Sensitivity of Raman spectroscopy to normal patient variability

Science.gov (United States)

Vargis, Elizabeth; Byrd, Teresa; Logan, Quinisha; Khabele, Dineo; Mahadevan-Jansen, Anita

2011-11-01

Many groups have used Raman spectroscopy for diagnosing cervical dysplasia; however, there have been few studies looking at the effect of normal physiological variations on Raman spectra. We assess four patient variables that may affect normal Raman spectra: Race/ethnicity, body mass index (BMI), parity, and socioeconomic status. Raman spectra were acquired from a diverse population of 75 patients undergoing routine screening for cervical dysplasia. Classification of Raman spectra from patients with a normal cervix is performed using sparse multinomial logistic regression (SMLR) to determine if any of these variables has a significant effect. Results suggest that BMI and parity have the greatest impact, whereas race/ethnicity and socioeconomic status have a limited effect. Incorporating BMI and obstetric history into classification algorithms may increase sensitivity and specificity rates of disease classification using Raman spectroscopy. Studies are underway to assess the effect of these variables on disease.

Software reliability growth models with normal failure time distributions

International Nuclear Information System (INIS)

Okamura, Hiroyuki; Dohi, Tadashi; Osaki, Shunji

2013-01-01

This paper proposes software reliability growth models (SRGM) where the software failure time follows a normal distribution. The proposed model is mathematically tractable and has sufficient ability of fitting to the software failure data. In particular, we consider the parameter estimation algorithm for the SRGM with normal distribution. The developed algorithm is based on an EM (expectation-maximization) algorithm and is quite simple for implementation as software application. Numerical experiment is devoted to investigating the fitting ability of the SRGMs with normal distribution through 16 types of failure time data collected in real software projects

Metabolic alterations due to caloric restriction and every other day feeding in normal and growth hormone receptor knockout mice.

Science.gov (United States)

Westbrook, Reyhan; Bonkowski, Michael S; Arum, Oge; Strader, April D; Bartke, Andrzej

2014-01-01

Mutations causing decreased somatotrophic signaling are known to increase insulin sensitivity and extend life span in mammals. Caloric restriction and every other day (EOD) dietary regimens are associated with similar improvements to insulin signaling and longevity in normal mice; however, these interventions fail to increase insulin sensitivity or life span in growth hormone receptor knockout (GHRKO) mice. To investigate the interactions of the GHRKO mutation with caloric restriction and EOD dietary interventions, we measured changes in the metabolic parameters oxygen consumption (VO2) and respiratory quotient produced by either long-term caloric restriction or EOD in male GHRKO and normal mice. GHRKO mice had increased VO2, which was unaltered by diet. In normal mice, EOD diet caused a significant reduction in VO2 compared with ad libitum (AL) mice during fed and fasted conditions. In normal mice, caloric restriction increased both the range of VO2 and the difference in minimum VO2 between fed and fasted states, whereas EOD diet caused a relatively static VO2 pattern under fed and fasted states. No diet significantly altered the range of VO2 of GHRKO mice under fed conditions. This provides further evidence that longevity-conferring diets cause major metabolic changes in normal mice, but not in GHRKO mice.

Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

Science.gov (United States)

Stubbs, Sharron A; Webber, Lisa J; Stark, Jaroslav; Rice, Suman; Margara, Raul; Lavery, Stuart; Trew, Geoffrey H; Hardy, Kate; Franks, Stephen

2013-08-01

Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. This was a laboratory-based study, using clinical tissue samples. A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

In vitro sensitivity of normal and hereditary retinoblastoma fibroblasts to DNA-damaging agents

International Nuclear Information System (INIS)

Woods, W.G.; Byrne, T.D.

1986-01-01

We investigated the ability of nine fibroblast cell strains from patients with the hereditary form of retinoblastoma (RB) to handle various types of DNA-damaging agents and compared the results with those obtained in nine normal strains. Cell strains were exposed to gamma-radiation, which causes DNA scission; actinomycin D, a DNA-intercalating agent; and mitomycin C, a bifunctional alkylating agent leading to DNA-DNA cross-linking. Cell strains were studied for their ability to survive in a cytotoxicity assay. Nine normal strains exhibited a mean D0 (inverse of the slope of the straight line portion of the survival curve) of 134-178 cGy after radiation exposure, compared to a range of 119-186 cGy in the nine RB strains (P = 0.33). Similarly, exposure to actinomycin D led to D0 values of 0.024-0.069 microgram/ml in the nine normal strains and D0 values of 0.016-0.067 microgram/ml in the RB strains (P = 0.64). The nine RB strains did exhibit a small overall increase in sensitivity after exposure to mitomycin C, with D0 values ranging from 0.14-0.32 microgram/ml versus 0.19-0.66 microgram/ml in the nine normal strains (P = 0.002); however, when the two most resistant normal strains were excluded from analysis, results were similar. Three RB cell strains derived from individuals who had either developed second cancers or who had a family history of additional sarcomas consistently exhibited increases in sensitivity to all three DNA-damaging agents studied compared with other hereditary RB cell strains as well as normal strains. The results suggest that normal human fibroblast cell strains exhibit a wide response to DNA-damaging agents, especially chemical agents. Most hereditary RB strains exhibit sensitivity well within the normal range; however, strains from RB patients predisposed to second cancers exhibit increases in sensitivity to DNA-damaging agents

Progressive loss of sensitivity to growth control by retinoic acid and transforming growth factor-beta at late stages of human papillomavirus type 16-initiated transformation of human keratinocytes.

Science.gov (United States)

Creek, K E; Geslani, G; Batova, A; Pirisi, L

1995-01-01

Retinoids (vitamin A and its natural and synthetic derivatives) have shown potential as chemopreventive agents, and diets poor in vitamin A and/or its precursor beta-carotene have been linked to an increased risk of cancer at several sites including the cervix. Human papillomavirus (HPV) plays an important role in the etiology of cervical cancer. We have developed an in vitro model of cancer progression using human keratinocytes (HKc) immortalized by HPV16 DNA (HKc/HPV16). Although immortal, early passage HKc/HPV16, like normal HKc, require epidermal growth factor (EGF) and bovine pituitary extract (BPE) for proliferation and undergo terminal differentiation in response to serum and calcium. However, following prolonged culture, growth factor independent HKc/HPV16 lines that no longer require EGF and BPE can be selected (HKc/GFI). Further selection of HKc/GFI produces lines that are resistant to serum- and calcium- induced terminal differentiation (HKc/DR). HKc/DR, but not early passage HKc/HPV16, are susceptible to malignant conversion following transfection with viral Harvey ras or Herpes simplex virus type II DNA. We have investigated the sensitivity of low to high passage HKc/HPV16 and HKc/GFI to growth control by all-trans-retinoic acid (RA, an active metabolite of vitamin A). Early passage HKc/HPV16 are very sensitive to growth inhibition by RA, and in these cells RA decreases the expression of the HPV16 oncogenes E6 and E7. However, as the cells progress in culture they lose their sensitivity to RA. Growth inhibition by RA may be mediated through the cytokine transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell proliferation. RA treatment of HKc/HPV16 and HKc/GFI results in a dose-and time-dependent induction (maximal of 3-fold) in secreted levels of TGF-beta. Also, Northern blot analysis of mRNA isolated from HKc/HPV16 demonstrated that RA treatment induced TGF-beta 1 and TGF-beta 2 expression about 3- and 50-fold, respectively

Role of growth factors in the growth of normal and transformed cells

International Nuclear Information System (INIS)

Lokeshwar, V.B.

1989-01-01

Growth factors play an important role in the growth of normal cells. However, their untimely and/or excess production leads to neoplastic transformation. The role of growth factors in the growth of normal cells was studied by investigating the mechanism of transmodulation of the cell surface EGF receptor number by protamine. Protamine increased the EGF stimulated mitogenic response in Swiss mouse 3T3 cells and A431 cells by increasing the number of functionally active EGF receptors. Protamine also increased EGF receptor number in plasma membranes and solubilized membranes. This was evidenced by an increase in both 125 I-EGF-EGF-receptor complex and EGF stimulated phosphorylation of the EGF receptor. The solubilized EGF receptor was retained on a protamine-agarose gel indicating that protamine might increase EGF receptor number by directly activating cryptic EGF receptors in the plasma membranes. The role of growth factors in neoplastic transformation was studied by investigating the role of the oncogene v-sis in the growth of Simian sarcoma virus (SSV) transformed cells. The product of the oncogene v-sis is 94% homologous to the B chain of PDGF. This study found that (i) v-sis gene product is synthesized as a 32 kDa unglycosylated monomer which is glycosylated, dimerized and proteolytically processed into p36, p72, p68, p58, p44 and p27 mol. wt. species respectively. (ii) p36, p72, p68 and p58 are very likely formed in the endoplasmic reticulum and/or Golgi complex. A fraction of newly synthesized p72, p68 and p58 is degraded intracellularly at a fast rate. (iii) p44 is a secretory product which remains tightly associated with the cell surface. p44 is recaptured by the cells through interaction with cell surface PDGF receptors and degraded into p27. (iv) During long term cultures p44 is extracellularly cleaved into a 27 kDa product

Climate sensitivity of shrub growth across the tundra biome

DEFF Research Database (Denmark)

Myers-Smith, Isla H.; Elmendorf, Sarah C.; Beck, Pieter S.A.

2015-01-01

Rapid climate warming in the tundra biome has been linked to increasing shrub dominance1–4. Shrub expansion can modify climate by altering surface albedo, energy and water balance, and permafrost2,5–8, yet the drivers of shrub growth remain poorly understood. Dendroecological data consisting...... of multi-decadal time series of annual shrub growth provide an underused resource to explore climate–growth relationships. Here, we analyse circumpolar data from 37 Arctic and alpine sites in 9 countries, including 25 species, and 42,000 annual growth records from 1,821 individuals. Our analyses...... demonstrate that the sensitivity of shrub growth to climate was: (1) heterogeneous, with European sites showing greater summer temperature sensitivity than North American sites, and (2) higher at sites with greater soil moisture and for taller shrubs (for example, alders and willows) growing at their northern...

Normal variation in early parental sensitivity predicts child structural brain development.

Science.gov (United States)

Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning

2015-10-01

Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Renal artery pulsatility index and renal volume: Normal fetuses versus growth-retarded fetuses

International Nuclear Information System (INIS)

Lee, Kyung Soon; Woo, Bock Hi

2001-01-01

To evaluate the blood flow velocity waveform of the renal artery and renal volume of growth-retarded fetuses and to compare them with those of normal fetuses. Pulsatility index of the renal artery and renal volume measured by three-dimensional ultrasonography were obtained from seventy eight normal fetuses at the gestational age from twenty five to thirty nine weeks and eighteen intrauterine growth retarded fetuses whose weight was below ten percentile at birth. We studied changes of the pulsatility index of the renal artery and renal volume according to the gestational age and compared with those of growth-retarded fetuses. Pulsatility index (PI) of the fetal renal artery decreased throughout the gestational period (r=0.703, p<0.0001). In growth-retarded fetuses, despite of abnormal doppler velocity waveform of the middle cerebral artery, which was showing fetal hypoxia, the renal PI was not increased significantly. The fetal renal volume increased throughout the gestational period (r=0.834, p<0.0001) whereas in growth-retarded fetuses, all renal volume was below fifth percentile of normal fetuses. In growth-retarded fetuses, fetal renal volume was decreased significantly without change of the renal vascular flow. Therefore, the fetal renal volume measured by three-dimensional ultrasonography may be a helpful parameter in the diagnosis of growth-retarded fetuses.

Renal artery pulsatility index and renal volume: Normal fetuses versus growth-retarded fetuses

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Soon; Woo, Bock Hi [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

2001-06-15

To evaluate the blood flow velocity waveform of the renal artery and renal volume of growth-retarded fetuses and to compare them with those of normal fetuses. Pulsatility index of the renal artery and renal volume measured by three-dimensional ultrasonography were obtained from seventy eight normal fetuses at the gestational age from twenty five to thirty nine weeks and eighteen intrauterine growth retarded fetuses whose weight was below ten percentile at birth. We studied changes of the pulsatility index of the renal artery and renal volume according to the gestational age and compared with those of growth-retarded fetuses. Pulsatility index (PI) of the fetal renal artery decreased throughout the gestational period (r=0.703, p<0.0001). In growth-retarded fetuses, despite of abnormal doppler velocity waveform of the middle cerebral artery, which was showing fetal hypoxia, the renal PI was not increased significantly. The fetal renal volume increased throughout the gestational period (r=0.834, p<0.0001) whereas in growth-retarded fetuses, all renal volume was below fifth percentile of normal fetuses. In growth-retarded fetuses, fetal renal volume was decreased significantly without change of the renal vascular flow. Therefore, the fetal renal volume measured by three-dimensional ultrasonography may be a helpful parameter in the diagnosis of growth-retarded fetuses.

Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role?

Science.gov (United States)

Setia, Sajita; Sridhar, M G; Koner, B C; Bobby, Zachariah; Bhat, Vishnu; Chaturvedula, Lata

2007-02-01

Thyroid hormones are necessary for normal brain development. We studied thyroid hormone profile and insulin sensitivity in intrauterine growth retarded (IUGR) newborns to find correlation between insulin sensitivity and thyroid status in IUGR newborns. Fifty IUGR and fifty healthy control infants were studied at birth. Cord blood was collected for determination of T(3), T(4), TSH, glucose and insulin levels. IUGR newborns had significantly lower insulin, mean+/-S.D., 5.25+/-2.81 vs. 11.02+/-1.85microU/ml, but significantly higher insulin sensitivity measured as glucose to insulin ratio (G/I), 9.80+/-2.91 vs. 6.93+/-1.08 compared to healthy newborns. TSH was also significantly higher 6.0+/-2.70 vs. 2.99+/-1.05microU/ml with significantly lower T(4), 8.65+/-1.95 vs. 9.77+/-2.18microg/dl, but similar T(3) levels, 100.8+/-24.36 vs. 101.45+/-23.45ng/dl. On stepwise linear regression analysis in IUGR infants, insulin sensitivity was found to have a significant negative association with T(4) and significant positive association with TSH. Thyroid hormones may play a role in increased insulin sensitivity at birth in IUGR.

On the fission gas release from oxide fuels during normal grain growth

International Nuclear Information System (INIS)

Paraschiv, M.C.; Paraschiv, A.; Glodeanu, F.

1997-01-01

A mathematical formalism for calculating the fission gas release from oxide fuels considering an arbitrary distribution of fuel grain size with only zero boundary condition for gas diffusion at the grain boundary is proposed. It has also been proved that it becomes unnecessary to consider the grain volume distribution function for fission products diffusion when the grain boundary gas resolution is considered, if thermodynamic forces on grain boundaries are only time dependent. In order to highlight the effect of the normal grain growth on fission gas release from oxide fuels Hillert's and Lifshitz and Slyozov's theories have been selected. The last one was used to give an adequate treatment of normal grain growth for the diffusion-controlled grain boundary movement in oxide fuels. It has been shown that during the fuel irradiation, the asymptotic form of the grain volume distribution functions given by Hillert and Lifshitz and Slyozov models can be maintained but the grain growth rate constant becomes time dependent itself. Experimental results have been used to correlate the two theoretical models of normal grain growth to the fission gas release from oxide fuels. (orig.)

Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

Science.gov (United States)

Vucic, Steve; Kiernan, Matthew C

2008-03-01

Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

Sensitivity Analysis of a Riparian Vegetation Growth Model

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Michael Nones

2016-11-01

Full Text Available The paper presents a sensitivity analysis of two main parameters used in a mathematic model able to evaluate the effects of changing hydrology on the growth of riparian vegetation along rivers and its effects on the cross-section width. Due to a lack of data in existing literature, in a past study the schematization proposed here was applied only to two large rivers, assuming steady conditions for the vegetational carrying capacity and coupling the vegetal model with a 1D description of the river morphology. In this paper, the limitation set by steady conditions is overcome, imposing the vegetational evolution dependent upon the initial plant population and the growth rate, which represents the potential growth of the overall vegetation along the watercourse. The sensitivity analysis shows that, regardless of the initial population density, the growth rate can be considered the main parameter defining the development of riparian vegetation, but it results site-specific effects, with significant differences for large and small rivers. Despite the numerous simplifications adopted and the small database analyzed, the comparison between measured and computed river widths shows a quite good capability of the model in representing the typical interactions between riparian vegetation and water flow occurring along watercourses. After a thorough calibration, the relatively simple structure of the code permits further developments and applications to a wide range of alluvial rivers.

Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

Science.gov (United States)

VanNasdale, Dean Allan, Jr.

2011-12-01

The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

Chemical modification of conventional cancer radiotherapy. Tumor sensitization combined with normal tissue protection

International Nuclear Information System (INIS)

Kagiya, Tsutomu

2006-01-01

Nitrotriazole radiosensitizer, Sanazole (AK-2123, N-(2'-methoxyethyl)-2-(3''-nitro-1''-triazolyl) acetamide) developed by Kyoto University group was studied by 18 groups of 7 countries on fundamental aspects and clinical studies by 30 groups of 12 countries, and reported its effects on tumor sensitization of conventional cancer radiotherapy. On the other hand, the glucosides of vitamin C (Ascorbic acid glucoside, (AsAG) and water soluble derivative of vitamin-E (α-tocopherol glucoside, TMG) developed by Kyoto University group were studied fundamentally by 4 groups of 4 countries and clinically by 2 groups of 2 countries, and reported their effects on normal tissue protection in cancer treatments. These two studies of tumor sensitization and normal tissue protection were proposed as an advanced strategy of conventional cancer radiotherapy. (author)

Assessment of retinal sensitivity using a time-saving strategy in normal individuals

Directory of Open Access Journals (Sweden)

Suzumura H

2012-11-01

Full Text Available Hirotaka Suzumura,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Ryoko Hyodo,4 Tairo Kimura5 1Eye Department, Nakano General Hospital, Tokyo, 2Yoshikawa Eye Clinic, Tokyo, 3Department of Ophthalmology, Ehime University, Ehime, 4Eye Department, Minami Matsuyama Hospital, Ehime, 5Ueno Eye Clinic, Tokyo, JapanBackground: The purpose of this study was to compare retinal sensitivities in normal individuals obtained using the Swedish Interactive Threshold Algorithm Standard (SITA-S on the Humphrey field analyzer with those obtained using the Dynamic strategy on the Octopus.Methods: Prior to visual field examinations, the background luminance, stimulus size, and exposure time with the Octopus 101 were conformed to the Humphrey field analyzer II settings. Volunteers over 20 years of age without apparent ophthalmic abnormalities were examined with the SITA-S central 30-2 program followed by the Dynamic 32 program. Eye with corrected visual acuity ≥0.8, refraction ≥ −6.0 diopters, and fields with satisfactory levels of reliability in SITA-S and Dynamic were selected.Results: Sixty-seven eyes from 67 normal individuals of mean age 51.3 ± 16.3 (range 22–76 years satisfied the selection criteria and were analyzed. Mean retinal sensitivity was significantly (P < 0.0001 higher with SITA-S (29.0 ± 2.4 dB than with Dynamic (26.8 ± 2.1 dB. Changes in retinal sensitivity with increasing age were significantly (P = 0.0003 greater with Dynamic (−0.09 ± 0.04 dB/year; 95% confidence interval [CI] −0.10 to −0.08 dB/year than with SITA-S (−0.07 ± 0.04 dB/year, 95% CI −0.08 to −0.06 dB/year. When classifying the visual field into three areas (central, mid-peripheral, and peripheral, retinal sensitivities with SITA-S were significantly higher in all areas than with Dynamic (P < 0.0001 for all three areas.Conclusion: Differences in Dynamic and SITA-S strategies may contribute to the differences in retinal sensitivities observed in normal individuals

Interface crack growth for anisotropic plasticity with non-normality effects

DEFF Research Database (Denmark)

Tvergaard, Viggo; Legarth, Brian Nyvang

2007-01-01

A plasticity model with a non-normality plastic flow rule is used to analyze crack growth along an interface between a solid with plastic anisotropy and an elastic substrate. The fracture process is represented in terms of a traction-separation law specified on the crack plane. A phenomenological...... an oscillating stress singularity, and with conditions of small scale yielding this solution is applied as boundary conditions on the outer edge of the region analyzed. Crack growth resistance curves are calculated numerically, and the effect of the near-tip mode mixity on the steady-state fracture toughness...

Enhanced insulin sensitivity in prepubertal children with constitutional delay of growth and development.

Science.gov (United States)

Wilson, Dyanne A; Hofman, Paul L; Miles, Harriet L; Sato, Tim A; Billett, Nathalie E; Robinson, Elizabeth M; Cutfield, Wayne S

2010-02-01

To test the hypothesis that prepubertal children with presumed constitutional delay of growth and development (CDGD) have enhanced insulin sensitivity and, therefore, insulin sensitivity is associated with later onset of puberty. Twenty-one prepubertal children with presumed CDGD and 23 prepubertal control children, underwent a frequently sampled intravenous glucose tolerance test to evaluate insulin sensitivity and other markers of insulin, glucose, and growth regulation. Children in the CDGD group were shorter and leaner than control subjects. Children with presumed CDGD were 40% more insulin sensitive (17.0 x 10(-4) min(-1)/[mU/L] versus 12.1 x 10(-4) min(-1)/[mU/L]; P = .0006) and had reduced acute insulin response, thus maintaining euglycemia (216 mU/L versus 330 mU/L; P = .02) compared with control subjects. In addition, the CDGD group had lower serum insulin-like growth factor binding protein 3 levels (3333 ng/mL versus 3775 ng/mL; P = .0004) and a trend toward lower serum insulin-like growth factor-II levels (794 ng/mL versus 911 ng/mL; P = .06). Prepubertal children with presumed CDGD have enhanced insulin sensitivity, supporting the hypothesis that insulin sensitivity is associated with timing of puberty. It may signify long-term biological advantages with lower risk of metabolic syndrome and malignancy. Copyright 2010 Mosby, Inc. All rights reserved.

Caffeine as a repair inhibitor and its action on the normal cell cycle in protozoa

International Nuclear Information System (INIS)

Eades, M.; Calkins, J.; Wheeler, J.

1987-01-01

Caffeine has been demonstrated to inhibit repair of ionizing radiation damage, UV, and chemical DNA damage. The mechanism of caffeine action is not completely established at the present time but it has been clearly demonstrated that excision repair is inhibited in prokaryotes. The levels of caffeine which inhibit DNA repair are well tolerated by unirradiated organisms but radiation might impose an extra stress which would cause the irradiated organism to die from the normal caffeine sensitive function. The authors have tested synchronized protozoans at various times in the growth cycle for caffeine sensitivity. They infer sensitivity by the measured disruption of the normal growth cycle induced by a pulse treatment with lethal levels of caffeine. Some parts (G1) of the cell cycle show little sensitivity while late cycle (late S) may be quite sensitive. The relationship of cyclic caffeine sensitivity to repair inhibition is not obvious

Using wavelength-normalized optical spectroscopy to improve the accuracy of bacteria growth rate quantification

Science.gov (United States)

McBirney, Samantha E.; Trinh, Kristy; Wong-Beringer, Annie; Armani, Andrea M.

2017-02-01

One of the fundamental analytical measurements performed in microbiology is monitoring and characterizing cell concentration in culture media. Measurement error will give rise to reproducibility problems in a wide range of applications, from biomanufacturing to basic research. Therefore, it is critical that the generated results are consistent. Single wavelength optical density (OD) measurements have become the preferred approach. Here, we compare the conventional OD600 technique with a multi-wavelength normalized scattering optical spectroscopy method to measure the growth rates of Pseudomonas aeruginosa and Staphylococcus aureus, two of the leading nosocomial pathogens with proven abilities to develop resistance. The multi-wavelength normalization process minimizes the impact of bacteria byproducts and environmental noise on the signal, thereby accurately quantifying growth rates with high fidelity at low concentrations. In contrast, due to poor absorbance and scattering at 600 nm, the classic OD600 measurement method is able to detect bacteria but cannot quantify the growth rate reliably. Our wavelength-normalization protocol to detect bacteria growth rates can be readily and easily adopted by research labs, given that it only requires the use of a standard spectrophotometer and implementation of straightforward data analysis. Measuring and monitoring bacteria growth rates play a critical role in a wide range of settings, spanning from therapeutic design and development to diagnostics and disease prevention. Having a full understanding of the growth cycles of bacteria known to cause severe infections and diseases will lead to a better understanding of the pathogenesis of these illnesses, leading to better treatment and, ultimately, the development of a cure.

Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

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Diana Bayer

2012-04-01

Full Text Available Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl-diphenyltetrazolium bromide assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes.Functional Foods in Health and Disease 2012, 2(4:72-85 Conclusions: The three tea extracts studied altered leukemic T lymphocyte

The effects of topical diclofenac, topical flurbiprofen, and humidity on corneal sensitivity in normal dogs.

Science.gov (United States)

Dorbandt, Daniel M; Labelle, Amber L; Mitchell, Mark A; Hamor, Ralph E

2017-03-01

To determine the immediate and chronic effects of topical 0.1% diclofenac and 0.03% flurbiprofen on corneal sensitivity in normal canine eyes. Eighteen normal, nonbrachycephalic dogs. A prospective, randomized, masked, crossover study was performed. To determine the immediate effects associated with treatment, the study drug was instilled into the eye every 5 min for five doses, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment and every 15 min post-treatment for 60 min. To determine the chronic effects, the study drug was instilled every 12 h for 30 days, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment on days 0 and 30. A washout period of at least 30 days occurred between drug crossover. Ambient temperature and humidity were measured throughout the study. After multiple instillations, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.67) or flurbiprofen (P = 0.54), with a median sensitivity of 25 mm (1.8 g/mm 2 ). After chronic dosing, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.82) or flurbiprofen (P = 0.56), with a median sensitivity of 35 mm (1.0 g/mm 2 ). Decreasing ambient humidity was associated with an increase in sensitivity measurements (P = 0.0001). Neither diclofenac nor flurbiprofen had an effect on corneal sensitivity after multiple-drops or twice-daily dosing for 30 days. Ambient humidity may have an effect on corneal sensitivity measurements, with a longer filament length eliciting a blink response at lower humidity. © 2016 American College of Veterinary Ophthalmologists.

Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity.

Science.gov (United States)

Baillargeon, Jean-Patrice; Carpentier, André

2007-10-01

To determine the effect of reducing insulin secretion on hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome (PCOS) and normal metabolic insulin sensitivity. Transversal assessment at baseline and prospective follow-up of lean PCOS group after 8 days of diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which suppresses LH. Clinical research center of an academic hospital. Nine lean women (body mass index PCOS and normal insulin levels, as well as 17 lean healthy women. Lean PCOS women were reassessed after 8 days of diazoxide and after 1 month of leuprolide, which suppresses LH. Androgen levels and insulin-stimulated glucose disposal (metabolic insulin sensitivity), determined by euglycemic-hyperinsulinemic clamp (M-value). Mean M-value of lean PCOS women (48.5 micromol/kg.min) was similar to lean control subjects (52.9 micromol/kg.min). They also had comparable anthropometric measures, lipids, fibrinogen, and plasminogen activator inhibitor 1. The LH did not change significantly after diazoxide, but was almost suppressed after leuprolide in the PCOS group. Androstenedione decreased significantly after diazoxide and even more after leuprolide. However, free T significantly decreased only after diazoxide in lean PCOS women. Diazoxide also increased SHBG significantly in this group. In women with typical PCOS and normal insulin levels and metabolic insulin sensitivity, reducing insulin secretion significantly decreased androgen and increased SHBG levels. These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.

Influence of lead on normal and abnormal cell-growth and on certain organs

Energy Technology Data Exchange (ETDEWEB)

Bell, W B

1924-02-09

The general poisonous effects of lead are described. Descriptions and discussions are presented concerning the toxic effects of lead preparations on heart, intestine, uterus, kidney, and blood. The influence of lead on normal growth is discussed, including effects on the development of hyacynth bulbs, the germination of seeds, the germination of frog's eggs, and the growth of tadpoles. The influences of lead on the cells concerned in the implantation of the ovum are also discussed. The effects of lead on abnormal cell growth are discussed. 17 references, 8 figures.

Metabolic regulation of mycobacterial growth and antibiotic sensitivity.

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Seung-Hun Baek

2011-05-01

Full Text Available Treatment of chronic bacterial infections, such as tuberculosis (TB, requires a remarkably long course of therapy, despite the availability of drugs that are rapidly bacteriocidal in vitro. This observation has long been attributed to the presence of bacterial populations in the host that are "drug-tolerant" because of their slow replication and low rate of metabolism. However, both the physiologic state of these hypothetical drug-tolerant populations and the bacterial pathways that regulate growth and metabolism in vivo remain obscure. Here we demonstrate that diverse growth-limiting stresses trigger a common signal transduction pathway in Mycobacterium tuberculosis that leads to the induction of triglyceride synthesis. This pathway plays a causal role in reducing growth and antibiotic efficacy by redirecting cellular carbon fluxes away from the tricarboxylic acid cycle. Mutants in which this metabolic switch is disrupted are unable to arrest their growth in response to stress and remain sensitive to antibiotics during infection. Thus, this regulatory pathway contributes to antibiotic tolerance in vivo, and its modulation may represent a novel strategy for accelerating TB treatment.

Sensitivity of ring growth and carbon allocation to climatic variation vary within ponderosa pine trees.

Science.gov (United States)

Kerhoulas, Lucy P; Kane, Jeffrey M

2012-01-01

Most dendrochronological studies focus on cores sampled from standard positions (main stem, breast height), yet vertical gradients in hydraulic constraints and priorities for carbon allocation may contribute to different growth sensitivities with position. Using cores taken from five positions (coarse roots, breast height, base of live crown, mid-crown branch and treetop), we investigated how radial growth sensitivity to climate over the period of 1895-2008 varies by position within 36 large ponderosa pines (Pinus ponderosa Dougl.) in northern Arizona. The climate parameters investigated were Palmer Drought Severity Index, water year and monsoon precipitation, maximum annual temperature, minimum annual temperature and average annual temperature. For each study tree, we generated Pearson correlation coefficients between ring width indices from each position and six climate parameters. We also investigated whether the number of missing rings differed among positions and bole heights. We found that tree density did not significantly influence climatic sensitivity to any of the climate parameters investigated at any of the sample positions. Results from three types of analyses suggest that climatic sensitivity of tree growth varied with position height: (i) correlations of radial growth and climate variables consistently increased with height; (ii) model strength based on Akaike's information criterion increased with height, where treetop growth consistently had the highest sensitivity and coarse roots the lowest sensitivity to each climatic parameter; and (iii) the correlation between bole ring width indices decreased with distance between positions. We speculate that increased sensitivity to climate at higher positions is related to hydraulic limitation because higher positions experience greater xylem tensions due to gravitational effects that render these positions more sensitive to climatic stresses. The low sensitivity of root growth to all climatic variables

A frozen-thawed in vitro-matured bovine oocyte derived calf with normal growth and fertility.

Science.gov (United States)

Otoi, T; Yamamoto, K; Koyama, N; Tachikawa, S; Suzuki, T

1996-08-01

The growth and fertility of a female calf obtained from a frozen-thawed bovine oocyte was assessed. The birth weight of the calf was lower than the mean birth weight of calves from in vitro fertilized embryos (IVF-controls) and calves obtained by artificial insemination (AI-controls). The growth rate of the calf up to 6 months was slower than that of the IVF-controls, but similar to that of the AI-controls. When the calf developed into a heifer (200 kg), she was inseminated with frozen semen and 280 days later delivered a male calf. The chromosoms of this cow were normal. These findings suggest that the growth and fertility of the calf derived from the frozen oocyte are normal.

Deuterium oxide normalizes blood pressure and vascular calcium uptake in Dahl salt-sensitive hypertensive rats

International Nuclear Information System (INIS)

Vasdev, S.; Prabhakaran, V.; Sampson, C.A.

1990-01-01

This study examined the effect of 25% deuterium oxide in drinking water on systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas of Dahl salt-sensitive rats on 0.4% (low) and 8% (high) sodium chloride (salt) diet. Twenty-four rats were divided into four groups. Groups I and II were on the low salt diet and groups III and IV on the high salt diet from 6 weeks of age. Additionally, at 10 weeks of age groups I and III were placed on 100% water and groups II and IV on 25% deuterium oxide. At 14 weeks, systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas were significantly higher (p less than 0.01) in rats on the high salt diet as compared with those on the low salt diet. Deuterium oxide intake normalized systolic blood pressure and aortic calcium uptake but not aortic rubidium 86 uptake in hypertensive rats on the high salt diet. Deuterium oxide had no effect on blood pressure or aortic calcium uptake in rats on the low salt diet. The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in salt-sensitive Dahl rats. Furthermore, deuterium oxide appears to normalize elevated blood pressure in salt-sensitive hypertensive rats by normalizing elevated vascular (aortic) calcium uptake

Self-reported cold sensitivity in normal subjects and in patients with traumatic hand injuries or hand-arm vibration syndrome

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Dahlin Lars B

2010-05-01

Full Text Available Abstract Background Cold sensitivity is a common and disabling complaint following hand injuries. The main purpose of this study was to describe self-reported consequences of cold sensitivity and the association with disability and health-related quality of life in patients with hand injuries or hand-arm vibration syndrome (HAVS and in normal subjects. Methods Responses to the Cold Intolerance Symptom Severity (CISS questionnaire, Potential Work Exposure Scale (PWES, Disability of the Arm, Shoulder and Hand (DASH and Short-Form 36 questionnaire (SF-36 were investigated in normal subjects (n = 94, hand injured patients (amputation and nerve injuries, n = 88 and patients with HAVS (n = 30. The results are presented as median (range, percent and mean deviation from norms. The Kruskal Wallis Test or Mann-Whitney U-Test were used to identify significant differences between multiple groups or subgroups. The Spearman rank correlation was used to study the relationship between cold sensitivity and disability. Results Abnormal cold sensitivity (CISS score > 50 was seen in 75% and 45% of patients with HAVS and a traumatic hand injury, respectively. Patients were significantly more exposed to cold in their work environment than the normal population, with a consequently negative effect on work ability due to cold sensitivity. Patients with abnormal cold sensitivity were more seriously disabled and had a poorer health-related quality of life than patients with normal cold sensitivity [higher DASH scores and e.g. significantly larger mean deviation from norms in the subscales Role Physical and Bodily Pain (SF-36]. Conclusion Severe and abnormal cold sensitivity may have a profound impact on work capacity, leisure, disability and health-related quality of life. It is frequently seen in patients with traumatic hand injuries and particularly apparent in patients with HAVS.

Variations in the Sensitivity of Shrub Growth to Climate Change along Arctic Environmental and Biotic Gradients

Science.gov (United States)

Beck, P. S. A.; Myers-Smith, I. H.; Elmendorf, S.; Georges, D.

2015-12-01

Despite evidence of rapid shrub expansion at many Arctic sites and the profound effects this has on ecosystem structure, biogeochemical cycling, and land-atmosphere feedbacks in the Arctic, the drivers of shrub growth remain poorly understood. The compilation of 41,576 annual shrub growth measurements made around the Arctic, allowed for the first systematic evaluation of the climate sensitivity of Arctic shrub growth, i.e. the strength of the relationship between annual shrub growth and monthly climate variables. The growth measurements were taken on 1821 plants of 25 species at 37 arctic and alpine sites, either as annual ring widths or as stem increments. We evaluated climate sensitivity of shrub growth for each genus-by-site combination in this data set based on the performance and parameters of linear mixed models that used CRU TS3.21 climate data as predictors of shrub growth between 1950 and 2010. 76% of genus-by-site combinations showed climate sensitive growth, but climate-growth relationships varied with soil moisture, species canopy height, and geographic position within the species ranges. Shrubs growing at sites with more soil moisture showed greater climate sensitivity, suggesting that water availability might limit shrub growth if continued warming isn't matched by a steady increase in soil moisture. Tall shrub species growing at their northern range limit were particularly climate sensitive causing climate sensitivity of shrubs to peak at the transition between Low and High Arctic, where carbon storage in permafrost is greatest. Local and regional studies have documented matching spatial and temporal patterns in dendrochronological measurements and satellite observations of vegetation indices both in boreal and Arctic regions. Yet the circumarctic comparison of patterns in dendrochronological and remote sensing data sets yielded poor levels of agreement. In much of the Arctic, steep environmental gradients generate fine spatial patterns of vegetation

Proteome Differences in Placenta and Endometrium between Normal and Intrauterine Growth Restricted Pig Fetuses.

Directory of Open Access Journals (Sweden)

Fang Chen

Full Text Available Uteroplacental tissue plays a key role in substance exchanges between maternal and fetal circulation, and, therefore, in the growth and development of fetuses. In this study, proteomics and western blotting were applied to investigate the changes of proteome in the placenta and endometrium of normal and intrauterine growth restriction (IUGR porcine fetuses during mid to late pregnancy (D60, 90, and 110 of gestation. Our results showed that proteins participating in cell structure, energy metabolism, stress response, cell turnover, as well as transport and metabolism of nutrients were differentially expressed in placenta and endometrium between normal and IUGR fetuses. Analysis of functions of these proteins suggests reductions in ATP production and nutrients transport, increases in oxidative stress and apoptosis, and impairment of cell metabolism in IUGR fetuses. Collectively, our findings aid in understanding of the mechanisms responsible for uteroplacental dysfunction in IUGR fetus, and are expected to provide new strategies to reduce fetal growth restriction in pigs and other mammals.

Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

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Magnusson Magnus K

2010-07-01

Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

Canine tracheal epithelial cells are more sensitive than rat tracheal epithelial cells to transforming growth factor beta induced growth inhibition

International Nuclear Information System (INIS)

Hubbs, A.F.; Hahn, F.F.; Kelly, G.; Thomassen, D.G.

1988-01-01

Transforming growth factor beta (TGFβ) markedly inhibited growth of canine tracheal epithelial (CTE) cells. Reduced responsiveness to TGFβ-induced growth inhibition accompanied neoplastic progression of these cells from primary to transformed to neoplastic. This was similar to the relationship between neoplastic progression and increased resistance to TGFβ-induced growth inhibition seen for rat tracheal epithelial (RTE) cells. The canine cells were more sensitive than rat cells to TGFβ-induced growth inhibition at all stages in the neoplastic process. (author)

Growth monitoring in children with low and normal birth weight up to two years: A retrospective cohort study

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Mina Danaei

2016-09-01

Full Text Available Objective: This study was conducted aimed to compare the growth indices in 2 years old children with a history of low birth weight with normal birth weight children.Methods: Current retrospective cohort study on all two-year children with low birth weight and three times the normal weight children covered by health centers of Kahnooj, was conducted in 2015. Cares at birth, 1, 2, 4, 6, 7, 9, 12, 15, 18 and 24 months of age were studied and, child growth indices (weight, height, head circumference, along with some demographic variables were studied. Information were entered SPSS version 20 and the analysis was performed.Results: There were significant differences in children's growth of both groups in all periods of care. Despite the same slope, growth pattern in children showed a significant difference. Young mother, girl sex of baby and preterm birth are predictor factors of low birth weight.Conclusion: Trends and growth patterns of weight, height and head circumference in underweight children have significant difference with normal children and, despite the same slope, these children can not compensate for the backwardness of its growth to the age of two. So you need to plot separate growth curves for these children and, possible preventive measures should be taken to prevent bearing underweight baby.

Kidney function and size in normal subjects before and during growth hormone administration for one week

DEFF Research Database (Denmark)

Gammelgaard, Jens; Orskov, H; Andersen, A R

1981-01-01

Kidney function and size were studied in seven normal male subjects before and after administration of highly purified human growth hormone for 1 week. Glomerular filtration rate, renal plasma flow (steady-state infusion technique with urinary collections using 125I-iothalamate and 131I-hippuran)......Kidney function and size were studied in seven normal male subjects before and after administration of highly purified human growth hormone for 1 week. Glomerular filtration rate, renal plasma flow (steady-state infusion technique with urinary collections using 125I-iothalamate and 131I...

Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia.

NARCIS (Netherlands)

Imel, E.A.; Peacock, M.; Pitukcheewanont, P.; Heller, H.J.; Ward, LM; Shulman, D.; Kassem, M.; Rackoff, P.; Zimering, M.; Dalkin, A.; Drobny, E.; Colussi, G.; Shaker, J.L.; Hoogendoorn, E.H.; Hui, S.L.; Econs, M.J.

2006-01-01

CONTEXT: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in

Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia

DEFF Research Database (Denmark)

Imel, Erik A; Peacock, Munro; Pitukcheewanont, Pisit

2006-01-01

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors t...

Stability and Sensitive Analysis of a Model with Delay Quorum Sensing

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Zhonghua Zhang

2015-01-01

Full Text Available This paper formulates a delay model characterizing the competition between bacteria and immune system. The center manifold reduction method and the normal form theory due to Faria and Magalhaes are used to compute the normal form of the model, and the stability of two nonhyperbolic equilibria is discussed. Sensitivity analysis suggests that the growth rate of bacteria is the most sensitive parameter of the threshold parameter R0 and should be targeted in the controlling strategies.

Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

Science.gov (United States)

Balaz, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Gajdosechova, Lucia; Vlcek, Miroslav; Janakova, Zuzana; Fedeles, Jozef; Pura, Mikulas; Gasperikova, Daniela; Smith, Steven R; Tkacova, Ruzena; Klimes, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

2015-02-01

Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown. © 2014 The Obesity Society.

Sensitivity of Fit Indices to Misspecification in Growth Curve Models

Science.gov (United States)

Wu, Wei; West, Stephen G.

2010-01-01

This study investigated the sensitivity of fit indices to model misspecification in within-individual covariance structure, between-individual covariance structure, and marginal mean structure in growth curve models. Five commonly used fit indices were examined, including the likelihood ratio test statistic, root mean square error of…

Normal function of the hypothalamic-pituitary growth axis in three dwarf Friesian foals.

Science.gov (United States)

de Graaf-Roelfsema, E; Back, W; Keizer, H A; Stout, T A E; van der Kolk, J H

2009-09-26

Serial blood samples were collected from three dwarf Friesian foals to examine their endogenous growth hormone (GH) profiles, and the integrity of the GH-insulin-like growth factor-1 (IGF-1) axis was tested in one of them by examining its responses to the administration of GH-releasing hormone (GHRH) and to 10 days of treatment with recombinant equine GH. The basal serum concentrations of IGF-1 in the three dwarf foals were compared with those in nine age-matched normal foals. All the dwarf foals secreted endogenous GH. Stimulation with 7.0 microg/kg GHRH led to a 1400 per cent increase in plasma GH concentration in the dwarf foal tested, and 10 daily subcutaneous treatments with 20 microg/kg recombinant equine GH led to a 100 per cent increase in its serum IGF-1 concentration. The basal serum concentrations of IGF-1 in the dwarf foals were not significantly different from those of the normal foals.

Expression of UV-irradiated adenovirus in normal and UV-sensitive Chinese hamster ovary cells

International Nuclear Information System (INIS)

Rainbow, A.J.

1985-01-01

The chinese hamster ovary (CHO) cell mutants UV-20, UV-24, and UV-41 are abnormally sensitive to UV and harbour various defects lin their ability to repair cellular DNA. This study has examined the expression of UV-irradiated AD2 in these cells. HCR of UV-irradiated Ad2, as measured by viral structural antigen (Vag) formation or progeny production, was found to be similar for the normal and the UV-sensitive CHO strains. UV-irradiation of Ad2 (1200 J/m/sup 2/) resulted in a delay of Vag expression of 18 hours in normal human fibroblasts, which is thought to reflect the time required for removal of UV-induced lesions from the DNA before viral DNA synthesis can proceed. However, a similar UV-irradiation of Ad2 did not result in a delay of Vag expression for infection of CHO cells, suggesting that UV-induced lesions in Ad2 DNA do not inhibit its replication in CHO cells. These results indicate a fundamental difference in the processing of UV-irradiated AD2-DNA in CHO as compared to human cells

Statistical mechanics of normal grain growth in one dimension: A partial integro-differential equation model

International Nuclear Information System (INIS)

Ng, Felix S.L.

2016-01-01

We develop a statistical-mechanical model of one-dimensional normal grain growth that does not require any drift-velocity parameterization for grain size, such as used in the continuity equation of traditional mean-field theories. The model tracks the population by considering grain sizes in neighbour pairs; the probability of a pair having neighbours of certain sizes is determined by the size-frequency distribution of all pairs. Accordingly, the evolution obeys a partial integro-differential equation (PIDE) over ‘grain size versus neighbour grain size’ space, so that the grain-size distribution is a projection of the PIDE's solution. This model, which is applicable before as well as after statistically self-similar grain growth has been reached, shows that the traditional continuity equation is invalid outside this state. During statistically self-similar growth, the PIDE correctly predicts the coarsening rate, invariant grain-size distribution and spatial grain size correlations observed in direct simulations. The PIDE is then reducible to the standard continuity equation, and we derive an explicit expression for the drift velocity. It should be possible to formulate similar parameterization-free models of normal grain growth in two and three dimensions.

Osteoarthritic human cartilage is more sensitive to transforming growth factor beta than is normal cartilage

NARCIS (Netherlands)

Lafeber, F. P.; Vander Kraan, P. M.; Huber-Bruning, O.; Vanden Berg, W. B.; Bijlsma, J. W.

1993-01-01

Osteoarthritis is a degenerative joint disease, characterized by the destruction of the articular cartilage. One of the first changes in the osteoarthritic articular cartilage is a reduction in proteoglycan content. In this study we demonstrate that transforming growth factor beta (TGF beta), a

Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

Science.gov (United States)

Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

2018-05-01

Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

Epidermal growth factor receptor-induced activato protein 1 activity controls density-dependent growht inhibition in normal rat kidney fibroblasts.

NARCIS (Netherlands)

Hornberg, J.J.; Dekker, H.; Peters, P.H.J.; Langerak, P.; Westerhoff, H.V.; Lankelma, J.; Zoelen, E.J.J.

2006-01-01

Density-dependent growth inhibition secures tissue homeostasis. Dysfunction of the mechanisms, which regulate this type of growth control is a major cause of neoplasia. In confluent normal rat kidney (NRK) fibroblasts, epidermal growth factor (EGF) receptor levels decline, ultimately rendering these

Growth of normal or irradiated vaginal epithelium in in vivo cultures

International Nuclear Information System (INIS)

Tileva, M.

1975-01-01

Growth of normal or irradiated vaginal epithelium was studied by the method of F.M.Lazarenko (1959). Pieces of vaginal mucosa from immature albino rats, normal or exposed to 1000 or 2000 R, were embedded in celloidin and implanted into the abdominal wall of female immature rats. Implants were recovered for histological examinations from day 1 to day 10 after surgery. At day 1 post implantation, vaginal epithelium was found to have dedifferentiated. Cells showed a high mitotic index (MI = 16.2%). Cell proliferation progressed further to attain a peak rate at 3 days (MI = 32.7%). At 5 days, newly formed structures began to differentiate, and concurrently manifested a gradual decrease in cell proliferative activity (at 10 days, MI = 15.6%). Following exposure to 1000 R, vaginal epithelium displayed a similar pattern of growth and differentiation, the only difference from non-irradiated epithelium being that there was a transient mitotic delay over the first 3 days; mitotic rates reached a peak at 5 days (MI = 47.0%), were still high at 7 days (MI = 31.3%), and fell to 19% at 10 days. With this longer proliferation period, newly formed structures appeared ''luxuriant''. After a dose of 2000 R, vaginal epithelium failed to show any signs of growth at all investigated time intervals. These data are in agreement with evidence obtained by K.M.Svetikova (1961) and L.I.Chekulaeva (1969, 1974) for a good restitutional ability of epithelia of epidermal origin following exposure to 1200 R X-rays. By Warren' rule (1944), i.e., that cells should be considered radiosensitive if severely damaged by less than 2500 R, vaginal epithelium cells may be designated as relatively susceptible to radiation. (author)

Effect of noisy stimulation on neurobiological sensitization systems and its role for normal and pathological physiology

Science.gov (United States)

Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian

2004-03-01

Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.

Haloxyfop mode of action in liquid cultures of proso millet: An analysis of haloxyfop sensitivity changes during growth

International Nuclear Information System (INIS)

Irzyk, G.P.

1989-01-01

Haloxyfop is a grass-selective herbicide that inhibits acetyl-CoA carboxylase in species that are not tolerant to the herbicide. Liquid cultures of proso millet (Panicum miliaceum) cells treated with haloxyfop at different phases of growth exhibited different levels of sensitivity to the herbicide. Treatment of 1-d cultures with 1 μM haloxyfop completely inhibited growth within 48 h. In contrast, 1 mM haloxyfop was required to elicit a similar response in 4-, 7-, or 10-d cultures. Calculated IC 50 values indicated a 300-fold decrease in haloxyfop sensitivity during the period from 1 to 4 d. This period of growth coincided with the greatest increase in cell number during culture growth and suggested that dividing cells are most sensitive to haloxyfop. Uptake and metabolism of 14 C-haloxyfop in 1-d and 4-d cultures were compared. In both cultures, amounts of radiolabel uptake were similar. Almost all radioactivity extracted from 1- and 4-d cells was present as the parent compound. These results suggested that the sensitivity change was related to other factors. Acetyl-CoA carboxylase activity of proso millet cells, measured in vitro by the acetyl-CoA-dependent incorporation of 14 C-bicarbonate into an acid-stable product, was essentially constant during culture growth. Micromolar concentrations of haloxyfop significantly inhibited acetyl-CoA carboxylase activity from both sensitive and insensitive cultures. Thus, the change in the sensitivity of cultures to haloxyfop was not correlated with changes in acetyl-CoA carboxylase abundance, activity, or sensitivity to haloxyfop during culture growth. In vivo incorporation of 14 C-acetate into lipids was decreased by 1 μM haloxyfop in both 1-d and 4-d cultures at the earliest sampling times but the amount of inhibition was significantly greater in the sensitive cultures

Neuronal growth on L- and D-cysteine self-assembled monolayers reveals neuronal chiral sensitivity.

Science.gov (United States)

Baranes, Koby; Moshe, Hagay; Alon, Noa; Schwartz, Shmulik; Shefi, Orit

2014-05-21

Studying the interaction between neuronal cells and chiral molecules is fundamental for the design of novel biomaterials and drugs. Chirality influences all biological processes that involve intermolecular interaction. One common method used to study cellular interactions with different enantiomeric targets is the use of chiral surfaces. Based on previous studies that demonstrated the importance of cysteine in the nervous system, we studied the effect of L- and D-cysteine on single neuronal growth. L-Cysteine, which normally functions as a neuromodulator or a neuroprotective antioxidant, causes damage at elevated levels, which may occur post trauma. In this study, we grew adult neurons in culture enriched with L- and D-cysteine as free compounds or as self-assembled monolayers of chiral surfaces and examined the effect on the neuronal morphology and adhesion. Notably, we have found that exposure to the L-cysteine enantiomer inhibited, and even prevented, neuronal attachment more severely than exposure to the D-cysteine enantiomer. Atop the L-cysteine surfaces, neuronal growth was reduced and degenerated. Since the cysteine molecules were attached to the surface via the thiol groups, the neuronal membrane was exposed to the molecular chiral site. Thus, our results have demonstrated high neuronal chiral sensitivity, revealing chiral surfaces as indirect regulators of neuronal cells and providing a reference for studying chiral drugs.

Balanced levels of nerve growth factor are required for normal pregnancy progression.

Science.gov (United States)

Frank, Pierre; Barrientos, Gabriela; Tirado-González, Irene; Cohen, Marie; Moschansky, Petra; Peters, Eva M; Klapp, Burghard F; Rose, Matthias; Tometten, Mareike; Blois, Sandra M

2014-08-01

Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P(+) nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation. © 2014 Society for Reproduction and Fertility.

Contrast sensitivity measured by two different test methods in healthy, young adults with normal visual acuity.

Science.gov (United States)

Koefoed, Vilhelm F; Baste, Valborg; Roumes, Corinne; Høvding, Gunnar

2015-03-01

This study reports contrast sensitivity (CS) reference values obtained by two different test methods in a strictly selected population of healthy, young adults with normal uncorrected visual acuity. Based on these results, the index of contrast sensitivity (ICS) is calculated, aiming to establish ICS reference values for this population and to evaluate the possible usefulness of ICS as a tool to compare the degree of agreement between different CS test methods. Military recruits with best eye uncorrected visual acuity 0.00 LogMAR or better, normal colour vision and age 18-25 years were included in a study to record contrast sensitivity using Optec 6500 (FACT) at spatial frequencies of 1.5, 3, 6, 12 and 18 cpd in photopic and mesopic light and CSV-1000E at spatial frequencies of 3, 6, 12 and 18 cpd in photopic light. Index of contrast sensitivity was calculated based on data from the three tests, and the Bland-Altman technique was used to analyse the agreement between ICS obtained by the different test methods. A total of 180 recruits were included. Contrast sensitivity frequency data for all tests were highly skewed with a marked ceiling effect for the photopic tests. The median ICS for Optec 6500 at 85 cd/m2 was -0.15 (95% percentile 0.45), compared with -0.00 (95% percentile 1.62) for Optec at 3 cd/m2 and 0.30 (95% percentile 1.20) FOR CSV-1000E. The mean difference between ICSFACT 85 and ICSCSV was -0.43 (95% CI -0.56 to -0.30, p<0.00) with limits of agreement (LoA) within -2.10 and 1.22. The regression line on the difference of average was near to zero (R2=0.03). The results provide reference CS and ICS values in a young, adult population with normal visual acuity. The agreement between the photopic tests indicated that they may be used interchangeably. There was little agreement between the mesopic and photopic tests. The mesopic test seemed best suited to differentiate between candidates and may therefore possibly be useful for medical selection purposes. �

Defining the residual risk of adverse perinatal outcome in growth restricted fetuses with normal umbilical artery blood flow.

LENUS (Irish Health Repository)

O'Dwyer, Vicky

2014-07-25

To determine the cause of adverse perinatal outcome in fetal growth restriction(FGR) where umbilical artery Doppler(UA) was normal, as identified from the Prospective Observational Trial to Optimize Pediatric Health(PORTO). We compared cases of adverse outcome where UA Doppler was normal and abnormal.

Inhibitor production by normal rat tracheal epithelial cells influences the frequency of spontaneous and X-ray-induced enhanced growth variants

International Nuclear Information System (INIS)

Terzaghi-Howe, M.

1989-01-01

A cell culture model was used to assay for the induction of cell populations with enhanced growth capacity in culture in irradiated normal rat tracheal epithelial cells (NTEC). Some growth conditions appear to favor the proliferation of both normal and carcinogen-exposed populations, while others appear to select for populations previously exposed to carcinogen. In the present report we focus on what growth conditions are critical for controlling the emergence of spontaneous and X-ray induced proliferating epithelial foci (PEF) and what factor(s) directly influences the relative frequency of PEF in irradiated and control NTEC cultures. (author)

Arabidopsis ZED1-related kinases mediate the temperature-sensitive intersection of immune response and growth homeostasis.

Science.gov (United States)

Wang, Zhicai; Cui, Dayong; Liu, Jing; Zhao, Jingbo; Liu, Cheng; Xin, Wei; Li, Yuan; Liu, Na; Ren, Dongtao; Tang, Dingzhong; Hu, Yuxin

2017-07-01

Activation of the immune response in plants antagonizes growth and development in the absence of pathogens, and such an autoimmune phenotype is often suppressed by the elevation of ambient temperature. However, molecular regulation of the ambient temperature-sensitive intersection of immune response and growth is largely elusive. A genetic screen identified an Arabidopsis mutant, zed1-D, by its high temperature-dependent growth retardation. A combination of molecular, cytological and genetic approaches was used to investigate the molecular basis behind the temperature-sensitive growth and immune response in zed1-D. A dominant mutation in HOPZ-ETI-DEFICIENT 1 (ZED1) is responsible for a high temperature-dependent autoimmunity and growth retardation in zed1-D. The autoimmune phenotype in zed1-D is dependent on the HOPZ-ACTIVATED RESISTANCE 1 (ZAR1). ZED1 and some ZED1-related kinases (ZRKs) are induced by elevated temperature and function cooperatively to suppress the immune response by modulating the transcription of SUPPRESSOR OF NPR1-1 CONSTITUTIVE 1 (SNC1) in the absence of pathogens. Our data reveal a previously unidentified role of ZRKs in the ambient temperature-sensitive immune response in the absence of pathogens, and thus reveals a possible molecular mechanism underlying the temperature-mediated intersection of immune response and growth in plants. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Acromegaly with Normal Insulin-Like Growth Factor-1 Levels and Congestive Heart Failure as the First Clinical Manifestation

Directory of Open Access Journals (Sweden)

Hyae Min Lee

2015-09-01

Full Text Available The leading cause of morbidity and mortality in patients with acromegaly is cardiovascular complications. Myocardial exposure to excessive growth hormone can cause ventricular hypertrophy, hypertension, arrhythmia, and diastolic dysfunction. However, congestive heart failure as a result of systolic dysfunction is observed only rarely in patients with acromegaly. Most cases of acromegaly exhibit high levels of serum insulin-like growth factor-1 (IGF-1. Acromegaly with normal IGF-1 levels is rare and difficult to diagnose. Here, we report a rare case of an acromegalic patient whose first clinical manifestation was severe congestive heart failure, despite normal IGF-1 levels. We diagnosed acromegaly using a glucose-loading growth hormone suppression test. Cardiac function and myocardial hypertrophy improved 6 months after transsphenoidal resection of a pituitary adenoma.

Title: The Comparison of Anxiety Sensitivity and Happiness in Irritable Bowel Syndrome Patients with Normal Matched Group in Shiraz

Directory of Open Access Journals (Sweden)

2012-09-01

Full Text Available Background & Objective: The purpose of this study was the comparison of anxiety sensitivity and happiness between patients with Irritable Bowel Syndrome (IBS and normal matched group. Materials & Methods: The Subjects were 35 (21 females and 14 male IBS patients diagnosed by gastroenterologist and 35 (25 female and 10 males normal matched group all in 14– 63 old age. Anxiety Sensitivity Index (ASI-R, Oxford Happiness Questionnaire (OHQ, and a checklist applied as measures of anxiety sensitivity, happiness and demographic information. Results: Data analysis indicates that IBS patients significantly are higher than matched group in fear of publicly observable symptoms (P= 0.032, fear of cardiovascular symptoms (P= 0.01, fear of gastrointestinal symptoms (P= 0.001, fear of dissociative and neurological symptoms (P= 0.018, & general anxiety sensitivity (P= 0.003, and lower in joy (P= 0.005, control (P= 0.008, self- esteem (P= 0.001 calm (P= 0.006 and general happiness (P= 0.001. Although no significant differences were found in life satisfaction (P= 0.083 & efficacy (P= 0.09, fear of respiratory symptoms (P= 0.067, and fear of cognitive control deficiency (p= 0.097. Conclusion: As a psychological variable anxiety sensitivity can predict treatment seeking of IBS patient, and happiness negatively influenced by both anxiety sensitivity and IBS.

An efficient computational method for global sensitivity analysis and its application to tree growth modelling

International Nuclear Information System (INIS)

Wu, Qiong-Li; Cournède, Paul-Henry; Mathieu, Amélie

2012-01-01

Global sensitivity analysis has a key role to play in the design and parameterisation of functional–structural plant growth models which combine the description of plant structural development (organogenesis and geometry) and functional growth (biomass accumulation and allocation). We are particularly interested in this study in Sobol's method which decomposes the variance of the output of interest into terms due to individual parameters but also to interactions between parameters. Such information is crucial for systems with potentially high levels of non-linearity and interactions between processes, like plant growth. However, the computation of Sobol's indices relies on Monte Carlo sampling and re-sampling, whose costs can be very high, especially when model evaluation is also expensive, as for tree models. In this paper, we thus propose a new method to compute Sobol's indices inspired by Homma–Saltelli, which improves slightly their use of model evaluations, and then derive for this generic type of computational methods an estimator of the error estimation of sensitivity indices with respect to the sampling size. It allows the detailed control of the balance between accuracy and computing time. Numerical tests on a simple non-linear model are convincing and the method is finally applied to a functional–structural model of tree growth, GreenLab, whose particularity is the strong level of interaction between plant functioning and organogenesis. - Highlights: ► We study global sensitivity analysis in the context of functional–structural plant modelling. ► A new estimator based on Homma–Saltelli method is proposed to compute Sobol indices, based on a more balanced re-sampling strategy. ► The estimation accuracy of sensitivity indices for a class of Sobol's estimators can be controlled by error analysis. ► The proposed algorithm is implemented efficiently to compute Sobol indices for a complex tree growth model.

Exclusion of UV-B radiation from normal solar spectrum on the growth of mung bean and maize

International Nuclear Information System (INIS)

Pal, M.; Sharma, A.; Abrol, Y.P.; Sengupta, U.K.

1997-01-01

The increase in UV-B radiation due to depletion of the ozone layer has potentially harmful effects on plant growth and performance. The bulk of these studies conducted in growth chambers, greenhouses or in the field use different types of exposure systems which may be responsible for differences in the sensitivity of a crop to UV-B radiation. A field study using selective filters to remove the UV-B portion of the solar spectrum was conducted with mung bean (a dicotyledonous C 3 plant) and maize (a monocotyledonous C 4 plant) to determine the sensitivity of these crop plants to ambient UV-B levels without disturbing the microenvironment. Mung bean was found to be sensitive to ambient UV-B levels in terms of leaf area development, plant height attained and net photosynthesis, while maize was found to be unaffected by ambient UV-B levels (22.8 |GmW cm −2 nm −1 ) found in Delhi, India (28°38′N, 77°13′E). The level of ambient UV-B radiation thus appears to be inhibitory for optimal growth of plants, especially dicotyledonous mung bean. (author)

A Monte Carlo/response surface strategy for sensitivity analysis: application to a dynamic model of vegetative plant growth

Science.gov (United States)

Lim, J. T.; Gold, H. J.; Wilkerson, G. G.; Raper, C. D. Jr; Raper CD, J. r. (Principal Investigator)

1989-01-01

We describe the application of a strategy for conducting a sensitivity analysis for a complex dynamic model. The procedure involves preliminary screening of parameter sensitivities by numerical estimation of linear sensitivity coefficients, followed by generation of a response surface based on Monte Carlo simulation. Application is to a physiological model of the vegetative growth of soybean plants. The analysis provides insights as to the relative importance of certain physiological processes in controlling plant growth. Advantages and disadvantages of the strategy are discussed.

Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.

Science.gov (United States)

Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen

2009-04-14

The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin

OpenAIRE

Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C.; Gomella, Leonard G.; Belfiore, Antonino; Black, Peter C.; Iozzo, Renato V.; Morrione, Andrea

2016-01-01

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play...

Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

Energy Technology Data Exchange (ETDEWEB)

Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

2002-06-01

A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

International Nuclear Information System (INIS)

Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko

2002-01-01

A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 μg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

Sensitive double-antibody method for simultaneous determination of insulin and growth hormone

International Nuclear Information System (INIS)

Koparanova, O.; Sotirov, G.; Tyrkolev, N.

1982-01-01

A method is described for simultaneous determination of insulin and growth hormone in one sample, using double-antibody technique. The method is characterized by appreciable sensitivity (2.5 μE/ml for insulin and a.2 ng/ml for growth hormone), exactness (variation quotient 6-16 per cent) and reproducibility (96.9-117 per cent). There was no statistically significant difference in the insulin and growth hormone values of the same sera, determined by the here suggested and the standard methods. The necessary test material for examination of either hormone is minimal (0.2 ml). One may thus extend the possibilities for radioimmunologic determination of insulin and growth hormone, when only minor amounts of serum or other biological fluid are available. The method is also less time consuming. Results are reported of statistical processing of an experimental model and different sera determined by the standard method and the one described by the authors. (author)

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

International Nuclear Information System (INIS)

Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan; Zhang, Jing; Chai, Hongyan; Tang, Tian; Chen, Honglei; Yue, Jiang; Li, Ying; Yang, Jing

2015-01-01

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

Energy Technology Data Exchange (ETDEWEB)

Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chen, Honglei [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yue, Jiang [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Li, Ying, E-mail: lyying0@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

2015-07-15

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

Large-scale grain growth in the solid-state process: From "Abnormal" to "Normal"

Science.gov (United States)

Jiang, Minhong; Han, Shengnan; Zhang, Jingwei; Song, Jiageng; Hao, Chongyan; Deng, Manjiao; Ge, Lingjing; Gu, Zhengfei; Liu, Xinyu

2018-02-01

Abnormal grain growth (AGG) has been a common phenomenon during the ceramic or metallurgy processing since prehistoric times. However, usually it had been very difficult to grow big single crystal (centimeter scale over) by using the AGG method due to its so-called occasionality. Based on the AGG, a solid-state crystal growth (SSCG) method was developed. The greatest advantages of the SSCG technology are the simplicity and cost-effectiveness of the technique. But the traditional SSCG technology is still uncontrollable. This article first summarizes the history and current status of AGG, and then reports recent technical developments from AGG to SSCG, and further introduces a new seed-free, solid-state crystal growth (SFSSCG) technology. This SFSSCG method allows us to repeatedly and controllably fabricate large-scale single crystals with appreciable high quality and relatively stable chemical composition at a relatively low temperature, at least in (K0.5Na0.5)NbO3(KNN) and Cu-Al-Mn systems. In this sense, the exaggerated grain growth is no longer 'Abnormal' but 'Normal' since it is able to be artificially controllable and repeated now. This article also provides a crystal growth model to qualitatively explain the mechanism of SFSSCG for KNN system. Compared with the traditional melt and high temperature solution growth methods, the SFSSCG method has the advantages of low energy consumption, low investment, simple technique, composition homogeneity overcoming the issues with incongruent melting and high volatility. This SFSSCG could be helpful for improving the mechanical and physical properties of single crystals, which should be promising for industrial applications.

Different parts, different stories: climate sensitivity of growth is stronger in root collars vs. stems in tundra shrubs.

Science.gov (United States)

Ropars, Pascale; Angers-Blondin, Sandra; Gagnon, Marianne; Myers-Smith, Isla H; Lévesque, Esther; Boudreau, Stéphane

2017-08-01

Shrub densification has been widely reported across the circumpolar arctic and subarctic biomes in recent years. Long-term analyses based on dendrochronological techniques applied to shrubs have linked this phenomenon to climate change. However, the multi-stemmed structure of shrubs makes them difficult to sample and therefore leads to non-uniform sampling protocols among shrub ecologists, who will favor either root collars or stems to conduct dendrochronological analyses. Through a comparative study of the use of root collars and stems of Betula glandulosa, a common North American shrub species, we evaluated the relative sensitivity of each plant part to climate variables and assessed whether this sensitivity is consistent across three different types of environments in northwestern Québec, Canada (terrace, hilltop and snowbed). We found that root collars had greater sensitivity to climate than stems and that these differences were maintained across the three types of environments. Growth at the root collar was best explained by spring precipitation and summer temperature, whereas stem growth showed weak and inconsistent responses to climate variables. Moreover, sensitivity to climate was not consistent among plant parts, as individuals having climate-sensitive root collars did not tend to have climate-sensitive stems. These differences in sensitivity of shrub parts to climate highlight the complexity of resource allocation in multi-stemmed plants. Whereas stem initiation and growth are driven by microenvironmental variables such as light availability and competition, root collars integrate the growth of all plant parts instead, rendering them less affected by mechanisms such as competition and more responsive to signals of global change. Although further investigations are required to determine the degree to which these findings are generalizable across the tundra biome, our results indicate that consistency and caution in the choice of plant parts are a key

From forensic toxicology to biological chemistry: Normal arsenic and the hazards of sensitivity during the nineteenth century.

Science.gov (United States)

Bertomeu-Sánchez, José Ramón

2016-06-01

This paper reviews the cultural meanings, social uses and circulations of arsenic in different legal, medical and popular settings. The focus is on nineteenth-century France. In the first section, I review the advent of the Marsh test for arsenic, which is commonly regarded as a milestone in the history of toxicology. I claim that the high sensitivity of the Marsh test introduced puzzling problems for forensic doctors, the most disturbing one being the so-called 'normal arsenic.' I reconstruct early research on normal arsenic and the ensuing controversies in courts, academies and salons. A report from the French Academy of Science converted normal arsenic from a big discovery to an experimental mistake. In the next section, I study how these disturbing conclusions were perceived by toxicologists all over Europe and how normal arsenic disappeared from view by the middle of the nineteenth century. Finally, I review the return of normal arsenic thanks to Armand Gautier and Gabriel Bertrand, who introduced an innovative research framework and so prompted the displacement of arsenic from criminal toxicology to pharmacology and nutrition science. The last section will also show that the issue of normal arsenic was recaptured in public debates concerning criminal poisoning at the beginning of the twentieth century. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rac1 Dosage Is Crucial for Normal Endochondral Bone Growth.

Science.gov (United States)

Suzuki, Dai; Bush, Jason R; Bryce, Dawn-Marie; Kamijo, Ryutaro; Beier, Frank

2017-10-01

Rac1, a member of the small Rho GTPase family, plays multiple cellular roles. Studies of mice conditionally lacking Rac1 have revealed essential roles for Rac1 in various tissues, including cartilage and limb mesenchyme, where Rac1 loss produces dwarfism and long bone shortening. To gain further insight into the role of Rac1 in skeletal development, we have used transgenic mouse lines to express a constitutively active (ca) Rac1 mutant protein in a Cre recombinase-dependent manner. Overexpression of caRac1 in limb bud mesenchyme or chondrocytes leads to reduced body weight and shorter bones compared with control mice. Histological analysis of growth plates showed that caRac1;Col2-Cre mice displayed ectopic hypertrophic chondrocytes in the proliferative zone and enlarged hypertrophic zones. These mice also displayed a reduced proportion of proliferating cell nuclear antigen-positive cells in the proliferative zone and nuclear β-catenin localization in the ectopic hypertrophic chondrocytes. Importantly, overexpression of caRac1 partially rescued the phenotypes of Rac1fl/fl;Col2-Cre and Rac1fl/fl;Prx1-Cre conditional knockout mice, including body weight, bone length, and growth plate disorganization. These results suggest that tight regulation of Rac1 activity is necessary for normal cartilage development. Copyright © 2017 Endocrine Society.

Catch-up growth in Malawian babies, a longitudinal study of normal and low birthweight babies born in a malarious endemic area

NARCIS (Netherlands)

Kalanda, B.F.; Buuren, S. van; Verhoeff, F.H.; Brabin, B.J.

2005-01-01

Introduction: Infant growth has not been studied in developing countries in relation to maternal factors related to malaria in pregnancy and maternal illiteracy. Objective: To describe growth patterns in infants with low and normal birthweight and determine maternal risk factors for infant

Characterization of new radiation-sensitive mutant, Escherichia coli K-12 radC102

International Nuclear Information System (INIS)

Felzenszwalb, I.; Sargentini, N.J.; Smith, K.C.

1984-01-01

A new radiation-sensitive mutant, radC, has been isolated. The radC gene is located at 81.0 min on the Escherichia coli K-12 linkage map. The radC mutation sensitized cells to uv radiation, but unlike most DNA repair mutations, sensitization to X rays was observed only for rich medium-grown cells. For cells grown in rich medium, the radC mutant was normal for γ radiation mutagenesis, but showed less uv-radiation mutagenesis than the wild-type strain; it showed normal amount of X- and uv-radiation-induced DNA degradation, and it wasapprox. =60% deficient in recombination ability. The radC strain was normal for host cell reactivation of γ and uv-irradiated bacteriophage the radC mutation did not sensitize a recA strain, but did sensitize a radA and a polA strain to X and uv radiation and a uvrA strain to uv radiation. Therefore, it is suggested that the radC gene product plays a role in the growth medium-dependent, recA gene-dependent repair of DNA single-strand breaks after X irradiation, and in postreplication repair after uv irradiation

Genes contributing to pain sensitivity in the normal population

DEFF Research Database (Denmark)

Williams, Frances M.K.; Scollen, Serena; Cao, Dandan

2012-01-01

Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to s...

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

Science.gov (United States)

Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

2014-04-01

Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin Sensitivity during the Early Postnatal Period

Directory of Open Access Journals (Sweden)

Tong-yan Han

2010-01-01

Full Text Available Objective. To investigate the relationship between weight catch-up growth and insulin sensitivity in small for gestational age (SGA infants. Methods. Forty-four singleton SGA subjects met the inclusion criteria and finished-3-month followup. Body weight, length, fasting glucose, and fasting insulin (FI levels were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and homeostasis model assessment (HOMA. Results. According to the change of weight Z-score, forty-four subjects were divided into two groups: noncatch-up growth (NCUG and catch-up growth (CUG. By 3 months of age, the body weight, body length and BMI of NCUG group were significantly lower than those of CUG group. The FI and HOMA were significantly higher in NCUG group. The change of weight Z-score during 3 months was inversely related to the HOMA at 3 months. Conclusion. Our data exemplified that no weight catch-up growth during the first 3 months was associated with impaired insulin sensitivity in SGA infants.

Role of IgG4 in histamine release from human basophil leucocytes. I. Sensitization of cells from normal donors

DEFF Research Database (Denmark)

Poulsen, L K; Stahl Skov, P; Mosbech, H

1988-01-01

Several conflicting reports on the ability of IgG4 to mediate type I allergic reactions have appeared lately. We have developed a model system for testing this possibility, using passive sensitization of basophil leucocytes from normal individuals. At first, the system was optimized with regard t...

Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

International Nuclear Information System (INIS)

Salem, M.A.M.; Phares, C.K.

1986-01-01

The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U- 14 C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10 5 cells/ml) were incubated with either [ 125 I]insulin or [ 125 I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and 14 C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro

The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells.

Science.gov (United States)

Kheradmand, Fatemeh; Hashemnia, Seyyed Mohammad Reza; Valizadeh, Nasim; Roshan-Milani, Shiva

2016-01-01

Growth factors play an essential role in the development of tumor and normal cells like testicular leydig cells. Treatment of cancer with anti-cancer agents like imatinib mesylate may interfere with normal leydig cell activity, growth and fertility through failure in growth factors' production or their signaling pathways. The purpose of the study was to determine cellular viability and the levels of, platelet derived growth factor (PDGF) and stem cell factor (SCF) in normal mouse leydig cells exposed to imatinib, and addressing the effect of imatinib on fertility potential. The mouse TM3 leydig cells were treated with 0 (control), 2.5, 5, 10 and 20 μM imatinib for 2, 4 and 6 days. Each experiment was repeated three times (15 experiments in each day).The cellular viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, one-way ANOVA with Tukey's post hoc and Kruskal-Wallis test were performed. A p-value less than 0.05 was considered statistically significant. With increasing drug concentration, cellular viability decreased significantly (pcellular viability, PDGF and SCF levels. Imatinib may reduce fertility potential especially at higher concentrations in patients treated with this drug by decreasing cellular viability. The effect of imatinib on leydig cells is associated with PDGF stimulation. Of course future studies can be helpful in exploring the long term effects of this drug.

Growth acceleration and photosynthesis of the scenedesmus algae and cocconeis algae in deuterium water

International Nuclear Information System (INIS)

Liu Feng; Wang Wenqing

1998-01-01

In order to find new way to treat the radioactive tritium waste water, scenedesmus algae and cocconeis algae are cultured in medium which contains 30% (w) deuterium water. During different time, activities of photosymthesis, absorption spectrum, growth rate and low-temperature fluorescence spectrum are measured. Accelerated growth is found in the deuterium water compared to the normal water. Activities of photosynthesis show the similar result (F v /F m ) to the growth data. It is also concluded from low-temperature fluorescence spectra that algae activities in the deuterium water, which are expressed by PS I/PS II, are more sensitive than those in the normal water

Expression of a TGF-{beta} regulated cyclin-dependent kinase inhibitor in normal and immortalized airway epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Tierney, L.A.; Bloomfield, C.; Johnson, N.F. [and others

1995-12-01

Tumors arising from epithelial cells, including lung cancers are frequently resistant to factors that regulate growth and differentiation in normal in normal cells. Once such factor is transforming growth factor-{Beta} (TGF-{Beta}). Escape from the growth-inhibitory effects of TGF-{Beta} is thought to be a key step in the transformation of airway epithelial cells. most lung cancer cell lines require serum for growth. In contrast, normal human bronchial epithelial (NHBE) cells are exquisitely sensitive to growth-inhibitory and differentiating effects of TGF-{Beta}. The recent identification of a novel cyclin-dependent kinase inhibitor, p15{sup INK4B}, which is regulated by TGF-{Beta}, suggests a mechanism by which TGF-{Beta} mediates growth arrest in NHBE cells. The purpose of this study was two-fold: (1) to determine if p15{sup INK4B} is induced by TGF-{Beta} in NHBE cells or immortalized bronchial epithelial (R.1) cells and if that induction corresponds to a G1/S cell-cycle arrest; (2) to determine the temporal relationship between p15{sup INK4B} induction, cell-cycle arrest, and the phosphorylation state of the pRB because it is thought that p15{sup INK4B} acts indirectly by preventing phosphorylation of the RB gene product. In this study, expression of p15{sup INK4B} was examined in NHBE cells and R.1 cells at different time intervals following TGF-{Beta} treatment. The expression of this kinase inhibitor and its relationship to the cell and the pRb phosphorylation state were examined in cells that were both sensitive (NHBE) and resistant (R.1) to the effects of TGF-{Beta}. These results suggest that the cyclin-dependent kinase inhibitor, p15{sup INK4B}, is involved in airway epithelial cell differentiation and that loss or reduction of expression plays a role in the resistance of transformed or neoplastic cells to the growth-inhibitory effects of TGF-{Beta}.

Kidney function in normal man during short-term growth hormone infusion

DEFF Research Database (Denmark)

Parving, H H; Noer, I; Mogensen, C E

1978-01-01

Kidney function was studied in 9 normal males before and during a 2 h growth hormone (GH) infusion of 50 ng/kg/min. The following variables were measured during each 20 min clearance period: glomerular filtration rate, GFR, effective renal plasma flow, RPF (steady state infusion technique...... with urinary collections using [125I]iothalamate and [131I]iodohippurate), and urinary albumin and beta2-microglobulin excretion rates (radioimmunoassays). The GH infusion resulted in a 10-fold increase in plasma GH concentration. All the above mentioned variables remained practically unchanged during...... the infusion except for a small (-5%) but significant decrease in renal plasma flow (P less than 0.01). Our negative results contrast to the findings of increased GFR and RPF during prolonged GH administration and suggest that GH requires several hours or days for its renal effects to become manifest....

Studies on level of cytokines and expression of connexin43 in tumor and normal cells in culture conditions

International Nuclear Information System (INIS)

Asati, V.; Pandey, B.N.

2016-01-01

Factors secreted from the tumor cells in culture medium have been known to facilitate the growth of fresh cultures and also to affect the cellular radio-sensitivity. Moreover, expression of gap junction proteins like connexin-43 is known as a key player in cell survival and proliferation. The present study is aimed to evaluate the effects of conditioned medium on the growth of respective tumor/normal cells and the expression of connexin-43 in these cells

Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue.

Science.gov (United States)

Taurone, Samanta; Bianchi, Enrica; Attanasio, Giuseppe; Di Gioia, Cira; Ierinó, Rocco; Carubbi, Cecilia; Galli, Daniela; Pastore, Francesco Saverio; Giangaspero, Felice; Filipo, Roberto; Zanza, Christian; Artico, Marco

2015-07-01

Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular

Evaluation of the transforming growth factor-beta activity in normal and dry eye human tears by CCL-185 cell bioassay.

Science.gov (United States)

Zheng, Xiaofen; De Paiva, Cintia S; Rao, Kavita; Li, De-Quan; Farley, William J; Stern, Michael; Pflugfelder, Stephen C

2010-09-01

To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye. Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay. The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P tears and 37.6% TGF-beta in normal tears were found to be biologically active. The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where

Treatment of erythrocytes with the 2-cys peroxiredoxin inhibitor, Conoidin A, prevents the growth of Plasmodium falciparum and enhances parasite sensitivity to chloroquine.

Directory of Open Access Journals (Sweden)

Mariana Brizuela

Full Text Available The human erythrocyte contains an abundance of the thiol-dependant peroxidase Peroxiredoxin-2 (Prx2, which protects the cell from the pro-oxidant environment it encounters during its 120 days of life in the blood stream. In malarial infections, the Plasmodium parasite invades red cells and imports Prx2 during intraerythrocytic development, presumably to supplement in its own degradation of peroxides generated during cell metabolism, especially hemoglobin (Hb digestion. Here we demonstrate that an irreversible Prx2 inhibitor, Conoidin A (2,3-bis(bromomethyl-1,4-dioxide-quinoxaline; BBMQ, has potent cytocidal activity against cultured P. falciparum. Parasite growth was also inhibited in red cells that were treated with BBMQ and then washed prior to parasite infection. These cells remained susceptible to merozoite invasion, but failed to support normal intraerythrocytic development. In addition the potency of chloroquine (CQ, an antimalarial drug that prevents the detoxification of Hb-derived heme, was significantly enhanced in the presence of BBMQ. CQ IC50 values decreased an order of magnitude when parasites were either co-incubated with BBMQ, or introduced into BBMQ-pretreated cells; these effects were equivalent for both drug-resistant and drug-sensitive parasite lines. Together these results indicate that treatment of red cells with BBMQ renders them incapable of supporting parasite growth and increases parasite sensitivity to CQ. We also propose that molecules such as BBMQ that target host cell proteins may constitute a novel host-directed therapeutic approach for treating malaria.

The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

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Arpita Chatterjee

2018-01-01

Full Text Available Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs, ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

Improvement of insulin sensitivity in response to exercise training in type 2 diabetes mellitus is associated with vascular endothelial growth factor A expression.

Science.gov (United States)

Wagner, Henrik; Fischer, Helene; Degerblad, Marie; Alvarsson, Michael; Gustafsson, Thomas

2016-09-01

Insulin sensitivity changes in response to exercise training demonstrate a large variation. Vascular endothelial growth factor A could promote increased insulin sensitivity through angiogenesis. We investigated associations between changes in expression of key genes and insulin sensitivity, aerobic capacity and glycaemic control following exercise training in diabetes mellitus type 2. Subjects with diabetes mellitus type 2 underwent 12 weeks of structured exercise. Euglycaemic clamp, exercise test and HbA1c were performed. Muscle biopsies were obtained for mRNA expression. A total of 16 subjects completed the study. Change in vascular endothelial growth factor A expression was positively associated with an increase in insulin sensitivity (p = 0.004) and with a decrease in HbA1c (p = 0.034). Vascular endothelial growth factor A receptor-1 expression showed similar associations. The variation in physical adaptation to exercise training in diabetes mellitus type 2 was associated with changes in expression of vascular endothelial growth factor A in muscle. This difference in induced gene expression could contribute to the variation in exercise training effects on insulin sensitivity. Measures of capillary blood flow need to be assessed in future studies. © The Author(s) 2016.

Supra-salt normal fault growth during the rise and fall of a diapir: Perspectives from 3D seismic reflection data, Norwegian North Sea

Science.gov (United States)

Tvedt, Anette B. M.; Rotevatn, Atle; Jackson, Christopher A.-L.

2016-10-01

Normal faulting and the deep subsurface flow of salt are key processes controlling the structural development of many salt-bearing sedimentary basins. However, our detailed understanding of the spatial and temporal relationship between normal faulting and salt movement is poor due to a lack of natural examples constraining their geometric and kinematic relationship in three-dimensions. To improve our understanding of these processes, we here use 3D seismic reflection and borehole data from the Egersund Basin, offshore Norway, to determine the structure and growth of a normal fault array formed during the birth, growth and decay of an array of salt structures. We show that the fault array and salt structures developed in response to: (i) Late Triassic-to-Middle Jurassic extension, which involved thick-skinned, sub-salt and thin-skinned supra-salt faulting with the latter driving reactive diapirism; (ii) Early Cretaceous extensional collapse of the walls; and (iii) Jurassic-to-Neogene, active and passive diapirism, which was at least partly coeval with and occurred along-strike from areas of reactive diapirism and wall collapse. Our study supports physical model predictions, showcasing a three-dimensional example of how protracted, multiphase salt diapirism can influence the structure and growth of normal fault arrays.

Controlled synthesis of ZnO branched nanorod arrays by hierarchical solution growth and application in dye-sensitized solar cells

International Nuclear Information System (INIS)

Fang Xiaoming; Peng Lihua; Shang Xiaoying; Zhang Zhengguo

2011-01-01

We demonstrate the controlled synthesis of ZnO branched nanorod arrays on fluorine-doped SnO 2 -coated glass substrates by the hierarchical solution growth method. In the secondary growth, the concentration of Zn(NO 3 ) 2 /hexamethylenetetramine plays an important role in controlling the morphology of the branched nanorod arrays, besides that of diaminopropane used as a structure-directing agent to induce the growth of branches. The population density and morphology of the branched nanorod arrays depend on those of the nanorod arrays obtained from the primary growth, which can be modulated though the concentration of Zn(NO 3 ) 2 /hexamethylenetetramine in the primary growth solution. The dye-sensitized ZnO branched nanorod arrays exhibit much stronger optical absorption as compared with its corresponding primary nanorod arrays, suggesting that the addition of the branches improves light harvesting. The dye-sensitized solar cell based on the optimized ZnO branched nanorod array reaches a conversion efficiency of 1.66% under the light radiation of 1000 W/m 2 . The branched nanorod arrays can also be applied in other application fields of ZnO.

Group normalization for genomic data.

Science.gov (United States)

Ghandi, Mahmoud; Beer, Michael A

2012-01-01

Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN), to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

Basis for slow growth on non-fermentable substrates by a saccharomyces cerevisiae mutant UV-sensitive for rho- production

International Nuclear Information System (INIS)

Crosby, B.; Colson, A.M.; Briquet, M.; Goffeau, A.; Moustacchi, E.

1978-01-01

The mutant uvsp 72 of Saccharomyces cerevisiae UV-sensitive for rho - production displays slower growth on media containing non-fermentable carbon sources such as glycerol or lactate. The slower growth on glycerol is not due to any deficiency in glycerol catabolism or mitochondrial oxidative phosphorylation. No modifications of the sensitivity to ethidium bromide of the mitochondrial ATPase activity could be detected. A mathematical model is presented which accounts for slower growth of uvsp 72 on the sole basis of the continuous and elevated rho - production in the mutant strain. This model, which estimates the rate of mutation from the rate of growth and vice versa, has been verified experimentally in the case of uvsp 72. The model has been generalised, so that it can be used for any microbial population subject to constant and high rates of any type of mutation providing that the mutant is stable, and either unable to grow or able to grow at this own rate different from that of the parental strain. (orig.) [de

Growing into obesity: patterns of height growth in those who become normal weight, overweight, or obese as young adults.

Science.gov (United States)

Stovitz, Steven D; Demerath, Ellen W; Hannan, Peter J; Lytle, Leslie A; Himes, John H

2011-01-01

To study whether patterns of height growth differ by adult obesity status, and determine the contribution of subcutaneous fatness as an explanatory variable for any differences. A multicenter, prospective longitudinal cohort assessed in 3rd grade (8.8 years), 5th grade (11.1 years), 8th grade (14.1 years), and 12th grade (18.3 years). Exposures were young adult obesity status classified by CDC adult BMI categories at 12th grade. Skinfolds were measured in third, fifth, and eighth grades. Outcome was mean height (cm) at the four measurements using repeated-measures ANCOVA for young adult obesity status, and height increments between grades by adult obesity status in sequential models including initial height and, secondarily, initial skinfolds. Adjusted for age, and race/ethnicity, young adult obesity status explained a small, but statistically significant amount of height growth among both females and males within each of the three intervals. Compared with normal weight young adults, overweight or obese young adults stood taller in childhood, but had relatively less growth in height throughout the teenage years. There was no association between adult height and weight status. Skinfolds explained only a small amount of the height patterns in the three weight groups. Childhood and adolescent height growth patterns differ between those who become young adults who are normal weight and those who become overweight or obese. Since differences in fatness explain only a small amount of these height growth patterns, research is needed to identify other determinants. Copyright © 2011 Wiley-Liss, Inc.

Follicular localization of growth differentiation factor 8 and its receptors in normal and polycystic ovary syndrome ovaries.

Science.gov (United States)

Lin, Ting-Ting; Chang, Hsun-Ming; Hu, Xiao-Ling; Leung, Peter C K; Zhu, Yi-Min

2018-05-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and its etiology has not been characterized. Growth differentiation factor 8 (GDF8) is a member of the transforming growth factor-β superfamily that plays a critical role in the regulation of ovarian functions. However, the expression pattern of GDF8 in the human ovary is not yet clear. This study examined the cellular distribution of GDF8 and its putative cellular receptors (ACVR2A, ACVR2B, and ALK5) in a series of normal (n = 34) and PCOS ovaries (n = 14). The immunostaining of GDF8, ACVR2A, ACVR2B, and ALK5 was detected in the oocytes regardless of the developmental stage. All these proteins were localized in antral follicles in normal and PCOS ovaries, and the expression of these proteins increased with increasing follicle diameter. A significantly higher expression of GDF8 was detected in the granulosa cells than in the matched theca cells (TCs). These proteins were also localized in the luteal cells of the corpus luteum. Granulosa cells and TCs of large antral follicles in PCOS ovaries display a higher expression of these proteins. The higher expression levels of GDF8 and its functional receptors (ACVR2A, ACVR2B, and ALK5) in antral follicles of PCOS ovaries than those in normal ovaries suggest the possible involvement of dysregulated GDF8 in the pathogenesis of PCOS.

9-AAA inhibits growth and induces apoptosis in human melanoma A375 and rat prostate adenocarcinoma AT-2 and Mat-LyLu cell lines but does not affect the growth and viability of normal fibroblasts.

Science.gov (United States)

Korohoda, Włodzimierz; Hapek, Anna; Pietrzak, Monika; Ryszawy, Damian; Madeja, Zbigniew

2016-11-01

The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-AAA had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines. Visible effects on the cell growth and survival of tumor cell lines were observed after 24-48 h of treatment with 9-AAA, and increased over time. The inhibition of cancer cell growth was found to be due to the gradually increasing number of cells dying by apoptosis, which was observed using two methods, direct counting and FlowSight analysis. Simultaneously, cell motile activity decreased to the same degree in cancer and normal cells within the first 8 h of incubation in the presence of 9-AAA. The results presented in the current study suggest that short-lasting tests for potential anticancer substances can be insufficient; which may result in cell type-dependent differences in the responses of cells to tested compounds that act with a delay being overlooked. The observed differences in responses between normal human fibroblasts and cancer cells to 9-AAA show the requirement for additional studies to be performed simultaneously on differently reacting cancer and normal cells, to determine the molecular mechanisms responsible for these differences.

Brain structural correlates of reward sensitivity and impulsivity in adolescents with normal and excess weight.

Directory of Open Access Journals (Sweden)

Laura Moreno-López

Full Text Available INTRODUCTION: Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. METHODS: Fifty-two adolescents (16 with normal weight and 36 with excess weight were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ, the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM was used to assess possible between-group differences in regional gray matter (GM and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices and motivation/impulse control (hippocampus, prefrontal cortex. RESULTS: Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. CONCLUSION: Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.

Sensitivity Analysis of Fatigue Crack Growth Model for API Steels in Gaseous Hydrogen.

Science.gov (United States)

Amaro, Robert L; Rustagi, Neha; Drexler, Elizabeth S; Slifka, Andrew J

2014-01-01

A model to predict fatigue crack growth of API pipeline steels in high pressure gaseous hydrogen has been developed and is presented elsewhere. The model currently has several parameters that must be calibrated for each pipeline steel of interest. This work provides a sensitivity analysis of the model parameters in order to provide (a) insight to the underlying mathematical and mechanistic aspects of the model, and (b) guidance for model calibration of other API steels.

Global gene expression profiling related to temperature-sensitive growth abnormalities in interspecific crosses between tetraploid wheat and Aegilops tauschii.

Directory of Open Access Journals (Sweden)

Ryusuke Matsuda

Full Text Available Triploid wheat hybrids between tetraploid wheat and Aegilops tauschii sometimes show abnormal growth phenotypes, and the growth abnormalities inhibit generation of wheat synthetic hexaploids. In type II necrosis, one of the growth abnormalities, necrotic cell death accompanied by marked growth repression occurs only under low temperature conditions. At normal temperature, the type II necrosis lines show grass-clump dwarfism with no necrotic symptoms, excess tillers, severe dwarfism and delayed flowering. Here, we report comparative expression analyses to elucidate the molecular mechanisms of the temperature-dependent phenotypic plasticity in the triploid wheat hybrids. We compared gene and small RNA expression profiles in crown tissues to characterize the temperature-dependent phenotypic plasticity. No up-regulation of defense-related genes was observed under the normal temperature, and down-regulation of wheat APETALA1-like MADS-box genes, considered to act as flowering promoters, was found in the grass-clump dwarf lines. Some microRNAs, including miR156, were up-regulated, whereas the levels of transcripts of the miR156 target genes SPLs, known to inhibit tiller and branch number, were reduced in crown tissues of the grass-clump dwarf lines at the normal temperature. Unusual expression of the miR156/SPLs module could explain the grass-clump dwarf phenotype. Dramatic alteration of gene expression profiles, including miRNA levels, in crown tissues is associated with the temperature-dependent phenotypic plasticity in type II necrosis/grass-clump dwarf wheat hybrids.

A Study of Relationship between the Acoustic Sensitivity of Vestibular System and the Ability to Trigger Sound-Evoked Muscle Reflex of the Middle Ear in Adults with Normal Hearing

Directory of Open Access Journals (Sweden)

S.F. Emami

2014-07-01

Full Text Available Introduction & Objective: The vestibular system is sound sensitive and the sensitivity is related to the saccule. The vestibular afferents are projected to the middle ear muscles (such as the stapedius. The goal of this research was studying the relationship between the vestibular hearing and the sound-evoked muscle reflex of the middle ear to 500 HZ. Materials & Methods: This study was a cross sectional-comparison done in audiology department of Sheikholreis C‍‍linic (Hamadan, Iran. The study groups consisted of thirty healthy people and thirty patients with benign paroxysmal positional vertigo. Inclusion criteria of the present study were to have normal hearing on pure tone audiometry, acoustic reflex, and speech discrimination scores. Based on ipsilateral acoustic reflex test at 500HZ, they were divided to normal and abnormal groups. Then they were evaluated by cervical vestibular evoked myogenic potentials (cVEMPs and finally classified in three groups (N Normal ear , (CVUA Contra lateral vertiginous ear with unaffected saccular sensitivity to sound,(IVA Ipsilateral vertiginous ear with affected saccular sensitivity to sound. Results: Thirty affected ears (IVA with decreased vestibular excitability as detected by ab-normal cVEMPs, revealed abnormal findings of acoustic reflex at 500HZ. Whereas, both un-affected (CVUA and normal ears (N had normal results. Multiple comparisons of mean values of cVEMPs (p13,n23 and acoustic reflex at500HZ among the three groups were sig-nificant. The correlation between acoustic reflex at 500HZ and p13 latencies was significant. The n23 latencies showed significant correlation with acoustic reflex at 500HZ. Conclusion: The vestibular sensitivity to sound retains the ability to trigger sound-evoked re-flex of the middle ear at 500 HZ. (Sci J Hamadan Univ Med Sci 2014; 21 (2:99-104

Group normalization for genomic data.

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Mahmoud Ghandi

Full Text Available Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN, to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie

2016-04-21

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

2016-01-01

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Radioimmunoassay of canine growth hormone

International Nuclear Information System (INIS)

Eigenmann, J.E.; Eigenmann, R.Y.

1981-01-01

A sensitive radioimmunoassay (RIA) for canine growth hormone (GH) was developed. Antibodies were elicited in rhesus monkeys. One antiserum exhibited a working titer at a dilution of 1:500 000. Radioiodination was performed enzymatically employing lactoperoxidase. Logit-log transformation and least squares fitting resulted in straight line fitting of the standard curve between 0.39 and 50 ng/ml. Formation of large-molecular [ 125 I]GH during storage caused diminished assay sensitivity. Therefore [ 125 I]GH was re-purified by gel chromatography. Using this procedure, high and reproducible assay sensitivity was obtained. Tracer preparations were used for as long as 3 months after iodination. Diluted plasma from normal and acromegalic dogs resulted in a dose-response curve parallel to the standard curve. Canine prolactin exhibited a cross-reactivity of 2%. The within-assay coefficient of variation (CV) was 3.8 and the between-assay CV was 7.2%. Mean plasma GH concentration in normal dogs was 1.92 +- 0.14 ng/ml (mean +- SEM.) GH levels in acromegalic dogs were appreciably higher. Insulin-induced hypoglycaemia, arginine and ornithine administration resulted in inconsistent and sluggish GH increment. A better response was obtained by injecting a low dose of clonidine. Clonidine administration to hypopituitary dogs resulted in absent or poor GH increment. (author)

Cell biological effects of total body irradiation on growth and differentiation of acute myelogenous leukemia cells compared to normal bone marrow

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Greenberger, J S; Weichselbaum, R R; Botnick, L E; Sakakeeny, M; Moloney, W C

1979-01-01

Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compared to the effect on normal marrow granulocytic stem cells (CFUc) in vitro. Little difference from that of normal CFUc was found in the radiosensitivity of two mouse myeloid leukemia cell lines. The effect of TBI on growth of WEHI-3 or J774 cells in millipore diffusion chambers was stimulatory. These AML cell lines as well as others derived from Friend or Abelson virus infected in vitro long term mouse marrow cultures showed some morphologic differentiation by 7 days growth in diffusion chambers in irradiated heterologous rat hosts, but immature cells predominated by day 21. Thus, evidence in murine models of AML indicates that residual AML cells surviving chemotherapy will show no greater susceptibility to radiation killing compared to normal stem cells and will rapidly repopulate the irradiated host.

Comparison of heat and/or radiation sensitivity and membrane composition of seven X-ray-transformed C3H 10T1/2 cell lines and normal C3H 10T1/2 cells

International Nuclear Information System (INIS)

Raaphorst, G.P.; Vadasz, J.A.; Azzam, E.I.; Sargent, M.D.; Borsa, J.; Einspenner, M.

1985-01-01

C3H 10T1/2 mouse embryo cells were transformed by X-irradiation, and seven transformed clones were isolated and propagated as cell lines. Some of these cell lines produced tumors in syngeneic mice and grew in agarose while the normal C3H 10T1/2 cell line did not possess these characteristics. Exponentially growing cell cultures with comparable cell-cycle distributions as measured by flow cytometry were tested for heat and X-ray sensitivity. The heat and X-ray sensitivity varied randomly compared to the normal cell line. One cell line was more heat resistant and one more heat sensitive than the normal cell line, and the others had sensitivities comparable to the normal cell line. Measurements on some of the biochemical parameters of the particulate fraction of cells after sonication and 24,000 X g centrifugation showed that altered thermal sensitivity was not correlated with protein, cholesterol, or phospholipid content of this fraction

Does priming with sex steroids improve the diagnosis of normal growth hormone secretion in short children?

Directory of Open Access Journals (Sweden)

Ashraf Soliman

2014-01-01

Full Text Available Introduction: There is still controversy for priming with sex steroid before growth hormone (GH testing. Objective: We studied GH response to stimulation in 92 children >9 years with idiopathic short stature (height standard deviation score [HtSDS]-2. They were divided randomly into two groups. Children in Group 1 (n = 50 were primed with premarin in girls and testosterone in boys and those in Group 2 were not primed (n = 42. All children were tested using standard clonidine test and their serum insulin-like growth factor-I concentration (IGF-I. Additionally the growth and GH-IGF-I data of the two groups of children were compared with those for 32 short children (HtSDS 9 years. The peak GH response to clonidine provocation test did not differ before (n = 42 versus after 9 years (n = 32 of age. Conclusions: In this randomized study priming with sex steroids before GH testing did not significantly increase the yield of diagnosing short patients with normal GH secretion. In addition, GH response to provocation did not vary significantly between young (9 years short children.

Evaluation of insulin-like growth factor-1 and insulin like growth factor binding protein-3 in diagnosis of growth hormone deficiency in short-stature children

International Nuclear Information System (INIS)

Ali, A.; Hashim, R.; Khan, F.A.; Sattar, A.; Ijaz, A.; Manzoor, S.M.; Younas, M.

2009-01-01

Growth Hormone Deficiency (GHD) is conventionally diagnosed and confirmed by diminished peak Growth Hormone (GH) levels to provocative testing. Serum Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are under the influence of GH and reflect the spontaneous endogenous GH secretion. Owing to the absence of a circadian rhythm, it is possible to take individual measurements of IGF-1 and IGFBP-3 at any time of the day for evaluation of GH status instead of subjecting the individual to cumbersome provocative tests. Objectives of this study were to compare IGF-1 and IGFBP-3 assays with Exercise and L-Dopa stimulation tests in the diagnosis of growth hormone deficiency in short stature children using ITT as gold standard. Methods: This validation study was conducted at Department of Chemical Pathology and Endocrinology, AFIP, Rawalpindi, from November 2005 to October 2006. Fifty-two short stature children were included in the study. Basal samples for GH levels and simultaneous IGF-1 and IGFBP-3 measurements were obtained and afterwards all children were subjected to sequential exercise and LDopa stimulation tests. Insulin Tolerance Test (ITT) was performed one week later with all the necessary precautionary measures. On the basis of ITT results, children were divided into two groups, i.e., 31 growth hormone deficient and 21 Normal Variant Short Stature (NVSS). Results: The diagnostic value of exercise stimulation test remained highest with sensitivity 90.3%, specificity 76.0%, Positive Predictive Value (PPV) 84.84%, Negative Predictive Value (NPV) 84.2% and accuracy 84.6%. The conventional L-Dopa stimulation had sensitivity 96.7%, specificity 38.0%, PPV 69.7%, NPV 88.8 % and accuracy 73.0%. The serum IGF-1 and IGFBP-3 levels were positively correlated with post ITT peak GH levels (r= 0.527, r=0.464 respectively, both p<0.001). The diagnostic value of IGF-1 had sensitivity 83.87%, specificity 76.2%, PPV 83.87%, NPV 76.2% and

Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

Science.gov (United States)

Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

2017-10-01

Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Observed forest sensitivity to climate implies large changes in 21st century North American forest growth.

Science.gov (United States)

Charney, Noah D; Babst, Flurin; Poulter, Benjamin; Record, Sydne; Trouet, Valerie M; Frank, David; Enquist, Brian J; Evans, Margaret E K

2016-09-01

Predicting long-term trends in forest growth requires accurate characterisation of how the relationship between forest productivity and climatic stress varies across climatic regimes. Using a network of over two million tree-ring observations spanning North America and a space-for-time substitution methodology, we forecast climate impacts on future forest growth. We explored differing scenarios of increased water-use efficiency (WUE) due to CO2 -fertilisation, which we simulated as increased effective precipitation. In our forecasts: (1) climate change negatively impacted forest growth rates in the interior west and positively impacted forest growth along the western, southeastern and northeastern coasts; (2) shifting climate sensitivities offset positive effects of warming on high-latitude forests, leaving no evidence for continued 'boreal greening'; and (3) it took a 72% WUE enhancement to compensate for continentally averaged growth declines under RCP 8.5. Our results highlight the importance of locally adapted forest management strategies to handle regional differences in growth responses to climate change. © 2016 John Wiley & Sons Ltd/CNRS.

EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR).

Science.gov (United States)

Brouillet, S; Murthi, P; Hoffmann, P; Salomon, A; Sergent, F; De Mazancourt, P; Dakouane-Giudicelli, M; Dieudonné, M N; Rozenberg, P; Vaiman, D; Barbaux, S; Benharouga, M; Feige, J-J; Alfaidy, N

2013-02-01

Identifiable causes of fetal growth restriction (FGR) account for 30 % of cases, but the remainders are idiopathic and are frequently associated with placental dysfunction. We have shown that the angiogenic factor endocrine gland-derived VEGF (EG-VEGF) and its receptors, prokineticin receptor 1 (PROKR1) and 2, (1) are abundantly expressed in human placenta, (2) are up-regulated by hypoxia, (3) control trophoblast invasion, and that EG-VEGF circulating levels are the highest during the first trimester of pregnancy, the period of important placental growth. These findings suggest that EG-VEGF/PROKR1 and 2 might be involved in normal and FGR placental development. To test this hypothesis, we used placental explants, primary trophoblast cultures, and placental and serum samples collected from FGR and age-matched control women. Our results show that (1) EG-VEGF increases trophoblast proliferation ([(3)H]-thymidine incorporation and Ki67-staining) via the homeobox-gene, HLX (2) the proliferative effect involves PROKR1 but not PROKR2, (3) EG-VEGF does not affect syncytium formation (measurement of syncytin 1 and 2 and β hCG production) (4) EG-VEGF increases the vascularization of the placental villi and insures their survival, (5) EG-VEGF, PROKR1, and PROKR2 mRNA and protein levels are significantly elevated in FGR placentas, and (6) EG-VEGF circulating levels are significantly higher in FGR patients. Altogether, our results identify EG-VEGF as a new placental growth factor acting during the first trimester of pregnancy, established its mechanism of action, and provide evidence for its deregulation in FGR. We propose that EG-VEGF/PROKR1 and 2 increases occur in FGR as a compensatory mechanism to insure proper pregnancy progress.

Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

Science.gov (United States)

Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

2017-12-09

Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

In situ spectroscopic ellipsometry as a surface sensitive tool to probe thin film growth

International Nuclear Information System (INIS)

Liu, C.

1999-01-01

Sputtered thin film and multilayer x-ray mirrors are made routinely at the Advanced Photon Source (APS) for the APS users. Precise film growth control and characterization are very critical in fabricating high-quality x-ray mirrors. Film thickness calibrations are carried out using in situ and ex situ spectroscopic ellipsometry, interferometry, and x-ray scattering. To better understand the growth and optical properties of different thin film systems, we have carried out a systematic study of sputtered thin films of Au, Rh, Pg Pd, Cu, and Cr, using in situ ellipsometry. Multiple data sets were obtained in situ for each film material with incremental thicknesses and were analyzed with their correlation in mind. We found that in situ spectroscopic ellipsometry as a surface-sensitive tool can also be used to probe the growth and morphology of the thin film system. This application of in situ spectroscopic ellipsometry for metal thin film systems will be discussed

Radioimmunoassay of human growth hormone and its application in pituitary dysfunction studies

International Nuclear Information System (INIS)

Asolkar, S.V.; Sivaprasad, N.; Shah, K.B.; Mani, R.S.; Deshpande, A.

1981-01-01

A simple, specific and sensitive Radioimmunoassay (RIA) has been developed for the measurement of Human Growth Hormone (HGH) in serum samples. 123 I-labelled HGH has been used as a tracer and dextran coated charcoal system has been employed to separate antibody bound hormone from the unbound one. The assay offers sensitivity of 0.16 ng/ml with a reproducibility of 7% intraassay and inter-assay variations. Serum HGH levels were measured at fasting-resting state and during insulin stimulation test in (1) 15 normal subjects (controls) and (2) 31 patients with stunted growth, whereas (3) in 7 acromegalic patients the same were measured at fasting-resting state and after oral glucose administration. This procedure has been used to distinguish dwarfs due to growth hormone deficiency from other conditions unrelated to pituitary disease and to confirm acromegaly. (author)

The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

Energy Technology Data Exchange (ETDEWEB)

Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel); Shoshani-Dror, Dana [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel); Weksler-Zangen, Sarah [Diabetes Research Unit, Hebrew University Hadassah Medical School and Hospital, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester, MN (United States); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)

2012-12-01

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

International Nuclear Information System (INIS)

Ergaz, Zivanit; Shoshani-Dror, Dana; Guillemin, Claire; Neeman-azulay, Meytal; Fudim, Liza; Weksler-Zangen, Sarah; Stodgell, Christopher J.; Miller, Richard K.; Ornoy, Asher

2012-01-01

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy.

Science.gov (United States)

Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K

2014-05-01

Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiation and glucocorticoids

Energy Technology Data Exchange (ETDEWEB)

Amos, T.A.S.; Lewis, J.L.; Grand, F.H.; Gooding, R.P.; Goldman, J.M.; Gordon, M.Y. [Royal Postgraduate Medical School, London (United Kingdom)

1995-10-01

Inhibition of apoptosis (genetically programmed active cell death) by p210 BCR-ABL expression is a mechanism that might contribute to clonal expansion in chronic myeloid leukaemia (CML). Since cell death following exposure to ionizing radiation and many chemotherapeutic agents can occur by the apoptotic pathway, inhibition of apoptosis would be expected to confer a relative resistance to these treatments. Similarly, cells deprived of growth factors in vitro die by apoptosis, and inhibition of apoptosis would therefore be expected to allow cells to survive better in growth factor-deprived conditions. We found that the survival of normal and CML myeloid progenitors was the same after in vitro incubation in deprived conditions and after treatment with X-irradiation or glucocorticoids. We also found that mature cells in colonies produced by CML progenitors (CFU-GM) did not survive better than those produced by normal progenitor cells. Flow cytometric analysis of propidium iodide-stained cells provided a direct indication that the degree of apoptosis may correspond to the degree of deprivation. These results suggest that inhibition of apoptosis may not be the primary mechanism whereby BCR-ABL influences the expansion of the malignant clone in CML. (Author).

Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiation and glucocorticoids

International Nuclear Information System (INIS)

Amos, T.A.S.; Lewis, J.L.; Grand, F.H.; Gooding, R.P.; Goldman, J.M.; Gordon, M.Y.

1995-01-01

Inhibition of apoptosis (genetically programmed active cell death) by p210 BCR-ABL expression is a mechanism that might contribute to clonal expansion in chronic myeloid leukaemia (CML). Since cell death following exposure to ionizing radiation and many chemotherapeutic agents can occur by the apoptotic pathway, inhibition of apoptosis would be expected to confer a relative resistance to these treatments. Similarly, cells deprived of growth factors in vitro die by apoptosis, and inhibition of apoptosis would therefore be expected to allow cells to survive better in growth factor-deprived conditions. We found that the survival of normal and CML myeloid progenitors was the same after in vitro incubation in deprived conditions and after treatment with X-irradiation or glucocorticoids. We also found that mature cells in colonies produced by CML progenitors (CFU-GM) did not survive better than those produced by normal progenitor cells. Flow cytometric analysis of propidium iodide-stained cells provided a direct indication that the degree of apoptosis may correspond to the degree of deprivation. These results suggest that inhibition of apoptosis may not be the primary mechanism whereby BCR-ABL influences the expansion of the malignant clone in CML. (Author)

Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

Science.gov (United States)

Shechter, M; Ginsberg, S; Scheinowitz, M; Feinberg, M S; Laron, Z

2007-04-01

Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress. Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol). LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively). FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

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Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

2018-03-15

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Delayed growth

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... Slow rate of growth; Retarded growth and development; Growth delay Images Toddler development References Cooke DW, Divall SA, Radovick S. Normal and aberrant growth in children. In: Melmed S, Polonsky KS, Larsen PR, ...

Starvation-induced activation of ATM/Chk2/p53 signaling sensitizes cancer cells to cisplatin

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Shi Yandong

2012-12-01

Full Text Available Abstract Background Optimizing the safety and efficacy of standard chemotherapeutic agents such as cisplatin (CDDP is of clinical relevance. Serum starvation in vitro and short-term food starvation in vivo both stress cells by the sudden depletion of paracrine growth stimulation. Methods The effects of serum starvation on CDDP toxicity were investigated in normal and cancer cells by assessing proliferation, cell cycle distribution and activation of DNA-damage response and of AMPK, and were compared to effects observed in cells grown in serum-containing medium. The effects of short-term food starvation on CDDP chemotherapy were assessed in xenografts-bearing mice and were compared to effects on tumor growth and/or regression determined in mice with no diet alteration. Results We observed that serum starvation in vitro sensitizes cancer cells to CDDP while protecting normal cells. In detail, in normal cells, serum starvation resulted in a complete arrest of cellular proliferation, i.e. depletion of BrdU-incorporation during S-phase and accumulation of the cells in the G0/G1-phase of the cell cycle. Further analysis revealed that proliferation arrest in normal cells is due to p53/p21 activation, which is AMPK-dependent and ATM-independent. In cancer cells, serum starvation also decreased the fraction of S-phase cells but to a minor extent. In contrast to normal cells, serum starvation-induced p53 activation in cancer cells is both AMPK- and ATM-dependent. Combination of CDDP with serum starvation in vitro increased the activation of ATM/Chk2/p53 signaling pathway compared to either treatment alone resulting in an enhanced sensitization of cancer cells to CDDP. Finally, short-term food starvation dramatically increased the sensitivity of human tumor xenografts to cisplatin as indicated not only by a significant growth delay, but also by the induction of complete remission in 60% of the animals bearing mesothelioma xenografts, and in 40% of the

Sensitivity and specificity of normality tests and consequences on reference interval accuracy at small sample size: a computer-simulation study.

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Le Boedec, Kevin

2016-12-01

According to international guidelines, parametric methods must be chosen for RI construction when the sample size is small and the distribution is Gaussian. However, normality tests may not be accurate at small sample size. The purpose of the study was to evaluate normality test performance to properly identify samples extracted from a Gaussian population at small sample sizes, and assess the consequences on RI accuracy of applying parametric methods to samples that falsely identified the parent population as Gaussian. Samples of n = 60 and n = 30 values were randomly selected 100 times from simulated Gaussian, lognormal, and asymmetric populations of 10,000 values. The sensitivity and specificity of 4 normality tests were compared. Reference intervals were calculated using 6 different statistical methods from samples that falsely identified the parent population as Gaussian, and their accuracy was compared. Shapiro-Wilk and D'Agostino-Pearson tests were the best performing normality tests. However, their specificity was poor at sample size n = 30 (specificity for P Box-Cox transformation) on all samples regardless of their distribution or adjusting, the significance level of normality tests depending on sample size would limit the risk of constructing inaccurate RI. © 2016 American Society for Veterinary Clinical Pathology.

Evaluation of effect of high frequency electromagnetic field on growth and antibiotic sensitivity of bacteria.

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Salmen, Saleh H; Alharbi, Sulaiman A; Faden, Asmaa A; Wainwright, M

2018-01-01

This study was aimed to evaluate the impact of high frequency electromagnetic fields (HF-EMF at 900 and 1800 MHz) on DNA, growth rate and antibiotic susceptibility of S. aureus , S. epidermidis , and P. aeruginosa . In this study, bacteria were exposed to 900 and 1800 MHz for 2 h and then inoculated to new medium when their growth rate and antibiotic susceptibility were evaluated. Results for the study of bacterial DNA unsuccessful to appearance any difference exposed and non-exposed S. aureus and S. epidermidis . Exposure of S. epidermidis and S. aureus to electromagnetic fields mostly produced no statistically significant decrease in bacterial growth, except for S. aureus when exposure to 900 MHz at 12 h. Exposure of P. aeruginosa to electromagnetic fields at 900 MHz however, lead to a significant reduction in growth rate, while 1800 MHz had insignificant effect. With the exception of S. aureus , treated with amoxicillin (30 µg) and exposed to electromagnetic fields, radiation treatment had no significant effect on bacterial sensitivity to antibiotics.

Diagnostic Usefulness of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor Binding Protein 3 in Children with Suspected Pituitary Dwarfism.

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Zelazowska-Rutkowska, Beata; Trusiak, Marta; Bossowski, Artur; Cylwik, Bogdan

2018-05-01

Pituitary dwarfism (also known as short stature) is a medical condition in which the pituitary gland does not produce enough growth hormone (GH). To confirm the diagnosis of growth hormone deficiency the overnight profile of GH secretion and GH provocative tests are usually performed; however, due to wide GH fluctuations throughout the day and night and the invasiveness of stimulation tests, their clinical utility is limited. Therefore, screening for IGF-1 (insulin-like growth factor 1) and IGFBP-3 (insulin-like growth factor binding protein type 3) is proposed, suggesting that these tests provide a more accurate reflection of the mean plasma GH level, although the results of these tests are still problematic. In this context, the aim of this study was to assess the diagnostic usefulness of IGF-1 and IGFBP-3 in children with suspected pituitary dwarfism. Studies were carried out in 127 children with abnormal growth and low spontaneous 24-hour plasma GH profiles and abnormal results of GH stimulation tests. Fasting serum IGF-1 and IGFBP-3 were determined by chemiluminescent quantitative measurement using the IMMULITE 1000 IGF-1 and IGFBP-3 kits (Siemens Healthcare Diagnostics, United Kingdom) on the IMMULITE 1000 analyzer (Siemens Healthcare Diagnostics, USA). Results were compared to the normal range by children's age. Mean serum IGF-1 concentrations were within the lower normal range (41.7% cases), and 58.3% results were below the normal reference range in the study group. The average serum IGFBP-3 levels were within the lower normal range. We conclude that IGF-1 test can be a useful tool in the diagnosis of pituitary dwarfism in children suspected of this condition, but due to relatively poor sensitivity the testing cannot be performed alone, but in combination with other tests. The IGFBP-3 test is not useful for the diagnosis of this disease.

Long-wave theory for a new convective instability with exponential growth normal to the wall.

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Healey, J J

2005-05-15

A linear stability theory is presented for the boundary-layer flow produced by an infinite disc rotating at constant angular velocity in otherwise undisturbed fluid. The theory is developed in the limit of long waves and when the effects of viscosity on the waves can be neglected. This is the parameter regime recently identified by the author in a numerical stability investigation where a curious new type of instability was found in which disturbances propagate and grow exponentially in the direction normal to the disc, (i.e. the growth takes place in a region of zero mean shear). The theory describes the mechanisms controlling the instability, the role and location of critical points, and presents a saddle-point analysis describing the large-time evolution of a wave packet in frames of reference moving normal to the disc. The theory also shows that the previously obtained numerical solutions for numerically large wavelengths do indeed lie in the asymptotic long-wave regime, and so the behaviour and mechanisms described here may apply to a number of cross-flow instability problems.

Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

International Nuclear Information System (INIS)

Travis, Elizabeth L.

1996-01-01

Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

Developmental axon stretch stimulates neuron growth while maintaining normal electrical activity, intracellular calcium flux, and somatic morphology.

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Loverde, Joseph R; Pfister, Bryan J

2015-01-01

Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury.

Developmental Axon Stretch Stimulates Neuron Growth While Maintaining Normal Electrical Activity, Intracellular Calcium Flux, and Somatic Morphology

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Joseph R Loverde

2015-08-01

Full Text Available Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18 % applied over 5 minutes. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25 % strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury.

Extreme Thermal Sensitivity and Pain-Induced Sensitization in a Fibromyalgia Patient

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Fong Wong

2010-01-01

Full Text Available During the course of a psychophysical study of fibromyalgia syndrome (FMS, one of the subjects with a long history of headache and facial pain displayed an extraordinarily severe thermal allodynia. Her stimulus-response function for ratings of cutaneous heat pain revealed a sensitivity clearly beyond that of normal controls and most FMS subjects. Specially designed psychophysical methods showed that heat sensitivity sometimes increased dramatically within a series of stimuli. Prior exposure to moderate heat pain served as a trigger for allodynic ratings of series of normally neutral thermal stimulation. These observations document a case of breakthrough pain sensitivity with implications for mechanisms of FMS pain.

Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase.

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Gao, Yuanyuan; Fotovati, Abbas; Lee, Cathy; Wang, Michelle; Cote, Gilbert; Guns, Emma; Toyota, Brian; Faury, Damien; Jabado, Nada; Dunn, Sandra E

2009-12-01

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor where 5 years. In adults, GBM is the most common type of brain tumor. It is rarer in children, where it constitutes approximately 15% of all brain tumors diagnosed. These tumors are often invasive, making surgical resection difficult. Further, they can be refractory to current therapies such as temozolomide. The current dogma is that temozolomide resistance rests on the expression of O6-methylguanine-DNA methyltransferase (MGMT) because it cleaves methylated DNA adducts formed by the drug. Our laboratory recently reported that another drug resistance gene known as the Y-box binding protein-1 (YB-1) is highly expressed in primary GBM but not in normal brain tissues based on the evaluation of primary tumors. We therefore questioned whether GBM depend on YB-1 for growth and/or response to temozolomide. Herein, we report that YB-1 inhibition reduced tumor cell invasion and growth in monolayer as well as in soft agar. Moreover, blocking this protein ultimately delayed tumor onset in mice. Importantly, inhibiting YB-1 enhanced temozolomide sensitivity in a manner that was independent of MGMT in models of adult and pediatric GBM. In conclusion, inhibiting YB-1 may be a novel way to improve the treatment of GBM.

Suppression of Homologous Recombination by insulin-like growth factor-1 inhibition sensitizes cancer cells to PARP inhibitors

International Nuclear Information System (INIS)

Amin, Oreekha; Beauchamp, Marie-Claude; Nader, Paul Abou; Laskov, Ido; Iqbal, Sanaa; Philip, Charles-André; Yasmeen, Amber; Gotlieb, Walter H.

2015-01-01

Impairment of homologous recombination (HR) is found in close to 50 % of ovarian and breast cancer. Tumors with BRCA1 mutations show increased expression of the Insulin-like growth factor type 1 receptor (IGF-1R). We previously have shown that inhibition of IGF-1R results in growth inhibition and apoptosis of ovarian tumor cells. In the current study, we aimed to investigate the correlation between HR and sensitivity to IGF-1R inhibition. Further, we hypothesized that IGF-1R inhibition might sensitize HR proficient cancers to Poly ADP ribose polymerase (PARP) inhibitors. Using ovarian and breast cancer cellular models with known BRCA1 status, we evaluated their HR functionality by RAD51 foci formation assay. The 50 % lethal concentration (LC50) of Insulin-like growth factor type 1 receptor kinase inhibitor (IGF-1Rki) in these cells was assessed, and western immunoblotting was performed to determine the expression of proteins involved in the IGF-1R pathway. Moreover, IGF-1R inhibitors were added on HR proficient cell lines to assess mRNA and protein expression of RAD51 by qPCR and western blot. Also, we explored the interaction between RAD51 and Insulin receptor substance 1 (IRS-1) by immunoprecipitation. Next, combination effect of IGF-1R and PARP inhibitors was evaluated by clonogenic assay. Cells with mutated/methylated BRCA1 showed an impaired HR function, and had an overactivation of the IGF-1R pathway. These cells were more sensitive to IGF-1R inhibition compared to HR proficient cells. In addition, the IGF-IR inhibitor reduced RAD51 expression at mRNA and protein levels in HR proficient cells, and sensitized these cells to PARP inhibitor. Targeting IGF-1R might lead to improved personalized therapeutic approaches in cancer patients with HR deficiency. Targeting both PARP and IGF-1R might increase the clinical efficacy in HR deficient patients and increase the population of patients who may benefit from PARP inhibitors

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin.

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Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C; Gomella, Leonard G; Belfiore, Antonino; Black, Peter C; Iozzo, Renato V; Morrione, Andrea

2016-06-28

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer.

PLATINUM SENSITIVE 2 LIKE impacts growth, root morphology, seed set, and stress responses.

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Amr R A Kataya

Full Text Available Eukaryotic protein phosphatase 4 (PP4 is a PP2A-type protein phosphatase that is part of a conserved complex with regulatory factors PSY2 and PP4R2. Various lines of Arabidopsis thaliana with mutated PP4 subunit genes were constructed to study the so far completely unknown functions of PP4 in plants. Mutants with knocked out putative functional homolog of the PSY2 LIKE (PSY2L gene were dwarf and bushy, while plants with knocked out PP4R2 LIKE (PP4R2L looked very similar to WT. The psy2l seedlings had short roots with disorganized morphology and impaired meristem. Seedling growth was sensitive to the genotoxin cisplatin. Global transcript analysis (RNA-seq of seedlings and rosette leaves revealed several groups of genes, shared between both types of tissues, strongly influenced by knocked out PSY2L. Receptor kinases, CRINKLY3 and WAG1, important for growth and development, were down-regulated 3-7 times. EUKARYOTIC ELONGATION FACTOR5A1 was down-regulated 4-6 fold. Analysis of hormone sensitive genes indicated that abscisic acid levels were high, while auxin, cytokinin and gibberellic acid levels were low in psy2l. Expression of specific transcription factors involved in regulation of anthocyanin synthesis were strongly elevated, e.g. the master regulator PAP1, and intriguingly TT8, which is otherwise mainly expressed in seeds. The psy2l mutants accumulated anthocyanins under conditions where WT did not, pointing to PSY2L as a possible upstream negative regulator of PAP1 and TT8. Expression of the sugar-phosphate transporter GPT2, important for cellular sugar and phosphate homeostasis, was enhanced 7-8 times. Several DNA damage response genes, including the cell cycle inhibitor gene WEE1, were up-regulated in psy2l. The activation of DNA repair signaling genes, in combination with phenotypic traits showing aberrant root meristem and sensitivity to the genotoxic cisplatin, substantiate the involvement of Arabidopsis PSY2L in maintenance of genome

Enhanced sensitivity in non-enzymatic glucose detection by improved growth kinetics of Ni-based nanostructures

Science.gov (United States)

Urso, M.; Pellegrino, G.; Strano, V.; Bruno, E.; Priolo, F.; Mirabella, S.

2018-04-01

Ni-based nanostructures are attractive catalytic materials for many electrochemical applications, among which are non-enzymatic sensing, charge storage, and water splitting. In this work, we clarify the synthesis kinetics of Ni(OH)2/NiOOH nanowalls grown by chemical bath deposition at room temperature and at 50 °C. We applied the results to non-enzymatic glucose sensing, reaching a highest sensitivity of 31 mA cm-2mM-1. Using scanning electron microscopy, x-ray diffraction analysis and Rutherford backscattering spectrometry we found that the growth occurs through two regimes: first, a quick random growth leading to disordered sheets of Ni oxy-hydroxide, followed by a slower growth of well-aligned sheets of Ni hydroxide. A high growth temperature (50 °C), leading mainly to well-aligned sheets, offers superior electrochemical properties in terms of charge storage, charge carrier transport and catalytic action, as confirmed by cyclic voltammetry and electrochemical impedance spectroscopy analyses. The reported results on the optimization and application of low-cost synthesis of these Ni-based nanostructures have a large potential for application in catalysis, (bio)sensing, and supercapacitors areas.

Temperature sensitivity of void nucleation and growth parameters for single crystal copper: a molecular dynamics study

International Nuclear Information System (INIS)

Rawat, S; Chavan, V M; Warrier, M; Chaturvedi, S

2011-01-01

The effect of temperature on the void nucleation and growth is studied using the molecular dynamics (MD) code LAMMPS (Large-Scale Atomic/Molecular Massively Parallel Simulator). Single crystal copper is triaxially expanded at 5 × 10 9  s −1 strain rate keeping the temperature constant. It is shown that the nucleation and growth of voids at these atomistic scales follows a macroscopic nucleation and growth (NAG) model. As the temperature increases there is a steady decrease in the nucleation and growth thresholds. As the melting point of copper is approached, a double-dip in the pressure–time profile is observed. Analysis of this double-dip shows that the first minimum corresponds to the disappearance of the long-range order due to the creation of stacking faults and the system no longer has a FCC structure. There is no nucleation of voids at this juncture. The second minimum corresponds to the nucleation and incipient growth of voids. We present the sensitivity of NAG parameters to temperature and the analysis of double-dip in the pressure–time profile for single crystal copper at 1250 K

Normalized Point Source Sensitivity for Off-Axis Optical Performance Evaluation of the Thirty Meter Telescope

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Seo, Byoung-Joon; Nissly, Carl; Troy, Mitchell; Angeli, George

2010-01-01

The Normalized Point Source Sensitivity (PSSN) has previously been defined and analyzed as an On-Axis seeing-limited telescope performance metric. In this paper, we expand the scope of the PSSN definition to include Off-Axis field of view (FoV) points and apply this generalized metric for performance evaluation of the Thirty Meter Telescope (TMT). We first propose various possible choices for the PSSN definition and select one as our baseline. We show that our baseline metric has useful properties including the multiplicative feature even when considering Off-Axis FoV points, which has proven to be useful for optimizing the telescope error budget. Various TMT optical errors are considered for the performance evaluation including segment alignment and phasing, segment surface figures, temperature, and gravity, whose On-Axis PSSN values have previously been published by our group.

Normal flora of conjunctiva and lid margin, as well as its antibiotic sensitivity, in patients undergoing cataract surgery at Phramongkutklao Hospital

OpenAIRE

Ratnumnoi,Ravee; Keorochana,Narumon; Sonthisombat,Chavalit

2017-01-01

Ravee Ratnumnoi, Narumon Keorochana, Chavalit Sontisombat Department of Ophthalmology, Phramongkutklao Hospital, Bangkok, Thailand Objective: This study aimed to evaluate the normal flora of conjunctiva and lid margin, as well as its antibiotic sensitivity. Design: This was a prospective cross-sectional study. Patients and methods: A prospective study was conducted on 120 patients who underwent cataract surgery at the Phramongkutklao Hospital from September 2014 to October 2014. Conjunctiva...

Increased pain sensitivity but normal function of exercise induced analgesia in hip and knee osteoarthritis--treatment effects of neuromuscular exercise and total joint replacement.

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Kosek, E; Roos, E M; Ageberg, E; Nilsdotter, A

2013-09-01

To assess exercise induced analgesia (EIA) and pain sensitivity in hip and knee osteoarthritis (OA) and to study the effects of neuromuscular exercise and surgery on these parameters. The dataset consisted of knee (n = 66) and hip (n = 47) OA patients assigned for total joint replacement at Lund University Hospital undergoing pre-operative neuromuscular exercise and 43 matched controls. Sensitivity to pressure pain was assessed by pressure algometry at 10 sites. Subjects were then instructed to perform a standardized static knee extension. Pressure pain thresholds (PPTs) were assessed at the contracting quadriceps muscle (Q) and at the resting deltoid muscle (D) before and during contraction. The relative increase in PPTs during contraction was taken as a measure of localized (Q) or generalized (D) EIA. Patients were assessed at baseline, following on average 12 weeks of neuromuscular exercise and 3 months following surgery. We found a normal function of EIA in OA patients at baseline. Previous studies have reported beneficial effects of physical exercise on pain modulation in healthy subjects. However, no treatment effects on EIA were seen in OA patients despite the increase in muscle strength following neuromuscular exercise and reduced pain following surgery. Compared to controls, OA patients had increased pain sensitivity and no beneficial effects on pain sensitivity were seen following treatment. To our knowledge, this is the first study of EIA in OA patients. Despite increased pain sensitivity, OA patients had a normal function of EIA. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effects of topical flurbiprofen sodium, diclofenac sodium, ketorolac tromethamine and benzalkonium chloride on corneal sensitivity in normal dogs

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Raquel de Araújo Cantarella

2017-08-01

Full Text Available To evaluate corneal sensitivity by using the Cochet-Bonnet® esthesiometer in normal canine eyes at different time points following instillation of three different topical non-steroidal anti-inflammatory drugs (flurbiprofen sodium 0.03%, diclofenac sodium 0.1% and ketorolac tromethamine 0.5% and benzalkonium chloride 0.01%. Six healthy mixed breed dogs from the same litter were used in two different stages. First, one drop of flurbiprofen sodium 0.03% and diclofenac sodium 0.1% in each eye; second, one drop of ketorolac tromethamine 0.5% and benzalkonium chloride 0.01% in each eye. Baseline esthesiometry was obtained before eye drop application and every 15 minutes thereafter until a total of 105 minutes of evaluation time. A one-week interval was allowed between the two treatment phases. Statistical analysis was used to compare means according to time of evaluation and drug used. Diclofenac sodium 0.1% decreased corneal sensitivity at 75 and 90 minutes (P > 0.015 with possible interference on neuronal nociceptive activity and analgesic effect while ketorolac tromethamine 0.5% did not show any variation for esthesiometry means along the evaluation. Flurbiprofen sodium 0.03% resulted in increased esthesiometry values 30 minutes after instillation (P > 0.013, increasing corneal sensitivity and possibly producing a greater irritant corneal effect over its analgesic properties. Benzalkonium chloride 0.01% significantly increased corneal sensitivity at 15 minutes of evaluation (P > 0.001, most likely resulting from its irritating effect. Esthesiometry did not allow a definite conclusion over the analgesic effect of the NSAIDs tested; however it was effective in detecting fluctuations in corneal sensitivity.

Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

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Brandt, Benny; Mazaki-Tovi, Shali; Hemi, Rina; Yinon, Yoav; Schiff, Eyal; Mashiach, Roy; Kanety, Hannah; Sivan, Eyal

2015-05-01

Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, Pinsulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Infrastructure mitigates the sensitivity of child growth to local agriculture and rainfall in Nepal and Uganda.

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Shively, Gerald E

2017-01-31

This paper investigates linear growth and weight gain among 11,946 children below the age of 5 y in Nepal and Uganda, testing the hypothesis that child growth is sensitive to precipitation during key periods in a child's early life. The paper also tests the importance of the economic and physical environments in which children reside. Outcomes are not completely explained by agricultural performance or the observed characteristics of children or their households. Associations between height-for-age z-score (HAZ) and weight-for-height z-score (WHZ) and rainfall are generally positive, but patterns are heterogeneous. At the mean, an increase of 1 SD in agricultural season rainfall is associated with a 0.05- to 0.25-point higher z-score, which translates into increases of roughly 4-13% for HAZ and 1-7% for WHZ. Nutrition sensitivity to rainfall is greater in Nepal, where rainfall is lower on average and wider ranging, than in Uganda. Health and transport infrastructure help to buffer children from the deleterious nutritional effects of precipitation shortfalls, underscoring the role of broadly based economic development in promoting child nutrition.

Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy

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Liu, Juntao; Mao, Zhangfan; Huang, Jie; Xie, Songping; Liu, Tianshu; Mao, Zhifu, E-mail: 48151660@qq.com

2014-02-21

Highlights: • Notch signaling pathway members are expressed lower levels in CD133+ cells. • CD133+ cells are not as sensitive as CD133− cells to chemotherapy. • GSI could inhibit the growth of both CD133+ and CD133− cells. • Blockade of Notch signaling pathway enhanced the effect of chemotherapy with CDDP. • DAPT/CDDP co-therapy caused G2/M arrest and elimination in CD133+ cells. - Abstract: Cancer stem cells (CSCs) are believed to play an important role in tumor growth and recurrence. These cells exhibit self-renewal and proliferation properties. CSCs also exhibit significant drug resistance compared with normal tumor cells. Finding new treatments that target CSCs could significantly enhance the effect of chemotherapy and improve patient survival. Notch signaling is known to regulate the development of the lungs by controlling the cell-fate determination of normal stem cells. In this study, we isolated CSCs from the human lung adenocarcinoma cell line A549. CD133 was used as a stem cell marker for fluorescence-activated cell sorting (FACS). We compared the expression of Notch signaling in both CD133+ and CD133− cells and blocked Notch signaling using the γ-secretase inhibitor DAPT (GSI-IX). The effect of combining GSI and cisplatin (CDDP) was also examined in these two types of cells. We observed that both CD133+ and CD133− cells proliferated at similar rates, but the cells exhibited distinctive differences in cell cycle progression. Few CD133+ cells were observed in the G{sub 2}/M phase, and there were half as many cells in S phase compared with the CD133− cells. Furthermore, CD133+ cells exhibited significant resistance to chemotherapy when treated with CDDP. The expression of Notch signaling pathway members, such as Notch1, Notch2 and Hes1, was lower in CD133+ cells. GSI slightly inhibited the proliferation of both cell types and exhibited little effect on the cell cycle. The inhibitory effects of DPP on these two types of cells were

Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

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Yallapu Murali M

2010-04-01

Full Text Available Abstract Background Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. Methods Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid (PLGA nanoparticle formulation of curcumin (Nano-CUR was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. Results Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre

A model for hormonal control of the menstrual cycle: structural consistency but sensitivity with regard to data.

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Selgrade, J F; Harris, L A; Pasteur, R D

2009-10-21

This study presents a 13-dimensional system of delayed differential equations which predicts serum concentrations of five hormones important for regulation of the menstrual cycle. Parameters for the system are fit to two different data sets for normally cycling women. For these best fit parameter sets, model simulations agree well with the two different data sets but one model also has an abnormal stable periodic solution, which may represent polycystic ovarian syndrome. This abnormal cycle occurs for the model in which the normal cycle has estradiol levels at the high end of the normal range. Differences in model behavior are explained by studying hysteresis curves in bifurcation diagrams with respect to sensitive model parameters. For instance, one sensitive parameter is indicative of the estradiol concentration that promotes pituitary synthesis of a large amount of luteinizing hormone, which is required for ovulation. Also, it is observed that models with greater early follicular growth rates may have a greater risk of cycling abnormally.

Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats.

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Liu, Xiaomei; Qi, Ying; Gao, Hong; Jiao, Yisheng; Gu, Hui; Miao, Jianing; Yuan, Zhengwei

2013-01-01

It is well recognized that intrauterine growth restriction leads to the development of insulin resistance and type 2 diabetes mellitus in adulthood. To investigate the mechanisms behind this "metabolic imprinting" phenomenon, we examined the impact of maternal undernutrition on insulin signaling pathway and the ATP sensitive potassium channel expression in the hypothalamus of intrauterine growth restriction fetus. Intrauterine growth restriction rat model was developed through maternal low protein diet. The expression and activated levels of insulin signaling molecules and K(ATP) protein in the hypothalami which were dissected at 20 days of gestation, were analyzed by western blot and real time PCR. The tyrosine phosphorylation levels of the insulin receptor substrate 2 and phosphatidylinositol 3'-kinase p85α in the hypothalami of intrauterine growth restriction fetus were markedly reduced. There was also a downregulation of the hypothalamic ATP sensitive potassium channel subunit, sulfonylurea receptor 1, which conveys the insulin signaling. Moreover, the abundances of gluconeogenesis enzymes were increased in the intrauterine growth restriction livers, though no correlation was observed between sulfonylurea receptor 1 and gluconeogenesis enzymes. Our data suggested that aberrant intrauterine milieu impaired insulin signaling in the hypothalamus, and these alterations early in life might contribute to the predisposition of the intrauterine growth restriction fetus toward the adult metabolic disorders.

Relative sensitivity of Normalized Difference Vegetation Index (NDVI) and Microwave Polarization Difference Index (MPDI) for vegetation and desertification monitoring

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Becker, Francois; Choudhury, Bhaskar J.

1988-01-01

A simple equation relating the Microwave Polarization Difference Index (MPDI) and the Normalized Difference Vegetation Index (NDVI) is proposed which represents well data obtained from Nimbus 7/SMMR at 37 GHz and NOAA/AVHRR Channels 1 and 2. It is found that there is a limit which is characteristic of a particular type of cover for which both indices are equally sensitive to the variation of vegetation, and below which MPDI is more efficient than NDVI. The results provide insight into the relationship between water content and chlorophyll absorption at pixel size scales.

Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

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Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

2018-03-01

Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensitivity of T-Lymphocytes to Hormones of the Anterior Pituitary Gland.

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Tishevskaya, N V; Gevorkyan, N M; Kozlova, N I

2017-01-01

The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and β-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.

On the sensitivity of protein data bank normal mode analysis: an application to GH10 xylanases

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Tirion, Monique M.

2015-12-01

Protein data bank entries obtain distinct, reproducible flexibility characteristics determined by normal mode analyses of their three dimensional coordinate files. We study the effectiveness and sensitivity of this technique by analyzing the results on one class of glycosidases: family 10 xylanases. A conserved tryptophan that appears to affect access to the active site can be in one of two conformations according to x-ray crystallographic electron density data. The two alternate orientations of this active site tryptophan lead to distinct flexibility spectra, with one orientation thwarting the oscillations seen in the other. The particular orientation of this sidechain furthermore affects the appearance of the motility of a distant, C terminal region we term the mallet. The mallet region is known to separate members of this family of enzymes into two classes.

On the sensitivity of protein data bank normal mode analysis: an application to GH10 xylanases

International Nuclear Information System (INIS)

Tirion, Monique M

2015-01-01

Protein data bank entries obtain distinct, reproducible flexibility characteristics determined by normal mode analyses of their three dimensional coordinate files. We study the effectiveness and sensitivity of this technique by analyzing the results on one class of glycosidases: family 10 xylanases. A conserved tryptophan that appears to affect access to the active site can be in one of two conformations according to x-ray crystallographic electron density data. The two alternate orientations of this active site tryptophan lead to distinct flexibility spectra, with one orientation thwarting the oscillations seen in the other. The particular orientation of this sidechain furthermore affects the appearance of the motility of a distant, C terminal region we term the mallet. The mallet region is known to separate members of this family of enzymes into two classes. (paper)

Perinatal Changes of Cardiac Troponin-I in Normal and Intrauterine Growth-Restricted Pregnancies

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Nicoletta Iacovidou

2007-01-01

Full Text Available Intrauterine growth restriction (IUGR implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart. Serum cardiac Troponin-I (cTnI, a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state, and their 20 IUGR and 20 appropriate-for-gestational-age (AGA neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r≥.498, P≤.025 in all cases in the AGA and r≥.615, P≤.009 in all cases in the IUGR group. These results may indicate (a normal heart function, due to heart sparing, in the IUGR group (b potential crossing of the placental barrier by cTnI in both groups

Flux sensitivity of a piecewise normal and superconducting metal loop

International Nuclear Information System (INIS)

Buettiker, M.; Klapwijk, T.M.

1986-01-01

We consider a loop composed of a superconducting segment and a normal segment with an Aharonov-Bohm flux through the hole of the loop. The normal segment is assumed to be long compared to the superconducting coherence length xi but short compared to a mean inelastic diffusion length. The elementary excitation spectrum of the ground state of this loop is periodic with period hc/2e as long as the superconducting segment is larger than xi. If the superconducting segment length becomes of the order of xi, quasiparticles can tunnel through the superconducting gap and give rise to an excitation spectrum which is periodic with period hc/e. .AE

Regional polarization sensitivity of articular cartilage by using polarization sensitive optical coherence tomography

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Xie, Tuqiang; Guo, Shuguang; Chen, Zhongping; Peavy, George M.

2007-02-01

In this study, PS-OCT is used to image fresh bovine joints to investigate the orientation of collagen fibrils in relation to optical phase retardation to better understand the distribution of normal matrix orientation and articular cartilage birefringence in different regions of a whole joint. Understanding and mapping variations in matrix organization and orientation within the normal joint is an important issue in potential applications of PS-OCT for evaluation and diagnosis of degenerative joint disease (DJD). The experimental results demonstrate that articular cartilage is not polarization sensitive on the edge of the medial, but polarization sensitive on the lateral edge of the tibial plateau. The collagen orientation on the edge of the joint is different from the central areas of the joint. Normal articular cartilage demonstrates regional polarization sensitivity within joints that is important to understand in order to accurately assess cartilage health by PS-OCT.

IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition.

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Reid, Tirissa J; Jin, Zhezhen; Shen, Wei; Reyes-Vidal, Carlos M; Fernandez, Jean Carlos; Bruce, Jeffrey N; Kostadinov, Jane; Post, Kalmon D; Freda, Pamela U

2015-12-01

Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

The Assessment of Cognitive Emotion Regulation Strategies, Sensory Processing Sensitivity and Anxiety Sensitivity in Patients with Multiple Sclerosis

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Esmeil Soleymani

2016-11-01

Full Text Available Abstract Background: The purpose of this study was to compare the cognitive emotional regulation strategies, sensory processing sensitivity and anxiety sensitivity in patients with multiple sclerosis and normal people. Materials and Methods: Statistical population of this study was all of patients with multiple sclerosis that referred to M.S association of Iran in the tehran. Sample of this study was 30 individuals of patients with multiple sclerosis selected by available sampling method and were matched with 30 individuals of normal people. Two groups completed cognitive emotion regulation, high sensory processing sensitivity and anxiety sensitivity questionnaires. Data were analyzed by one-way analysis of variance and Multivariate Analysis of Variance. Results: The results indicated that there is significant difference between two groups in view of cognitive emotion regulation strategies in which the mean of scores of patients with multiple sclerosis in maladaptive strategies of self- blame, catastrophizing and other blame were more than normal people and mean of scores of them in adaptive strategies of positive refocusing, positive reappraisal and putting into perspective were less than normal people. The results also indicated that there is a significant difference between two groups in anxiety sensitivity and sensory processing sensitivity. Conclusion: The most of emotional problems in patients with multiple sclerosis can be the result of more application of maladaptive strategies of cognitive emotion regulation, high sensory processing sensitivity and high anxiety sensitivity.

Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

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Nicoletta Iacovidou

2008-01-01

Full Text Available Ischemia-modified albumin (IMA is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—‘‘brain sparing effect’’. Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035, and offspring of multigravidas (P = .021. In conclusion, ‘‘brain sparing effect’’ is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

Sensitivity of open-water ice growth and ice concentration evolution in a coupled atmosphere-ocean-sea ice model

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Shi, Xiaoxu; Lohmann, Gerrit

2017-09-01

A coupled atmosphere-ocean-sea ice model is applied to investigate to what degree the area-thickness distribution of new ice formed in open water affects the ice and ocean properties. Two sensitivity experiments are performed which modify the horizontal-to-vertical aspect ratio of open-water ice growth. The resulting changes in the Arctic sea-ice concentration strongly affect the surface albedo, the ocean heat release to the atmosphere, and the sea-ice production. The changes are further amplified through a positive feedback mechanism among the Arctic sea ice, the Atlantic Meridional Overturning Circulation (AMOC), and the surface air temperature in the Arctic, as the Fram Strait sea ice import influences the freshwater budget in the North Atlantic Ocean. Anomalies in sea-ice transport lead to changes in sea surface properties of the North Atlantic and the strength of AMOC. For the Southern Ocean, the most pronounced change is a warming along the Antarctic Circumpolar Current (ACC), owing to the interhemispheric bipolar seasaw linked to AMOC weakening. Another insight of this study lies on the improvement of our climate model. The ocean component FESOM is a newly developed ocean-sea ice model with an unstructured mesh and multi-resolution. We find that the subpolar sea-ice boundary in the Northern Hemisphere can be improved by tuning the process of open-water ice growth, which strongly influences the sea ice concentration in the marginal ice zone, the North Atlantic circulation, salinity and Arctic sea ice volume. Since the distribution of new ice on open water relies on many uncertain parameters and the knowledge of the detailed processes is currently too crude, it is a challenge to implement the processes realistically into models. Based on our sensitivity experiments, we conclude a pronounced uncertainty related to open-water sea ice growth which could significantly affect the climate system sensitivity.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

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Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

2016-01-01

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

Comparison of blood lead levels of mothers and cord blood in intrauterine growth retarded neonates and normal term neonates

International Nuclear Information System (INIS)

Iranpour, R.; Besharati, Amir A.; Nasseri, F.; Hashemipour, M.; Kelishadi, R.; Balali-Mood, M.

2007-01-01

Objective was to compare the blood lead levels of mothers and cord blood in intrauterine growth retarded (IUGR) neonates and normal term neonates. From April 2005, we carried out a cross-sectional, prospective study in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were measured in the umbilical cord and maternal venous blood samples in the 32 mother-infant pairs with IUGR full term neonates and 34 mother-infant pairs with normal full term neonates. Blood-lead levels were analyzed by atomic absorption spectrometry. The mean lead concentration in neonates of IUGR and normal groups was not significantly different (107.47+- 16.75 versus 113.08+-19.08 ug/L, p=0.2). The mean lead concentration in mothers of IUGR group was lower than normal groups, but this difference was not significant (124.56+-19.71 versus 135.26+-26.91 ug/L, p=0.07). Maternal lead levels were strongly related with related with cord blood in both IUGR and normal groups (r=0.8, p 100ug/L by the centers for disease control; however, this was not statistically different between the groups. Our results indicate that the mean lead level was not higher in IUGR neonates, and the whole blood lead was not related to the birth weight. In addition, maternal and cord blood lead levels were strongly correlated, and there were remarkable lead burdens on both the mothers and their neonates in this industrial area. (author)

A sensitive electrochemiluminescence cytosensor for quantitative evaluation of epidermal growth factor receptor expressed on cell surfaces

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Tang, Yanjuan; Zhang, Shaolian; Wen, Qingqing; Huang, Hongxing; Yang, Peihui, E-mail: typh@jnu.edu.cn

2015-06-30

Highlights: • EGF-cytosensor was used for evaluating EGFR expression level on cell surfaces. • CdSQDs and EGF were coated on magnetic beads (MBs) for ECL-probe. • Good sensitivity was achieved due to the signal amplification of ECL-probe. - Abstract: A sensitive electrochemiluminescence (ECL) strategy for evaluating the epidermal growth factor receptor (EGFR) expression level on cell surfaces was designed by integrating the specific recognition of EGFR expressed on MCF-7 cell surfaces with an epidermal growth factor (EGF)-funtionalized CdS quantum dots (CdSQDs)-capped magnetic bead (MB) probe. The high sensitivity of ECL probe of EGF-funtionalized CdSQD-capped-MB was used for competitive recognition with EGFR expressed on cell surfaces with recombinant EGFR protein. The changes of ECL intensity depended on both the cell number and the expression level of EGFR receptor on cell surfaces. A wide linear response to cells ranging from 80 to 4 × 10{sup 6} cells mL{sup −1} with a detection limit of 40 cells mL{sup −1} was obtained. The EGF-cytosensor was used to evaluate EGFR expression levels on MCF-7 cells, and the average number of EGFR receptor on single MCF-7 cells was 1.35 × 10{sup 5} with the relative standard deviation of 4.3%. This strategy was further used for in-situ and real-time evaluating EGFR receptor expressed on cell surfaces in response to drugs stimulation at different concentration and incubation time. The proposed method provided potential applications in the detection of receptors on cancer cells and anticancer drugs screening.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

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Sang Soo Lee

2017-03-01

Full Text Available Growth hormone (GH is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD caused by pituitary stalk interruption syndrome (PSIS. The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD. Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Sensitivity of Photosynthetic Gas Exchange and Growth of Lodgepole Pine to Climate Variability Depends on the Age of Pleistocene Glacial Surfaces

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Osborn, B.; Chapple, W.; Ewers, B. E.; Williams, D. G.

2014-12-01

The interaction between soil conditions and climate variability plays a central role in the ecohydrological functions of montane conifer forests. Although soil moisture availability to trees is largely dependent on climate, the depth and texture of soil exerts a key secondary influence. Multiple Pleistocene glacial events have shaped the landscape of the central Rocky Mountains creating a patchwork of soils differing in age and textural classification. This mosaic of soil conditions impacts hydrological properties, and montane conifer forests potentially respond to climate variability quite differently depending on the age of glacial till and soil development. We hypothesized that the age of glacial till and associated soil textural changes exert strong control on growth and photosynthetic gas exchange of lodgepole pine. We examined physiological and growth responses of lodgepole pine to interannual variation in maximum annual snow water equivalence (SWEmax) of montane snowpack and growing season air temperature (Tair) and vapor pressure deficit (VPD) across a chronosequence of Pleistocene glacial tills ranging in age from 700k to 12k years. Soil textural differences across the glacial tills illustrate the varying degrees of weathering with the most well developed soils with highest clay content on the oldest till surfaces. We show that sensitivity of growth and carbon isotope discrimination, an integrated measure of canopy gas exchange properties, to interannual variation SWEmax , Tair and VPD is greatest on young till surfaces, whereas trees on old glacial tills with well-developed soils are mostly insensitive to these interannual climate fluctuations. Tree-ring widths were most sensitive to changes in SWEmax on young glacial tills (p < 0.01), and less sensitive on the oldest till (p < 0.05). Tair correlates strongly with δ13C values on the oldest and youngest tills sites, but shows no significant relationship on the middle aged glacial till. It is clear that

Selecting short-statured children needing growth hormone testing: Derivation and validation of a clinical decision rule

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Bréart Gérard

2008-07-01

Full Text Available Abstract Background Numerous short-statured children are evaluated for growth hormone (GH deficiency (GHD. In most patients, GH provocative tests are normal and are thus in retrospect unnecessary. Methods A retrospective cohort study was conducted to identify predictors of growth hormone (GH deficiency (GHD in children seen for short stature, and to construct a very sensitive and fairly specific predictive tool to avoid unnecessary GH provocative tests. GHD was defined by the presence of 2 GH concentration peaks Results The initial study included 167 patients, 36 (22% of whom had GHD, including 5 (3% with certain GHD. Independent predictors of GHD were: growth rate Conclusion We have derived and performed an internal validation of a highly sensitive decision rule that could safely help to avoid more than 2/3 of the unnecessary GH tests. External validation of this rule is needed before any application.

Growth hormone insensitivity syndrome: A sensitive approach

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Soumik Goswami

2012-01-01

Full Text Available Patients with Growth Hormone Insensitivity have characteristic phenotypic features and severe short stature. The underlying basis are mutations in the growth hormone receptor gene which gives rise to a characteristic hormonal profile. Although a scoring system has been devised for the diagnosis of this disorder, it has not been indisputably validated. The massive expense incurred in the diagnosis and treatment of this condition with suboptimal therapeutic response necessitates a judicious approach in this regard in our country.

Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

International Nuclear Information System (INIS)

Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R.

1990-01-01

Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV

Normal Cerebellar Growth by Using Three-dimensional US in the Preterm Infant from Birth to Term-corrected Age.

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Benavente-Fernández, Isabel; Rodríguez-Zafra, Enrique; León-Martínez, Jesús; Jiménez-Gómez, Gema; Ruiz-González, Estefanía; Fernández-Colina, Rosalía Campuzano; Lechuga-Sancho, Alfonso M; Lubián-López, Simón P

2018-04-03

Purpose To establish cross-sectional and longitudinal reference values for cerebellar size in preterm infants with normal neuroimaging findings and normal 2-year neurodevelopmental outcome by using cranial ultrasonography (US). Materials and Methods This prospective study consecutively enrolled preterm infants admitted to a neonatal intensive care unit from June 2011 to June 2014 with a birth weight of less than or equal to 1500 g and/or gestational age (GA) of less than or equal to 32 weeks. They underwent weekly cranial US from birth to term-equivalent age and magnetic resonance (MR) imaging at term-equivalent age. The infants underwent neurodevelopmental assessments at age 2 years with Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). Patients with adverse outcomes (death or abnormal neuroimaging findings and/or BSID-III score of growth in preterm infants, which may be included in routine cranial US. © RSNA, 2018 Online supplemental material is available for this article.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

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Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

2015-06-15

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

International Nuclear Information System (INIS)

Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

2015-01-01

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy

Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

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Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

2012-12-13

Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

Early dietary treated patients with phenylketonuria can achieve normal growth and body composition.

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Rocha, Júlio C; van Spronsen, Francjan J; Almeida, Manuela F; Ramos, Elisabete; Guimarães, João T; Borges, Nuno

2013-01-01

In the past, overtreatment may have resulted in growth impairment in patients with phenylketonuria. The paper aims to investigate height and body composition in early treated patients with phenylketonuria who were diagnosed between 1981 and 2008. A cross-sectional study of 89 patients with phenylketonuria and 78 controls aged (mean ± SD, in years) 14.4 ± 6.6 and 15.9 ± 7.1, respectively, was undertaken, including anthropometric and body composition evaluation using bioelectrical impedance. Median Phe concentrations in the last year before study enrollment were used as a measure of metabolic control. Natural protein and amino acid mixture intakes were recorded in patients. No statistically significant differences were found on height z-scores between patients and controls aged less than 19 years (p=0.301), although all patients with classical phenylketonuria revealed negative height z-scores, resulting in a mean ± SD of -0.65 ± 0.41. Among participants aged 19 years or more, median (p25-p75) of height was significantly higher in controls [168.0 cm (159.2-174.8)] than in patients [160.5 cm (151.9-167.5)] (p=0.017). No significant differences were found between patients and controls regarding fat mass, fat free mass, muscular mass, body cell mass index and phase angle. Our results suggest that early and continuously treated patients with phenylketonuria born after 1992 can achieve normal growth and body composition, although the negative height z-score in patients with classical phenylketonuria strengthens the continuous need to optimize the quality of their protein intake. © 2013 Elsevier Inc. All rights reserved.

Quantitative automated microscopy (QuAM elucidates growth factor specific signalling in pain sensitization

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Levine Jon D

2010-12-01

Full Text Available Abstract Background Dorsal root ganglia (DRG-neurons are commonly characterized immunocytochemically. Cells are mostly grouped by the experimenter's eye as "marker-positive" and "marker-negative" according to their immunofluorescence intensity. Classification criteria remain largely undefined. Overcoming this shortfall, we established a quantitative automated microscopy (QuAM for a defined and multiparametric analysis of adherent heterogeneous primary neurons on a single cell base. The growth factors NGF, GDNF and EGF activate the MAP-kinase Erk1/2 via receptor tyrosine kinase signalling. NGF and GDNF are established factors in regeneration and sensitization of nociceptive neurons. If also the tissue regenerating growth factor, EGF, influences nociceptors is so far unknown. We asked, if EGF can act on nociceptors, and if QuAM can elucidate differences between NGF, GDNF and EGF induced Erk1/2 activation kinetics. Finally, we evaluated, if the investigation of one signalling component allows prediction of the behavioral response to a reagent not tested on nociceptors such as EGF. Results We established a software-based neuron identification, described quantitatively DRG-neuron heterogeneity and correlated measured sample sizes and corresponding assay sensitivity. Analysing more than 70,000 individual neurons we defined neuronal subgroups based on differential Erk1/2 activation status in sensory neurons. Baseline activity levels varied strongly already in untreated neurons. NGF and GDNF subgroup responsiveness correlated with their subgroup specificity on IB4(+- and IB4(--neurons, respectively. We confirmed expression of EGF-receptors in all sensory neurons. EGF treatment induced STAT3 translocation into the nucleus. Nevertheless, we could not detect any EGF induced Erk1/2 phosphorylation. Accordingly, intradermal injection of EGF resulted in a fundamentally different outcome than NGF/GDNF. EGF did not induce mechanical hyperalgesia, but blocked

The effects of environmental deuterium on normal and neoplastic cultured cell development

International Nuclear Information System (INIS)

Bild, W.; Schuller, T.; Zhihai, Qin; Blankenstein, T.; Nastasa, V.; Haulica, I.

2000-01-01

The powdered culture media (RPMI - 1640) were reconstituted either with normal distilled water (150 ppm deuterium) either with deuterium - depleted water (DDW) in various concentrations (30, 60, 90 ppm) and sterilized by filtration with 0.2 μm filters. The cell lines used were NIH (normal mouse fibroblasts), RAG (mouse renal carcinoma) and TS/A (mouse mammary adenocarcinoma). In auxiliary tests, BAIBC mouse splenocytes in direct culture were used, stimulated for growth with concanavalin A or LPS (bacterial lipopolysaccharide). The estimation of the growth was made using the MTT assay or direct counting with trypan blue exclusion. The following results were obtained: Deuterium - depleted water had a stimulating effect on cell growth, the most important stimulating action being from the 90 ppm deuterium-water. The growth curves show, in a first phase, a stimulation of the rapid -growing neoplastic cells, followed by a slower growth of the normal cells. Amiloride 100 mM blocking of the Na + /K + membrane pump did not affect the cell growth curves, while the lansoprazole 100 mM blocking of the K + /H + ATP-ase brought the growth curves at the level of those with normal water. This might show an eventual involvement of the K + /H + antiport in the stimulating effects of the DDW. (authors)

Insulin sensitivity and insulin secretion at birth in intrauterine growth retarded infants.

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Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Lata; Vinayagamoorti, R; John, Mathew

2006-06-01

To study insulin sensitivity, secretion and relation of insulin levels with birth weight and ponderal index in intrauterine growth retarded (IUGR) infants at birth. We studied 30 IUGR and 30 healthy newborns born at term by vaginal delivery in Jipmer, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of plasma glucose and insulin. When compared with healthy newborns, IUGR newborns had lower plasma glucose levels (mean 2.3+/-0.98 versus 4.1+/-0.51 mmol/L, p<0.001); lower plasma insulin levels (mean 4.5+/-2.64 versus 11.03+/-1.68 microU/L, p<0.001); higher insulin sensitivity calculated using G/I ratio (mean 11.6+/-5.1 versus 6.7+/-0.31, p<0.001), HOMA IS (mean 5.5+/-6.0 versus 0.53+/-0.15, p<0.001), and QUICKI (mean 0.47+/-0.12 versus 0.34+/-0.02, p<0.001); and decreased pancreatic beta-cell function test measured as I/G (mean 0.10+/-0.037 versus 0.15+/-0.006, p<0.001). A positive correlation was identified between insulin levels and birth weight in both the healthy control group (r2 = 0.17, p = 0.024) and IUGR group (r2 = 0.13, p = 0.048). However correlation of insulin levels with ponderal index was much more confident in both healthy control (r2 = 0.90, p<0.001) and IUGR groups (r2 = 0.28, p = 0.003). Insulin status correlated both with birth weight and ponderal index more confidently in control group than in IUGR group. At birth, IUGR infants are hypoglycaemic, hypoinsulinaemic and display increased insulin sensitivity and decreased pancreatic beta-cell function. Insulin levels correlate with ponderal index much more confidently than with birth weight.

Crop yield response to water stress imposed at different growth stages

International Nuclear Information System (INIS)

Iqbal, M.; Mahmood Shah, M.; Wisal, M.

1995-01-01

Potato requires sufficient soil moisture and fertilization to produce high yields but the present water resoures are limited compared to the cultivable land, field experiments were conduced from 1991 to 1995 to study relationship between yield and crop water use as a function of water stress imposed at different growth stages. The irrigation treatments involved application of full and stress watering s selectively at four growth stages : Establishment , Flowering Tuber formation and ripening. In full watering, full water requirements of the crop were met, i.e., ET sub a = ET sub m whereas in stress watering about half the amount of full watering was applied, i.e., ET sub a < ET sub m. Changes in moisture content of the soil pre files after irrigation were monitored with the help of neutron moisture probe in order to compute ET sub a by the water balance method. The results obtained showed that the tuber yield was produced by full watering ( T 1) and the lowest by continuous stress watering (T 2). A plot of relative yield against relative evapotranspiration deficit revealed that ripening was the lest sensitive whereas early development followed by flowering the most sensitive growth stage to water stress. The crop water use efficiencies were generally higher in the treatments where a combination of normal and stress watering was applied compared to where all - normal watering s were applied. The traditional irrigation practice resulted in wasteful water application with relatively lower yields, hence the results from this project will have high value for the farming community to get this higher yields with scarce water resources. The studies with labelled fertilizer showed that planting and earthing - up were equally important growth stages of potato for applying fertilizer for its efficient utilization. 3 figs; 25 tabs; 12 refs (Author)

Modification of the cellular heat sensitivity of cucumber by growth under supplemental ultraviolet-B radiation

International Nuclear Information System (INIS)

Caldwell, C.R.

1994-01-01

The effect of ultraviolet B (UV-B) radiation on the thermal sensitivity of cucumber (Cucumis sativus L.) was studied using UV-B-sensitive cv Poinsett 76 and UV-B-resistant cv Ashley grown under control and elevated (300 mW m -2 ) UV-B radiation levels. Using both cotyledon and leaf discs, the ability of the tissue to reduce triphenyl tetrazolium chloride (TTC) was determined after treatment at 50 degrees C for various times. Semilogarithmic plots of TTC reduction as a function of time at 50 degrees were curvilinear. They were monophasic for the control cucumber and biphasic for cucumber grown in the presence of elevated UV-B. Treatment of cucumber plants at 37 degrees C for 24 h or of tissue discs at acute UV-B levels for 1 h further modified their response to elevated temperature. These results suggest that growth of cucumber under enhanced UV-B radiation levels increased its ability to withstand elevated temperatures. 19 refs., 2 figs., 2 tabs

Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis.

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Fan, Yu; Wang, Ye; Wang, Ke

2015-12-18

Cyclooxygenase-2-derived prostaglandin E2 (PGE2), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE2 stimulated lung cancer cell growth and progression through PGE2 receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE2 in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE2. The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE2. PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE2 receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. We demonstrated that PGE2 increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE2 on normal cell growth. The PGE2-induced PDK1 expression was blocked by an antagonist of the PGE2 receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE2 was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE2. In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. PGE2 increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell

Steel billet reheat simulation with growth of oxide layer and investigation on zone temperature sensitivity

International Nuclear Information System (INIS)

Dubey, Satish Kumar; Srinivasan, P.

2014-01-01

This paper presents a three-dimensional heat conduction numerical model and simulation of steel billet reheating in a reheat furnace. The model considers the growth of oxide scale on the billet surfaces. Control-volume approach and implicit scheme of finite difference method are used to discretize the transient heat conduction equation. The model is validated with analytical results subject to limited conditions. Simulations are carried out for predictions of three-dimensional temperature filed in the billet and oxide scale growth on the billet surfaces. The model predictions are in agreement with expected trends. It was found that the effect of oxide scale on billet heating is considerable. In order to investigate the effect of zone temperatures on the responses, a parametric sensitivity subject to six responses of interest are carried out using analysis of mean approach. The simulation approach and parametric study presented will be useful and applicable to the steel industry.

Growth mechanism of titanium dioxide nanowires for dye-sensitized solar cells

International Nuclear Information System (INIS)

Boercker, J E; Enache-Pommer, E; Aydil, E S

2008-01-01

Mesoporous films made of titanium dioxide nanowires are desirable for dye-sensitized solar cells because nanowires provide direct conduction pathways for photogenerated electrons. Anatase titanium dioxide nanowires with polycrystalline microstructure were synthesized on titanium foil using a three-step process. First, the top surface of the titanium foil was transformed to Na 2 Ti 2 O 4 (OH) 2 nanotubes through hydrothermal oxidation in NaOH. Next, the Na 2 Ti 2 O 4 (OH) 2 nanotubes were converted to H 2 Ti 2 O 4 (OH) 2 nanotubes by ion exchange. Finally, the H 2 Ti 2 O 4 (OH) 2 nanotubes were converted to polycrystalline anatase nanowires through a topotactic transformation. The film morphology evolution, crystal structure transformations and growth mechanism are described in detail. Titanium foil reacts with NaOH to form Na 2 Ti 2 O 4 (OH) 2 sheets, which exfoliate and spiral into nanotubes. The Na 2 Ti 2 O 4 (OH) 2 nanotubes are immersed in HCl solution to replace the Na + ions with H + ions. During the topotactic transformation of H 2 Ti 2 O 4 (OH) 2 nanotubes to anatase TiO 2 nanowires, the sheets made of edge bonded TiO 6 octahedra in the H 2 Ti 2 O 4 (OH) 2 nanotubes dehydrate and move towards each other to form anatase crystals oriented along the nanotube axis which creates a polycrystalline nanowire. These mesoporous TiO 2 nanowire films were suitable for use as dye-sensitized solar cell photoanodes

Short-term arginine deprivation results in large-scale modulation of hepatic gene expression in both normal and tumor cells: microarray bioinformatic analysis

Directory of Open Access Journals (Sweden)

Sabo Edmond

2006-09-01

Full Text Available Abstract Background We have reported arginine-sensitive regulation of LAT1 amino acid transporter (SLC 7A5 in normal rodent hepatic cells with loss of arginine sensitivity and high level constitutive expression in tumor cells. We hypothesized that liver cell gene expression is highly sensitive to alterations in the amino acid microenvironment and that tumor cells may differ substantially in gene sets sensitive to amino acid availability. To assess the potential number and classes of hepatic genes sensitive to arginine availability at the RNA level and compare these between normal and tumor cells, we used an Affymetrix microarray approach, a paired in vitro model of normal rat hepatic cells and a tumorigenic derivative with triplicate independent replicates. Cells were exposed to arginine-deficient or control conditions for 18 hours in medium formulated to maintain differentiated function. Results Initial two-way analysis with a p-value of 0.05 identified 1419 genes in normal cells versus 2175 in tumor cells whose expression was altered in arginine-deficient conditions relative to controls, representing 9–14% of the rat genome. More stringent bioinformatic analysis with 9-way comparisons and a minimum of 2-fold variation narrowed this set to 56 arginine-responsive genes in normal liver cells and 162 in tumor cells. Approximately half the arginine-responsive genes in normal cells overlap with those in tumor cells. Of these, the majority was increased in expression and included multiple growth, survival, and stress-related genes. GADD45, TA1/LAT1, and caspases 11 and 12 were among this group. Previously known amino acid regulated genes were among the pool in both cell types. Available cDNA probes allowed independent validation of microarray data for multiple genes. Among genes downregulated under arginine-deficient conditions were multiple genes involved in cholesterol and fatty acid metabolism. Expression of low-density lipoprotein receptor was

Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

Science.gov (United States)

Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

2016-06-01

Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

Relationship of radiation sensitivity and aberrant DNA synthesis in repair deficient CHO cells

International Nuclear Information System (INIS)

Newman, C.N.; Hagler, H.; Miller, J.H.

1986-11-01

Comparison of alkaline sucrose gradient profiles of pulse-labeled DNA from a normal CHO cell line and its radiation-sensitive mutant, xrs-5, reveals significant differences in the replicon elongation/maturation process in these two cells. During a one hr period of growth subsequent to labeling, the molecular weight of pulse-labeled DNA from the mutant cell increases considerably more rapidly than that of the parent cell. For xrs-5, the presence of 2 mM deoxycytidine (CdR) in the culture medium reduces the replication rate to one approaching that of the parent cell growing in the standard medium. Corresponding uv resistance of the mutant likewise increases to nearly that of the parent cell line. These results suggest that the locus conferring radiation sensitivity to xrs-5 affects the DNA replisome complex and that replicative activity and radiation sensitivity are jointly modulated by CdR. 19 refs., 4 figs

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells.

Science.gov (United States)

Karimpoor, Mahroo; Yebra-Fernandez, Eva; Parhizkar, Maryam; Orlu, Mine; Craig, Duncan; Khorashad, Jamshid S; Edirisinghe, Mohan

2018-04-01

The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells. © 2018 The Author(s).

Relationship between Inflammation markers, Coagulation Activation and Impaired Insulin Sensitivity in Obese Healthy Women

International Nuclear Information System (INIS)

Soliman, S.Et; Shousha, M.A.

2011-01-01

Obesity, insulin resistance syndrome, and atherosclerosis are closely linked phenomena, often connected with a chronic low grade inflammatory state and pro thrombotic hypo fibrinolytic condition. This study investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. The study included 36 healthy obese women (body mass index ≥ 30), with normal insulin sensitivity (NIS, n = 18) or impaired insulin sensitivity (IIS, n 18), and 10 non obese women (body mass index < 25).Impaired insulin sensitivity patients had significantly higher levels of high sensitivity C-reactive protein (hs-CRP), transforming growth factor -β1(TGF-β1), plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragments 1 + 2 (F1 + 2) compared with either control subjects or normal insulin sensitivity patients. On the other hand, NIS patients had higher hs-CRP, TGF-β1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-β1, hs-CRP, PAI-1; factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-β1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-β1 and the insulin sensitivity index were independently related to F1 + 2. These results document an in vivo relationship between insulin sensitivity and coagulation activation in obesity. Here we report that obesity is associated with higher TGF-β, PAI-1, prothrombin fragments 1 and 2 (F1 + 2), and activated factor VII (VIIa) plasma levels, and that insulin resistance exacerbates these alterations. The elevated TGF-β1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease

Manipulating Rayleigh-Taylor Growth Using Adjoints

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Kord, Ali; Capecelatro, Jesse

2017-11-01

It has been observed that initial interfacial perturbations affect the growth of Rayleigh-Taylor (RT) instabilities. However, it remains to be seen to what extent the perturbations alter the RT growth rate. Direct numerical simulations (DNS) provide a powerful means for studying the effects of initial conditions (IC) on the growth rate. However, a brute-force approach for identifying optimal initial perturbations is not practical via DNS. In addition, identifying sensitivity of the RT growth to the large number of parameters used in defining the IC is computationally expensive. A discrete adjoint is formulated to measure sensitivities of multi-mode RT growth to ICs in a high-order finite difference framework. The sensitivity is used as a search direction for adjusting the initial perturbations to both maximize and suppress the RT growth rate during its non-linear regime. The modes that contribute the greatest sensitivity are identified, and optimized perturbation energy spectrum are reported. PhD Student, Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI.

Effects of normalization on quantitative traits in association test

Science.gov (United States)

2009-01-01

Background Quantitative trait loci analysis assumes that the trait is normally distributed. In reality, this is often not observed and one strategy is to transform the trait. However, it is not clear how much normality is required and which transformation works best in association studies. Results We performed simulations on four types of common quantitative traits to evaluate the effects of normalization using the logarithm, Box-Cox, and rank-based transformations. The impact of sample size and genetic effects on normalization is also investigated. Our results show that rank-based transformation gives generally the best and consistent performance in identifying the causal polymorphism and ranking it highly in association tests, with a slight increase in false positive rate. Conclusion For small sample size or genetic effects, the improvement in sensitivity for rank transformation outweighs the slight increase in false positive rate. However, for large sample size and genetic effects, normalization may not be necessary since the increase in sensitivity is relatively modest. PMID:20003414

Effects of normalization on quantitative traits in association test

Directory of Open Access Journals (Sweden)

Yap Von Bing

2009-12-01

Full Text Available Abstract Background Quantitative trait loci analysis assumes that the trait is normally distributed. In reality, this is often not observed and one strategy is to transform the trait. However, it is not clear how much normality is required and which transformation works best in association studies. Results We performed simulations on four types of common quantitative traits to evaluate the effects of normalization using the logarithm, Box-Cox, and rank-based transformations. The impact of sample size and genetic effects on normalization is also investigated. Our results show that rank-based transformation gives generally the best and consistent performance in identifying the causal polymorphism and ranking it highly in association tests, with a slight increase in false positive rate. Conclusion For small sample size or genetic effects, the improvement in sensitivity for rank transformation outweighs the slight increase in false positive rate. However, for large sample size and genetic effects, normalization may not be necessary since the increase in sensitivity is relatively modest.

Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

Science.gov (United States)

Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

2014-09-01

Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth.

Science.gov (United States)

Li, Hongde; Chawla, Geetanjali; Hurlburt, Alexander J; Sterrett, Maria C; Zaslaver, Olga; Cox, James; Karty, Jonathan A; Rosebrock, Adam P; Caudy, Amy A; Tennessen, Jason M

2017-02-07

L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification, and cell differentiation. However, despite the ability of L-2HG to interfere with a broad range of cellular processes, this molecule is often characterized as a metabolic waste product. Here, we demonstrate that Drosophila larvae use the metabolic conditions established by aerobic glycolysis to both synthesize and accumulate high concentrations of L-2HG during normal developmental growth. A majority of the larval L-2HG pool is derived from glucose and dependent on the Drosophila estrogen-related receptor (dERR), which promotes L-2HG synthesis by up-regulating expression of the Drosophila homolog of lactate dehydrogenase (dLdh). We also show that dLDH is both necessary and sufficient for directly synthesizing L-2HG and the Drosophila homolog of L-2-hydroxyglutarate dehydrogenase (dL2HGDH), which encodes the enzyme that breaks down L-2HG, is required for stage-specific degradation of the L-2HG pool. In addition, dLDH also indirectly promotes L-2HG accumulation via synthesis of lactate, which activates a metabolic feed-forward mechanism that inhibits dL2HGDH activity and stabilizes L-2HG levels. Finally, we use a genetic approach to demonstrate that dLDH and L-2HG influence position effect variegation and DNA methylation, suggesting that this compound serves to coordinate glycolytic flux with epigenetic modifications. Overall, our studies demonstrate that growing animal tissues synthesize L-2HG in a controlled manner, reveal a mechanism that coordinates glucose catabolism with L-2HG synthesis, and establish the fly as a unique model system for studying the endogenous functions of L-2HG during cell growth and proliferation.

Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth

Science.gov (United States)

Li, Hongde; Chawla, Geetanjali; Hurlburt, Alexander J.; Sterrett, Maria C.; Zaslaver, Olga; Cox, James; Karty, Jonathan A.; Rosebrock, Adam P.; Caudy, Amy A.

2017-01-01

L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification, and cell differentiation. However, despite the ability of L-2HG to interfere with a broad range of cellular processes, this molecule is often characterized as a metabolic waste product. Here, we demonstrate that Drosophila larvae use the metabolic conditions established by aerobic glycolysis to both synthesize and accumulate high concentrations of L-2HG during normal developmental growth. A majority of the larval L-2HG pool is derived from glucose and dependent on the Drosophila estrogen-related receptor (dERR), which promotes L-2HG synthesis by up-regulating expression of the Drosophila homolog of lactate dehydrogenase (dLdh). We also show that dLDH is both necessary and sufficient for directly synthesizing L-2HG and the Drosophila homolog of L-2-hydroxyglutarate dehydrogenase (dL2HGDH), which encodes the enzyme that breaks down L-2HG, is required for stage-specific degradation of the L-2HG pool. In addition, dLDH also indirectly promotes L-2HG accumulation via synthesis of lactate, which activates a metabolic feed-forward mechanism that inhibits dL2HGDH activity and stabilizes L-2HG levels. Finally, we use a genetic approach to demonstrate that dLDH and L-2HG influence position effect variegation and DNA methylation, suggesting that this compound serves to coordinate glycolytic flux with epigenetic modifications. Overall, our studies demonstrate that growing animal tissues synthesize L-2HG in a controlled manner, reveal a mechanism that coordinates glucose catabolism with L-2HG synthesis, and establish the fly as a unique model system for studying the endogenous functions of L-2HG during cell growth and proliferation. PMID:28115720

Targeted deletion of hepatocyte Ikkβ confers growth advantages

International Nuclear Information System (INIS)

Koch, Katherine S.; Maeda, Shin; He, Guobin; Karin, Michael; Leffert, Hyam L.

2009-01-01

Mice lacking hepatocyte IKKβ (Ikkβ Δhep ) are defective in TNFα-activation of hepatocellular transcription factor NF-κB, and highly susceptible to hepatotoxicity. Following diethylnitrosamine (DEN) exposure, Ikkβ Δhep mice develop more hepatocellular carcinoma (HCC) than control mice due partly to enhanced DEN-induced hepatocyte death. Here we show that Ikkβ Δhep hepatocytes display growth advantages over normal hepatocytes consisting of precocious PCNA and cyclin D1 expression during liver regeneration (shortened hepatocyte G 0 → G 1 transitions), and enhanced recovery efficiency, cyclin D1 expression and cell proliferation after plating. Ex vivo deletion of Ikkβ also accelerates hepatocyte growth. Ikkβ Δhep hepatocyte proliferative responses show heightened sensitivity to TGFα and TNFα, and heightened expression of fibronectin, collagens I/III, nidogen, β-actin and integrin β1 mRNAs. These findings suggest that altered mitogen signaling and expression of extracellular matrix and its associated components underlie growth advantages. Increased HCC development in Ikkβ Δhep mice may also be caused by growth advantages of surviving Ikkβ-deleted hepatocytes.

Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

Science.gov (United States)

Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

2013-01-01

Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. 14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR. PMID:24204949

Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype.

Directory of Open Access Journals (Sweden)

Mark Robert Dilworth

Full Text Available Fetal growth restriction (FGR is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th centile of customised growth charts. Sildenafil citrate (SC, Viagra™, a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8% in P0 mice following maternal SC treatment (0.4 mg/ml via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056. Additionally, 75% of the P0 fetal weights were below the 5(th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas

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Meagan B. Myers

2016-04-01

Full Text Available Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs, examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E. As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10−3 to 4.6 × 10−2 in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells.

Rhythm-based heartbeat duration normalization for atrial fibrillation detection.

Science.gov (United States)

Islam, Md Saiful; Ammour, Nassim; Alajlan, Naif; Aboalsamh, Hatim

2016-05-01

Screening of atrial fibrillation (AF) for high-risk patients including all patients aged 65 years and older is important for prevention of risk of stroke. Different technologies such as modified blood pressure monitor, single lead ECG-based finger-probe, and smart phone using plethysmogram signal have been emerging for this purpose. All these technologies use irregularity of heartbeat duration as a feature for AF detection. We have investigated a normalization method of heartbeat duration for improved AF detection. AF is an arrhythmia in which heartbeat duration generally becomes irregularly irregular. From a window of heartbeat duration, we estimate the possible rhythm of the majority of heartbeats and normalize duration of all heartbeats in the window based on the rhythm so that we can measure the irregularity of heartbeats for both AF and non-AF rhythms in the same scale. Irregularity is measured by the entropy of distribution of the normalized duration. Then we classify a window of heartbeats as AF or non-AF by thresholding the measured irregularity. The effect of this normalization is evaluated by comparing AF detection performances using duration with the normalization, without normalization, and with other existing normalizations. Sensitivity and specificity of AF detection using normalized heartbeat duration were tested on two landmark databases available online and compared with results of other methods (with/without normalization) by receiver operating characteristic (ROC) curves. ROC analysis showed that the normalization was able to improve the performance of AF detection and it was consistent for a wide range of sensitivity and specificity for use of different thresholds. Detection accuracy was also computed for equal rates of sensitivity and specificity for different methods. Using normalized heartbeat duration, we obtained 96.38% accuracy which is more than 4% improvement compared to AF detection without normalization. The proposed normalization

Verbal Processing Reaction Times in "Normal" and "Poor" Readers.

Science.gov (United States)

Culbertson, Jack; And Others

After it had been determined that reaction time (RT) was a sensitive measure of hemispheric dominance in a verbal task performed by normal adult readers, the reaction times of three groups of subjects (20 normal reading college students, 12 normal reading third graders and 11 poor reading grade school students) were compared. Ss were exposed to…

Microenvironment around tumors and their radiation sensitivity. The possibility of molecular target for radiation sensitization

Energy Technology Data Exchange (ETDEWEB)

Akimoto, Tetsuo; Ishikawa, Hitoshi [Gunma Univ., Maebashi (Japan). School of Medicine; Mitsuhashi, Norio [Tokyo Women' s Medical Coll. (Japan)

2001-12-01

There have been scarce studies concerning the effect of microenvironment around tumors on their radiation sensitivity and this review describes the influence of environmental factors of cell adhesion, growth factors, cytokines, hypoxia and angiogenesis on the sensitivity and response to radiation and on the signal transduction to consider the possibility of molecular target for radiation sensitization. Cell-cell adhesion and cell-matrix interaction in response to radiation may have a role in inducing apoptotic process like anti-apoptotic or pro-apoptotic one. Growth factors and cytokines can affect the tumor response to radiation in more extent than p53 gene status since apoptosis induction is not always an indication of radiation sensitivity in many tumors clinically encountered. Radiation sensitivity is low in tumor cells under hypoxic conditions and it is important to know the relationship between those hypoxic cell response and angiogenesis by factors like HIF (hypoxia-inducible factor)-1. Molecular targets for radiation sensitization are now under development and both basic and clinical studies are important for future application of those sensitizing agents for the radiotherapy of tumors. (K.H.)

Microenvironment around tumors and their radiation sensitivity. The possibility of molecular target for radiation sensitization

International Nuclear Information System (INIS)

Akimoto, Tetsuo; Ishikawa, Hitoshi

2001-01-01

There have been scarce studies concerning the effect of microenvironment around tumors on their radiation sensitivity and this review describes the influence of environmental factors of cell adhesion, growth factors, cytokines, hypoxia and angiogenesis on the sensitivity and response to radiation and on the signal transduction to consider the possibility of molecular target for radiation sensitization. Cell-cell adhesion and cell-matrix interaction in response to radiation may have a role in inducing apoptotic process like anti-apoptotic or pro-apoptotic one. Growth factors and cytokines can affect the tumor response to radiation in more extent than p53 gene status since apoptosis induction is not always an indication of radiation sensitivity in many tumors clinically encountered. Radiation sensitivity is low in tumor cells under hypoxic conditions and it is important to know the relationship between those hypoxic cell response and angiogenesis by factors like HIF (hypoxia-inducible factor)-1. Molecular targets for radiation sensitization are now under development and both basic and clinical studies are important for future application of those sensitizing agents for the radiotherapy of tumors. (K.H.)

Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

Science.gov (United States)

Mohamadzadeh, M; Müller, M; Hultsch, T; Enk, A; Saloga, J; Knop, J

1994-12-01

To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

Temperature modulates coccolithophorid sensitivity of growth, photosynthesis and calcification to increasing seawater pCO₂.

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Scarlett Sett

Full Text Available Increasing atmospheric CO₂ concentrations are expected to impact pelagic ecosystem functioning in the near future by driving ocean warming and acidification. While numerous studies have investigated impacts of rising temperature and seawater acidification on planktonic organisms separately, little is presently known on their combined effects. To test for possible synergistic effects we exposed two coccolithophore species, Emiliania huxleyi and Gephyrocapsa oceanica, to a CO₂ gradient ranging from ∼0.5-250 µmol kg⁻¹ (i.e. ∼20-6000 µatm pCO₂ at three different temperatures (i.e. 10, 15, 20°C for E. huxleyi and 15, 20, 25°C for G. oceanica. Both species showed CO₂-dependent optimum-curve responses for growth, photosynthesis and calcification rates at all temperatures. Increased temperature generally enhanced growth and production rates and modified sensitivities of metabolic processes to increasing CO₂. CO₂ optimum concentrations for growth, calcification, and organic carbon fixation rates were only marginally influenced from low to intermediate temperatures. However, there was a clear optimum shift towards higher CO₂ concentrations from intermediate to high temperatures in both species. Our results demonstrate that the CO₂ concentration where optimum growth, calcification and carbon fixation rates occur is modulated by temperature. Thus, the response of a coccolithophore strain to ocean acidification at a given temperature can be negative, neutral or positive depending on that strain's temperature optimum. This emphasizes that the cellular responses of coccolithophores to ocean acidification can only be judged accurately when interpreted in the proper eco-physiological context of a given strain or species. Addressing the synergistic effects of changing carbonate chemistry and temperature is an essential step when assessing the success of coccolithophores in the future ocean.

Micromycetes sensitiveness to heavy metals

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O. N. Korinovskaya

2011-07-01

Full Text Available The sensitivity of 33 micromycete species to nitric compounds of copper, lead, zinc, nickel and cadmium has been determined. Absidia butleri Lendn, Mortierella vanesae Dixon-Stewart, Cunninghamella echinulata Thaxte, Curvularia tuberculata Jain, Cladosporium cladosporiodes (Fresen G. A. de Vries and Fusarium solani (C. Mart. Appel et Wollenw are sensitive to minimal content of the heavy metals (0.75 of maximum permissible concentration (MPC in the growth medium. At the same time Trixoderma longibrachiatiim Rifai, Alternaria alternatа (Fr. Keissl and Penicillium sp. 4 demonstrated moderate growth under maximal concentration (50 MPC. It is determined that minimal content of the heavy metals in the initial stage of influence (up to 48 h promotes growth of only Fusarium oxysporum E. F. Sm. et Swingle, while retards growth of the other species.

Proteoglycans in Leiomyoma and Normal Myometrium

Science.gov (United States)

Barker, Nichole M.; Carrino, David A.; Caplan, Arnold I.; Hurd, William W.; Liu, James H.; Tan, Huiqing; Mesiano, Sam

2015-01-01

Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression. PMID:26423601

Hemoglobin is essential for normal growth of Arabidopsis organs

DEFF Research Database (Denmark)

Hebelstrup, Kim Henrik; Hunt, Peter; Dennis, Elizabeth

2006-01-01

In Arabidopsis thaliana, the class I hemoglobin AHb1 is transiently expressed in the hydathodes of leaves and in floral buds from young inflorescences. Nitric oxide (NO) accumulates to high levels in these organs when AHb1 is silenced, indicating an important role in metabolizing NO. AHb1-silenced...... lines are viable but show a mutant phenotype affecting the regions where AHb1 is expressed. Arabidopsis lines with an insertional knockout or overexpression of AHb2, a class II 3-on-3 hemoglobin, were generated. Seedlings overexpressing AHb2 show enhanced survival of hypoxic stress. The AHb2 knockout...... lines develop normally. However, when AHb2 knockout is combined with AHb1 silencing, seedlings die at an early vegetative stage suggesting that the two 3-on-3 hemoglobins, AHb1 and AHb2, together play an essential role for normal development of Arabidopsis seedlings. In conclusion, these results...

Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

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Malemud Charles J

2004-10-01

Full Text Available Abstract Background Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. Methods Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. Results Serum growth hormone levels failed to correlate with age (r2 = 3.03 in the entire group of normal subjects (i.e. 20 – 80 years. In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092. Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269 in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p 55 yrs systemic lupus erythematosus patients. Conclusions These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal

Monitoring the effects of atmospheric ethylene near polyethylene manufacturing plants with two sensitive plant species

International Nuclear Information System (INIS)

Tonneijck, A.E.G.; Berge, W.F. ten; Jansen, B.P.

2003-01-01

Atmospheric ethylene from polyethylene manufacturing plants adversely affected the number of flowers and growth of field-grown marigold and petunia. - Data of a multi-year (1977-1983) biomonitoring programme with marigold and petunia around polyethylene manufacturing plants was analysed to assess plant responses to atmospheric ethylene and to determine the area at risk for the phytotoxic effects of this pollutant. In both species, flower formation and growth were severely reduced close to the emission sources and plant performance improved with increasing distance. Plants exposed near the border of the research area had more flowers than the unexposed control while their growth was normal. Measurements of ethylene concentrations at a border site revealed that the growing season mean was 61.5 μg m -3 in 1982 and 15.6 μg m -3 in 1983. In terms of number of flowers, petunia was more sensitive than marigold and adverse effects were observed within ca. 400 m distance from the sources for marigold and within ca. 460 m for petunia. The area at risk (ca. 870 m) for ethylene-induced growth reduction was also limited to the industrial zone. Plants were more sensitive to ethylene in terms of growth reduction than in terms of inhibition of flowering. In the Netherlands, maximum permissible levels of ethylene are currently based on information from laboratory and greenhouse studies. Our results indicate that these levels are rather conservative in protecting field-grown plants against ethylene-induced injury near polyethylene manufacturing plants

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

International Nuclear Information System (INIS)

Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

2012-01-01

Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

Energy Technology Data Exchange (ETDEWEB)

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

2012-11-15

Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

Loss-of-normal-feedwater sensitivity studies for AP600 behavior characterization

International Nuclear Information System (INIS)

Saiu, G.

1996-01-01

Activity concerning the development of a RELAP5/MOD3 model to simulate the Westinghouse Electric Corporation AP600 is summarized. The aim is to gain initial insight into the capability of RELAP5 to simulate the behavior of AP600 safety features. A-loss-of-normal-feedwater event is studied. Of the transients that must be investigated, this transient has been chosen to be one of the most relevant because the response of the AP600 to a loss-of-normal-feedwater event differs significantly from that of current pressurized water reactors in the extensive use of passive safety features peculiar to the AP600. Also, strong interactions among the AP600 safety systems, which should be further analyzed to permit full optimization of the system actuation logic and operation, are shown. Finally, a loss of normal feedwater without reactor scram, performed to investigate short-term plant behavior, shows that the pressure peak is affected by critical discharge flow coefficients applied to the pressurizer safety valves, while a relatively small reduction of the pressure peak is observed when both heat exchangers of the passive heat removal system are operating as opposed to the case in which only one is available. The data used for this study are derived from the Standard Safety Analysis Report configuration of the Westinghouse AP600 as of 1992

Patterns of pulmonary maturation in normal and abnormal pregnancy.

Science.gov (United States)

Goldkrand, J W; Slattery, D S

1979-03-01

Fetal pulmonary maturation may be a variable event depending on various feto-maternal environmental and biochemical influences. The patterns of maturation were studied in 211 amniotic fluid samples from 123 patients (normal 55; diabetes 23; Rh sensitization 19; preeclampsia 26). The phenomenon of globule formation from the amniotic fluid lipid extract and is relation to pulmonary maturity was utilized for this analysis. Validation of this technique is presented. A normal curve was constructed from 22 to 42 weeks; gestation and compared to the abnormal pregnancies. Patients with class A, B, and C diabetes and Rh-sensitized pregnancies had delayed pulmonary maturation. Patients with class D diabetes and preclampsia paralleled the normal course of maturation. A discussion of these results and their possible cause is presented.

Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests

International Nuclear Information System (INIS)

Arts, Gertie H.P.; Belgers, J. Dick M.; Hoekzema, Conny H.; Thissen, Jac T.N.M.

2008-01-01

The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root endpoints, reflecting root growth, were most sensitive in the toxicity tests, while endpoints relating to biomass, growth and shoot length were less sensitive. The endpoints with the lowest coefficients of variation were not necessarily the endpoints, which were toxicologically most sensitive. Differences in sensitivity were in the range of 10-1000 for different macrophyte-specific endpoints. No macrophyte species was consistently the most sensitive. Criteria to select endpoints in macrophyte toxicity tests should include toxicological sensitivity, variance and ecological relevance. Hence, macrophyte toxicity tests should comprise an array of endpoints, including very sensitive endpoints like those relating to root growth. - A range of endpoints is more representative of macrophyte fitness than biomass and growth only

Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth.

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Harmon, Kristin A; Gerard, Lori; Jensen, Dalan R; Kealey, Elizabeth H; Hernandez, Teri L; Reece, Melanie S; Barbour, Linda A; Bessesen, Daniel H

2011-10-01

We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P fasting insulin (r = 0.49, P fasting triglycerides (r = 0.67, P fasting FFAs (r = 0.54, P obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?

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Lubbers, Ellen R.; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

2013-01-01

Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH versus IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying the effects of GH on adiponectin are depot-specific. Interestingly rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity. PMID:23261955

Cultured cells from a severe combined immunodeficient mouse have a slower than normal rate of repair of potentially lethal damage sensitive to hypertonic treatment

International Nuclear Information System (INIS)

Kimura, H.; Terado, T.; Ikebuchi, M.; Aoyama, T.; Komatsu, K.; Nozawa, A.

1995-01-01

The effects of hypertonic 0.5 M NaCl treatment after irradiation on the repair of DNA damage were examined in fibroblasts of the severe combined immunodeficient (scid) mouse. These cells are hypersensitive to ionizing radiation because of a deficiency in the repair of double-strand breaks. Hypertonic treatment caused radiosensitization due to a fixation of potentially lethal damage (PLD) in scid cells, demonstrating that scid cells normally repair PLD. To assess the kinetics of the repair of PLD, hypertonic treatment was delayed for various times after irradiation. Potentially lethal damage was repaired during these times in isotonic medium at 37 degrees C. It was found that the rate of repair of PLD was much slower in scid cells than in BALB/c 3T3 cells, which have a open-quotes wild-typeclose quotes level of radiosensitivity. This fact indicates that the scid mutation affects the type of repair of PLD that is sensitive to 0.5 M NaCl treatment. In scid hybrid cells containing fragments of human chromosome 8, which complements the radiosensitivity of the scid cells, the rate of repair was restored to a normal level. An enzyme encoded by a gene on chromosome 8 may also be connected with PLD which is sensitive to hypertonic treatment. 29 refs., 3 figs

Omega-3 fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells.

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Abdi, J; Garssen, J; Faber, J; Redegeld, F A

2014-12-01

The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to enhance the effect of chemotherapeutic drugs in clinical studies in cancer patients and to induce apoptotic tumor cell death in vitro. Until now, EPA and DHA have never been investigated in multiple myeloma (MM). Human myeloma cells (L363, OPM-1, OPM-2 and U266) and normal peripheral blood mononuclear cells were exposed to EPA and DHA, and effects on mitochondrial function and apoptosis, caspase-3 activation, gene expression and drug toxicity were measured. Exposure to EPA and DHA induced apoptosis and increased sensitivity to bortezomib in MM cells. Importantly, they did not affect viability of normal human peripheral mononuclear cells. Messenger RNA expression arrays showed that EPA and DHA modulated genes involved in multiple signaling pathways including nuclear factor (NF) κB, Notch, Hedgehog, oxidative stress and Wnt. EPA and DHA inhibited NFκB activity and induced apoptosis through mitochondrial perturbation and caspase-3 activation. Our study suggests that EPA and DHA induce selective cytotoxic effects in MM and increase sensitivity to bortezomib and calls for further exploration into a potential application of these n-3 polyunsaturated fatty acids in the therapy of MM. Copyright © 2014 Elsevier Inc. All rights reserved.

Hopanoid-free Methylobacterium extorquens DM4 overproduces carotenoids and has widespread growth impairment.

Directory of Open Access Journals (Sweden)

Alexander S Bradley

Full Text Available Hopanoids are sterol-like membrane lipids widely used as geochemical proxies for bacteria. Currently, the physiological role of hopanoids is not well understood, and this represents one of the major limitations in interpreting the significance of their presence in ancient or contemporary sediments. Previous analyses of mutants lacking hopanoids in a range of bacteria have revealed a range of phenotypes under normal growth conditions, but with most having at least an increased sensitivity to toxins and osmotic stress. We employed hopanoid-free strains of Methylobacterium extorquens DM4, uncovering severe growth defects relative to the wild-type under many tested conditions, including normal growth conditions without additional stressors. Mutants overproduce carotenoids-the other major isoprenoid product of this strain-and show an altered fatty acid profile, pronounced flocculation in liquid media, and lower growth yields than for the wild-type strain. The flocculation phenotype can be mitigated by addition of cellulase to the medium, suggesting a link between the function of hopanoids and the secretion of cellulose in M. extorquens DM4. On solid media, colonies of the hopanoid-free mutant strain were smaller than wild-type, and were more sensitive to osmotic or pH stress, as well as to a variety of toxins. The results for M. extorquens DM4 are consistent with the hypothesis that hopanoids are important for membrane fluidity and lipid packing, but also indicate that the specific physiological processes that require hopanoids vary across bacterial lineages. Our work provides further support to emerging observations that the role of hopanoids in membrane robustness and barrier function may be important across lineages, possibly mediated through an interaction with lipid A in the outer membrane.

Physical Development: What's Normal? What's Not?

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... Stages Listen Español Text Size Email Print Share Physical Development: What’s Normal? What’s Not? Page Content Article ... growth . The timing and speed of a child's physical development can vary a lot, because it is ...

Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

Science.gov (United States)

Kosmala, Wojciech; Jedrzejuk, Diana; Derzhko, Roksolana; Przewlocka-Kosmala, Monika; Mysiak, Andrzej; Bednarek-Tupikowska, Grazyna

2012-05-01

Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. One hundred sixty-eight subjects (age, 38±7 years) with BMI affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=-0.17, P<0.006), C-reactive protein (β=-0.20, P<0.002) and abdominal fat deposit (β=-0.20, P<0.003); for tissue S velocity, PICP (β=-0.21, P<0.002) and abdominal fat deposit (β=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (β=-0.30, P<0.0001), PICP (β=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both β=0.18, P<0.01) and HOMA IR (β=0.16, P<0.04). In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

Growth, carbon-isotope discrimination, and drought-associated mortality across a Pinus ponderosa elevational transect

Science.gov (United States)

McDowell, N.G.; Allen, Craig D.; Marshall, L.

2010-01-01

Drought- and insect-associated tree mortality at low-elevation ecotones is a widespread phenomenon but the underlying mechanisms are uncertain. Enhanced growth sensitivity to climate is widely observed among trees that die, indicating that a predisposing physiological mechanism(s) underlies tree mortality. We tested three, linked hypotheses regarding mortality using a ponderosa pine (Pinus ponderosa) elevation transect that experienced low-elevation mortality following prolonged drought. The hypotheses were: (1) mortality was associated with greater growth sensitivity to climate, (2) mortality was associated with greater sensitivity of gas exchange to climate, and (3) growth and gas exchange were correlated. Support for all three hypotheses would indicate that mortality results at least in part from gas exchange constraints. We assessed growth using basal area increment normalized by tree basal area [basal area increment (BAI)/basal area (BA)] to account for differences in tree size. Whole-crown gas exchange was indexed via estimates of the CO2 partial pressure difference between leaf and atmosphere (pa−pc) derived from tree ring carbon isotope ratios (δ13C), corrected for temporal trends in atmospheric CO2 and δ13C and elevation trends in pressure. Trees that survived the drought exhibited strong correlations among and between BAI, BAI/BA, pa−pc, and climate. In contrast, trees that died exhibited greater growth sensitivity to climate than trees that survived, no sensitivity of pa−pc to climate, and a steep relationship between pa−pc and BAI/BA. The pa−pc results are consistent with predictions from a theoretical hydraulic model, suggesting trees that died had a limited buffer between mean water availability during their lifespan and water availability during drought – i.e., chronic water stress. It appears that chronic water stress predisposed low-elevation trees to mortality during drought via constrained gas exchange. Continued intensification of

Growth mechanism of titanium dioxide nanowires for dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Boercker, J E; Enache-Pommer, E; Aydil, E S [Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Avenue SE, Minneapolis, MN 55455 (United States)], E-mail: aydil@umn.edu

2008-03-05

Mesoporous films made of titanium dioxide nanowires are desirable for dye-sensitized solar cells because nanowires provide direct conduction pathways for photogenerated electrons. Anatase titanium dioxide nanowires with polycrystalline microstructure were synthesized on titanium foil using a three-step process. First, the top surface of the titanium foil was transformed to Na{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} nanotubes through hydrothermal oxidation in NaOH. Next, the Na{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} nanotubes were converted to H{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} nanotubes by ion exchange. Finally, the H{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} nanotubes were converted to polycrystalline anatase nanowires through a topotactic transformation. The film morphology evolution, crystal structure transformations and growth mechanism are described in detail. Titanium foil reacts with NaOH to form Na{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} sheets, which exfoliate and spiral into nanotubes. The Na{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} nanotubes are immersed in HCl solution to replace the Na{sup +} ions with H{sup +} ions. During the topotactic transformation of H{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} nanotubes to anatase TiO{sub 2} nanowires, the sheets made of edge bonded TiO{sub 6} octahedra in the H{sub 2}Ti{sub 2}O{sub 4}(OH){sub 2} nanotubes dehydrate and move towards each other to form anatase crystals oriented along the nanotube axis which creates a polycrystalline nanowire. These mesoporous TiO{sub 2} nanowire films were suitable for use as dye-sensitized solar cell photoanodes.

Drought-induced legacy effects in wood growth across the Eastern and Midwestern U.S. are mediated by site climate, tree age, and drought sensitivity

Science.gov (United States)

Kannenberg, S.; Maxwell, J. T.; Pederson, N.; D'Orangeville, L.; Phillips, R.

2017-12-01

While it is widely known that drought reduces carbon (C) uptake in temperate forests, tree growth can also remain stagnant post-drought despite favorable climatic conditions. While such "legacy effects" are well established, the degree to which these effects depend on species identity or variability in site conditions is poorly quantified. We sought to uncover how site, species, climate, and tree age interact to affect the presence and magnitude of legacy effects in temperate trees following drought. To do this, we assembled dendrochronological records of 18 common species across 94 sites in Eastern and Midwestern U.S. forests and quantified drought-induced changes in wood growth in the year of the drought (hereafter "drought sensitivity") and the years after the drought (i.e., legacy effects). We predicted that species particularly prone to hydraulic damage (e.g., oaks) would have the least drought sensitivity yet experience larger legacy effects, and that this effect would be exacerbated at arid sites. Across all species and sites, wood growth was reduced by 14% in the year of the drought and by 7% post-drought. Surprisingly, legacy effects were smaller for oak species and larger across species known to be more drought sensitive (e.g. tulip poplar, maple, birch). As a result, we observed a positive relationship between a species' drought sensitivity and that species' legacy effect. These legacy effects were similar in size across a range of drought severities. Surprisingly, legacy effects were smaller in more arid sites - contrary to previous investigations in dryland ecosystems - perhaps indicating the role of adaptation in mediating a tree's recovery from drought. In addition, many species actually decreased the size of their legacy effects as they aged, despite no change in drought responses. Our results run contrary to our predictions, as species with the greatest drought sensitivity had the least ability to recover, and that younger mesic forests- not arid

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

International Nuclear Information System (INIS)

Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

1984-01-01

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response

Association of Tumor Growth Factor-β and Interferon-γ Serum Levels With Insulin Resistance in Normal Pregnancy.

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Sotoodeh Jahromi, Abdolreza; Sanie, Mohammad Sadegh; Yusefi, Alireza; Zabetian, Hassan; Zareian, Parvin; Hakimelahi, Hossein; Madani, Abdolhossien; Hojjat-Farsangi, Mohammad

2015-09-28

Pregnancy is related to change in glucose metabolism and insulin production. The aim of our study was to determine the association of serum IFN-γ and TGF- β levels with insulin resistance during normal pregnancy. This cross sectional study was carried out on 97 healthy pregnant (in different trimesters) and 28 healthy non-pregnant women. Serum TGF-β and IFN- γ level were measured by ELISA method. Pregnant women had high level TGF-β and low level IFN-γ as compared non-pregnant women. Maternal serum TGF-β concentration significantly increased in third trimester as compared first and second trimester of pregnancy. Maternal serum IFN-γ concentration significantly decreased in third trimester as compared first and second trimester of pregnancy. Pregnant women exhibited higher score of HOMA IR as compared non-pregnant women. There were association between gestational age with body mass index (r=0.28, P=0.005), TGF-β (r=0.45, PInsulin resistance and TGF-β (r=0.17, p=0.05). Our findings suggest that changes in maternal cytokine level in healthy pregnant women were anti-inflammatory. Furthermore, Tumor Growth Factor-β appears has a role in induction insulin resistance in healthy pregnant women. However, further studies needed to evaluate role of different cytokines on insulin resistance in normal pregnancy.

Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.

Science.gov (United States)

Ketel, Iris J G; Stehouwer, Coen D A; Serné, Erik H; Korsen, Ted J M; Hompes, Peter G A; Smulders, Yvo M; de Jongh, Renate T; Homburg, Roy; Lambalk, Cornelis B

2008-09-01

Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). Obese women were more insulin resistant than normal-weight women (P PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent

Superoxide dismutase amplifies organismal sensitivity to ionizing radiation

International Nuclear Information System (INIS)

Scott, M.D.; Meshnick, S.R.; Eaton, J.W.

1989-01-01

Although increased superoxide dismutase (SOD) activity is often associated with enhanced resistance of cells and organisms to oxidant challenges, few direct tests of the antioxidant importance of this enzyme have been carried out. To assess the importance of SOD in defending against gamma-radiation, we employed Escherichia coli with deficient, normal, and super-normal enzyme activities. Surprisingly, the radiation sensitivity of E. coli actually increases as bacterial SOD activity increases. Elevated intracellular SOD activity sensitizes E. coli to radiation-induced mortality, whereas SOD-deficient bacteria show normal or decreased radiosensitivity. Toxic effects of activated oxygen species are involved in this phenomenon; bacterial SOD activity has no effect on radiation sensitivity under anaerobic conditions or on the lethality of other, non-oxygen-dependent, toxins such as ultraviolet radiation

Ammonia produced by bacterial colonies promotes growth of ampicillin-sensitive Serratia sp. by means of antibiotic inactivation.

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Cepl, Jaroslav; Blahůšková, Anna; Cvrčková, Fatima; Markoš, Anton

2014-05-01

Volatiles produced by bacterial cultures are known to induce regulatory and metabolic alterations in nearby con-specific or heterospecific bacteria, resulting in phenotypic changes including acquisition of antibiotic resistance. We observed unhindered growth of ampicillin-sensitive Serratia rubidaea and S. marcescens on ampicillin-containing media, when exposed to volatiles produced by dense bacterial growth. However, this phenomenon appeared to result from pH increase in the medium caused by bacterial volatiles rather than alterations in the properties of the bacterial cultures, as alkalization of ampicillin-containing culture media to pH 8.5 by ammonia or Tris exhibited the same effects, while pretreatment of bacterial cultures under the same conditions prior to antibiotic exposure did not increase ampicillin resistance. Ampicillin was readily inactivated at pH 8.5, suggesting that observed bacterial growth results from metabolic alteration of the medium, rather than an active change in the target bacterial population (i.e. induction of resistance or tolerance). However, even such seemingly simple mechanism may provide a biologically meaningful basis for protection against antibiotics in microbial communities growing on semi-solid media. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Growth hormone deficiency in cleft lip and palate patients

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Shahin AbdollahiFakhim

2015-11-01

Full Text Available Introduction: Failure to thrive (FTT is relatively common among cleft patients, most commonly attributed to feeding problems during the first months of life. Close association between midline clefts and pituitary gland abnormalities prompted us to determine the frequency of growth hormone deficiency in cleft patients, which is easily treated. Methods: Any cleft patient with FTT was studied and when the patient’s height was under the 3rd percentile of normal, growth hormone was checked after clonidine administration. Growth hormone was checked before and 30, 60 and 90 minutes after clonidine use. Results: Of 670 patients with cleft lip or palate, 31 patients (4% had some kind of growth retardation according to weight, height or head circumstance. Eighteen patients were under the 3rd percentile of normal height. Growth hormone deficiency was detected in 8 patients out of 18 patients and overall frequency of growth hormone deficiency among cleft patients with growth retardation was 25.8% (8 out of 31. Seven patients of 8 were male whereas one was female and half of the patients were syndromic. Conclusion: Cleft patients have many problems with normal feeding and all kind of support should be provided to achieve near-normal feeding and they should be monitored for normal growth. Any patient with growth retardation, especially height decrease, should be assessed for growth hormone deficiency.

Fibroblast-mediated in vivo and in vitro growth promotion of tumorigenic rat thyroid carcinoma cells but not normal Fisher rat thyroid follicular cells.

Science.gov (United States)

Saitoh, Ohki; Mitsutake, Norisato; Nakayama, Toshiyuki; Nagayama, Yuji

2009-07-01

It is known that genetic abnormalities in oncogenes and/or tumor suppressor genes promote carcinogenesis. Numerous recent articles, however, have demonstrated that epithelial-stromal interaction also plays a critical role for initiation and progression of carcinoma cells. Furthermore, ionizing radiation induces alterations in the tissue microenvironments that promote carcinogenesis. There is little or no information on epithelial-stromal interaction in thyroid carcinoma cells. The objective of this study was to determine if epithelial-stromal interaction influenced the growth of thyroid carcinoma cells in vivo and in vitro and to determine if radiation had added or interacting effects. Normal Fisher rat thyroid follicular cells (FRTL5 cells) and tumorigenic rat thyroid carcinoma cells (FRTL-Tc cells) derived from FRTL5 cells were employed. The cells were injected into thyroids or subcutaneously into left flanks of rats alone or in combination with skin-derived fibroblasts. In groups of rats, fibroblasts were irradiated with 0.1 or 4 Gy x-ray 3 days before inoculation. In vitro growth of FRTL-Tc and FRTL-5 cells were evaluated using the fibroblast-conditioned medium and in a co-culture system with fibroblasts. The in vivo experiments demonstrated that FRTL-Tc cells injected intrathyroidally grew faster than those injected subcutaneously, and that admixed fibroblasts enhanced growth of subcutaneous FRTL-Tc tumors, indicating that the intrathyroidal milieu, particularly in the presence of fibroblasts, confer growth-promoting advantage to thyroid carcinoma cells. This in vivo growth-promoting effect of fibroblasts on FRTL-Tc cells was duplicated in the in vitro experiments using the fibroblast-conditioned medium. Thus, our data demonstrate that this effect is mediated by soluble factor(s), is reversible, and is comparable to that of 10% fetal bovine serum. However, normal FRTL5 cells did not respond to the fibroblast-conditioned medium. Furthermore, high- and low

Effects of ultraviolet irradiation on the cell cycle in normal and UV-sensitive cell lines with reference to the nature of the defect in xeroderma pigmentosum variant

International Nuclear Information System (INIS)

Imray, P.; Mangan, T.; Saul, A.; Kidson, C.

1983-01-01

Analysis of the distribution of cells through the phases of the cell cycle by DNA flow cytofluorimetry has been utilized to investigate the effects of ultraviolet (UV) irradiation on cell-cycle progression in normal and UV-sensitive lymphoblastoid cell lines. In time-course studies only slight perturbation of DNA distribution was seen in normal cells, or UV-sensitive familial melanoma (FM) lines in the 48 h following irradiation. Xeroderma pigmentosum (XPA) excision-deficient cells showed a large increase in the proportion of cells in S phase 16-40 h post-irradiation. XP variant (XPV) cells were blocked in G 1 and S phases with the complete absence of cells with G 2 DNA content 16-28 h after irradiation. By 48 h post-irradiation the DNA distribution of XPA and XPV cells had returned to that of an unirradiated control. When colcemid was added to the cultures immediately after irradiation to prevent mitotic cells dividing and re-entering the cell cycle, progression through the first cycle after irradiation was followed. UV irradiation did not affect the rate of movement of cells out of G 1 into S phase in normal, FM or XPA cells. The proportion of cells in S phase was increased in UV-irradiated cultures in these cell types and the number of cells entering the G 2 +M compartment was reduced. (orig./AJ)

Shape-dependent regulation of proliferation in normal and malignant human cells and its alteration by interferon

International Nuclear Information System (INIS)

Kulesh, D.A.; Greene, J.J.

1986-01-01

The relationship between cell morphology, proliferation, and contact inhibition was studied in normal and malignant human cells which varied in their sensitivity to contact inhibition. Their ability to proliferate was examined under conditions where the cells were constrained into different shapes by plating onto plastic surfaces coated with poly(2-hydroxyethyl methacrylate). Poly(2-hydroxyethyl methacrylate) can precisely vary the shape of cells without toxicity. Cell proliferation was quantitated by cell counts and labeling indices were determined by autoradiography. The normal JHU-1 foreskin fibroblasts and IMR-90 lung fibroblasts exhibited contact-inhibited growth with a saturation density of 2.9 X 10(5) and 2.0 X 10(5) cells/cm2, respectively. These cells also exhibited stringent dependency on cell shape with a mitotic index of less than 3% at poly(2-hydroxyethyl methacrylate) concentrations at which the cells were rounded versus a labeling index of 75-90% when the cells were flat. The malignant bladder carcinoma line RT-4 exhibited partial contact-inhibited growth. Its dependency on cell shape was less stringent than that of normal cells with a mitotic index of 37-40% when rounded and 79% when flat. The malignant fibrosarcoma line, HT1080, was not contact inhibited and was entirely shape independent with a mitotic index of 70-90% regardless of cell shape. Treatment of HT1080 cells with low concentration of human fibroblast interferon (less than 40 units/ml) restored shape-dependent proliferation while having little effect on normal cells. Subantiproliferative doses of interferon were also shown to restore contact-inhibited proliferation control to malignant cells previously lacking it

Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction.

Science.gov (United States)

Ayala Ramírez, Paola; García Robles, Reggie; Rojas, Juan Diego; Bermúdez, Martha; Bernal, Jaime

2012-07-01

to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls. messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy.

Intrauterine growth-restricted piglets have similar gastric emptying rates but lower rectal temperatures and altered blood values when compared with normal-weight piglets at birth

DEFF Research Database (Denmark)

Williams, Charlotte Amdi; Klarlund, M. V.; Pedersen, Janni Hales

2016-01-01

Intrauterine growth-restricted (IUGR) piglets have lower survival rates and are more likely to have empty stomachs 24 h after birth than normal piglets. Although hypoglycemia may result from low colostrum intake per se, it is not known if slow gastric emptying may be an additional risk factor...... that the gastric emptying rate and blood glucose would be lower in IUGR piglets. We investigated gastric emptying rates in normal and IUGR piglets and blood glucose and rectal temperatures at birth and after 15, 30, 60, and 120 min. In addition, blood parameters relevant for metabolism were studied. Forty......-eight piglets (24 normal and 24 IUGR) were classified at birth as either normal or IUGR on the basis of head morphology. Piglets were removed from the sow at birth before suckling, and birth weight was recorded. Pooled porcine colostrum was tube-fed to all piglets at 12 mL/kg BW as soon as possible after birth...

A specific and sensitive method for visualization of tumor necrosis factor in the murine central nervous system

DEFF Research Database (Denmark)

Lambertsen, K L; Drøjdahl, N; Owens, T

2001-01-01

-PCR and Western blot analysis on homogenates prepared from microdissected brain regions. Advantages and disadvantages of the methods are discussed with emphasis on the specificity and sensitivity of the histological procedures. Our strategy for detection of TNF mRNA and protein provides a solid basis...... for clarifying the cellular synthesis, regulation and function of TNF in the normal, injured or diseased CNS. Furthermore, the methodology can readily be applied in studies of other cytokines and growth factors in the CNS....

Regulation of epidermal growth factor receptor signaling and erlotinib sensitivity in head and neck cancer cells by miR-7.

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Felicity C Kalinowski

Full Text Available Elevated expression and activity of the epidermal growth factor receptor (EGFR/protein kinase B (Akt signaling pathway is associated with development, progression and treatment resistance of head and neck cancer (HNC. Several studies have demonstrated that microRNA-7 (miR-7 regulates EGFR expression and Akt activity in a range of cancer cell types via its specific interaction with the EGFR mRNA 3'-untranslated region (3'-UTR. In the present study, we found that miR-7 regulated EGFR expression and Akt activity in HNC cell lines, and that this was associated with reduced growth in vitro and in vivo of cells (HN5 that were sensitive to the EGFR tyrosine kinase inhibitor (TKI erlotinib (Tarceva. miR-7 acted synergistically with erlotinib to inhibit growth of erlotinib-resistant FaDu cells, an effect associated with increased inhibition of Akt activity. Microarray analysis of HN5 and FaDu cell lines transfected with miR-7 identified a common set of downregulated miR-7 target genes, providing insight into the tumor suppressor function of miR-7. Furthermore, we identified several target miR-7 mRNAs with a putative role in the sensitization of FaDu cells to erlotinib. Together, these data support the coordinate regulation of Akt signaling by miR-7 in HNC cells and suggest the therapeutic potential of miR-7 alone or in combination with EGFR TKIs in this disease.

Metabolomics data normalization with EigenMS.

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Yuliya V Karpievitch

Full Text Available Liquid chromatography mass spectrometry has become one of the analytical platforms of choice for metabolomics studies. However, LC-MS metabolomics data can suffer from the effects of various systematic biases. These include batch effects, day-to-day variations in instrument performance, signal intensity loss due to time-dependent effects of the LC column performance, accumulation of contaminants in the MS ion source and MS sensitivity among others. In this study we aimed to test a singular value decomposition-based method, called EigenMS, for normalization of metabolomics data. We analyzed a clinical human dataset where LC-MS serum metabolomics data and physiological measurements were collected from thirty nine healthy subjects and forty with type 2 diabetes and applied EigenMS to detect and correct for any systematic bias. EigenMS works in several stages. First, EigenMS preserves the treatment group differences in the metabolomics data by estimating treatment effects with an ANOVA model (multiple fixed effects can be estimated. Singular value decomposition of the residuals matrix is then used to determine bias trends in the data. The number of bias trends is then estimated via a permutation test and the effects of the bias trends are eliminated. EigenMS removed bias of unknown complexity from the LC-MS metabolomics data, allowing for increased sensitivity in differential analysis. Moreover, normalized samples better correlated with both other normalized samples and corresponding physiological data, such as blood glucose level, glycated haemoglobin, exercise central augmentation pressure normalized to heart rate of 75, and total cholesterol. We were able to report 2578 discriminatory metabolite peaks in the normalized data (p<0.05 as compared to only 1840 metabolite signals in the raw data. Our results support the use of singular value decomposition-based normalization for metabolomics data.

Specificity of tumor necrosis factor toxicity for human mammary carcinomas relative to normal mammary epithelium and correlation with response to doxorubicin

International Nuclear Information System (INIS)

Dollbaum, C.; Creasey, A.A.; Dairkee, S.H.; Hiller, A.J.; Rudolph, A.R.; Lin, L.; Vitt, C.; Smith, H.S.

1988-01-01

By using a unique short-term culture system capable of growing both normal and malignant breast epithelial tissue, human recombinant tumor necrosis factor (TNF) showed preferential cytotoxicity to malignant cells as compared to the corresponding nonmalignant cells. Most of the malignant specimens were sensitive to TNF with 13 of 18 specimens showing 90% inhibition of clonal growth (ID 90 ). In contrast, all 13 nonmalignant specimens tested clustered at the resistant end of the TNF response spectrum. This differential sensitivity to TNF was seen in three cases in which malignant and nonmalignant breast epithelial tissues from the same patient were studied. To investigate the mechanism of resistance to TNF by normal cells, the presence of receptors for TNF was determined. Five of six cultures showed specific binding of 125 I-labeled TNF and there was no relationship between the degree of resistance and the degree of specific binding. Simultaneous comparison of tumor responsiveness to doxorubicin and TNF revealed a positive correlation in ID 90 values; these results may have important implications for the clinical use of TNF in cancer patients heavily pretreated with doxorubicin

Modeling error distributions of growth curve models through Bayesian methods.

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Zhang, Zhiyong

2016-06-01

Growth curve models are widely used in social and behavioral sciences. However, typical growth curve models often assume that the errors are normally distributed although non-normal data may be even more common than normal data. In order to avoid possible statistical inference problems in blindly assuming normality, a general Bayesian framework is proposed to flexibly model normal and non-normal data through the explicit specification of the error distributions. A simulation study shows when the distribution of the error is correctly specified, one can avoid the loss in the efficiency of standard error estimates. A real example on the analysis of mathematical ability growth data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-99 is used to show the application of the proposed methods. Instructions and code on how to conduct growth curve analysis with both normal and non-normal error distributions using the the MCMC procedure of SAS are provided.

Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure

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Ariungerel Gerelchuluun

2018-02-01

Full Text Available Suberoylanilide hydroxamic acid (SAHA is a histone deacetylase inhibitor, which has been widely utilized throughout the cancer research field. SAHA-induced radiosensitization in normal human fibroblasts AG1522 and lung carcinoma cells A549 were evaluated with a combination of γ-rays, proton, and carbon ion exposure. Growth delay was observed in both cell lines during SAHA treatment; 2 μM SAHA treatment decreased clonogenicity and induced cell cycle block in G1 phase but 0.2 μM SAHA treatment did not show either of them. Low LET (Linear Energy Transfer irradiated A549 cells showed radiosensitization effects on cell killing in cycling and G1 phase with 0.2 or 2 μM SAHA pretreatment. In contrast, minimal sensitization was observed in normal human cells after low and high LET radiation exposure. The potentially lethal damage repair was not affected by SAHA treatment. SAHA treatment reduced the rate of γ-H2AX foci disappearance and suppressed RAD51 and RPA (Replication Protein A focus formation. Suppression of DNA double strand break repair by SAHA did not result in the differences of SAHA-induced radiosensitization between human cancer cells and normal cells. In conclusion, our results suggest SAHA treatment will sensitize cancer cells to low and high LET radiation with minimum effects to normal cells.

Growth impairment due to transient hypercortisolism.

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Armour, K; Chalew, S; Kowarski, A A

1986-01-01

Cushing's syndrome in childhood is generally recognized by classical features such as truncal obesity, striae, easy bruising, moon facies, hypertension and growth retardation. Exceptionally, Cushing's syndrome has been reported to present as growth failure alone. We diagnosed transient hypercortisolism in 6 children who had poor growth as their only presenting abnormality. The 6 children all had integrated concentrations of cortisols (IC-F) (14.1 +/- 1.7 micrograms/dl; mean +/- 1 SD) which exceeded the IC-F in healthy children and adults (5.7 +/- 1.5 micrograms/dl; P less than 0.001). The IC-F of these 6 index cases overlapped the range of IC-F in patients with pathologically proven Cushing's syndrome (20.2 +/- 4.7 micrograms/dl). Four of the 6 patients were treated with human growth hormone for 8 months and showed a marked improvement in their growth rates. Four patients have entered puberty and are growing at normal rates. Three of the 6 children had normal repeat IC-Fs, subsequently, at a time they had normal growth rates. In 1-1/2 to 3 years of follow-up, none of the patients developed any other stigmata of Cushing's syndrome. We conclude that transient hypercortisolism, documented by the IC-F, may cause growth failure without other symptoms of Cushing's syndrome. Growth hormone therapy may improve the growth rate of these children at the time of their poor growth.

Fluoride-sensitivity of growth and acid production of oral Actinomyces: comparison with oral Streptococcus.

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Kawashima, Junko; Nakajo, Kazuko; Washio, Jumpei; Mayanagi, Gen; Shimauchi, Hidetoshi; Takahashi, Nobuhiro

2013-12-01

Actinomyces are predominant oral bacteria; however, their cariogenic potential in terms of acid production and fluoride sensitivity has not been elucidated in detail and compared with that of other caries-associated oral bacteria, such as Streptococcus. Therefore, this study aimed to elucidate and compare the acid production and growth of Actinomyces and Streptococcus in the presence of bicarbonate and fluoride to mimic conditions in the oral cavity. Acid production from glucose was measured by pH-stat at pH 5.5 and 7.0 under anaerobic conditions. Growth rate was assessed by optical density in anaerobic culture. Although Actinomyces produced acid at a lower rate than did Streptococcus, their acid production was more tolerant of fluoride (IDacid production 50 = 110-170 ppm at pH 7.0 and 10-13 ppm at pH 5.5) than that of Streptococcus (IDacid production 50 = 36-53 ppm at pH 7.0 and 6.3-6.5 ppm at pH 5.5). Bicarbonate increased acid production by Actinomyces with prominent succinate production and enhanced their fluoride tolerance (IDacid production 50 = 220-320 ppm at pH 7.0 and 33-52 ppm at pH 5.5). Bicarbonate had no effect on these variables in Streptococcus. In addition, although the growth rate of Actinomyces was lower than that of Streptococcus, Actinomyces growth was more tolerant of fluoride (IDgrowth 50 = 130-160 ppm) than was that of Streptococcus (IDgrowth 50 = 27-36 ppm). These results indicate that oral Actinomyces are more tolerant of fluoride than oral Streptococcus, and bicarbonate enhances the fluoride tolerance of oral Actinomyces. Because of the limited number of species tested here, further study is needed to generalize these findings to the genus level. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

Changes in glycosaminoglycans and proteoglycans of normal breast and fibroadenoma during the menstrual cycle.

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de Lima, Cilene Rebouças; de Arimatéa dos Santos Junior, José; Nazário, Afonso Celso Pinto; Michelacci, Yara M

2012-07-01

Fibroadenoma is the most common breast tumor in young women, and its growth and metabolism may be under hormonal control. In the present paper we described the proteoglycan (PG) composition and synthesis rate of normal breast and fibroadenoma during the menstrual cycle. Samples of fibroadenoma and adjacent normal breast tissue were obtained at surgery. PGs were characterized by agarose gel electrophoresis and enzymatic degradation with glycosaminoglycan (GAG) lyases, and immunolocalized by confocal microscopy. To assess the synthesis rate, PGs were metabolic labeled by 35S-sulfate. The concentration of PGs in normal breast was higher during the secretory phase. Fibroadenoma contained and synthesized more PGs than their paired controls, but the PG concentrations varied less with the menstrual cycle and, in contrast to normal tissue, peaked in the proliferative phase. The main mammary GAGs are heparan sulfate (HS, 71%-74%) and dermatan sulfate (DS, 26%-29%). The concentrations of both increased in fibroadenoma, but DS increased more, becoming 35%-37% of total. The DS chains contained more β-d-glucuronic acid (IdoUA/GlcUA ratios were >10 in normal breast and 2-7 in fibroadenoma). The 35S-sulfate incorporation rate revealed that the in vitro synthesis rate of DS was higher than HS. Decorin was present in both tissues, while versican was found only in fibroadenoma. In normal breast, the PG concentration varied with the menstrual cycle. It was increased in fibroadenoma, especially DS. PGs are increased in fibroadenoma, but their concentrations may be less sensitive to hormonal control. Copyright © 2012 Elsevier B.V. All rights reserved.

Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

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Woolf, N; Pearson, B E; Bondzie, P A; Meyer, R D; Lavaei, M; Belkina, A C; Chitalia, V; Rahimi, N

2017-09-18

Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

Plasmodium falciparum transfected with ultra bright NanoLuc luciferase offers high sensitivity detection for the screening of growth and cellular trafficking inhibitors.

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Mauro F Azevedo

Full Text Available Drug discovery is a key part of malaria control and eradication strategies, and could benefit from sensitive and affordable assays to quantify parasite growth and to help identify the targets of potential anti-malarial compounds. Bioluminescence, achieved through expression of exogenous luciferases, is a powerful tool that has been applied in studies of several aspects of parasite biology and high throughput growth assays. We have expressed the new reporter NanoLuc (Nluc luciferase in Plasmodium falciparum and showed it is at least 100 times brighter than the commonly used firefly luciferase. Nluc brightness was explored as a means to achieve a growth assay with higher sensitivity and lower cost. In addition we attempted to develop other screening assays that may help interrogate libraries of inhibitory compounds for their mechanism of action. To this end parasites were engineered to express Nluc in the cytoplasm, the parasitophorous vacuole that surrounds the intraerythrocytic parasite or exported to the red blood cell cytosol. As proof-of-concept, these parasites were used to develop functional screening assays for quantifying the effects of Brefeldin A, an inhibitor of protein secretion, and Furosemide, an inhibitor of new permeation pathways used by parasites to acquire plasma nutrients.

A new method for registration of kinesthetic evoked potentials for studies of proprioceptive sensitivity in normal subjects and patients with organic lesions in the brain.

Science.gov (United States)

Gordeev, S A; Voronin, S G

2015-01-01

The proprioceptive sensitivity of healthy volunteers and convalescents after acute cerebrovascular episodes was studied by a new neurophysiological method for registration of kinesthetic evoked potentials emerging in response to passive 50(o) bending of the hand in the wrist joint with the angular acceleration of 350 rad/sec(2). Kinesthetic evoked potentials were recorded above the somatosensory cortex projection areas in the hemispheres contra- and ipsilateral to the stimulated limb. The patients exhibited significantly longer latencies and lesser amplitudes of the early components of response in the involved hemisphere in comparison with normal subjects. The method for registration of the kinesthetic evoked potentials allows a more detailed study of the mechanisms of kinesthetic sensitivity in health and in organic involvement of the brain.

Monitoring the effects of atmospheric ethylene near polyethylene manufacturing plants with two sensitive plant species

Energy Technology Data Exchange (ETDEWEB)

Tonneijck, A.E.G.; Berge, W.F. ten; Jansen, B.P

2003-05-01

Atmospheric ethylene from polyethylene manufacturing plants adversely affected the number of flowers and growth of field-grown marigold and petunia. - Data of a multi-year (1977-1983) biomonitoring programme with marigold and petunia around polyethylene manufacturing plants was analysed to assess plant responses to atmospheric ethylene and to determine the area at risk for the phytotoxic effects of this pollutant. In both species, flower formation and growth were severely reduced close to the emission sources and plant performance improved with increasing distance. Plants exposed near the border of the research area had more flowers than the unexposed control while their growth was normal. Measurements of ethylene concentrations at a border site revealed that the growing season mean was 61.5 {mu}g m{sup -3} in 1982 and 15.6 {mu}g m{sup -3} in 1983. In terms of number of flowers, petunia was more sensitive than marigold and adverse effects were observed within ca. 400 m distance from the sources for marigold and within ca. 460 m for petunia. The area at risk (ca. 870 m) for ethylene-induced growth reduction was also limited to the industrial zone. Plants were more sensitive to ethylene in terms of growth reduction than in terms of inhibition of flowering. In the Netherlands, maximum permissible levels of ethylene are currently based on information from laboratory and greenhouse studies. Our results indicate that these levels are rather conservative in protecting field-grown plants against ethylene-induced injury near polyethylene manufacturing plants.

HRE-type genes are regulated by growth-related changes in internal oxygen concentrations during the normal development of potato (Solanum tuberosum) tubers.

Science.gov (United States)

Licausi, Francesco; Giorgi, Federico Manuel; Schmälzlin, Elmar; Usadel, Björn; Perata, Pierdomenico; van Dongen, Joost Thomas; Geigenberger, Peter

2011-11-01

The occurrence of hypoxic conditions in plants not only represents a stress condition but is also associated with the normal development and growth of many organs, leading to adaptive changes in metabolism and growth to prevent internal anoxia. Internal oxygen concentrations decrease inside growing potato tubers, due to their active metabolism and increased resistance to gas diffusion as tubers grow. In the present work, we identified three hypoxia-responsive ERF (StHRE) genes whose expression is regulated by the gradual decrease in oxygen tensions that occur when potato tubers grow larger. Increasing the external oxygen concentration counteracted the modification of StHRE expression during tuber growth, supporting the idea that the actual oxygen levels inside the organs, rather than development itself, are responsible for the regulation of StHRE genes. We identified several sugar metabolism-related genes co-regulated with StHRE genes during tuber development and possibly involved in starch accumulation. All together, our data suggest a possible role for low oxygen in the regulation of sugar metabolism in the potato tuber, similar to what happens in storage tissues during seed development.

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

Science.gov (United States)

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Downregulation of Akt1 Inhibits Anchorage-Independent Cell Growth and Induces Apoptosis in Cancer Cells

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Xuesong Liu

2001-01-01

Full Text Available The serine/threonine kinases, Akti/PKBα, Akt2/PKBβ, and Akt3/PKBγ, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an AM antisense oligonucleotide (AS to specifically downregulate Akti protein in both cancer and normal cells. Our data indicate that AM AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FRCS analysis and a caspase activity assay. Conversely, Akti AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF, fibroblast from muscle (FBM, and mammary gland epithelial 184135 cells. In addition, AM AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akti is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of AM may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.

Normalization of energy-dependent gamma survey data.

Science.gov (United States)

Whicker, Randy; Chambers, Douglas

2015-05-01

Instruments and methods for normalization of energy-dependent gamma radiation survey data to a less energy-dependent basis of measurement are evaluated based on relevant field data collected at 15 different sites across the western United States along with a site in Mongolia. Normalization performance is assessed relative to measurements with a high-pressure ionization chamber (HPIC) due to its "flat" energy response and accurate measurement of the true exposure rate from both cosmic and terrestrial radiation. While analytically ideal for normalization applications, cost and practicality disadvantages have increased demand for alternatives to the HPIC. Regression analysis on paired measurements between energy-dependent sodium iodide (NaI) scintillation detectors (5-cm by 5-cm crystal dimensions) and the HPIC revealed highly consistent relationships among sites not previously impacted by radiological contamination (natural sites). A resulting generalized data normalization factor based on the average sensitivity of NaI detectors to naturally occurring terrestrial radiation (0.56 nGy hHPIC per nGy hNaI), combined with the calculated site-specific estimate of cosmic radiation, produced reasonably accurate predictions of HPIC readings at natural sites. Normalization against two to potential alternative instruments (a tissue-equivalent plastic scintillator and energy-compensated NaI detector) did not perform better than the sensitivity adjustment approach at natural sites. Each approach produced unreliable estimates of HPIC readings at radiologically impacted sites, though normalization against the plastic scintillator or energy-compensated NaI detector can address incompatibilities between different energy-dependent instruments with respect to estimation of soil radionuclide levels. The appropriate data normalization method depends on the nature of the site, expected duration of the project, survey objectives, and considerations of cost and practicality.

Normal Brain-Skull Development with Hybrid Deformable VR Models Simulation.

Science.gov (United States)

Jin, Jing; De Ribaupierre, Sandrine; Eagleson, Roy

2016-01-01

This paper describes a simulation framework for a clinical application involving skull-brain co-development in infants, leading to a platform for craniosynostosis modeling. Craniosynostosis occurs when one or more sutures are fused early in life, resulting in an abnormal skull shape. Surgery is required to reopen the suture and reduce intracranial pressure, but is difficult without any predictive model to assist surgical planning. We aim to study normal brain-skull growth by computer simulation, which requires a head model and appropriate mathematical methods for brain and skull growth respectively. On the basis of our previous model, we further specified suture model into fibrous and cartilaginous sutures and develop algorithm for skull extension. We evaluate the resulting simulation by comparison with datasets of cases and normal growth.

Differential expression and processing of transforming growth factor beta induced protein (TGFBIp) in the normal human cornea during postnatal development and aging

DEFF Research Database (Denmark)

Karring, Henrik; Runager, Kasper; Valnickova, Zuzana

2010-01-01

Transforming growth factor beta induced protein (TGFBIp, also named keratoepithelin) is an extracellular matrix protein abundant in the cornea. The purpose of this study was to determine the expression and processing of TGFBIp in the normal human cornea during postnatal development and aging...... trimming events from the N-terminus of mature TGFBIp generate TGFBIp isoforms which form a similar "zig-zag" pattern when separated by 2-D polyacrylamide gel electrophoresis (PAGE). This study shows that in humans TGFBIp is more abundant in mature corneas than in the developing cornea...... and that the processing of TGFBIp changes during postnatal development of the cornea. In addition, TGFBIp appears to be degraded in a highly orchestrated manner in the normal human cornea with the resulting C-terminal fragments being retained in the cornea. The age-related changes in the expression and processing...

Two different in vitro growth patterns for erythroid precursors in 18 patients with pure erythrocytosis

International Nuclear Information System (INIS)

Clement, S.; Eberlin, A.; Najean, Y.; Chedeville, A.

1982-01-01

Growth patterns of marrow and blood erythroid progenitors were studied in 18 cases of pure erythrocytosis using different doses of erythropoietin. 8 cases demonstrated ''spontaneous'' growth of CFU-E and blood BFU-E as observed in myeloproliferative disorders, but without an excess of circulating CFU-GM. 3 of these patients also had other symptoms of a pan-myelopathy. All these cases showed good sensitivity to 32 P myelo-suppression. 10 cases demonstrated growth patterns of erythroid progenitors similar to those observed in normal subjects, except for an excess of blood BFU-E, which suggests an abnormality of homeostatic regulation. In 5 of these cases, myelo-suppression was not effective. It is suggested that a stem cell study could differentiate patients with pure erythrocytosis due to ''autonomous'' abnormal stem cell growth from cases due to abnormal regulation factors, and that such a discrimination might be usefull for the choice of theraphy. (authors)

Chemo-tolerance and sensitization by short-term fasting: The autophagy connection

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Gustav Van Niekerk

2016-11-01

Full Text Available Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy towards cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to up-regulate autophagy, an evolutionarily conserved catabolic process that is up-regulated in response to various cell stressors. Here we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. Firstly, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts.

Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor.

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Ojeda, Norma B; Royals, Thomas P; Alexander, Barbara T

2013-04-01

This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg(-1)·min(-1)) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls (P back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced (P < 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats.

Myeloperoxidase in the plasma and placenta of normal pregnant women and women with pregnancies complicated by preeclampsia and intrauterine growth restriction.

Science.gov (United States)

Hung, T-H; Chen, S-F; Lo, L-M; Li, M-J; Yeh, Y-L; Hsieh, T-T

2012-04-01

Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n = 40) and those who subsequently developed PE (n = 20), IUGR (n = 11) or both (PE + IUGR, n = 8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE + IUGR. The MPO concentrations were measured using ELISA. Women with PE + IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE + IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE + IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor. Copyright © 2012 Elsevier Ltd. All rights reserved.

Responses of vibrissa-sensitive cortical neurons in normal and prenatally x-irradiated rat

International Nuclear Information System (INIS)

Ito, M.; Kawabata, M.; Shoji, R.

1979-01-01

Rats were irradiated by 200 R of x ray on day 17 of gestation through the body wall of the mother. When they underwent the following electrophysiological tests at the age of 3 to 4 month, the somatosensory cortex showed a lack of layers II, III, IV, and Va. Spike responses to quick whisker deflections were recorded from single cells in the somatosenory cortex of normal and prenatally x-irradiated rats. For the irradiated rats the response latency was prolonged when compared to the normal controls. Cortical laminar analysis of field potentials revealed that there was no difference in the latency of these potentials between the two groups, suggesting that vibrissal sensory signals reach the cortical level normally even in the irradiated rats. The prolonged latency of the irradiated cortical neuronal response could thus be ascribed to an abnormal intracortical delay, which was most likely associated with the failure of development of layer IV stellate cells in these preparations

Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

International Nuclear Information System (INIS)

Harris, Peter S; Foreman, Nicholas K; Vibhakar, Rajeev; Venkataraman, Sujatha; Alimova, Irina; Birks, Diane K; Donson, Andrew M; Knipstein, Jeffrey; Dubuc, Adrian; Taylor, Michael D; Handler, Michael H

2012-01-01

Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. Analysis of gene expression in two independent cohorts revealed that PLK1 mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (SOX2) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells. Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants further investigation

Expression patterns of regulatory RNAs, including lncRNAs and tRNAs, during postnatal growth of normal and dystrophic (mdx) mouse muscles, and their response to taurine treatment.

Science.gov (United States)

Butchart, Lauren C; Terrill, Jessica R; Rossetti, Giulia; White, Robert; Filipovska, Aleksandra; Grounds, Miranda D

2018-06-01

Post-natal skeletal muscle growth in mice is very rapid and involves complex changes in many cells types over the first 6 weeks of life. The acute onset of dystropathology also occurs around 3 weeks of age in the mdx mouse model of the human disease Duchenne Muscular Dystrophy (DMD). This study investigated (i) alterations in expression patterns of regulatory non-coding RNAs (ncRNAs) in vivo, including miRNAs, lncRNAs and tRNAs, during early growth of skeletal muscles in normal control C57Bl/10Scsn (C57) compared with dystrophic mdx mice from 2 to 6 weeks of postnatal age, and revealed inherent differences in vivo for levels of 3 ncRNAs between C57 and mdx muscles before the onset of dystropathology. Since the amino acid taurine has many benefits and reduces disease severity in mdx mice, this study also (ii) determined the impact of taurine treatment on these expression patterns in mdx muscles at the onset of dystropathology (3 weeks) and after several bouts of myonecrosis and regeneration (6 weeks). Taurine treatment of mdx mice only altered ncRNA levels when administered from 18 days to 6 weeks of age, but a deficiency in tRNA levels was rectified earlier in mdx skeletal muscles treated from 14 days to 3 weeks. Myogenesis in tissue culture was also used to (iii) compare ncRNA expression patterns for both strains, and (iv) the response to taurine treatment. These analyses revealed intrinsic differences in ncRNA expression patterns during myogenesis between strains, as well as increased sensitivity of mdx ncRNA levels to taurine treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prolactin-sensitive neurons express estrogen receptor-α and depend on sex hormones for normal responsiveness to prolactin.

Science.gov (United States)

Furigo, Isadora C; Kim, Ki Woo; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; de Alencar, Amanda; Pedroso, João A B; Metzger, Martin; Donato, Jose

2014-05-30

Estrogens and prolactin share important target tissues, including the gonads, brain, liver, kidneys and some types of cancer cells. Herein, we sought anatomical and functional evidence of possible crosstalk between prolactin and estrogens in the mouse brain. First, we determined the distribution of prolactin-responsive neurons that express the estrogen receptor α (ERα). A large number of prolactin-induced pSTAT5-immunoreactive neurons expressing ERα mRNA were observed in several brain areas, including the anteroventral periventricular nucleus, medial preoptic nucleus, arcuate nucleus of the hypothalamus, ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH), medial nucleus of the amygdala and nucleus of the solitary tract. However, although the medial preoptic area, periventricular nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus, retrochiasmatic area, dorsomedial subdivision of the VMH, lateral hypothalamic area, dorsomedial nucleus of the hypothalamus and ventral premammillary nucleus contained significant numbers of prolactin-responsive neurons, these areas showed very few pSTAT5-immunoreactive cells expressing ERα mRNA. Second, we evaluated prolactin sensitivity in ovariectomized mice and observed that sex hormones are required for a normal responsiveness to prolactin as ovariectomized mice showed a lower number of prolactin-induced pSTAT5 immunoreactive neurons in all analyzed brain nuclei compared to gonad-intact females. In addition, we performed hypothalamic gene expression analyses to determine possible post-ovariectomy changes in components of prolactin signaling. We observed no significant changes in the mRNA expression of prolactin receptor, STAT5a or STAT5b. In summary, sex hormones exert a permissive role in maintaining the brain's prolactin sensitivity, most likely through post-transcriptional mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Insulin sensitivity and albuminuria

DEFF Research Database (Denmark)

Pilz, Stefan; Rutters, Femke; Nijpels, Giel

2014-01-01

OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

Drought sensitivity changes over the last century at the North American savanna-forest boundary

Science.gov (United States)

Heilman, K.; McLachlan, J. S.

2017-12-01

Future environmental changes can affect the sensitivity of tree growth to climate. Theses changes are of particular concern at biome boundaries where tree distribution could shift as a result of changes in both drought and drought sensitivity. One such region is the North American savanna-forest boundary, where increased CO2 and droughts could alter savanna and forest ecosystem distributions in two contrasting ways: 1). More severe droughts may increase drought sensitivity, favoring open savanna ecosystems or, 2). Increases in water use efficiency resulting from higher atmospheric CO2 may decrease drought sensitivity, promoting forest expansion. This study sought to understand whether the past 100 years of climate and CO2 changes have impacted regional tree growth-climate sensitivity. To test for these climate sensitivity changes, we measured the sensitivity of Quercus spp. radial growth to Palmer Drought Severity Index (PDSI). Tree growth sensitivity to climate can vary according to many factors, including: stand structure, available moisture, and tree age. To control for these factors, we sampled tree growth-climate responses at sites in both open and closed forests, and at both low and high annual precipitation. Within each site, we compared growth responses to climate between trees established under high CO2 conditions after 1950 (high CO2 young), and tree established before 1950 under low CO2 levels (low CO2 young). At most sites, low CO2 young have a higher drought sensitivity than higher CO2 young. These changes in the sensitivity to drought are consistent with CO2 enhancement of water use efficiency. Furthermore, these differences in drought sensitivity are higher at sites with high temperature and low precipitation, suggesting that the alleviation of drought is more likely in hot and dry regions. Thus, if CO2 enhancement is indeed occurring in these systems, lower growth sensitivity to drought in hot and dry regions could favor increased forest growth. If

Robust Growth Determinants

OpenAIRE

Doppelhofer, Gernot; Weeks, Melvyn

2011-01-01

This paper investigates the robustness of determinants of economic growth in the presence of model uncertainty, parameter heterogeneity and outliers. The robust model averaging approach introduced in the paper uses a flexible and parsi- monious mixture modeling that allows for fat-tailed errors compared to the normal benchmark case. Applying robust model averaging to growth determinants, the paper finds that eight out of eighteen variables found to be significantly related to economic growth ...

Seismic sensitivity of normal-mode coupling to Lorentz stresses in the Sun

Science.gov (United States)

Hanasoge, Shravan M.

2017-09-01

Understanding the governing mechanism of solar magnetism remains an outstanding challenge in astrophysics. Seismology is the most compelling technique to infer the internal properties of the Sun and stars. Waves in the Sun, nominally acoustic, are sensitive to the emergence and cyclical strengthening of magnetic field, evidenced by measured changes in resonant oscillation frequencies that are correlated with the solar cycle. The inference of internal Lorentz stresses from these measurements has the potential to significantly advance our appreciation of the dynamo. Indeed, seismological inverse theory for the Sun is well understood for perturbations in composition, thermal structure and flows but, is not fully developed for magnetism, owing to the complexity of the ideal magnetohydrodynamic (MHD) equation. Invoking first-Born perturbation theory to characterize departures from spherically symmetric hydrostatic models of the Sun and applying the notation of generalized spherical harmonics, we calculate sensitivity functions of seismic measurements to the general time-varying Lorentz stress tensor. We find that eigenstates of isotropic (I.e. acoustic only) background models are dominantly sensitive to isotropic deviations in the stress tensor and much more weakly than anisotropic stresses (and therefore challenging to infer). The apple cannot fall far from the tree.

Contrast sensitivity abnormalities in deaf individuals

Directory of Open Access Journals (Sweden)

Masoud Khorrami-Nejad

2018-01-01

Conclusion: Hearing impaired boys are at a greater risk for contrast sensitivity abnormalities than boys with normal hearing. The larger frequency of contrast sensitivity abnormalities in high spatial frequencies than in other frequencies may demonstrate greater defects in the central visual system compared with the periphery in individuals with hearing loss.

Review: Adiponectin – The Missing Link between Maternal Adiposity, Placental Transport and Fetal Growth?

Science.gov (United States)

Aye, Irving L. M. H.; Powell, Theresa L.; Jansson, Thomas

2012-01-01

Adiponectin has well-established insulin-sensitizing effects in non-pregnant individuals. Pregnant women who are obese or have gestational diabetes typically have low circulating levels of adiponectin, which is associated with increased fetal growth. Lean women, on the other hand, have high circulating levels of adiponectin. As a result, maternal serum adiponectin is inversely correlated to fetal growth across the full range of birth weights, suggesting that maternal adiponectin may limit fetal growth. In the mother, adiponectin is predicted to promote insulin sensitivity and stimulate glucose uptake in maternal skeletal muscle thereby reducing nutrient availability for placental transfer. Adiponectin prevents insulin-stimulated amino acid uptake in cultured primary human trophoblast cells by modulating insulin receptor substrate phosphorylation. Furthermore, chronic administration of adiponectin to pregnant mice inhibits placental insulin and mammalian target of rapamycin complex 1 (mTORC1) signaling, down-regulates the activity and expression of key placental nutrient transporters and decreases fetal growth. Preliminary findings indicate that adiponectin binds to the adiponectin receptor-2 on the trophoblast cell and activates p38 MAPK and PPAR-α, which inhibits the insulin/IGF-1 signaling pathway. In contrast to maternal adiponectin, recent reports suggest that fetal adiponectin may promote expansion of adipose tissue and stimulate fetal growth. Regulation of placental function by adiponectin constitutes a novel physiological mechanism by which the endocrine functions of maternal adipose tissue influence fetal growth. These findings may help us better understand the factors determining birth weight in normal pregnancies and in pregnancy complications associated with altered maternal adiponectin levels such as obesity and gestational diabetes. PMID:23245987

Homeorhetic hormones, metabolites and accelerated growth ...

African Journals Online (AJOL)

Blood samples were drawn from surgically implanted catheters in the caudal aorta and vena cava during normal growth, maintenance (zero) growth and accelerated growth.These samples were assayed for glucose, free fatty acids, glycerol, alanine, lysine, growth hormone, insulin and thyroxine. It was found that during the ...

Charge collection and absorption-limited x-ray sensitivity of pixellated x-ray detectors

International Nuclear Information System (INIS)

Kabir, M. Zahangir; Kasap, S.O.

2004-01-01

The charge collection and absorption-limited x-ray sensitivity of a direct conversion pixellated x-ray detector operating in the presence of deep trapping of charge carriers is calculated using the Shockley-Ramo theorem and the weighting potential of the individual pixel. The sensitivity of a pixellated x-ray detector is analyzed in terms of normalized parameters; (a) the normalized x-ray absorption depth (absorption depth/photoconductor thickness), (b) normalized pixel width (pixel size/thickness), and (c) normalized carrier schubwegs (schubweg/thickness). The charge collection and absorption-limited sensitivity of pixellated x-ray detectors mainly depends on the transport properties (mobility and lifetime) of the charges that move towards the pixel electrodes and the extent of dependence increases with decreasing normalized pixel width. The x-ray sensitivity of smaller pixels may be higher or lower than that of larger pixels depending on the rate of electron and hole trapping and the bias polarity. The sensitivity of pixellated detectors can be improved by ensuring that the carrier with the higher mobility-lifetime product is drifted towards the pixel electrodes

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

Science.gov (United States)

Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

2015-10-13

Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

Influence of nutrient medium composition on uranium toxicity and choice of the most sensitive growth related endpoint in Lemna minor.

Science.gov (United States)

Horemans, Nele; Van Hees, May; Saenen, Eline; Van Hoeck, Arne; Smolders, Valérie; Blust, Ronny; Vandenhove, Hildegarde

2016-01-01

Uranium (U) toxicity is known to be highly dependent on U speciation and bioavailability. To assess the impact of uranium on plants, a growth inhibition test was set up in the freshwater macrophyte Lemna minor. First growth media with different compositions were tested in order to find a medium fit for testing U toxicity in L. minor. Following arguments were used for medium selection: the ability to sustain L. minor growth, a high solubility of U in the medium and a high percentage of the more toxic U-species namely UO2(2+). Based on these selection criteria a with a low phosphate concentration of 0.5 mg L(-1) and supplemented with 5 mM MES (2-(N-morpholino)ethanesulfonic acid) to ensure pH stability was chosen. This medium also showed highest U toxicity compared to the other tested media. Subsequently a full dose response curve for U was established by exposing L. minor plants to U concentrations ranging from 0.05 μM up to 150 μM for 7 days. Uranium was shown to adversely affect growth of L. minor in a dose dependent manner with EC10, EC30 and EC50 values ranging between 1.6 and 4.8 μM, 7.7-16.4 μM and 19.4-37.2 μM U, respectively, depending on the growth endpoint. Four different growth related endpoints were tested: frond area, frond number, fresh weight and dry weight. Although differences in relative growth rates and associated ECx-values calculated on different endpoints are small (maximal twofold difference), frond area is recommended to be used to measure U-induced growth effects as it is a sensitive growth endpoint and easy to measure in vivo allowing for measurements over time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of immunological methods for detection of bovine growth hormone (BGH) produced in E. coli

International Nuclear Information System (INIS)

Rosner, A.; Zwang, R.; Aviv, H.

1982-01-01

The use of several immunological methods for studies on synthesis of bovine growth hormone (BGH) by E. coli is described here. The ELISA procedure was shown to be the least sensitive and unfit for assaying BGH in E. coli extracts. The solid-phase radioimmunoassay (RIA) proved to be highly sensitive, but since E. coli extract itself (not containing BGH) interfered with the immunological reaction, its use for measuring BGH was practically limited. The best adequate procedure proved to be radioimmunoassay in solution, which was not adversely affected by the E. coli extract and was sufficiently sensitive to detect nanogram quantities of BGH. The size of the BGH produced by normal bacterial cells was investigated by protein fractionation, transfer to nitrocellulose paper and detection by anti-BGH serum. This method also served for semi-quantitative determination of BGH in the bacterial extract. (Auth.)

Evaluation of immunological methods for detection of bovine growth hormone (BGH) produced in E. coli

Energy Technology Data Exchange (ETDEWEB)

Rosner, A; Zwang, R; Aviv, H [Weizmann Institute of Science, Rehovot (Israel). Dept. of Virology

1982-07-30

The use of several immunological methods for studies on synthesis of bovine growth hormone (BGH) by E. coli is described here. The ELISA procedure was shown to be the least sensitive and unfit for assaying BGH in E. coli extracts. The solid-phase radioimmunoassay (RIA) proved to be highly sensitive, but since E. coli extract itself (not containing BGH) interfered with the immunological reaction, its use for measuring BGH was practically limited. The most adequate procedure proved to be radioimmunoassay in solution, which was not adversely affected by the E. coli extract and was sufficiently sensitive to detect nanogram quantities of BGH. The size of the BGH produced by normal bacterial cells was investigated by protein fractionation, transfer to nitrocellulose paper and detection by anti-BGH serum. This method also served for semi-quantitative determination of BGH in the bacterial extract.

Differences in correlation of mRNA gene expression in mice sensitive and resistant to radiation-induced pulmonary fibrosis

International Nuclear Information System (INIS)

Johnston, C.J.; Piedboeuf, B.; Finkelstein, J.N.; Baggs, R.; Rubin, P.

1995-01-01

Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The purpose of this study was to determine if extracellular matrix protein and transforming growth factor β mRNA expression are altered late in the course of pulmonary fibrosis after irradiation, and then to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Radiation-sensitive (C57BL/6) and radiation-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabeled cDNA probes for collagens I, III and IV, fibronectin, and transforming growth factor β 1 and β 3 . Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceralde-hyde-3-phosphate dehydrogenase. Alterations in mRNA abundance were observed in the sensitive mice at all times, while levels in the resistant mice were unaffected until 26 weeks after irradiation. The relationship between extracellular matrix protein per se and increased mRNA abundance suggests that late matrix protein accumulation may be a function of gene expression. Differences in levels of transforming growth factor βmRNA may lead to strain-dependent variation in fibrotic response and may also contribute to the radiation-induced component of pulmonary fibrosis. 32 refs., 5 figs

Effects of octreotide infusion, surgery and estrogen on suppression of height increase and 20K growth hormone ratio in a girl with gigantism due to a growth hormone-secreting macroadenoma.

Science.gov (United States)

Minagawa, M; Yasuda, T; Someya, T; Kohno, Y; Saeki, N; Hashimoto, Y

2000-01-01

We treated an extremely tall 13-year-old girl with a growth hormone (GH)-secreting macroadenoma and GH levels of 120-495 ng/ml with a combination of preoperative octreotide infusion, surgery and postoperative octreotide infusion plus estrogen, which resulted in reduced tumor size prior to surgery, reduced GH levels and completely suppressed growth after surgery. 20K GH is produced by alternative splicing of 22K GH mRNA and the ratio of 20K GH to 22K GH is within a small range in the normal population and high in a GH-secreting tumor. The 20K/22K GH ratio in this patient was persistently elevated during each phase of the treatment and may serve as a sensitive index of tumor-derived GH secretion. Copyright 2000 S. Karger AG, Basel.

Orientations of dendritic growth during solidification

Science.gov (United States)

Lee, Dong Nyung

2017-03-01

Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.

Methylglyoxal and other carbohydrate metabolites induce lanthanum-sensitive Ca2+ transients and inhibit growth in E. coli.

Science.gov (United States)

Campbell, Anthony K; Naseem, Riffat; Holland, I Barry; Matthews, Stephanie B; Wann, Kenneth T

2007-12-01

The results here are the first demonstration of a family of carbohydrate fermentation products opening Ca2+ channels in bacteria. Methylglyoxal, acetoin (acetyl methyl carbinol), diacetyl (2,3 butane dione), and butane 2,3 diol induced Ca2+ transients in Escherichia coli, monitored by aequorin, apparently by opening Ca2+ channels. Methylglyoxal was most potent (K(1/2) = 1 mM, 50 mM for butane 2,3 diol). Ca2+ transients depended on external Ca2+ (0.1-10 mM), and were blocked by La3+ (5 mM). The metabolites affected growth, methylglyoxal being most potent, blocking growth completely up to 5 h without killing the cells. But there was no affect on the number of viable cells after 24 h. These results were consistent with carbohydrate products activating a La3+-sensitive Ca2+ channel, rises in cytosolic Ca2+ possibly protecting against certain toxins. They have important implications in bacterial-host cell signalling, and where numbers of different bacteria compete for the same substrates, e.g., the gut in lactose and food intolerance.

Characterization of mitomycin-C-sensitive mouse lymphoma L5178Y cell mutants

International Nuclear Information System (INIS)

Inaba, Hiroko; Shiomi, Naoko; Shiomi, Tadahiro; Sato, Koki; Yoshida, Michihiro.

1985-01-01

Twenty-six mutants showing high sensitivity to mytomicin-C (MMC) were isolated from mouse lymphoma L5178Y cells by a replica-plating technique. Twenty-five of the mutants were 5 - 10 times more sensitive to MMC than were parental cells, and showed normal sensitivity to U.V. light and x-rays. From a complementation analysis, 5 mutants (MC s ) isolated from independently mutagenized cell populations were classified into two groups. These mutants possessed recessive character for MMC-sensitivity and there were at least two genes involved in the MMC-sensitivity. As for DNA-damaging factors, such as photoadducts of 8-methoxypsoralen (8-MOP) and 3-carbethoxysoralen (3-CPs), MC s mutants showed higher sensitivity to photoadducts of 8-MOP than to (3-CPs). MC s mutants were also highly sensitive to a DNA cross-linking agent, cisplatin. Characterization of the sensitivity of mouse MC s mutants was analogous to that of Fanconi's anemia (FA)-derived cells. Low concentrations (10 ng/ml) of MMC induced chromosome aberration in a high incidence in mouse MC s cells, as well as in FA cells. The frequency of MMC-induced chromosome aberrations was normal in hybrid cells between normal human diploid somatic cells and mouse mutants and between FA cells and mouse wild cells, and hereditary deficiency became normal by hybrization. (Namekawa, K.)

Normalization of tumor microenvironment by neem leaf glycoprotein potentiates effector T cell functions and therapeutically intervenes in the growth of mouse sarcoma.

Directory of Open Access Journals (Sweden)

Subhasis Barik

Full Text Available We have observed restriction of the murine sarcoma growth by therapeutic intervention of neem leaf glycoprotein (NLGP. In order to evaluate the mechanism of tumor growth restriction, here, we have analyzed tumor microenvironment (TME from sarcoma bearing mice with NLGP therapy (NLGP-TME, in comparison to PBS-TME. Analysis of cytokine milieu within TME revealed IL-10, TGFβ, IL-6 rich type 2 characters was switched to type 1 microenvironment with dominance of IFNγ secretion within NLGP-TME. Proportion of CD8(+ T cells was increased within NLGP-TME and these T cells were protected from TME-induced anergy by NLGP, as indicated by higher expression of pNFAT and inhibit related downstream signaling. Moreover, low expression of FasR(+ cells within CD8(+ T cell population denotes prevention from activation induced cell death. Using CFSE as a probe, better migration of T cells was noted within TME from NLGP treated mice than PBS cohort. CD8(+ T cells isolated from NLGP-TME exhibited greater cytotoxicity to sarcoma cells in vitro and these cells show higher expression of cytotoxicity related molecules, perforin and granzyme B. Adoptive transfer of NLGP-TME exposed T cells, but not PBS-TME exposed cells in mice, is able to significantly inhibit the growth of sarcoma in vivo. Such tumor growth inhibition by NLGP-TME exposed T cells was not observed when mice were depleted for CD8(+ T cells. Accumulated evidences strongly suggest NLGP mediated normalization of TME allows T cells to perform optimally to inhibit the tumor growth.

The hypoxic tumor microenvironment and drug resistance against EGFR inhibitors: preclinical study in cetuximab-sensitive head and neck squamous cell carcinoma cell lines.

Science.gov (United States)

Boeckx, Carolien; Van den Bossche, Jolien; De Pauw, Ines; Peeters, Marc; Lardon, Filip; Baay, Marc; Wouters, An

2015-06-02

Increased expression of the epidermal growth factor receptor (EGFR) is observed in more than 90% of all head and neck squamous cell carcinomas (HNSCC). Therefore, EGFR has emerged as a promising therapeutic target. Nevertheless, drug resistance remains a major challenge and an important potential mechanism of drug resistance involves the hypoxic tumor microenvironment. Therefore, we investigated the cytotoxic effect of the EGFR-targeting agents cetuximab and erlotinib under normoxia versus hypoxia. Three cetuximab-sensitive HNSCC cell lines (SC263, LICR-HN2 and LICR-HN5) were treated with either cetuximab or erlotinib. Cells were incubated under normal or reduced oxygen conditions (<0.1% O2) for 24 or 72 h immediately after drug addition. Cell survival was assessed with the sulforhodamine B assay. Cetuximab and erlotinib established a dose-dependent growth inhibition under both normal and prolonged reduced oxygen conditions in all three HNSCC cell lines. However, a significantly increased sensitivity to cetuximab was observed in SC263 cells exposed to hypoxia for 72 h (p = 0.05), with IC50 values of 2.38 ± 0.59 nM, 0.64 ± 0.38 nM, and 0.10 ± 0.05 nM under normoxia, hypoxia for 24 h and hypoxia for 72 h, respectively. LICR-HN5 cells showed an increased sensitivity towards erlotinib when cells were incubated under hypoxia for 24 h (p = 0.05). Our results suggest that both EGFR-inhibitors cetuximab and erlotinib maintain their growth inhibitory effect under hypoxia. These results suggest that resistance to anti-EGFR therapy in HNSCC is probably not the result of hypoxic regions within the tumor and other mechanisms are involved.

Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

Science.gov (United States)

Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

2017-04-01

Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

Your Baby's Growth: 12 Months

Science.gov (United States)

... Safe Videos for Educators Search English Español Your Baby's Growth: 12 Months KidsHealth / For Parents / Your Baby's ... doubled his or her birth weight. Is My Baby Growing Normally? Babies' growth begins to slow as ...

Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor

International Nuclear Information System (INIS)

Matsumoto, K.; Hashimoto, K.; Yoshikawa, K.; Nakamura, T.

1991-01-01

Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes

MR imaging of the ankle: Normal variants

International Nuclear Information System (INIS)

Noto, A.M.; Cheung, Y.; Rosenberg, Z.S.; Norman, A.; Leeds, N.E.

1987-01-01

Thirty asymptomatic ankles were studied with high-resolution surface coil MR imaging. The thirty ankles were reviewed for identification or normal structures. The MR appearance of the deltoid and posterior to talo-fibular ligaments, peroneous brevis and longus tendons, and posterior aspect of the tibial-talar joint demonstrated several normal variants not previously described. These should not be misinterpreted as pathologic processes. The specific findings included (1) cortical irregularity of the posterior tibial-talar joint in 27 of 30 cases which should not be mistaken for osteonecrois; (2) normal posterior talo-fibular ligament with irregular and frayed inhomogeneity, which represents a normal variant in seven of ten cases; and (3) fluid in the shared peroneal tendons sheath which may be confused for a longitudinal tendon tear in three of 30 cases. Ankle imaging with the use of MR is still a relatively new procedure. Further investigation is needed to better define normal anatomy as well as normal variants. The authors described several structures that normally present with variable MR imaging appearances. This is clinically significant in order to maintain a high sensitivity and specificity in MR imaging interpretation

Cross Correlation versus Normalized Mutual Information on Image Registration

Science.gov (United States)

Tan, Bin; Tilton, James C.; Lin, Guoqing

2016-01-01

This is the first study to quantitatively assess and compare cross correlation and normalized mutual information methods used to register images in subpixel scale. The study shows that the normalized mutual information method is less sensitive to unaligned edges due to the spectral response differences than is cross correlation. This characteristic makes the normalized image resolution a better candidate for band to band registration. Improved band-to-band registration in the data from satellite-borne instruments will result in improved retrievals of key science measurements such as cloud properties, vegetation, snow and fire.

Circulating vascular endothelial growth factor during the normal menstrual cycle

NARCIS (Netherlands)

Kusumanto, YH; Hospers, GAP; Sluiter, WJ; Dam, WA; Meijer, C; Mulder, NH

2004-01-01

Background: The purpose of the study was to investigate whether cycle-related variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would increase the metastatic potential at specific times during the menstrual cycle. Materials and Methods: VEGF levels in serum and whole blood

Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

International Nuclear Information System (INIS)

Bentzen, Soeren M.

1997-01-01

A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF 2 . Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF 2 . Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity

Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

International Nuclear Information System (INIS)

Plevova, P.

2002-01-01

Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

Leuconostoc mesenteroides growth in food products: prediction and sensitivity analysis by adaptive-network-based fuzzy inference systems.

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Hue-Yu Wang

Full Text Available BACKGROUND: An adaptive-network-based fuzzy inference system (ANFIS was compared with an artificial neural network (ANN in terms of accuracy in predicting the combined effects of temperature (10.5 to 24.5°C, pH level (5.5 to 7.5, sodium chloride level (0.25% to 6.25% and sodium nitrite level (0 to 200 ppm on the growth rate of Leuconostoc mesenteroides under aerobic and anaerobic conditions. METHODS: THE ANFIS AND ANN MODELS WERE COMPARED IN TERMS OF SIX STATISTICAL INDICES CALCULATED BY COMPARING THEIR PREDICTION RESULTS WITH ACTUAL DATA: mean absolute percentage error (MAPE, root mean square error (RMSE, standard error of prediction percentage (SEP, bias factor (Bf, accuracy factor (Af, and absolute fraction of variance (R (2. Graphical plots were also used for model comparison. CONCLUSIONS: The learning-based systems obtained encouraging prediction results. Sensitivity analyses of the four environmental factors showed that temperature and, to a lesser extent, NaCl had the most influence on accuracy in predicting the growth rate of Leuconostoc mesenteroides under aerobic and anaerobic conditions. The observed effectiveness of ANFIS for modeling microbial kinetic parameters confirms its potential use as a supplemental tool in predictive mycology. Comparisons between growth rates predicted by ANFIS and actual experimental data also confirmed the high accuracy of the Gaussian membership function in ANFIS. Comparisons of the six statistical indices under both aerobic and anaerobic conditions also showed that the ANFIS model was better than all ANN models in predicting the four kinetic parameters. Therefore, the ANFIS model is a valuable tool for quickly predicting the growth rate of Leuconostoc mesenteroides under aerobic and anaerobic conditions.

Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation

International Nuclear Information System (INIS)

Gast, Klaus K.; Biedermann, Alexander; Herweling, Annette; Schreiber, Wolfgang G.; Schmiedeskamp, Joerg; Mayer, Eckhard; Heussel, Claus P.; Markstaller, Klaus; Eberle, Balthasar; Kauczor, Hans-Ulrich

2008-01-01

Oxygen-sensitive 3 He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO 2 ) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3 He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acquired on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3 He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO 2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3 He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3 He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients. (orig.)

Growth in pediatric renal transplant recipients.

Science.gov (United States)

Vasudevan, A; Phadke, K

2007-04-01

One of the fundamental challenges in managing pediatric renal transplant recipient is to ensure normal growth and development. The goal of renal transplant is not just to prolong life but to optimize quality of life. Short stature during childhood may be associated with academic underachievement and development of comorbidities such as attention deficit hyperactivity disorder, learning disability, and mood disorders. The most important factors affecting growth are use of corticosteroids, allograft function, and age and height deficit at the time of transplant. Aggressive conservative management of chronic renal failure and early use of growth hormone therapy will help in optimizing height at time of transplant. Early transplant, steroid minimization or withdrawal, and growth hormone therapy will help in achieving normal adult height in a majority of renal post transplant population. Steroid avoidance to achieve good growth still needs to be validated.

Epithelial-mesenchymal transition increases tumor sensitivity to COX-2 inhibition by apricoxib.

Science.gov (United States)

Kirane, Amanda; Toombs, Jason E; Larsen, Jill E; Ostapoff, Katherine T; Meshaw, Kathryn R; Zaknoen, Sara; Brekken, Rolf A; Burrows, Francis J

2012-09-01

Although cyclooxygenase-2 (COX-2) inhibitors, such as the late stage development drug apricoxib, exhibit antitumor activity, their mechanisms of action have not been fully defined. In this study, we characterized the mechanisms of action of apricoxib in HT29 colorectal carcinoma. Apricoxib was weakly cytotoxic toward naive HT29 cells in vitro but inhibited tumor growth markedly in vivo. Pharmacokinetic analyses revealed that in vivo drug levels peaked at 2-4 µM and remained sufficient to completely inhibit prostaglandin E(2) production, but failed to reach concentrations cytotoxic for HT29 cells in monolayer culture. Despite this, apricoxib significantly inhibited tumor cell proliferation and induced apoptosis without affecting blood vessel density, although it did promote vascular normalization. Strikingly, apricoxib treatment induced a dose-dependent reversal of epithelial-mesenchymal transition (EMT), as shown by robust upregulation of E-cadherin and the virtual disappearance of vimentin and ZEB1 protein expression. In vitro, either anchorage-independent growth conditions or forced EMT sensitized HT29 and non-small cell lung cancer cells to apricoxib by 50-fold, suggesting that the occurrence of EMT may actually increase the dependence of colon and lung carcinoma cells on COX-2. Taken together, these data suggest that acquisition of mesenchymal characteristics sensitizes carcinoma cells to apricoxib resulting in significant single-agent antitumor activity.

Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells.

Science.gov (United States)

Liu, Xunxian; Allen, Jeffrey D; Arnold, Julia T; Blackman, Marc R

2008-04-01

Prostate stromal and epithelial cell communication is important in prostate functioning and cancer development. Primary human stromal cells from normal prostate stromal cells (PRSC) maintain a smooth muscle phenotype, whereas those from prostate cancer (6S) display reactive and fibroblastic characteristics. Dihydrotestosterone (DHT) stimulates insulin-like growth factor-I (IGF-I) production by 6S but not PSRC cells. Effects of reactive versus normal stroma on normal human prostate epithelial (NPE or PREC) cells are poorly understood. We co-cultured NPE plus 6S or PRSC cells to compare influences of different stromal cells on normal epithelium. Because NPE and PREC cells lose androgen receptor (AR) expression in culture, DHT effects must be modulated by associated stromal cells. When treated with camptothecin (CM), NPE cells, alone and in stromal co-cultures, displayed a dose-dependent increase in DNA fragmentation. NPE/6S co-cultures exhibited reduced CM-induced cell death with exposure to DHT, whereas NPE/PRSC co-cultures exhibited CM-induced cell death regardless of DHT treatment. DHT blocked CM-induced, IGF-I-mediated, NPE death in co-cultured NPE/6S cells without, but not with, added anti-IGF-I and anti-IGF-R antibodies. Lycopene consumption is inversely related to human prostate cancer risk and inhibits IGF-I and androgen signaling in rat prostate cancer. In this study, lycopene, in dietary concentrations, reversed DHT effects of 6S cells on NPE cell death, decreased 6S cell IGF-I production by reducing AR and beta-catenin nuclear localization and inhibited IGF-I-stimulated NPE and PREC growth, perhaps by attenuating IGF-I's effects on serine phosphorylation of Akt and GSK3beta and tyrosine phosphorylation of GSK3. This study expands the understanding of the preventive mechanisms of lycopene in prostate cancer.

Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

Science.gov (United States)

Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

1998-08-01

We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

Feedforward somatosensory inhibition is normal in cervical dystonia.

Science.gov (United States)

Ferrè, Elisa R; Ganos, Christos; Bhatia, Kailash P; Haggard, Patrick

2015-03-01

Insufficient cortical inhibition is a key pathophysiological finding in dystonia. Subliminal sensory stimuli were reported to transiently inhibit somatosensory processing. Here we investigated whether such subliminal feedforward inhibition is reduced in patients with cervical dystonia. Sixteen cervical dystonia patients and 16 matched healthy controls performed a somatosensory detection task. We measured the drop in sensitivity to detect a threshold-level digital nerve shock when it was preceded by a subliminal conditioning shock, compared to when it was not. Subliminal conditioning shocks reduced sensitivity to threshold stimuli to a similar extent in both patients and controls, suggesting that somatosensory subliminal feedforward inhibition is normal in cervical dystonia. Somatosensory feedforward inhibition was normal in this group of cervical dystonia patients. Our results qualify previous concepts of a general dystonic deficit in sensorimotor inhibitory processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunohistochemical expression of Insulin-like growth factor-1, Transforming growth factor-beta1, and Vascular endothelial growth factor in parathyroid adenoma and hyperplasia

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Hamide Sayar

2014-01-01

Full Text Available Background: Insulin-like growth factor (IGF, transforming growth factor-beta1 (TGF-β1, and vascular endothelial growth factor (VEGF are commonly studied growth factors, but little data are available on the immunohistochemical expression of these factors in parathyroid lesions. Materials and Methods: Tissue specimens from 36 patients with primary hyperparathyroidism (P-HPT (26 adenomas and 10 primary hyperplasias were examined. Normal parathyroid tissue adjacent to the adenoma or area of hyperplasia was used as control tissue. Preoperative laboratory testing [serum Ca and P, creatinine and parathormone levels (PTH] which led to the diagnosis of P-HPT had been performed, the size and weight of the parathyroid glands measured, and postoperative serum PTH levels determined. Paraffin-embedded parathyroid tissue specimens were stained with antibodies to IGF-1, VEGF, and TGF-β1 using standard immunohistochemical procedures. Results: IGF-1 immunoreactivity was seen in 50% of hyperplasia and in 46% of adenoma samples, but in 87% of normal parathyroid tissue in the vicinity of the adenomas (P = 0.005. TGF-β1 immunoreactivity was observed in 90% of hyperplasia, in 92% of adenoma samples, and in 95% of normal tissues around adenomas. VEGF immunoreactivity was observed in 70% of hyperplastic and 65% of adenomatous tissues, as well as in 54% of normal tissues in the vicinity of the adenoma. No significant differences in the expression of IGF-1, TGF-β1, and VEGF were observed between primary adenomas compared to hyperplasia samples (P > 0.05. Conclusions: Parathyroid tissue is clearly a site for production of IGF-1, TGF-β1, and VEGF. IGF-1 receptor activity was higher in normal parathyroid tissue compared to hyperplastic and adenomatous tissue.

Sensitivity of root-knot nematodes to gamma irradiation, salinity and plant growth regulator, cycocel

Energy Technology Data Exchange (ETDEWEB)

Sweelam, M E [Econ. Entomology Dept., Fac. Agric. Menoufia University Shebin El-Kom, (Egypt)

1995-10-01

The experiment was carried out at the experimental station of the faculty of agriculture, Menoufia Univ. To determine the sensitivity of root-knot nematode, Meloidogyne Javanica infecting tomato plants exposed to different doses of gamma irradiation 0,20,40,60,80 Gy, salinity levels 0. 1000, 2000, 4000 ppm and the plant growth regulator cycocel 0,200 ppm. Treated seeds were planted clay pots and salinity levels and cycocel concentrations were applied. Fresh weights and nematode populations were computed 3 months after application. Results indicated that 20 Gy, 1000 ppm salinity and cycocel gave the highest fresh weight of shoots and roots. The developmental stages and egg-laying females of nematode decreased by the increasing of irradiation dose and salinity levels. Root-knot galls decreased with 40 and 60 Gy, while significant increase was observed with 0 and 80 Gy, salinity levels decreased root galls. Cycocel decreased nematode population, egg-lying females and root-knot galls.

Sensitivity of root-knot nematodes to gamma irradiation, salinity and plant growth regulator, cycocel

International Nuclear Information System (INIS)

Sweelam, M.E.

1995-01-01

The experiment was carried out at the experimental station of the faculty of agriculture, Menoufia Univ. To determine the sensitivity of root-knot nematode, Meloidogyne Javanica infecting tomato plants exposed to different doses of gamma irradiation 0,20,40,60,80 Gy, salinity levels 0. 1000, 2000, 4000 ppm and the plant growth regulator cycocel 0,200 ppm. Treated seeds were planted clay pots and salinity levels and cycocel concentrations were applied. Fresh weights and nematode populations were computed 3 months after application. Results indicated that 20 Gy, 1000 ppm salinity and cycocel gave the highest fresh weight of shoots and roots. The developmental stages and egg-laying females of nematode decreased by the increasing of irradiation dose and salinity levels. Root-knot galls decreased with 40 and 60 Gy, while significant increase was observed with 0 and 80 Gy, salinity levels decreased root galls. Cycocel decreased nematode population, egg-lying females and root-knot galls

Adolescent idiopathic scoliosis (AIS, environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy

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Burwell R Geoffrey

2011-12-01

Full Text Available Abstract Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS. Discordant findings for monozygotic (MZ twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may

Normalization of similarity-based individual brain networks from gray matter MRI and its association with neurodevelopment in infants with intrauterine growth restriction.

Science.gov (United States)

Batalle, Dafnis; Muñoz-Moreno, Emma; Figueras, Francesc; Bargallo, Nuria; Eixarch, Elisenda; Gratacos, Eduard

2013-12-01

Obtaining individual biomarkers for the prediction of altered neurological outcome is a challenge of modern medicine and neuroscience. Connectomics based on magnetic resonance imaging (MRI) stands as a good candidate to exhaustively extract information from MRI by integrating the information obtained in a few network features that can be used as individual biomarkers of neurological outcome. However, this approach typically requires the use of diffusion and/or functional MRI to extract individual brain networks, which require high acquisition times and present an extreme sensitivity to motion artifacts, critical problems when scanning fetuses and infants. Extraction of individual networks based on morphological similarity from gray matter is a new approach that benefits from the power of graph theory analysis to describe gray matter morphology as a large-scale morphological network from a typical clinical anatomic acquisition such as T1-weighted MRI. In the present paper we propose a methodology to normalize these large-scale morphological networks to a brain network with standardized size based on a parcellation scheme. The proposed methodology was applied to reconstruct individual brain networks of 63 one-year-old infants, 41 infants with intrauterine growth restriction (IUGR) and 22 controls, showing altered network features in the IUGR group, and their association with neurodevelopmental outcome at two years of age by means of ordinal regression analysis of the network features obtained with Bayley Scale for Infant and Toddler Development, third edition. Although it must be more widely assessed, this methodology stands as a good candidate for the development of biomarkers for altered neurodevelopment in the pediatric population. © 2013 Elsevier Inc. All rights reserved.

MRI of normal and pathological fetal lung development

International Nuclear Information System (INIS)

Kasprian, Gregor; Balassy, Csilla; Brugger, Peter C.; Prayer, Daniela

2006-01-01

Normal fetal lung development is a complex process influenced by mechanical and many biochemical factors. In addition to ultrasound, fetal magnetic resonance imaging (MRI) constitutes a new method to investigate this process in vivo during the second and third trimester. The techniques of MRI volumetry, assessment of signal intensities, and MRI spectroscopy of the fetal lung have been used to analyze this process and have already been applied clinically to identify abnormal fetal lung growth. Particularly in conditions such as oligohydramnios and congenital diaphragmatic hernia (CDH), pulmonary hypoplasia may be the cause of neonatal death. A precise diagnosis and quantification of compromised fetal lung development may improve post- and perinatal management. The main events in fetal lung development are reviewed and MR volumetric data from 106 normal fetuses, as well as different examples of pathological lung growth, are provided

MRI of normal and pathological fetal lung development

Energy Technology Data Exchange (ETDEWEB)

Kasprian, Gregor [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: gregor.kasprian@meduniwien.ac.at; Balassy, Csilla [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Prayer, Daniela [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)

2006-02-15

Normal fetal lung development is a complex process influenced by mechanical and many biochemical factors. In addition to ultrasound, fetal magnetic resonance imaging (MRI) constitutes a new method to investigate this process in vivo during the second and third trimester. The techniques of MRI volumetry, assessment of signal intensities, and MRI spectroscopy of the fetal lung have been used to analyze this process and have already been applied clinically to identify abnormal fetal lung growth. Particularly in conditions such as oligohydramnios and congenital diaphragmatic hernia (CDH), pulmonary hypoplasia may be the cause of neonatal death. A precise diagnosis and quantification of compromised fetal lung development may improve post- and perinatal management. The main events in fetal lung development are reviewed and MR volumetric data from 106 normal fetuses, as well as different examples of pathological lung growth, are provided.

Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer

DEFF Research Database (Denmark)

Maae, Else; Olsen, Dorte Aalund; Steffensen, Karina Dahl

2012-01-01

Placenta growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) are angiogenic growth factors interacting competitively with the same receptors. VEGF-A is essential in both normal and pathologic conditions, but the functions of PlGF seem to be restricted to pathologic conditions s...

Pattern visual evoked potentials in dyslexic versus normal children

Directory of Open Access Journals (Sweden)

Javad Heravian

2015-01-01

Conclusion: The sensitivity of PVEP has high validity to detect visual deficits in children with dyslexic problem. However, no significant difference was found between dyslexia and normal children using high contrast stimuli.

Growth curves for Laron syndrome.

Science.gov (United States)

Laron, Z; Lilos, P; Klinger, B

1993-01-01

Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls completed their growth between the age of 16-19 years to a final mean (SD) height of 119 (8.5) cm whereas the boys continued growing beyond the age of 20 years, achieving a final height of 124 (8.5) cm. At all ages the upper to lower body segment ratio was more than 2 SD above the normal mean. These growth curves constitute a model not only for primary, hereditary insulin-like growth factor-I (IGF-I) deficiency (Laron syndrome) but also for untreated secondary IGF-I deficiencies such as growth hormone gene deletion and idiopathic congenital isolated growth hormone deficiency. They should also be useful in the follow up of children with Laron syndrome treated with biosynthetic recombinant IGF-I. PMID:8333769

Climate Change Sensitivity of Multi-Species Afforestation in Semi-Arid Benin

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Florent Noulèkoun

2018-06-01

Full Text Available The early growth stage is critical in the response of trees to climate change and variability. It is not clear, however, what climate metrics are best to define the early-growth sensitivity in assessing adaptation strategies of young forests to climate change. Using a combination of field experiments and modelling, we assessed the climate sensitivity of two promising afforestation species, Jatropha curcas L. and Moringa oleifera Lam., by analyzing their predicted climate–growth relationships in the initial two years after planting on degraded cropland in the semi-arid zone of Benin. The process-based WaNuLCAS model (version 4.3, World Agroforestry Centre, Bogor, Indonesia was used to simulate aboveground biomass growth for each year in the climate record (1981–2016, either as the first or as the second year of tree growth. Linear mixed models related the annual biomass growth to climate indicators, and climate sensitivity indices quantified climate–growth relationships. In the first year, the length of dry spells had the strongest effect on tree growth. In the following year, the annual water deficit and length of dry season became the strongest predictors. Simulated rooting depths greater than those observed in the experiments enhanced biomass growth under extreme dry conditions and reduced sapling sensitivity to drought. Projected increases in aridity implied significant growth reduction, but a multi-species approach to afforestation using species that are able to develop deep-penetrating roots should increase the resilience of young forests to climate change. The results illustrate that process-based modelling, combined with field experiments, can be effective in assessing the climate–growth relationships of tree species.

Involvement of ENaC in the development of salt-sensitive hypertension.

Science.gov (United States)

Pavlov, Tengis S; Staruschenko, Alexander

2017-08-01

Salt-sensitive hypertension is associated with renal and vascular dysfunctions, which lead to impaired fluid excretion, increased cardiac output, and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron that plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions. In this mini-review, we summarize recent studies investigating the role of ENaC in the development of salt-sensitive hypertension. On the basis of experimental data obtained from the Dahl salt-sensitive rats, we and others have demonstrated that abnormal ENaC activation in response to a dietary NaCl load contributes to the development of high blood pressure in this model. The role of different humoral factors, such as the components of the renin-angiotensin-aldosterone system, members of the epidermal growth factors family, arginine vasopressin, and oxidative stress mediating the effects of dietary salt on ENaC are discussed in this review to highlight future research directions and to determine potential molecular targets for drug development. Copyright © 2017 the American Physiological Society.

From shunting inhibition to dynamic normalization: Attentional selection and decision-making in brief visual displays.

Science.gov (United States)

Smith, Philip L; Sewell, David K; Lilburn, Simon D

2015-11-01

Normalization models of visual sensitivity assume that the response of a visual mechanism is scaled divisively by the sum of the activity in the excitatory and inhibitory mechanisms in its neighborhood. Normalization models of attention assume that the weighting of excitatory and inhibitory mechanisms is modulated by attention. Such models have provided explanations of the effects of attention in both behavioral and single-cell recording studies. We show how normalization models can be obtained as the asymptotic solutions of shunting differential equations, in which stimulus inputs and the activity in the mechanism control growth rates multiplicatively rather than additively. The value of the shunting equation approach is that it characterizes the entire time course of the response, not just its asymptotic strength. We describe two models of attention based on shunting dynamics, the integrated system model of Smith and Ratcliff (2009) and the competitive interaction theory of Smith and Sewell (2013). These models assume that attention, stimulus salience, and the observer's strategy for the task jointly determine the selection of stimuli into visual short-term memory (VSTM) and the way in which stimulus representations are weighted. The quality of the VSTM representation determines the speed and accuracy of the decision. The models provide a unified account of a variety of attentional phenomena found in psychophysical tasks using single-element and multi-element displays. Our results show the generality and utility of the normalization approach to modeling attention. Copyright © 2014 Elsevier B.V. All rights reserved.

Three-dimensional analysis of mandibular growth and tooth eruption

DEFF Research Database (Denmark)

Krarup, S.; Darvann, Tron Andre; Larsen, Per

2005-01-01

Normal and abnormal jaw growth and tooth eruption are topics of great importance for several dental and medical disciplines. Thus far, clinical studies on these topics have used two-dimensional (2D) radiographic techniques. The purpose of the present study was to analyse normal mandibular growth...

A ΔdinB mutation that sensitizes Escherichia coli to the lethal effects of UV- and X-radiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Mei-Chong W.; Franco, Magdalena; Vargas, Doris M. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Hudman, Deborah A. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States); White, Steven J. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Fowler, Robert G., E-mail: rfowler@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Sargentini, Neil J. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States)

2014-05-15

Highlights: • We describe Δ(dinB-yafN)883(::kan), a novel dinB allele, referred to as ΔdinB883, a deletion that sensitizes E. coli cells to UV irradiation. • This UV radiation sensitivity is most acute in the early logarithmic phase of culture growth. • This UV radiation sensitivity is completely dependent upon a functional umuDC operon. • Sequencing reveals ΔdinB883 retains the proximal 161 nucleotides, i.e., 54 amino acids, of the wild-type sequence. • The ΔdinB883 mutant is hypothesized to produce a peptide of 83 amino acids, DinB883, that compromises UmuDC function. - Abstract: The DinB (PolIV) protein of Escherichia coli participates in several cellular functions. We investigated a dinB mutation, Δ(dinB-yafN)883(::kan) [referred to as ΔdinB883], which strongly sensitized E. coli cells to both UV- and X-radiation killing. Earlier reports indicated dinB mutations had no obvious effect on UV radiation sensitivity which we confirmed by showing that normal UV radiation sensitivity is conferred by the ΔdinB749 allele. Compared to a wild-type strain, the ΔdinB883 mutant was most sensitive (160-fold) in early to mid-logarithmic growth phase and much less sensitive (twofold) in late log or stationary phases, thus showing a growth phase-dependence for UV radiation sensitivity. This sensitizing effect of ΔdinB883 is assumed to be completely dependent upon the presence of UmuDC protein; since the ΔdinB883 mutation did not sensitize the ΔumuDC strain to UV radiation killing throughout log phase and early stationary phase growth. The DNA damage checkpoint activity of UmuDC was clearly affected by ΔdinB883 as shown by testing a umuC104 ΔdinB883 double-mutant. The sensitivities of the ΔumuDC strain and the ΔdinB883 ΔumuDC double-mutant strain were significantly greater than for the ΔdinB883 strain, suggesting that the ΔdinB883 allele only partially suppresses UmuDC activity. The ΔdinB883 mutation partially sensitized (fivefold) uvrA and uvr

Serum levels of growth hormone binding protein in children with normal and precocious puberty

DEFF Research Database (Denmark)

Juul, A; Fisker, Sidse; Scheike, Thomas Harder

2000-01-01

To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty.......To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty....

Abscisic Acid Content and Stomatal Sensitivity to CO(2) in Leaves of Xanthium strumarium L. after Pretreatments in Warm and Cold Growth Chambers.

Science.gov (United States)

Raschke, K; Pierce, M; Popiela, C C

1976-01-01

The degree of stomatal sensitivity to CO(2) was positively correlated with the content of abscisic acid of leaves of Xanthium strumarium grown in a greenhouse and then transferred for 24 hours or more to a cold (5/10 C, night/day) or a warm growth chamber (20/23 C). This correlation did not exist in plants kept in the greehouse continuously (high abscisic acid, no CO(2) sensitivity), nor in plants transferred from the cold to the warm chamber (low abscisic acid, high CO(2) sensitivity). The abscisic acid content of leaves was correlated with water content only within narrow limits, if at all. At equal water contents, prechilled leaves contained more abscisic acid than leaves of plants pretreated in the warm chamber. There appear to be at least two compartments for abscisic acid in the leaf.

High-sensitivity chemiluminescence immunoassays for detection of growth hormone doping in sports.

Science.gov (United States)

Bidlingmaier, Martin; Suhr, Jennifer; Ernst, Andrea; Wu, Zida; Keller, Alexandra; Strasburger, Christian J; Bergmann, Andreas

2009-03-01

Recombinant human growth hormone (rhGH) is abused in sports, but adequate routine doping tests are lacking. Analysis of serum hGH isoform composition has been shown to be effective in detecting rhGH doping. We developed and validated selective immunoassays for isoform analysis with potential utility for screening and confirmation in doping tests. Monoclonal antibodies with preference for pituitary hGH (phGH) or rhGH were used to establish 2 pairs of sandwich-type chemiluminescence assays with differential recognition of rhGH (recA and recB) and phGH (pitA and pitB). We analyzed specimens from volunteers before and after administration of rhGH and calculated ratios between the respective rec- and pit-assay results. Functional sensitivities were <0.05 microg/L, with intra- and interassay imprecision < or =8.4% and < or =13.7%, respectively. In 2 independent cohorts of healthy subjects, rec/pit ratios (median range) were 0.84 (0.09-1.32)/0.81 (0.27-1.21) (recA/pitA) and 0.68 (0.08-1.20)/0.80 (0.25-1.36) (recB/pitB), with no sex difference. In 20 recreational athletes, ratios (median SD) increased after a single injection of rhGH, reaching 350% (73%) (recA/pitA) and 400% (93%) (recB/pitB) of baseline ratios. At a moderate dose (0.033 mg/kg), mean recA/pitA and recB/pitB ratios remained significantly increased for 18 h (men) and 26 h (women). After high-dose rhGH (0.083 mg/kg), mean rec/pit ratios remained increased for 32 h (recA/pitA) and 34 h (recB/pitB) in men and were still increased after 36 h in women. Using sensitive chemiluminescence assays with preferential recognition of phGH or rhGH, detection of a single injection of rhGH was possible for up to 36 h.

Ex vivo characterization of normal and adenocarcinoma colon samples by Mueller matrix polarimetry.

Science.gov (United States)

Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ashraf, Sumara; Ahmad, Shakil; Ikram, Masroor

2015-05-01

Mueller matrix polarimetry along with polar decomposition algorithm was employed for the characterization of ex vivo normal and adenocarcinoma human colon tissues by polarized light in the visible spectral range (425-725 nm). Six derived polarization metrics [total diattenuation (DT ), retardance (RT ), depolarization(ΔT ), linear diattenuation (DL), retardance (δ), and depolarization (ΔL)] were compared for normal and adenocarcinoma colon tissue samples. The results show that all six polarimetric properties for adenocarcinoma samples were significantly higher as compared to the normal samples for all wavelengths. The Wilcoxon rank sum test illustrated that total retardance is a good candidate for the discrimination of normal and adenocarcinoma colon samples. Support vector machine classification for normal and adenocarcinoma based on the four polarization properties spectra (ΔT , ΔL, RT ,and δ) yielded 100% accuracy, sensitivity, and specificity, while both DTa nd DL showed 66.6%, 33.3%, and 83.3% accuracy, sensitivity, and specificity, respectively. The combination of polarization analysis and given classification methods provides a framework to distinguish the normal and cancerous tissues.

Biological Traits of Botrytis cinerea Pers. Isolates Differently Sensitive to Dicarboximides

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Brankica Tanović

2007-01-01

Full Text Available A study of biological characteristics of both field and laboratory isolates revealed that highly resistant isolates were morphologically different from their original wild types. The majority of them were less pathogenic and produced less sclerotia than the original ones.Significant negative correlation between osmotic sensitivity and the degree of resistance was recorded. The correlation between micelium growth rate and resistance to dicarboximides was also significant and negative. Growth medium, acidity and growth temperature had less effect on the micelium growth rate of the highly resistant isolates than on the sensitive ones.

Comparison of low-normal and high-normal IGF-1 target levels during growth hormone replacement therapy : A randomized clinical trial in adult growth hormone deficiency

NARCIS (Netherlands)

van Bunderen, Christa C; Lips, Paul; Kramer, Mark H H; Drent, Madeleine L

BACKGROUND: Current guidelines state that the goals of growth hormone (GH) therapy in adults should be an appropriate clinical response, avoidance of side effects, and an IGF-1 value within the age-adjusted reference range. There are no published studies on the target level for IGF-1 that offer

Constitutional growth delay pattern of growth in velo-cardio-facial syndrome: longitudinal follow up and final height of two cases.

Science.gov (United States)

Turan, Serap; Ozdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

2008-01-01

We report two patients with velo-cardio-facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS -3.4 SDS), but showed spontaneous catch-up and ended up with a final height of -2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty.

Managing a sensitive project

International Nuclear Information System (INIS)

Etcheber, Pascal

1998-01-01

A 'sensitive' project needs to be managed differently from a 'normal' project. This statement might seem simple enough. However, it does not seem to be a simple task to prove it in twenty minutes. This paper is an attempt to share with the audience some of the experiences the company had dealing with sensitive projects. It describes what a sensitive project is, though of all people, the 'nuclear' should know. Then the common mistakes are described, that are made in the hoping that some personal experiences are recognised. Finally the company's strategy is shown, how we foster third party support and the main tools to be used. Ultimately, success is ensured by having a sufficient quantity of allies. A sensitive project does not die because it has too many opponents, but because it has too few allies. Finding and helping allies to act is the thrust of our activity. It enables sensitive projects which deserve to succeed to do so, where traditional management fails miserably

Nuclear Symbiosis - A Means to Achieve Sustainable Nuclear Growth while Limiting the Spread of Sensitive Nuclear Technology

International Nuclear Information System (INIS)

Shropshire, David

2009-01-01

Global growth of nuclear energy in the 21st century is creating new challenges to limit the spread of nuclear technology without hindering adoption in countries now considering nuclear power. Independent nuclear states desire autonomy over energy choices and seek energy independence. However, this independence comes with high costs for development of new indigenous fuel cycle capabilities. Nuclear supplier states and expert groups have proposed fuel supply assurance mechanisms such as fuel take-back services, international enrichment services and fuel banks in exchange for recipient state concessions on the development of sensitive technologies. Nuclear states are slow to accept any concessions to their rights under the Non-Proliferation Treaty. To date, decisions not to develop indigenous fuel cycle capabilities have been driven primarily by economics. However, additional incentives may be required to offset a nuclear state's perceived loss of energy independence. This paper proposes alternative economic development incentives that could help countries decide to forgo development of sensitive nuclear technologies. The incentives are created through a nuclear-centered industrial complex with 'symbiotic' links to indigenous economic opportunities. This paper also describes a practical tool called the 'Nuclear Materials Exchange' for identifying these opportunities.

Effects of hyperthermia and ionizing radiation in normal and ataxia telangiectasia human fibroblast lines

International Nuclear Information System (INIS)

Mitchel, R.E.J.; Chan, A.; Smith, B.P.; Child, S.D.; Paterson, M.C.

1984-01-01

The effects of 45 0 C hyperthermia and γ radiation have been studied in three normal human fibroblast lines (GM38, GM730, WI38) and compared to the effects in two lines derived from patients with the hereditary disease ataxia telangiectasia (AR3BI, AT5BI). All lines, both normal and γ-sensitive AT, showed a similar resistance to killing by heat alone, suggesting that the defect responsible for the increased radiation sensitivity in AT lines does not confer increased heat sensitivity. Shouldered survival curves were obtained in each case indicating the ability to accumulate sublethal heat damage. All normal and AT cell lines exhibited increased resistance to the lethal effects of heat in response to a thermal stress, indicating that the defect that causes radiosensitivity in AT cell lines does not prevent the induction of thermotolerance. It was hypothesized that in normal cells, this heat treatment inactivates the process which is already defective in AT lines, and that this process may be required for the proper rejoining of double-strand breaks produced during the repair of other radiation-induced lesions

Growth of cells superinoculated onto irradiated and nonirradiated confluent monolayers

International Nuclear Information System (INIS)

Matsuoka, H.; Ueo, H.; Sugimachi, K.

1990-01-01

We prepared confluent monolayers of normal BALB/c 3T3 cells and compared differences in the growth of four types of cells superinoculated onto these nonirradiated and irradiated monolayers. The test cells were normal BALB/c 3T3 A31 cells, a squamous cell carcinoma from a human esophageal cancer (KSE-1), human fetal fibroblasts, and V-79 cells from Chinese hamster lung fibroblasts. Cell growth was checked by counting the cell number, determining [3H]thymidine incorporation and assessing colony formation. We found that on nonirradiated monolayers, colony formation of human fetal fibroblasts and normal BALB/c 3T3 cells was completely inhibited. On irradiated cells, test cells did exhibit some growth. KSE-1 cells, which had a low clonogenic efficiency on plastic surfaces, formed colonies on both irradiated and nonirradiated cells. On these monolayers, the clonogenic efficiency of V-79 cells was also higher than that on plastic surfaces. We conclude that the nonirradiated monolayer of BALB/c 3T3 cells completely inhibits the growth of superinoculated normal BALB/c 3T3 and human fetal fibroblasts, while on the other hand, they facilitate the growth of neoplastic KSE-1 and V-79 cells by providing a surface for cell adherence and growth, without affecting the presence of normal cells in co-cultures

Adenylate kinase I does not affect cellular growth characteristics under normal and metabolic stress conditions.

Science.gov (United States)

de Bruin, Wieke; Oerlemans, Frank; Wieringa, Bé

2004-07-01

Adenylate kinase (AK)-catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy in cells of fully differentiated tissues with highly variable energy demand, such as muscle and brain. To investigate if AK isoenzymes have a comparable function in the energy-demand management of proliferating cells, AK1 and AK1beta were expressed in mouse neuroblastoma N2a cells and in human colon carcinoma SW480 cells. Glucose deprivation, galactose feeding, and metabolic inhibitor tests revealed a differential energy dependency for these two cell lines. N2a cells showed a faster proliferation rate and strongest coupling to mitochondrial activity, SW480 proliferation was more dependent on glycolysis. Despite these differences, ectopic expression of AK1 or AK1beta did not affect their growth characteristics under normal conditions. Also, no differential effects were seen under metabolic stress upon treatment with mitochondrial and glycolytic inhibitors in in vitro culture or in solid tumors grown in vivo. Although many intimate connections have been revealed between cell death and metabolism, our results suggest that AK1- or AK1beta-mediated high-energy phosphoryl transfer is not a modulating factor in the survival of tumor cells during episodes of metabolic crisis.

Changes in contrast sensitivity after surgery for macula-on rhegmatogenous retinal detachment.

Science.gov (United States)

Okamoto, Fumiki; Sugiura, Yoshimi; Okamoto, Yoshifumi; Hiraoka, Takahiro; Oshika, Tetsuro

2013-10-01

To evaluate changes in contrast sensitivity after surgery for macula-on rhegmatogenous retinal detachment (RRD). Prospective, interventional, consecutive, case-control study. This study included 84 eyes of 84 patients with unilateral macula-on RRD undergoing primary scleral buckling or vitrectomy without postoperative macular complication. We examined the logarithm of the minimal angle of resolution best-corrected visual acuity (logMAR BCVA) and contrast sensitivity at 4 spatial frequencies (3, 6, 12, and 18 cycles/degree) using the CSV-1000E (Vector Vision) before and after surgery. From the data obtained with the CSV-1000E, the area under the log contrast sensitivity function was calculated. The logMAR BCVA and contrast sensitivity in the contralateral normal eyes also were measured and were used as normal controls. Clinical data were collected, including age, gender, surgical procedures, the number of retinal tears, circumferential dimension of retinal tears, and area of retinal detachment, to determine the clinical factors related to visual function. Preoperative contrast sensitivity was significantly worse in eyes with RRD than in normal controls, but the preoperative logMAR BCVA was not different from that of normal controls. Contrast sensitivity decreased significantly after surgery, but logMAR BCVA did not change by surgery. Multiple regression analysis revealed that postoperative contrast sensitivity had a significant correlation with the circumferential dimension of retinal tears, whereas no clinical parameters were associated significantly with postoperative BCVA. Surgery for macula-on RRD did not change visual acuity, whereas contrast sensitivity was affected significantly in association with the extent of retinal tears. Copyright © 2013 Elsevier Inc. All rights reserved.

Normal bacterial flora from vaginas of Criollo Limonero cows.

Science.gov (United States)

Zambrano-Nava, Sunny; Boscán-Ocando, Julio; Nava, Jexenia

2011-02-01

In order to describe the normal bacterial flora in vaginas of Criollo Limonero cows, 51 healthy multiparous cows, at least 90-day postpartum, were selected. Duplicated swabs (N = 102) were taken from the vaginal fornix of cows to perform aerobic and anaerobic cultures as well as conventional biochemical tests. Out of 102 swabs, bacterial growth was obtained in 55 (53.9%) while the remaining 47 (46.1%) did not exhibited any bacterial growth. Of the 55 bacterial growths, 23 (41.8%) were aerobic whereas 32 (58.1%) were anaerobic. Likewise, 29 (52.72%) of bacterial growths were pure and 26 (47.27%) were mixed. Under both aerobic and anaerobic conditions, Gram positive bacteria were predominant (81.82% and 73.08%, respectively) over Gram negative bacteria (18.18% and 26.92%, respectively). Isolated bacteria were Arcanobacterium pyogenes (22.92%), Staphylococcus aureus (15.63%), Staphylococcus coagulase negative (17.71%), Erysipelothrix rhusiopathiae (6.25%), Bacteroides spp. (13.54%), and Peptostreptococcus spp. (7.29%). In conclusion, normal vaginal bacterial flora of Criollo Limonero cows was predominantly Gram positive and included A. pyogenes, S. aureus, coagulase negative Staphylococcus, E. rhusiopathiae, Bacteroides spp., and Peptostreptococcus spp. In Criollo Limonero cattle, adaptive aspects such as development of humoral and physical mechanisms for defense, and bacterial adaptation to host deserve research attention.

Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

Directory of Open Access Journals (Sweden)

Kristyn Dunlop

2015-02-01

Full Text Available The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.

Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity.

Science.gov (United States)

Dunlop, Kristyn; Cedrone, Megan; Staples, James F; Regnault, Timothy R H

2015-02-12

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.

Normalization of Gravitational Acceleration Models

Science.gov (United States)

Eckman, Randy A.; Brown, Aaron J.; Adamo, Daniel R.

2011-01-01

Unlike the uniform density spherical shell approximations of Newton, the con- sequence of spaceflight in the real universe is that gravitational fields are sensitive to the nonsphericity of their generating central bodies. The gravitational potential of a nonspherical central body is typically resolved using spherical harmonic approximations. However, attempting to directly calculate the spherical harmonic approximations results in at least two singularities which must be removed in order to generalize the method and solve for any possible orbit, including polar orbits. Three unique algorithms have been developed to eliminate these singularities by Samuel Pines [1], Bill Lear [2], and Robert Gottlieb [3]. This paper documents the methodical normalization of two1 of the three known formulations for singularity-free gravitational acceleration (namely, the Lear [2] and Gottlieb [3] algorithms) and formulates a general method for defining normalization parameters used to generate normalized Legendre Polynomials and ALFs for any algorithm. A treatment of the conventional formulation of the gravitational potential and acceleration is also provided, in addition to a brief overview of the philosophical differences between the three known singularity-free algorithms.

Establishing the proteome of normal human cerebrospinal fluid.

Directory of Open Access Journals (Sweden)

Steven E Schutzer

2010-06-01

Full Text Available Knowledge of the entire protein content, the proteome, of normal human cerebrospinal fluid (CSF would enable insights into neurologic and psychiatric disorders. Until now technologic hurdles and access to true normal samples hindered attaining this goal.We applied immunoaffinity separation and high sensitivity and resolution liquid chromatography-mass spectrometry to examine CSF from healthy normal individuals. 2630 proteins in CSF from normal subjects were identified, of which 56% were CSF-specific, not found in the much larger set of 3654 proteins we have identified in plasma. We also examined CSF from groups of subjects previously examined by others as surrogates for normals where neurologic symptoms warranted a lumbar puncture but where clinical laboratory were reported as normal. We found statistically significant differences between their CSF proteins and our non-neurological normals. We also examined CSF from 10 volunteer subjects who had lumbar punctures at least 4 weeks apart and found that there was little variability in CSF proteins in an individual as compared to subject to subject.Our results represent the most comprehensive characterization of true normal CSF to date. This normal CSF proteome establishes a comparative standard and basis for investigations into a variety of diseases with neurological and psychiatric features.

DNA amplification is rare in normal human cells

International Nuclear Information System (INIS)

Wright, J.A.; Watt, F.M.; Hudson, D.L.; Stark, G.R.; Smith, H.S.; Hancock, M.C.

1990-01-01

Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10 8 cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of onogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency

Economics of Future Growth in Photovoltaics Manufacturing

Energy Technology Data Exchange (ETDEWEB)

Basore, Paul A.; Chung, Donald; Buonassisi, Tonio

2015-06-14

The past decade's record of growth in the photovoltaics manufacturing industry indicates that global investment in manufacturing capacity for photovoltaic modules tends to increase in proportion to the size of the industry. The slope of this proportionality determines how fast the industry will grow in the future. Two key parameters determine this slope. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units $/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service life of the assets (capacity-normalized capital demand rate, CapDR, units $/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a small improvement in CapIR to ensure future growth in photovoltaics. Any accompanying improvement in CapDR will accelerate that growth.

Effect of hormone treatment on spontaneous and radiation-induced chromosomal breakage in normal and dwarf mice

International Nuclear Information System (INIS)

Buul, P.P.W. van; Buul-Offers, S. van

1982-01-01

Treatment of dwarf mice with growth hormone, insulin and testosterone had no effect on the spontaneous frequencies of micronuclei (MN) in bone-marrow cells, whereas thyroxine decreased these frequencies. The induction of MN by X-rays and mitomycin C was significantly lower in dwarf mice than in normal mice. Treatment with thyroxine plus growth hormone restored normal radiosensitivity in dwarfs. (orig.)

FK506 Binding Protein Mediates Glioma Cell Growth and Sensitivity to Rapamycin Treatment by Regulating NF-κB Signaling Pathway

Directory of Open Access Journals (Sweden)

Wei Jiang

2008-03-01

Full Text Available FK506 binding protein 5 (FKBP5 belongs to a family of immunophilins named for their ability to bind immunosuppressive drugs, also known as peptidyl-prolyl cis-trans isomerases, and also with chaperones to help protein folding. Using glioma cDNA microarray analysis, we found that FKBP5 was overexpressed in glioma tumors. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. The roles of FKBP5 in glioma cells were then examined. We found that cell growth was suppressed after FKBP5 expression was inhibited by short interfering RNA transfection and enhanced by FKBP5 overexpression. Electrophoretic mobility shift assay showed that nuclear factor-kappa B (NF-κB and DNA binding was enhanced by FKBP5 overexpression. The expression level of I-kappa B alpha and phosphorylated NF-κB was regulated by the expression of FKBP5. These data suggest that FKBP5 is involved in NF-κB pathway activation in glioma cells. In addition, FKBP5 overexpression in rapamycin-sensitive U87 cells blocked the cells' response to rapamycin treatment, whereas rapamycin-resistant glioma cells, both PTEN-positive and -negative, were synergistically sensitive to rapamycin after FKBP5 was knocked down, suggesting that the FKBP5 regulates glioma cell response to rapamycin treatment. In conclusion, our study demonstrates that FKBP5 plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-κB pathway.

Glycoside Hydrolase MoGls2 Controls Asexual/Sexual Development, Cell Wall Integrity and Infectious Growth in the Rice Blast Fungus.

Directory of Open Access Journals (Sweden)

Mengying Li

Full Text Available N-linked glycosylation is a way of glycosylation for newly synthesized protein, which plays a key role in the maturation and transport of proteins. Glycoside hydrolases (GHs are essential in this process, and are involved in processing of N-linked glycoproteins or degradation of carbohydrate structures. Here, we identified and characterized MoGls2 in Magnaporthe oryzae, which is a yeast glucosidase II homolog Gls2 and is required for trimming the final glucose in N-linked glycans and normal cell wall synthesis. Target deletion of MoGLS2 in M. oryzae resulted in a reduced mycelial growth, an increased conidial production, delayed conidial germination and loss the ability of sexual reproduction. Pathogenicity assays revealed that the ΔMogls2 mutant showed significantly decreased in virulence and infectious growth. Further studies showed that the mutant was less sensitive to salt and osmotic stress, and increased sensitivity to cell wall stresses. Additionally, the ΔMogls2 mutant showed a defect in cell wall integrity. Our results indicate that MoGls2 is a key protein for the growth and development of M. oryzae, involving in the regulation of asexual/sexual development, stress response, cell wall integrity and infectious growth.

Constitutional Growth Delay Pattern of Growth in Velo−Cardio−Facial Syndrome: Longitudinal follow up and final height of two cases

Science.gov (United States)

Özdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

2008-01-01

We report two patients with velo−cardio−facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS −3.4 SDS), but showed spontaneous catch−up and ended up with a final height of −2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty. Conflict of interest:None declared. PMID:21318064

Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

International Nuclear Information System (INIS)

Garcia, J.F.; Ebbe, S.N.; Hollander, L.; Cutting, H.O.; Miller, M.E.; Cronkite, E.P.

1982-01-01

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 μl of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use

Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.

Science.gov (United States)

Joó, József Gábor; Rigó, János; Börzsönyi, Balázs; Demendi, Csaba; Kornya, László

2017-06-01

We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2 α : 0.92; p intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.

Thyroxine modifies the effects of growth hormone in Ames dwarf mice.

Science.gov (United States)

Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M

2015-04-01

Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early-life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity.

Micromycetes sensitiveness to heavy metals

OpenAIRE

O. N. Korinovskaya; V. N. Gryshko

2011-01-01

The sensitivity of 33 micromycete species to nitric compounds of copper, lead, zinc, nickel and cadmium has been determined. Absidia butleri Lendn, Mortierella vanesae Dixon-Stewart, Cunninghamella echinulata Thaxte, Curvularia tuberculata Jain, Cladosporium cladosporiodes (Fresen) G. A. de Vries and Fusarium solani (C. Mart.) Appel et Wollenw are sensitive to minimal content of the heavy metals (0.75 of maximum permissible concentration (MPC)) in the growth medium. At the same time Trixoderm...

Volumetric analysis of the normal infant brain and in intrauterine growth retardation

DEFF Research Database (Denmark)

Toft, P B; Leth, H; Ring, P B

1995-01-01

and the volumes were determined by encircling each structure of interest on every slice. Segmentation into grey matter, white matter and CSF was done by semi-automatic discriminant analysis. Growth charts for the cerebrum, cerebellum, corpora striata, thalami, ventricles, and grey and white matter are provided...... for infants with appropriate birth weight. The striatal (P = 0.02) and thalamic (P matter to white matter (G/W-ratio) increased (P = 0.01). In the neonatal patients, brain volumes were independently associated...... growth retardation reduces grey matter volume more than white matter....

In vivo potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by the radiation sensitizer benznidazole

International Nuclear Information System (INIS)

Siemann, D.W.; Morrissey, S.; Wolf, K.

1983-01-01

Recent studies in mouse tumor systems have indicated a potential therapeutic advantage in combining the radiosensitizer misonidazole (MISO) with cancer chemotherapy drugs. One agent the antitumor activity of which has been enhanced to a greater extent than its hematological or gastrointestinal toxicities is the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Recently, sensitizers more lipophylic than MISO have been reported to give greater tumor response enhancement when combined with CCNU. The present studies compared the potential therapeutic benefit of combining MISO (partition coefficient, 0.43) or benznidazole (BENZO) (partition coefficient, 8.5) in KHT sarcoma or RIF-1 tumor-bearing C3H mice. Both sensitizers were administered i.p. and given either 30 min before (BENZO) or simultaneously with (MISO) the chemotherapeutic agent. Survival of clonogenic tumor cells assessed 22 to 24 hr after treatment or in situ tumor growth delay were used as assays of tumor response. Normal tissue toxicity was determined using the drug dose yielding 50% animal lethality in 30 days end point. When combined with CCNU, doses of MISO (5.0 mmol/kg) or BENZO (0.3 mmol/kg) were found to yield approximately equivalent increases in both the tumor effect (enhancement ratio, approximately 1.8 to 2.0) and normal tissue toxicity (enhancement ratio approximately 1.3 to 1.4). Both sensitizers therefore led to a therapeutic benefit. However, although a approximately 10-fold lower dose of the more lipophylic sensitizer BENZO proved to be as effective as MISO at enhancing the tumoricidal effects of CCNU, this dose reduction did not result in a greater therapeutic gain for BENZO

Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis.

Science.gov (United States)

Joseph, Franklin; Ahmad, Aftab M; Ul-Haq, Mazhar; Durham, Brian H; Whittingham, Pauline; Fraser, William D; Vora, Jiten P

2008-05-01

Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH-deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor-1 (IGF-1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half-hourly blood and 3-h urine samples were collected. PTH, calcium (Ca), phosphate (PO(4)), nephrogenous cyclic AMP (NcAMP), beta C-telopeptide of type 1 collagen (betaCTX), procollagen type I amino-terminal propeptide (PINP), and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t-test and general linear model ANOVAs for repeated measures were used where appropriate. IGF-1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 +/- 8.9 versus 140.9 +/- 10.8 mug/liter; p bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long-term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age

Abscisic Acid Content and Stomatal Sensitivity to CO2 in Leaves of Xanthium strumarium L. after Pretreatments in Warm and Cold Growth Chambers 1

Science.gov (United States)

Raschke, Klaus; Pierce, Margaret; Popiela, Chu Chen

1976-01-01

The degree of stomatal sensitivity to CO2 was positively correlated with the content of abscisic acid of leaves of Xanthium strumarium grown in a greenhouse and then transferred for 24 hours or more to a cold (5/10 C, night/day) or a warm growth chamber (20/23 C). This correlation did not exist in plants kept in the greehouse continuously (high abscisic acid, no CO2 sensitivity), nor in plants transferred from the cold to the warm chamber (low abscisic acid, high CO2 sensitivity). The abscisic acid content of leaves was correlated with water content only within narrow limits, if at all. At equal water contents, prechilled leaves contained more abscisic acid than leaves of plants pretreated in the warm chamber. There appear to be at least two compartments for abscisic acid in the leaf. PMID:16659416

Transforming growth factor-beta. En potent multifunktionel voekstfaktor for normale og maligne celler

DEFF Research Database (Denmark)

Nørgaard, P; Damstrup, L; Spang-Thomsen, M

1992-01-01

The polypeptide growth factor transforming growth factor-beta (TGF-beta) is a multifunctional regulator of basic cellular functions: proliferation, differentiation, cell adhesion and interactions with the extracellular matrix. TGF-beta is part of a regulatory network of which our knowledge is sti...... possibilities for therapeutic intervention in the physiological and patophysiological functions of TGF-beta. Udgivelsesdato: 1992-Nov-30...

Growth failure, somatomedin and growth hormone levels in juvenile diabetes mellitus--a pilot study.

Science.gov (United States)

Nash, H

1979-06-01

Growth hormone (hGH) responsiveness to exercise and somatomedin C (SmC) activity were measured in ten children with insulin-deficient diabetes mellitus. Four of the ten children showed a significant degree of growth retardation. Normal SmC activity was found in association with elevated hGH levels. The hypothesis that growth-retarded diabetics have a failure of Sm production despite high hGH levels (analogous to malnutrition and Laron dwarfism) was not substantiated by this study. Chronic deficiency of insulin, itself a somatomedin, may play a major role in diabetic growth failure.

Comparative investigation of indicators of growth and behavioral disorders in children with normal, low, and very low birth weight at pre-school age in Isfahan during 2015

Directory of Open Access Journals (Sweden)

Marzieh Yousefi

2017-01-01

Full Text Available Introduction: Birth weight is one of the most important indicators of infant's health and could predict their health condition in future. This study was conducted to determine and compare indicators of growth [weight, height, and body mass index (BMI] and behavioral disorders in children with normal, low, and very low birth weight at pre-school age. Materials and Methods: In this descriptive analytical study, 236 children (126 with normal weight, 100 with low birth weight, and 10 with very low birth weight at pre-school age were investigated in three groups. Data collection tools were a two-part questionnaire including the Rutter Children Behavior Questionnaire for parents, and parents' and children's demographic characteristics questionnaire, scale, and stadiometer. Data were analyzed using descriptive statistics, variance analysis, Chi square, and Kruskal–Wallis tests. Results: The mean of weight, height, and BMI at pre-school age in three groups had a significant difference (P = 0.009 and it was lower in the group with very low birth weight than the other two groups; however, the difference between the group with normal birth weight and the group with low birth weight was not significant (P = 0.10. The mean score of behavioral disorder had no significant difference between groups (P = 0.49. Conclusions: Results showed that children with very low birth weight grew less than the other two groups. Therefore, this group needs special attention and long-term follow-up for taking care of them to ensure better growth. It is recommended to conduct more extended studies to evaluate behavioral disorders in these children.

Expression of vascular endothelial growth factor in third-trimester placentas is not increased in growth-restricted fetuses.

Science.gov (United States)

Tse, J Y; Lao, T T; Chan, C C; Chiu, P M; Cheung, A N

2001-01-01

Vascular endothelial growth factor (VEGF) is considered the growth factor that stimulates vasculogenesis and angiogenesis. Recent studies have demonstrated its role in regulating placental growth and invasion. Its expression can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought to be associated with inadequate placental perfusion, which might result from a failure in the development of the villous vascular network. Our present study was undertaken to examine the relationship between VEGF expression and IUGR in pregnancies with preserved umbilical artery end-diastolic flow. VEGF Expression was determined by immunohistochemical analysis of placentas from 17 pregnancies with normal infant birth weight and 17 pregnancies complicated by IUGR. We found no significant differences in the expression of VEGF in villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua between IUGR and normal pregnancies. However, in both groups there was a strong correlation in the expression of VEGF with villous syncytiotrophoblasts and intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar scores at birth were significantly correlated with VEGF staining in both syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong correlation also was found between cord hematocrit and VEGF staining in villous syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts was not correlated with cord hemoglobin or hematocrit. Our results suggest that VEGF acts in an autocrine and paracrine fashion in both normal and IUGR placentas, and its expression can have an effect on the well being of the infant at birth.

Petunia cultivar sensitivity to ozone and sulfur dioxide

Energy Technology Data Exchange (ETDEWEB)

Elkiey, T.; Ormrod, D.P.

1979-01-01

Ozone and sulfur dioxide are widespread pollutants in many of the areas in which petunias are grown as bedding-plants. Controlled environment experiments were conducted to evaluate the sensitivity of Capri, White Magic and White Cascade to separate or combined O3 and SO2 at 2 growth stages. Relative cultivar sensitivity was the same for O3, SO2 or O3 + SO2, with Capri leaves least injured and White Cascade leaves most injured. Visible injury symptoms were similar in all cultivars. Leaves of intermediate age were most sensitive, but early vegetative plants were more sensitive to O3 than plants in immediate prefloral stage. Severity of leaf injury was generally greater from the combined gases than from the single gases, and the combination treatment at the early vegetative stage significantly reduced plant growth and flower weight 4 weeks later. 29 references, 4 figures, 7 tables.

Effects of flow rate on crack growth in sensitized type 304 stainless steel in high-temperature aqueous solutions

International Nuclear Information System (INIS)

Kwon, H.S.; Wuensche, A.; Macdonald, D.D.

2000-01-01

Intergranular stress corrosion cracking (IGSCC) in weld-sensitized, Type 304 (UNS S30400) (1) stainless steel (SS) remains a major threat to the integrity of heat transport circuits (HTC) in boiling water reactors (BWR), in spite of extensive research over the last 30 years. Effects of flow rate on intergranular crack growth in sensitized Type 304 stainless steel (UNS S30400) in distilled water containing 15 ppm or 25 ppm (2.59 x 10 -4 or 4.31 x 10 -4 m) sodium chloride (NaCl) at 250 C were examined using compact tension (CT) specimens under constant loading conditions. On increasing the flow rate, the crack growth rate (CGR) drastically increased, but later decreased to a level that was lower than the initial value. The initial increase in CGR was attributed to an enhanced rate of mass transfer of oxygen to the external surface, where it consumed the current emanating from the crack mouth. However, the subsequent decrease in CGR was attributed to crack flushing, which is a delayed process because of the time required to destroy the aggressive conditions that exist within the crack. Once flushing destroyed the aggressive crack environment, CGR decreased with increasing flow rate. The time over which CGR increased after an increase in the flow rate depended on how fast crack flushing occurred by fluid flow; the higher the flow rate and the greater the crack opening, the faster the crack flushing and the shorter the transition time. Finally, intergranular cracks propagated faster in regions nearer both sides of the Ct specimens, where the oxygen supply to the external surface was enhanced under stirring conditions and where minimal resistance existed to current flow from the crack tip to the external surfaces. This observation provided evidence that the crack's internal and external environments were coupled electrochemically

To what degree does the missing-data technique influence the estimated growth in learning strategies over time? A tutorial example of sensitivity analysis for longitudinal data.

Science.gov (United States)

Coertjens, Liesje; Donche, Vincent; De Maeyer, Sven; Vanthournout, Gert; Van Petegem, Peter

2017-01-01

Longitudinal data is almost always burdened with missing data. However, in educational and psychological research, there is a large discrepancy between methodological suggestions and research practice. The former suggests applying sensitivity analysis in order to the robustness of the results in terms of varying assumptions regarding the mechanism generating the missing data. However, in research practice, participants with missing data are usually discarded by relying on listwise deletion. To help bridge the gap between methodological recommendations and applied research in the educational and psychological domain, this study provides a tutorial example of sensitivity analysis for latent growth analysis. The example data concern students' changes in learning strategies during higher education. One cohort of students in a Belgian university college was asked to complete the Inventory of Learning Styles-Short Version, in three measurement waves. A substantial number of students did not participate on each occasion. Change over time in student learning strategies was assessed using eight missing data techniques, which assume different mechanisms for missingness. The results indicated that, for some learning strategy subscales, growth estimates differed between the models. Guidelines in terms of reporting the results from sensitivity analysis are synthesised and applied to the results from the tutorial example.

A mixture theory model of fluid and solute transport in the microvasculature of normal and malignant tissues. II: Factor sensitivity analysis, calibration, and validation.

Science.gov (United States)

Schuff, M M; Gore, J P; Nauman, E A

2013-12-01

The treatment of cancerous tumors is dependent upon the delivery of therapeutics through the blood by means of the microcirculation. Differences in the vasculature of normal and malignant tissues have been recognized, but it is not fully understood how these differences affect transport and the applicability of existing mathematical models has been questioned at the microscale due to the complex rheology of blood and fluid exchange with the tissue. In addition to determining an appropriate set of governing equations it is necessary to specify appropriate model parameters based on physiological data. To this end, a two stage sensitivity analysis is described which makes it possible to determine the set of parameters most important to the model's calibration. In the first stage, the fluid flow equations are examined and a sensitivity analysis is used to evaluate the importance of 11 different model parameters. Of these, only four substantially influence the intravascular axial flow providing a tractable set that could be calibrated using red blood cell velocity data from the literature. The second stage also utilizes a sensitivity analysis to evaluate the importance of 14 model parameters on extravascular flux. Of these, six exhibit high sensitivity and are integrated into the model calibration using a response surface methodology and experimental intra- and extravascular accumulation data from the literature (Dreher et al. in J Natl Cancer Inst 98(5):335-344, 2006). The model exhibits good agreement with the experimental results for both the mean extravascular concentration and the penetration depth as a function of time for inert dextran over a wide range of molecular weights.

DNA-mediated gene transfer into human diploid fibroblasts derived from normal and ataxia-telangiectasia donors: parameters for DNA transfer and properties of DNA transformants

International Nuclear Information System (INIS)

Debenham, P.G.; Webb, M.B.T.; Masson, W.K.; Cox, R.

1984-01-01

An investigation was made of the feasibility of DNA-mediated gene transfer into human diploid fibroblasts derived from patients with the radiation sensitive syndrome ataxia-telangiectasia (A-T) and from a normal donor. Although they are markedly different in their growth characteristics, both normal and A-T strains give similar frequencies for DNA transfer in a model system using the recombinant plasmid pSV2-gpt. pSV2-gpt DNA transformants arise with a frequency between 10 -5 and 10 -4 per viable cell. Analysis of such transformants, although possible, is severely handicapped by the limited clonal life span of diploid human cells. Despite these problems it may be concluded that diploid human fibroblasts are competent recipients for DNA-mediated gene transfer and the putative repair deficiency of A-T does not markedly effect the efficiency of this process. (author)

In vitro cholesteatoma growth and secretion of cytokines.

Science.gov (United States)

Helgaland, Tore; Engelen, Bart; Olsnes, Carla; Aarstad, Hans Jørgen; Vassbotn, Flemming S

2010-07-01

Our results show a significant difference between skin and cholesteatoma biology in vitro. Cholesteatoma disease is a process of destruction characterized by uncontrolled growth of squamous epithelial cells in the middle ear or temporal bone. The pathophysiology behind the cholesteatoma development is controversial, and the mechanisms driving the cholesteatoma growth, migration and destructive properties is still unclear. We aimed to provide a method to study the effect of various compounds on cholesteatoma and skin tissue growth, as well as to further investigate the biological differences between normal skin and cholesteatoma tissue. We have established a method to study cholesteatoma biopsy tissue in vitro. Cholesteatoma tissues from patients undergoing surgery for chronic otitis were grown in culture medium and compared to growth patterns and behaviour of normal retroauricular skin. Conditioned medium was analysed for various secreted cytokines. We found a radial outgrowth of keratinocyte epithelium from the circular biopsies. After 5 days of culture we found a significant growth of both cholesteatoma and skin-derived cells. Cholesteatoma samples showed higher growth rate as compared with skin control cultures from the same patient. Moreover, the cholesteatoma cells showed higher production of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6 as compared with normal skin.

Visual Contrast Sensitivity in Early-Stage Parkinson's Disease.

Science.gov (United States)

Ming, Wendy; Palidis, Dimitrios J; Spering, Miriam; McKeown, Martin J

2016-10-01

Visual impairments are frequent in Parkinson's disease (PD) and impact normal functioning in daily activities. Visual contrast sensitivity is a powerful nonmotor sign for discriminating PD patients from controls. However, it is usually assessed with static visual stimuli. Here we examined the interaction between perception and eye movements in static and dynamic contrast sensitivity tasks in a cohort of mildly impaired, early-stage PD patients. Patients (n = 13) and healthy age-matched controls (n = 12) viewed stimuli of various spatial frequencies (0-8 cyc/deg) and speeds (0°/s, 10°/s, 30°/s) on a computer monitor. Detection thresholds were determined by asking participants to adjust luminance contrast until they could just barely see the stimulus. Eye position was recorded with a video-based eye tracker. Patients' static contrast sensitivity was impaired in the intermediate spatial-frequency range and this impairment correlated with fixational instability. However, dynamic contrast sensitivity and patients' smooth pursuit were relatively normal. An independent component analysis revealed contrast sensitivity profiles differentiating patients and controls. Our study simultaneously assesses perceptual contrast sensitivity and eye movements in PD, revealing a possible link between fixational instability and perceptual deficits. Spatiotemporal contrast sensitivity profiles may represent an easily measurable metric as a component of a broader combined biometric for nonmotor features observed in PD.

Serial hemodynamic measurement in normal pregnancy, preeclampsia, and intrauterine growth restriction

NARCIS (Netherlands)

Rang, Saskia; van Montfrans, Gert A.; Wolf, Hans

2008-01-01

OBJECTIVE: The study hypothesis was that hemodynamic measurements in conjunction with uterine artery Doppler could enable selection of women at risk for the development of preeclampsia or fetal growth restriction. STUDY DESIGN: Systolic (SBP) and diastolic blood pressure, heart rate (RR), cardiac

SlLAX1 is Required for Normal Leaf Development Mediated by Balanced Adaxial and Abaxial Pavement Cell Growth in Tomato.

Science.gov (United States)

Pulungan, Sri Imriani; Yano, Ryoichi; Okabe, Yoshihiro; Ichino, Takuji; Kojima, Mikiko; Takebayashi, Yumiko; Sakakibara, Hitoshi; Ariizumi, Tohru; Ezura, Hiroshi

2018-06-01

Leaves are the major plant organs with a primary function for photosynthesis. Auxin controls various aspects of plant growth and development, including leaf initiation, expansion and differentiation. Unique and intriguing auxin features include its polar transport, which is mainly controlled by the AUX1/LAX and PIN gene families as influx and efflux carriers, respectively. The role of AUX1/LAX genes in root development is well documented, but the role of these genes in leaf morphogenesis remains unclear. Moreover, most studies have been conducted in the plant model Arabidopsis thaliana, while studies in tomato are still scarce. In this study, we isolated six lines of the allelic curly leaf phenotype 'curl' mutants from a γ-ray and EMS (ethyl methanesulfonate) mutagenized population. Using a map-based cloning strategy combined with exome sequencing, we observed that a mutation occurred in the SlLAX1 gene (Solyc09g014380), which is homologous to an Arabidopsis auxin influx carrier gene, AUX1 (AtAUX1). Characterization of six alleles of single curl mutants revealed the pivotal role of SlLAX1 in controlling tomato leaf flatness by balancing adaxial and abaxial pavement cell growth, which has not been reported in tomato. Using TILLING (Targeting Induced Local Lesions IN Genome) technology, we isolated an additional mutant allele of the SlLAX1 gene and this mutant showed a curled leaf phenotype similar to other curl mutants, suggesting that Solyc09g014380 is responsible for the curl phenotype. These results showed that SlLAX1 is required for normal leaf development mediated by balanced adaxial and abaxial pavement cell growth in tomato.

A search for distinctive features of demand-led growth models

Directory of Open Access Journals (Sweden)

Sergio Parrinello

2014-09-01

Full Text Available This paper aims at a critical and constructive assessment of some extensions of Keynes’s analysis of effective demand to the long period and growth. A criticism is addressed to a single-cause interpretation of the demand-led growth models and to the notion of normal capacity utilization adopted in such models. A positive argument tries to find a distinctive characterization of those extensions in the productive and financial conditions that make effective the autonomous changes in aggregate demand. It suggests a notion of normal capacity utilization as a range of distributions of normal utilization, related to the cost minimizing choice of techniques and to the persistence of the long term expectations of normal prices underlying the investment decisions. In such a context a long-period analysis with normal prices should avoid a dual steady growth where constant relative prices of capital goods correspond to constant proportions among the stocks of fixed capital.

Computer simulation of sensitization in stainless steels

Energy Technology Data Exchange (ETDEWEB)

Logan, R W

1983-12-20

Stainless steel containers are prime candidates for the containment of nuclear waste in tuff rock. The thermal history of a container involves exposure to temperatures of 500 to 600/sup 0/C when it is welded and possibly filled with molten waste glass, followed by hundreds of years exposure in the 100 to 300/sup 0/C range. The problems of short- and long-term sensitization in stainless steels have been addressed by two computer programs. The TTS program uses classical nucleation and growth theory plus experimental input to predict the onset of precipitation or sensitization under complex thermal histories. The FEMGB program uses quadratic finite-element methods to analyze diffusion processes and chromium depletion during precipitate growth. The results of studies using both programs indicate that sensitization should not be a problem in any of the austenitic stainless steels considered. However, more precise information on the process thermal cycles, especially during welding of the container, is needed. Contributions from dislocation pipe diffusion could promote long-term low-temperature sensitization.

Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis

Energy Technology Data Exchange (ETDEWEB)

Tartaglio, Virginia [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Rennie, Emilie A. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Cahoon, Rebecca [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Baidoo, Edward [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Mortimer, Jennifer C. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Cahoon, Edgar B. [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Scheller, Henrik V. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

2016-09-19

Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway. Plants homozygous for the iput1 loss-of-function mutation were unobtainable, and so the developmental effects of reduced GIPC glucuronosylation could not be analyzed in planta. Using a pollen-specific rescue construct, we have here isolated homozygous iput1 mutants. The iput1 mutants show severe dwarfism, compromised pollen tube guidance, and constitutive activation of salicyclic acid-mediated defense pathways. The mutants also possess reduced GIPCs, increased ceramides, and an increased incorporation of short-chain fatty acids and dihydroxylated bases into inositol phosphorylceramides and GIPCs. The assignment of a direct role for GIPC glycan head groups in the impaired processes in iput1 mutants is complicated by the vast compensatory changes in the sphingolipidome; however, our results reveal that the glycosylation steps of GIPC biosynthesis are important regulated components of sphingolipid metabolism. In conclusion, this study corroborates previously suggested roles for GIPC glycans in plant growth and defense, suggests important role s for them in reproduction and demonstrates that the entire sphingolipidome is sensitive to their status.

Oral manifestations in growth hormone disorders

Directory of Open Access Journals (Sweden)

Gaurav Atreja

2012-01-01

Full Text Available Growth hormone is of vital importance for normal growth and development. Individuals with growth hormone deficiency develop pituitary dwarfism with disproportionate delayed growth of skull and facial skeleton giving them a small facial appearance for their age. Both hyper and hypopituitarism have a marked effect on development of oro-facial structures including eruption and shedding patterns of teeth, thus giving an opportunity to treating dental professionals to first see the signs and symptoms of these growth disorders and correctly diagnose the serious underlying disease.

Growth and development of children with congenital heart disease.

Science.gov (United States)

Chen, Chi-Wen; Li, Chung-Yi; Wang, Jou-Kou

2004-08-01

Children with congenital heart disease (CHD) commonly experience delayed growth. Because growth and development are closely related, both should be considered when a child's progress is examined. This paper reports a study to evaluate and compare the growth and development of preschool children with CHD to those of normal preschool children. The heights and weights of 42 preschool children with CHD and 116 normal preschool children were compared with standard growth curves. Differences in development of personal and social skills, fine motor skills and adaptability, language, and gross motor skills were evaluated. Developmental skills were assessed using the Denver Developmental Screening Test II. A significant difference was found in both body height (P motor sections (P development. Learning about the growth and developmental differences between children with CHD and normal children may help parents of the former to detect problems associated with delayed growth and development earlier. These children and their families should have the opportunity to participate in a long-term, follow-up programme that provides information and encourages developmental progress. The results could serve as a reference for those in both clinical and community workers who provide nursing care to children with CHD.

Growth and development after hematopoietic cell transplant in children.

Science.gov (United States)

Sanders, J E

2008-01-01

Hematopoietic cell transplantation (HCT) following high-dose chemotherapy or chemoradiotherapy for children with malignant or nonmalignant hematologic disorders has resulted in an increasing number of long-term disease-free survivors. The preparative regimens include high doses of alkylating agents, such as CY with or without BU, and may include TBI. These agents impact the neuroendocrine system in growing children and their subsequent growth and development. Children receiving high-dose CY or BUCY have normal thyroid function, but those who receive TBI-containing regimens may develop thyroid function abnormalities. Growth is not impacted by chemotherapy-only preparative regimens, but TBI is likely to result in growth hormone deficiency and decreased growth rates that need to be treated with synthetic growth hormone therapy. Children who receive high-dose CY-only have normal development through puberty, whereas those who receive BUCY have a high incidence of delayed pubertal development. Following fractionated TBI preparative regimens, approximately half of the patients have normal pubertal development. These data demonstrate that the growth and development problems after HCT are dependent upon the preparative regimen received. All children should be followed for years after HCT for detection of growth and development abnormalities that are treatable with appropriate hormone therapy.

Continuous monitoring of back wall stress corrosion cracking growth in sensitized type 304 stainless steel weldment by means of potential drop techniques

OpenAIRE

SATO, Y; ATSUMI, T; SHOJI, T

2007-01-01

Stress corrosion cracking (SCC) tests on welded specimens of sensitized type 304SS with a thickness of 20 mm were performed in sodium thiosulphate solution at room temperature, with continuous monitoring of the SCC growth, using the techniques of modified induced current potential drop (MICPD), alternating current potential drop (ACPD) and direct current potential drop (DCPD). The MICPD and DCPD techniques permit continuous monitoring of the back wall SCC, which initiates from a fatigue pre-c...

Intrauterine growth restriction - part 2.

Science.gov (United States)

Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

2016-12-01

Small for gestational age (SGA) infants have been classically defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age, whereas intrauterine growth restriction (IUGR) has been defined as a rate of foetal growth that is less than normal for the population and for the growth potential of a specific infant. SGA infants have more frequent problems such as perinatal asphyxia, hypothermia, hypoglycaemia, polycythaemia and many more when compared with their appropriate for gestational age counterpart. They too have growth retardation and various major and subtle neurodevelopmental handicaps, with higher rates of perinatal and neonatal mortality. With the advent of newer technologies, even though the perinatal diagnosis of these SGA/IUGR foetuses has increased, but still perinatal morbidity and mortality rates are higher than normal foetuses and infants. In this part, we have covered neonatal IUGR classification, postnatal diagnosis, short-term and long-term complications faced by these IUGR infants.

Molecular characterization of transforming growth factor-beta3

NARCIS (Netherlands)

Dijke, ten P.

1991-01-01

Normal tissue homeostasis is controlled by a critical balance of positive and negative modulators. Chapter 2 gives an overview of the molecular aspects of growth control, in particular the role of growth factors and oncogene and anti-oncogene products. Uncontrolled growth of cancer cells

Growth hormone-mediated breakdown of body fat

DEFF Research Database (Denmark)

Johansen, T.; Malmlöf, K.; Richelsen, Bjørn

2003-01-01

regimen. Twelve-month-old rats fed first a high-fat diet or a low-fat diet for 14 weeks were injected with saline or growth hormone (4 mg/kg/d) for four days or three weeks in different combinations with either high- or low-fat diets. In adipose tissue, growth hormone generally inhibited lipoprotein...... lipase and also attenuated the inhibiting effect of insulin on hormone-sensitive lipase activity. Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle. Generally, plasma levels of free...... fatty acids, glycerol and cholesterol were reduced by growth hormone, and in combination with restricted high-fat feeding, triglyceride levels improved too. We conclude that growth hormone inhibits lipid storage in adipose tissue by reducing both lipoprotein lipase activity and insulin's inhibitory...

Urinary growth hormone levels in children with leukemia determined by a sensitive sandwich enzyme immunoassay

International Nuclear Information System (INIS)

Umezawa, Sachiko; Yano, Hisako; Tanaka, Toshiaki; Hibi, Itsuo; Tsukimoto, Ichiro; Ishikawa, Eiji; Mouri, Yoshikazu; Murakami, Yoshiaki.

1989-01-01

Elective cranial irradiation in central nervous leukemia leads to a long term survival; however, the influence upon the hypothalamus and hypophysis remains uncertain. Therefore, changes in SD scores of height and urinary growth hormone (U-GH) levels were determined in 23 leukemic patients previously treated with cranial elective irradition of 18 or 24 Gy, whose ages ranged from 4 to 16 years. Decreased SD scores of height was observed in 9 (90%) of 10 patients in whom treatment has been continuing (within 5 years after the onset) and in 6 (50%) of 12 patients in whom treatment had been completed (5 years or more after the onset). The level of U-GH was significantly decreased in leukemic patients during complete remission than in healthy children. U-HG levels were independent of radiation doses. In evaluable 14 patients, the blood concentration of somatomedin C (SM-C) was within the normal range. Although there was a discrepancy between U-CH and SM-C levels, further follow-up of these leukemic patients is required. (N.K.)

Subjective Evaluation of Sound Quality for Normal-hearing and Hearing-i,paired Listeners

DEFF Research Database (Denmark)

Nielsen, Lars Bramsløw

1992-01-01

11 hearing-impaired (HI) and 12 normal-hearing (NH) subjects have performed sound quality ratings on 6 perceptual scales (Loudness, Clarity, Sharpness, Fullness, Spaciousness and Overall judgement). The signals for the rating experiment consisted of running speech and music with or without......, but the normal-hearing group was slightly more reliable. There were significant differences between stimuli and between subjects, with stimuli affecting the ratings the most. Normal-hearing and hearing-impaired subjects showed similar trends, but normal-hearing listeners were generally more sensitive, i...

Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

Science.gov (United States)

Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

2014-03-05

Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression. Copyright © 2013 Elsevier

Limit of sensitivity of low-background counting equipment

International Nuclear Information System (INIS)

Homann, S.G.

1991-01-01

The Hazards Control Department's Radiological Measurements Laboratory (RML) analyzes many types of sample media in support of the Laboratory's health and safety program. The Department has determined that the equation for the minimum limit of sensitivity, MDC(α,β) = 2.71 + 3.29 (r b t s ) 1/2 is also adequate for RML counting systems with very-low-background levels. This paper reviews the normal distribution case and address the special case of determining the limit of sensitivity of a counting system when the background count rate is well known and small. In the latter case, we must use an exact test procedure based on the binomial distribution. However, the error in using the normal distribution for calculating a detection system's limit of sensitivity is not significant even as the total observed number of counts approaches or equals zero. 2 refs., 4 figs

CT assessment of normal splenic size in children

International Nuclear Information System (INIS)

Prassopoulos, P.; Cavouras, D.

1994-01-01

The size of the normal spleen was estimated by CT in 153 children, examined with indication unrelated to splenic disease. In each patient the width, thickness, length and volume of the spleen were calculated. Measurements were also normalized to the transverse diameter of the body of the first lumbar vertebra. The spleen underwent significant growth during the first 4 years of life and reached maximum size at the age of 13. There were no differences in splenic volume between boys and girls. Splenic thickness correlated best with normal splenic volume. The strongest correlation was also found between splenic thickness and volume in a group of 45 children with clinically evident splenomegaly. Splenic thickness, an easy-to-use measurement, may be employed in everyday practice to represent splenic volume on CT. (orig.)

Biomechanical Analysis of Normal Brain Development during the First Year of Life Using Finite Strain Theory.

Science.gov (United States)

Kim, Jeong Chul; Wang, Li; Shen, Dinggang; Lin, Weili

2016-12-02

The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework.

Morphogenesis and crystallization of ZnS microspheres by a soft template-assisted hydrothermal route: synthesis, growth mechanism, and oxygen sensitivity.

Science.gov (United States)

Yang, Liangbao; Han, Jun; Luo, Tao; Li, Minqiang; Huang, Jiarui; Meng, Fanli; Liu, Jinhuai

2009-01-05

Almost monodisperse ZnS microspheres have been synthesized on a large scale by a hydrothermal route, in which tungstosilicate acid (TSA) was used as a soft template. By controlling the reaction conditions, such as reaction temperature, pH value of the solutions, and the reaction medium, almost monodisperse microspheres can be synthesized. The structure of these microspheres is sensitive to the reaction conditions. The growth mechanism of these nearly monodisperse microspheres was examined. Oxygen sensing is realized from ZnS microspheres. The current through the ZnS microspheres under UV illumination increases as the oxygen concentration decreases.

GC-Content Normalization for RNA-Seq Data

Science.gov (United States)

2011-01-01

Background Transcriptome sequencing (RNA-Seq) has become the assay of choice for high-throughput studies of gene expression. However, as is the case with microarrays, major technology-related artifacts and biases affect the resulting expression measures. Normalization is therefore essential to ensure accurate inference of expression levels and subsequent analyses thereof. Results We focus on biases related to GC-content and demonstrate the existence of strong sample-specific GC-content effects on RNA-Seq read counts, which can substantially bias differential expression analysis. We propose three simple within-lane gene-level GC-content normalization approaches and assess their performance on two different RNA-Seq datasets, involving different species and experimental designs. Our methods are compared to state-of-the-art normalization procedures in terms of bias and mean squared error for expression fold-change estimation and in terms of Type I error and p-value distributions for tests of differential expression. The exploratory data analysis and normalization methods proposed in this article are implemented in the open-source Bioconductor R package EDASeq. Conclusions Our within-lane normalization procedures, followed by between-lane normalization, reduce GC-content bias and lead to more accurate estimates of expression fold-changes and tests of differential expression. Such results are crucial for the biological interpretation of RNA-Seq experiments, where downstream analyses can be sensitive to the supplied lists of genes. PMID:22177264

River profile response to normal fault growth and linkage: an example from the Hellenic forearc of south-central Crete, Greece

Science.gov (United States)

Gallen, Sean F.; Wegmann, Karl W.

2017-02-01

Topography is a reflection of the tectonic and geodynamic processes that act to uplift the Earth's surface and the erosional processes that work to return it to base level. Numerous studies have shown that topography is a sensitive recorder of tectonic signals. A quasi-physical understanding of the relationship between river incision and rock uplift has made the analysis of fluvial topography a popular technique for deciphering relative, and some argue absolute, histories of rock uplift. Here we present results from a study of the fluvial topography from south-central Crete, demonstrating that river longitudinal profiles indeed record the relative history of uplift, but several other processes make it difficult to recover quantitative uplift histories. Prior research demonstrates that the south-central coastline of Crete is bound by a large ( ˜ 100 km long) E-W striking composite normal fault system. Marine terraces reveal that it is uplifting between 0.1 and 1.0 mm yr-1. These studies suggest that two normal fault systems, the offshore Ptolemy and onshore South-Central Crete faults, linked together in the recent geologic past (ca. 0.4-1 My BP). Fault mechanics predict that when adjacent faults link into a single fault the uplift rate in footwalls of the linkage zone will increase rapidly. We use this natural experiment to assess the response of river profiles to a temporal jump in uplift rate and to assess the applicability of the stream power incision model to this setting. Using river profile analysis we show that rivers in south-central Crete record the relative uplift history of fault growth and linkage as theory predicts that they should. Calibration of the commonly used stream power incision model shows that the slope exponent, n, is ˜ 0.5, contrary to most studies that find n ≥ 1. Analysis of fluvial knickpoints shows that migration distances are not proportional to upstream contributing drainage area, as predicted by the stream power incision model

Anxiety and beta-adrenergic receptor function in a normal population.

Science.gov (United States)

Kang, Eun-Ho; Yu, Bum-Hee

2005-06-01

Many studies have shown a close relationship between anxiety and beta-adrenergic receptor function in patients with anxiety disorders. This study examined the relationship between beta-adrenergic receptor function and anxiety levels in a normal population. Subjects for this study included 36 men and 44 women between the ages of 20 and 40 years whose Body Mass Index (BMI) was between 18 and 26. All of them were healthy subjects who had no previous history of medical or psychiatric illnesses. The authors measured the Spielberger State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Chronotropic 25 Dose (CD25) of isoproterenol, previously developed to assess in vivo beta-adrenergic receptor sensitivity. We also examined correlations between log normalized CD25 and mood states. The mean of CD25 was 2.64+/-1.37 mug and the mean of CD25 in men was significantly higher (i.e., lower beta-adrenergic receptor sensitivity) than that of women (3.26+/-1.35 vs. 2.14+/-1.17 microg; t = 3.99, p anxiety (r = -0.344, p = 0.002), trait anxiety (r = -0.331, p = 0.003), and BDI (r = -0.283, p = 0.011). CD25 was positively correlated with BMI (r = 0.423, p anxiety, and BMI. The sensitivity of beta-adrenergic receptors increased as anxiety levels became higher in a normal population. Thus, the relationship between anxiety and beta-adrenergic receptor function in healthy subjects may be different from that of patients with anxiety disorders.

Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy.

Science.gov (United States)

Zhang, Li; Takara, Kazuhiro; Yamakawa, Daishi; Kidoya, Hiroyasu; Takakura, Nobuyuki

2016-01-01

Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well-described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post-treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Is the assumption of normality or log-normality for continuous response data critical for benchmark dose estimation?

International Nuclear Information System (INIS)

Shao, Kan; Gift, Jeffrey S.; Setzer, R. Woodrow

2013-01-01

Continuous responses (e.g. body weight) are widely used in risk assessment for determining the benchmark dose (BMD) which is used to derive a U.S. EPA reference dose. One critical question that is not often addressed in dose–response assessments is whether to model the continuous data as normally or log-normally distributed. Additionally, if lognormality is assumed, and only summarized response data (i.e., mean ± standard deviation) are available as is usual in the peer-reviewed literature, the BMD can only be approximated. In this study, using the “hybrid” method and relative deviation approach, we first evaluate six representative continuous dose–response datasets reporting individual animal responses to investigate the impact on BMD/BMDL estimates of (1) the distribution assumption and (2) the use of summarized versus individual animal data when a log-normal distribution is assumed. We also conduct simulation studies evaluating model fits to various known distributions to investigate whether the distribution assumption has influence on BMD/BMDL estimates. Our results indicate that BMDs estimated using the hybrid method are more sensitive to the distribution assumption than counterpart BMDs estimated using the relative deviation approach. The choice of distribution assumption has limited impact on the BMD/BMDL estimates when the within dose-group variance is small, while the lognormality assumption is a better choice for relative deviation method when data are more skewed because of its appropriateness in describing the relationship between mean and standard deviation. Additionally, the results suggest that the use of summarized data versus individual response data to characterize log-normal distributions has minimal impact on BMD estimates. - Highlights: • We investigate to what extent the distribution assumption can affect BMD estimates. • Both real data analysis and simulation study are conducted. • BMDs estimated using hybrid method are more

Is the assumption of normality or log-normality for continuous response data critical for benchmark dose estimation?

Energy Technology Data Exchange (ETDEWEB)

Shao, Kan, E-mail: Shao.Kan@epa.gov [ORISE Postdoctoral Fellow, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Gift, Jeffrey S. [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Setzer, R. Woodrow [National Center for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

2013-11-01

Continuous responses (e.g. body weight) are widely used in risk assessment for determining the benchmark dose (BMD) which is used to derive a U.S. EPA reference dose. One critical question that is not often addressed in dose–response assessments is whether to model the continuous data as normally or log-normally distributed. Additionally, if lognormality is assumed, and only summarized response data (i.e., mean ± standard deviation) are available as is usual in the peer-reviewed literature, the BMD can only be approximated. In this study, using the “hybrid” method and relative deviation approach, we first evaluate six representative continuous dose–response datasets reporting individual animal responses to investigate the impact on BMD/BMDL estimates of (1) the distribution assumption and (2) the use of summarized versus individual animal data when a log-normal distribution is assumed. We also conduct simulation studies evaluating model fits to various known distributions to investigate whether the distribution assumption has influence on BMD/BMDL estimates. Our results indicate that BMDs estimated using the hybrid method are more sensitive to the distribution assumption than counterpart BMDs estimated using the relative deviation approach. The choice of distribution assumption has limited impact on the BMD/BMDL estimates when the within dose-group variance is small, while the lognormality assumption is a better choice for relative deviation method when data are more skewed because of its appropriateness in describing the relationship between mean and standard deviation. Additionally, the results suggest that the use of summarized data versus individual response data to characterize log-normal distributions has minimal impact on BMD estimates. - Highlights: • We investigate to what extent the distribution assumption can affect BMD estimates. • Both real data analysis and simulation study are conducted. • BMDs estimated using hybrid method are more

Sensory-specific satiety in obese and normal-weight women

NARCIS (Netherlands)

Snoek, H.M.; Huntjens, L.; Gemert, L.J. van; Graaf, C. de; Weenen, H.

2004-01-01

Background: Sensory-specific satiety has been found to play an important role in food choice and meal termination, and it might be a factor contributing to obesity. Objective: We hypothesized that obese and normal-weight people have different sensitivities to sensory-specific satiety for high-fat

Normal-Mode Splitting in a Weakly Coupled Optomechanical System

Science.gov (United States)

Rossi, Massimiliano; Kralj, Nenad; Zippilli, Stefano; Natali, Riccardo; Borrielli, Antonio; Pandraud, Gregory; Serra, Enrico; Di Giuseppe, Giovanni; Vitali, David

2018-02-01

Normal-mode splitting is the most evident signature of strong coupling between two interacting subsystems. It occurs when two subsystems exchange energy between themselves faster than they dissipate it to the environment. Here we experimentally show that a weakly coupled optomechanical system at room temperature can manifest normal-mode splitting when the pump field fluctuations are antisquashed by a phase-sensitive feedback loop operating close to its instability threshold. Under these conditions the optical cavity exhibits an effectively reduced decay rate, so that the system is effectively promoted to the strong coupling regime.

The sensitivity of an actinic reticuloid cell strain to near-ultraviolet radiation and its modification by Trolox-C, a vitamin E analogue

International Nuclear Information System (INIS)

Kralli, A.; Moss, S.H.

1987-01-01

Near-UV radiation (365 nm)-induced lethality, as measured by colony-forming ability, showed an actinic reticuloid cell strain to be sensitive relative to normal human fibroblasts, when irradiated at 25 0 C. This effect was not seen after far-UV (254 nm) irradiation. Trolox-C, a water-soluble analogue of vitamin E, incorporated in the pre-irradiation growth medium or in the post-irradiation plating medium, protected the actinic reticuloid cells to the extent that they were as resistant as normal cells. Plating medium containing Trolox-C did not provide differential protection against inactivation of the two cell strains by wavelengths in the far-UV region. The protection provided by Trolox-C, an analogue of the natural antioxidant vitamin E, suggests some free radical involvement in the aetiology of the disease. (author)

Requirements of blue, UV-A, and UV-B light for normal growth of higher plants, as assessed by actions spectra for growth and related phenomena

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, T. [Kobe Women`s Univ., Higashisuma (Japan)

1994-12-31

It is very important for experimental purposes, as well as for the practical use of plants when not enough sunlight is available. To grow green higher plants in their normal forms under artificial lighting constructing efficient and economically reasonable lighting systems is not an easy task. One possible approach would be to simulate sunlight in intensity and the radiation spectrum, but its high construction and running costs are not likely to allow its use in practice. Sunlight may be excessive in irradiance in some or all portions of the spectrum. Reducing irradiance and removing unnecessary wavebands might lead to an economically feasible light source. However, removing or reducing a particular waveband from sunlight for testing is not easy. Another approach might be to find the wavebands required for respective aspects of plant growth and to combine them in a proper ratio and intensity. The latter approach seems more practical and economical, and the aim of this Workshop lies in advancing this approach. I summarize our present knowledge on the waveband requirements of higher plants for the regions of blue, UV-A and UV-B.

Models of the Economic Growth and their Relevance

Directory of Open Access Journals (Sweden)

Nicolae MOROIANU

2012-06-01

Full Text Available Until few years ago, the economic growth was something perfect normal, part of an era marked by the transformation speed. Normality itself has been transformed and we currently are influenced by other rules, unknown yet, which should answer the question: “How do we return to the economic growth?” The economic growth and the models aiming to solve this problem concern the economic history even since its beginnings. In this paper we would like to find out what is the relevance that the well-known macroeconomic models still have and which might be their applicability level in a framework created by a black swan event type.

Growth hormone deficiency in a Nigerian child with Turner's syndrome

African Journals Online (AJOL)

IRORO YARHERE

Growth hormone treatment early in the course of management of a child with Turner syndrome may help achieve normal final height. Keywords: Turner's syndrome, short stature, growth hormone deficiency, growth hormone ..... cognitive deficit.

Growth curves for Laron syndrome.

OpenAIRE

Laron, Z; Lilos, P; Klinger, B

1993-01-01

Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls co...

Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children

DEFF Research Database (Denmark)

Jensen, Rikke Beck; Thankamony, Ajay; Day, Felix

2015-01-01

with spontaneous postnatal weight gain (regression coefficient [B]: 0.12 SD scores per allele; 95% confidence interval [CI], 0.01-0.23; P = .03) and also in response to GH therapy with first-year height velocity (B: 0.18 cm/y per allele; 95% CI, 0.02-0.35; P = .03) and change in IGF-1 (B: 0.17 SD scores per allele......PURPOSE: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity. METHOD: Combined multiallele single nucleotide polymorphism......; 95% CI, 0.00-0.32; P = .03). The association with first-year height velocity was independent of reported predictors of response to GH therapy (adjusted P = .04). The insulin secretion allele score (GS-InSec) was positively associated with spontaneous postnatal height gain (B: 0.15; 95% CI, 0...

Growth Modeling of the Maternal Cytokine Milieu throughout Normal Pregnancy: Macrophage-Derived Chemokine Decreases as Inflammation/Counterregulation Increases

Directory of Open Access Journals (Sweden)

Shernan G. Holtan

2015-01-01

Full Text Available Several recent studies have shown differences in the maternal immune milieu at different phases of pregnancy, but most studies have been cross-sectional or of relatively few time points. Levels of 42 cytokines were determined using a multiplex bead-based assay on archived serum from a cohort of pregnant women N=16 at median of 18 time points tested, from the first trimester through to parturition, per woman. Unconditional growth modeling was then used to determine time-dependent changes in levels of these cytokines. Macrophage-derived chemokine (MDC, aka CCL22 decreases as pregnancy progresses. IL-1β, IL-6, IL-8, IL-12p70, IL-13, IL-15, IP-10, and FLT3-ligand increase as a function of gestational weeks, and IFNα2, IL-1ra, IL-3, IL-9, IL-12p40, and soluble CD40 ligand increase as a function of trimester. As pregnancy normally progresses, a maternal shift away from a type 2-biased immune response and toward an inflammatory/counterregulatory response is observed.

Radiation sensitivity of human malignant lymphocytes

International Nuclear Information System (INIS)

Seshadri, R.; Matthews, C.; Morley, A.A.

1985-01-01

A simple and rapid in vitro technique to assess the sensitivity of human malignant lymphocytes to roentgen irradiation is described. A variety of established malignant lymphocyte cell lines were cloned in microwells and clone survival was used as the end-point. The survival of the clonogenic malignant lymphocyte down to a fraction of approximately 0.001 could be measured accurately. Except for a T-cell line, the radiation sensitivities of the cell lines were similar to that of normal T-lymphocytes. (orig.)

PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice

Science.gov (United States)

Zinker, Bradley A.; Rondinone, Cristina M.; Trevillyan, James M.; Gum, Rebecca J.; Clampit, Jill E.; Waring, Jeffrey F.; Xie, Nancy; Wilcox, Denise; Jacobson, Peer; Frost, Leigh; Kroeger, Paul E.; Reilly, Regina M.; Koterski, Sandra; Opgenorth, Terry J.; Ulrich, Roger G.; Crosby, Seth; Butler, Madeline; Murray, Susan F.; McKay, Robert A.; Bhanot, Sanjay; Monia, Brett P.; Jirousek, Michael R.

2002-01-01

The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA1C. Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, were increased and PI3-kinase p85α expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes. PMID:12169659

Growth of maize coleoptiles in the presence of natural and synthetic growth regulators. Growth correlations

Directory of Open Access Journals (Sweden)

Ewa Raczek

2014-01-01

Full Text Available The effect of natural (IAA, FC, ABA and synthetic (2,4-D growth substances on the increase of the fresh weight of maize coleoptile segments and change of the pH of the incubation medium, accepted here as criteria of maize coleoptile growth, was studied. The growth of maize coleoptiles depended on the concentration of the growth substances, as well as, on the composition of the incubation medium. The highest stimulation of coleoptile growth was seen with FC at a concentration of 10-4M, whereas ABA at 10-3 M gave the highest inhibition of maize coleoptile fresh weight increase and caused alkalization of the medium. The presence of K+ ions in the incubation medium enhanced the stimulatory effect of IAA and FC on the increase of the coleoptile fresh weight, whereas the presence of these ions and phosphate buffer abolished the growth-promoting effect of IAA and FC. The best correlation of the "fresh weight" and "pH" effects was found in the case of the growth of maize coleoptiles in the presence of FC (rxy = 0.67. The inhibition of maize coleoptile growth in the presence of high concentrations of IAA can be explained by the destructive effect of natural auxin at these concentrations on the integrity of mitochondrial membranes, and therefore on the normal functioning of mitochondria.

Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

Science.gov (United States)

Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

2016-10-04

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

Body weight and sensitivity of screening mammography

DEFF Research Database (Denmark)

Njor, Sisse H.; von Euler-Chelpin, My; Tjønneland, Anne

2016-01-01

benefit more from screening than other women. Methods: We combined data from the Danish Diet, Cancer and Health study and the organised population-based screening mammography programme in Copenhagen, Denmark. Women were categorised according to body mass index (BMI) (...Aim: Obese women tend to participate less in breast cancer screening than normal weight women. However, obese women have fattier breast than normal weight women, and screening mammography works better in fatty than in dense breasts. One might, therefore, hypothesise that obese women would actually......, and 35+). We measured recall rate, sensitivity and specificity for subsequent screens with a 2-year follow-up period. Results: The study included 6787 women. The recall rate varied from 1.4% for women with BMI women with BMI 35+, test for trend p = 0.86. Sensitivity varied from 42% (95...

Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance.

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Li, Weiping; Li, Qifu

2012-01-01

To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, PPCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, PPCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m². In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m² indicated impaired β cell function in PCOS women with normal glucose tolerance.

Assessment of pain sensitivity in patients with deep bite and sex- and age-matched controls

DEFF Research Database (Denmark)

Sonnesen, Ane Liselotte; Svensson, Peter

2011-01-01

AIMS: To compare pain sensitivity between deep bite patients and a sex- and age-matched control group with normal occlusion. METHODS: Pain sensitivity was assessed by injections of the excitatory amino acid glutamate into the masseter and brachioradialis muscles. Intensity of glutamate-evoked pai...... of gender-related differences in somatosensory sensitivity and for the first time indicate that subjects with deep bite may be more sensitive to glutamate-evoked pain and thermal stimuli.......AIMS: To compare pain sensitivity between deep bite patients and a sex- and age-matched control group with normal occlusion. METHODS: Pain sensitivity was assessed by injections of the excitatory amino acid glutamate into the masseter and brachioradialis muscles. Intensity of glutamate-evoked pain...

Continuous wet-process growth of ZnO nanoarrays for wire-shaped photoanode of dye-sensitized solar cell.

Science.gov (United States)

Tao, Pan; Guo, Wanwan; Du, Jun; Tao, Changyuan; Qing, Shenglan; Fan, Xing

2016-09-15

Well-aligned ZnO nanorod arrays have been grown on metal-plated polymer fiber via a mild wet process in a newly-designed continuous reactor, aiming to provide wire-shaped photoanodes for wearable dye-sensitized solar cells. The growth conditions were systematically optimized with the help of computational flow-field simulation. The flow field in the reactor will not only affect the morphology of the ZnO nanorod⧹nanowire but also affect the pattern distribution of nanoarray on the electrode surface. Unlike the sectional structure from the traditional batch-type reactor, ZnO nanorods with finely-controlled length and uniform morphology could be grown from the continuous reactor. After optimization, the wire-shaped ZnO-type photoanode grown from the continuous reactor exhibited better photovoltaic performance than that from the traditional batch-type reactor. Copyright © 2016 Elsevier Inc. All rights reserved.

Bulimia nervosa in overweight and normal-weight women.

Science.gov (United States)

Masheb, Robin; White, Marney A

2012-02-01

The aim of the present study was to examine overweight bulimia nervosa (BN) in a community sample of women. Volunteers (n = 1964) completed self-report questionnaires of weight, binge eating, purging, and cognitive features. Participants were classified as overweight (body mass index ≥25) or normal weight (body mass index <25). Rates of BN within the overweight and normal-weight classes did not differ (6.4% vs 7.9%). Of the 131 participants identified as BN, 64% (n = 84) were classified as overweight BN and 36% (n = 47) as normal-weight BN. The overweight BN group had a greater proportion of ethnic minorities and reported significantly less restraint than the normal-weight BN group. Otherwise, the 2 groups reported similarly, even in terms of purging and depression. In summary, rates of BN did not differ between overweight and normal-weight women. Among BN participants, the majority (two thirds) were overweight. Differences in ethnicity and restraint, but little else, were found between overweight and normal-weight BN. Findings from the present study should serve to increase awareness of the weight range and ethnic diversity of BN, and highlight the need to address weight and cultural sensitivity in the identification and treatment of eating disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of compensatory growth on feed intake, growth rate and ...

African Journals Online (AJOL)

in feed utilization from the 0,65 and to the ad libitum group. More severe restrictions ... to manage his animals at the lowest possible cost. Normally after a time of feed ... tory growth can be explained in terms of a reduction of maintenance ...

A study of the normal interpedicular distance of the spine in Korean teenagers (Estimation of normal range by roentgenographic measurement)

International Nuclear Information System (INIS)

Lee, Myung Uk

1979-01-01

The radiological measurement of the interpedicular disease using a routine antero-posterior view of the spine gives important clinical criteria in evaluation of the intraspinal tumor and stenosis of the spinal canal, and aids for diagnosis of the lesions. In 1934 Elsberg and Dyke reported values of interpedicular distance as determined on roentgenograms for spine of white adult, and in 1968 Song prepared normal values of interpedicular distance for Korean adult. The present investigation was undertaken to provide normal interpedicular distance of Korean teenagers. The author observed the antero-posterior films of the spine of 200 normal teenagers which were composed of 100 male and 100 female. The normal values of the interpedicular distance of Korean teenagers were obtained, as well as 90% tolerance range for clinical use. In this statistical analysis, there were noted significant differences between male and female, and each age groups. It was observed that average male measurement were consistently larger than female by about 1 mm and the growth of the spinal canal appeared to be continued.

The Development and Validation of the Vocalic Sensitivity Test.

Science.gov (United States)

Villaume, William A.; Brown, Mary Helen

1999-01-01

Notes that presbycusis, hearing loss associated with aging, may be marked by a second dimension of hearing loss, a loss in vocalic sensitivity. Reports on the development of the Vocalic Sensitivity Test, which controls for the verbal elements in speech while also allowing for the vocalics to exercise their normal metacommunicative function of…

Foliar Abscisic Acid-To-Ethylene Accumulation and Response Regulate Shoot Growth Sensitivity to Mild Drought in Wheat

Science.gov (United States)

Valluru, Ravi; Davies, William J.; Reynolds, Matthew P.; Dodd, Ian C.

2016-01-01

Although, plant hormones play an important role in adjusting growth in response to environmental perturbation, the relative contributions of abscisic acid (ABA) and ethylene remain elusive. Using six spring wheat genotypes differing for stress tolerance, we show that young seedlings of the drought-tolerant (DT) group maintained or increased shoot dry weight (SDW) while the drought-susceptible (DS) group decreased SDW in response to mild drought. Both the DT and DS groups increased endogenous ABA and ethylene concentrations under mild drought compared to control. The DT and DS groups exhibited different SDW response trends, whereby the DS group decreased while the DT group increased SDW, to increased concentrations of ABA and ethylene under mild drought, although both groups decreased ABA/ethylene ratio under mild drought albeit at different levels. We concluded that SDW of the DT and DS groups might be distinctly regulated by specific ABA:ethylene ratio. Further, a foliar-spray of low concentrations (0.1 μM) of ABA increased shoot relative growth rate (RGR) in the DS group while ACC (1-aminocyclopropane-1-carboxylic acid, ethylene precursor) spray increased RGR in both groups compared to control. Furthermore, the DT group accumulated a significantly higher galactose while a significantly lower maltose in the shoot compared to the DS group. Taken all together, these results suggest an impact of ABA, ethylene, and ABA:ethylene ratio on SDW of wheat seedlings that may partly underlie a genotypic variability of different shoot growth sensitivities to drought among crop species under field conditions. We propose that phenotyping based on hormone accumulation, response and hormonal ratio would be a viable, rapid, and an early–stage selection tool aiding genotype selection for stress tolerance. PMID:27148292

Endogenous growth and economic capacity: Theory and empirical evidence for the NAFTA countries

Directory of Open Access Journals (Sweden)

Ignacio Perrotini-Hernàndez

2017-09-01

Full Text Available he paper sheds light on the relevance of economic capacity utilisation, capital accumulation and effective demand for the endogeneity of the natural growth rate with respect to normal, depressive and expansive growth regimes. Apart from contributing to fill this theoretical gap, a new model is developed for estimating the elasticity of the natural growth rate, with a specific focus on Canada, Mexico and the United States, throughout the pre-NAFTA and post-NAFTA periods. It is shown that growth regimes are related to the utilisation of economic capacity, while the elasticities of the expansive and depressive natural rates of growth vis-à-vis the normal rate are related to effective demand. It is also found that the normal, depressive and expansive natural rates of growth decreased since the inception of NAFTA, due to the concomitant decline in the growth rate of economic capacity. JEL Classification: O47, O51, O54

Corticocortical feedback increases the spatial extent of normalization.

Science.gov (United States)

Nassi, Jonathan J; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T

2014-01-01

Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a "normalization pool." Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing.

Normal and abnormal grain growth in fine-grained Nd-Fe-B sintered magnets prepared from He jet milled powders

Energy Technology Data Exchange (ETDEWEB)

Bittner, F., E-mail: f.bittner@ifw-dresden.de [IFW Dresden, Institute for Metallic Materials, PO Box 270116, 01171 Dresden (Germany); Technische Universität Dresden, Institute of Materials Science, 01062 Dresden (Germany); Woodcock, T.G. [IFW Dresden, Institute for Metallic Materials, PO Box 270116, 01171 Dresden (Germany); Schultz, L. [IFW Dresden, Institute for Metallic Materials, PO Box 270116, 01171 Dresden (Germany); Technische Universität Dresden, Institute of Materials Science, 01062 Dresden (Germany); Schwöbel, C. [Technische Universität Darmstadt, Materialwissenschaft, Alarich-Weiß-Str. 16, 64287 Darmstadt (Germany); Gutfleisch, O. [Technische Universität Darmstadt, Materialwissenschaft, Alarich-Weiß-Str. 16, 64287 Darmstadt (Germany); Fraunhofer ISC, Projektgruppe für Werkstoffkreisläufe und Ressourcenstrategie IWKS, Rodenbacher Chaussee 4, 63457 Hanau (Germany); Zickler, G.A.; Fidler, J. [Technische Universität Wien, Institute of Solid State Physics, Wiedner Hauptstr. 8-10, 1040 Wien (Austria); Üstüner, K.; Katter, M. [Vacuumschmelze GmbH & Co. KG, 63412 Hanau (Germany)

2017-03-15

Fine-grained, heavy rare earth free Nd-Fe-B sintered magnets were prepared from He jet milled powders with an average particle size of 1.5 µm by low temperature sintering at 920 °C or 980 °C. A coercivity of >1600 kA/m was achieved for an average grain size of 1.68 µm. Transmission electron microscopy showed that the distribution and composition of intergranular and grain boundary junction phases was similar to that in conventionally processed magnets. Microstructural analysis on different length scales revealed the occurrence of abnormal grain growth, which is unexpected for sintering temperatures below 1000 °C. A larger area fraction of abnormal grains was observed in the sample sintered at 920 °C compared to that sintered at 980 °C. Microtexture investigation showed a better crystallographic alignment of the abnormal grains compared to the fine-grained matrix, which is explained by a size dependent alignment of the powder particles during magnetic field alignment prior to sintering. Slightly larger particles in the initial powder show a better alignment and will act as nucleation sites for abnormal grain growth. Magneto-optical Kerr investigations confirmed the lower switching field of the abnormal grains compared to the fine-grained matrix. The demagnetisation curve of the sample sintered at 920 °C showed reduced rectangularity and this was attributed to a cooperative effect of the larger fraction of abnormal grains with low switching field and, as a minor effect, a reduced degree of crystallographic texture in this sample compared to the material sintered at 980 °C, which did not show the reduced rectangularity of the demagnetisation curve. - Highlights: • He Jet milling to reduce Nd-Fe-B grain size and to enhance coercivity. • Normal and abnormal grain growth observed for low temperature sintering. • Well oriented abnormal grown grains explained by size dependent field alignment. • Poor rectangularity is caused by low nucleation field of

Normal and abnormal grain growth in fine-grained Nd-Fe-B sintered magnets prepared from He jet milled powders