of 382 non-vasectomized, azoospermic men

    DEFF Research Database (Denmark)

    Fedder, Jens

    2017-01-01

    Testicular hyperechogenic foci (THF) are associated with Klinefelter’s syndrome, cryptorchidism, infertility, and testicular germ cell neoplasia. The aims of the study were to evaluate THF in relation to etiology of azoospermia and to Sertoli cell dysfunction. The structures inside the scrotum...... technique for detection of cytokeratin-18 (CK-18). The prevalence of THF was 13.4%. uTHF was found in 11 men (2.9%), the pattern was bilateral in four while other four had bTHF in the other testis. pTHF was detected in eight cases (2.1%), and except for one case with Klinefelter’s syndrome, pTHF was in all...

  4. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    International Nuclear Information System (INIS)

    Chiolo, Irene; Tang, Jonathan; Georgescu, Walter; Costes, Sylvain V.

    2013-01-01

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment

  5. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Tang, Jonathan; Georgescu, Walter; Costes, Sylvain V.

    2013-10-01

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  6. Effect of phenytoin on cortical epileptic foci in cerveau isolé rats.

    Science.gov (United States)

    Mares, P

    1994-01-01

    The action of phenytoin was studied in acute experiments in rats with brainstem transection at the midcollicular level. Symmetrical epileptogenic foci were elicited in sensorimotor cortical areas of both hemispheres by local application of penicillin. Seven rats formed a control group, ten animals were pretreated with phenytoin (60 mg/kg i.p., 10 min before penicillin application). Synchronization of interictal discharges in control rats was delayed in comparison to animals with an intact brainstem; phenytoin did not influence this synchronization. Spontaneous transition of interictal into ictal activity was not abolished by phenytoin, i.e. in cerveau isolé preparations phenytoin lost this activity. The loss of anticonvulsant activity was not complete. Ictal episodes were modified; they started as very short ones and their duration progressively increased. Structures localized below the level of transection represent a site of at least one of the mechanisms of phenytoin anticonvulsant action.

  7. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats

    Directory of Open Access Journals (Sweden)

    Orner Gayle A

    2006-02-01

    Full Text Available Abstract Chlorophyllin (CHL is a promising chemopreventive agent believed to block cancer primarily by inhibiting carcinogen uptake through the formation of molecular complexes with the carcinogens. However, recent studies suggest that CHL may have additional biological effects particularly when given after the period of carcinogen treatment. This study examines the post-initiation effects of CHL towards aflatoxin B1 (AFB1-induced preneoplastic foci of the liver and colon. The single concentration of CHL tested in this study (0.1% in the drinking water had no significant effects on AFB1-induced foci of the liver and colons of rats.

  8. Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles

    Science.gov (United States)

    2012-01-01

    Background Little is known about the cellular effects of exposure to mixed beams of high and low linear energy transfer radiation. So far, the effects of combined exposures have mainly been assessed with clonogenic survival or cytogenetic methods, and the results are contradictory. The gamma-H2AX assay has up to now not been applied in this context, and it is a promising tool for investigating the early cellular response to mixed beam irradiation. Purpose To determine the dose response and repair kinetics of gamma-H2AX ionizing radiation-induced foci in VH10 human fibroblasts exposed to mixed beams of 241Am alpha particles and X-rays. Results VH10 human fibroblasts were irradiated with each radiation type individually or both in combination at 37°C. Foci were scored for repair kinetics 0.5, 1, 3 and 24 h after irradiation (one dose per irradiation type), and for dose response at the 1 h time point. The dose response effect of mixed beam was additive, and the relative biological effectiveness for alpha particles (as compared to X-rays) was of 0.76 ± 0.52 for the total number of foci, and 2.54 ± 1.11 for large foci. The repair kinetics for total number of foci in cells exposed to mixed beam irradiation was intermediate to that of cells exposed to alpha particles and X-rays. However, for mixed beam-irradiated cells the frequency and area of large foci were initially lower than predicted and increased during the first 3 hours of repair (while the predicted number and area did not). Conclusions The repair kinetics of large foci after mixed beam exposure was significantly different from predicted based on the effect of the single dose components. The formation of large foci was delayed and they did not reach their maximum area until 1 h after irradiation. We hypothesize that the presence of low X-ray-induced damage engages the DNA repair machinery leading to a delayed DNA damage response to the more complex DNA damage induced by alpha particles. PMID:23121736

  9. The Focinator - a new open-source tool for high-throughput foci evaluation of DNA damage

    International Nuclear Information System (INIS)

    Oeck, Sebastian; Malewicz, Nathalie M.; Hurst, Sebastian; Rudner, Justine; Jendrossek, Verena

    2015-01-01

    The quantitative analysis of foci plays an important role in many cell biological methods such as counting of colonies or cells, organelles or vesicles, or the number of protein complexes. In radiation biology and molecular radiation oncology, DNA damage and DNA repair kinetics upon ionizing radiation (IR) are evaluated by counting protein clusters or accumulations of phosphorylated proteins recruited to DNA damage sites. Consistency in counting and interpretation of foci remains challenging. Many current software solutions describe instructions for time-consuming and error-prone manual analysis, provide incomplete algorithms for analysis or are expensive. Therefore, we aimed to develop a tool for costless, automated, quantitative and qualitative analysis of foci. For this purpose we integrated a user-friendly interface into ImageJ and selected parameters to allow automated selection of regions of interest (ROIs) depending on their size and circularity. We added different export options and a batch analysis. The use of the Focinator was tested by analyzing γ-H2.AX foci in murine prostate adenocarcinoma cells (TRAMP-C1) at different time points after IR with 0.5 to 3 Gray (Gy). Additionally, measurements were performed by users with different backgrounds and experience. The Focinator turned out to be an easily adjustable tool for automation of foci counting. It significantly reduced the analysis time of radiation-induced DNA-damage foci. Furthermore, different user groups were able to achieve a similar counting velocity. Importantly, there was no difference in nuclei detection between the Focinator and ImageJ alone. The Focinator is a costless, user-friendly tool for fast high-throughput evaluation of DNA repair foci. The macro allows improved foci evaluation regarding accuracy, reproducibility and analysis speed compared to manual analysis. As innovative option, the macro offers a combination of multichannel evaluation including colocalization analysis and the

  10. The Adequacy of the Q Methodology for Clinical Validation of Nursing Diagnoses Related to Subjective Foci.

    Science.gov (United States)

    Miguel, Susana; Caldeira, Sílvia; Vieira, Margarida

    2018-04-01

    This article describes the adequacy of the Q methodology as a new option for the validation of nursing diagnoses related to subjective foci. Discussion paper about the characteristics of the Q methodology. This method has been used in nursing research particularly related to subjective concepts and includes both a quantitative and qualitative dimension. The Q methodology seems to be an adequate and innovative method for the clinical validation of nursing diagnoses. The validation of nursing diagnoses related to subjective foci using the Q methodology could improve the level of evidence and provide nurses with clinical indicators for clinical reasoning and for the planning of effective interventions. Descrever a adequação da metodologia Q como uma nova opção para a validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos. MÉTODOS: Artigo de discussão sobre as características da metodologia Q. Este método tem sido utilizado na pesquisa em enfermagem relacionada com conceitos subjetivos e inclui em simultâneo uma vertente qualitativa e quantitativa. CONCLUSÕES: A metodologia Q parece ser uma opção metodológica adequada para a validação clínica de diagnósticos de enfermagem. IMPLICAÇÕES PARA A PRÁTICA: A utilização da metodologia Q na validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos pode melhorar o nível e evidência e facilitar o raciocínio clínico dos enfermeiros, ao providenciar indicadores clínicos também necessários ao desenvolvimento de intervenções efetivas. © 2016 NANDA International, Inc.

  11. γH2AX foci as a marker for DNA double-strand breaks

    International Nuclear Information System (INIS)

    Deckbar, Dorothee

    2009-01-01

    Full text: The DNA double-strand break (DSB) is the most deleterious lesion of all DNA damages. Left unrepaired or being mis-rejoined it can lead to chromosome aberrations which compromise the genomic stability and carry the potential to initiate carcinogenesis. So DSB repair mechanisms are under intensive investigation for many years. As older techniques had to utilize non-physiological doses to monitor DSB repair, they did not allow repair studies on the cellular level or after in vivo irradiation. But during the last years, an upcoming method allows the detection of a single DSB after physiologically relevant doses. To maintain the genomic integrity after the occurrence of a DSB, cellular mechanisms have evolved that detect and repair DSBs and even halt cell cycle progression to provide time for repair. In these processes, one of the first steps is the phosphorylation of the histone H2AX at serine 139 (γH2AX). Within minutes after DSB induction, large numbers of H2AX molecules are phosphorylated around the break site leading to the accumulation of proteins involved in chromatin remodelling, to damage signal amplification, and eventually to checkpoint activation and DSB repair. The finding that DSB-surrounding proteins can be visualized as foci in immunofluorescence microscopy opened up new opportunities in cancer biology and radiation biology. It was now for the first time possible to measure DSB repair after physiologically relevant doses of ionizing radiation, i.e. after doses used for therapeutic as well as for diagnostic purposes. First reports even describe the measurement of DSB repair after in vivo irradiation in mice and humans. This did not only improve the basic research investigating the mechanisms of DSB repair but also the research on low-dose effects and radiation protection. So the potential of γH2AX foci analysis as a predictive marker for radiosensitivity or radiation induced side effects is actually discussed. (author)

  12. [Epizootic and epidemic manifestation of natural foci of tularemia in Moscow region (1965-2013)].

    Science.gov (United States)

    Demidova, T N; Popov, V P; Polukhina, A N; Orlov, D S; Mescheryakova, I S; Mikhailova, T V

    2015-01-01

    Detection of contemporary features of tularemia focimanifestations, determination of territories of high epidemic risk in various landscape zones and creation of a map of foci territories of Moscow Region for isolation of tularemia infectious agent cultures and registered human morbidity for justified planning of prophylaxis measures. Report materials of epizootologic examinations of natural foci for 1965-2013, 156 maps of epidemiologic examination of cases of human infection with tularemia, results of studies of casting of predatory birds and dung of predatory mammals were used. Registered morbidity and isolation of tularemia infectious agent cultures from 1965 to date were applied to an electronic map of Moscow Region by sign method using modern. GIS-technologies (MapInfo 10.5 program). Electronic maps Ingit at 1:200,000 scale, as well as Google Earth program were used to search for base points. Analysis of morbidity has revealed structure change in human tularemia morbidity--an increase of the fraction of urban population and a decrease of the fraction of patients among rural inhabitants, unimmunized against this infection are mostly ill. The presence of DNA of tularemia causative agent in biological objects in the complex with serologic and bacteriological studies was shown to allow to detect flaccid epizootics even at low numbers of rodents. Cartographic reflection of registered morbidity and isolation of tularemia infectious agent cultures allowed to show territories with various degrees of epizootic activity and epidemic manifestation. Positive results of serologic and molecular-genetic studies of environmental objects gives evident on epizootic activity and constant risk of aggravation of epidemic situation for this infection.

  13. [Alternatives to femtosecond laser technology: subnanosecond UV pulse and ring foci for creation of LASIK flaps].

    Science.gov (United States)

    Vogel, A; Freidank, S; Linz, N

    2014-06-01

    In refractive corneal surgery femtosecond (fs) lasers are used for creating LASIK flaps, dissecting lenticules and for astigmatism correction by limbal incisions. Femtosecond laser systems are complex and expensive and cutting precision is compromised by the large focal length associated with the commonly used infrared (IR) wavelengths. Based on investigations of the cutting dynamics, novel approaches for corneal dissection using ultraviolet A (UVA) picosecond (ps) pulses and ring foci from vortex beams are presented. Laser-induced bubble formation in corneal stroma was investigated by high-speed photography at 1-50 million frames/s. Using Gaussian and vortex beams of UVA pulses with durations between 200 and 850 ps the laser energy needed for easy removal of flaps created in porcine corneas was determined and the quality of the cuts by scanning electron microscopy was documented. Cutting parameters for 850 ps are reported also for rabbit eyes. The UV-induced and mechanical stress were evaluated for Gaussian and vortex beams. The results show that UVA picosecond lasers provide better cutting precision than IR femtosecond lasers, with similar processing times. Cutting energy decreases by >50 % when the laser pulse duration is reduced to 200 ps. Vortex beams produce a short, donut-shaped focus allowing efficient and precise dissection along the corneal lamellae which results in a dramatic reduction of the absorbed energy needed for cutting and of mechanical side effects as well as in less bubble formation in the cutting plane. A combination of novel approaches for corneal dissection provides the option to replace femtosecond lasers by compact UVA microchip laser technology. Ring foci are also of interest for femtosecond laser surgery, especially for improved lenticule excision.

  14. Clinical Application of Foci Contralateral Facial Artery Myomucosal Flap for Tongue Defect Repair

    Directory of Open Access Journals (Sweden)

    Mengxiong Pan, MS

    2018-02-01

    Full Text Available Summary:. This study aims to investigate the clinical efficacy of foci contralateral facial artery myomucosal flap (FAMF in repairing the defect of tongue after tumor resection. There were 10 cases who received the operation to repair tongue tissue defects caused by tumor resection from January 2010 to January 2016. FAMF flap size ranged from 2.5 × 3 cm to 5 × 5 cm. All flaps survived after surgery, and no local necrosis occurred. For the donor and receptor sites of 10 cases, 8 cases got wounds healed at stage I, wound dehiscence of donor site occurred in 2 cases, and the dehisced wounds were healed after local cleaning. All 10 patients were followed up for 13 months to 5 years, with an average of 2 years and 4 months. No obvious deformity appeared on face after surgery, and there was no mouth floor leakage. After surgery, 3 cases had clinical manifestations of facial nerve marginal mandibular branch injury and returned to normal in 3 months. All patients had a limitation for mouth opening after surgery, 9 cases returned to normal after 1 year, and 1 case still had a mild limitation for mouth opening. There was no impact on patients’ eating, swallowing, language, or other functions. The foci contralateral FAMF surgery is simple and brings ideal plastic effect, high survival rate of flap, less donor site lesion, simple postoperative care, no breaking after surgery, and no impact on radical cure of tumor, which is suitable for repairing defect of tongue.

  15. The IEC-publication 336/1981 - new formulation of the standards for X-ray foci

    International Nuclear Information System (INIS)

    Geldner, E.; Schnitger, H.

    1982-01-01

    With the new IEC-standard for foci a clear distinction has been made between application oriented focus classification, expressed by the focus nominal value as a dimensionless number and the detectable real geometric focus measured in the sense of the principle 'Truth in advertising'. Now, even regions of a size [de

  16. Phylogeny and Classification of Yersinia pestis Through the Lens of Strains From the Plague Foci of Commonwealth of Independent States

    Directory of Open Access Journals (Sweden)

    Vladimir V. Kutyrev

    2018-05-01

    Full Text Available The established phylogeny of the etiological agent of plague, Yersinia pestis, is not perfect, as it does not take into account the strains from numerous natural foci of Commonwealth of Independent States (CIS. We have carried out PCR and SNP typing of 359 strains and whole genome sequencing of 51 strains from these plague foci and determined the phylogenetic diversity of the strains circulating here. They belong to 0.ANT3, 0.ANT5, 2.ANT3, 4.ANT branches of antique biovar, 2.MED0, 2.MED1 branches of medieval biovar and to 0.PE2, 0.PE4a. 0.PE4h, 0.PE4t branches. Based on the studies of 178 strains from 23 plague foci of CIS countries, it was determined that the population structure of 2.MED strains is subdivided into Caucasian–Caspian and Central Asian–Chinese branches. In Central-Caucasian high-mountain plague foci in the Russian Federation (RF the most deeply diverged branch of medieval biovar, 2.MED0, has been found. With the data obtained, the current population structure of Y. pestis species has been refined. New subspecies classification is developed, comprising seven subspecies: pestis, caucasica (0.PE2, angolica (0.PE3, central asiatica (0.PE4, tibetica (0.PE7, ulegeica (0.PE5, and qinghaica (0.PE10.

  17. Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic

    Directory of Open Access Journals (Sweden)

    Youn-Bok Lee

    2013-12-01

    Full Text Available The GGGGCC (G4C2 intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

  18. AFSC/RACE/EcoFOCI: 2011 Gulf of Alaska Late Larval Survey DY11-02/2DY11

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A total of 70 stations were occupied. The standard FOCI grid and line 8 were samped. At each station we sampled using paired 20 and 60 cm Bongo frames (150 and 500...

  19. Novel characteristics of CtIP at damage-induced foci following the initiation of DNA end resection

    International Nuclear Information System (INIS)

    Fujisawa, Hiroshi; Fujimori, Akira; Okayasu, Ryuichi; Uesaka, Mitsuru; Yajima, Hirohiko

    2015-01-01

    Highlights: • CtIP becomes hyperphosphorylated and forms foci following cell irradiation. • CtIP accumulates in foci subsequent to the peak of hyperphosphorylation. • CtIP is maintained in a hypophosphorylated state at later times. • CtIP is continuously recruited to DNA double strand breaks downstream of resection. • CtIP presumably have a distinct role following the initiation of resection. - Abstract: Homologous recombination (HR) is a major repair pathway for DNA double strand breaks (DSBs), and end resection, which generates a 3′-single strand DNA tail at the DSB, is an early step in the process. Resection is initiated by the Mre11 nuclease together with CtIP. Here, we describe novel characteristics of CtIP at DSBs. At early times following exposure of human cells to ionizing radiation, CtIP localized to the DSB, became hyperphosphorylated and formed foci in an ATM-dependent manner. At later times, when the initiation of resection had occurred, CtIP foci persist but CtIP is maintained in a hypophosphorylated state, which is dependent on ATM and ATR. Exposure to cycloheximide revealed that CtIP turns over at DSB sites downstream of resection. Our findings provide strong evidence that CtIP is continuously recruited to DSBs downstream of both the initiation and extension step of resection, strongly suggesting that CtIP has functions in addition to promoting the initiation of resection during HR

  20. Localization of higher grade tumor foci in potential candidates for active surveillance who opt for radical prostatectomy

    Science.gov (United States)

    Hong, Sung Kyu; Eastham, James A.; Fine, Samson W.

    2013-01-01

    Purpose: To investigate actual intraprostatic location of higher graded tumor foci undetected via standard transrectal ultrasound-guided prostate biopsy amongst patients who would be clinically considered appropriate candidates for active surveillance (AS) but underwent radical prostatectomy (RP). Methods: We reviewed entirely-submitted and whole-mounted RP specimens from 169 men who were deemed appropriate for AS clinically, but opted for RP and were found to have higher grade tumors. For each case, tumor nodules were circled and color-coded in a grade-specific manner and digitally scanned to created tumor maps. The locations of tumor foci with Gleason grade ≥4 were stratified by specific sites: anterior, anterolateral, lateral only (not clearly anterior or posterior), posterior, and posterolateral area. Results: Of 169 patients, 86% had clinical stage T1c and 14% T2a. RP Gleason score 7 in all but two men. Higher-grade tumor foci were localized to: anterior (n=66, 39%), anterolateral (n=4, 2%), lateral only (not clearly anterior or posterior) (n=5, 3%), posterior (n=52, 31%), and posterolateral (n=42, 25%) prostate, respectively. Conclusions: Among patients deemed clinically appropriate for AS, higher-grade tumor foci missed by standard prostate biopsies were localized to both the anterior and posterior prostate, without predominance of a particular area. These findings lend additional support to performing repeat standard prostate biopsy in potential candidates for AS and should be considered in efforts to optimize current biopsy strategies for the selection of AS patients. PMID:24392439

  1. A spherical harmonics intensity model for 3D segmentation and 3D shape analysis of heterochromatin foci.

    Science.gov (United States)

    Eck, Simon; Wörz, Stefan; Müller-Ott, Katharina; Hahn, Matthias; Biesdorf, Andreas; Schotta, Gunnar; Rippe, Karsten; Rohr, Karl

    2016-08-01

    The genome is partitioned into regions of euchromatin and heterochromatin. The organization of heterochromatin is important for the regulation of cellular processes such as chromosome segregation and gene silencing, and their misregulation is linked to cancer and other diseases. We present a model-based approach for automatic 3D segmentation and 3D shape analysis of heterochromatin foci from 3D confocal light microscopy images. Our approach employs a novel 3D intensity model based on spherical harmonics, which analytically describes the shape and intensities of the foci. The model parameters are determined by fitting the model to the image intensities using least-squares minimization. To characterize the 3D shape of the foci, we exploit the computed spherical harmonics coefficients and determine a shape descriptor. We applied our approach to 3D synthetic image data as well as real 3D static and real 3D time-lapse microscopy images, and compared the performance with that of previous approaches. It turned out that our approach yields accurate 3D segmentation results and performs better than previous approaches. We also show that our approach can be used for quantifying 3D shape differences of heterochromatin foci. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Explanation for excessive DNA single-strand breaks and endogenous repair foci in pluripotent mouse embryonic stem cells.

    Science.gov (United States)

    Banáth, J P; Bañuelos, C A; Klokov, D; MacPhail, S M; Lansdorp, P M; Olive, P L

    2009-05-01

    Pluripotent mouse embryonic stem cells (mES cells) exhibit approximately 100 large gammaH2AX repair foci in the absence of measurable numbers of DNA double-strand breaks. Many of these cells also show excessive numbers of DNA single-strand breaks (>10,000 per cell) when analyzed using the alkaline comet assay. To understand the reasons for these unexpected observations, various methods for detecting DNA strand breaks were applied to wild-type mES cells and to mES cells lacking H2AX, ATM, or DNA-PKcs. H2AX phosphorylation and expression of other repair complexes were measured using flow and image analysis of antibody-stained cells. Results indicate that high numbers of endogenous gammaH2AX foci and single-strand breaks in pluripotent mES cells do not require ATM or DNA-PK kinase activity and appear to be associated with global chromatin decondensation rather than pre-existing DNA damage. This will limit applications of gammaH2AX foci analysis in mES cells to relatively high levels of initial or residual DNA damage. Excessive numbers of single-strand breaks in the alkaline comet assay can be explained by the vulnerability of replicating chromatin in mES cells to osmotic shock. This suggests that caution is needed in interpreting results with the alkaline comet assay when applied to certain cell types or after treatment with agents that make chromatin vulnerable to osmotic changes. Differentiation of mES cells caused a reduction in histone acetylation, gammaH2AX foci intensity, and DNA single-strand breakage, providing a link between chromatin structural organization, excessive gammaH2AX foci, and sensitivity of replicating mES cell chromatin to osmotic shock.

  3. FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis.

    Directory of Open Access Journals (Sweden)

    Alex D Herbert

    Full Text Available Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ.

  4. Visualisation of γH2AX Foci Caused by Heavy Ion Particle Traversal; Distinction between Core Track versus Non-Track Damage

    Science.gov (United States)

    Nakajima, Nakako Izumi; Brunton, Holly; Watanabe, Ritsuko; Shrikhande, Amruta; Hirayama, Ryoichi; Matsufuji, Naruhiro; Fujimori, Akira; Murakami, Takeshi; Okayasu, Ryuichi; Jeggo, Penny; Shibata, Atsushi

    2013-01-01

    Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET) damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm) ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ) in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci) represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle. PMID:23967070

  5. Radioiodination and Biological Evaluation of some Drugs for Inflammatory Foci Imaging

    International Nuclear Information System (INIS)

    El Refaie, M.S.A.

    2011-01-01

    A radiopharmaceutical is defined as a chemical or pharmaceutical preparation labeled with a radionuclide in tracer or therapeutic concentration, used as a diagnostic or therapeutic agent. A radiopharmaceutical agent is usually administrated into a vein. Depending on which type of scan is being performed, the imaging will be done either immediately, a few hours later, or even several days after the injection. Imaging time varies, generally ranging from 20 to 45 minutes.In this thesis, we are more interested in the drugs that can be used for the treatment of all kinds of inflammation whether septic or aseptic. The inflammation by itself can be a controllable disease, but as the inflammation, specially the chronic type, can be the reason and the beginning of many more serious diseases as autoimmune disease, pulmonary disease, cardiovascular disease, neurological disease and cancer, the study and the early diagnosis of the inflammation can prevent many future problems for the patient. The study of the inflammation has been discussed before by labeling drugs with Iodine-125 for the imaging of inflammatory foci like etodolac, meloxicam, piroxicam and other drugs.

  6. Phylogenetic Analysis of Entomoparasitic Nematodes, Potential Control Agents of Flea Populations in Natural Foci of Plague

    Science.gov (United States)

    Koshel, E. I.; Aleshin, V. V.; Eroshenko, G. A.; Kutyrev, V. V.

    2014-01-01

    Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit Yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus, Microtus socialis, and Allactaga major), the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema, Psyllotylenchus, and Spilotylenchus), constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida). We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina. PMID:24804197

  7. Motivational foci and asthma medication tactics directed towards a functional day

    Directory of Open Access Journals (Sweden)

    Lötvall Jan

    2011-10-01

    Full Text Available Abstract Background There appears to be an obvious gap between a medical and patient adherence perspective. Deviating from a medication prescription could be regarded as fairly irrational, but with respect to patients' goals and/or concerns it could be seen as understandable. Thus, the aim was to elucidate adherence reasoning in relation to asthma medication. Methods This was a qualitative study; data collection and analysis procedures were conducted according to Grounded Theory methodology. Eighteen persons, aged 22 with asthma and regular asthma medication treatment, were interviewed. Results The emerged theoretical model illustrated that adherence to asthma medication was motivated by three foci, all directed towards a desired outcome in terms of a functional day as desired by the patient. A promotive focus was associated with the ambition to achieve a positive asthma outcome by being adherent either to the received prescription or to a self-adjusted dosage. A preventive focus was intended to ensure avoidance of a negative asthma outcome either by sticking to the prescription or by preventively overusing the medication. A permissive focus was associated with unstructured adherence behaviour in which medication intake was primarily triggered by asthma symptoms. Conclusions As all participants had consciously adopted functioning medication tactics that directed them towards the desired goal of a functional day. In an effort to bridge the gap between a patient- and a medical adherence perspective, patients need support in defining their desired functionality and guidance in developing a person-based medication tactic.

  8. A review of Web information seeking research: considerations of method and foci of interest

    Directory of Open Access Journals (Sweden)

    Konstantina Martzoukou

    2005-01-01

    Full Text Available Introduction. This review shows that Web information seeking research suffers from inconsistencies in method and a lack of homogeneity in research foci. Background. Qualitative and quantitative methods are needed to produce a comprehensive view of information seeking. Studies also recommend observation as one of the most fundamental ways of gaining direct knowledge of behaviour. User-centred research emphasises the importance of holistic approaches, which incorporate physical, cognitive, and affective elements. Problems. Comprehensive studies are limited; many approaches are problematic and a consistent methodological framework has not been developed. Research has often failed to ensure appropriate samples that ensure both quantitative validity and qualitative consistency. Typically, observation has been based on simulated rather than real information needs and most studies show little attempt to examine holistically different characteristics of users in the same research schema. Research also deals with various aspects of cognitive style and ability with variant definitions of expertise and different layers of user experience. Finally the effect of social and cultural elements has not been extensively investigated. Conclusion. The existing limitations in method and the plethora of different approaches allow little progress and fewer comparisons across studies. There is urgent need for establishing a theoretical framework on which future studies can be based so that information seeking behaviour can be more holistically understood, and results can be generalised.

  9. Freezing of enkephalinergic functions by multiple noxious foci: a source of pain sensitization?

    Directory of Open Access Journals (Sweden)

    François Cesselin

    Full Text Available BACKGROUND: The functional significance of proenkephalin systems in processing pain remains an open question and indeed is puzzling. For example, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM from segments of the spinal cord related to the stimulated area of the body, but does increase its release from other segments. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that, in the rat, a noxious mechanical stimulus applied to either the right or the left hind paw elicits a marked increase of MELM release during perifusion of either the whole spinal cord or the cervico-trigeminal area. However, these stimulatory effects were not additive and indeed, disappeared completely when the right and left paws were stimulated simultaneously. CONCLUSION/SIGNIFICANCE: We have concluded that in addition to the concept of a diffuse control of the transmission of nociceptive signals through the dorsal horn, there is a diffuse control of the modulation of this transmission. The "freezing" of Met-enkephalinergic functions represents a potential source of central sensitization in the spinal cord, notably in clinical situations involving multiple painful foci, e.g. cancer with metastases, poly-traumatism or rheumatoid arthritis.

  10. IGF-IEc expression is increased in secondary compared to primary foci in neuroendocrine neoplasms.

    Science.gov (United States)

    Alexandraki, Krystallenia I; Philippou, Anastassios; Boutzios, Georgios; Theohari, Irini; Koutsilieris, Michael; Delladetsima, Ioanna Kassiani; Kaltsas, Gregory A

    2017-10-03

    Different Insulin-like growth factor-I (IGF-I) mRNA transcripts are produced by alternative splicing and particularly the IGF-IEc isoform has been implicated in the development and/or progression of various types of cancer. In the present study, we examined the potential role of IGF-IEc expression as a new immunohistochemical marker of aggressiveness in neuroendocrine neoplasms (NENs). We utilized immunohistochemical analysis in tissue specimens of 47 patients with NENs, to evaluate the expression of IGF-IEc (%) and Ki-67 proliferation index (%). Specimens from patients with tumors of different tissue origin, of either primary or metastatic lesions and of different grade were examined. Cytoplasmic IGF-IEc staining was found in 23 specimens of NENs or NECs: 10 pancreatic, 4 small bowel, 3 gastric, 1 lung, 1 uterine and 4 poorly differentiated of unknown primary origin. Ki-67 and IGF-IEc expression was positively correlated in all the samples studied (r=0.31, p=0.03). IGF-1Ec expression was more prevalent in specimens originating from metastatic foci with high Ki-67 compared to primary sites with low Ki-67 expression (p=0.036). These findings suggest a possible role of IGF-IEc in NEN tumorigenesis and progression to metastases that could be used as an additional new marker of a more aggressive behavior and a potential drugable target.

  11. Population genetics of Glossina palpalis palpalis from central African sleeping sickness foci

    Directory of Open Access Journals (Sweden)

    Solano Philippe

    2011-07-01

    Full Text Available Abstract Background Glossina palpalis palpalis (Diptera: Glossinidae is widespread in west Africa, and is the main vector of sleeping sickness in Cameroon as well as in the Bas Congo Province of the Democratic Republic of Congo. However, little is known on the structure of its populations. We investigated G. p. palpalis population genetic structure in five sleeping sickness foci (four in Cameroon, one in Democratic Republic of Congo using eight microsatellite DNA markers. Results A strong isolation by distance explains most of the population structure observed in our sampling sites of Cameroon and DRC. The populations here are composed of panmictic subpopulations occupying fairly wide zones with a very strong isolation by distance. Effective population sizes are probably between 20 and 300 individuals and if we assume densities between 120 and 2000 individuals per km2, dispersal distance between reproducing adults and their parents extends between 60 and 300 meters. Conclusions This first investigation of population genetic structure of G. p. palpalis in Central Africa has evidenced random mating subpopulations over fairly large areas and is thus at variance with that found in West African populations of G. p. palpalis. This study brings new information on the isolation by distance at a macrogeographic scale which in turn brings useful information on how to organise regional tsetse control. Future investigations should be directed at temporal sampling to have more accurate measures of demographic parameters in order to help vector control decision.

  12. Specific dose-dependent damage of Lieberkuehn crypts promoted by large doses of type 2 ribosome-inactivating protein nigrin b intravenous injection to mice

    International Nuclear Information System (INIS)

    Gayoso, M.J.; Munoz, R.; Arias, Y.; Villar, R.; Rojo, M.A.; Jimenez, P.; Ferreras, J.M.; Aranguez, I.; Girbes, T.

    2005-01-01

    Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin at ribosomal level but 10 5 and 5 x 10 3 times less toxic for animal cell cultures and mice, respectively, than ricin. The purpose of the present study was to analyze the effects of intravenous injection of large amounts of nigrin b to the mouse. Injection through the tail vein of 16 mg/kg body weight killed all mice studied before 2 days. Analysis of several major tissues by light microscopy did not reveal gross nigrin b-promoted changes, except in the intestines which appeared highly damaged. As a consequence of the injury, the villi and crypt structures of the small intestine disappeared, leading to profuse bleeding and death. In contrast, intravenous injection of 5 mg/kg body weight was not lethal to mice but did trigger reversible toxic effects. In both cases, lethal and sub-lethal doses, the target of nigrin b appeared to be the highly proliferating stem cells of the intestinal crypts, which had undergone apoptotic changes. In contrast to nigrin b, the injection of 3 μg/kg of ricin kills all mice in 5 days but does not trigger apoptosis in the crypts. Therefore, the effect seen with sub-lethal nigrin b concentrations seems to be specific. Nigrin b killed COLO 320 human colon adenocarcinoma cells with an IC 50 of 3.1 x 10 -8 M and the effect was parallel to the extent of DNA fragmentation of these cells. Accordingly, despite the low general toxicity exerted by nigrin b as compared with ricin, intravenous injection of large amounts of nigrin b is able to kill mouse intestinal stem cells without threatening the lives of the animals, thereby opening a door for its use for the targeting of intestinal stem cells

  13. The Sommersdorf mummies-An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany.

    Science.gov (United States)

    Alterauge, Amelie; Kellinghaus, Manuel; Jackowski, Christian; Shved, Natallia; Rühli, Frank; Maixner, Frank; Zink, Albert; Rosendahl, Wilfried; Lösch, Sandra

    2017-01-01

    Sommersdorf Castle (Bavaria, Germany) is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle's church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT), was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases.

  14. The Sommersdorf mummies—An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany

    Science.gov (United States)

    Kellinghaus, Manuel; Jackowski, Christian; Shved, Natallia; Rühli, Frank; Maixner, Frank; Zink, Albert; Rosendahl, Wilfried; Lösch, Sandra

    2017-01-01

    Sommersdorf Castle (Bavaria, Germany) is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle’s church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT), was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases. PMID:28859116

  15. Is the presence of 6 or fewer crypt apoptotic bodies sufficient for diagnosis of graft versus host disease? A decade of experience at a single institution.

    Science.gov (United States)

    Lin, Jingmei; Fan, Rong; Zhao, Zijin; Cummings, Oscar W; Chen, Shaoxiong

    2013-04-01

    Histopathology assessment is crucial for the diagnosis of graft versus host disease (GVHD), as the presence of crypt apoptosis is the cardinal criterion required. However, crypt apoptosis is not limited to GVHD; it also occurs in other conditions such as infection, drug reaction, or inflammatory reactions unrelated to GVHD. To better determine whether the presence of 6 or fewer apoptotic bodies is sufficient for the diagnosis of GVHD, we retrospectively reviewed 78 colon biopsies from 66 patients who received either hematopoietic stem cell (HSCT) or cord blood cell transplantation and whose colon biopsies exhibited apoptotic bodies. Among them, 41 cases contained 6 or fewer apoptotic bodies in the colon biopsy. These biopsies were compared with 141 colon biopsy controls that showed no significant pathologic changes as well as 16 colon biopsies with cytomegalovirus colitis from patients without a history of bone marrow transplantation. Among the 41 cases reviewed, 7 patients had coexisting GVHD in other organs (skin or liver). However, gastrointestinal symptoms of at least 4 HSCT patients whose colon biopsies contained 6 or fewer apoptotic bodies completely resolved in the absence of further intervention for GVHD. The discrepancy between pathologic findings and the clinical course may be due to confounding factors, such as infection or medication-induced injury. Our data suggest that identifying 6 or fewer crypt apoptotic bodies in colon biopsies from HSCT patients is worth reporting in order to alert the clinicians of the possibility of GVHD but not sufficient to render a diagnosis on the pathologic grounds alone. The colon biopsies containing 6 or fewer apoptotic bodies represent a heterogenous group. We suggest this group to be classified as indeterminate for GVHD, instead of diagnosing GVHD outright. Synthesis of all clinical, endoscopic, and pathologic information, including the status of infection, coexisting GVHD involvement in the other organs, and

  16. Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci

    International Nuclear Information System (INIS)

    Djuzenova, Cholpon S; Elsner, Ines; Katzer, Astrid; Worschech, Eike; Distel, Luitpold V; Flentje, Michael; Polat, Bülent

    2013-01-01

    High expression of constitutive histone γ-H2AX, a sensitive marker of DNA damage, might be indicative of defective DNA repair pathway or genomic instability. 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. This study explores the relationship between the clinical radiosensitivity of tumor patients and the expression/induction of γ-H2AX and 53BP1 in vitro. Using immunostaining, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53 BP1 in peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=57) undergoing radiotherapy (RT). Cells from apparently healthy donors (n=12) served as references. Non-irradiated cells from controls and unselected BC patients exhibited similar baseline levels of DNA damage assessed by γ-H2AX and 53BP1 foci. At the same time, the γ-H2AX assay of in vitro irradiated cells revealed significant differences between the control group and the group of unselected BC patients with respect to the initial (0.5 Gy, 30 min) and residual (2 Gy, 24 h post-radiation) DNA damage. The numbers of 53BP1 foci analyzed in 35 BC patients were significantly higher than in controls only in case of residual DNA damage. A weak correlation was found between residual foci of both proteins tested. In addition, cells from cancer patients with an adverse acute skin reaction (grade 3) to RT showed significantly increased radiation-induced γ-H2AX foci and their protracted disappearance compared to the group of BC patients with normal skin reaction (grade 0–1). The mean number of γ-H2AX foci after 5 clinical fractions was significantly higher than that before RT, especially in clinically radiosensitive patients. The γ-H2AX assay may have potential for screening individual radiosensitivity of breast cancer patients.

  17. Effect of carbamazepine (Tegretol) on seizure and EEG patterns in monkeys with alumina-induced focal motor and hippocampal foci.

    Science.gov (United States)

    David, J; Grewal, R S

    1976-12-01

    Qualitative and quantitative aspects of chronic carbamazepine (Tegretol) medication on focal seizures and associated interictal EEG abnormalities in Rhesus monkeys with alumina-induced foci in either the sensorimotor cortex or the hipocampus was investigated. In both groups of animals, carbamazepine produced qualitative control of visible seizures and reduced intracortical spike propagation, but did not cause complete normalization of the background EEG; quantitative indices, such as spike density and amount of paroxysmal discharge representative of abnormal EEG activity, were significantly reduced with respect to predrug values during medication and after cessation as well. Threshold to pentylenetetrazol was elevated by carbamazepine in both groups of epileptic monkeys. Aggressivity and other clinical manifestations in monekys with hippocampal foci were markedly reduced by carbamazepine.

  18. Typical features of the foci in case of largescale radiation accidents and their influence on organization of medical care

    International Nuclear Information System (INIS)

    Vorontsov, I.V.; Zhilyaev, E.G.; Ivanov, V.B.; El'kin, A.I.; Chernetsov, A.A; Kotov, Yu.A.

    1995-01-01

    The paper studied typical features of foci in case of large-scale radiation accidents, which differ from foci after nuclear explosion by the components of radioactive substances, small particle dispersity, their higher solubility, longer period of radiation contamination and its irregularity. It complicates special treatment, creates difficulties in evaluation of radiation situation and in carrying out sanitary-hygienic measures. The leading radiation factor is external radiation exposure, but in the initial period close to Nuclear Power Plant, the contribution of internal radiation exposure due to inhalation of radioactive substances is very important and should be taken into consideration when rating radiation exposure Besides, there must be taken into account considerable contribution of non-radiation factors (stress, toxic effects, social-economic conditions etc.) in aggravation of health condition of people. The above specific features require corrections in classic approach to prophylaxis and treatment of radiation injuries. 18 refs.; 4 tabs

  19. Natural foci of Borrelia lusitaniae in a mountain region of Central Europe.

    Science.gov (United States)

    Tarageľová, Veronika Rusňáková; Mahríková, Lenka; Selyemová, Diana; Václav, Radovan; Derdáková, Markéta

    2016-03-01

    Lyme borreliosis is the most prevalent tick-borne disease in Europe. It is caused by spirochaetes of the Borrelia burgdorferi sensu lato (s.l.) complex and transmitted to humans by ticks of the genus Ixodes. Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana are the most common genospecies in Central Europe. In contrast, Borrelia lusitaniae predominates in Mediterranean countries such as Portugal, Morocco, and Tunisia. In Slovakia, its prevalence is low and restricted to only a few sites. The aim of our research was to study the expansion of ticks into higher altitudes in the ecosystem of the Malá Fatra mountains (north Slovakia) and their infection with B. burgdorferi s.l. pathogens. Questing ticks were collected by flagging in seven years (2004, 2006-2011) at three different altitudes: low (630-660 m above sea level (ASL)), intermediate (720-750 m ASL), and high (1040-1070 m ASL). Tick abundance was highest at the lowest altitude and lowest at the highest altitude. The average infection prevalence of B. burgdorferi s.l. in nymphs and adults was 16.8% and 36.2%, respectively. The number of infected ticks decreased from 38.5% at the lowest altitude to 4.4% at the highest altitude. B. lusitaniae was the most frequently found genospecies (>60% of the ticks found positive for B. burgdorferi s.l.) in all sites in all the studied years with the exception of 2008 when B. afzelii predominated (62%). Our study confirms the spread of Ixodes ricinus ticks to higher altitudes in Slovakia. The discovery that our mountain study sites were a natural foci of B. lusitaniae was unexpected because this genospecies is usually associated with lizards and xerothermic habitats. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  1. The Historical Distribution of Main Malaria Foci in Spain as Related to Water Bodies

    Directory of Open Access Journals (Sweden)

    Arturo Sousa

    2014-08-01

    Full Text Available The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS, using the Inverse Distance Weighted (IDW interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura, the presence of another vector (Anopheles labranchiae besides A. atroparvus (Levante or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia. In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.

  2. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  3. Fast and Simple Detection of Yersinia pestis Applicable to Field Investigation of Plague Foci

    Science.gov (United States)

    Simon, Stéphanie; Demeure, Christian; Lamourette, Patricia; Filali, Sofia; Plaisance, Marc; Créminon, Christophe; Volland, Hervé; Carniel, Elisabeth

    2013-01-01

    Yersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. There is now a convenient and effective test (F1-dipstick) for the rapid identification of Y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the F1 capsule is mostly produced at 37°C. The plasminogen activator (PLA), a key virulence factor encoded by a Y. pestis-specific plasmid, is synthesized both at 20°C and 37°C, making it a good candidate antigen for environmental detection of Y. pestis by immunological methods. A recombinant PLA protein from Y. pestis synthesized by an Escherichia coli strain was used to produce monoclonal antibodies (mAbs). PLA-specific mAbs devoid of cross-reactions with other homologous proteins were further cloned. A pair of mAbs was selected based on its specificity, sensitivity, comprehensiveness, and ability to react with Y. pestis strains grown at different temperatures. These antibodies were used to develop a highly sensitive one-step PLA-enzyme immunoassay (PLA-EIA) and an immunostrip (PLA-dipstick), usable as a rapid test under field conditions. These two PLA-immunometric tests could be valuable, in addition to the F1-disptick, to confirm human plague diagnosis in non-endemic areas (WHO standard case definition). They have the supplementary advantage of allowing a rapid and easy detection of Y. pestis in environmental and flea samples, and would therefore be of great value for surveillance and epidemiological investigations of plague foci. Finally, they will be able to detect natural or genetically engineered F1-negative Y. pestis strains in human patients and environmental samples. PMID:23383008

  4. Transmission of persistent ionizing radiation-induced foci through cell division in human primary cells

    Energy Technology Data Exchange (ETDEWEB)

    Vaurijoux, Aurelie, E-mail: aurelie.vaurijoux@irsn.fr [Institut de Radioprotection et de Sureté Nucléaire (IRSN), Laboratoire de Dosimétrie Biologique, BP 17, 92262 Fontenay aux roses cedex (France); Voisin, Pascale; Freneau, Amelie [Institut de Radioprotection et de Sureté Nucléaire (IRSN), Laboratoire de Dosimétrie Biologique, BP 17, 92262 Fontenay aux roses cedex (France); Barquinero, Joan Francesc [Universitat Autònoma de Barcelona, Faculty of Biosciences, 08193 Cerdanyola del Vallès (Spain); Gruel, Gaetan [Institut de Radioprotection et de Sureté Nucléaire (IRSN), Laboratoire de Dosimétrie Biologique, BP 17, 92262 Fontenay aux roses cedex (France)

    2017-03-15

    Highlights: • Persistent IRIF do not permanently block cell proliferation. • Persistent IRIF are transmitted in part and sometimes asymmetrically to daughter cells. • IRIF differ in their nature before and after the first cell division. - Abstract: Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24 h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5 Gy had at least one of these persistent IRIF 24 h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells.

  5. Transmission of persistent ionizing radiation-induced foci through cell division in human primary cells

    International Nuclear Information System (INIS)

    Vaurijoux, Aurelie; Voisin, Pascale; Freneau, Amelie; Barquinero, Joan Francesc; Gruel, Gaetan

    2017-01-01

    Highlights: • Persistent IRIF do not permanently block cell proliferation. • Persistent IRIF are transmitted in part and sometimes asymmetrically to daughter cells. • IRIF differ in their nature before and after the first cell division. - Abstract: Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24 h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5 Gy had at least one of these persistent IRIF 24 h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells.

  6. Detecting Foci of Malaria Transmission with School Surveys: A Pilot Study in the Gambia.

    Directory of Open Access Journals (Sweden)

    Ebako N Takem

    Full Text Available In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community.The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses.A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7 [range 4-21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124 [95% CI = 12.2-16.3] with marked variation between schools (range 3-25%, p<0.001, while the seroprevalence was 7.8% (234/2994 [95%CI = 6.4-9.8] for MSP119, 11.6% (364/2997 [95%CI = 9.4-14.5] for MSP2, and 20.0% (593/2973 [95% CI = 16.5-23.2 for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920.This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous.

  7. Squamous cell hyperplastic foci: precursors of cutaneous papillomas induced in SENCAR mice by a two-stage carcinogenesis regimen.

    Science.gov (United States)

    Binder, R L; Johnson, G R; Gallagher, P M; Stockman, S L; Sundberg, J P; Conti, C J

    1998-10-01

    We have conducted a series of experiments to characterize the lesions that are precursors of cutaneous papillomas in SENCAR mice initiated with 7,12-dimethylbenz(a)anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The first grossly detectable lesions at sites where papillomas subsequently developed were papules, slightly raised areas of skin ranging in diameter from 0.25 to approximately 1.5 mm. Papules were first detected in DMBA-initiated mice 21 days after the start of dosing with TPA. Of 78 DMBA/TPA-induced papules tracked during 15 weeks of TPA treatments, 68% progressed to papillomas, 9% persisted as papules, and 22% completely regressed. Histological evaluation of serial sections of 69 DMBA/TPA-induced papules revealed that they were focal hyperplastic lesions that we refer to as squamous cell hyperplastic foci (SCHF). These hyperproliferative lesions appeared to progress through two distinct stages. Stage I SCHF were characterized as regular hyperplastic foci involving the interfollicular epidermis and the outer root sheaths of 1 or more hair follicles down to the level of the sebaceous glands. Stage II SCHF were foci of irregular epithelial hyperplasia with increased fibrovascular stroma and involved from 3 to >10 hair follicles. Prominent dilated capillaries and inflammatory cell infiltrates were frequently associated with both stage I and II SCHF. Ha-ras gene codon 61 mutations were detected in 7 of 10 stage I SCHF and 13 of 14 stage II SCHF microdissected from histological sections and 7 of 7 of whole papules by mutation-specific PCR analysis. These data provide molecular evidence that SCHF are foci of initiated cells. Further study of these lesions may contribute to more fully defining the sequence of molecular and cellular changes necessary for tumorigenesis in mouse skin. SCHF may also have utility as early indicators of potential skin tumorigenicity in cancer bioassays.

  8. Dose-response relationship of γ-H2AX foci induction in human lymphocytes after X-rays exposure

    International Nuclear Information System (INIS)

    Mandina, Tania; Roch-Lefevre, Sandrine H.; Voisin, Pascale; Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne; Garcia, Omar; Voisin, Philippe; Roy, Laurence

    2011-01-01

    Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of γ-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and γ-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y (0.5h) = 11.66D + 0.15 (R 2 = 0.99), Y (5h) = 2.44D + 0.15 (R 2 = 0.99), Y (8h) = 1.57D + 0.22 (R 2 = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using γ-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in γ-H2AX foci kinetics after gamma- and X-irradiation in vitro.

  9. Localization of higher grade tumor foci in potential candidates for active surveillance who opt for radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Sung Kyu Hong

    2013-12-01

    Conclusions: Among patients deemed clinically appropriate for AS, higher-grade tumor foci missed by standard prostate biopsies were localized to both the anterior and posterior prostate, without predominance of a particular area. These findings lend additional support to performing repeat standard prostate biopsy in potential candidates for AS and should be considered in efforts to optimize current biopsy strategies for the selection of AS patients.

  10. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Wiegant, Wouter W. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Waisfisz, Quinten [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Medhurst, Annette L. [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N. Copernicus University, Bydgoszcz (Poland)]. E-mail: m.z.zdzienicka@lumc.nl

    2006-02-22

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination.

  11. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    International Nuclear Information System (INIS)

    Godthelp, Barbara C.; Wiegant, Wouter W.; Waisfisz, Quinten; Medhurst, Annette L.; Arwert, Fre; Joenje, Hans; Zdzienicka, Malgorzata Z.

    2006-01-01

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination

  12. Genotyping and phylogenetic analysis of Yersinia pestis by MLVA: insights into the worldwide expansion of Central Asia plague foci.

    Directory of Open Access Journals (Sweden)

    Yanjun Li

    Full Text Available BACKGROUND: The species Yersinia pestis is commonly divided into three classical biovars, Antiqua, Medievalis, and Orientalis, belonging to subspecies pestis pathogenic for human and the (atypical non-human pathogenic biovar Microtus (alias Pestoides including several non-pestis subspecies. Recent progress in molecular typing methods enables large-scale investigations in the population structure of this species. It is now possible to test hypotheses about its evolution which were proposed decades ago. For instance the three classical biovars of different geographical distributions were suggested to originate from Central Asia. Most investigations so far have focused on the typical pestis subspecies representatives found outside of China, whereas the understanding of the emergence of this human pathogen requires the investigation of strains belonging to subspecies pestis from China and to the Microtus biovar. METHODOLOGY/PRINCIPAL FINDINGS: Multi-locus VNTR analysis (MLVA with 25 loci was performed on a collection of Y. pestis isolates originating from the majority of the known foci worldwide and including typical rhamnose-negative subspecies pestis as well as rhamnose-positive subspecies pestis and biovar Microtus. More than 500 isolates from China, the Former Soviet Union (FSU, Mongolia and a number of other foci around the world were characterized and resolved into 350 different genotypes. The data revealed very close relationships existing between some isolates from widely separated foci as well as very high diversity which can conversely be observed between nearby foci. CONCLUSIONS/SIGNIFICANCE: The results obtained are in full agreement with the view that the Y. pestis subsp. pestis pathogenic for humans emerged in the Central Asia region between China, Kazakhstan, Russia and Mongolia, only three clones of which spread out of Central Asia. The relationships among the strains in China, Central Asia and the rest of the world based on the MLVA

  13. Dose-response relationship of {gamma}-H2AX foci induction in human lymphocytes after X-rays exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mandina, Tania [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Roch-Lefevre, Sandrine H.; Voisin, Pascale [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France); Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Garcia, Omar, E-mail: omar@cphr.edu.cu [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Voisin, Philippe; Roy, Laurence [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France)

    2011-09-15

    Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of {gamma}-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and {gamma}-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y{sub (0.5h)} = 11.66D + 0.15 (R{sup 2} = 0.99), Y{sub (5h)} = 2.44D + 0.15 (R{sup 2} = 0.99), Y{sub (8h)} = 1.57D + 0.22 (R{sup 2} = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using {gamma}-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in {gamma}-H2AX foci kinetics after gamma- and X-irradiation in vitro.

  14. Evidence supporting pre-radiation elimination of oral foci of infection in head and neck cancer patients to prevent oral sequelae. A systematic review.

    Science.gov (United States)

    Schuurhuis, Jennifer M; Stokman, Monique A; Witjes, Max J H; Dijkstra, Pieter U; Vissink, Arjan; Spijkervet, Frederik K L

    2015-03-01

    Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral foci of infection to prevent post-radiation oral problems. The evidence for the efficacy of dental screening is unclear. In this systematic review, we analyzed available evidence on the efficacy of pre-radiation elimination of oral foci of infection in preventing oral sequelae. A search was conducted (MEDLINE/EMBASE) for papers published up to May 2014. Papers on head-neck cancer patients subjected to pre-radiation dental screening, (chemo)radiation and oral follow-up were included. Of the 1770 identified papers, 20 studies fulfilled the inclusion criteria of which 17 were retrospective. A great heterogeneity in patient groups, dental screening techniques, definitions of oral foci of infection and techniques for eliminating foci was found. Most papers lacked essential details on how dental screening was performed and a clear definition of an oral focus of infection. The evidence for efficacy of elimination of oral foci of infection to prevent post-radiotherapy oral sequelae was inconclusive. Consequently, the efficacy of pre-radiation elimination of oral foci of infection remains unclear. No conclusions can be drawn about a definition of an oral focus of infection and whether pre-radiation elimination of these foci should be mandatory. We therefore suggest prospective studies with well-defined criteria for oral foci of infection, a clear description of which foci were eliminated and how, a detailed description of pre-radiation dental screening, clearly described patient and tumor characteristics, and a detailed dental history and dental status. Subsequently, oral problems that occur post-radiation should be systematically recorded. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells.

    Science.gov (United States)

    Osipov, Andreyan N; Pustovalova, Margarita; Grekhova, Anna; Eremin, Petr; Vorobyova, Natalia; Pulin, Andrey; Zhavoronkov, Alex; Roumiantsev, Sergey; Klokov, Dmitry Y; Eremin, Ilya

    2015-09-29

    Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

  16. Crowns and Crypts

    Indian Academy of Sciences (India)

    size of the ring. Metal cat- ion of appropriate size is trapped in this cavity to form a stable ... The formation of auride ion (Au-), characterisation of the so- called zind .... method of synthesis of these complexes is the use of so-called. 'template ...

  17. Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in hairless mouse skin in vivo

    Science.gov (United States)

    BUSSAU, L. J.; VO, L. T.; DELANEY, P. M.; PAPWORTH, G. D.; BARKLA, D. H.; KING, R. G.

    1998-01-01

    Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of the skin of hairless mice in vivo. Application of acridine orange enabled imaging of the layers of the epidermis. The corneocytes of the stratum corneum, the keratinocytes in the basal layers and redundant hair follicles were visualised at depths greater than 100 μm. Cellular and nuclear membranes of keratinocytes of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging of the skin after injection of FITC-dextran revealed an extensive network of blood vessels with a size range up to 20 μm. Blood cells could be seen moving through dermal vessels and the blood circulation through the dermal vascular bed was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves fibres around the hair follicles and subsurface blood vessels. Comparison was made between images obtained in vivo using FOCI and in vitro scanning electron microscopy and conventional histology. FOCI offers the potential to study dynamic events in vivo, such as blood flow, skin growth, nerve regeneration and many pathological processes, in ways which have not previously been possible. PMID:9643419

  18. MET Signaling Mediates Intestinal Crypt-Villus Development, Regeneration, and Adenoma Formation and Is Promoted by Stem Cell CD44 Isoforms.

    Science.gov (United States)

    Joosten, Sander P J; Zeilstra, Jurrit; van Andel, Harmen; Mijnals, R Clinton; Zaunbrecher, Joost; Duivenvoorden, Annet A M; van de Wetering, Marc; Clevers, Hans; Spaargaren, Marcel; Pals, Steven T

    2017-10-01

    Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor (EGF) receptor signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET coreceptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice. We established organoid cultures from ISCs stimulated with HGF or EGF and assessed intestinal differentiation by immunohistochemistry. Mice with total epithelial disruption of MET (Ah Cre /Met fl/fl /LacZ) or ISC-specific disruption of MET (Lgr5 Creert2 /Met fl/fl /LacZ) and control mice (Ah Cre /Met +/+ /LacZ, Lgr5 Creert2 /Met +/+ /LacZ) were exposed to 10 Gy total body irradiation; intestinal tissues were collected, and homeostasis and regeneration were assessed by immunohistochemistry. We investigated adenoma organoid expansion stimulated by HGF or EGF using adenomas derived from Lgr5 Creert2 /Met fl/fl /Apc fl/fl and Lgr5 Creert2 /Met +/+ /Apc fl/fl mice. The same mice were evaluated for adenoma prevalence and size. We also quantified adenomas in Ah Cre /Met fl/fl /Apc fl/+ mice compared with Ah Cre /Met +/+ /Apc fl/+ control mice. We studied expansion of organoids generated from crypts and adenomas, stimulated by HGF or EGF, that were derived from mice expressing different CD44 splice variants (Cd44 +/+ , Cd44 -/- , Cd44 s/s , or Cd44 v4-10/v4-10 mice). Crypts incubated with EGF or HGF expanded into self-organizing mini-guts with similar levels of efficacy and contained all differentiated cell lineages. MET-deficient mice did not have defects in intestinal homeostasis. Total body irradiation reduced numbers of proliferating crypts in Ah Cre

  19. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Science.gov (United States)

    Gruel, Gaëtan; Villagrasa, Carmen; Voisin, Pascale; Clairand, Isabelle; Benderitter, Marc; Bottollier-Depois, Jean-François; Barquinero, Joan Francesc

    2016-01-01

    Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to

  20. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Directory of Open Access Journals (Sweden)

    Gaëtan Gruel

    Full Text Available Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This

  1. THE LIVER OF WOODCHUCKS CHRONICALLY INFECTED WITH THE WOODCHUCK HEPATITIS VIRUS CONTAINS FOCI OF VIRUS CORE ANTIGEN NEGATIVE HEPATOCYTES WITH BOTH ALTERED AND NORMAL MORPHOLOGY

    Science.gov (United States)

    Xu, Chunxiao; Yamamoto, Toshiki; Zhou, Tianlun; Aldrich, Carol E.; Frank, Katy; Cullen, John M.; Jilbert, Allison R.; Mason, William S.

    2007-01-01

    The livers of woodchucks chronically infected with woodchuck hepatitis virus (WHV) contain foci of morphologically altered hepatocytes (FAH) with “basophilic”, “amphophilic” and “clear cell” phenotypes, which are possibly pre-neoplastic in nature. Interestingly, most fail to express detectable levels of WHV proteins and nucleic acids. We studied sections of WHV-infected liver tissue to determine if all foci of hepatocytes that failed to express detectable levels of WHV, as assessed by immunoperoxidase staining for WHV core antigen, could be classified morphologically as FAH. We found that at least half of the foci of WHV core antigen negative hepatocytes did not show clear morphological differences in either H&E or PAS (periodic acid Schiff) stained sections from surrounding hepatocytes, and were therefore not designated as FAH. In the second approach, we assayed core antigen negative foci for the presence of fetuin B, a serum protein produced by normal hepatocytes, but not by neoplastic hepatocytes in hepatocellular carcinomas. Basophilic and amphophilic FAH had reduced levels of fetuin B compared to hepatocytes present in the surrounding liver; fetuin B staining was detected in clear cell FAH but the level could not be accurately assessed because of the displacement of fetuin B to the cell periphery by accumulated glycogen. The foci of morphologically normal WHV core antigen negative hepatocytes had similar levels of fetuin B to that of the surrounding hepatocytes. The co-existence of at least four types of WHV core antigen negative foci, including those with no obvious morphologic changes, raises the possibility that the different foci arise from distinct primary events. We hypothesize that a common event is loss of the ability to express WHV, allowing these hepatocytes to escape immune mediated cell death and to undergo clonal expansion to form distinct foci. PMID:17078989

  2. RAD18 and associated proteins are immobilized in nuclear foci in human cells entering S-phase with ultraviolet light-induced damage

    International Nuclear Information System (INIS)

    Watson, Nicholas B.; Nelson, Eric; Digman, Michelle; Thornburg, Joshua A.; Alphenaar, Bruce W.; McGregor, W. Glenn

    2008-01-01

    Proteins required for translesion DNA synthesis localize in nuclear foci of cells with replication-blocking lesions. The dynamics of this process were examined in human cells with fluorescence-based biophysical techniques. Photobleaching recovery and raster image correlation spectroscopy experiments indicated that involvement in the nuclear foci reduced the movement of RAD18 from diffusion-controlled to virtual immobility. Examination of the mobility of REV1 indicated that it is similarly immobilized when it is observed in nuclear foci. Reducing the level of RAD18 greatly reduced the focal accumulation of REV1 and reduced UV mutagenesis to background frequencies. Fluorescence lifetime measurements indicated that RAD18 and RAD6A or polη only transferred resonance energy when these proteins colocalized in damage-induced nuclear foci, indicating a close physical association only within such foci. Our data support a model in which RAD18 within damage-induced nuclear foci is immobilized and is required for recruitment of Y-family DNA polymerases and subsequent mutagenesis. In the absence of damage these proteins are not physically associated within the nucleoplasm

  3. The environmental monitoring of Cultural Heritage through Low Cost strategies: The frescoes of the crypt of St. Francesco d'Assisi's, Irsina (Basilicata, Southern Italy)

    Science.gov (United States)

    Sileo, Maria; Gizzi, Fabrizio; Masini, Nicola

    2015-04-01

    One of the main tools of assessment and diagnosis used to define appropriate strategies for the preservation of cultural heritage is the environmental monitoring. To achieve an environmental monitoring are needed high costs of purchase and maintenance, high costs of instrumental and for the management of the plants and processing of results. These costs imply that the technologies for environmental monitoring are not as common but their use is limited to the study very famous monuments or sites. To extend the use and dissemination of such technologies to a greater number of monuments, through the project Pro_Cult (Advanced methodological approaches and technologies for Protection and Security of Cultural Heritage) a research aimed at testing low cost technologies has been performed. The aim of the research is to develop low cost monitoring systems, assessing their effectiveness in a comparative way with commercial high cost ones. To this aim an environmental monitoring system using the Arduino system was designed and developed. It is an electronics prototyping platform based on open-source hardware and software flexible and user friendly. This system is connected to sensors for the detection of environmental parameters of non high purchase cost but with respect to the medium potential detection sensors accurately. This low cost system was tested in the framework of a microclimate monitoring project of the crypt of St. Francis of Assisi in Irsina (Southern Italy) enriched by a precious cycle of medieval frescoes. The aim of this research was to compare two monitoring systems, the first, at low cost, using Arduino system, and the second, a standard commercial product for a full yearly cycle and assess the reliability and the results obtained by the two systems. This paper shows the results of the comparative analysis of an entire monitoring yearly cycle in relation to the problems of degradation affecting the paintings of medieval crypt [1]. The obtained results

  4. Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

    Directory of Open Access Journals (Sweden)

    Isam M A Zarroug

    Full Text Available The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs.A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010. Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests.Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies than Galabat (8,202 flies. In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month, and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month while none of flies were collected in August-October (MBR = 0 bites/person/month. In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month and September 2010 (N = 1,163, MBR = 6,978 bites/person/month, whereas, none appeared in collection from April to

  5. Temporal and spatial distribution characteristics in the natural plague foci of Chinese Mongolian gerbils based on spatial autocorrelation.

    Science.gov (United States)

    Du, Hai-Wen; Wang, Yong; Zhuang, Da-Fang; Jiang, Xiao-San

    2017-08-07

    The nest flea index of Meriones unguiculatus is a critical indicator for the prevention and control of plague, which can be used not only to detect the spatial and temporal distributions of Meriones unguiculatus, but also to reveal its cluster rule. This research detected the temporal and spatial distribution characteristics of the plague natural foci of Mongolian gerbils by body flea index from 2005 to 2014, in order to predict plague outbreaks. Global spatial autocorrelation was used to describe the entire spatial distribution pattern of the body flea index in the natural plague foci of typical Chinese Mongolian gerbils. Cluster and outlier analysis and hot spot analysis were also used to detect the intensity of clusters based on geographic information system methods. The quantity of M. unguiculatus nest fleas in the sentinel surveillance sites from 2005 to 2014 and host density data of the study area from 2005 to 2010 used in this study were provided by Chinese Center for Disease Control and Prevention. The epidemic focus regions of the Mongolian gerbils remain the same as the hot spot regions relating to the body flea index. High clustering areas possess a similar pattern as the distribution pattern of the body flea index indicating that the transmission risk of plague is relatively high. In terms of time series, the area of the epidemic focus gradually increased from 2005 to 2007, declined rapidly in 2008 and 2009, and then decreased slowly and began trending towards stability from 2009 to 2014. For the spatial change, the epidemic focus regions began moving northward from the southwest epidemic focus of the Mongolian gerbils from 2005 to 2007, and then moved from north to south in 2007 and 2008. The body flea index of Chinese gerbil foci reveals significant spatial and temporal aggregation characteristics through the employing of spatial autocorrelation. The diversity of temporary and spatial distribution is mainly affected by seasonal variation, the human

  6. DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available PURPOSE: In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. METHODS AND MATERIALS: In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. RESULTS: Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. CONCLUSIONS: Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

  7. The p150 subunit of CAF-1 causes association of SUMO2/3 with the DNA replication foci

    International Nuclear Information System (INIS)

    Uwada, Junsuke; Tanaka, Niina; Yamaguchi, Yutaro; Uchimura, Yasuhiro; Shibahara, Kei-ichi; Nakao, Mitsuyoshi; Saitoh, Hisato

    2010-01-01

    The small ubiquitin-related modifier 2/3 (SUMO2/3) can be post-translationally conjugated to a wide variety of proteins constituting chromatin, the platform for genetic and epigenetic regulation. Nevertheless, it is unclear how SUMO2/3 and SUMO2/3-modified proteins are delivered to the chromatin fibers. Here we report that the largest subunit of chromatin assembly factor 1 (CAF-1), human p150, interacts directly and preferentially with SUMO2/3. Amino acid residue of 98-105 in p150 is essential and sufficient for SUMO2/3 interaction. p150-SUMO2/3 interaction coincided with regions that replicate chromatin fibers, because accumulation of the proliferating cell nuclear antigen (PCNA), and incorporation of bromodeoxyuridine (BrdU) were detected at foci co-localized with both p150 and SUMO2/3 during the S-phase in a cell line expressing epitope-tagged p150. Although inhibition of SUMO2/3 expression had only a small effect on p150 deposition on the replication sites, depletion of p150 led to delocalization of SUMO2/3 from the replication foci. Furthermore, p150 mutants deficient in SUMO2/3 interaction, caused a major reduction of SUMO2/3 at the replication foci. Thus, our findings suggest an expanded role of p150 as a SUMO2/3-interacting factor, and raise the intriguing possibility that p150 plays a role in promoting delivery of SUMO2/3 or SUMO2/3-modified proteins (or both) on chromatin fibers during replication.

  8. Hidden sylvatic foci of the main vector of Chagas disease Triatoma infestans: threats to the vector elimination campaign?

    Directory of Open Access Journals (Sweden)

    Leonardo A Ceballos

    2011-10-01

    Full Text Available Establishing the sources of reinfestation after residual insecticide spraying is crucial for vector elimination programs. Triatoma infestans, traditionally considered to be limited to domestic or peridomestic (abbreviated as D/PD habitats throughout most of its range, is the target of an elimination program that has achieved limited success in the Gran Chaco region in South America.During a two-year period we conducted semi-annual searches for triatomine bugs in every D/PD site and surrounding sylvatic habitats after full-coverage spraying of pyrethroid insecticides of all houses in a well-defined rural area in northwestern Argentina. We found six low-density sylvatic foci with 24 T. infestans in fallen or standing trees located 110-2,300 m from the nearest house or infested D/PD site detected after insecticide spraying, when house infestations were rare. Analysis of two mitochondrial gene fragments of 20 sylvatic specimens confirmed their species identity as T. infestans and showed that their composite haplotypes were the same as or closely related to D/PD haplotypes. Population studies with 10 polymorphic microsatellite loci and wing geometric morphometry consistently indicated the occurrence of unrestricted gene flow between local D/PD and sylvatic populations. Mitochondrial DNA and microsatellite sibship analyses in the most abundant sylvatic colony revealed descendents from five different females. Spatial analysis showed a significant association between two sylvatic foci and the nearest D/PD bug population found before insecticide spraying.Our study shows that, despite of its high degree of domesticity, T. infestans has sylvatic colonies with normal chromatic characters (not melanic morphs highly connected to D/PD conspecifics in the Argentinean Chaco. Sylvatic habitats may provide a transient or permanent refuge after control interventions, and function as sources for D/PD reinfestation. The occurrence of sylvatic foci of T. infestans in

  9. [Outstanding Soviet zoologist and parasitologist E. N. Pavlovsky--the creator of the theory of natural foci of disease].

    Science.gov (United States)

    Pavlovskyĭ, L N

    2011-01-01

    The article presents information on the outstanding Soviet Zoology and Parasitology, Academician of the Academy of Sciences of the USSR Academy of Medical Sciences of the USSR, Hero of Socialist Labour, Lieutenant-General of the Medical Service E. N. Pavlovsky, the author of more than 1500 scientific papers, the founder of scientific school, one of the few scholars the twentieth century, approaching the level of scientists and encyclopedists. Considered its contribution to the study of natural foci of diseases has promoted the development of environmental trends in parasitology.

  10. Hypersensitive responses of cells in the thymus, spleen, and intestinal crypt of mice to interphase death after treatment with x rays and chemical mutagens

    International Nuclear Information System (INIS)

    Kinuta, Masakatsu

    1986-01-01

    Upon whole-body exposure of mice to X rays or administration of chemical mutagens, cells in thymus, spleen and intestinal crypt undergo sensitive response to interphase death. We developed an effective method for detecting dead cells in the interphase by scoring stained cells in situ in exposed tissues after staining frozen section with erythrosin B. Cell killing was detected at doses as low as 1 % of lethal doses after treatment with X rays and chemicals. Strain N4 was highly sensitive to interphase-cell-death and hybrids of N4 and resistant strain HT or C3H were also sensitive to cell-death, indicating a dominant trait of the sensitive cell-death response. (author)

  11. The influence of androgens, anti-androgens, and castration on cell proliferation in the jejunal and colonic crypt epithelia, and in dimethylhydrazine-induced adenocarcinoma of rat colon.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1982-01-01

    Androgenic hormones have previously been shown to promote cell proliferation in the small intestine of rat and androgen receptors have been demonstrated in carcinomata of the large intestine of rat. In this study the influence of testosterone and of castration on epithelial cell proliferation in the small intestine, the large intestine and in dimethylhydrazine-induced colonic tumours is compared. Cell proliferation in the small intestine and in colonic tumours was accelerated by testosterone treatment, and cell proliferation in colonic tumours, but not in the small intestine, was retarded following castration. Cell proliferation in colonic tumours was also inhibited by the anti-androgenic drug, Flutamide. Testosterone and castration each failed to influence cell proliferation in the colonic crypt epithelium of both normal and carcinogen-treated animals.

  12. Molecular features of colorectal polyps presenting Kudo’s type II mucosal crypt pattern: are they based on the same mechanism of tumorigenesis?

    Science.gov (United States)

    Shinmura, Kensuke; Konishi, Kazuo; Yamochi, Toshiko; Kubota, Yutaro; Yano, Yuichiro; Katagiri, Atsushi; Muramoto, Takashi; Kihara, Toshihiro; Tojo, Masayuki; Konda, Kenichi; Tagawa, Teppei; Yanagisawa, Fumito; Kogo, Mari; Makino, Reiko; Takimoto, Masafumi; Yoshida, Hitoshi

    2014-01-01

    Background and study aims: The molecular features of serrated polyps (SPs) with hyperplastic crypt pattern, also called Kudo’s type II observed by chromoendoscopy, were evaluated. Methods: The clinicopathological and molecular features of 114 SPs with a hyperplastic pit pattern detected under chromoendoscopy (five dysplastic SPs, 63 sessile serrated adenoma/polyps (SSA/Ps), 36 microvesicular hyperplastic polyps (MVHPs), and 10 goblet cell-rich hyperplastic polyps (GCHPs)) were examined. The frequency of KRAS and BRAF mutations and CpG island methylator phenotype (CIMP) were investigated. Results: Dysplastic SPs and SSA/Ps were frequently located in the proximal colon compared to others (SSA/Ps vs. MVHPs or GCHPs, P GCHP (60 % for dysplastic SPs, 44 % for SSA/Ps, 47 % for MVHPs, and 0 % for GCHPs). The frequency of CIMP was higher in dysplastic SPs or SSA/Ps than in MVHPs or GCHPs (60 % for dysplastic SPs, 56 % for SSA/Ps, 32 % for MVHPs, and 10 % for GCHPs) (SSA/Ps vs. GCHP, P = 0.0068). When serrated neoplasias (SNs) and MVHPs were classified into proximal and distal lesions, the frequency of CIMP was significantly higher in the proximal compared to the distal SNs (64 % vs. 11 %, P = 0.0032). Finally, multivariate analysis showed that proximal location and BRAF mutation were significantly associated with an increased risk of CIMP. Conclusions: Distinct molecular features were observed between proximal and distal SPs with hyperplastic crypt pattern. Proximal MVHPs may develop more frequently through SSA/Ps to CIMP cancers than distal MVHPs. PMID:26134964

  13. Molecular features of colorectal polyps presenting Kudo's type II mucosal crypt pattern: are they based on the same mechanism of tumorigenesis?

    Science.gov (United States)

    Shinmura, Kensuke; Konishi, Kazuo; Yamochi, Toshiko; Kubota, Yutaro; Yano, Yuichiro; Katagiri, Atsushi; Muramoto, Takashi; Kihara, Toshihiro; Tojo, Masayuki; Konda, Kenichi; Tagawa, Teppei; Yanagisawa, Fumito; Kogo, Mari; Makino, Reiko; Takimoto, Masafumi; Yoshida, Hitoshi

    2014-09-01

    The molecular features of serrated polyps (SPs) with hyperplastic crypt pattern, also called Kudo's type II observed by chromoendoscopy, were evaluated. The clinicopathological and molecular features of 114 SPs with a hyperplastic pit pattern detected under chromoendoscopy (five dysplastic SPs, 63 sessile serrated adenoma/polyps (SSA/Ps), 36 microvesicular hyperplastic polyps (MVHPs), and 10 goblet cell-rich hyperplastic polyps (GCHPs)) were examined. The frequency of KRAS and BRAF mutations and CpG island methylator phenotype (CIMP) were investigated. Dysplastic SPs and SSA/Ps were frequently located in the proximal colon compared to others (SSA/Ps vs. MVHPs or GCHPs, P GCHP (60 % for dysplastic SPs, 44 % for SSA/Ps, 47 % for MVHPs, and 0 % for GCHPs). The frequency of CIMP was higher in dysplastic SPs or SSA/Ps than in MVHPs or GCHPs (60 % for dysplastic SPs, 56 % for SSA/Ps, 32 % for MVHPs, and 10 % for GCHPs) (SSA/Ps vs. GCHP, P = 0.0068). When serrated neoplasias (SNs) and MVHPs were classified into proximal and distal lesions, the frequency of CIMP was significantly higher in the proximal compared to the distal SNs (64 % vs. 11 %, P = 0.0032). Finally, multivariate analysis showed that proximal location and BRAF mutation were significantly associated with an increased risk of CIMP. Distinct molecular features were observed between proximal and distal SPs with hyperplastic crypt pattern. Proximal MVHPs may develop more frequently through SSA/Ps to CIMP cancers than distal MVHPs.

  14. Dicentric chromosomes and γ-H2AX foci formation in lymphocytes of human blood samples exposed to a CT scanner: A direct comparison of dose response relationships

    International Nuclear Information System (INIS)

    Golfier, S.; Jost, G.; Pietsch, H.; Lengsfeld, P.; Eckardt-Schupp, F.; Schmid, E.; Voth, M.

    2009-01-01

    Experiments using the induction of dicentric chromosomes (dicentrics) as well as the γ-H2AX foci formation in lymphocytes of blood samples from a healthy donor were performed to directly evaluate the radiation sensitivity of both biological endpoints. For computed tomography scans at dose levels from 0.025 to 1 Gy, a linear-quadratic dose - response relationship for dicentrics and a linear dose - response relationship for γ-H2AX foci were obtained. The coefficients of the dose - response relationship for dicentrics are α = (3.76 ± 0.29) x 10 -2 Gy -1 and β = (5.54 ± 0.45) x 10 -2 Gy -2 , the linear coefficient for γ-H2AX foci is (7.38 ± 0.11) Gy -1 . The findings indicate that scoring of dicentrics as well as microscopic analysis of γ-H2AX foci are sensitive methods to quantify a radiation-induced biological damage at low doses. However, since γ-H2AX foci can be partially repaired within a few hours, biological damages present for days or even months, which constitute the clinically relevant endpoints, can only be quantified reliably by scoring of chromosome aberrations. Thus currently the quantification of dicentrics or reciprocal translocations remains the recommended method for estimating the effect of exposures to low dose levels of radiation ('biological dosimetry'). However, owing to the high radiation sensitivity of the γ-H2AX foci assay observed in the present study, further investigations on the effectiveness of low-linear energy transfer radiation qualities in producing γ-H2AX foci in lymphocytes from healthy donors should be performed. (authors)

  15. Frugivorous birds influence the spatial organization of tropical forests through the generation of seedling recruitment foci under zoochoric trees

    Science.gov (United States)

    Trolliet, Franck; Forget, Pierre-Michel; Doucet, Jean-Louis; Gillet, Jean-François; Hambuckers, Alain

    2017-11-01

    Animal-mediated seed dispersal is recognized to influence the spatial organization of plant communities but little is known about how frugivores cause such patterns. Here, we explored the role of hornbills and primates in generating recruitment foci under two zoochoric trees, namely Staudtia kamerunensis (Myristicaceae) and Dialium spp. (Fabaceae - Caesalpiniodea) in a forest-savanna mosaic landscape in D.R. Congo. We also examined the influence of the availability of fruits in the neighborhood and the amount of forest cover in the landscape on such clumping patterns. The density and species richness of hornbill-dispersed and the density of primate-dispersed seedlings were significantly higher under Staudtia kamerunensis trees than at control locations. However, we did not find such patterns under Dialium spp. trees compared to control locations except for the density of hornbill-dispersed seedlings which was lower at control locations. Also, we found that an increasing amount of forest cover in the landscape was associated with an increase in the density of hornbill-dispersed seedlings, although the tendency was weak (R2 = 0.065). We concluded that S. kamerunensis acts as a recruitment foci and plays a structuring role in Afrotropical forests. Hornbills were probably the main frugivore taxon responsible for the clumping under that tree and appear as a key ecological component in fragmented and disturbed landscapes where the diversity of large frugivores such as primates is reduced. Our findings improve our understanding of the causal mechanisms responsible for the spatial organization of tropical forests.

  16. Comparison of benzodiazepine receptor and regional cerebral blood flow imagings of epileptiform foci in hippocampal kindled rabbits

    International Nuclear Information System (INIS)

    Kurokawa, Kenzo

    1993-01-01

    To compare the benzodiazepine (Bz) receptor imaging and regional cerebral blood flow (rCBF) imaging in the detection of epileptic foci, the distribution pattern of the Bz receptor and rCBF in hippocampal kindled rabbits was examined by a double tracer autoradiography using ethyl 7-[ 125 I]-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1, 5-a][1,4] benzodiazepine-3-carboxylate ( 125 I-Ro 16-0154) and 99m Tc-hexamethyl-propyleneamine oxime ( 99m Tc-HMPAO). In visual and quantitative analyses, 125 I-Ro 16-0154 accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled CA1 region mimicking a primary epileptic focus. 125 I-Ro 16-0154 accumulation was moderately decreased in the ipsilateral temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. 99m Tc-HMPAO accumulation was found to be decreased in the ipsilateral CA1, frontal, temporal and dentate gyri. However, the decrease was much more slight and less extensive than that in 125 I-Ro 16-0154 accumulation. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy. (author)

  17. Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

    Science.gov (United States)

    Cucinotta, Francis, A.; Pluth, Janice M.; Anderson, Jennifer A.; Harper, Jane V.; O'Neill, Peter

    2007-01-01

    We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower.

  18. Microscopic evaluation of nuclear foci (gamma H2AX) in cells irradiated with protons and lithium ions

    International Nuclear Information System (INIS)

    Bracalente, C.; Molinari, Beatriz L.; Duran, Hebe; Ibanez, I.; Palmieri, M.; Kreiner, Andres J.; Burlon, Alejandro; Valda, Alejandro; Davidson, J.; Davidson, M.; Vazquez, Monica; Ozafran, Mabel J.

    2007-01-01

    Full text: The special properties of both physical and biological radiation particles with high-LET (Linear Transfer of Energy) have led to its increased use in cancer therapy. In this work, the effect of high and low LET radiation on cell lines with different radiosensitivity (Irs-20 and CHO-10B2) quantifying the number and size of nuclear foci obtained from histone H2AX (γH2AX) phosphorylation which plays an important role in DNA damage reparation is compared. Foci detection was performed by immunocytochemical methods and fluorescence microscopy. The cells cultures were irradiated with plateau-phase protons (14 MeV, LET: 3 keV/μ), on Bragg peak (3 MeV. LET: 14 KeV/μ) and with Lithium ions (7 MeV, LET: 250 KeV//μ) on the Tandar accelerator. A clonogenic analysis of the two cell lines was made. Irradiation with protons (low LET) showed a significant difference (p [es

  19. Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

    Science.gov (United States)

    Persinger, Michael A

    2009-01-01

    To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

  20. Effect of microwave and ionizing radiation on formation of DNA of repair foci in lymphocytes from cord blood; Vplyv mikrovlnneho a ionizacneho ziarenia na tvorbu DNA opravnych fokusov v lymfocytoch z pupocnikovej krvi

    Energy Technology Data Exchange (ETDEWEB)

    Durdik, M.; Markova, E.; Belyaev, I. [Slovenska akademia vied, Ustav experimentalnej onkologie, 83391 Bratislava (Slovakia)

    2013-04-16

    Different types of radiation are affecting us nowadays. Electromagnetic radiation which is produced mainly by mobile phones, Wi-fi and base stations is affecting us practically all of the time. Long term effects of this type of radiation are not fully examined. It is very important to know effects of radiation that influence us so much like electromagnetic radiation. DNA double strand breaks (DSBs) are the most deleterious types of DNA damage. Several proteins involved in DNA repair and DNA damage signaling have been shown to produce discrete foci in response to ionizing radiation. These foci are believed to co-localize to DSB and referred to as ionizing radiation-induced foci or DNA repair foci. Ionizing radiation is known to induce formation of radiation induced foci which are very hard to analyze exactly. That's why the second aim of this work was to compare two automatized systems for analysis of DNA repair foci, METAFER and ImageStream. (authors)

  1. Effect of a hyperlipidic diet rich in omegas 3, 6 and 9 on aberrant crypt formation in rat colonic mucosa Efeito de uma dieta hiperlipídica rica em ômegas 3, 6 e 9 na formação de criptas aberrantes em mucosa cólica de ratos

    Directory of Open Access Journals (Sweden)

    Idália Maria Brasil Burlamaqui

    2012-01-01

    Full Text Available PURPOSE: To determine whether a hypercaloric and hyperlipidic diet enriched with polyunsaturated fatty acids influences the formation of aberrant crypt foci (ACF in colonic mucosa of Wistar rats treated with azoxymethane (AOM. METHODS: At eight weeks of life, the rats were assigned to four groups: Group I―standard diet (STD not treated with AOM; Group II―hypercaloric and hyperlipidic diet (FED, not treated with AOM; Group III―STD, treated with AOM; Group IV―FED, treated with AOM. At 16 weeks, the animals were injected intraperitoneal with 0.9% saline solution (Group I and II or AOM at 15mg/Kg (Groups III and IV once a week for two weeks. Fifteen weeks later, the animals were euthanized. RESULTS: FED promoted weight gain in Groups II and IV compared to Groups I and III, respectively. The groups did not differ with regard to the total number of ACF. The Chi-square test revealed no predominance of the presence of foci with OBJETIVO: Determinar se uma dieta hipercalórica, hiperlipídica, rica em ácidos graxos poliinsaturados (FED tem influência na formação de focos de cripta aberrante (FCA em mucosa cólica de ratos Wistar expostos ao azoximetano (AOM. MÉTODOS: Com oito semanas de vida, os ratos foram distribuídos em quatro grupos: Grupo I: Dieta padrão (SD sem AOM; Grupo II: FED, sem AOM; Grupo III: SD, com AOM; Grupo IV: FED com AOM. Com 16 semanas, os animais dos grupos I e II receberam injeções intraperitoneais de solução salina 0,9%, enquanto os dos grupos III e IV receberam AOM na dose de 15mg/Kg de peso, 1 vez por semana por duas semanas. Quinze semanas após, os animais foram mortos. RESULTADOS: FED promoveu aumento de peso nos grupos II e IV em relação aos grupos I e III. Não houve aumento significante no número total de FCA entre os grupos. Em relação à multiplicidade das criptas por FCA, o teste do qui-quadrado mostrou que não houve predominância da presença <4 criptas por foco. Contudo, focos ≥5 criptas

  2. Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52

    International Nuclear Information System (INIS)

    Veelen, Lieneke R. van; Essers, Jeroen; Rakt, Mandy W.M.M. van de; Odijk, Hanny; Pastink, Albert; Zdzienicka, MaIgorzata Z.; Paulusma, Coen C.; Kanaar, Roland

    2005-01-01

    Homologous recombination is of major importance for the prevention of genomic instability during chromosome duplication and repair of DNA damage, especially double-strand breaks. Biochemical experiments have revealed that during the process of homologous recombination the RAD52 group proteins, including Rad51, Rad52 and Rad54, are involved in an essential step: formation of a joint molecule between the broken DNA and the intact repair template. Accessory proteins for this reaction include the Rad51 paralogs and BRCA2. The significance of homologous recombination for the cell is underscored by the evolutionary conservation of the Rad51, Rad52 and Rad54 proteins from yeast to humans. Upon treatment of cells with ionizing radiation, the RAD52 group proteins accumulate at the sites of DNA damage into so-called foci. For the yeast Saccharomyces cerevisiae, foci formation of Rad51 and Rad54 is abrogated in the absence of Rad52, while Rad51 foci formation does occur in the absence of the Rad51 paralog Rad55. By contrast, we show here that in mammalian cells, Rad52 is not required for foci formation of Rad51 and Rad54. Furthermore, radiation-induced foci formation of Rad51 and Rad54 is impaired in all Rad51 paralog and BRCA2 mutant cell lines tested, while Rad52 foci formation is not influenced by a mutation in any of these recombination proteins. Despite their evolutionary conservation and biochemical similarities, S. cerevisiae and mammalian Rad52 appear to differentially contribute to the DNA-damage response

  3. Computer-aided diagnosis of interictal 18F-FDG PET images for presurgical evaluation of epileptic foci in extratemporal lobe epilepsy

    International Nuclear Information System (INIS)

    Imabayashi, Etsuko

    2003-01-01

    Interictal 18 F-FDG PET is beneficial to patients with epilepsy to define the epileptic foci before operation, especially to decide the laterality of temporal lobe epilepsy (TLE). However usefulness has not been clearly established in extra TLE. We retrospectively applied Z-score analysis to interictal preoperative 18 F-FDG PET images for detection of the epileptic foci in order to achieve better performance. Seventeen epileptic patients (women/men; 8/9, age; 11-55 yrs) underwent resection of epileptic foci with good outcome (Engel's stage of I or II) even after more than a year from operation. Presurgical 18 F-FDG PET images were spatially normalized using statistical parametric mapping 99 (SPM99) with an original Japanese template for 18 F-FDG and compared with normal database constructed from 31 healthy volunteers (women/men; 14/17, age; 19-59 yrs). A software program, easy Z-score imaging system (eZIS), for analysis of patient data was developed by calculating Z-score in each voxel and visualizing the score in a standardized stereotactic space; Z-score=(normal mean-patient's value)/a standard deviation of normal data. Detectability of epileptic foci for this computer-aided analysis was compared with visual inspection of original 18 F-FDG PET images by five radiologists without any clinical information. In all cases, there was significant reduction of glucose metabolism in the operated area. The sensitivities of the detection of epileptic foci obtained from visual inspection were 47-59%. In contrast to, computer analysis by eZIS showed 71% sensitivity when we defined the highest Z-score in the cerebrum to be the focus diagnosed by eZIS. Computer-aided diagnosis with eZIS for 18 F-FDG PET study is useful for detecting epileptic foci in extra TLE. (author)

  4. γ-H2AX foci are increased in lymphocytes in vivo in young children 1 h after very low-dose X-irradiation: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Halm, Brunhild M.; Franke, Adrian A.; Lai, Jennifer F. [University of Hawaii Cancer Center, Honolulu, HI (United States); Turner, Helen C.; Brenner, David J.; Zohrabian, Vatche M. [Columbia University Medical Center, Center for Radiological Research, New York, NY (United States); DiMauro, Robert [Kapi' olani Medical Center for Women and Children, Honolulu, HI (United States)

    2014-10-15

    Computed tomography (CT) is an imaging modality involving ionizing radiation. The presence of γ-H2AX foci after low to moderate ionizing radiation exposure has been demonstrated; however it is unknown whether very low ionizing radiation exposure doses from CT exams can induce γ-H2AX formation in vivo in young children. To test whether very low ionizing radiation doses from CT exams can induce lymphocytic γ-H2AX foci (phosphorylated histones used as a marker of DNA damage) formation in vivo in young children. Parents of participating children signed a consent form. Blood samples from three children (ages 3-21 months) undergoing CT exams involving very low blood ionizing radiation exposure doses (blood doses of 0.22-1.22 mGy) were collected immediately before and 1 h post CT exams. Isolated lymphocytes were quantified for γ-H2AX foci by a technician blinded to the radiation status and dose of the patients. Paired t-tests and regression analyses were performed with significance levels set at P < 0.05. We observed a dose-dependent increase in γ-H2AX foci post-CT exams (P = 0.046) among the three children. Ionizing radiation exposure doses led to a linear increase of foci per cell in post-CT samples (102% between lowest and highest dose). We found a significant induction of γ-H2AX foci in lymphocytes from post-CT samples of three very young children. When possible, CT exams should be limited or avoided by possibly applying non-ionizing radiation exposure techniques such as US or MRI. (orig.)

  5. γ-H2AX foci are increased in lymphocytes in vivo in young children 1 h after very low-dose X-irradiation: a pilot study

    International Nuclear Information System (INIS)

    Halm, Brunhild M.; Franke, Adrian A.; Lai, Jennifer F.; Turner, Helen C.; Brenner, David J.; Zohrabian, Vatche M.; DiMauro, Robert

    2014-01-01

    Computed tomography (CT) is an imaging modality involving ionizing radiation. The presence of γ-H2AX foci after low to moderate ionizing radiation exposure has been demonstrated; however it is unknown whether very low ionizing radiation exposure doses from CT exams can induce γ-H2AX formation in vivo in young children. To test whether very low ionizing radiation doses from CT exams can induce lymphocytic γ-H2AX foci (phosphorylated histones used as a marker of DNA damage) formation in vivo in young children. Parents of participating children signed a consent form. Blood samples from three children (ages 3-21 months) undergoing CT exams involving very low blood ionizing radiation exposure doses (blood doses of 0.22-1.22 mGy) were collected immediately before and 1 h post CT exams. Isolated lymphocytes were quantified for γ-H2AX foci by a technician blinded to the radiation status and dose of the patients. Paired t-tests and regression analyses were performed with significance levels set at P < 0.05. We observed a dose-dependent increase in γ-H2AX foci post-CT exams (P = 0.046) among the three children. Ionizing radiation exposure doses led to a linear increase of foci per cell in post-CT samples (102% between lowest and highest dose). We found a significant induction of γ-H2AX foci in lymphocytes from post-CT samples of three very young children. When possible, CT exams should be limited or avoided by possibly applying non-ionizing radiation exposure techniques such as US or MRI. (orig.)

  6. Role Breadth Self-Efficacy and Foci of Proactive Behavior: Moderating Role of Collective, Relational, and Individual Self-Concept.

    Science.gov (United States)

    Hwang, Pin-Chyuan; Han, Ming-Chuan; Chiu, Su-Fen

    2015-01-01

    This study aims to identify the interactive effect of role breadth self-efficacy (RBSE) and the three levels of self-concept (collective, relational, and individual) in predicting of different foci of proactive behaviors. Results from 259 matched responses from an airline company in Taiwan showed that RBSE had a positive effect on (1) pro-organizational proactive behavior among those with higher collective self-concept, (2) pro-supervisor proactive behavior among those with higher relational self-concept, and (3) pro-self proactive behavior among those with higher individual self-concept. Our findings provide insights into the moderating role of different levels of self-concept on RBSE-proactive behavior process in terms of specific targets or beneficiaries. Further implications for organizational research and practice are discussed.

  7. [An assessment of the status of natural foci of Crimean-Congo hemorrhagic fever in the Crimea].

    Science.gov (United States)

    Markeshin, S Ia; Smirnova, S E; Evstaf'ev, I L

    1992-04-01

    The parasitological data and the results of the virological and serological investigations of materials, collected in nature and in the course of study of the immune structure of the population, are indicative of the circulation of CHF virus in the Crimea and the possibility of human infection. Data on spontaneous infection of four species of Ixodes ticks with CHF virus have been confirmed, including the data, obtained for the first time for this region, on the participation of Dermacentor marginatus in this process. The study has revealed, also for the first time, that, together with European brown hares, the natural foci of this infection may be maintained by scilly shrews, common voles and European wood mice. Low activity of the Crimean focus may be the result of active land reclamation, keeping the cattle stalled in most of the stock-breeding farms of the region, as well as a sharp decline in the number of hares at the territories of hunting preserves.

  8. [An evaluation of the status of natural foci of Crimean-Congo hemorrhagic fever in the Crimea].

    Science.gov (United States)

    Markeshin, S Ia; Smirnova, S E; Evstaf'ev, I L

    1991-09-01

    Parasitological data, the results of virological and serological investigations of materials, collected in nature and during the study of the immune structure of the population and indicative of the circulation of CCHF, virus in the Crimea and the possibility of human infection, are presented. The data on the spontaneous CCHF virus infection of 4 tick species belonging to the genus Ixodes have been confirmed, and evidence on the participation of Dermacentor marginatus in this process obtained for the first time in this region. The study has revealed for the first time that, besides European brown hares, scilly shrews, common voles and field mice may contribute to the maintenance of the natural foci of this infection. The low activity of the Crimean focus of CCHF may be the result of the intensive use of land, the widely spread stall-feeding of cattle, as well as a sharp decrease in the number of hares on the territories of hunting preserves.

  9. Endometrioid like yolk sac tumor of the testis with small teratomatous foci: A case report and review of the literature.

    Science.gov (United States)

    Hazarika, Prabir

    2015-01-01

    I have reported a case of endometrioid like yolk sac tumor of the testis in a 20-year-old boy. Endometrioid like yolk sac tumor is a rare tumor. A few cases have been reported in ovary. In case of male, a case of pure glandular endometrioid like yolk sac tumor is reported in a 43 years male in right undescended testis and another case of abdominal metastasis showing endometrioid pattern from mixed testicular germ cell tumor comprising of teratoma and embryonal carcinoma. My patient was a 20-year-old male presented with painless enlargement of right testis. Grossly the tumor was glistening creamish white with a multicystic appearance. Histopathological examination showed the tumor to be composed of glandular elements resembling early secretory endometrium, foci of keratinized thin squamous epithelium and a single focus of benign cartilage. The glandular elements show immunohistochemical positivity for AFP, cytokeratin 7 (CK7) and epithelial membrane antigen (EMA).

  10. Endometrioid like yolk sac tumor of the testis with small teratomatous foci: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Prabir Hazarika

    2015-01-01

    Full Text Available I have reported a case of endometrioid like yolk sac tumor of the testis in a 20-year-old boy. Endometrioid like yolk sac tumor is a rare tumor. A few cases have been reported in ovary. In case of male, a case of pure glandular endometrioid like yolk sac tumor is reported in a 43 years male in right undescended testis and another case of abdominal metastasis showing endometrioid pattern from mixed testicular germ cell tumor comprising of teratoma and embryonal carcinoma. My patient was a 20-year-old male presented with painless enlargement of right testis. Grossly the tumor was glistening creamish white with a multicystic appearance. Histopathological examination showed the tumor to be composed of glandular elements resembling early secretory endometrium, foci of keratinized thin squamous epithelium and a single focus of benign cartilage. The glandular elements show immunohistochemical positivity for AFP, cytokeratin 7 (CK7 and epithelial membrane antigen (EMA.

  11. X-ray induced formation of γ-H2AX foci after full-field digital mammography and digital breast-tomosynthesis.

    Directory of Open Access Journals (Sweden)

    Siegfried A Schwab

    Full Text Available PURPOSE: To determine in-vivo formation of x-ray induced γ-H2AX foci in systemic blood lymphocytes of patients undergoing full-field digital mammography (FFDM and to estimate foci after FFDM and digital breast-tomosynthesis (DBT using a biological phantom model. MATERIALS AND METHODS: The study complies with the Declaration of Helsinki and was performed following approval by the ethic committee of the University of Erlangen-Nuremberg. Written informed consent was obtained from every patient. For in-vivo tests, systemic blood lymphocytes were obtained from 20 patients before and after FFDM. In order to compare in-vivo post-exposure with pre-exposure foci levels, the Wilcoxon matched pairs test was used. For in-vitro experiments, isolated blood lymphocytes from healthy volunteers were irradiated at skin and glandular level of a porcine breast using FFDM and DBT. Cells were stained against the phosphorylated histone variant γ-H2AX, and foci representing distinct DNA damages were quantified. RESULTS: Median in-vivo foci level/cell was 0.086 (range 0.067-0.116 before and 0.094 (0.076-0.126 after FFDM (p = 0.0004. In the in-vitro model, the median x-ray induced foci level/cell after FFDM was 0.120 (range 0.086-0.140 at skin level and 0.035 (range 0.030-0.050 at glandular level. After DBT, the median x-ray induced foci level/cell was 0.061 (range 0.040-0.081 at skin level and 0.015 (range 0.006-0.020 at glandular level. CONCLUSION: In patients, mammography induces a slight but significant increase of γ-H2AX foci in systemic blood lymphocytes. The introduced biological phantom model is suitable for the estimation of x-ray induced DNA damages in breast tissue in different breast imaging techniques.

  12. Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors

    OpenAIRE

    Smetana, Ondrej; Sanchez-Calderon, Lenin; Lincker, Frédéric; Genestier, Julie; Schmit, Anne-Catherine; Houlné, Guy; Chabouté, Marie Edith

    2012-01-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (cH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of cH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional respo...

  13. Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

    Science.gov (United States)

    Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

    2011-01-01

    Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

  14. Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification

    Science.gov (United States)

    Wilson, Korey A.; Elefanty, Andrew G.; Stanley, Edouard G.; Gilbert, David M.

    2016-01-01

    ABSTRACT Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification. PMID:27433885

  15. Intestinal Bacterial Communities of Trypanosome-Infected and Uninfected Glossina palpalis palpalis from Three Human African Trypanomiasis Foci in Cameroon

    Directory of Open Access Journals (Sweden)

    Franck Jacob

    2017-08-01

    Full Text Available Glossina sp. the tsetse fly that transmits trypanosomes causing the Human or the Animal African Trypanosomiasis (HAT or AAT can harbor symbiotic bacteria that are known to play a crucial role in the fly's vector competence. We hypothesized that other bacteria could be present, and that some of them could also influence the fly's vector competence. In this context the objectives of our work were: (a to characterize the bacteria that compose the G. palpalis palpalis midgut bacteriome, (b to evidence possible bacterial community differences between trypanosome-infected and non-infected fly individuals from a given AAT and HAT focus or from different foci using barcoded Illumina sequencing of the hypervariable V3-V4 region of the 16S rRNA gene. Forty G. p. palpalis flies, either infected by Trypanosoma congolense or uninfected were sampled from three trypanosomiasis foci in Cameroon. A total of 143 OTUs were detected in the midgut samples. Most taxa were identified at the genus level, nearly 50% at the species level; they belonged to 83 genera principally within the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Prominent representatives included Wigglesworthia (the fly's obligate symbiont, Serratia, and Enterobacter hormaechei. Wolbachia was identified for the first time in G. p. palpalis. The average number of bacterial species per tsetse sample was not significantly different regarding the fly infection status, and the hierarchical analysis based on the differences in bacterial community structure did not provide a clear clustering between infected and non-infected flies. Finally, the most important result was the evidence of the overall very large diversity of intestinal bacteria which, except for Wigglesworthia, were unevenly distributed over the sampled flies regardless of their geographic origin and their trypanosome infection status.

  16. Normal physiologic and Benign foci with F-18 FDG avidity on PET/CT in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soon Ah; Lee, Kwang Man; Choi, Un Jong; Kim, Hun Soo; Kim, Hye Won; Song, Jeong Hoon [College of Medicine, Wonkwnag University, Iksan (Korea, Republic of)

    2010-12-15

    The aim of this study was to evaluate the physiologic and benign F-18 fluorodeoxyglucose (FDG) avid foci in patients with breast cancer. On 309 F-18 FDG PET/CT scans of 241 women with breast cancer, the hypermetabolic lesions compared with the surrounding normal region were evaluated retrospectively. Available reports of other relevant radiological imaging medical records, and follow-up PET/CT were reviewed for explanations of the abnormal uptake. Among the 70 physiologic foci, muscular uptake of the lower neck following the surgical and/or radiation therapy of ipsilateral breast (29%), hypermetabolic ovaries (16%) and uterine (10%) uptake during the ovulatory and menstrual phases during the normal menstrual cycle were identified, and also hypermetabolic brown fat in cold-induced thermogenesis (7%), non-specific bowel uptake (35%) were observed. Among the 147 benign lesions, sequelae of the chest wall and breasts following surgical and/or radiation therapy, were often observed (27%). Hypermetabolic thyroid glands were noted as adenomas and chronic thyroiditis (18%). Reactive hyperplasia of cervical or mediastinal lymph nodes (32%), degenerative osteoarthritis and healed fractures (15%), hypermetabolic benign lung lesions (6%) were observed. Altered physiologic and benign F-18 FDG uptake in the cervical muscle and chest wall following ipsilateral breast surgery or radiotherapy were common, and also normal physiologic uptake in ovary and uterus, brown fat, thyroid were considered as predominant findings in women patients with breast cancer. Knowledge of these findings might aid in the interpretation of FDG PET/CT in patients with breast cancer

  17. Tick-borne encephalitis virus isolates from natural foci of the Irkutsk region: clarification of the genotype landscape.

    Science.gov (United States)

    Mel'nikova, Ol'ga V; Adel'shin, R V; Korzun, V M; Trushina, Yu N; Andaev, E I

    The Irkutsk region is the unique territory where all known subtypes of tick-borne encephalitis virus (TBEV) circulate. In the last years, the phenomenon of changes in TBEV subtypes (substitution of the Far-Eastern subtype by the Siberian one) was noted in some regions of the Russian Federation. The results of individual investigation of 11522 Ixodes persulcatus ticks and brain specimens from 81 small mammals collected in natural foci of the Irkutsk region during 2006-2014 are presented in the article. More than 60 TBEV strains have been isolated and studied by virological methods; E gene fragments (1193 b.p.) of 68 isolates have been typed. The majority of the strains (irrespective of subtype) were of high virulence for laboratory mice (LM) in case of both intracerebral and subcutaneous inoculation of virus. All isolates from warm-blooded small mammals and humans were of high virulence for LM, but placed in the same clusters of the phylogenetic tree with ticks collected in the same area. Tick-borne strains of different virulence also did not form separate clusters on the tree. Phylogenetic analysis showed that modern TBEV genotypic landscape of the studied territory is changing toward absolute predominance of the Siberian subtype (94.1%). This subtype is represented by two groups with prototype strains “Zausaev” and “Vasilchenko”. The “Vasilchenko” group of strains is spread on the whole territory under study; the strains of “Zausaev” group were isolated previously in the Irkutsk suburbs. The European subtype of TBEV circulates in natural foci of Pribaikalie permanently (at least 5% of the random sampling); the strains are of high virulence for LM. The Far-Eastern TBEV subtype was not found within the group of isolates collected in 20062014. The phylogenetic relationship of the strains under study had a higher correlation with the place of isolation than with the year or source.

  18. Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to ⁶⁰Co γ-rays and p(66)+ Be(40) neutrons.

    Science.gov (United States)

    Vandersickel, Veerle; Beukes, Philip; Van Bockstaele, Bram; Depuydt, Julie; Vral, Anne; Slabbert, Jacobus

    2014-02-01

    To investigate both the formation of micronuclei (MN) and the induction and subsequent loss of phosphorylated histone H2AX foci (γH2AX foci) after in vitro exposure of human lymphocytes to either (60)Co γ-rays or p(66)+ Be(40) neutrons. MN dose response (DR) curves were obtained by exposing isolated lymphocytes of 10 different donors to doses ranging from 0-4 Gy γ-rays or 0-2 Gy neutrons. Also, γH2AX foci DR curves were obtained following exposure to doses ranging from 0-0.5 Gy of either γ-rays or neutrons. Foci kinetics for lymphocytes for a single donor exposed to 0.5 Gy γ-rays or neutrons were studied up to 24 hours post-irradiation. Micronuclei yields following neutron exposure were consistently higher compared to that from (60)Co γ-rays. All MN yields were over-dispersed compared to a Poisson distribution. Over-dispersion was higher after neutron irradiation for all doses > 0.1 Gy. Up to 4 hours post-irradiation lower yields of neutron-induced γH2AX foci were observed. Between 4 and 24 hours the numbers of foci from neutrons were consistently higher than that from γ-rays. The half-live of foci disappearance is only marginally longer for neutrons compared to that from γ-rays. Foci formations were more likely to be over-dispersed for neutron irradiations. Although neutrons are more effective to induce MN, the absolute number of induced γH2AX foci are less at first compared to γ-rays. With time neutron-induced foci are more persistent. These findings are helpful for using γH2AX foci in biodosimetry and to understand the repair of neutron-induced cellular damage.

  19. Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.

    Science.gov (United States)

    Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N

    2009-05-01

    A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high-grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high-grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3-4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology-histology mismatch. (c) 2009 Wiley-Liss, Inc.

  20. Differential effect of IP- and IV-injected nitrogen mustard on subsequently-irradiated intestinal crypts: implications for 'dose-effect factors' predicted by experimental, combined modality therapy

    International Nuclear Information System (INIS)

    Moore, J.V.

    1984-01-01

    In experimental chemotherapy-radiotherapy, cytotoxic drugs are almost invariably injected by the intraperitoneal (IP) route. This contrasts with normal clinical practice, which is to employ the intravenous (IV) route. We have used a clonogenic assay of gastrointestinal (GI) injury in mice to show that a given administered dose of nitrogen mustard (HN 2 ), injected IP, results in a much greater reduction in the subsequent radiation dose required to achieve an isoeffect, than if the drug is injected IV. At an administered dose of 3.5 mg kg -1 of HN 2 (the animal LDsub(10/30) for IP injection), the radiation dose-reduction factor for 10% survival of intestinal crypts, was 1.94 for IP HN 2 and only 1.28 for IV HN 2 . Even the grossly-equitoxic (mouse LDsub(10/30)) dose of IV HN 2 resulted in a smaller predicted radiation dose reduction for GI injury, by a factor of 1.45. The validity of using the IP route in combined chemotherapy-radiotherapy studies designed to generate quantitative estimates of toxicity is discussed. (author)

  1. Evidence supporting pre-radiation elimination of oral foci of infection in head and neck cancer patients to prevent oral sequelae. A systematic review

    NARCIS (Netherlands)

    Schuurhuis, Jennifer M.; Stokman, Monique A.; Witjes, Max J. H.; Dijkstra, Pieter U.; Vissink, Arjan; Spijkervet, Frederik K. L.

    Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral foci of infection to prevent post-radiation oral problems. The evidence for the efficacy of dental screening is unclear. In this systematic review, we analyzed available evidence on the efficacy of

  2. Positive /sup 67/Ga-citrate scintigraphy: Vertebral, satellite lymph node and gallbladder foci in a case of gastroenteritis with salmonella

    Energy Technology Data Exchange (ETDEWEB)

    Popa, N; Lens, E; Dubois, J L; Blase, F

    1982-03-01

    We report a case of salmonella gastroenteritis with recurrent fever and sepsis, slight transient lumbar pain and positive /sup 67/Ga-citrate scintigraphy. The /sup 67/Ga scan made a major contribution to the positive diagnosis of a subclinical spondylodiscite and to the correct treatment leading to the disappearance of the infectious foci.

  3. γ-H2AX foci analysis in human lymphocytes: a biological tool for assessment of early triage during mass exposure of radiation

    International Nuclear Information System (INIS)

    Nayak, Akshay Kumar A.; Mumbrekar, Kamalesh D.; Satish Rao, B.S.

    2014-01-01

    Emergence of nuclear terrorism and increased use of nuclear technology for industry, energy production, and defence purpose has also increased the risk of mass exposure to radiation. During these scenarios of mass exposure to radiation, an efficient system which would measure the dose absorbed by an individual is required for early triage management. The present study aims to establish γ-H2AX as a biomarker for management of early triage. Radiation induced DNA DSB studied in lymphocytes isolated from 10 healthy individuals and challenged with 2 Gy of X-rays in vitro showed a gradual decrease in number of foci signals. As the persistence of foci signals is important for biodosimetry, phosphatase inhibitors like Calyculin A, Fostriecin and Okadiac Acid were used. Calyculin A was found to be the better inhibitor showing a 2 fold increase in retention of foci signals at 6 hours. The dose response curve was performed in lymphocytes isolated from healthy individuals by fluorescent microscopy and flow cytometry. Although both the methods indicated a linear increase in foci signals, microscopic analysis was found to be more sensitive. Influence of age and gender on dose response curve was studied and no significant difference was found. The effect of confounding factors like genetic factors and smoking habits on the dose response curve is being investigated. (author)

  4. Ionizing radiation-induced DNA double-strand break and repair assessed by γ-H2AX foci analysis in neurons in mice

    International Nuclear Information System (INIS)

    Dong Xiaorong; Wu Gang; Ruebe Claudia; Ruebe Christian

    2009-01-01

    Objective: To investigate if the γ-H2AX foci is a precise index for the DSB formation and repair in mature neurons of brain in vivo after clinically relevant doses irradiation. Methods: For the DSB formation experiment, the mature neurons in the neocortex of brain tissue of C57BL/6 mice were analyzed at 10 rain after whole-body irradiation with 0.1, 0.5 and 1.0 Gy. For the DSB repair kinetics experiment, the mature neurons in the neocortex of brain tissue of repair-proficient (C57BL/6 mice) and repair-deficient mouse strains (BALB/c, A-T and SCID mice) were analyzed at 0.5, 2.5, 5, 24 and 48 h after whole-body irradiation with 2 Gy. The mature neurons in the neocortex of brain tissue of sham-irradiated mice of each strain served as controls. γ-H2AX immunohistochemistry and γ-H2AX and NeuN double immunofluorescence analysis was used to measure DSBs formation and repair in the mature neurons in the neocortex of brain tissue of the different mouse strains. Results: For the DSB formation experiment, γ-H2AX foci levels with a clear linear close correlation and very low backgrounds in the nuclei in the neocortex of brain tissue were observed. Scoring the loss of γ-H2AX foci allowed us to verify the different, genetically determined DSB repair deficiencies, including the minor impairment of BALB/c mice. Repair-proficient C57BL/6 mice exhibited the fastest decrease in foci number with time, and displayed low levels of residual damage at 24 h and 48 h post-irradiation. In contrast, SCID mice showed highly increased γ-H2AX foci levels at all repair times (0.5 h to 48 h) while A-T mice exhibited a lesser defect which was most significant at later repair times (≥ 5 h). Radiosensitive BALB/c mice exhibited slightly elevated foci numbers compared with C57BL/6 mice at 5 h and 24 h but not at 48 h post-irradiation. Conclusion: Quantifying the γ-H2AX foci in normal tissue represents a sensitivie tool for the detection of induction and repair of radiation-induced DSBs at

  5. Induction and Persistence of Large γH2AX Foci by High Linear Energy Transfer Radiation in DNA-Dependent protein kinase–Deficient Cells

    International Nuclear Information System (INIS)

    Bracalente, Candelaria; Ibañez, Irene L.; Molinari, Beatriz; Palmieri, Mónica; Kreiner, Andrés; Valda, Alejandro

    2013-01-01

    Purpose: To evaluate the cell response to DNA double-strand breaks induced by low and high linear energy transfer (LET) radiations when the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), an essential protein of the nonhomologous end-joining repair pathway, lacks kinase activity. Methods and Materials: CHO10B2, a Chinese hamster ovary cell line, and its derived radiosensitive mutant cell line, irs-20, lacking DNA-PKcs activity, were evaluated after 0 to 3 Gy of γ-rays, plateau and Bragg peak protons, and lithium beams by clonogenic assay, and as a measurement of double-strand breaks, phosphorylated H2AX (γH2AX) foci number and size were quantified by immunocytofluorescence. Results: Irs-20 exhibited greater radiosensitivity and a higher amount of γH2AX foci than CHO10B2 at 6 hours after irradiation for all types of radiations. Remarkably, CHO10B2 and irs-20 maintained their difference in radiosensitivity after high-LET radiation. Six hours after low-LET radiations, irs-20 did not reach basal levels of γH2AX at high doses, whereas CHO10B2 recovered basal levels for all doses. After high-LET radiation, only CHO10B2 exhibited a reduction in γH2AX foci, but it never reached basal levels. Persistent foci in irs-20 confirmed a repair deficiency. Interestingly, after 30 minutes of high-LET radiation both cell lines exhibited large foci (size >0.9 μm 2 ) related to the damage nature, whereas at 6 hours irs-20 showed a higher amount of large foci than CHO10B2, with a 7-fold increase at 3 Gy, that could also be associated to radiosensitivity. Conclusions: We demonstrated, for the first time, an association between deficient DNA-PKcs activity and not only high levels of H2AX phosphorylation but also persistence and size increase of γH2AX foci after high-LET irradiation

  6. Induction and Persistence of Large γH2AX Foci by High Linear Energy Transfer Radiation in DNA-Dependent protein kinase–Deficient Cells

    Energy Technology Data Exchange (ETDEWEB)

    Bracalente, Candelaria; Ibañez, Irene L. [Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires (Argentina); Molinari, Beatriz [Departamento de Radiobiología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires (Argentina); Palmieri, Mónica [Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires (Argentina); Kreiner, Andrés [Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires (Argentina); Gerencia de Investigación y Aplicaciones, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires (Argentina); Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires (Argentina); Valda, Alejandro [Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires (Argentina); and others

    2013-11-15

    Purpose: To evaluate the cell response to DNA double-strand breaks induced by low and high linear energy transfer (LET) radiations when the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), an essential protein of the nonhomologous end-joining repair pathway, lacks kinase activity. Methods and Materials: CHO10B2, a Chinese hamster ovary cell line, and its derived radiosensitive mutant cell line, irs-20, lacking DNA-PKcs activity, were evaluated after 0 to 3 Gy of γ-rays, plateau and Bragg peak protons, and lithium beams by clonogenic assay, and as a measurement of double-strand breaks, phosphorylated H2AX (γH2AX) foci number and size were quantified by immunocytofluorescence. Results: Irs-20 exhibited greater radiosensitivity and a higher amount of γH2AX foci than CHO10B2 at 6 hours after irradiation for all types of radiations. Remarkably, CHO10B2 and irs-20 maintained their difference in radiosensitivity after high-LET radiation. Six hours after low-LET radiations, irs-20 did not reach basal levels of γH2AX at high doses, whereas CHO10B2 recovered basal levels for all doses. After high-LET radiation, only CHO10B2 exhibited a reduction in γH2AX foci, but it never reached basal levels. Persistent foci in irs-20 confirmed a repair deficiency. Interestingly, after 30 minutes of high-LET radiation both cell lines exhibited large foci (size >0.9 μm{sup 2}) related to the damage nature, whereas at 6 hours irs-20 showed a higher amount of large foci than CHO10B2, with a 7-fold increase at 3 Gy, that could also be associated to radiosensitivity. Conclusions: We demonstrated, for the first time, an association between deficient DNA-PKcs activity and not only high levels of H2AX phosphorylation but also persistence and size increase of γH2AX foci after high-LET irradiation.

  7. mRNA decay proteins are targeted to poly(A+ RNA and dsRNA-containing cytoplasmic foci that resemble P-bodies in Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Itzel López-Rosas

    Full Text Available In higher eukaryotes, mRNA degradation and RNA-based gene silencing occur in cytoplasmic foci referred to as processing bodies (P-bodies. In protozoan parasites, the presence of P-bodies and their putative role in mRNA decay have yet to be comprehensively addressed. Identification of P-bodies might provide information on how mRNA degradation machineries evolved in lower eukaryotes. Here, we used immunofluorescence and confocal microscopy assays to investigate the cellular localization of mRNA degradation proteins in the human intestinal parasite Entamoeba histolytica and found evidence of the existence of P-bodies. Two mRNA decay factors, namely the EhXRN2 exoribonuclease and the EhDCP2 decapping enzyme, were localized in cytoplasmic foci in a pattern resembling P-body organization. Given that amoebic foci appear to be smaller and less rounded than those described in higher eukaryotes, we have named them "P-body-like structures". These foci contain additional mRNA degradation factors, including the EhCAF1 deadenylase and the EhAGO2-2 protein involved in RNA interference. Biochemical analysis revealed that EhCAF1 co-immunoprecipitated with EhXRN2 but not with EhDCP2 or EhAGO2-2, thus linking deadenylation to 5'-to-3' mRNA decay. The number of EhCAF1-containing foci significantly decreased after inhibition of transcription and translation with actinomycin D and cycloheximide, respectively. Furthermore, results of RNA-FISH assays showed that (i EhCAF1 colocalized with poly(A(+ RNA and (ii during silencing of the Ehpc4 gene by RNA interference, EhAGO2-2 colocalized with small interfering RNAs in cytoplasmic foci. Our observation of decapping, deadenylation and RNA interference proteins within P-body-like foci suggests that these structures have been conserved after originating in the early evolution of eukaryotic lineages. To the best of our knowledge, this is the first study to report on the localization of mRNA decay proteins within P

  8. Dynamic contrast-enhanced MRI for automatic detection of foci @]@of residual or recurrent disease after prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Parra, N.A.; Orman, Amber; Abramowitz, Matthew; Pollack, Alan; Stoyanova, Radka [University of Miami Miller School of Medicine, Department of Radiation Oncology, Miami, FL (United States); Padgett, Kyle [University of Miami Miller School of Medicine, Department of Radiation Oncology, Miami, FL (United States); University of Miami Miller School of Medicine, Department of Radiology, Miami, FL (United States); Casillas, Victor [University of Miami Miller School of Medicine, Department of Radiology, Miami, FL (United States); Punnen, Sanoj [University of Miami Miller School of Medicine, Department of Urology, Miami, FL (United States)

    2017-01-15

    This study aimed to develop an automated procedure for identifying suspicious foci of residual/recurrent disease in the prostate bed using dynamic contrast-enhanced-MRI (DCE-MRI) in prostate cancer patients after prostatectomy. Data of 22 patients presenting for salvage radiotherapy (RT) with an identified gross tumor volume (GTV) in the prostate bed were analyzed retrospectively. An unsupervised pattern recognition method was used to analyze DCE-MRI curves from the prostate bed. Data were represented as a product of a number of signal-vs.-time patterns and their weights. The temporal pattern, characterized by fast wash-in and gradual wash-out, was considered the ''tumor'' pattern. The corresponding weights were thresholded based on the number (1, 1.5, 2, 2.5) of standard deviations away from the mean, denoted as DCE1.0,.., DCE2.5, and displayed on the T2-weighted MRI. The resultant four volumes were compared with the GTV and maximum pre-RT prostate-specific antigen (PSA) level. Pharmacokinetic modeling was also carried out. Principal component analysis determined 2-4 significant patterns in patients' DCE-MRI. Analysis and display of the identified suspicious foci was performed in commercial software (MIM Corporation, Cleveland, OH, USA). In general, DCE1.0/DCE1.5 highlighted larger areas than GTV. DCE2.0 and GTV were significantly correlated (r = 0.60, p < 0.05). DCE2.0/DCA2.5 were also significantly correlated with PSA (r = 0.52, 0.67, p < 0.05). K{sup trans} for DCE2.5 was statistically higher than the GTV's K{sup trans} (p < 0.05), indicating that the automatic volume better captures areas of malignancy. A software tool was developed for identification and visualization of the suspicious foci in DCE-MRI from post-prostatectomy patients and was integrated into the treatment planning system. (orig.) [German] Entwicklung eines automatischen Analyseverfahrens, um nach Prostatektomie mittels dynamischer kontrastmittelverstaerkter

  9. Replication protein A and γ-H2AX foci assembly is triggered by cellular response to DNA double-strand breaks

    International Nuclear Information System (INIS)

    Balajee, Adayabalam S.; Geard, Charles R.

    2004-01-01

    Human replication protein A (RPA p34), a crucial component of diverse DNA excision repair pathways, is implicated in DNA double-strand break (DSB) repair. To evaluate its role in DSB repair, the intranuclear dynamics of RPA was investigated after DNA damage and replication blockage in human cells. Using two different agents [ionizing radiation (IR) and hydroxyurea (HU)] to generate DSBs, we found that RPA relocated into distinct nuclear foci and colocalized with a well-known DSB binding factor, γ-H2AX, at the sites of DNA damage in a time-dependent manner. Colocalization of RPA and γ-H2AX foci peaked at 2 h after IR treatment and subsequently declined with increasing postrecovery times. The time course of RPA and γ-H2AX foci association correlated well with the DSB repair activity detected by a neutral comet assay. A phosphatidylinositol-3 (PI-3) kinase inhibitor, wortmannin, completely abolished both RPA and γ-H2AX foci formation triggered by IR. Additionally, radiosensitive ataxia telangiectasia (AT) cells harboring mutations in ATM gene product were found to be deficient in RPA and γ-H2AX colocalization after IR. Transfection of AT cells with ATM cDNA fully restored the association of RPA foci with γ-H2AX illustrating the requirement of ATM gene product for this process. The exact coincidence of RPA and γ-H2AX in response to HU specifically in S-phase cells supports their role in DNA replication checkpoint control. Depletion of RPA by small interfering RNA (SiRNA) substantially elevated the frequencies of IR-induced micronuclei (MN) and apoptosis in human cells suggestive of a role for RPA in DSB repair. We propose that RPA in association with γ-H2AX contributes to both DNA damage checkpoint control and repair in response to strand breaks and stalled replication forks in human cells

  10. Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.

    Science.gov (United States)

    Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

    2016-05-01

    Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34+Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.

    Science.gov (United States)

    Park, Min A; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

    2017-11-01

    Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical

  12. High levels of γ-H2AX foci and cell membrane oxidation in adolescents with type 1 diabetes

    International Nuclear Information System (INIS)

    Giovannini, Caterina; Piaggi, Simona; Federico, Giovanni; Scarpato, Roberto

    2014-01-01

    Highlights: • We aimed to detect signs of very early damage in peripheral cells of T1DM adolescents. • T1DM patients had high levels of oxidized cells and reduced expression of iNOS and NO. • Highly mutagenic lesions were markedly increased in the diabetic group, mainly in females. • The observed damage might increase the risk of cancer in the patients later in life. - Abstract: Oxidative stress caused by an excess of free radicals is implicated in the pathogenesis and development of type 1 diabetes mellitus (T1DM) and, in turn, it can lead to genome damage, especially in the form of DNA double-strand break (DSB). The DNA DSB is a potentially carcinogenic lesion for human cells. Thus, we aimed to evaluate whether the level of oxidative stress was increased in peripheral blood lymphocytes of a group of affected adolescents. In 35 T1DM adolescents and 19 healthy controls we assessed: (1) spontaneous and H 2 O 2 -induced oxidation of cell membrane using a fluorescence lipid probe; (2) spontaneous and LPS-induced expression of iNOS protein and indirect NO determination via cytofluorimetric analysis of O 2 − ; (3) immunofluorescent detection of the basal level of histone H2AX phosphorylation (γ-H2AX foci), a well-validated marker of DNA DSB. In T1DM, the frequencies of oxidized cells, both spontaneous and H 2 O 2 -induced (47.13 ± 0.02) were significantly higher than in controls (35.90 ± 0.03). Patients showed, in general, both a reduced iNOS expression and production of NO. Furthermore, the level of spontaneous nuclear damage, quantified as γ-H2AX foci, was markedly increased in T1DM adolescents (6.15 ± 1.08% of γ-H2AX + cells; 8.72 ± 2.14 γ-H2AXF/n; 9.26 ± 2.37 γ-H2AXF/np), especially in females. In the present study, we confirmed the role that oxidative stress plays in the disease damaging lipids of cell membrane and, most importantly, causing genomic damage in circulating white blood cells of affected adolescents. This also indicates that

  13. Pediatric eMental healthcare technologies: a systematic review of implementation foci in research studies, and government and organizational documents.

    Science.gov (United States)

    Gehring, Nicole D; McGrath, Patrick; Wozney, Lori; Soleimani, Amir; Bennett, Kathryn; Hartling, Lisa; Huguet, Anna; Dyson, Michele P; Newton, Amanda S

    2017-06-21

    Researchers, healthcare planners, and policymakers convey a sense of urgency in using eMental healthcare technologies to improve pediatric mental healthcare availability and access. Yet, different stakeholders may focus on different aspects of implementation. We conducted a systematic review to identify implementation foci in research studies and government/organizational documents for eMental healthcare technologies for pediatric mental healthcare. A search of eleven electronic databases and grey literature was conducted. We included research studies and documents from organization and government websites if the focus included eMental healthcare technology for children/adolescents (0-18 years), and implementation was studied and reported (research studies) or goals/recommendations regarding implementation were made (documents). We assessed study quality using the Mixed Methods Appraisal Tool and document quality using the Appraisal of Guidelines for Research & Evaluation II. Implementation information was grouped according to Proctor and colleagues' implementation outcomes-acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, and sustainability-and grouped separately for studies and documents. Twenty research studies and nine government/organizational documents met eligibility criteria. These articles represented implementation of eMental healthcare technologies in the USA (14 studies), United Kingdom (2 documents, 3 studies), Canada (2 documents, 1 study), Australia (4 documents, 1 study), New Zealand (1 study), and the Netherlands (1 document). The quality of research studies was excellent (n = 11), good (n = 6), and poor (n = 1). These eMental health studies focused on the acceptability (70%, n = 14) and appropriateness (50%, n = 10) of eMental healthcare technologies to users and mental healthcare professionals. The quality of government and organizational documents was high (n = 2), medium (n = 6

  14. STUDIO DEL GRAVIMETRO WORDEN N. 50 E SUA APPLICAZIONE PER UN RILIEVO GEOFISICO DI DETTAGLIO ALLE FOCI DEL TIMAYO

    Directory of Open Access Journals (Sweden)

    c. morelli

    1951-06-01

    Full Text Available II gravimetro Worden viene descritto nei particolari, e ne vieneesposta la teoria. Rettifiche e tarature a scopo geofisico vengono esposteper il Worden n. 50. In particolare, ne viene studiata la deriva egli e f f e t t i su di essa degli urti, della pressione e della temperatura:esso risulta compensato per la temperatura, ma ne risente per fortigradienti. La deriva osservata risulta compresa fra — 0,03 e -f- 0,15mgal/ora, col valore medio di -(- 0,05 mgal/ora. Opportune cautelesono quindi necessarie per determinarla ed eliminarne l ' e f f e t t o dairisultati. Con le norme indicate, la precisione di una misura a scopogeo fisico è di 0,03 mgal.A scopo sperimentale, il gravimetro è stato quindi applicato aduna prospezione di dettaglio nella bonifica alle foci del Timavo. Sonostate eseguite 52 stazioni, tutte ripetute due o più volte. Le anomaliesecondo Bouguer consentono di ricavare indicazioni sulla topografiadel fondo roccioso sottostante.

  15. Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats.

    Science.gov (United States)

    Bastide, Nadia M; Naud, Nathalie; Nassy, Gilles; Vendeuvre, Jean-Luc; Taché, Sylviane; Guéraud, Françoise; Hobbs, Ditte A; Kuhnle, Gunter G; Corpet, Denis E; Pierre, Fabrice H F

    2017-01-01

    Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, α-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this nitroso compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.

  16. Polymerase Chain Reaction Pool Screening Used To Compare Prevalence of Infective Black Flies in Two Onchocerciasis Foci in Northern Sudan

    Science.gov (United States)

    Higazi, Tarig B.; Zarroug, Isam M. A.; Mohamed, Hanan A.; Mohamed, Wigdan A.; Deran, Tong Chor M.; Aziz, Nabil; Katabarwa, Moses; Hassan, Hassan K.; Unnasch, Thomas R.; Mackenzie, Charles D.; Richards, Frank

    2011-01-01

    Onchocerciasis remains an important debilitating disease in many areas of Africa, including Sudan. The status of infection transmission in 2007 was assessed in the vectors of two disease foci in Sudan: Abu Hamed in northern Sudan, which has received at least 10 years of annual treatment and Galabat focus in eastern Sudan, where only minor, largely undocumented treatment activity has occurred. Assessment of more than 30,000 black flies for Onchocerca volvulus infectious stage L3 larvae by using an O-150 polymerase chain reaction protocol showed that black fly infectivity rates were 0.84 (95% confidence interval = 0.0497–1.88) per 10,000 flies for Abu Hamed and 6.9 (95% confidence interval = 1.1–16.4) infective flies per 10,000 for Galabat. These results provide entomologic evidence for suppressed Onchocerca volvulus transmission in the Abu Hamed focus and a moderate transmission rate of the parasite in the Galabat focus. PMID:21540385

  17. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

    Directory of Open Access Journals (Sweden)

    Felix R Stahl

    Full Text Available Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

  18. Use of γ-H2AX Foci Assay on Human Peripheral Blood Lymphocytes as Sensitive Biomarker of Exposure

    International Nuclear Information System (INIS)

    Gajski, G.; Garaj-Vrhovac, V.; Geric, M.; Filipic, M.; Nunic, J.; Straser, A.; Zegura, B.

    2013-01-01

    In modern medicine, it is impossible to imagine diagnostics and treatments without equipment that emit radiation (X-ray, CT, PET, etc.). At the same time there is a need to minimize the amount of radiation that the patient will gain during such medical examination. In that manner ALARA (As Low As Reasonably Achievable) principle and dosimetry are the bases of assuring patients safety. The induction of gamma phosphorylated H2AX histone is newly developed tool in biodosimetry, which is more sensitive for the detection of radiation caused DNA damage than currently used micronucleus and comet assay. Gamma phosphorylation of H2AX histone is a consequence of DNA double strand breaks and its role is to trigger the DNA repair mechanisms. In this study, we tested the effect of 2 and 4 Gy X-rays on human peripheral blood lymphocytes from two healthy volunteers using γ-H2AX foci assay. The FITC signal from labelled antibodies was monitored using flow cytometry and clearly demonstrated the difference in control samples and irradiated samples. There was also the difference between the exposed blood samples from the two volunteers. The results of present study reveal new sensitive method that is capable of detecting changes in DNA when exposed to different doses of radiation, and thus potentially optimizing the ALARA principle.(author)

  19. Spatial distribution and ecological environment analysis of great gerbil in Xinjiang Plague epidemic foci based on remote sensing

    International Nuclear Information System (INIS)

    Gao, Mengxu; Wang, Juanle; Li, Qun; Cao, Chunxiang

    2014-01-01

    Yersinia pestis (Plague bacterium) from great gerbil was isolated in 2005 in Xinjiang Dzungarian Basin, which confirmed the presence of the plague epidemic foci. This study analysed the spatial distribution and suitable habitat of great gerbil based on the monitoring data of great gerbil from Chinese Center for Disease Control and Prevention, as well as the ecological environment elements obtained from remote sensing products. The results showed that: (1) 88.5% (277/313) of great gerbil distributed in the area of elevation between 200 and 600 meters. (2) All the positive points located in the area with a slope of 0–3 degree, and the sunny tendency on aspect was not obvious. (3) All 313 positive points of great gerbil distributed in the area with an average annual temperature from 5 to 11 °C, and 165 points with an average annual temperature from 7 to 9 °C. (4) 72.8% (228/313) of great gerbil survived in the area with an annual precipitation of 120–200mm. (5) The positive points of great gerbil increased correspondingly with the increasing of NDVI value, but there is no positive point when NDVI is higher than 0.521, indicating the suitability of vegetation for great gerbil. This study explored a broad and important application for the monitoring and prevention of plague using remote sensing and geographic information system

  20. Molecular Evidence of a Trypanosoma brucei gambiense Sylvatic Cycle in the Human African Trypanosomiasis Foci of Equatorial Guinea

    Directory of Open Access Journals (Sweden)

    Carlos eCordon-Obras

    2015-07-01

    Full Text Available Gambiense trypanosomiasis is considered an anthroponotic disease. Consequently, control programs are generally aimed at stopping transmission of Trypanosoma brucei gambiense (T. b. gambiense by detecting and treating human cases. However, the persistence of numerous foci despite efforts to eliminate this disease questions this strategy as unique tool to pursue the eradication. The role of animals as a reservoir of T. b. gambiense is still controversial, but could partly explain maintenance of the infection at hypo-endemic levels. In the present study, we evaluated the presence of T. b. gambiense in wild animals in Equatorial Guinea. The infection rate ranged from 0.8% in the insular focus of Luba to more than 12% in Mbini, a focus with a constant trickle of human cases. The parasite was detected in a wide range of animal species including four species never described previously as putative reservoirs. Our study comes to reinforce the hypothesis that animals may play a role in the persistence of T. b. gambiense transmission, being particularly relevant in low transmission settings. Under these conditions the integration of sustained vector control and medical interventions should be considered to achieve the elimination of Gambiense trypanosomiasis.

  1. Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability.

    Directory of Open Access Journals (Sweden)

    Piotr Lewitowicz

    Full Text Available Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important.Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution.The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity.Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.

  2. Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet.

    Science.gov (United States)

    Zeng, Huawei; Ishaq, Suzanne L; Liu, Zhenhua; Bukowski, Michael R

    2018-04-01

    The increasing worldwide incidence of colon cancer has been linked to obesity and consumption of a high-fat Western diet. To test the hypothesis that a high-fat diet (HFD) promotes colonic aberrant crypt (AC) formation in a manner associated with gut bacterial dysbiosis, we examined the susceptibility to azoxymethane (AOM)-induced colonic AC and microbiome composition in C57/BL6 mice fed a modified AIN93G diet (AIN, 16% fat, energy) or an HFD (45% fat, energy) for 14 weeks. Mice receiving the HFD exhibited increased plasma leptin, body weight, body fat composition and inflammatory cell infiltration in the ileum compared with those in the AIN group. Consistent with the gut inflammatory phenotype, we observed an increase in colonic AC, plasma interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1 and inducible nitric oxide synthase in the ileum of the HFD-AOM group compared with the AIN-AOM group. Although the HFD and AIN groups did not differ in bacterial species number, the HFD and AIN diets resulted in different bacterial community structures in the colon. The abundance of certain short-chain fatty acid (SCFA) producing bacteria (e.g., Barnesiella) and fecal SCFA (e.g., acetic acid) content were lower in the HFD-AOM group compared with the AIN and AIN-AOM groups. Furthermore, we identified a high abundance of Anaeroplasma bacteria, an opportunistic pathogen in the HFD-AOM group. Collectively, we demonstrate that an HFD promotes AC formation concurrent with an increase of opportunistic pathogenic bacteria in the colon of C57BL/6 mice. Published by Elsevier Inc.

  3. Reliability of a Fully Automated Interpretation of γ-H2AX Foci in Lymphocytes of Moderately Trained Subjects under Resting Conditions

    Directory of Open Access Journals (Sweden)

    Juliane Heydenreich

    2014-01-01

    Full Text Available Background. Analysis of γ-H2AX foci is a promising approach to evaluate exercise-induced DNA damage. However, baseline levels and day-to-day variability of γ-H2AX foci have not been investigated in healthy subjects at rest. Methods. Blood was taken from eight moderately trained healthy males (29 ± 3 yrs, 1.84 ± 0.03 m, and 85 ± 6 kg at two separate days (M1/M2 after 24-hour exercise cessation. Number of γ-H2AX foci per 100 lymphocytes (N, number of foci per affected lymphocyte (NAL, percentage of affected lymphocytes (PAL, and diameter (D of γ-H2AX foci were analyzed (mean ± SD. Differences between M1 and M2 were analyzed using paired t-tests (α = 0.05. Day-to-day variability was evaluated by calculating the coefficients of variation (CV%, bias, and limits of agreement (LoA. Results. There were no statistically significant differences between M1 (N: 7.6 ± 4.4, NAL: 1.2 ± 0.2, PAL: 5.9 ± 2.6%, and D: 0.63 ± 0.07 and M2 (N: 8.4 ± 4.6, NAL: 1.3 ± 0.1, PAL: 6.9 ± 4.2%, and D: 0.66 ± 0.06. CV was calculated to be 98.5% (N, 88.9% (PAL, 11.3% (NAL, and 8.0% (D. Bias (LoA was 0.75 (−15.2/13.7, −0.02 (−0.36/0.33, −1.0 (−11.9/9.9, and −0.04 (−0.16/0.09, respectively. Conclusions. Background level in healthy subjects is approximately 0.07 to 0.09 γ-H2AX foci/cell. NAL and D are reliable measures.

  4. High levels of γ-H2AX foci and cell membrane oxidation in adolescents with type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Giovannini, Caterina [Unità di Genetica, Dipartimento di Biologia, Pisa University, Pisa (Italy); Piaggi, Simona [Sezione di Patologia Sperimentale, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Pisa University, Pisa (Italy); Federico, Giovanni [Unità di Endocrinologia Pediatrica e Diabete, Dipartimento di Medicina Clinica e Sperimentale Pisa University, Pisa (Italy); Scarpato, Roberto, E-mail: roberto.scarpato@unipi.it [Unità di Genetica, Dipartimento di Biologia, Pisa University, Pisa (Italy)

    2014-12-15

    Highlights: • We aimed to detect signs of very early damage in peripheral cells of T1DM adolescents. • T1DM patients had high levels of oxidized cells and reduced expression of iNOS and NO. • Highly mutagenic lesions were markedly increased in the diabetic group, mainly in females. • The observed damage might increase the risk of cancer in the patients later in life. - Abstract: Oxidative stress caused by an excess of free radicals is implicated in the pathogenesis and development of type 1 diabetes mellitus (T1DM) and, in turn, it can lead to genome damage, especially in the form of DNA double-strand break (DSB). The DNA DSB is a potentially carcinogenic lesion for human cells. Thus, we aimed to evaluate whether the level of oxidative stress was increased in peripheral blood lymphocytes of a group of affected adolescents. In 35 T1DM adolescents and 19 healthy controls we assessed: (1) spontaneous and H{sub 2}O{sub 2}-induced oxidation of cell membrane using a fluorescence lipid probe; (2) spontaneous and LPS-induced expression of iNOS protein and indirect NO determination via cytofluorimetric analysis of O{sub 2}{sup −}; (3) immunofluorescent detection of the basal level of histone H2AX phosphorylation (γ-H2AX foci), a well-validated marker of DNA DSB. In T1DM, the frequencies of oxidized cells, both spontaneous and H{sub 2}O{sub 2}-induced (47.13 ± 0.02) were significantly higher than in controls (35.90 ± 0.03). Patients showed, in general, both a reduced iNOS expression and production of NO. Furthermore, the level of spontaneous nuclear damage, quantified as γ-H2AX foci, was markedly increased in T1DM adolescents (6.15 ± 1.08% of γ-H2AX{sup +} cells; 8.72 ± 2.14 γ-H2AXF/n; 9.26 ± 2.37 γ-H2AXF/np), especially in females. In the present study, we confirmed the role that oxidative stress plays in the disease damaging lipids of cell membrane and, most importantly, causing genomic damage in circulating white blood cells of affected adolescents

  5. Evaluation of 99mTcN-moxifloxacin dithiocarbamate, as a potential radiopharmaceutical for scintigraphic localization of infectious foci

    International Nuclear Information System (INIS)

    Syed Qaiser Shah; Muhammad Rafiullah Khan

    2011-01-01

    In the current study radio complexation of the moxifloxacin dithiocarbamate (MXND) with technetium-99m ( 99m Tc) using the [ 99m Tc-N] 2+ core through legend exchange reaction was explored. The 99m TcN-MXND complex was biologically evaluated as a potential radiopharmaceutical for in vivo scintigraphy using artificially infected male sprague-dawley rats (MSDR) with Staphylococcus aureus (S. aureus). The radiochemistry of the complex was explored in terms of radiochemical purity (RCP), in vitro stability in serum at 37 deg C for 16 h, in vitro binding with S. aureus and biodistribution in artificially infected with S. aureus MSDR. It was observed that the complex showed stability of more than 90% up to 4 h after reconstitution with a maximum RCP value of 97.55 ± 0.42% at 30 min. The complex showed significantly in vitro stability in serum at 37 deg C with an insignificant free species up to 16.50% within 16 h. In vitro saturated binding with S. aureus was noted up to 120 min with maximum value of 73.25% at 90 min of incubation. Almost sixfold uptake was noted in the infected muscle of the MSDR as compared to inflamed and normal muscle. The 97.55 ± 0.42% RCP values, stability in serum with insignificant untagged 16.50% species, 73.25% in vitro binding with S. aureus and sixfold uptake in the target organ posed the 99m TcN-MXND complex as a promising radiopharmaceutical for S. aureus infectious foci. (author)

  6. Senescent mouse cells fail to overtly regulate the HIRA histone chaperone and do not form robust Senescence Associated Heterochromatin Foci

    Directory of Open Access Journals (Sweden)

    Enders Greg H

    2010-06-01

    Full Text Available Abstract Background Cellular senescence is a permanent growth arrest that occurs in response to cellular stressors, such as telomere shortening or activation of oncogenes. Although the process of senescence growth arrest is somewhat conserved between mouse and human cells, there are some critical differences in the molecular pathways of senescence between these two species. Recent studies in human fibroblasts have defined a cell signaling pathway that is initiated by repression of a specific Wnt ligand, Wnt2. This, in turn, activates a histone chaperone HIRA, and culminates in formation of specialized punctate domains of facultative heterochromatin, called Senescence-Associated Heterochromatin Foci (SAHF, that are enriched in the histone variant, macroH2A. SAHF are thought to repress expression of proliferation-promoting genes, thereby contributing to senescence-associated proliferation arrest. We asked whether this Wnt2-HIRA-SAHF pathway is conserved in mouse fibroblasts. Results We show that mouse embryo fibroblasts (MEFs and mouse skin fibroblasts, do not form robust punctate SAHF in response to an activated Ras oncogene or shortened telomeres. However, senescent MEFs do exhibit elevated levels of macroH2A staining throughout the nucleus as a whole. Consistent with their failure to fully activate the SAHF assembly pathway, the Wnt2-HIRA signaling axis is not overtly regulated between proliferating and senescent mouse cells. Conclusions In addition to the previously defined differences between mouse and human cells in the mechanisms and phenotypes associated with senescence, we conclude that senescent mouse and human fibroblasts also differ at the level of chromatin and the signaling pathways used to regulate chromatin. These differences between human and mouse senescence may contribute to the increased propensity of mouse fibroblasts (and perhaps other mouse cell types to become immortalized and transformed, compared to human cells.

  7. NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain

    International Nuclear Information System (INIS)

    Kobayashi, J.; Chen, D.J.; Sakamoto, S.; Matsuura, S.; Tanimoto, K.; Komatsu, K.

    2003-01-01

    Full text: DNA double-strand breaks (DSBs) represent the most potentially serious damage to a genome, and hence, many repair proteins are recruited to nuclear damage sites by as yet poorly characterized sensor mechanisms. Histone H2AX, one of histone H2A family, is phosphorylated within a few minutes in response to ionizing radiation (IR) and the phosphorylated H2AX (gamma-H2AX) forms foci at the region of DSBs. Moreover, Histone H2AX is essential for the IR-induced focus formation of DNA repair proteins such as BRCA1, NBS1 and 53BP1. Hence, we investigated that the function of histone H2AX for the recruitment of NBS1/hMRE11/ hRAD50 complex to DSBs sites. We clarify that NBS1 physically interacts with histone H2AX independent of DNA. We also show that the NBS1-binding can occur in the absence of interaction with hMRE11 or BRCA1. Furthermore, this NBS1 physical interaction was reduced when anti-gamma-H2AX antibody was introduced into normal cells. We also demonstrate that the FHA/BRCT domain of NBS1 is essential for this physical interaction by the immunoprecipitation studies and a pull-down assay with recombinant FHA/BRCT domain. These findings suggest that the FHA/BRCT domain have a crucial role for both binding to histone and for re-localization of hMRE11/hRAD50 nuclease complex to the vicinity of DNA damage

  8. Serosurvey Reveals Exposure to West Nile Virus in Asymptomatic Horse Populations in Central Spain Prior to Recent Disease Foci.

    Science.gov (United States)

    Abad-Cobo, A; Llorente, F; Barbero, M Del Carmen; Cruz-López, F; Forés, P; Jiménez-Clavero, M Á

    2017-10-01

    West Nile fever/encephalitis (WNF) is an infectious disease affecting horses, birds and humans, with a cycle involving birds as natural reservoirs and mosquitoes as transmission vectors. It is a notifiable disease, re-emerging in Europe. In Spain, it first appeared in horses in the south (Andalusia) in 2010, where outbreaks occur every year since. However, in 2014, an outbreak was declared in horses in central Spain, approximately 200 km away from the closest foci in Andalusia. Before that, evidence of West Nile virus (WNV) circulation in central Spain had been obtained only from wildlife, but never in horses. The purpose of this work was to perform a serosurvey to retrospectively detect West Nile virus infections in asymptomatic horses in central Spain from 2011 to 2013, that is before the occurrence of the first outbreaks in the area. For that, serum samples from 369 horses, collected between September 2011 and November 2013 in central Spain, were analysed by ELISA (blocking and IgM) and confirmed by virus neutralization, proving its specificity using parallel titration with another flavivirus (Usutu virus). As a result, 10 of 369 horse serum samples analysed gave positive results by competitive ELISA, 5 of which were confirmed as positive to WNV by virus neutralization (seropositivity rate: 1.35%). One of these WNV seropositive samples was IgM-positive. Chronologically, the first positive samples, including the IgM-positive, corresponded to sera collected in 2012 in Madrid province. From these results, we concluded that WNV circulated in asymptomatic equine populations of central Spain at least since 2012, before the first disease outbreak reported in this area. © 2016 Blackwell Verlag GmbH.

  9. [Morphological substrate and pathogenetic mechanisms of pelvic pain syndrome in endometriosis. Part II. Peripheral nerve tissue remodeling in the foci of endometriosis].

    Science.gov (United States)

    Kogan, E A; Ovakimyan, A S; Paramonova, N B; Faizullina, N M; Kazachenko, I F; Adamyan, L V

    2016-01-01

    Endometriosis (EM) is morphologically characterized by the development of extrauterine endometrioid heterotopies, the major clinical symptoms of which is chronic pelvic pain, which is a serious problem not only in modern gynecology, but also in public health as a whole. to investigate neurogenic markers in the foci of EM of various sites and histological structure in women with and without pain syndrome. The investigation was performed using the operative material (resected segments of the intestine, bladder, rectovaginal septum, and small pelvic peritoneum) obtained from 52 women with an intraoperative and morphologically verified diagnosis of EM and (Group 1) and without (Group 2) pain syndrome. Immunohistochemical examination was made on paraffin-embedded tissue sections in accordance with the standard protocols, by using the antibodies: 1) anti-PGP 9.5 polyclonal rabbit antibodies; 2) mouse anti-human neurofilament (NF) protein monoclonal antibodies (Clone 2F1); 3) mouse anti-nerve growth factor (NGF) monoclonal antibodies; 4) monoclonal mouse anti-human NGF receptor p75 (NGFRp75) antibodies (Dako, Denmark). Our findings demonstrate differences in the expression of PGP 9.5, NFs, NGF, and NGFRp75 in the foci and adjacent tissue in painful and painless EM irrespective of the locations of heterotopies. The found molecular features are a manifestation of the remodeling of nerve fibers and nerve endings in the foci of EM and PGP9.5, NGF, and NGFRp75 give rise to nerve fiber neoformation and pain syndrome in EM. At the same time, the immunohistochemical phenotype of EM foci does not depend on their site and reflects the presence or absence of pain syndrome.

  10. [Immunohistochemical study of the specific features of expression of matrix metalloproteinases 1, 9 in the photoaged skin, the foci of actinic keratosis and basal cell carcinoma].

    Science.gov (United States)

    Kuznetsova, E V; Snarskaya, E S; Zavalishina, L E; Tkachenko, S B

    Matrix metalloproteinases (MMPs) mediate the degradation of all types of collagens and other extracellular matrix components (elastin, proteoglycans, and laminin), their synthesis and accumulation play a key role in the hydrolysis of basement membrane. MMPs are involved in a wide range of proteolytic processes in the presence of different physiological and pathological changes, including inflammation, wound healing, angiogenesis, and carcinogenesis. to study the specific features of MMP-1 and MMP-9 expression in different stages of skin photoaging, in the foci of actinic keratosis and basal cell carcinoma by immunohistochemical examination. 12 samples of the healthy skin (6 samples of the eyelid skin with Glogau grade II photoaging; 6 ones of eyelid skin with Glogau grades III-IV photoaging) and biopsies from 8 foci of actinic keratosis and from 8 ones of basal cell carcinoma were examined. A positive reaction to MMPs was shown as different brown staining intensity in the cytoplasm of keratinocytes/tumor cells. MMP-1 and MMP-9 expression was recorded in 67% of the histological specimens of the Glogau grade III photoaged skin and in 100% of those of Glogau grade IV. In the foci of actinic keratosis, the expression of MMP-1 was observed in 62.5% of cases and that of MMP-9 was seen in 87.5%. In basal cell carcinoma, the expression of MMP-1 and MMP-9 was detected in all investigated samples. The immunomorphological findings are indicative of the important role of the level of MMP-1 and MMP-9 expression that is associated with the degree of progression of skin photoaging processes. Minimal MMP-1 and MMP-9 expression was recorded even in grades III-IV photoaging and in the foci of actinic keratosis. Intense MMP-1 and MMP-9 expression was detected in malignant skin epithelial neoplasms as different clinicomorphological types of basal cell carcinoma.

  11. p53 is involved in clearance of ionizing radiation-induced RAD51 foci in a human colon cancer cell line

    International Nuclear Information System (INIS)

    Orre, Lukas M.; Stenerloew, Bo; Dhar, Sumeer; Larsson, Rolf; Lewensohn, Rolf; Lehtioe, Janne

    2006-01-01

    We have investigated p53-related differences in cellular response to DNA damaging agents, focusing on p53s effects on RAD51 protein level and sub-cellular localization post exposure to ionizing radiation. In a human colon cancer cell line, HCT116 and its isogenic p53-/- subcell line we show here p53-independent RAD51 foci formation but interestingly the resolution of RAD51 foci showed clear p53 dependence. In p53 wt cells, but not in p53-/- cells, RAD51 protein level decreased 48 h post irradiation and fluorescence immunostaining showed resolution of RAD51 foci and relocalization of RAD51 to nucleoli at time points corresponding to the decrease in RAD51 protein level. Both cell lines rejoined DNA double strand breaks efficiently with similar kinetics and p53 status did not influence sensitivity to DNA damaging agents. We suggest that p53 has a role in RAD51 clearance post DSB repair and that nucleoli might be sites of RAD51 protein degradation

  12. Analysis of ecological context for identifying vegetation and animal conservation planning foci: An example from the arid South-western USA

    Science.gov (United States)

    Hamazaki, T.; Thompson, B.C.; Locke, B.A.; Boykin, K.G.

    2003-01-01

    In developing conservation strategies, it is important to maximize effects of conservation within a specified land tract and to maximize conservation effects on surrounding area (ecological context). The authors proposed two criteria to select biotic entities for conservation foci: (1) the relative occurrence of fauna or flora in a tract is greater than that of an ecological context region; and (2) occurrence of the fauna or flora is relatively limited in the ecological context region. Using extensive spatial data on vegetation and wildlife habitat distribution, the authors identified strategic vegetation and fauna conservation foci for the 400 000 ha Fort Bliss military reservation in New Mexico and Texas relative to a 164 km radius ecological context region intersecting seven ecological zones and the predicted habitat distribution of 616 animal species. The authors set two specific criteria: (1) predicted area of a species' occurrence is 5% (Fort Bliss is 4.2% of the region). These criteria selected one vegetation class and 40 animal species. Further, these vegetation and animal foci were primarily located in two areas of Fort Bliss. Sensitivity analyses with other analytical radii corroborated the context radius used. Conservation of the two areas and associated taxa will maximize the contribution of Fort Bliss's conservation efforts in its ecological proximity. This relatively simple but information-rich process represents economical and defensible preliminary contextual analysis for detailed conservation planning.

  13. Suppression of transformed foci, induced by alpha radiation of C3H 10T1/2 cells, by untransformed cells

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Gemmell, M.A.; Henning, C.B.

    1978-01-01

    The C3H 10T1/2 CL8 cell line obtained from a mouse embryo has been widely used for screening chemical carcinogens. Transformed foci are easily distinguishable in this system as crisscrossed, piled-up cells which stain more deeply than the surrounding untransformed cells. When these foci are ringcloned and subcultured, they have been shown to give rise to malignant tumors in C3H immunodepressed mice. Previous work showed that such malignant transformations, which occurred with a dose dependent frequency, could be induced by alpha particle irradiation. The present study, in turn, demonstrates that the expression of these transformations can be completely suppressed by co-cultivating the transformed cells with a large number of untransformed cells. The precise ratio of the number of untransformed cells to transformed cells to give complete suppression was found to vary in different experiments. Maximum effects were seen when a small number of transformed cells in low passage were used. These experiments may provide at least a partial explanation for the greatly increased frequency of transformations per cell irradiated in vitro, compared with the number of tumors observed after irradiation of the same number of cells in vivo. In addition, if conditions could be optimized whereby transformed foci could reproducibly be eliminated by the use of a known number of untransformed cells, this might have important applications in the prevention and treatment of certain human cancers

  14. Capsule, septum, and T2 hyperintense foci for differentiation between large hepatocellular carcinoma (≥5 cm) and intrahepatic cholangiocarcinoma on gadoxetic acid MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Jiyoung; Hong, Seong Sook; Kim, Hyun-joo [Soonchunhyang University College of Medicine, Department of Radiology, Seoul Hospital, Seoul (Korea, Republic of); Kim, Young Kon; Min, Ji Hye; Jeong, Woo Kyung [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Choi, Seo-Youn [Soonchunhyang University College of Medicine, Department of Radiology, Bucheon Hospital, Bucheon (Korea, Republic of); Ahn, Soohyun; Ahn, Hyeon Seon [Research Institute for Future Medicine, Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    To determine the added value of capsule, septum, and T2 hyperintense foci for differentiating large hepatocellular carcinoma (HCC; ≥ 5 cm) from intrahepatic cholangiocarcinoma (ICC) using gadoxetic acid MRI. The study included 116 patients (94 men, 22 women; mean age, 56.8 years) with surgically confirmed HCCs (n = 87, 5.0-18.0 cm) or ICCs (n = 29, 5.0-14.0 cm) who underwent gadoxetic acid MRI. Three observers independently reviewed MRIs in two sessions, examining enhancement patterns only and then adding capsule, septum, and T2 hyperintense foci. Reviewers used a five-point scale to score accuracy, sensitivity, and specificity. A significant increase was observed in accuracy when ancillary features (96.1-98.3%) were added compared to enhancement pattern only (83.6-88.4%; p ≤ 0.02). Sensitivity was significantly increased with combined reading (97.1-98.3%) compared to enhancement features only (81.6-88.5%; p ≤ 0.006) for two observers, with no difference in specificity (84.5-89.7% vs. 86.2-98.3%; p > 0.05). We found substantial to excellent interobserver agreement for ancillary features (0.598-0.976). Adding capsule, septum, and T2 hyperintense foci to enhancement patterns for gadoxetic acid MRI increased diagnostic performance for characterizing large HCC by differentiating it from ICC. (orig.)

  15. [Evaluation of modern epizootic activity of natural tularemia foci in Voronezh region using immune-serological and molecular-genetic study of main carriers of the disease].

    Science.gov (United States)

    Meshcheriakova, I S; Trankvilevskiĭ, D V; Kvasov, D A; Mikhaĭlova, T V; Kormilitsina, M I; Demidova, T N; Stepkin, Iu I; Zhukov, V I

    2015-01-01

    Improvement of monitoring and prognosis of epidemic manifestations of natural foci of tularemia on the territory of Voronezh region using immune-serological and molecular-genetic study of main carriers of the disease. 539 small mammals captured during summer period of 2011 in 4 districts of North-Eastern part of Voronezh region were studied. Animal organs were studied by serologic (search for Francisella tularensis antigens) and molecular-biologic (detection of F. tularensis DNA) methods. Tularemia antigen was detected using passive hemagglutination reaction (PHAR) with erythrocytic tularemia immunoglobulin diagnosticum. Real-time polymerase chain reaction (RT-PCR) was applied for detection of tularemia causative agent DNA. Complex study revealed epizootic activity of natural foci of tularemia in the examined territory. F. tularensis antigen and/or DNA were detected in 82 objects (15.2%). Use of RT-PCR allowed to additionally detect samples with relatively low content of F. tularensis DNA substrate, when antigen was not detected in samples. High sensitivity and specificity of the RT-PCR was ensured by inclusion of specific probes (tu14-PR2 and ISFTu2P). The results obtained give evidence on functioning and epizootic activity of natural foci of tularemia in Voronezh region that requires constant monitoring of the territory and prophylaxis measures, first of all vaccination of risk groups by live tularemia vaccine.

  16. IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci

    Directory of Open Access Journals (Sweden)

    Lee Eunyoung

    2012-01-01

    Full Text Available Abstract Background Murine experimental autoimmune encephalomyelitis (EAE, a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive. Methods We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγRCNSKO and vice versa (IFNγRperiKO. Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration. Results Incidence and severity of atypical EAE were more pronounced in IFNγRCNSKO as compared to IFNγRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγRCNSKO mice were only minimally infiltrated, while the same areas of IFNγRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFNγRCNSKO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1

  17. Bodies Folded in Migrant Crypts

    DEFF Research Database (Denmark)

    Galis, Vasilis; Tzokas, Spyros; Tympas, Aristotle

    2016-01-01

    This article considers media narratives that suggest that hiding in trucks, buses, and other vehicles to cross borders has, in fact, been a common practice in the context of migration to, and within, Europe. We aim to problematize how the tension between the materiality of bordering practices...

  18. Some aspects of entomological determinants of Phlebotomus orientalis in highland and lowland visceral leishmaniasis foci in northwestern Ethiopia.

    Directory of Open Access Journals (Sweden)

    Esayas Aklilu

    Full Text Available Visceral leishmaniasis (VL is one of the major public health problems in northwest Ethiopia, mainly in Libo-Kemkem and Metema districts, where Phlebotomus orientalis is the most probable vector of the disease. The aim of this study was to determine the physiological age, host preference and vectorial potential of P. orientalis in the highland and lowland foci of the region. Sand flies were collected using CDC light traps between May 2011 and April 2012 in Libo-Kemkem and October 2012 and September 2013 in Metema from household compounds, farm field and mixed forest. Females belonging to Phlebotomus were dissected for physiological age determination and Leishmania detection and isolation. Leishmania infections in sand flies were investigated using molecular methods. Freshly fed Phlebotomus females were tested to identify blood meal sources using PCR-RLB and ELISA. A total of 1149 (936 from Libo-Kemkem and 213 from Metema blood unfed female P. orientalis were dissected for age determination. The parity rate was 45.6% and 66.2% in Libo-Kemkem and Metema, respectively. None of 798 female P. orientalis dissected (578 from Libo-Kemkem and 220 from Metema was infected with Leishmania parasites. A total of 347 P. orientalis specimens collected from Libo-Kemkem were processed using PCR, of which 10 (2.8% specimens were found with DNA of Leishmania spp. Of a total 491 freshly fed female P. orientalis analyzed for blood meal origins by RLB-PCR and ELISA, 57.6% (67.8% from Libo-Kemkem and 49.8% from Metema were found to contain bovine blood while 4.9% (3.7% from Libo-Kemkem and 5.7% from Metema were of human blood. In conclusion, the present study showed parity difference between the two populations of P. orientalis and that both populations have strong zoophilic behavior. Based on the presented evidences, the species is strongly implicated as a vector of kala-azar in both areas. Therefore, vector control should be a component of a strategy to manage

  19. Persistence of gamma-H2AX and 53BP1 foci in proliferating and nonproliferating human mammary epithelial cells after exposure to gamma-rays or iron ions

    Energy Technology Data Exchange (ETDEWEB)

    Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V.; Barcellos-Hoff, Mary Helen; Parvin, Bahram; Rydberg, Bjorn

    2010-12-22

    To investigate {gamma}-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionizing radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced {gamma}-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both {gamma}-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after {gamma}-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. Conclusions: The disappearance of radiation induced {gamma}-H2AX and 53BP1 foci in HMEC have different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent {gamma}-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodeling.

  20. Ictal 99mTc-ECD brain SPECT imaging: localization of seizure foci and correlation with semiology in temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Kang, Do Young; Ryu, Jin Sook; Lee, Hee Kyung; Ma, Hyeo Il; Lee, Sang Ahm; Lee, Jung Kyo; Kang, Joong Koo

    1997-01-01

    The purpose of this study was to evaluate the usefulness of ictal 99m Tc-ECD brain SPECT in temporal lobe epilepsy (TLE) patients for presurgical localization of seizure foci, and to correlate ictal SPECT patterns with the semiology of seizure. ictal 99m Tc-ECD Brain SPECT was performed in 23 TLE patients whose MRI showed unilateral hippocampal atrophy (18 patients), other focal temporal lesions (4 patients) and normal finding (1 patient). Under CCTV monitoring, injection was done during ictal period in all patients with the mean delay of 38.5±17.3 sec (mean seizure duration : 90.5±35.9 sec). Ictal 99m Tc-ECD Brain SPECT was visually analysed by three blinded observers. All patients underwent temporal lobectomy with a minimum 3 months follow-up (range 3-29 months) ; all had good post-surgical seizure control (Engel's calssification class I). Ictal 99m Tc-ECD Brain SPECT showed unilateral temporal hyperperfusion concordant with epileptic foci in 22/23 (95.7%), whereas non-lateralization in 1/23 (4.3%). The hyperperfusion of the ipsilateral basal ganglia was present in 72.7% (16/22) of patients with dystonic/tonic posture of the contralateral hand. The contralateral cerebellar hyperperfusion was observed in the 7/22 (32%). The group with secondary generalized tonic clonic seizure (GTC) had brain stem and bilateral thalamic hyperperfusion in 4/7 (57.1%) while the group without secondary GTC had the same hyperperfusion in 1/16 (6.3%). There was statistically significant difference in brain stem and bilateral thalamic perfusion between two groups. Ictal 99m Tc-ECD Brain SPECT is a useful modality in pre-surgical localization of the epileptic foci and well correlated with the semiology of seizure

  1. [Correlative factors related to the density of Meriones unguiculatus in the Meriones unguiculatus plague foci of Hebei province, 2001-2013].

    Science.gov (United States)

    Niu, Y F; Kang, X P; Yan, D; Zhang, Y H; Liu, G; Kang, D M; Liu, H Z; Shi, X M; Li, Y G

    2016-08-10

    To explore the yearly, monthly and habitat-related distribution and their relations with Meriones unguiculatus density in the Hebei Meriones unguiculatus plague foci, from 2001 to 2013. Data related to Meriones unguiculatus was gathered through the monitoring programs set up at the national and provincial Meriones unguiculatus plague foci in Hebei province, from 2001 to 2013. According to the yearly density of Meriones unguiculatus, criteria set for the three groups under study, were as follows:'high-risk group'-when the rodent density was≥1.00 under rodents/hm(2),'warning group'-when the rodents/hm(2)>rodent density> 0.20,'standard group'-when rodents/hm(2) rodent density≤0.20 rodents/hm(2). Differences of habitats and monthly distribution among the three groups were compared, under the Kruskal-Wallis H rank sum test while their relations were under the multiple correspondence analysis. The Meriones unguiculatus densities were higher than 1.00 rodents/hm(2), far above the set national standards, in the monitoring area, between 2001 and 2005. From 2005, though the rodent densities began to decrease, however, figures from 2008 to 2013 were still among 0.20 to 1.00 rodents/hm(2). The distribution of habitats in the three groups showed that the Meriones unguiculatus densities were all different in habitats and the difference was statistically significant (Pplague increased in Hebei Meriones unguiculatus plague foci. Based on the distribution of Meriones unguiculatus, programs should be set to monitor the rodent in arable land and wasteland, in April and June, to reduce the prevalence of animals plague.

  2. Proof-of-Principle of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: Final Results of a Study in Mali and Senegal

    Science.gov (United States)

    Traore, Mamadou O.; Sarr, Moussa D.; Badji, Alioune; Bissan, Yiriba; Diawara, Lamine; Doumbia, Konimba; Goita, Soula F.; Konate, Lassana; Mounkoro, Kalifa; Seck, Amadou F.; Toe, Laurent; Toure, Seyni; Remme, Jan H. F.

    2012-01-01

    Background Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment. Methodology/Principal Findings Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination. Conclusion/Significance The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa. PMID:23029586

  3. In vitro studies for the introduction of γ-H2AX foci as an indicator of radiation damage in peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Mandina, Tania; Garcia, Omar; Roch-Lefevre, Sandrine; Voisin, Pascale; Voisin, Philippe; Roy, Laurence

    2008-01-01

    Biological indicators are used for assessing DNA damage and repair in cells exposed to ionising radiation. DNA Double-strand breaks (DSBs) have been known as one of the most significant lesion producing lethal and mutagenic effects in irradiated cells. A new biological marker for DSBs is the presence of γ-H2AX foci in cells nucleus after exposure to ionising radiation. γ-H2AX formation was analysed in human lymphocytes. The blood was obtained from a same donor in three different occasions and exposed to doses of 0, 0.2 and 0.5 Gy of gamma rays with a dose-rate of 1.2 Gy/min. After blood irradiation the lymphocytes were incubated 30 minutes at 37 C degrees, isolated, fixed with paraformaldehyde, and spread on a microscope slide using a Cytospin. The slides were stored at -20 C degrees and immuno-stained the next day and 14, 16, 27 and 37 days after irradiation to test the influence of the storage time on results. The number of foci per cell was scored automatically, in about 200 cells per dose using HISTOLAB and CARTOGRAPH software. The mean of number of foci/cell for samples was as follow 0 Gy= 0.15 ± 0.04, 0.2 Gy =2.06 ± 0.25 and 0.5 Gy=5.21 ± 0.36 without appreciable effect of the storage time on the final results. Nevertheless some aspects require additional research, particularly the background values of the assay. A higher variability of DNA damage was observed for control samples, than for exposed ones. The influence of the number of cells scored on this variability should be tested. (author)

  4. Multivoxel magnetic resonance spectroscopy identifies enriched foci of cancer stem-like cells in high-grade gliomas

    Directory of Open Access Journals (Sweden)

    He T

    2017-01-01

    samples (23.6%±3.8% vs 18.3%±3.3%, 25.2%±4.5% vs 19.8%±2.8%, 24.5%±3.8% vs 17.8%±2.2%, respectively; all P<0.001. Western blot demonstrated that relative CD133 and nestin protein expression in high Cho/Cr ratio regions was significantly higher than that in low Cho/Cr ratio tissue samples (0.50±0.17 vs 0.30±0.08, 0.45±0.13 vs 0.27±0.07, respectively; both P<0.001. The protein expression levels of CD133 and nestin were highly correlated with Cho/Cr ratios (r=0.897 and r=0.861, respectively. Conclusion: Cho/Cr ratios correlate with the distribution of CSLCs in high-grade gliomas, and this may assist in identifying foci enriched with CSLCs and thus improve the management of high-grade gliomas. Keywords: high-grade glioma, 1H-MRS, cancer stem-like cells, choline, creatine, Cho/Cr

  5. Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells.

    Science.gov (United States)

    Pustovalova, Margarita; Astrelina, Тatiana A; Grekhova, Anna; Vorobyeva, Natalia; Tsvetkova, Anastasia; Blokhina, Taisia; Nikitina, Victoria; Suchkova, Yulia; Usupzhanova, Daria; Brunchukov, Vitalyi; Kobzeva, Irina; Karaseva, Тatiana; Ozerov, Ivan V; Samoylov, Aleksandr; Bushmanov, Andrey; Leonov, Sergey; Izumchenko, Evgeny; Zhavoronkov, Alex; Klokov, Dmitry; Osipov, Andreyan N

    2017-11-21

    Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γН2АХ foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γН2АХ foci still present at 24 h. Notably, these low dose induced residual γН2АХ foci were not co-localized with рАТМ foci and were observed predominantly in the proliferating Кi67 positive (Кi67+) cells. The number of γН2АХ foci and the fraction of nonproliferating (Кi67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γН2АХ foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AХ foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.

  6. Persistence of Gamma-H2AX Foci in Irradiated Bronchial Cells Correlates with Susceptibility to Radiation Associated Lung Cancer in Mice

    Science.gov (United States)

    Ochola, Donasian O.; Sharif, Rabab; Bedford, Joel S.; Keefe, Thomas J.; Kato, Takamitsu A.; Fallgren, Christina M.; Demant, Peter; Costes, Sylvain V.; Weil, Michael M.

    2018-01-01

    The risk of developing radiation-induced lung cancer differs between different strains of mice, but the underlying cause of the strain differences is unknown. Strains of mice also differ in their ability to efficiently repair DNA double strand breaks resulting from radiation exposure. We phenotyped mouse strains from the CcS/Dem recombinant congenic strain set for their efficacy in repairing DNA double strand breaks during protracted radiation exposures. We monitored persistent gamma-H2AX radiation induced foci (RIF) 24 hours after exposure to chronic gamma-rays as a surrogate marker for repair deficiency in bronchial epithelial cells for 17 of the CcS/Dem strains and the BALB/cHeN founder strain. We observed a very strong correlation R2 = 79.18%, P cancer percent incidence measured in the same strains. Interestingly, spontaneous levels of foci in non-irradiated strains also showed good correlation with lung cancer incidence (R2=32.74%, P =0.013). These results suggest that genetic differences in DNA repair capacity largely account for differing susceptibilities to radiation-induced lung cancer among CcS/Dem mouse strains and that high levels of spontaneous DNA damage is also a relatively good marker of cancer predisposition. In a smaller pilot study, we found that the repair capacity measured in peripheral blood leucocytes also correlated well with radiogenic lung cancer susceptibility, raising the possibility that such phenotyping assay could be used to detect radiogenic lung cancer susceptibility in humans.

  7. An ImageJ-based algorithm for a semi-automated method for microscopic image enhancement and DNA repair foci counting

    International Nuclear Information System (INIS)

    Klokov, D.; Suppiah, R.

    2015-01-01

    Proper evaluation of the health risks of low-dose ionizing radiation exposure heavily relies on the ability to accurately measure very low levels of DNA damage in cells. One of the most sensitive methods for measuring DNA damage levels is the quantification of DNA repair foci that consist of macromolecular aggregates of DNA repair proteins, such as γH2AX and 53BP1, forming around individual DNA double-strand breaks. They can be quantified using immunofluorescence microscopy and are widely used as markers of DNA double-strand breaks. However this quantification, if performed manually, may be very tedious and prone to inter-individual bias. Low-dose radiation studies are especially sensitive to this potential bias due to a very low magnitude of the effects anticipated. Therefore, we designed and validated an algorithm for the semi-automated processing of microscopic images and quantification of DNA repair foci. The algorithm uses ImageJ, a freely available image analysis software that is customizable to individual cellular properties or experimental conditions. We validated the algorithm using immunolabeled 53BP1 and γH2AX in normal human fibroblast AG01522 cells under both normal and irradiated conditions. This method is easy to learn, can be used by nontrained personnel, and can help avoiding discrepancies in inter-laboratory comparison studies examining the effects of low-dose radiation. (author)

  8. Yersinia pestis strains of ancient phylogenetic branch 0.ANT are widely spread in the high-mountain plague foci of Kyrgyzstan.

    Science.gov (United States)

    Eroshenko, Galina A; Nosov, Nikita Yu; Krasnov, Yaroslav M; Oglodin, Yevgeny G; Kukleva, Lyubov M; Guseva, Natalia P; Kuznetsov, Alexander A; Abdikarimov, Sabyrzhan T; Dzhaparova, Aigul K; Kutyrev, Vladimir V

    2017-01-01

    Fifty six Yersinia pestis strains, isolated over the period of more than 50 years in three high-mountain foci of Kyrgyzstan (Tien Shan, Alai, and Talas), have been characterized by means of PCR and single nucleotide polymorphism (SNP) typing methods. Seven of these strains were also characterized by means of whole genome sequencing and genome-wide SNP phylogenetic analysis. It was found that forty two strains belong to 0.ANT2, 0.ANT3 and 0.ANT5 phylogenetic branches. From these, strains of 0.ANT2 and 0.ANT3 branches were earlier detected in China only, whereas 0.ANT5 phylogenetic branch was identified for Y. pestis phylogeny for the first time. According to the results of genome-wide SNP analysis, 0.ANT5 strains are ones of the most closely related to Y. pestis strain responsible for the Justinianic Plague. We have also found out that four of the studied strains belong to the phylogenetic branch 2.MED1, and ten strains from Talas high-mountain focus belong to the phylogenetic branch 0.PE4 (sub-branch 0.PE4t). Established diversity of Y. pestis strains and extensive dissemination of the strains pertaining to the 0.ANT branch confirm the antiquity of the mentioned above plague foci and suggest that strains of the 0.ANT branch, which serve as precursors for all highly virulent Y. pestis strains, had their origin in the Tien Shan mountains.

  9. An ImageJ-based algorithm for a semi-automated method for microscopic image enhancement and DNA repair foci counting

    Energy Technology Data Exchange (ETDEWEB)

    Klokov, D., E-mail: dmitry.klokov@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Suppiah, R. [Queen' s Univ., Dept. of Biomedical and Molecular Sciences, Kingston, Ontario (Canada)

    2015-06-15

    Proper evaluation of the health risks of low-dose ionizing radiation exposure heavily relies on the ability to accurately measure very low levels of DNA damage in cells. One of the most sensitive methods for measuring DNA damage levels is the quantification of DNA repair foci that consist of macromolecular aggregates of DNA repair proteins, such as γH2AX and 53BP1, forming around individual DNA double-strand breaks. They can be quantified using immunofluorescence microscopy and are widely used as markers of DNA double-strand breaks. However this quantification, if performed manually, may be very tedious and prone to inter-individual bias. Low-dose radiation studies are especially sensitive to this potential bias due to a very low magnitude of the effects anticipated. Therefore, we designed and validated an algorithm for the semi-automated processing of microscopic images and quantification of DNA repair foci. The algorithm uses ImageJ, a freely available image analysis software that is customizable to individual cellular properties or experimental conditions. We validated the algorithm using immunolabeled 53BP1 and γH2AX in normal human fibroblast AG01522 cells under both normal and irradiated conditions. This method is easy to learn, can be used by nontrained personnel, and can help avoiding discrepancies in inter-laboratory comparison studies examining the effects of low-dose radiation. (author)

  10. Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic γ-ray-irradiation in the rat liver

    International Nuclear Information System (INIS)

    Ida, Katsuya; Nakamura, Satoshi; Muro, Hiroyuki; Takai, Michikatsu; Kaneko, Masao

    1995-01-01

    Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. γ-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by γ-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given PB than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver. (author)

  11. Comparison of small mammal prevalence of Leishmania (Leishmania) mexicana in five foci of cutaneous leishmaniasis in the State of Campeche, Mexico.

    Science.gov (United States)

    Van Wynsberghe, N R; Canto-Lara, S B; Sosa-Bibiano, E I; Rivero-Cárdenas, N A; Andrade-Narváez, F J

    2009-01-01

    In the Yucatan Peninsula of Mexico, 95% of the human cases of Cutaneous Leishmaniasis are caused by Leishmania (Leishmania) mexicana with an incidence rate of 5.08 per 100,000 inhabitants. Transmission is limited to the winter months (November to March). One study on wild rodents has incriminated Ototylomys phyllotis and Peromyscus yucatanicus as primary reservoirs of L. (L.) mexicana in the focus of La Libertad, Campeche. In the present study, the prevalence of both infection and disease caused by L. (L.) mexicana in small terrestrial mammals were documented during five transmission seasons (1994-2004) in five foci of Leishmaniasis in the state of Campeche. Foci separated by only 100 km, with similar relative abundances of small mammals, were found to differ significantly in their prevalence of both symptoms and infection. Transmission rates and reservoir species seemed to change in space as well as in time which limited the implementation of effective control measures of the disease even in a small endemic area such as the south of the Yucatan Peninsula.

  12. Microwaves from GSM mobile telephones affect 53BP1 and gamma-H2AX foci in human lymphocytes from hypersensitive and healthy persons.

    Science.gov (United States)

    Markovà, Eva; Hillert, Lena; Malmgren, Lars; Persson, Bertil R R; Belyaev, Igor Y

    2005-09-01

    The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (gamma-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/gamma-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects.

  13. Evidence of tuberculosis among children in medieval (13th–15th century Wrocław: A case study of hip joint tuberculosis in a juvenile skeleton excavated from the crypt of the St. Elizabeth church

    Directory of Open Access Journals (Sweden)

    Cieślik Agata Izabela

    2017-06-01

    Full Text Available Paleopathological examinations of the skeletal remains of people who died centuries ago are material source of knowledge about health and diseases in the past. In this article, a case of skeletal tuberculosis from historical (13th-15th c. Wrocław, Poland has been presented. The juvenile skeleton excavated from grave No 93, from the crypt located under the church of St. Elizabeth, displayed pathological lesions within the right hip joint resulting from a chronic inflammation, which might have been assigned to signs typical for skeletal tuberculosis. The results of macroscopic and radiological analyses appeared to be consistent, and allowed to determine a reliable diagnosis of this paleopathological case.

  14. MRI of the normal brain from early childhood to middle age. Pt. 1. Appearances on T2- and proton density-weighted images and occurrence of incidental high-signal foci

    International Nuclear Information System (INIS)

    Autti, T.; Raininko, R.; Vanhanen, S.L.; Kallio, M.; Santavuori, P.

    1994-01-01

    The magnetic resonance images of 67 healthy subjects aged 4-50 years were studied for differences in general signal intensity between the different brain structures, the frequency of focal intensity changes in the brain, and variations in size of the cerebrospinal fluid (CSF) spaces. In adults over 25 years of age the thalamus gave lower signal than the putamen or caudate nucleus. Definite periventricular high signal was found in the white matter of one third of subjects of all ages. Small (< 5 mm in diameter) high signal foci were found in the cerebral white matter on T2-weighted images in 27 % of subjects (20 % of healthy children and adolescents and 34 % of adults). They gave high signal on both short and long echoes in 11 % of children and adolescents and in 22 % of adults; 51 % of all foci gave high signal with both echoes. This does not support the hypothesis that they are caused mainly by enlarged Virchow-Robin spaces. Of the high signal foci on T2-weighted images, 86 % were in watershead areas. Two foci were found in one subject in the periventricular watershed area (beside the tips of the frontal horns) and they were never seen in the other deep white matter regions. In healthy, relatively young subjects with no known risk factors, high signal foci other than Virchow-Robin spaces, were common; neither their prevalence nor their number correlated with age in this series. A few slightly large sulci were found in some adults. (orig.)

  15. 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation.

    Science.gov (United States)

    Hagiwara, Yoshihiko; Niimi, Atsuko; Isono, Mayu; Yamauchi, Motohiro; Yasuhara, Takaaki; Limsirichaikul, Siripan; Oike, Takahiro; Sato, Hiro; Held, Kathryn D; Nakano, Takashi; Shibata, Atsushi

    2017-12-12

    DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1-2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation. Herein, by using three dimensional (3D)-structured illumination microscopy, we identified the formation of 3D widespread γH2AX foci after high LET carbon-ion irradiation. The large γH2AX foci in G 2 -phase cells encompassed multiple foci of replication protein A (RPA), a marker of DSBs undergoing resection during homologous recombination. Furthermore, we demonstrated by 3D analysis that the distance between two individual RPA foci within γH2AX foci was approximately 700 nm. Together, our findings suggest that high LET heavy-ion particles induce clustered DSB formation on a scale of approximately 1 μm 3 . These closely localised DSBs are considered to be a risk for the formation of chromosomal rearrangement after heavy-ion irradiation.

  16. [Occurrence of sand flies (Diptera, Psychodidae) in leishmaniasis foci in an ecotourism area around the Lençóis Maranhenses National Park, Brazil].

    Science.gov (United States)

    Rebêlo, José Manuel Macário; Assunção Júnior, Antonildes Nascimento; Silva, Orleans; Moraes, Jorge Luiz Pinto

    2010-01-01

    The distribution and relative abundance of sand fly species were studied in the municipality of Barreirinhas, Maranhão State, Brazil, around the Lençóis Maranhenses National Park, from January to June 2005, August 2004, July 2005, and September/2008. A total of 6,658 specimens were captured. The most frequent species were Lutzomyia whitmani (46.6%), L. longipalpis (29.9%), L. evandroi (17.1%), and L. lenti (4.8%), while L. termitophila, L. flaviscutellata, L. migonei, L. infraspinosa, L. sordellii, L. wellcomei, L. antunesi, and L. trinidadensis represented 1.6%. The presence of Leishmania vector species explains the high detection rate for tegumentary leishmaniasis in 2000 (308.2), 2001 (310.9), 2002 (338.2), and 2005 (313.6) and active foci of human visceral leishmaniasis in the municipality of Barreirinhas.

  17. Lead facilitates foci formation in a Balb/c-3T3 two-step cell transformation model: role of Ape1 function.

    Science.gov (United States)

    Hernández-Franco, Pablo; Silva, Martín; Franco, Rodrigo; Valverde, Mahara; Rojas, Emilio

    2018-04-01

    Several possible mechanisms have been examined to gain an understanding on the carcinogenic properties of lead, which include among others, mitogenesis, alteration of gene expression, oxidative damage, and inhibition of DNA repair. The aim of the present study was to explore if low concentrations of lead, relevant for human exposure, interfere with Ape1 function, a base excision repair enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30 μM induced APE1 mRNA and upregulation of protein expression. This increase in mRNA expression is consistent throughout the chronic exposure. Additionally, we also found an impaired function of Ape1 through molecular beacon-based assay. To evaluate the impact of lead on foci formation, a Balb/c-3T3 two-step transformation model was used. Balb/c-3T3 cells were pretreated 1 week with low concentrations of lead before induction of transformation with n-methyl-n-nitrosoguanidine (MNNG) (0.5 μg/mL) and 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.1 μg/mL) (a classical two-step protocol). Morphological cell transformation increased in response to lead pretreatment that was paralleled with an increase in Ape1 mRNA and protein overexpression and an impairment of Ape1 activity and correlating with foci number. In addition, we found that lead pretreatment and MNNG (transformation initiator) increased DNA damage, determined by comet assay. Our data suggest that low lead concentrations (5, 30 μM) could play a facilitating role in cellular transformation, probably through the impaired function of housekeeping genes such as Ape1, leading to DNA damage accumulation and chromosomal instability, one of the most important hallmarks of cancer induced by chronic exposures.

  18. Palliative Care Research--A Systematic Review of foci, designs and methods of research conducted in Sweden between 2007 and 2012.

    Science.gov (United States)

    Henoch, Ingela; Carlander, Ida; Holm, Maja; James, Inger; Sarenmalm, Elisabeth Kenne; Hagelin, Carina Lundh; Lind, Susanne; Sandgren, Anna; Öhlén, Joakim

    2016-03-01

    In 2007, a literature review was undertaken of palliative care research from Sweden during the 1970s-2006, paving the way for a follow-up study to explore the recent developments. The aim was to systematically examine palliative care research from Sweden between 2007 and 2012, with special attention to methods, designs and research foci. A literature review was undertaken. The databases Academic search elite, Age line, Ahmed, Cinahl, PsychInfo, PubMed, Scopus, Soc abstracts, Web of science and Libris were reviewed for Swedish palliative care research studies published from 2007 to 2012, applying the search criteria 'palliative care OR palliative medicine OR end-of-life care OR terminal care OR hospice care OR dying OR death'. A total of 263 papers met the inclusion criteria, indicating an increased volume of research compared to the 133 articles identified in the previous review. Common study foci were symptom assessment and management, experiences of illness and care planning. Targeting non-cancer-specific populations and utilisation of population-based register studies were identified as new features. There was continued domination of cross-sectional, qualitative and mono-disciplinary studies, not including ethnic minority groups, nonverbally communicable people or children research has expanded in volume from 2007 to 2012 compared to during the 1970s to 2006, with increasing participation of non-cancer-specific populations. A domination of qualitative approaches and small, cross-sectional studies with few interventions is still characteristic. Still more strategies are needed to expand the knowledge development of palliative care to respond to demographical, epidemiological, therapeutic and healthcare structure changes. © 2015 Nordic College of Caring Science.

  19. Transformations of C3H 10T1/2 cells by Benzo(a)pyrene and subsequent attempts at suppression of transformed foci by untransformed cells and Vitamin A

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Gemmell, M.A.

    1978-01-01

    The mouse embryo cell line (C3H 10T1/2 CL8) has been shown here, in agreement with findings by others, to be transformed by benzo(a)pyrene (BP). Transformation studies were carried out at two different concentrations (0.25 μg BP/ml and 2.5 μg BP/ml) and two different cell densities (200 and 1000 cells/60 mm dish). Transformation frequencies per surviving cell were found to be greatest when the higher concentration of BP was used with the lower cell density. A comparison of these results with earlier alpha-irradiation experiments demonstrated the greater effectiveness of BP as a transforming agent in this cell system, although the foci produced by the two agents were morphologically similar. Attempts made to eliminate the expression of BP transformed foci by two different techniques were unsuccessful, although one of these had previously been shown to be effective with cells transformed by alpha particle irradiation. The two systems tested were treatment with retinyl acetate, a common nutritional form of Vitamin A and the previously successful technique - growth of transformed cells with large numbers of untransformed cells. The differences between the BP-induced transformations and those induced by alpha particle irradiation may result from intrinsic differences in the mechanism of action of the two carcinogenic agents, differences in the number of cell generations between the induction of the transformed foci and the subsequent treatment of the cells, or genetic differences between different foci

  20. Mean frequency and relative fluorescence intensity measurement of γ-H2AX foci dose response in PBL exposed to γ-irradiation: An inter- and intra-laboratory comparison and its relevance for radiation triage.

    Science.gov (United States)

    Venkateswarlu, Raavi; Tamizh, Selvan G; Bhavani, Manivannan; Kumar, Arun; Alok, Amit; Karthik, Kanagaraj; Kalra, Namita; Vijayalakshmi, J; Paul, Solomon F D; Chaudhury, N K; Venkatachalam, Perumal

    2015-12-01

    Measurement of γ-H2AX protein changes in the peripheral blood lymphocytes (PBL) of individuals exposed to ionizing radiation is a simple, sensitive, and rapid assay for radiation triage and early marker of dose estimation. The qualitative and quantitative measurements of the protein changes were examined using flow cytometry and microscopy. Whole blood and isolated lymphocytes were exposed in vitro between 0.1 and 5 Gy doses of (60) Co γ-radiation at a dose rate of 1 Gy/min. Radiation induced γ-H2AX foci frequency (n = 3) and relative fluorescence intensity (n = 7) in PBL was measured at 0.5 and 2 hrs postexposure. The observed dose response for γ-H2AX foci frequency at both time points, for whole blood and isolated lymphocytes did not show any significant (P > 0.05) differences. However, when compared with γ-H2AX foci frequency scored manually (microscopy), the semiautomated analysis (captured images) showed a better correlation (r(2) = 0.918) than that obtained with automated (Metafer) scoring (r(2) = 0.690). It is noteworthy to mention that, the γ-H2AX foci frequency quantified using microscopy showed a dose dependent increase up to 2 Gy and the relative fluorescence intensity (RFI) measured with flow cytometry revealed an increase up to 5 Gy in the PBL exposed in vitro. Moreover, a better correlation was observed between the γ-H2AX foci frequency obtained by manual scoring and RFI (r(2) = 0.910). Kinetic studies showed that the γ-H2AX foci remain more or less unchanged up to 4 hrs and reduces gradually over 48 hrs of postexposure at 37°C. Further, inter and intra-laboratory comparisons showed consistency in the scoring of γ-H2AX foci frequency by manual and semiautomated scoring. The overall results suggest that measurement of γ-H2AX (microscopy and flow cytometry) should be employed within 4 to 6 hrs for a reliable dosimetry either by sharing the work load between the laboratories or investing more manpower; however, triage can be possible even up

  1. Species composition of sand flies and bionomics of Phlebotomus papatasi and P. sergenti (Diptera: Psychodidae) in cutaneous leishmaniasis endemic foci, Morocco.

    Science.gov (United States)

    Boussaa, Samia; Kahime, Kholoud; Samy, Abdallah M; Salem, Abdelkrim Ben; Boumezzough, Ali

    2016-02-02

    Cutaneous Leishmaniasis (CL) is one of the most neglected tropical diseases in Morocco. Leishmania major and L. tropica are the main culprits identified in all endemic foci across the country. These two etiological agents are transmitted by Phlebotomus papatasi and P. sergenti, the two most prevalent sand fly species in Morocco. Previous studies reflected gaps of knowledge regarding the environmental fingerprints that affect the distribution of these two potential vectors across Morocco. The sand flies were collected from 48 districts across Morocco using sticky paper traps. Collected specimens were preserved in 70% ethanol for further processing and identification. Male and female densities were calculated in each site to examine their relations to the environmental conditions across these sites. The study used 19 environmental variables including precipitation, aridity, elevation, soil variables and a composite representing maximum, minimum and mean of day- and night-time Land Surface Temperature (LST), and Normalized Difference Vegetation Index (NDVI). A total of 11,717 specimens were collected during this entomological survey. These specimens represented 11 species of two genera; Phlebotomus and Sergentomyia. Correlations of the sand fly densities with the environmental variables were estimated to identify the variables which influence the distribution of the two potential vectors, Phlebotomus papatasi and P. sergenti, associated with all CL endemic foci across the country. The density of P. papatasi was most affected by temperature changes. The study showed a significant positive correlation between the densities of both sexes of P. papatasi and night-time temperatures. Both P. papatasi and P. sergenti showed a negative correlation with aridity, but, such correlation was only significant in case of P. papatasi. NDVI showed a positive correlation only with densities of P. sergenti, while, soil PH and soil water stress were negatively correlated with the

  2. Oviposition ecology and species composition of Aedes spp. and Aedes aegypti dynamics in variously urbanized settings in arbovirus foci in southeastern Côte d'Ivoire.

    Science.gov (United States)

    Zahouli, Julien B Z; Utzinger, Jürg; Adja, Maurice A; Müller, Pie; Malone, David; Tano, Yao; Koudou, Benjamin G

    2016-09-29

    Aedes mosquito-transmitted outbreaks of dengue and yellow fever have been reported from rural and urban parts of Côte d'Ivoire. The present study aimed at assessing Aedes spp. oviposition ecology in variously urbanized settings within arbovirus foci in southeastern Côte d'Ivoire. Aedes spp. eggs were sampled using a standard ovitrap method from January 2013 to April 2014 in different ecosystems of rural, suburban and urban areas. Emerged larvae were reared until the adult stage for species identification. Aedes spp. oviposition ecology significantly varied from rural-to-urban areas and according to the ecozones and the seasons. Species richness of Aedes spp. gradually decreased from rural (eight species) to suburban (three species) and urban (one species) areas. Conversely, emerged adult Aedes spp. mean numbers were higher in the urban (1.97 Aedes/ovitrap/week), followed by the suburban (1.44 Aedes/ovitrap/week) and rural (0.89 Aedes/ovitrap/week) areas. Aedes aegypti was the only species in the urban setting (100 %), and was also the predominant species in suburban (85.5 %) and rural (63.3 %) areas. The highest Ae. aegypti mean number was observed in the urban (1.97 Ae. aegypti/ovitrap/week), followed by the suburban (1.20 Ae. aegypti/ovitrap/week) and rural (0.57 Ae. aegypti/ovitrap/week) areas. Aedes africanus (9.4 %), Ae. dendrophilus (8.0 %), Ae. metallicus (1.3 %) in the rural, and Ae. vittatus (6.5 %) and Ae. metallicus (1.2 %) in the suburban areas each represented more than 1 % of the total Aedes fauna. In all areas, Aedes species richness and abundance were higher in the peridomestic zones and during the rainy season, with stronger variations in species richness in the rural and in abundance in the urban areas. Besides, the highest Culex quinquefasciatus abundance was found in the urban areas, while Eretmapodites chrysogaster was restricted to the rural areas. Urbanization correlates with a substantially higher abundance in Aedes mosquitoes and

  3. Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci.

    Science.gov (United States)

    Smeets, Daniel; Markaki, Yolanda; Schmid, Volker J; Kraus, Felix; Tattermusch, Anna; Cerase, Andrea; Sterr, Michael; Fiedler, Susanne; Demmerle, Justin; Popken, Jens; Leonhardt, Heinrich; Brockdorff, Neil; Cremer, Thomas; Schermelleh, Lothar; Cremer, Marion

    2014-01-01

    A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs). We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an 'autosomal Barr body' with less compacted chromatin and incomplete RNAP II exclusion. 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform

  4. Skull deformations in craniosynostosis and endocrine disorders: morphological and tomographic analysis of the skull from the crypt of the Silesian Piasts in Brzeg (16th-17th century), Poland.

    Science.gov (United States)

    Kozłowski, T; Cybulska, M; Błaszczyk, B; Krajewska, M; Jeśman, C

    2014-10-01

    of morphological and tomographic (CT) studies of the skull that was found in the crypt of the Silesian Piasts in the St. Jadwiga church in Brzeg (Silesia, Poland) are presented and discussed here. The established date of burial of probably a 20-30 years old male was 16th-17th century. The analyzed skull showed premature obliteration of the major skull sutures. It resulted in the braincase deformation, similar to the forms found in oxycephaly and microcephaly. Tomographic analysis revealed gross pathology. Signs of increased intracranial pressure, basilar invagination and hypoplasia of the occipital bone were observed. Those results suggested the occurrence of the very rare Arnold-Chiari syndrome. Lesions found in the sella turcica indicated the development of pituitary macroadenoma, which resulted in the occurrence of discreet features of acromegaly in the facial bones. The studied skull was characterized by a significantly smaller size of the neurocranium (horizontal circumference 471 mm, cranial capacity ∼ 1080 ml) and strongly expressed brachycephaly (cranial index=86.3), while its height remained within the range for non-deformed skulls. A narrow face, high eye-sockets and prognathism were also observed. Signs of alveolar process hypertrophy with rotation and displacement of the teeth were noted. The skull showed significant morphological differences compared to both normal and other pathological skulls such as those with pituitary gigantism, scaphocephaly and microcephaly. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. Radiofrequency catheter ablation of idiopathic ventricular arrhythmias originating from intramural foci in the left ventricular outflow tract: efficacy of sequential versus simultaneous unipolar catheter ablation.

    Science.gov (United States)

    Yamada, Takumi; Maddox, William R; McElderry, H Thomas; Doppalapudi, Harish; Plumb, Vance J; Kay, G Neal

    2015-04-01

    Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides. © 2015 American Heart Association, Inc.

  6. Evaluation of natural foci of Panstrongylus megistus in a forest fragment in Porto Alegre, State of Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Jose Eloy dos Santos Jr

    2013-09-01

    Full Text Available Introduction Panstrongylus megistus is commonly found in wild environments of the State of Rio Grande do Sul, Brazil. The aim of this study was to characterize the network of refuges used by triatomine in a forest fragment of Porto Alegre and to identify Trypanosoma cruzi infection, associated hosts and the epidemiological importance of both hosts and triatomines. Methods Techniques including the spool-and-line method and active searching (transects were used to identify natural foci. Results The food source for each triatomine was determined using the precipitin test, and the infection of marsupials was determined by xenodiagnosis. A total of 33 adults (domestic environment and 27 nymphs (wild environment of P. megistus were found in addition to 43 Didelphis albiventris specimens. The infection rates of triatomine adults, triatomine nymphs and opossums with T. cruzi I were 64%, 73% and 69%, respectively. Birds, rodents and opossums were the main resources used by triatomine. Conclusions This work presents the first characterization of a natural focus of P. megistus in Rio Grande do Sul. The natural characteristics of this focus and its implication in the transmission of T. cruzi are discussed.

  7. Human herpesvirus 6B U19 protein is a PML-regulated transcriptional activator that localizes to nuclear foci in a PML-independent manner

    DEFF Research Database (Denmark)

    Kofod-Olsen, Emil; Ross-Hansen, Katrine; Mikkelsen, Jacob Giehm

    2008-01-01

    Human herpesvirus 6B (HHV-6B) contains an IE-B domain spanning open reading frames U16/17-U19, based on homology with human cytomegalovirus. Here, the protein product, U19, of the HHV-6B U19 gene is identified as a 47 kDa transcriptional activator. HHV-6B infection or overexpression of U19...... transactivated the RANTES promoter. Mutational analysis of the promoter indicated that transactivation was not critically dependent on the promoter sites CRE, NF-kappaB, ISRE or NF-IL6. ND10 are nuclear substructures that are involved in several cellular regulatory pathways, including those controlling gene...... structure, U19 also localized to the centre of ND10. Knockdown of PML by small interfering RNA did not prevent U19 localization to ND10-like foci, but instead led to a fourfold increase in U19-induced transcription from the RANTES promoter. Generation of four truncated U19 proteins indicated that the N...

  8. Isoenzymatic characterization of Phlebotomus ariasi and P. perniciosus of canine leishmaniasis foci from Eastern Pyrenean regions and comparison with other populations from Europe

    Directory of Open Access Journals (Sweden)

    Ballart Cristina

    2018-01-01

    Full Text Available An entomological survey was carried out in 2007 in two Pyrenean counties of Lleida province (north-eastern Spain, where cases of autochthonous canine leishmaniasis have been recently reported. Phlebotomus ariasi and P. perniciosus, vectors of Leishmania infantum in the Mediterranean area, were captured. The aim of the present study was to compare these phlebotomine populations with others captured in known leishmaniasis foci in Europe. Populations of these species were studied by analysing the polymorphism of seven enzymatic systems (HK, PGI, PGM, MDH, 6PGD, FUM and ACO and compared with other specimens from endemic regions of France, Italy, Malta, Portugal and Spain captured in other campaigns, and also with previously published results. Phlebotomus ariasi was more polymorphic than P. perniciosus. Only the ACO locus had diagnostic alleles, but some other alleles show high characteristic frequencies for each species. The neighbour-joining trees separated two population groups in both species. On the basis of the isoenzyme study results, sand fly populations of the Pyrenean region in Lleida province are closely related to those of other nearby leishmaniasis endemic regions in France and Spain.

  9. γH2AX/53BP1 foci as a potential pre-treatment marker of HNSCC tumors radiosensitivity - preliminary methodological study and discussion

    Science.gov (United States)

    Falk, Martin; Horakova, Zuzana; Svobodova, Marketa; Masarik, Michal; Kopecna, Olga; Gumulec, Jaromir; Raudenska, Martina; Depes, Daniel; Bacikova, Alena; Falkova, Iva; Binkova, Hana

    2017-09-01

    In order to improve patients' post-treatment quality of life, a shift from surgery to non-surgical (chemo)radio-treatment is recognized in head and neck oncology. However, about half of HNSCC tumors are resistant to irradiation and an efficient marker of individual tumor radiosensitivity is still missing. We analyzed whether various parameters of DNA double strand break (DSB) repair determined in vitro can predict, prior to clinical treatment initiation, the radiosensitivity of tumors. We compared formation and decrease of γH2AX/53BP1 foci in 48 h after irradiating tumor cell primocultures with 2 Gy of γ-rays. To better understand complex tumor behavior, three different cell type primocultures - CD90-, CD90+, and a mixed culture of these cells - were isolated from 1 clinically radioresistant, 2 radiosensitive, and 4 undetermined HPV-HNSCC tumors and followed separately. While DSB repair was delayed and the number of persisting DSBs increased in the radiosensitive tumors, the results for the radioresistant tumor were similar to cultured normal human skin fibroblasts. Hence, DSB repair kinetics/efficiency may correlate with clinical response to radiotherapy for a subset of HNSCC tumors but the size (and therefore practical relevance) of this subset remains to be determined. The same is true for contribution of different cell type primocultures to tumor radioresistance.

  10. High affinity (3H) β-Alanine uptake by scar margins of ferric chloride-induced epileptogenic foci in rat isocortex

    International Nuclear Information System (INIS)

    Robitaille, Y.; Sherwin, A.

    1984-01-01

    Cortical astrocytes of normal mammalian brain are endowed with a high affinity uptake system for β-Alanine which is competitively inhibited by gamma aminobutyric acid (GABA), a neurotransmitter strongly implicated in epileptogenesis. The authors evaluated ( 3 H) β-Alanine uptake by reactive astrocytes proliferating within scar of epileptogenic foci induced in rat motor cortex by microinjections of 100 mM ferric chloride. Following in vitro incubation of scar tissue with ( 3 H) β-Alanine, ultrastructural morphometry of grain patterns at 5, 30 and 120 days post injection revealed early and significant grain count increases over astroglial processes, predominantly those related to perivascular glial end-feet. Astrocytic cell body and endothelial cell counts showed a more gradual and stepwise increase. Similar data were obtained by comparing visual and edited mean astrocytic grain counts. These results suggest that the enhanced uptake of reactive astrocytes may reflect a marked decrease of inhibitory GABAergic neurons within ferric chloride-induced scars. 7 figures, 1 table

  11. Comparison of the induction and disappearance of DNA double strand breaks and gamma-H2AX foci after irradiation of chromosomes in G1-phase or in condensed metaphase cells.

    Science.gov (United States)

    Kato, Takamitsu A; Okayasu, Ryuichi; Bedford, Joel S

    2008-03-01

    The induction and disappearance of DNA double strand breaks (DSBs) after irradiation of G1 and mitotic cells were compared with the gamma-H2AX foci assay and a gel electrophoresis assay. This is to determine whether cell cycle related changes in chromatin structure might influence the gamma-H2AX assay which depends on extensive phosphorylation and dephosphorylation of the H2AX histone variant surrounding DSBs. The disappearance of gamma-H2AX foci after irradiation was much slower for mitotic than for G1 cells. On the other hand, no difference was seen for the gel electrophoresis assay. Our data may suggest the limited accessibility of dephosphorylation enzyme in irradiated metaphase cells or trapped gamma-H2AX in condensed chromatin.

  12. Comparison of the induction and disappearance of DNA double strand breaks and γ-H2AX foci after irradiation of chromosomes in G1-phase or in condensed metaphase cells

    International Nuclear Information System (INIS)

    Kato, Takamitsu A.; Okayasu, Ryuichi; Bedford, Joel S.

    2008-01-01

    The induction and disappearance of DNA double strand breaks (DSBs) after irradiation of G1 and mitotic cells were compared with the γ-H2AX foci assay and a gel electrophoresis assay. This is to determine whether cell cycle related changes in chromatin structure might influence the γ-H2AX assay which depends on extensive phosphorylation and dephosphorylation of the H2AX histone variant surrounding DSBs. The disappearance of γ-H2AX foci after irradiation was much slower for mitotic than for G1 cells. On the other hand, no difference was seen for the gel electrophoresis assay. Our data may suggest the limited accessibility of dephosphorylation enzyme in irradiated metaphase cells or trapped γ-H2AX in condensed chromatin

  13. The socio-economic burden of human African trypanosomiasis and the coping strategies of households in the South Western Kenya foci.

    Directory of Open Access Journals (Sweden)

    Salome A Bukachi

    2017-10-01

    Full Text Available Human African Trypanosomiasis (HAT, a disease caused by protozoan parasites transmitted by tsetse flies, is an important neglected tropical disease endemic in remote regions of sub-Saharan Africa. Although the determination of the burden of HAT has been based on incidence, mortality and morbidity rates, the true burden of HAT goes beyond these metrics. This study sought to establish the socio-economic burden that households with HAT faced and the coping strategies they employed to deal with the increased burden.A mixed methods approach was used and data were obtained through: review of hospital records; structured interviews (152; key informant interviews (11; case narratives (12 and focus group discussions (15 with participants drawn from sleeping sickness patients in the south western HAT foci in Kenya. Quantitative data were analysed using descriptive statistics while qualitative data was analysed based on emerging themes.Socio-economic impacts included, disruption of daily activities, food insecurity, neglect of homestead, poor academic performance/school drop-outs and death. Delayed diagnosis of HAT caused 93% of the affected households to experience an increase in financial expenditure (ranging from US$ 60-170 in seeking treatment. Out of these, 81.5% experienced difficulties in raising money for treatment resorting to various ways of raising it. The coping strategies employed to deal with the increased financial expenditure included: sale of agricultural produce (64%; seeking assistance from family and friends (54%; sale/lease of family assets (22%; seeking credit (22% and use of personal savings (17%.Coping strategies outlined in this study impacted negatively on the affected households leading to further food insecurity and impoverishment. Calculation of the true burden of disease needs to go beyond incidence, mortality and morbidity rates to capture socio-economic variables entailed in seeking treatment and coping strategies of HAT

  14. Correlations of {sup 18}F-fluorothymidine uptake with pathological tumour size, Ki-67 and thymidine kinase 1 expressions in primary and metastatic lymph node colorectal cancer foci

    Energy Technology Data Exchange (ETDEWEB)

    Nakajo, Masatoyo; Nakajo, Masayuki [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Kajiya, Yoriko; Tani, Atsushi [Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Goto, Yuko; Higashi, Michiyo [Kagoshima University, Department of Human Pathology, Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544 (Japan); Jinguji, Megumi; Fukukura, Yoshihiko [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Tanaka, Sadao [Nanpuh Hospital, Department of Pathology, Kagoshima (Japan)

    2014-12-15

    To examine correlations of {sup 18}F-fluorothymidine (FLT) uptake with pathological tumour size and immunohistochemical Ki-67, and thymidine kinase 1 (TK-1) expressions in primary and metastatic node colorectal cancer foci. Thirty primary cancers (PCs) and 37 metastatic nodes (MNs) were included. FLT uptake was assessed by visual scores (non-visible: 0-1 and visible: 2-4), standardized uptake value (SUV), and correlated with size, Ki-67, and TK-1. SUV was measured in visible lesions. FLT heterogeneity was assessed by visual scores (no heterogeneous uptake: 0 and heterogeneous uptake: 1-4). Forty-two lesions were visible. The visible group showed significantly higher values than the non-visible group in size, Ki-67, and TK-1 (each p < 0.05). Size correlated significantly with visual score (PC; ρ = 0.74 and MN; ρ = 0.63), SUVmax (PC; ρ = 0.49, and MN; ρ = 0.76), and SUVmean (PC; ρ = 0.40 and MN; ρ = 0.76) (each p < 0.05). Visual score correlated significantly with size (ρ = 0.86), Ki-67max (ρ = 0.35), Ki-67mean (ρ = 0.38), TK-1max (ρ = 0.35) and TK-1mean (ρ = 0.25) (each p < 0.05). No significant correlations were found between FLT uptake and Ki-67 or TK-1 in 42 visible lesions (each p > 0.05). Heterogeneous FLT uptake was noted in 73 % (22/30) of PCs. FLT uptake correlated with size. Heterogeneous FLT distribution in colorectal cancers may be one of the causes of weak or lack of FLT uptake/Ki-67 or TK-1 correlation. (orig.)

  15. [Identification of anopheles breeding sites in the residual foci of low malaria transmission «hotspots» in Central and Western Senegal].

    Science.gov (United States)

    Sy, O; Konaté, L; Ndiaye, A; Dia, I; Diallo, A; Taïrou, F; Bâ, E L; Gomis, J F; Ndiaye, J L; Cissé, B; Gaye, O; Faye, O

    2016-02-01

    Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non-hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission.

  16. Community-Based Entomological Surveillance Reveals Urban Foci of Chagas Disease Vectors in Sobral, State of Ceará, Northeastern Brazil.

    Directory of Open Access Journals (Sweden)

    Cynara Carvalho Parente

    Full Text Available The aim of this work was to explore the potential risk of vector-borne Chagas disease in urban districts in northeastern Brazil, by analyzing the spatiotemporal distributions and natural infection rates with Trypanosoma cruzi of triatomine species captured in recent years. The main motivation of this work was an acute human case of Chagas disease reported in 2008 in the municipality of Sobral.We analyzed data from community-based entomological surveillance carried out from 2010 to 2014. Triatomine natural T. cruzi infection was assessed by examination of insect feces by optical microscopy. Sites of triatomine capture were georeferenced through Google Earth and analyzed with ArcGIS. A total of 191 triatomines were collected, consisting of 82.2% Triatoma pseudomaculata, 7.9% Rhodnius nasutus, 5.8% T. brasiliensis, 3.7% Panstrongylus lutzi, and 0.5% P. megistus, with an overall natural infection index of 17.8%. Most infestations were reported in the districts of Dom José (36.2%, Padre Palhano (24.7%, and Alto do Cristo (10.6%. The overwhelming majority of insects (185/96.9% were captured inside houses, and most insects tended to be collected in intermittent peaks. Moreover, captured triatomines tended to constitute colonies. The acute case reported in 2008 was found to be situated within a T. pseudomaculata hotspot.The triatomine collection events carried out by dwellers were aggregated in time and space into distinct foci, suggesting that insects are intermittently and artificially introduced into the city, possibly via accidental migration from their natural reservoirs. The relatively high T. cruzi infection rate indicates considerable circulation of the parasite in these areas, increasing the risk of vector-borne Chagas disease infection. These data suggest a need to strengthen epidemiological surveillance and integrate appropriate control actions targeting triatomines, T. cruzi reservoirs, and human populations. Our data also identify Chagas

  17. Confocal laser Raman microspectroscopy of biomineralization foci in UMR 106 osteoblastic cultures reveals temporally synchronized protein changes preceding and accompanying mineral crystal deposition.

    Science.gov (United States)

    Wang, Chuanyi; Wang, Yong; Huffman, Nichole T; Cui, Chaoying; Yao, Xiaomei; Midura, Sharon; Midura, Ronald J; Gorski, Jeff P

    2009-03-13

    Mineralization in UMR 106-01 osteoblastic cultures occurs within extracellular biomineralization foci (BMF) within 12 h after addition of beta-glycerol phosphate to cells at 64 h after plating. BMF are identified by their enrichment with an 85-kDa glycoprotein reactive with Maackia amurensis lectin. Laser Raman microspectroscopic scans were made on individual BMF at times preceding (64-76 h) and following the appearance of mineral crystals (76-88 h). The range of variation between spectra for different BMF in the same culture was rather small. In contrast, significant differences were observed for spectral bands at 957-960, 1004, and 1660 cm(-1) when normalized BMF spectra at different times were compared. Protein-dependent spectral bands at 1004 and 1660 cm(-1) increased and then decreased preceding the detection of hydroxyapatite crystals via the phosphate stretching peak at 959-960 cm(-1). When sodium phosphate was substituted for beta-glycerol phosphate, mineralization occurred 3-6 h earlier. Irrespective of phosphate source, the Raman full peak width at half-maximum ratio for 88 h cultures was similar to that for 10-day-old marrow ablation primary bone. However, if mineralization was blocked with serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride, 64-88-h BMF spectra remained largely invariant. In summary, Raman spectral data demonstrate for the first time that formation of hydroxyapatite crystals within individual BMF is a multistep process. Second, changes in protein-derived signals at 1004 and 1660 cm(-1) reflect events within BMFs that precede or accompany mineral crystal production because they are blocked by mineralization inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride. Finally, the low extent of spectral variability detected among different BMF at the same time point indicates that mineralization of individual BMF within a culture is synchronized.

  18. Confocal Laser Raman Microspectroscopy of Biomineralization Foci in UMR 106 Osteoblastic Cultures Reveals Temporally Synchronized Protein Changes Preceding and Accompanying Mineral Crystal Deposition*

    Science.gov (United States)

    Wang, Chuanyi; Wang, Yong; Huffman, Nichole T.; Cui, Chaoying; Yao, Xiaomei; Midura, Sharon; Midura, Ronald J.; Gorski, Jeff P.

    2009-01-01

    Mineralization in UMR 106-01 osteoblastic cultures occurs within extracellular biomineralization foci (BMF) within 12 h after addition of β-glycerol phosphate to cells at 64 h after plating. BMF are identified by their enrichment with an 85-kDa glycoprotein reactive with Maackia amurensis lectin. Laser Raman microspectroscopic scans were made on individual BMF at times preceding (64–76 h) and following the appearance of mineral crystals (76–88 h). The range of variation between spectra for different BMF in the same culture was rather small. In contrast, significant differences were observed for spectral bands at 957–960, 1004, and 1660 cm-1 when normalized BMF spectra at different times were compared. Protein-dependent spectral bands at 1004 and 1660 cm-1 increased and then decreased preceding the detection of hydroxyapatite crystals via the phosphate stretching peak at 959–960 cm-1. When sodium phosphate was substituted for β-glycerol phosphate, mineralization occurred 3–6 h earlier. Irrespective of phosphate source, the Raman full peak width at half-maximum ratio for 88 h cultures was similar to that for 10-day-old marrow ablation primary bone. However, if mineralization was blocked with serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride, 64–88-h BMF spectra remained largely invariant. In summary, Raman spectral data demonstrate for the first time that formation of hydroxyapatite crystals within individual BMF is a multistep process. Second, changes in protein-derived signals at 1004 and 1660 cm-1 reflect events within BMFs that precede or accompany mineral crystal production because they are blocked by mineralization inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride. Finally, the low extent of spectral variability detected among different BMF at the same time point indicates that mineralization of individual BMF within a culture is synchronized. PMID:19116206

  19. Role of endorectal MR imaging and MR spectroscopic imaging in defining treatable intraprostatic tumor foci in prostate cancer: Quantitative analysis of imaging contour compared to whole-mount histopathology

    International Nuclear Information System (INIS)

    Anwar, Mekhail; Westphalen, Antonio C.; Jung, Adam J.; Noworolski, Susan M.; Simko, Jeffry P.; Kurhanewicz, John; Roach, Mack; Carroll, Peter R.; Coakley, Fergus V.

    2014-01-01

    Purpose: To investigate the role of endorectal MR imaging and MR spectroscopic imaging in defining the contour of treatable intraprostatic tumor foci in prostate cancer, since targeted therapy requires accurate target volume definition. Materials and methods: We retrospectively identified 20 patients with prostate cancer who underwent endorectal MR imaging and MR spectroscopic imaging prior to radical prostatectomy and subsequent creation of detailed histopathological tumor maps from whole-mount step sections. Two experienced radiologists independently reviewed all MR images and electronically contoured all suspected treatable (⩾0.5 cm 3 ) tumor foci. Deformable co-registration in MATLAB was used to calculate the margin of error between imaging and histopathological contours at both capsular and non-capsular surfaces and the treatment margin required to ensure at least 95% tumor coverage. Results: Histopathology showed 17 treatable tumor foci in 16 patients, of which 8 were correctly identified by both readers and an additional 2 were correctly identified by reader 2. For all correctly identified lesions, both readers accurately identified that tumor contacted the prostatic capsule, with no error in contour identification. On the non-capsular border, the median distance between the imaging and histopathological contour was 1.4 mm (range, 0–12). Expanding the contour by 5 mm at the non-capsular margin included 95% of tumor volume not initially covered within the MR contour. Conclusions: Endorectal MR imaging and MR spectroscopic imaging can be used to accurately contour treatable intraprostatic tumor foci; adequate tumor coverage is achieved by expanding the treatment contour at the non-capsular margin by 5 mm

  20. The influence of x-ray contrast agents in computed tomography on the induction of dicentrics and {gamma}-H2AX foci in lymphocytes of human blood samples

    Energy Technology Data Exchange (ETDEWEB)

    Jost, G; Golfier, S; Pietsch, H; Lengsfeld, P; Voth, M [Bayer Schering Pharma AG, 13353 Berlin (Germany); Schmid, T E [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universitaet Muenchen, 81675 Munich (Germany); Eckardt-Schupp, F [Institute of Radiation Biology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg (Germany); Schmid, E [Institute for Cell Biology, Center for Integrated Protein Science, University of Munich, 80336 Muenchen (Germany)], E-mail: Ernst.Schmid@lrz.uni-muenchen.de

    2009-10-21

    The aim of this study was to investigate and quantify two biomarkers for radiation exposure (dicentrics and {gamma}-H2AX foci) in human lymphocytes after CT scans in the presence of an iodinated contrast agent. Blood samples from a healthy donor were exposed to CT scans in the absence or presence of iotrolan 300 at iodine concentrations of 5 or 50 mg ml{sup -1} blood. The samples were exposed to 0.025, 0.05, 0.1 and 1 Gy in a tissue equivalent body phantom. Chromosome aberration scoring and automated microscopic analysis of {gamma}-H2AX foci were performed in parts of the same samples. The theoretical physical dose enhancement factor (DEF) was calculated on the basis of the mass energy-absorption coefficients of iodine and blood and the photon energy spectrum of the CT tube. No significant differences in the yields of dicentrics and {gamma}-H2AX foci were observed in the absence or presence of 5 mg iodine ml{sup -1} blood up to 0.1 Gy, whereas at 1 Gy the yields were elevated for both biomarkers. At an iodine concentration of 50 mg ml{sup -1} serving as a positive control, a biological DEF of 9.5 {+-} 1.4 and 2.3 {+-} 0.5 was determined for dicentrics and {gamma}-H2AX foci, respectively. A physical DEF of 1.56 and 6.30 was calculated for 5 and 50 mg iodine ml{sup -1}, respectively. Thus, it can be concluded that in the diagnostic dose range (radiation and contrast dose), no relevant biological dose-enhancing effect could be detected, whereas a clear biological dose-enhancing effect could be found for a contrast dose well outside the diagnostic CT range for the complete radiation dose range with both methods.

  1. Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type- and insult-dependent manner, and follow expression of p16 (ink4a)

    Czech Academy of Sciences Publication Activity Database

    Košař, Martin; Bartkova, J.; Hubáčková, Soňa; Hodný, Zdeněk; Lukas, J.; Bartek, Jiří

    2011-01-01

    Roč. 10, č. 3 (2011), s. 457-468 ISSN 1538-4101 R&D Projects: GA ČR GA204/08/1418; GA ČR GA301/08/0353 Institutional research plan: CEZ:AV0Z50520514 Keywords : genotoxic and replicative stress * senescence-associated heterochromatin foci * DNA damage response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.359, year: 2011

  2. Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

    Energy Technology Data Exchange (ETDEWEB)

    Vadhavkar, Nikhil [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Pham, Christopher [University of Texas, Houston, TX (United States). MD Anderson Cancer Center; Georgescu, Walter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Deschamps, Thomas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Heuskin, Anne-Catherine [Univ. of Namur (Belgium). Namur Research inst. for Life Sciences (NARILIS), Research Center for the Physics of Matter and Radiation (PMR); Tang, Jonathan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Costes, Sylvain V. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2014-09-01

    In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicron level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model

  3. NOAA/EcoFOCI Chukchi Sea mooring time-series data, stations C1, C2, and C3, 2010-08-29 to 2012-08-21, including currents, temperature, salinity, oxygen, chlorophyll a, and nitrate data (NCEI Accession 0157701)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These EcoFOCI mooring time-series datasets consist of RCM-9 current data, Ecofluorometer, Seacat and nitrate data from moored instruments at 3 stations in the...

  4. Influência da suplementação de glutamina sobre o desempenho e o desenvolvimento de vilos e criptas do intestino delgado de frangos Influence of glutamine supplementation on performance and intestinal villous and crypt development in broiler chickens

    Directory of Open Access Journals (Sweden)

    A. Maiorka

    2000-10-01

    Full Text Available Investigou-se o efeito da suplementação de glutamina na dieta sobre o consumo de ração, ganho de peso e conversão alimentar e sobre a estrutura da mucosa intestinal de frangos. Foram utilizados 320 pintos de corte machos distribuídos em um delineamento inteiramente ao acaso com dois tratamentos e quatro repetições, sendo T1 suplementado com 1% de L-glutamina na dieta e T2 controle. Os índices de desempenho foram analisados aos 7, 21 e 49 dias de idade das aves. Aos 7 e 14 dias de idade oito aves foram sacrificadas para colheita de fragmentos de cada porção do intestino delgado para avaliação da morfometria intestinal em microscopia de luz em sistema analisador de imagens "Video Plan". As variáveis estudadas foram altura dos vilos, profundidade de cripta e relação vilo: cripta. A adição de 1% de glutamina à dieta de frangos não influenciou (P>0,05 o seu desempenho zootécnico. Entretanto, 1% de glutamina na ração foi capaz de alterar (PThis investigation was carried out in order to study the influence of glutamine supplementation in the ration on performance and on the intestinal structure development of broiler chickens. Three hundred and twenty day-old broiler chickens were used in a completely randomized experiment with two treatments and four repetitions, being T1 supplemented with 1% L-glutamine and T2 - control (not supplemented. The performance was evaluated (feed intake, body weight gain and feed conversion at 7, 21 and 49 days of age. At the same ages birds were sacrificed and samples from different parts of the intestine were collected (duodenum, jejunum and ileum to be submitted to morphometric studies under light microscopy using an image analysis system (Video Plan. The variables studied were villous height, crypt depth and villous:crypt ratio. It was demonstrated that 1% glutamine supplementation in the ration did not influence the broiler chicken performance (P>0.05 during the different phases of growth

  5. A novel statistical analysis method to improve the detection of hepatic foci of {sup 111}In-octreotide in SPECT/CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Magnander, Tobias [Department of Radiation Physics, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg (Sweden); Wikberg, E. [Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg (Sweden); Svensson, J. [Department of Oncology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Gjertsson, P. [Department of Clinical Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Wängberg, B. [Department of Surgery, The Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Båth, M.; Bernhardt, Peter [Department of Radiation Physics, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg (Sweden)

    2016-01-19

    Low uptake ratios, high noise, poor resolution, and low contrast all combine to make the detection of neuroendocrine liver tumours by {sup 111}In-octreotide single photon emission tomography (SPECT) imaging a challenge. The aim of this study was to develop a segmentation analysis method that could improve the accuracy of hepatic neuroendocrine tumour detection. Our novel segmentation was benchmarked by a retrospective analysis of patients categorized as either {sup 111}In-octreotide positive ({sup 111}In-octreotide(+)) or {sup 111}In-octreotide negative ({sup 111}In-octreotide(−)) for liver tumours. Following a 3-year follow-up period, involving multiple imaging modalities, we further segregated {sup 111}In-octreotide-negative patients into two groups: one with no confirmed liver tumours ({sup 111}In-octreotide(−)/radtech(−)) and the other, now diagnosed with liver tumours ({sup 111}In-octreotide(−)/radtech(+)). We retrospectively applied our segmentation analysis to see if it could have detected these previously missed tumours using {sup 111}In-octreotide. Our methodology subdivided the liver and determined normalized numbers of uptake foci (nNUF), at various threshold values, using a connected-component labelling algorithm. Plots of nNUF against the threshold index (ThI) were generated. ThI was defined as follows: ThI = (c{sub max} − c{sub thr})/c{sub max}, where c{sub max} is the maximal threshold value for obtaining at least one, two voxel sized, uptake focus; c{sub thr} is the voxel threshold value. The maximal divergence between the nNUF values for {sup 111}In-octreotide(−)/radtech(−), and {sup 111}In-octreotide(+) livers, was used as the optimal nNUF value for tumour detection. We also corrected for any influence of the mean activity concentration on ThI. The nNUF versus ThI method (nNUFTI) was then used to reanalyze the {sup 111}In-octreotide(−)/radtech(−) and {sup 111}In-octreotide(−)/radtech(+) groups. Of a total of 53 {sup 111}In

  6. Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) Combined with Positron Emission Tomography-Computed Tomography (PET-CT) and Video-Electroencephalography (VEEG) Have Excellent Diagnostic Value in Preoperative Localization of Epileptic Foci in Children with Epilepsy.

    Science.gov (United States)

    Wang, Gui-Bin; Long, Wei; Li, Xiao-Dong; Xu, Guang-Yin; Lu, Ji-Xiang

    2017-01-01

    BACKGROUND To investigate the effect that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has on surgical decision making relative to video-electroencephalography (VEEG) and positron emission tomography-computed tomography (PET-CT), and if the differences in these variables translates to differences in surgical outcomes. MATERIAL AND METHODS A total of 166 children with epilepsy undergoing preoperative DCE-MRI, VEEG, and PET-CT examinations, surgical resection of epileptic foci, and intraoperative electrocorticography (ECoG) monitoring were enrolled. All children were followed up for 12 months and grouped by Engles prognostic classification for epilepsy. Based on intraoperative ECoG as gold standard, the diagnostic values of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and combined application of DCE-MRI, VEEG, and PET-CT in preoperative localization for epileptic foci were evaluated. RESULTS The sensitivity of DCE-MRI, VEEG, and PET-CT was 59.64%, 76.51%, and 93.98%, respectively; the accuracy of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, and DCE-MRI combined with PET-CT was 57.58%, 67.72%, 91.03%, 91.23%, and 96.49%, respectively. Localization accuracy rate of the combination of DCE-MRI, VEEG, and PET-CT was 98.25% (56/57), which was higher than that of DCE-MRI combined with VEEG and of DCE-MRI combined with PET-CT. No statistical difference was found in the accuracy rate of localization between these three combined techniques. During the 12-month follow-up, children were grouped into Engles grade I (n=106), II (n=31), III (n=21), and IV (n=8) according to postoperative conditions. CONCLUSIONS All DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and DCE-MRI combined with VEEG and PET-CT examinations have excellent accuracy in preoperative localization of epileptic foci and present excellent postoperative efficiency, suggesting that these combined imaging methods are suitable for serving as the

  7. DNA Double-Strand Break Analysis by {gamma}-H2AX Foci: A Useful Method for Determining the Overreactors to Radiation-Induced Acute Reactions Among Head-and-Neck Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Goutham, Hassan Venkatesh; Mumbrekar, Kamalesh Dattaram [Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Manipal Hospital, Bangalore, Karnataka (India); Fernandes, Donald Jerard; Sharan, Krishna [Department of Radiotherapy and Oncology, Shiridi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Kanive Parashiva, Guruprasad; Kapaettu, Satyamoorthy [Division of Biotechnology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India); Bola Sadashiva, Satish Rao, E-mail: satishraomlsc@gmail.com [Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India)

    2012-12-01

    Purpose: Interindividual variability in normal tissue toxicity during radiation therapy is a limiting factor for successful treatment. Predicting the risk of developing acute reactions before initiation of radiation therapy may have the benefit of opting for altered radiation therapy regimens to achieve minimal adverse effects with improved tumor cure. Methods and Materials: DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of head-and-neck cancer patients undergoing chemoradiation therapy was analyzed by counting {gamma}-H2AX foci, neutral comet assay, and a modified version of neutral filter elution assay. Acute normal tissue reactions were assessed by Radiation Therapy Oncology Group criteria. Results: The correlation between residual DSBs and the severity of acute reactions demonstrated that residual {gamma}-H2AX foci in head-and-neck cancer patients increased with the severity of oral mucositis and skin reaction. Conclusions: Our results suggest that {gamma}-H2AX analysis may have predictive implications for identifying the overreactors to mucositis and skin reactions among head-and-neck cancer patients prior to initiation of radiation therapy.

  8. Location of quarries of non traditional stony materials in the architecture of Madrid: the Crypt of the Cathedral of Santa María la Real de la Almudena

    Directory of Open Access Journals (Sweden)

    Gómez-Heras, M.

    2004-06-01

    Full Text Available The combination between petrological data and historical documentation sources is necessary to establish an accurate methodology for the location of the original quarries of the stony materials used in a determinate historical building. The petrographical and petrophisical data correlation combined with a multivariate statistical analysis, by means of similarity indexes of both the materials in the building and the probable source geological formations, allows the location even when the documental sources would he incomplete or lost, or when the source areas would be modified. The works of location of original quarries used in architectural heritage are important since they allow improving the works of restoration on a building by means of the possibility of using identical materials for substitution or reintegration of decayed elements. The establishment of the original areas also offers the possibility of obtaining unaltered semipiés to evaluate the state and processes of decay of the building as well as to use this rough material to test the effectivity and durability of protective arid consolidant treatments in the building and monuments. The aim of this work has been to characterize and to locate the origin of the stony material in the stonework of the Crypt of the Cathedral of Santa María la Real de la Almudena (Madrid. These stone types came from quarries located in Viana de Jadraque (Guadalajara, Spain and in the central area of Portugal. These materials do not correspond with the traditional ones used in the city of Madrid and its presence is due to the opening of new ways of transport in the second half of the 19"' centuiy.

    Para establecer una metodología adecuada con el fin de localizar las canteras originales de los materiales pétreos de construcción utilizados en un determinado edificio histórico se necesita combinar datos petrológicos y fuentes de documentación histórica. La correlación de los datos petrogr

  9. Characterization of insulin-like-growth factor II (IGF II mRNA positive hepatic altered foci and IGF II expression in hepatocellular carcinoma during diethylnitrosamine-induced hepatocarcinogenesis in rats

    Directory of Open Access Journals (Sweden)

    Mukherjee Biswajit

    2005-08-01

    Full Text Available Abstract Background Insulin-like-growth factor II (IGF II has been implicated in the pathogenesis of neoplasm of different tissues, including liver of rats and men. This growth factor is believed to exert its effect during cellular proliferation. During the process of development of hepatocellular carcinoma (HCC, different hepatic altered foci appear. They are believed to be the putative precursors of HCC in rats and in men. Thus, to study the role of the gene in a defined model of hepatocarcinogenesis was the target to elucidate its role in various cancer phenotypes during the entire development stage of cancer, right from earlier preneoplastic lesions to HCC Methods Antisense in situ hybridization technique was used here to characterize the type(s of foci in which IGF II mRNA had expressed during the development of hepatocarcinogenesis-induced by diethylnitrosamine and promoted by phenobarbital in rats. Various focal lesions have been categorized depending on the stages and sizes along with IGF II expression patterns in them. Immunohistochemical detection for proliferating cell nuclear antigen (PCNA was made to detect the role of the gene in preneoplastic and neoplastic cellular proliferation. Results IGF II expression was located in the glycogen-storage acidophilic cell foci maximally followed by mixed cell lesions and the least in basophilic lesions. The expression of IGF II was found to be predominant in the HCC. The expression of gene was also located at the peripheral cells of spongiosis hepatis which are believed to be the precursor of ito cell carcinoma. It was noted that there is a direct correlation between IGF II expression and Immunohistochemical detection for PCNA. Conclusion It may be concluded that IGF II gene expression plays an important role during the development of neoplasia and the gene expresses in the sequence of events leading from glycogen-rich-acidophilic lesions to glycogen poor basophilic lesions to HCC with an

  10. Induction of glutathione S-transferase placental form positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks

    International Nuclear Information System (INIS)

    Shen Jun; Wanibuchi, Hideki; Salim, Elsayed I.; Wei Min; Doi, Kenichiro; Yoshida, Kaoru; Endo, Ginji; Morimura,; Fukushima, Shoji

    2003-01-01

    The carcinogenicity of monomethylarsonic acid (MMA(V)), a major metabolite of inorganic arsenics in human and experimental animals, was investigated in male Fischer 344 rats. A total of 129 rats at 10 weeks of age were randomly divided into three groups and received drinking water containing MMA(V) at doses of 0 (Control), 50, and 200 ppm ad libitum for 104 weeks. No significant differences were found between the control and the MMA(V)-treated groups regarding clinical signs, mortality, hematological, and serum biochemistry findings. Quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci in liver revealed a significant increase of numbers and areas in the 200 ppm MMA(V)-treated group. In the urinary bladder MMA(V) induced simple hyperplasia and significantly elevated the proliferating cell nuclear antigen (PCNA)-positive index in the urothelium. A variety of tumors developed in rats of all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats and there were no significant differences among the groups. Thus, it could be concluded that, under the present experimental conditions, MMA(V) induced lesions in the liver and urinary bladder, but did not cause tumor development in male F344 rats even after 2 years exposure

  11. ATM and SIRT6/SNF2H Mediate Transient H2AX Stabilization When DSBs Form by Blocking HUWE1 to Allow Efficient γH2AX Foci Formation

    Directory of Open Access Journals (Sweden)

    Yuko Atsumi

    2015-12-01

    Full Text Available In response to DNA double-strand breaks (DSBs, H2AX is rapidly phosphorylated at Ser139 to promote DSB repair. Here we show that H2AX is rapidly stabilized in response to DSBs to efficiently generate γH2AX foci. This mechanism operated even in quiescent cells that barely expressed H2AX. H2AX stabilization resulted from the inhibition of proteasome-mediated degradation. Synthesized H2AX ordinarily underwent degradation through poly-ubiquitination mediated by the E3 ligase HUWE1; however, H2AX ubiquitination was transiently halted upon DSB formation. Such rapid H2AX stabilization by DSBs was associated with chromatin incorporation of H2AX and halting of its poly-ubiquitination mediated by the ATM kinase, the sirtuin protein SIRT6, and the chromatin remodeler SNF2H. H2AX Ser139, the ATM phosphorylation site, was essential for H2AX stabilization upon DSB formation. Our results reveal a pathway controlled by ATM, SIRT6, and SNF2H to block HUWE1, which stabilizes H2AX and induces its incorporation into chromatin only when cells are damaged.

  12. Load Designs For MJ Dense Plasma Foci

    Science.gov (United States)

    Link, A.; Povlius, A.; Anaya, R.; Anderson, M. G.; Angus, J. R.; Cooper, C. M.; Falabella, S.; Goerz, D.; Higginson, D.; Holod, I.; McMahon, M.; Mitrani, J.; Koh, E. S.; Pearson, A.; Podpaly, Y. A.; Prasad, R.; van Lue, D.; Watson, J.; Schmidt, A. E.

    2017-10-01

    Dense plasma focus (DPF) Z-pinches are compact pulse power driven devices with coaxial electrodes. The discharge of DPF consists of three distinct phases: first generation of a plasma sheath, plasma rail gun phase where the sheath is accelerated down the electrodes and finally an implosion phase where the plasma stagnates into a z-pinch geometry. During the z-pinch phase, DPFs can produce MeV ion beams, x-rays and neutrons. Megaampere class DPFs with deuterium fills have demonstrated neutron yields in the 1012 neutrons/shot range with pulse durations of 10-100 ns. Kinetic simulations using the code Chicago are being used to evaluate various load configurations from initial sheath formation to the final z-pinch phase for DPFs with up to 5 MA and 1 MJ coupled to the load. Results will be presented from the preliminary design simulations. LLNL-ABS-734785 This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory (LLNL) under Contract DE-AC52-07NA27344 and with support from the Computing Grand Challenge program at LLNL.

  13. Sustainability and Environmental Economics: Some Critical Foci

    Science.gov (United States)

    I present five seminal concepts of environmental economic thought and discuss their applicability to the idea of sustainability. These five, Maximum Sustainable Yield and Steady-state, The Environmental Kuznet’s curve, Substitutability, Discount rate and Intergenerational equity...

  14. Interpolación espacial de la abundancia larval de Aedes aegypti para localizar focos de infestación Spatial interpolation of Aedes aegypti larvae abundance for locating infestation foci

    Directory of Open Access Journals (Sweden)

    Larry Niño

    2011-06-01

    Full Text Available OBJETIVO: Diseñar e implementar una metodología de vigilancia que localice los focos de infestación de Aedes aegypti con el empleo de larvitrampas y técnicas de interpolación espacial, las cuales permiten estimar la abundancia vectorial de forma continua en el espacio a partir del conteo de individuos colectados en el área de estudio. MÉTODOS: Se instalaron 228 larvitrampas -a razón de una por manzana- en la zona más densamente poblada de la comuna cinco de Villavicencio (Meta. Con la información regionalizada de la abundancia de larvas se realizaron interpolaciones espaciales con las técnicas polígonos de Voronoi, Kriging ordinario y ponderación de distancias inversas. RESULTADOS: Se presenta una metodología alternativa para la vigilancia del vector del dengue, basada en el uso de larvitrampas y técnicas de interpolación espacial, con las cuales se obtuvieron mapas de superficie sustentados en observaciones puntuales. CONCLUSIONES: Los resultados muestran que esta estrategia aventaja a los índices normalmente usados, dado que permite visualizar de manera continua el nivel de infestación vectorial y por ende el riesgo de transmisión de dengue de acuerdo al grado de infestación por A. aegypti. Es de esperar que su adopción contribuya a planificar, optimizar y evaluar con mayor efectividad las actividades de prevención y control.OBJECTIVE: Design and implement a surveillance method for locating Aedes aegypti infestation foci with the use of larvae traps and spatial interpolation techniques, which facilitate the ongoing estimation of vector abundance in the area by counting the individuals collected in the study area. METHODs: A total of 228 larvae traps were installed-at a rate of one per block-in the most densely populated area of commune five of Villavicencio (Meta. With regionalized information on larvae abundance, spatial interpolations were conducted with the Voronoi polygon, ordinary kriging, and inverse distance

  15. Histopatologia da infecção por Yersinia pestis em roedores de focos de peste do Nordeste brasileiro Histopathology of Yersinia pestis infection in rodents from plague foci of Brazilian Northeast

    Directory of Open Access Journals (Sweden)

    Eridan M. Coutinho

    1982-06-01

    foreign strains of Yersinia pestis have been studied. All the rodents, except the group of cavidae, had a bubosepticemic plague. From all the lesions described, liver multifocal coagulative necrosis, diffuse acute interstitial pneumonia and lymphoid atrophy of the spleen were the most frequent and so can be considered, for practical purposes, as histological indicators of plague infection, although they are not exclusively found in plague. The variety and intensiveness of lesions found in Zigodontomys L. pixuna, may explain the high mortality of this species of rodents, making easier the dissemination of plague in the natural foci of northeast Brazil. Similar histological lesions were detected in cricetidae and muridae. The resistance of cavidae to plague infection has become evident, since they survived to the acute phase of infection and developped an intensive histiocytic granulomatous reaction surrounding necrotic areas (abscesses. It is suggested thad these chronic lesions may harbour virulent bacilli and so explain periodic plague infection in local fleas, leading to reactivation of epizootics.

  16. LKB1 as the ghostwriter of crypt history

    NARCIS (Netherlands)

    Jansen, Marnix; Langeveld, Danielle; De Leng, Wendy W. J.; Milne, Anya N. A.; Giardiello, Francis M.; Offerhaus, G. Johan A.

    Familial cancer syndromes present rare insights into malignant tumor development. The molecular background of polyp formation and the cancer prone state in Peutz-Jeghers syndrome remain enigmatic to this day. Previously, we proposed that Peutz-Jeghers polyps are not pre-malignant lesions, but an

  17. On Hamlet's Crypt: Effi Briest, Asta Nielsen, Aand Britney Spears

    Directory of Open Access Journals (Sweden)

    Viola Kolarov

    2011-10-01

    Full Text Available This contribution looks at the way instinct is transmitted and represented as ghost appearance. The essay elaborates two basic theses: first, that instinct is not defined by creaturely heritage, since it is not a testable structure in itself, nor subject to mourning and developmental processes; and second, that works of fine literature and pop oeuvres alike may serve as carriers of a ghost transmission charged with instinctive heritage. The study represents a model for reading ghostly genealogies that complement the familiar and familial reproductive ones as it draws on traditions such as the adultery novel, continental philosophy, psychoanalysis, and Disney. Currently based in Berlin, Viola Kolarov has taught in the German Departments of the Johns Hopkins University and New York University. She has published on Shakespeare, contemporary art, film, and pop culture. Her forthcoming book, “Shakespeare and the Autobiography of the Machine Age,” rethinks Goethe, the German translation/transmission of Shakespeare, and the German literary tradition in the contexts of media technology. Originally from Berlin, Susanne Lanckowsky entered the Academy of Fine Arts Karlsruhe, class of Franz Ackermann, in 2007. Since 2009 she has shown solo and in group on numerous occasions and studied abroad with prestigious scholarship support for one semester at the Faculdade de Belas Artes Universidade do Porto, Portugal, and for another semester at the Escuela Nacional de Pintura, Escultura y Grabado La Esmeralda in Mexico.

  18. Stem cell self-renewal in intestinal crypt

    NARCIS (Netherlands)

    Simons, B.D.; Clevers, H.

    2011-01-01

    As a rapidly cycling tissue capable of fast repair and regeneration, the intestinal epithelium has emerged as a favored model system to explore the principles of adult stem cell biology. However, until recently, the identity and characteristics of the stem cell population in both the small intestine

  19. Tales from the Crypt: The Reemergence of Chile's Political Memory

    Science.gov (United States)

    Friedman, Mary Lusky

    2014-01-01

    Chilean novelists born during the 1970s who experienced as children the dictatorship of Augusto Pinochet are reappraising how the dictatorship may have harmed its second-generation survivors. Initially most of these writers ignored politics, focusing instead on blighted intimate relationships, and those few who did explore the aftereffects of…

  20. Prebiotics: an update

    African Journals Online (AJOL)

    Administrator

    food supplements) and prebiotics (i.e., non-digestible ..... the improved microbiota metabolically active for a prolonged period of time .... hibit the formation of aberrant crypt foci (ACF), a bio- .... Handbook of Dietary Fiber in Human Nutrition. G.A..

  1. Comparison of small mammal prevalence of Leishmania (Leishmania mexicana in five foci of cutaneous leishmaniasis in the State of Campeche, Mexico Comparación de las prevalencias de Leishmania (Leishmania mexicana en mamíferos pequeños en cinco focos de leishmaniosis cutánea en el estado de Campeche, México

    Directory of Open Access Journals (Sweden)

    N.R. Van Wynsberghe

    2009-04-01

    Full Text Available In the Yucatan Peninsula of Mexico, 95% of the human cases of Cutaneous Leishmaniasis are caused by Leishmania (Leishmania mexicana with an incidence rate of 5.08 per 100,000 inhabitants. Transmission is limited to the winter months (November to March. One study on wild rodents has incriminated Ototylomys phyllotis and Peromyscus yucatanicus as primary reservoirs of L. (L. mexicana in the focus of La Libertad, Campeche. In the present study, the prevalence of both infection and disease caused by L. (L. mexicana in small terrestrial mammals were documented during five transmission seasons (1994-2004 in five foci of Leishmaniasis in the state of Campeche. Foci separated by only 100 km, with similar relative abundances of small mammals, were found to differ significantly in their prevalence of both symptoms and infection. Transmission rates and reservoir species seemed to change in space as well as in time which limited the implementation of effective control measures of the disease even in a small endemic area such as the south of the Yucatan Peninsula.En la Península de Yucatán, México, la Leishmaniosis Cutánea es causada por Leishmania (L. mexicana en 95% de los casos humanos, con una incidencia de 5.08% por cada 100,000 habitantes. El ciclo de transmisión se limita a la estación de invierno (noviembre- marzo. Un estudio de mamíferos silvestres incrimina a Ototylomys phyllotis y Peromyscus yucatanicus como reservorios primarios de L. (L. mexicana en el foco de infección de La Libertad, Campeche. En el presente estudio, se documenta la prevalencia de infección/enfermedad causada por L. (L. mexicana en pequeños mamíferos, durante cinco estaciones de transmisión (1994-2004 en cinco focos de CL del estado de Campeche. Los focos separados por solamente 100 km. de distancia, aún cuando tienen abundancias relativas de pequeños roedores similares, fueron significativamente diferentes en relación a la prevalencia de síntomas así como de

  2. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zeilstra, Jurrit; Joosten, Sander P.J. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Wensveen, Felix M. [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Dessing, Mark C.; Schuetze, Denise M. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Eldering, Eric [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Spaargaren, Marcel [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Pals, Steven T., E-mail: s.t.pals@amc.uva.nl [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands)

    2011-03-04

    Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causes constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which

  3. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    International Nuclear Information System (INIS)

    Zeilstra, Jurrit; Joosten, Sander P.J.; Wensveen, Felix M.; Dessing, Mark C.; Schuetze, Denise M.; Eldering, Eric; Spaargaren, Marcel; Pals, Steven T.

    2011-01-01

    Research highlights: → Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. → Expression profiling of apoptosis-related genes in Apc Min/+ mice revealed the differential expression of pro-apoptotic Bok and Bax. → APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. → Blocking of β-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin causes constitutively active β-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc Min/+ mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of β-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the

  4. Origins, transformations and key foci in instrumental genesis

    DEFF Research Database (Denmark)

    Tamborg, Andreas Lindenskov

    This paper investigates the origins of the instrumental genesis and instrumental orchestrations frameworks. This is done by reviewing instrumented activity situations, instrumental genesis, and instrumental orchestrations with the purpose of identifying their epistemological assumptions, what the...... and instrumental orchestrations have potential shortcomings since the technologies that currently exist in school contexts are rather different from the technologies instrumental genesis was originally developed to study.......This paper investigates the origins of the instrumental genesis and instrumental orchestrations frameworks. This is done by reviewing instrumented activity situations, instrumental genesis, and instrumental orchestrations with the purpose of identifying their epistemological assumptions, what...

  5. Genetics Home Reference: familial focal epilepsy with variable foci

    Science.gov (United States)

    ... with FFEVF have developed psychiatric disorders (such as schizophrenia ), behavioral problems, or intellectual disability. It is unclear ... 5 links) American Epilepsy Society Brain Foundation (Australia) CURE: Citizens United for Research in Epilepsy Epilepsy Foundation ...

  6. Utilisation of radiolabeled antibiotic for the diagnosis of infectious foci

    International Nuclear Information System (INIS)

    Khammassi, Sabrine; Gharbi, Sabrine

    2009-01-01

    Nuclear imaging is a non-invasive exploration technique, used for rapid diagnostic of infectious disease .Thus, for osteoarticular infection scintigraphic techniques were proposed to ameliorate the diagnostic sensibility and the use of radiolabeled antibiotics as imaging agents of infectious loci become more and more recognized. In this work, a new sulfanil amid derivative, the N sulfanilamide-ferrocene-carboxamide was chemically synthesized then labeled with technetium-99m, with a radiochemical yield, 87 pour cent. In in-vitro studies were done with E.coli. first , the up-take of labeled molecule was estimated as 40 pour cent. Then, the bacteriostatic al effect of the molecule was de terminated by considering the Optical Density at 600 nm. The obtained results, encourage us to do more, with biodistribution on normal and infected mice; with Staphylococcus aureus. Then to carry out scintigraphic imaging with gamma camera to check out the potentiality of the molecule as an infectious imaging agent. (Author)

  7. A produção do lugar de transmissão da leishmaniose tegumentar: o caso da Localidade Pau da Fome na cidade do Rio de Janeiro, Brasil Production of transmission foci for cutaneous leishmaniasis: the case of Pau da Fome, Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Hélia Kawa

    2010-08-01

    Full Text Available Este trabalho analisa as características de um dos lugares de transmissão de maior relevância da leishmaniose tegumentar na cidade do Rio de Janeiro, Brasil, considerando sua configuração territorial e as relações desta com processos de organização do espaço. Utilizou-se o modelo de análise do processo de ocupação e organização do espaço urbano, em escala local, considerando-se as novas funções adquiridas pelos elementos espaciais expressos por diferentes relações de trabalho, uso do solo e valor da terra. Empregaram-se técnicas de geoprocessamento e de classificação de imagens obtidas por sensoriamento remoto, localização de domicílios e casos de leishmaniose tegumentar, associados a dados qualitativos sobre o processo histórico de ocupação e uso do solo. A análise mostrou áreas com distintas condições de vulnerabilidade, e que mudanças destas condições viabilizaram a produção da epidemia em um determinado período e sua posterior redução. O estudo contribui para o monitoramento da enfermidade em nível local e para a aplicação de medidas eficazes para as ações de vigilância e controle da leishmaniose tegumentar.This study analyzes the characteristics of one of the main foci for cutaneous leishmaniasis transmission in the city of Rio de Janeiro, Brazil, examining its territorial configuration and the relations with spatial organization processes. An analytical model was applied to the process of occupation and organization of urban space on a local scale, considering the new functions acquired by the spatial elements expressed by different work relations, land use, and land value. The study employed geoprocessing techniques and classification of images obtained by remote sensing, localization of households, and cases of cutaneous leishmaniasis, associated with qualitative data on the historical process of land occupation and use. The analysis detected areas with distinct conditions of vulnerability

  8. Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

    Directory of Open Access Journals (Sweden)

    M.V.O. Vespúcio

    2008-04-01

    Full Text Available Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH. Three groups of 32 male Wistar rats were treated as follows: group 1 (G1 had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC; G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32 did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH. Crypt fission index, ß-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ß-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.

  9. Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

    OpenAIRE

    Ho, Ket Li; Chong, Pei Pei; Yazan, Latifah Saiful; Ismail, Maznah

    2012-01-01

    Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rat...

  10. Tales from the crypt : Fingerprinting attacks on encrypted channels by way of retainting

    NARCIS (Netherlands)

    Valkering, Michael; Slowinska, Asia; Bos, Herbert

    2009-01-01

    Paradoxically, encryption makes it hard to detect, finge