B6C3F1 mice chronically exposed to 3,3′,4,4′-tetrachloroazobenzene (TCAB), a contaminant of dichloroaniline-derived herbicides, developed a number of neoplastic and nonneoplastic...Full Text Available
Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats...Full Text Available
Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for ...
Subchronic exposure to pharmacological levels of estrogenic compounds, including 17 beta-estradiol, diethylstilbestrol, and alpha-dienestrol, significantly increased the mortality of B6C3F1 female mice...Full Text Available
The objective of this study was to determine if genistein (GEN) modulation of the immune responses might contribute to the increased host resistances to tumors. A time-course study was performed...Full Text Available
Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be involved in colorectal carcinoma metastasis with an unknown mechanism. Here we demonstrated that PRL-3 expression was...Full Text Available
Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived...Full Text Available
Stearoyl-coenzyme A desaturase (SCD) is the rate-limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. In this study, we investigated the regulation of mouse SCD1 by liver X...Full Text Available
The effect of exposure to gamma rays on LPO contents in liver, spleen and kidney of mice and the anti-lipid-peroxidation of preparations of chinonin, tannic acid and squalene were reported. All these preparations were given by intragastric perfusion. For LPO, a modified method of TBA spectrophotometry was used for determination. The results show that LPO contents in tissues increased 72 h after whole-body exposure of mice to gamma rays, that in range of 0-4 Gy, there was a linear relationship between radiation doses and LPO contents, and that all three preparations were effective in reduction of the LPO content in liver, spleen and kidney of mice, with chinonin (at dose of 0.35 mg/mouse#centre dot#day) being more effective than tannic acid (at dose of 15 mg/mouse#centre dot#day) and squalene (at dose of 0.6 mg/mouse#centre dot#day).
The elucidation on the metabolic products of the {sup 99}mTc-antibody conjugates may provide insights and approaches that would reduce the undesirable deposition of radioactive species in normal tissue. In this investigation, the radiolabeled species in blood, urine, bile and extracts of liver and kidney obtained at different times after the injection of a model antibody, {sup 99}mTc, into mice were analyzed with various chromatographic methods. Ninety-nine to 100% of the radioactivity in serum was associated with intact Mab 170. The radioactivity in liver homogenate extract was strictly protein-bound to either intact Mab or low molecular weight species (LMW). In kidney extracts, the majority of the radioactivity was protein bound {sup 99}mTc, with less than 8% of the activity being non- protein bound . Multiple {sup 99}mTc -containing protein and non-protein species were found in urine and bile. Evidence supporting the presence of {sup ...
Rat lung and liver microsomes did not undergo lipid peroxidation in the absence of iron when incubated with NADPH and concentrations of paraquat ranging from 10/sup -7/ to 10/sup -2/ M. Paraquat also did not stimulate rat liver and lung microsomal peroxidation induced by added iron and NADPH, and was inhibitory at concentrations above 10 ..mu..M. Similarly, no stimulation of peroxidation was produced by paraquat in rabbit or human lung microsomes; however, under similar conditions, paraquat enhanced NADPH/iron-dependent peroxidation in mouse lung and liver microsomes obtained from rats sacrificed at 12, 18, and 24 hr following a lethal dose of paraquat (50 mg/kg, ip), there was no loss of vitamin E or increase in susceptibility to in vitro peroxidation which would be expected if lipid peroxidation had occurred in vivo although extensive lung damage developed during this time period. These results ...
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine ...
BackgroundIn recent years, near-infrared fluorescence (NIRF)-labeled iron nanoparticles have been synthesized and applied in a number of applications, including the labeling of human cells for monitoring the engraftment process, imaging tumors, sensoring the in vivo molecular environment surrounding nanoparticles and tracing their in vivo biodistribution. These studies demonstrate that NIRF-labeled iron nanoparticles provide an efficient probe for cell labeling. Furthermore, the in vivo imaging studies show excellent performance of the NIR fluorophores. However, there is a limited selection of NIRF-labeled iron nanoparticles with an optimal wavelength for imaging around 800 nm, where tissue autofluorescence is minimal. Therefore, it is necessary to develop additional alternative NIRF-labeled iron nanoparticles for application in this area.ResultsThis study manufactured 12-nm DMSA-coated Fe3O4 nanoparticles labeled with a near-infrared fluorophore, IRDye800CW (excitation/emission, ...
Laboratory studies have been carried out to determine the toxicity of methiocarb pellets to wild trapped wood mice in order to provide some background data prior to any further evaluation of hazard in the field. In this study, wood mice were exposed to dry and to dampened methiocarb pellets in order to reproduce field trial application conditions. Field observations of methiocarb pellets indicate that the physical character changes under dry and wet weather conditions. This may affect their relative attractiveness and potential toxicity to wood mice. The laboratory assessment of exposed wood mice included measurement of brain esterase activities, methiocarb residues in selected mouse tissue, carcasses, and histological evaluation of kidney, liver and lungs.
Obesity is associated with increased susceptibility to dyslipidemia, insulin resistance, and hypertension, a combination of traits that comprise the traditional definition of the metabolic syndrome. Recent evidence suggests that obesity is also associated with the development of nonalcoholic fatty liver disease (NAFLD). Despite the high prevalence of obesity and its related conditions, their etiologies and pathophysiology remains unknown. Both genetic and environmental factors contribute to the development of obesity and NAFLD. Previous genetic analysis of high-fat, diet-induced obesity in C57BL/6J (B6) and A/J male mice using a panel of B6-ChrA/J/NaJ chromosome substitution strains (CSSs) demonstrated that 17 CSSs conferred resistance to high-fat, diet-induced obesity. One of these CSS st...
A cDNA library was constructed using RNA isolated from the livers of chickens which had been treated with zinc. This library was screened with a RNA probe complementary to mouse metallothionein-I (MT), and eight chicken MT cDNA clones were obtained. All of the cDNA clones contained nucleotide sequences homologous to regions of the longest (375 bp) cDNA clone. The latter contained an open reading frame of 189 bp, and the deduced amino acid sequence indicates a protein of 63 amino acids of which 20 are cysteine residues. Amino acid composition and partial amino acid sequence analyses of purified chicken MT protein agreed with the amino acid composition and sequence deduced from the cloned cDNA. Amino acid sequence comparison establish that chicken MT shares extensive homology with mammalian MTs. Southern blot analysis of chicken DNA indicates that the chicken MT gene is not a part of a large family of related sequences, but rather is likely to be ...
Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular-targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177 Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for 90Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case ...
A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content or the absorption, metabolism, or excretion of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific radioactivity instead, the ...
/sup 203/Pb(NO/sub 3/)/sub 2/ was administered i.v. to pregnant C57BL mice at different stages, from day 8 to day 18 of gestation. The whole animals or excised uteri were subjected to autoradiography or were autopsied for scintillation counting of excised organs. Lead appeared in embryonic and fetal tissues at all stages of gestation. Early (approx. day 8-11) lead was restricted mainly to the embryonic blood, suggesting that free lead was essentially not transferred to the embryo but may have been incorporated in the embryonic hemoglobin when the erythrocytes were formed in the yolk sac placenta (an extraembryonic membrane). From day 12 and later, an uptake was seen in the liver and the cartilaginous skeleton, and from day 14, a strong accumulation was found in calcified bone. This means that the overall fetal concentration increases successively with gestational age of the conceptus. The uptake in fetal liver may be related to the ...
"2"0"3Pb(NO_3)_2 was administered i.v. to pregnant C57BL mice at different stages, from day 8 to day 18 of gestation. The whole animals or excised uteri were subjected to autoradiography or were autopsied for scintillation counting of excised organs. Lead appeared in embryonic and fetal tissues at all stages of gestation. Early (approx. day 8-11) lead was restricted mainly to the embryonic blood, suggesting that free lead was essentially not transferred to the embryo but may have been incorporated in the embryonic hemoglobin when the erythrocytes were formed in the yolk sac placenta (an extraembryonic membrane). From day 12 and later, an uptake was seen in the liver and the cartilaginous skeleton, and from day 14, a strong accumulation was found in calcified bone. This means that the overall fetal concentration increases successively with gestational age of the conceptus. The uptake in fetal liver may be related to the erythropoiesis taking ...
Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in ...
The existence of stem cells committed to the T lymphoid lineage was deduced from studying how rat T and B stem cells differ in their expression of membrane W3/13 antigen and in their susceptibility in vivo to gamma irradiation. Stem cell activity of rat bone marrow and fetal liver was measured in long-term radiation chimeras using B and T cell alloantigenic surface markers to identify the progeny of donor cells. Monoclonal mouse anti-rat thymocyte antibody W3/13 labeled approximately 40% of fetal liver cells and 60-70% of young rat bone marrow cells (40% brightly, 25% dimly). Bright, dim, and negative cells were separated on a fluorescence-activated cell sorter. All B and T lymphoid stem cells in fetal liver were W3/13 bright, as were B lymphoid stem cells in bone marrow. W3/13 dim bone marrow had over half the T cell repopulating activity of unseparated marrow but gave virtually no B cell repopulation. ...
Understanding risks from exposures to carcinogens and other chemicals depends upon measurement of their dose to target tissues and their reactivity with critical macromolecules. The authors have used AMS detection of radio-isotopes to assess doses and reactivities at low, environmentally relevant doses. Several biomedical investigations show the effectiveness of quantification of biologically important events at extremely high sensitivity with AMS. Specifically, they have measured the addition of environmental carcinogens such as 2-amino-3,8-dimethylimidazo[4,5-f]-quinoaxaline (MelQx), a chemical found in cooked food, to DNA at concentrations relevant to human exposure. Other low level detection problems in biology, such as immunoassay assessment of small environmental chemicals, is being developed with attomole sensitivity. AMS also aids the assessment of genotoxic risks from chemicals by quantifying the binding of labeled chemicals to DNA. The very toxic and potent carcinogen, ...
The Liver Carcinogenesis Section uses the modern technologies of molecular biology, cell biology, protein chemistry and genetics to investigate the biochemical and genetic pathways involved in human liver cancer.
The liver has enormous regenerative capacity. Following acute liver injury, hepatocyte division regenerates the parenchyma but, if this capacity is overwhelmed during massive or chronic liver...Full Text Available
Development of mouse models representing human spontaneous ovarian cancer has been hampered by the lack of understanding of the etiology of this very complex disease. Mouse models representing the different...Full Text Available
AbstractThe elucidation of the human and mouse genome sequence and developments in high-throughput genome analysis, and in computational tools, have made it possible to profile entire...Full Text Available
An antiserum was raised in a rabbit against highly purified human liver dihydropteridine reductase (EC 1.6.99.7). Dihydropteridine reductase from human liver, in human cultured fibroblasts and in continuous...Full Text Available
BackgroundSince implementation of the Model for End-stage Liver Disease (MELD), the number of simultaneous liver-kidney transplantations (SLKT) has increased in the United States. However, predictors and survival benefit of SLKT compared to liver transplantation alone (LTA) are not well defined. MethodsOrgan Procurement and Transplantation Network data of patients with end-stage liver disease (ESLD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 who had not been on dialysis while on the waiting list and underwent liver transplantation between 2002 and 2008 were analyzed. To identify predictors of undergoing SLKT versus LTA, multiple logistic regression analysis was performed. Cox proportional hazards regression analysis was used to assess the association between...
Adaptive radiation therapy for liver cancer has the potential to reduce normal tissue complications and enable dose escalation, allowing the potential for tumor control in this challenging site....Full Text Available
High molecular weight DNA from pleroceroid larvae of the tapeworm Spirometra mansonoides was purified from isolated nuclei by conventional techniques. The DNA so isolated has a melting temperature (Tm) of 87 degrees C and a guanine plus cytosine (G/C) content of 44%. 5-Methyl cytosine could not be detected in plerocercoid DNA by HPLC analysis of DNA hydrolysates, by radiolabeling 5'-termini of MspI digests with polynucleotide kinase, or by comparing restriction patterns generated by MspI and HpaII. Renaturation kinetics demonstrated that the genome of S. mansonoides contains repetitive as well as single copy sequences and has a genome size estimated at approx. 1.6 X 10(9) bp. Hybridization was carried out between plerocercoid DNA and cDNAs for human beta-actin, alpha-tubulin and growth hormone (hGH). Rationale for this analysis was based on known homologies among actin and tubulin genes in numerous species and on apparent similarities between hGH and a plerocercoid growth factor that ...
Whole-body retention and excretion following a single oral dose of radiolabeled lead (/sup 203/Pb) in chronically lead-exposed pregnant BK:W mice were examined over 10-13 days. This was compared with values in similarly treated nonpregnant females and in ip injected females. Whole-body and bone retention were greater in injected than in orally dosed nonpregnant females; gastrointestinal absorption was estimated from this difference. Whole-body retention in the pups was measured at birth and at the end of the experiment. Whole-body retentions in pregnant females and in their pups at birth were significantly raised after treatment at Gestational Day 17, but not after treatment at Gestational Day 11, 14, 20, 23, or 26. Pup body burdens at birth were significantly and positively correlated with maternal retention. Measurement of radioactivity in bone, kidney, brain, heart, and liver of adults at the end of the experiments showed significantly increased levels in bone ...
Whole-body retention and excretion following a single oral dose of radiolabeled lead ("2"0"3Pb) in chronically lead-exposed pregnant BK:W mice were examined over 10-13 days. This was compared with values in similarly treated nonpregnant females and in ip injected females. Whole-body and bone retention were greater in injected than in orally dosed nonpregnant females; gastrointestinal absorption was estimated from this difference. Whole-body retention in the pups was measured at birth and at the end of the experiment. Whole-body retentions in pregnant females and in their pups at birth were significantly raised after treatment at Gestational Day 17, but not after treatment at Gestational Day 11, 14, 20, 23, or 26. Pup body burdens at birth were significantly and positively correlated with maternal retention. Measurement of radioactivity in bone, kidney, brain, heart, and liver of adults at the end of the experiments showed significantly increased levels in bone and ...
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; ...
Mouse genetic resources include inbred strains, recombinant inbred lines, chromosome substitution strains, heterogeneous stocks, and the Collaborative Cross (CC). These resources were generated through...Full Text Available
The mouse is the leading organism for disease research. A rich resource of genetic variation occurs naturally in inbred and special strains owing to spontaneous mutations. However, one can also obtain...Full Text Available
Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments....Full Text Available
The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa...Full Text Available
BackgroundThe dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin...Full Text Available
A new strain of mouse hepatitis virus (MHV) was isolated from pooled gut suspensions from an epizootic of lethal enteritis in newborn mice. Negative-contrast electron microscopy showed an abundance...Full Text Available
Recently, there has been significant progress in the development of genetically-engineered mouse (GEM) models. By introducing genetic alterations and/or signaling alterations of human pancreatic cancer...Full Text Available
The first cell lineage specification in mouse embryo development is the formation of trophectoderm (TE) and inner cell mass (ICM) of the blastocyst. This article is to review and discuss the...Full Text Available
Normal mouse epidermis constitutively expresses prostaglandin-H synthase 1 (PGHS-1) but no PGHS-2. Acute inflammation and epidermal hyperplasia, (hyperplastic transformation), as evoked in adult mouse...Full Text Available
The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated...Full Text Available
Recombinant mouse UDP-glucose pyrophosphatase (UGPPase), encoded by the Nudt14 gene, was produced in Escherichia coli and purified close to homogeneity. The...Full Text Available
Reaggregated cells from 6- to 8-day-old mouse cerebella have been used to raise antibodies in rabbits. The interaction of these antibodies with cerebellar cell surface components was assessed by cytotoxicity...Full Text Available
In preimplantation mouse development, the first cell lineages to be established are the trophectoderm (TE) and inner cell mass. TE possesses epithelial features, including apical-basal cell polarity...Full Text Available
Transgenic mouse models have contributed considerably to our understanding of the cellular and molecular mechanisms by which androgens control spermatogenesis. Cell-selective ablation of the androgen...Full Text Available
Liver paste or foie gras, which is a French term meaning fatty liver, was produced traditionally from goose and duck. Chickens are also used in the making of foie gras. The present study deals with the properties and quality of raw chicken and duck liver in comparison with manufactured liver paste (foie gras). Raw chicken liver contained 24.60% protein, 6.00% fat, 1.40 % ash, and 66.80% moisture. The average mineral values were 83.65, 50.75, 5.29, 1.15, 0.154, 0.683, 0.317 and 0.066 {mu}g/g of Fe, Zn, Cu, Mn, Cd, Pb, Ni, and Cr, respectively. The processing of liver paste (Foie gras) changed the composition of raw liver due to a loss in moisture, a release of fat and the addition of butter as a fat source. Chicken liver paste contained 27.8% moisture, 10.1% protein, 58.2% fat, and 0.8% ash. Mineral contents were 68.90, ...
Subcellular-fractionation techniques were used to characterize the endocytic pathway followed by ricin in rat liver in vivo and tentatively identify the site(s) at which the ricin interchain disulphide...Full Text Available
In a significant percentage of examined cases of fulminant hepatitis, subacute hepatitis, chronic aggressive hepatitis, liver cirrhosis and chronic persistent hepatitis, Australia (hepatitis-associated)...Full Text Available
Verapamil administered before treatment, but not after treatment, had a beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury model. The possible activation of proteases converting...Full Text Available
BackgroundThe common liver fluke Fasciola hepatica is the agent of a zoonosis with significant economic consequences in livestock production worldwide, and increasing...Full Text Available
During 1975 we studied 100 patients--77 men and 23 women--who had a history of alcohol abuse and disturbed liver function test results. On presentation the women were less likely to be suspected of...Full Text Available
Two most important causes of portal hypertension are cirrhosis of liver and non-cirrhotic portal fibrosis (NCPF). The purpose of this study was to assess the scintigraphic appearances of "9"9"mTc sulfur colloid liver scan in differentiating liver cirrhosis from NCPF. Materials and Methods: Retrospective analysis records of 146 patients (91 male and 55 female) with diffuse hepatocellular disease was done for liver size, liver uptake, spleen size, spleen uptake, colloid shift to bone marrow and lungs. Results: Cirrhotic livers showed patchy and lower uptake than NCPF (59% vs. 20%, P-value 0.041). Spleen size was significantly increased in NCPF compared to cirrhosis (100% vs. 67%, P-value 0.0137). Significant colloid shift to bone marrow was noted in cirrhosis (84% vs. 7%, P-value<0.0001). Conclusion: "9"9"mTc sulfur colloid liver scan is a ...
BackgroundEfficient and safe transection of biological tissue in liver surgery is strongly dependent on the ability to address both parenchymal division and hemostasis simultaneously....Full Text Available
In this study we compared the molecular signalling elicited by rexinoids, selective retinoid X receptor (RXR)-activators, in several organs (i.e. liver, kidney,...Full Text Available
Liver biopsies in nine of 70 male alcoholics seen during a 12 month period showed predominantly portal fibrosis with fatty change, but little or no alcoholic hepatitis. None of the 30 female alcoholics...Full Text Available
After treatment with NN-di[14C]methylnitrosamine, samples of DNA were isolated from rat livers by a conventional phenol procedure and examined for the presence of phosphotriesters. A method of capable...Full Text Available
D-galactose, a monosaccharide rapidly phosphorylated within liver cells, is irreversibly removed from the portal circulation. We have studied the kinetic relations between the hepatic cell entry process...Full Text Available
Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause...Full Text Available
Fibrogenesis is a common feature of many diseases where there is severe insult to the liver. The hepatic stellate cell trans-differentiation into a myofibroblast has been identified as an important...Full Text Available
BackgroundHepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment...Full Text Available
Phenylalanine hydroxylase was purified from crude extracts of human livers which show enzyme activity by usine two different methods: (a) affinity chromatography and (b) immunoprecipitation with an...Full Text Available
Invasive prenatal testing has become an important way to evaluate fetuses at increased risk for hereditary disorders. In utero sampling of fetal skin, liver, and muscle may be required to diagnose before-birth...Full Text Available
Background:This study evaluated the outcomes of patients with complex or persistent thoracobiliary fistulae following penetrating liver trauma, who underwent endoscopic biliary intervention...Full Text Available
ObjectivesIn old age, there are marked changes in both the structure of the liver sinusoidal endothelial cell and liver perfusion. The objective of this study was...Full Text Available
Changes in RNA synthesis in liver nuclei were observed at different ages and after hypophysectomy and hormone replacement in female Sprague-Dawley rats. As determined by the incorporation of [3H]UMP...Full Text Available
The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray...Full Text Available
The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs...Full Text Available
Enolase is a multifunctional enzyme that plays important roles in many biological and disease processes. α-Enolase from human liver (hENO1) was expressed as a soluble protein and purified by...Full Text Available
1. The effect on rat liver peroxisomal beta-oxidation of feeding diets containing various amounts of dietary oils was investigated. With increasing amounts (5-25%, w/w) of soya-bean oil an apparent,...Full Text Available
Due to the widespread clinical use of imaging modalities such as ultrasonography, computed tomography and magnetic resonance imaging (MRI), previously unsuspected liver masses are increasingly being...Full Text Available
Hepatocellular carcinoma (HCC) is one of the most critical global health issues. With frequent association of viral liver disease, HCC is highly complex, harboring both cancer and chronic liver disease....Full Text Available
Studies on alcoholic liver injury mechanisms show a significant inhibition of the proteasome activity. To investigate this phenomenon, we isolated proteasome complexes from the liver of rats...Full Text Available
The two categories of anti-albumin antibodies (AAA), namely precipitins (AA-P) and agglutinins (AA-Aggl), were investigated in 260 patients with morphologically diagnosed chronic liver diseases (CLD)....Full Text Available
MRI plays an increasingly important role for assessment of patients with chronic liver disease. MRI has numerous advantages, including lack of ionizing radiation and the possibility of performing...Full Text Available
Penetrating liver wounds are related to many causes and rank second after blunt abdominal and liver trauma. In this report are examined the clinical and radiological findings of personal series of patients with penetrating trauma, especially by firearms and stab and cut wounds. It will also tried to define the diagnostic workup of these traumas, which is especially based on CT signs of liver damage and associated changes and which is of basic importance for following treatment, both surgical or conservative. In the last seven years it was retrospectively reviewed 31 cases of penetrating liver trauma. The patients were 19 men and 12 women, ranging in age 18 to 73 (mean 42), with penetrating liver injuries from firearms (16 patients) and stab (9 cases) wounds; 6 patients had injuries from different cases. Abdominal CT was carried out in emergency with the CT Angiography (CTA) ...
It is not known whether body weight alone can adjust for the volume of liver in the calculation of the chelating dose in {beta}-thalassaemia major patients, who frequently have iron overload and hepatitis. The hypothesis is that liver volume in children and adolescents suffering from {beta}-thalassaemia major is affected by ferritin level and liver function. Thirty-five {beta}-thalassaemia major patients aged 7-18 years and 35 age- and sex-matched controls had liver volume measured by MRI. Serum alanine aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia major patients. Body weight explained 65 and 86% of the change in liver volume in {beta}-thalassaemia major patients and age-matched control subjects, respectively. Liver volume/kilogram body weight was significantly higher (P<0.001) in thalassaemia major patients than in control ...
Isolated situs inversus of the stomach with otherwise normal position of the thoracic and abdominal viscera is an extremely rare anomaly occurring in two distinct forms. Because of its close relationship to the liver, the right-sided stomach may produce interesting and confusing changes in the liver scan. Two cases illustrate the radiologic features of the two principal types of isolated congenital dextrogastria and the effect of one type on the liver scan.
Intrahepatic cholangiocarcinoma is the second most common primary malignant hepatic neoplasm. We describe two cases of intrahepatic cholangiocarcinoma which initially presented as liver abscess both clinically and radiologically. Mucin-hypersecretion from the tumor cells and extensive necrosis or secondary bacterial infection was responsible for the radiologic appearance of a liver abscess.=20
α1-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation...Full Text Available
Deer Elk Bighorn Sheep American Pronghorn Moose Deer Mouse Carnivores Bobcat American Badger River Otter Red Fox Long-Tailed Weasel Coyote Grizzly Bear Mountain Lion Amphibians...
Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics...Full Text Available
The extent (density and diameter) of the native (preexisting) collateral circulation in healthy tissues and the capacity of collaterals to enlarge/remodel in obstructive arterial disease are important...Full Text Available
In mammals, primordial germ cells (PGCs) are generated in the extra-embryonic epiblast, and thereafter migrate into the developing gonads. Following the development of the gonads to the testes or ovaries, germ cells mature into sperms or eggs. In the present study, we report production and characterization of monoclonal antibodies (MAb) that recognize PGCs. Extracts from E12.5 mouse embryonic gonads were immunized as an antigen, and hybridomas were generated using the rat medial iliac lymph node method. The hybridoma supernatants were screened by immunohistochemical analyses of E12.5 mouse embryonic sections. The antibody, referred to herein as MAb 5B5, provided strong signals on PGCs. Moreover, immunofluorescence analyses using a variety of the tissue sections of mouse embryos revealed th...
These proceedings collect papers on the subject of lymphokines. Topics include: DNA-cloning of mouse and human lymphokine genes, inteferons, interleukins, gene expression, tumor necrosis factors, and recombinant DNA.
... accidentally released from a Soviet military laboratory (Meselson ... Robert Koch and Louis Pasteur worked to introduce ... species (eg, rat, mouse, dog, monkey) for ...
A successful boron neutron capture treatment (BNCT) of a patient with multiple liver metastases has been first given in Italy, by placing the removed organ into the thermal neutron column of the Triga research reactor of the University of Pavia. In Finland, FiR 1 Triga reactor with an epithermal neutron beam well suited for BNCT has been extensively used to irradiate patients with brain tumors such as glioblastoma and recently also head and neck tumors. In this work we have studied by MCNP Monte Carlo simulations, whether it would be beneficial to treat an isolated liver with epithermal neutrons instead of thermal ones. The results show, that the epithermal field penetrates deeper into the liver and creates a build-up distribution of the boron dose. Our results strongly encourage further studying of irradiation arrangement of an isolated liver with epithermal neutron fields.
Summary Background Systematic screening for liver fibrosis in heavy-drinking patients is a challenge. Aims To assess Fibroscan for non-invasive diagnosis of asymptomatic liver fibrosis in alcohol abuse patients, to determine diagnostic liver stiffness cut-off values and to compare performance of Fibroscan with seven non-invasive laboratory tests. Methods One hundred and three alcoholic patients were studied. Liver fibrosis was staged by METAVIR system. Fibroscan, Fibrotest, Fibrometer, Hepascore, APRI, PGA, PGAA and hyaluronic acid tests were performed. Liver stiffness cut-offs were determined using receiver-operating characteristic (ROC) curves. Results Liver stiffness was correlated with fibrosis (r = 0.72, P < 0.014), with median at 5.7, 6.3, 8.4, 15 and 47.3 kPa for F0 (n = 8), F1 (n =...
Two monoclonal antibodies, TAL-1B5 and TAL-3C3, specific for human Ia alpha-chain subunits have been produced by fusing P3/NSI/1-Ag4-1 mouse myeloma cells with spleen cells from a BALB/c mouse immunized...Full Text Available
Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose...Full Text Available
PurposeTo characterize differences in retinal ganglion cell (RGC) function in mouse strains relevant to disease models. C57BL/6J (B6) and DBA/2J (D2) are the two most common mouse...Full Text Available
To assess whether ring enhancements of liver metastases on Mn-DPDP enhanced, early MR images were well visualized on delayed images, as compared with those of hepatocellular carcinomas (HCC), and to investigate the detection accuracy and conspicuity of each tumor. Twenty patients with liver metastases and 15 with HCC were studied by Mn-DPDP enhanced, T1-weighted MR images. Peripheral ring enhancement and conspicuity were investigated. Differences in detection accuracy and frequency of ring enhancement in liver metastases and HCC were assessed. In liver metastases (n= 69), 44 cases (63.8%) without ring enhancement and 25 (36.2%) with were noted on early images. Sixteen cases (23.2%) without ring enhancement, 38 (55.1%) with ring enhancement similar to the early images, and 15 (21.7%) with prominent ring enhancement were noted on delayed images. In HCC (n=37), 36 cases (97.3%) without ring enhancement and ...
Although the radioisotope liver scan has primarily been of use in the detection of the intra-hepatic space occupying lesions, there has been an increasing awareness of its use in evaluation of liver function. In this study, the degree of hepatomegaly, changes in shape and mottling radiodensity on each lobe and splenic visualization in the liver scans done with colloidal radiogold were numerically expressed as scores under the arbitrary standard in 210 patients with liver cirrhosis. The clinical value of this scoring system was studied with special regards to the correlation between the radiogold hepatic uptake half time and conventional liver function tests. Following were the results; 1) The normal scan appeared in 6.7% of 210 patients with liver cirrhosis. 2) The colloidal radiogold hepatic uptake half time was abnormally and progressively prolonged in ...
The human smooth muscle myosin heavy chain locus (MYH11) was mapped by fluorescence in situ hybridization to the middle of the p arm of chromosome 16 using a genomic cosmid clone containing coding sequences of the gene as probe. Probe from coding sequence, when applied to Southern blots of a panel of hybrids containing different portions of human chromosome 16, localized the gene to 16p13.13-13.12. Coding sequence PCR primers, when used on the DNA from a CHO-mouse hybrid clone mapping panel informative for mouse chromosomes, showed that the gene was located on mouse chromosome 16. These results correct a recent assignment of MYH11 from 16q12.2 to the region of the 16p-arm inversion breakpoint seen in acute myelomonocytic leukemia (AMML) M4Eo and demonstrate that the conflicting data do not result from the presence of additional MYH genes on the q arm of the chromosome. Also, a new region of conserved synteny between human ...
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that factor(s) in the mouse ...
Staging bone scans or skeletal surveys were obtained of 97 patients with endometrial carcinoma. Of the 77 patients with Stage I or II disease, no metastases were identified at staging. Three patients in the entire series demonstrated bony metastases; all of these metastases were detectable by radionuclide bone scan and radiographic bone survey. Eighty-nine patients were examined with radionuclide liver/spleen scanning at the time of staging. Four of the 89 initial scans were interpreted as demonstrating hepatocellular disease, and all four patients had abnormal liver function studies. Only one patient demonstrated a possible hepatic metastasis at initial diagnosis. This patient also had abnormal liver function studies. Based on these results, bone surveys and radionuclide bone scans are not indicated as screening procedures in endometrial carcinoma. It is suggested that screening for liver metastases in ...
To evaluate the effect of plugging the biopsy tract in rabbit liver and the pathologic changes caused by plugging materials. Thirty-two New Zealand White rabbits were divided into four groups (eight rabbits in each) and compared with one another. They were labeled group A (control), B (gelfoam), C (fibrin sealant) or D (NBCA). the liver was exposed and biopsied with an 18G disposable biopsy gun. The inner Tru-cut needle was withdrawn and plugging was undertaken through the outer cannula of the biopsy gun. Bleeding times of each material were compared. The rabbits were sacrificed and pathologically evaluated for 17 days.
In acute liver failure following hepatitis, toxic insults, or after major liver surgery, there is an increased bacterial translocation from the gut. This may explain some of the infectious complications seen in these conditions. To elucidate mechanisms and find possible preventive measures, we investigated the effect of rectal administration of arginine and probiotic bacteria (Lactobacillus spp.) on bacterial translocation and the extent of liver failure. Sprague-Dawley rats were used and five different Lactobacillus strains (Lb. reuteri R2LC, Lb. rhamnosus DSM 6594 (= strain 271), Lb. plantarum DSM 9843 (= strain 299v), Lb. fermentum 8704:3 (= strain 245), and Lb. reuteri (= strain 108) were administered rectally once daily for 8 days with and without 2% arginine. Acute liver injury (ALI) was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight), and samples ...
A study was made of the uncoupling action of polychlorinated biphenyls (Kanechlor-400) on oxidative phosphorylation in rat liver mitochondria. Kanechlor-400 (KC-400) at 20 ..mu..g/ml stimulated state 4 respiration of rat liver mitochondria more than 4-fold with ..cap alpha..-ketoglutarate/malate as a substrate, and released the oligomycin-inhibited state 3 respiration. KC-400 also dissipated the membrane potential across the mitochondrial membranes; thus, it acts as an uncoupler of oxidative phosphorylation in rat liver mitochondria. KC-400 altered the permeability properties of mitochondrial membranes as evidenced by the release of endogenous K/sup +/ and the oxidation of exogenously supplied NADH. It is concluded that KC-400 produces a nonspecific increase in mitochondrial ion permeability, thereby dissipating membrane potential, which leads to the uncoupling.
SummaryMammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to...Full Text Available
Mycosis fungoides (MF) in deep-seated lymph nodes, spleen or liver appears to be associated with a lack of response of the disease to topical external therapy. Fourteen patients with mycosis fungoides...Full Text Available
Hypophosphatasia is a congenital disease characterized by deficiency of serum and tissue non-specific alkaline phosphatase activity. The disease occurs due to mutations in the liver/bone/kidney alkaline...Full Text Available
BackgroundHealth service databases of administrative type can be a useful tool for the study of progression of a disease, but the data reported in such sources could be affected...Full Text Available
Coumarin (1,2-benzopyrone) is occurring in food, and is also used in cosmetics. In order to perform a risk assessment for both oral and dermal exposure, we applied a physiologically based approach to model kinetics in humans by simulating both routes of exposure. The concentration-time profile in liver revealed a higher peak concentration (Cmax-hep) for the oral when compared to the dermal route. The area under the concentration-time curve in the liver (AUChep) was found the same for both routes if the same extent of absorption is assumed. Dose response information from published rat studies were used to identify the metric relevant for liver toxicity. Liver exposure levels resulting from doses and durations as outlined in the studies were simulated in a rat model. We obtained 31 data pair...
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with major morbidity and mortality. Therapeutic management is difficult, due to lack of conclusive data and individual disease...Full Text Available
Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of {sup 188}Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of {sup 188}Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of {sup 188}Re-TDD is a promising agent for liver cancer therapy.
Acute {gamma}-irradiation of rats at doses of 100 and 270 Gy stimulates lipid synthesis and changes the lipid composition of liver cell organelles. The content of cholesterol and cholesterol esters in microsomes increased at 100 Gy and decreased at 270 Gy, with total phospholipid content remaining unchanged. The lipid content in mitochondria decreased considerably 1 h after irradiation at 270 Gy. This change was significantly less pronounced 47 h later. Under chronic {gamma}-irradiation (0.129 Gy/day), cholesterol and cardiolipin in mitochondria increased. The changes in lipid content caused by acute irradiation are presumed to be related to activated synthesis of lipids in the liver. The modification of the lipid content of mitochondria observed in chronically irradiated rats may indicate that energy-metabolizing liver cell systems are involved in the adaptation to irradiation.
PURPOSE OF REVIEW: To review the recent literature on the prognostic value of biomarkers of liver fibrosis and impaired liver function in patients with chronic hepatitis C with or without HIV coinfection. RECENT FINDINGS: A combination of standard blood tests seems to be useful in identifying patients at risk of liver-related complications. Findings from studies investigating the validity of the Model for End-Stage Liver Disease (MELD) score in HIV-infected liver transplant candidates are conflicting. Two large studies of HIV/hepatitis C virus (HCV) coinfected patients have shown that plasma levels of the fibrosis marker hyaluronic acid are a strong predictor of clinical complications. A smaller study found hyaluronic acid and two other fibrosis tests, aspartate aminotransferase-to-platelet ratio index (APRI) and Fib-4, to be independent predictors of mortality when included in ...
Maintenance of genomic integrity in embryonic cells is pivotal to proper embryogenesis, organogenesis and to the continuity of species. Cultured mouse embryonic stem cells (mESCs), a model for early embryonic cells, differ from cultured somatic cells in their capacity to remodel chromatin, in their repertoire of DNA repair enzymes, and in the regulation of cell cycle checkpoints. Using 129XC3HF1 mESCs heterozygous for Aprt, we characterized loss of Aprt heterozygosity after exposure to ionizing radiation. We report here that the frequency of loss of heterozygosity mutants in mESCs can be induced several hundred-fold by exposure to 5-10Gy of X-rays. This induction is 50-100-fold higher than the induction reported for mouse adult or embryonic fibroblasts. The primary mechanism underlying the...
Abstract Crouzon syndrome is characterized by premature fusion of sutures and synchondroses. Recently, the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of micro-computed tomography (CT) scannings of the skulls of wild-type mice and Crouzon mice were analysed with respect to the dysmorphology caused by Crouzon syndrome. A computational craniofacial atlas was built automatically from the set of wild-type mouse micro-CT volumes using (1) affine and (2) non-rigid image registration. Subsequently, the atlas was deformed to match each subject from the two groups of mice. The accuracy of these registrations was measured by a comparison of manually placed landma...
1. Novel methods, using L-[ring-2-14C]tryptophan, are described for the measurement of tryptophan 2,3-dioxygenase activity and tryptophan accumulation in isolated rat liver cells. 2. The effects of...Full Text Available
A recombinant M13 clone (O42) containing a 65 b.p. cDNA fragment from human fetal liver mRNA coding for glyceraldehyde-3-phosphate dehydrogenase has been identified and it has been used to isolate from...Full Text Available
Non-alcoholic fatty liver disease is a serious health problem linked to obesity and type 2 diabetes. To investigate the biological outcome and therapeutic potential of hepatic fatty acid uptake inhibition,...Full Text Available
AimsThe prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated.Full Text Available
A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n=18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control "sham-operated" liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human ...
Ribosomal protein L 10 from the livers of trout, hen, and rat was found to be the main target for 2-nitro-4-azidobenzoyl-Phe-tRNA in affinity labelling experiments. Therefore, despite somewhat different electrophoretic mobilities, this protein seems to be involved in the organization of the peptidyl transferase centre in ribosomes of various vertebrates. (author).
Virtually all biomedical research makes use of a relatively small pool of laboratory-adapted, inbred, isogenic stocks of mice. Although the advantages of these models are many, there are a number of...Full Text Available
Significant emphasis has recently been placed on the characterization of the human cancer genome. This effort has been assisted by the development of new DNA sequencing technologies that allow...Full Text Available
Dominant mutations in sarcomere protein genes cause hypertrophic cardiomyopathy, an inherited human disorder with increased ventricular wall thickness, myocyte hypertrophy, and disarray. To understand...Full Text Available
The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I...Full Text Available
Advances in laboratory animal imaging have provided new resources for noninvasive biomedical research. Among these technologies is microcomputed tomography (microCT) which is widely used to obtain high...Full Text Available
BackgroundXenotropic Murine Leukemia Virus-related (XMRV) virus is a recently identified mouse gammaretrovirus that has the ability to infect certain human cells. In this study,...Full Text Available
As part of a combined study of the responses of the mouse adrenal gland and kidney to X-irradiation, the weight of adrenal glands, the relative volumes of the cortex and medulla and the aldosterone output were measured at predetermined times after irradiation of the left organs only.
Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium...Full Text Available
This unit presents two basic protocols that offer rapid assessments of anosmia (the absence of a sense of smell) in mice. The buried food test is used to check for the ability to smell volatile...Full Text Available
The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged ...
AbstractStudies performed to identify early events of ovarian cancer and to establish molecular markers to support early detection and development of chemopreventive regimens have been...Full Text Available
... from Dr. Austin Smith of the Institute for Stem Cell Research, University of Edinburgh) was modified from the CGR8 ... to thank Dr. Austin Smith, the Institute for Stem Cell Research, University of Edinbu...
Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is...Full Text Available
The activity of mice in their home cage is influenced greatly by the cycle of light and dark. In addition, home-cage activity shows remarkable time-dependent changes that result in a prominent temporal...Full Text Available
We have studied the functions of the intracellular RNAs of mouse mammary tumor virus (MMTV) by purification and translation in vitro. Two major size classes of MMTV RNA, 35S and 24S RNA, were isolated...Full Text Available
Trichloroethylene (TCE) is both acutely toxic and carcinogenic to the mouse lung following exposure by inhalation. In contrast, it is not carcinogenic in the rat lung and is markedly less toxic following...Full Text Available
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression...Full Text Available
BackgroundSeasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies...Full Text Available
Mouse models for the study of autistic-like behaviors are increasingly needed to test hypotheses about the causes of autism, and to evaluate potential treatments. Both the automated 3-chambered...Full Text Available
Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome type B) is a metabolic disorder with devastating clinical characteristics starting in early childhood and leading to premature death. A...Full Text Available
Vulnerability to abused drugs is influenced by multiple genes unique to each drug as well as to risk genes for polydrug abuse. If several inbred mouse strains respond to different drugs similarly,...Full Text Available
The integration sites for viral DNA in cells infected with Moloney murine leukemia virus (M-MuLV) were studied by restriction endonuclease cleavage of cellular DNA followed by electrophoresis in agarose...Full Text Available
PurposeThe size of neuronal populations is modulated by gene variants that influence cell production and survival, in turn influencing neuronal connectivity, function,...Full Text Available
Background:Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of...Full Text Available
Early detection of precancerous tissue has significantly improved survival of most cancers including colorectal cancer (CRC). Animal models designed to study the early stages of cancer are valuable...Full Text Available
The formation of mammalian secondary palate requires a series of developmental events such as growth, elevation and fusion. Despite recent advances in the field of palate development, the process...Full Text Available
BackgroundMacrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized...Full Text Available
The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII...Full Text Available
Purpose: Small animal micro-CT imaging is being used increasingly in preclinical biomedical research to provide phenotypic descriptions of genomic models. Most of this imaging is coincident...Full Text Available
In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls...Full Text Available
BackgroundApolipoprotein E (ApoE), a cholesterol carrier associated with atherosclerosis, is a major risk factor for Alzheimer's disease (AD). The low-density lipoprotein receptor...Full Text Available
The AKR mouse strain is characterized by a high incidence of spontaneous thymic lymphoma that appears in older animals (greater than 6 months of age) and is associated with novel provirus integrations...Full Text Available
There is increasing consensus that the uterotrophic estrogenicity assay should be coupled with other morphometric or molecular end points that might enhance its sensitivity. We have previously shown...Full Text Available
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human...Full Text Available
Mouse models have dramatically improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic...Full Text Available
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin(-)CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. Furthermore, this p53-null mouse mammary ...
BackgroundThe zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In...Full Text Available
BackgroundDue to the high morbidity and mortality of fulminant hepatitis, early diagnosis followed by early effective treatment is the key for prognosis improvement. So far, little...Full Text Available
BackgroundRecessive mutations in guanylate cyclase-1 (Gucy2d) are associated with severe, early onset Leber congenital amaurosis-1(LCA1). Gucy2d...Full Text Available
Inactivation of the RB tumor suppressor and activation of the MYC family of oncogenes are frequent events in a large spectrum of human cancers. Loss of RB function and MYC activation are thought to...Full Text Available
Fibroblast cell population kinetics in the developing molar periodontal ligament was investigated in 10, 12, 16 and 20 days old mice by autoradiography after the administration of [3H]thymidine. Labelled...Full Text Available
BackgroundNon-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize....Full Text Available
BackgroundBrevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in...Full Text Available
In the present study we have used the alkaline elution technique to study the effect of misonidazole (MISO) on the initial amount of DNA cross-linking in various normal and neoplastic tissues of C3H...Full Text Available
During asymmetric mitosis, both in male Drosophila germline stem cells and in mouse embryo neural progenitors, the mother centrosome is retained by the self-renewed cell; hence suggesting...Full Text Available
BackgroundDiurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling...Full Text Available
While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here...Full Text Available
Oocyte-cumulus cell bidirectional communication is essential for normal development of the oocyte and cumulus cells (CCs) within the follicle. We showed recently that addition of recombinant growth...Full Text Available
NG2 chondroitin sulfate proteoglycan is a surface marker of oligodendroglial progenitor cells (OPCs) in various species. In contrast to well-studied rat OPCs, however, we found that purified...Full Text Available
A novel therapeutic compound was found to induce bladder tumors in male rats. Given the location of the tumors and the increased amounts of calcium- and magnesium-containing solids found in the urine...Full Text Available
Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that has been linked to the phenotypes of obesity and type II diabetes. We recently reported that UCP2 expression is increased...Full Text Available
A tk{sup +/-} mouse embryonic stem (ES) cell line, designated 1G2, has been created in which one allele of the thymidine kinase (tk) gene was inactivated by targeted homologous recombination. This line is an analog of the mouse lymphoma tk{sup +/-} L5178Y cell line, which is used widely to assess the mutagenicity of chemical agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea (ENU) resulted in a dose-related increase in tribluorothymidine-resistant colonies. Mutant frequencies of 152 and 296 per 10{sup 6} cells were determined for 0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of 15 per 10{sup 6} cells. The data indicate that tk{sup +/-} 1G2 ES cells may be useful for the creation of a transgenic mouse model for assessing in vivo mutation using an endogenous autosomal gene. 45 refs., 2 figs., 1 tab.
OBJECTIVEPrevious studies showed that genetic deletion or pharmacological blockade of the receptor for advanced glycation end products (RAGE) prevents the early structural changes...Full Text Available
Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required to generate spontaneous...Full Text Available
Changes in the number of chromosomes, but also variations in the copy number of chromosomal regions have been described in various pathological conditions, such as cancer and aneuploidy, but also in...Full Text Available
Self-renewal of spermatogonial stem cells (SSCs) is the foundation for maintenance of spermatogenesis throughout life in males and for continuation of a species. The molecular mechanism underlying stem...Full Text Available
BackgroundMammalian antimicrobial peptides (AMPs) are effectors of the innate immune response. A multitude of signals coming from pathways of mammalian pathogen/pattern recognition...Full Text Available
Mice were killed 7, 11, 19, and 27 weeks after infection with strains of Schistosoma mansoni from Puerto Rico, Brazil, St Lucia, and Tanzania. The percentage recovery of adult worms...Full Text Available
We report the isolation of cDNA clones for the mouse {alpha}7 neuronal nicotinic acetylcholine receptor subunit (gene symbol Acra7), the only nicotinic receptor subunit known to bind a-bungarotoxin in mammalian brain. This gene may have relevance to nicotine sensitivity and to some electrophysiologic findings in schizophrenia. The mouse {alpha}7 subunit gene encodes a protein of 502 amino acids with substantial identity to the rat (99.6%), human (92.8%), and chicken (87.5%) amino acid sequences. The {alpha}7 gene was mapped to mouse chromosome 7 near the p locus with the following gene order from proximal to distal: Myod1-3.5 {+-}1.7 cM-Gas2-0.9 cM {+-} 0.9 cM-D7Mit70-1.8 {+-} 1.2 cM- Acra7-4.4 {+-}1.0 cM-Hras1-ps11/Igf1r/Snrp2a. The human gene was confirmed to map to the homologous region of human chromosome 15q13-q14. 26 refs., 3 figs.
During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates...Full Text Available
We sought to determine the effects of activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male...Full Text Available
BackgroundA fundamental requirement for the exploitation of embryonic stem (ES) cells in regenerative medicine is the ability to reproducibly derive sufficient numbers of cells of...Full Text Available
Cultured mouse or human embryonic stem (ES) cells provide access to all of the genes required to elaborate the fundamental components and physiological systems of a mammalian cell. Chemical or insertional...Full Text Available
BackgroundStorage of RBCs is necessary for an adequate blood supply. However, reports have identified potential negative sequelae of transfusing stored RBCs. An animal...Full Text Available
SUMMARYAmeloblastin (AMBN) is the second most abundant extracellular matrix protein produced by the epithelial cells called ameloblasts and is found mainly in forming dental enamel....Full Text Available
Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified...Full Text Available
Full text: Tumour ablation with radiofrequency (RF) energy is a relatively new procedure for the treatment of focal malignant disease. At our institution this is currently being used in the treatment of certain liver and lung lesions with the patients involved being enrolled in clinical trials. The poster describes the technique used at our institution for the placement of the radiofrequency ablation electrode using CT fluoroscopy. Criteria for patient selection are included. Complications from the procedure are described, as well as follow up appearances and results. Our results from the treatment of primary and secondary lesions in the liver correlate well with published literature. Treatment is still not as successful as surgical resection but there is significantly less morbidity. Where this method may be appropriate is when the patient is not a candidate for surgical resection. The treatment of colorectal metastases in the lung shows early ...
Survival curves were constructed from dose-incidence curves for apoptosis in the crypts of mouse small intestine, using the number of apoptotic cells after high doses (N{sub M}) as maximum cell population size. The mean lethal doses (D{sub 0}) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both D{sub 0} and N{sub M} values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. (author).
The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various ...
The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 ...
Computed tomography would be a better method to detect and characterize a Thorotrast-induced liver tumour. The selective opacification of the RES by Thorotrast creates an intrinsic opacification of the liver similar in effect to contrast agents being evaluated for liver CT, such as ethoioidized oil emulsion. The computed tomographic appearance of Thorotrast-associated cholangiocarcinoma is usually a large, inhomogenous mass composed of disordered area of tissue of high density due to Thorotrast deposits, and of very low density. Thorotrast-induced cholangiocarcinoma originates in the peripheral biliary tree suprounding the highest mean concentration of Thorotrast deposition, so that visible soft tissue masses in the higher density spots in the liver are not produced in the early stage. The tendency for the opacity of the liver to decrease slowly with time and result in an uneven ...
Cholangiocarcinoma is synonymous with bile duct carcinoma, and can originate in a small intrahepatic bile duct (peripheral type), a major intrahepatic duct including the hepatic hills, an extrahepatic duct, or near the papilla of Vater (central type). In a sense bile duct carcinoma of the peripheral type is cholangiocarcinoma of the liver; it has the same gross configuration as hepatocellular carcinoma, resulting in difficulty to differentiate on the CT. The authors studied CT findings of 14 cases of pathologically proven peripheral type cholangiocarcinoma of the liver during the last 4 years. The results were as follows: 1. Of 14 cases, 8 were female and 6 were male, and the age ranged from 5th to 7th decades. 2. Preoperative clinical diagnosis were as follows: hepatoma 8 cases, abscess 5 cases and metastasis 1 case in order of frequency. 3. Diagnosis were confirmed by hepatic lobectomy in 7 cases, wedge resection in 5 cases and needle biopsy ...
Blood kinetics and tissue distribution of 20, 80 and 110 nm silver nanoparticles were investigated in rats up to 16 days after intravenous administration once daily for 5 consecutive days. Following both single and repeated injection, silver nanoparticles disappeared rapidly from the blood and distributed to all organs evaluated (liver, lungs, spleen, brain, heart, kidneys and testes) regardless of size. The 20 nm particles distributed mainly to liver, followed by kidneys and spleen, whereas the larger particles distributed mainly to spleen followed by liver and lung. In the other organs evaluated, no major differences between the sizes were observed. Size-dependent tissue distribution suggests size-dependent toxicity and health risks. Repeated administration resulted in accumulation in li...
An assessment was undertaken of the risk of liver cancer in the USA associated with aflatoxin ingestion from peanuts. Both laboratory-animal data and epidemiological data collected from the scientific literature and several prominent mathematical extrapolation techniques were used. Risk estimates differed by a factor of greater than 1000 when the extrapolated results of three selected animal studies were analysed. Dose-response data for the male Fischer rat, the most sensitive mammalian species studied, produced an estimate of 158 cases of liver cancer per year in the USA at current levels of aflatoxin exposure. An estimate of 58 annual cases was predicted on the basis of epidemiological data of populations in Africa and Thailand.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease involving multiple hematopoietic cell lines. Characteristics of PNH are intrinsic hemolytic anemia, iron deficiency anemia and venous thrombosis. We report a case of PNH with characterostoc MR and CT findings. The signal intensity of renal cortex was lower than that of medulla on both T1-and T2-weighted MR imaging. On T2 weighted MR images, the liver showed very low signal intensity but the signal intensity of the spleen was normal. On precontrast CT the attenuation of renal cortex was higher than that of renal medulla and the attenuation of liver was higher than that of the spleen. These findings of MR imaging and CT were the result from the deposition of hemosiderin in the cells of proximal convoluted tubules and transfusional hemosiderosis of liver.
The distribution of Lipiodol in the liver and lungs following arterial or portal injection was studied in normal (n=55) and cirrhotic rats (n=20). Using magnified xeroradiography and radioisotope labeled tracers, it was found that Lipiodol was deposited mainly in the liver and lung after either arterial or portal administration. In control rats after arterial injection, deposits in the lung peaked after 2 hours and gradually declined over 48 hours; whereas after portal injection, the deposit steadily increased for 48 hours. Twenty-five percent of cirrhotic rats demonstrated a Lipiodol-induced miliary pattern in the lung. An increased number of portosystemic shunts in cirrhotic rats was also noted. These results suggest that cirrhosis of the liver may be a potential risk factor for developing pulmonary complications after Lipiodol administration. (orig.).
The present study was designed with an aim to analyze the effect of acute aluminium phosphide (ALP) exposure (10mg/kg b.wt, intragastrically) on the kinetic characteristics of cytochrome oxidase and energy metabolism in male Wistar rat liver mitochondria. Liver mitochondrial preparations from ALP-treated rats exhibited significant decrease (66%) in the activity of cytochrome oxidase suggesting that there was a decrease in the catalytic efficiency of the active oxidase molecules on ALP treatment. The decreased activity of cytochrome oxidase with altered NADH and succinic dehydrogenase activities might have contributed towards a significant decline in state 3 and state 4 respiration as observed. These alterations in the electron transport chain complexes in turn adversely affected the ATP sy...
Nano-sized silica is a promising material for disease diagnosis, cosmetics and drugs. For the successful application of nano-sized material in bioscience, evaluation of nano-sized material toxicity is important. We previously found that nano-sized silica particles with a diameter of 70nm showed acute liver failure in mice. Here, we performed histological analysis of major organs such as the liver, spleen, lung, kidney, brain and heart in mice, chronically injected with 70-nm silica particles for 4weeks. Histological analysis revealed hepatic microgranulation and splenic megakaryocyte accumulation in these 70-nm silica particles treated mice, while the kidney, lung, brain and heart remained unaffected. Thus, liver and spleen appear to be the major target organs for toxicity by the chronic a...
14 surgical patients with non-hepatobiliary diseases were studied with "9"9"mTc-EHIDA imaging to evaluate the effect of total parenteral nutrition (TPN) on the hepatobiliary function. Duration of TPN ranged from 6-56 days, 10 of the 14 patients Beijing within 10 days. The results showed that: (1) 11 of 14 patients had abnormal scintigraphic features. The most prominet findings were delayed liver excretion and prolonged blood clearance time. This fact suggests that not only the rate of excretion of the bile from the liver is decreased but the uptake ability of the hepatorcyte is also impaired. (2) The effect of TPN on liver function is reversible. It was concluded that in order to prevent irreversible damage of hepatobiliary function caused by TPN, the duration of TPN should not be too long and oral intake of nutrients should be resumed as soon as possible.
Abstract NorUDCA (24 norursodeoxycholic acid), the C23 homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine conjugated UDCA (C24) and norUDCA (C23) in isolated perfused rat liver (IPRL) and in natrium/taurocholate cotransporting polypeptide (Ntcp) transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predomi...
Glucose homeostasis requires the tight regulation of glucose utilization by liver, muscle and white or brown fat, and glucose production and release in the blood by liver. The major goal of maintaining glycemia at -5 mM is to ensure a sufficient flux of glucose to the brain, which depends mostly on this nutrient as a source of metabolic energy. This homeostatic process is controlled by hormones, mainly glucagon and insulin, and by autonomic nervous activities that control the metabolic state of liver, muscle and fat tissue but also the secretory activity of the endocrine pancreas. Activation or inhibition of the sympathetic or parasympathetic branches of the autonomic nervous systems are controlled by glucose-excited or glucose-inhibited neurons located at different anatomical sites, mainl...
Copper bioavailability was studied in rats using an extrinsic Cu label. Copper absorption from sunflower seeds (46%), peanuts (41%), cooked shrimp (50%), and cooked beef (40%) was as good or better than copper sulfate (46%). Copper from plant foods (sunflower seeds, garbanzo beans, peanuts) was absorbed equally as well as copper from animal foods (beef, shrimp, chicken liver), 39 +/- 7% vs 43 +/- 7%, P greater than 0.05. There was no significant difference in percentage Cu absorption between intrinsically labeled chicken liver and extrinsically labeled chicken liver. In a second experiment, Cu absorption was measured in the presence of glucose, fructose, sucrose, or cornstarch. There were no significant differences in Cu absorption due to different carbohydrates in a single meal.
Adaptive radiation therapy for liver cancer has the potential to reduce normal tissue complications and enable dose escalation, allowing the potential for tumor control in this challenging site. Using adaptive techniques to tailor treatment margins to reflect patient-specific breathing motions and image-guidance techniques can reduce the high dose delivered to surrounding normal tissues while ensuring that the prescription dose is delivered to the tumor. Several treatment planning and delivery techniques have been developed for use in the liver, including a margin to encompass the full breathing motion, mean position techniques, which evaluate the probability of tumor location during breathing, breath hold, gating, and tracking. Patient selection, clinical workflow, and quality assurance m...
The authors have studied the distribution of H-3 labelled schistosomicidal drug in mice by autoradiography. The H-3-labelled substances were found in liver and kidney and in successfully decreasing amounts in brain, lung, heart, fat, testis, pancreas and spleen. In various cells the silver granules were present mainly in the cytoplasms but a few in the nucleus. After administration of this labelled schistosomicidal drug, the mice were killed and studied in groups successively at 4, 8, 24 hrs. No difference in the distribution of silver granules were observed. This fact indicated that, this drug was rapidly absorbed and highly concentrated with a long duration of reservation in liver. All of these favours the schistosomicidal effect of the drug. As this drug was highly concentrated in the cytoplasm of liver cells, that might provide a pathophysiologic basis for the explanation of jaundice in the clinical practice. Moreover, ...
Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic ...
Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the calculation of the absorbed ...
Recently, a novel DNA virus designated SEN virus (SEN-V), which is thought to be related to posttransfusion hepatitis, was discovered. The aim of the present study was to clarify the relationship between...Full Text Available
BackgroundSelection programs for growth and stress traits in cultured fish are fundamental to the improvement of aquaculture production. The gilthead sea bream (Sparus aurata)...Full Text Available
Miriplatin, a cisplatin derivative with a high affinity for iodized oil, is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma. This case report...Full Text Available
An overall hypothesis for benzene-induced leukemia is proposed. Key components of the hypothesis include a) activation of benzene in the liver to phenolic metabolites; b) transport of these metabolites...Full Text Available
BackgroundThis study focuses on the role of an Internet-based group for people who have an autoimmune liver disease, primary biliary cirrhosis. Primary biliary...Full Text Available
Syndrome X is a combination or co-occurrence of several known cardiovascular risk factors (including central obesity, dyslipidemias, fatty liver disease, hyperinsulinemia, insulin resistance,...Full Text Available
Hibernators are unique among mammals in their ability to survive extended periods of time with core body temperatures near freezing and with dramatically reduced heart, respiratory, and metabolic rates...Full Text Available
Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional...Full Text Available
BackgroundTransarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers...Full Text Available
Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. We have investigated whether common cellular DNA domains might be rearranged, possibly...Full Text Available
Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different ...
Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different ...
Thiobenzamide (TB) is a potent hepatotoxin in rats, causing dose-dependent hyperbilirubinemia, steatosis, and centrolobular necrosis. These effects arise subsequent to and appear to result from...Full Text Available
Background:Liver resection of large hepatocellular carcinomas (HCC), measuring at least 10 cm remains a controversial debate. Multiple studies on HCCs treated with surgical resection...Full Text Available
Toxicogenomics provides the ability to examine in greater detail the underlying molecular events that precede and accompany toxicity, thus allowing prediction of adverse events at much earlier...Full Text Available
Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. While DMSO is generally thought of as being relatively inert, it...Full Text Available
Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in the United States. The only available treatment, N-acetylcysteine (NAC), has a limited...Full Text Available
In this study we use the multiple indicator dilution technique to outline the kinetic mechanisms underlying the uptake of rubidium, a cation which, in the steady state, is concentrated by hepatic parenchymal...Full Text Available
Recurrent tumour after radical pancreaticoduodenectomy may cause obstruction of the small bowel loop draining the liver. Roux-loop obstruction presents a particular therapeutic challenge, since the...Full Text Available
BackgroundIn rats, alcohol exposure during the period of rapid brain growth produces long-term changes in the free-running period, photoentrainment and phase-shifting...Full Text Available
Mitochondrial heat shock protein 70 (mtHSP70) is found to play a primary role in cellular defense against physiological stress like exposure to environmental contaminants and helpful in the maintenance...Full Text Available
Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This...Full Text Available
BackgroundCavernous hemangiomas are the most frequent neoplasms of the liver and in routine clinical practice they often need to be differentiated from malignant tumors and other...Full Text Available
Pancreatic islet transplantation into the liver provides a possibility to treat selected patients with brittle type 1 diabetes mellitus. However, massive early β-cell death increases the number...Full Text Available
The effect of chronic administration of phenobarbital on the binding of phorbol-12,13-dibutyrate (({sup 3}H)PDBu), an activator of protein kinase C (PKC), was examined in rat liver microsomes. A significant increase in the number of binding sites was observed in microsomes of Fisher 344 rats. However, no change appeared in liver cytosol binding of PDBu. Consequently, a translocation process of PKC is unlikely. The increase in ({sup 3}H)PDBu binding in liver microsomes is significant 24 h. after one injection of phenobarbital and reaches its maximum in 2 days. In other strains of rats (ACI and lean Zucker), significant differences were found in the increase of ({sup 3}H)PDBu binding in microsomes. Fisher 344 were the most sensitive, lean Zucker rats, the least sensitive. Those results parallel the pentoxy-resorufin O demethylase activity in the microsomes of the same animals. EC{sub 50} values for inhibition of ({sup ...
The principal cause of primary non-function in orthotopic liver transplantation is thought to be preservation injury to the microvasculature. We, therefore, evaluated if effluent levels of hyaluronate,...Full Text Available
Orthosiphon stamineus as medicinal plant is commonly used in Malaysia for treatment of hepatitis and jaundice; in this study, the ethanol extracts were applied to evaluate the...Full Text Available
Hepatobiliary scintigraphy is the only non-invasive technique providing real-time assessment of hepatocytes function and bile progression from the liver to the intestine; for this reason it is of great importance in the study of jaundice and many other disorders of the liver and the biliary tract in children. Ultrasonography is the initial method of evaluating the intra- and extrahepatic bile ducts dilatation: the differential diagnosis between biliary atresia and neonatal hepatitis cannot however be done without hepatobiliary scintigraphy. Cystic fibrosis patients also require hepatobiliary scintigraphy; liver and biliary tract disease can really occur independently of the underlying disease severity and the presence of steatorrhoea. Hepatobiliary imaging in children who have undergone liver transplantation is of major importance; it can assess vascularity, parenchymal function biliary drainage, ...
BackgroundExpansion of aquaculture is seriously limited by reductions in fish oil (FO) supply for aquafeeds. Terrestrial alternatives such as vegetable oils (VO) have been investigated...Full Text Available
An assessment has been made of biochemical alterations in renal and hepatic functions of 73 male operators employed for an average of 8.2 years (range 0.5-23 years) in a chemical plant producing chlorinated...Full Text Available
The CYP1A (EROD)-inducing potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3minutes or feet,4,4minutes or feet,5-pentachlorobiphenyl (PCB126) and benzo(k)fluoranthene (B(k)F) were studied in avian embryo livers. TCDD and PCB126 proved to be much more potent as inducers in the chicken than in the other species examined. This finding is consistent with a considerably higher sensitivity of the chicken compared with a number of other avian species to the embryotoxic effects of these compounds. Furthermore, the relative potencies of the tested Ah receptor agonists as CYP1A inducers differed substantially between species. B(k)F and PCB126 showed similar induction potencies in domestic duck embryos, whereas PCB126 is much more potent than B(k)F in the chicken. Also, the potency of PCB126,relative to that of TCDD, was much lower in quail embryo liver in vitro than in chicken embryo liver. Thus, there are large ...
The hepatic uptake rate for certain albumin-bound drugs and metabolites correlates poorly with their equilibrium unbound concentration in the plasma, suggesting that binding equilibrium may not always...Full Text Available
Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States....Full Text Available
BackgroundTrichloroethylene (TCE) is a suspected human carcinogen and a common ground-water contaminant. Chloral hydrate (CH) is the major metabolite of TCE formed in the liver by...Full Text Available
Cancers are highly heterogeneous and contain many passenger and driver mutations. To functionally identify tumor suppressor genes relevant to human cancer, we compiled pools of short harpin...Full Text Available
The use of complementary and alternative medicines is becoming increasingly popular in Western society. As a result the number of reported adverse reactions is increasing. Glucosamine is a herbal remedy...Full Text Available
Genetic test systems involving microorganisms and liver enzyme preparations may be insufficient to detect compounds that require breakdown by enzymes provided by the microbial flora of the intestinal...Full Text Available
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, which is closely related to hepatitis C and cirrhosis. The molecular mechanisms underlying the hepatocarcinogenesis induced by HCV...Full Text Available
Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of...Full Text Available
Through the use of a variety of post-labeling techniques, the nucleotide sequence of a major species of leucine tRNA from bovine liver was determined to be pG-G-U-A-G-C-G-U-G-m-G-C-ac-C-G-A-G-C-G-G-D-C-psi-A-A-G-G-C-m-G-C-U-G-G-A-psim-...Full Text Available
Single-shot spin-echo diffusion-weighted echo-planar imaging using a phased-array multicoil was performed to distinguish between normal and cirrhotic livers. Sets of 6 images with different b-value were acquired with breath-holding. Significant differences were observed between controls and cirrhosis cases in the signal ratios when the b-value was 383 s/mm{sup 2}, and apparent diffusion coefficients. (orig.)
Iodine-131 MIBG, a radiolabeled adrenergic neuron-blocking agent, decreased rapidly from the heart and liver of patients with adrenergic dysfunction and pheochromocytoma when compared with eight controls. However, there was no significant difference in the rate of (/sup 131/I)MIBG decrease in these organs between controls and patients in the intervals subsequent to 4 hr. These findings suggest that adrenergic neuronal uptake of (/sup 131/I)MIBG in these organs is smaller in the patients than in the controls. Measurements of time-activity relationships of radioiodinated MIBG may be useful for assessment of adrenergic function of these organs and thus of generalized disorders of adrenergic innervation.
We demonstrated that the intensity levels and lifetimes of two-photon autofluorescences (2PAF) in human liver tissues can be exploited to diagnose hepatocellular carcinoma (HCC). Excited by an infrared femtosecond laser, we suppressed the two-photon autofluorescences of most endogenous fluorophores and made red autofluorescences more specific to particular molecules in the cryo-sectioned human livers. Using such fluorescence contrast, we found HCC tissues have reduced levels of 2PAF and longer fluorescence lifetime.
Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a {lambda}gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu{sup 160}{yields}His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a {lambda}{sub max} at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, the former ...
Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a #lambda#gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu"1"6"0#->#His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a #lambda#_m_a_x at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, the former of ...
Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-#kappa#B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the ...
The influence of reconstituting a murine monoclonal IgG_1 antibody kit with pertechnetate Tc99m on antibody distribution in the liver, spleen and sternal bone marrow of patients was examined. The "9"9"mTc-labelled antibody used is directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen (CEA) and has been successfully applied for imaging tissue inflammation and bone marrow scanning. Radioactivity uptake was determined in the liver, spleen, bone marrow and a precordial background region in a consecutive series of 25 patients, examined with an antibody preparation, routinely radiolabelled according to the manufacturer's recommendations and in 14 patients, in whom the antibody was reconstituted with special care, avoiding bubble formation and dropping of buffer into the antibody-containing vial. Gentle compared with routine antibody reconstitution caused a highly significant reduction of the antibody uptake in the ...
ZnMT has been postulated to function in essential metal homeostasis and metal detoxication. This study was undertaken to evaluate the potential of liver ZnMT to mediate the interaction of Zn and Pb with the Zn metalloenzyme, ALAD. Pretreatment of rats with Zn activated liver ALAD and attenuated the inhibition of ALAD by Pb in vitro and in vivo. Liver cytosol from Zn-pretreated rats injected with /sup 203/Pb was fractionated via gel filtration and anion-exchange chromatography and disclosed that both Zn and /sup 203/Pb co-eluted in the MT fractions. Both purified ZnMT-I and ZnMT-II bound /sup 203/Pb in vitro as shown by gel filtration chromatography. Addition of purified liver ZnMT to purified bovine liver ALAD reaction mixtures increased enzyme activity by 2-fold and prevented inhibition of ALAD by Pb. Addition of apothionein alone decreased the activity of Zn-activated ALAD and ...
The hepatic artery chemoembolization with Lipiodol, doxorublicin. Gelfoam was performed in 14 mongrel dogs to evaluate embolic effect of these materials to normal liver parenchyma. Fourteen dogs were divided into four experimental groups according to the kinds of embolic materials. 3 dogs with 0.1ml/kg of Lipiodol (Group 1), 4 dogs with 0.1ml/kg of Lipiodol and 0.5mg/kg of doxorubicin (Group 2). 4 dogs with Lipiodol, doxorubicin and 150-300 pieces of 0.5 x 0.5cm sized Gelfoam (Group 3), 3 dogs with Gelfoam alone (Group 4). Follow-up liver function tests and liver CT were performed 1 day, 3 day, 1 week, 2 weeks and 3 weeks after embolization. Pathologic examination was performed 3 weeks after embolization. Lipiodol densities in group 1 were cleared 2 weeks after embolization, and in group 2, patch and nodular Lipiodol densities were changed to mottled and streaky densities 3 weeks after chemoembolization. In group 3, patch ...
We cloned and characterized horse preproendothelin-2 (PPET-2) cDNA from intestinal tissue. The cDNA encoded 178 amino acids of the PPET-2 polypeptide, in which a 21-amino-acid mature endothelin-2 peptide and a 16-amino acid endothelin-2-like peptide were found. For the open reading frame the correspondence of horse PPET-2 cDNA with those of the ferret, human, dog, mouse and rat was 85.1%, 84.9%, 82.1%, 77.8% and 77.2%, respectively. Analysis of the organ distribution of PPET-2 mRNA by reverse transcription-polymerase chain reaction demonstrated that the kidney, stomach and small intestine are major sites of expression of the PPET-2 gene. Surprisingly, the mRNA is not detected in the large intestine, where high expression is demonstrated in the mouse and rat. This difference may result from the underlying functional differences of the large intestine between a herbivore (horse) and an omnivore (mouse and rat). PMID:15838341
Yeast artificial chromosome (YAC) libraries have been difficult to construct with average insert sizes >400 kilobase pairs when DNA is size-fractionated in low-melting-point agarose. By using yeast chromosomes in mock cloning experiments, the authors found that polyamines should be present whenever agarose containing high molecular weight DNA is melted to protect DNA from degradation. By incorporating polyamines during the cloning procedure, they constructed YAC libraries from mouse and human DNA with average insert sizes of 700 and 620 kilobase pairs, respectively. Several genome equivalents of these YAC libraries were replicated onto the surface of many duplicate agar plates using a 40,000 multipin transfer device. High-density filter replicas were screened by hybridization, and 70 mouse YAC clones from 31 loci and 132 human YAC clones from 49 loci were isolated.
In experiments designed to detect new mutations affecting hemoglobin, we irradiated the male or female parent in reciprocal crosses of two mouse strains that differ in alleles at the hemoglobin (Hba, Hbb) loci as well as at five other specific loci. Offspring were analyzed for hemoglobin properties (electrophoretic pattern, solubility, crystal pattern), serum albumin differences, erythrocyte lysis, reticulocyte count, and external appearance. Five hemoglobin variants were found among the mutants. In three, the genetic contribution from the irradiated father was not expressed with regard to the #alpha#-chain; one carried a tandem duplication (the first known case in the mouse) involving Hbb; and one probably resulted from double nondisjunction of chromosome 7. The finding that major chromosome aberratios can mimic hemoglobin mutations indicates the need, in similar experiments, to follow F_1 screening with thorough cytogenetic analysis. The ...
The retinal degeneration 10 (rd10) mouse is a well-characterized model of autosomal recessive retinitis pigmentosa (RP), which carries a spontaneous mutation in the ? subunit of rod cGMP-phosphodiesterase (PDE?). Rd10 mouse exhibits photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration and remodeling of the inner retina. Here, we evaluate whether gene replacement using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can provide long-term therapy in this model. AAV8 (Y733F)-smCBA-PDE? was subretinally delivered to postnatal day 14 (P14) rd10 mice in one eye only. Six months after injection, spectral domain optical coherence tomography (SD-OCT), electroretinogram (ERG), optomotor behavior tests, and immunohistochemistry showed tha...
Objective: To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1@a,25(OH)"2D"3 or soluble receptor activator of nuclear factor-@kB ligand (s-RANKL). Materials and methods: Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10%) and tetracyclines (2.5, 5 and 10@mM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1@a,25(OH)"2D"3 (10nM) or s-RANKL (20ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1@a,25(OH)"2D"3 or s-R...
Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested ...
We used a 13-year time series of abundance estimates of breeding Northern Saw-whet Owls (Aegolius acadicus), and of small mammals from central Ontario, Canada, to assess the numerical response of the owls to small-mammal prey species. We found that the finite rate of increase of breeding owls was directly related to estimates of red-backed vole (Myodes gapperi) abundance. Thus, it appeared that the owls were nomadic, and made decisions about where to breed based on vole supply. The owls showed a much weaker response to deer mouse (Peromyscus maniculatus) abundance. Across all years, 55% of variation in owl rate of increase could be uniquely attributed to vole abundance, whereas only 3% could be attributed to mouse abundance. Consistent with the model of nomadism, there was only a weak rela...
The yellow Iranian scorpion Odontobuthus doriae can cause fatal envenoming, but its mechanism of action is unclear. One of the reported manifestations of envenoming is moderate to severe involuntary tremor of skeletal muscle. In order to understand better the mechanism of action of this venom on skeletal muscle function, we examined the effects of the venom in vitro on chick biventer cervicis (CBC) and mouse hemidiaphragm (MHD) nerve muscle preparations. O. doriae venom (0.3-10mg/ml) initially increased and then decreased twitch height. The venom also caused contracture in both preparations. In mouse triangularis sterni preparations, used for all intracellular recording techniques, the venom enhanced the release of acetylcholine and induced repetitive firing of nerve action potentials and ...
The present study was aimed at investigating effects of nickel (NiCl2) on secretion of testosterone (T), cell viability, ultrastructure and apoptosis in mouse Leydig cells. Testosterone release was measured after 48h of culture with 15.67, 31.25, 62.5, 125, 250, 500 and 1000mmol/L NiCl2 or without NiCl2 using radioimmunoassay. Cell viability was assessed by a MTT (metabolic activity assay). Quantification of apoptotic cells was performed using TUNEL assay and the ultrastructural changes were analyzed using transmission electron microscopy. The viability was decreased after addition of >=250mmol/L NiCl2. A concentration-dependent depression of T production was observed. The percentage of apoptotic cells was significantly increased only after addition of 125, 250 and 1000mmol/L NiCl2. After ...
The 50th anniversary of Mary Lyon?s 1961 Nature paper, proposing random inactivation in early embryonic life of one of the two X chromosomes in the cells of mammalian females, provides an opportunity to remember and celebrate the work of those involved. While the hypothesis was initially put forward by Lyon based on findings in the mouse, it was founded on earlier studies, notably the work of Susumu Ohno; it was also suggested independently by Beutler and colleagues using experimental evidence from a human X-linked disorder, glucose-6-phosphate dehydrogenase deficiency, and has proved to be of as great importance for human and medical genetics as it has for general mammalian genetics. Alongside the hypothesis itself, previous cytological studies of mouse and human chromosomes, and the obse...
Background Identifying susceptibility genes for endophenotypes by studying analogous behaviors across species is an important strategy for understanding the pathophysiology underlying psychiatric disorders. This approach provides novel biological pathways plus validated animal models critical for selective drug development. One such endophenotype is avoidance behavior. Methods In the present study, novel automated registration methods for longitudinal behavioral assessment in home cages are used to screen a panel of recently generated mouse chromosome substitution strains that are very powerful in quantitative trait loci (QTL) detection of complex traits. In this way, we identified chromosomes regulating avoidance behavior (increased sheltering preference) independent of motor activity lev...
Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments. As a first step toward identifying genes that regulate PPI, we performed a quantitative trait locus (QTL) screen of PPI phenotypes in a panel of mouse chromosome substitution strains (CSSs). We identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor...
Research on hematological disorders relies on suitable animal models. We retrospectively evaluated the use of the hematological parameters hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell count (WBC), and platelet count (PLT) in the phenotype-driven Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project as parameters for the generation of novel animal models for human diseases. The analysis was carried out on more than 16,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the levels of the chosen parameters. Identification of animals exhibiting altered valu...
The expression of motor activity levels in response to novel situations is under complex genetic and environmental control. Several genetic loci have been implicated in the regulation of this behavioral phenotype, but their relationship to epigenetic and epistatic interactions is relatively unknown. Here, we report on a quantitative trait locus (QTL) on mouse chromosome 1 for novelty-induced motor activity in the open field, using chromosome substitution strains derived from a high active host strain (C57BL/6J) and a low active donor strain (A/J). The QTL for open field (horizontal distance moved) peaked at the location of Kcnj9, however, QTL detection was initially masked by an interplay of both grandparent genetic origin and genetic co-factors influencing behavior on chromosome 1. Our fi...
Purpose Evaluation of the all-trans retinoic acid (t-RA) effects on in vitro maturation (IVM) and in vitro fertilization (IVF) of immature mouse oocytes in the presence and absence of granulosa cell monolayer. Methods Denuded oocytes isolated from mice ovaries and matured in IVM medium alone (Control I), IVM medium in the presence of granulosa cells (Control II), IVM medium with t-RA (Experimental I) and IVM medium simultaneously with t-RA and granulosa cells (Experimental II). After 24?h, matured oocytes were fertilized in T6 medium and their development was followed until the blastocyst stage. Metaphase II oocytes ploidy were evaluated by chromosome counting. Results The t-RA group compared to the control groups showed no obvious abnormalities. Additionally maturation and embryo developm...
Please cite this paper as: Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder - a preliminary study. Experimental Dermatology 2008; 17: 203-207. Abstract: Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6-/- mice. Three groups were fed a specific di...
Excessive physical activity plays an important role in the progression of anorexia nervosa (AN) by accelerating weight loss during dietary restriction. To search for mechanisms underlying this trait, a panel of mouse chromosome substitution strains derived from C57BL/6J and A/J strains was exposed to a scheduled feeding paradigm and to voluntary running wheel (RW) access. Here, we showed that A/J chromosomes 4, 12 and 13 contribute to the development of a disrupted RW activity in response to daily restricted feeding. This pattern is characterized by intense RW activity during the habitual rest phase and leads to accelerated body weight loss. Regions on mouse chromosomes 4, 12 and 13 display homology with regions on human chromosomes linked with anxiety and obsessionality in AN cohorts. The...
Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg/sup 2 +/ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.
Iodized oil has been used as a contrast agent in lymphangiography. One of the commercially available compounds is Lipidol Ultra-fluid(LUF) which contains 38% iodine by weight. Nakakuma et al(1979) reported that LUF was selectively retained in the hypervascular hepatocellular carcinoma when injected directly into the ligated hepatic artery. Since that time, it has been widely utilized in the detection as well as the therapeutic attempts of hepatocellular carcinoma, where it has been mixed with chemotherapeutic agents or labeled with radioactive I-131. Like all significant advances, the mechanism of lipid retention within the hepatocellular carcinoma is not clearly understood, and also there is a lack of information about the biodistribution and kinetics of I-131 Lipiodol. The apparent safety of this technique require confirmation. The present study was aimed to assess the biodistribution and kinetics of intraarterially injected I-131 Lipiodol and the histologic changes in canine ...
c-Jun N-terminal kinase 2 (JNK2) isoforms are transcribed from the jnk2 gene and are highly homologous with jnk1 and jnk3 transcriptional products....Full Text Available
Hypoxia causes abnormal neonatal pulmonary artery remodeling (PAR) and inhibition of alveolar development (IAD). Transforming growth factor (TGF)-β is an important regulator of lung development...Full Text Available
West Nile virus (WNV) is a mosquito-borne flavivirus that infects the central nervous system of humans and other animals. In this study, we found that C3H/HeN (C3H) mice exhibited a higher morbidity...Full Text Available
RNA interference (RNAi) is an effective tool for studying gene function in oocytes, but no studies have targeted somatic cells of primary cultured cumulus cell-oocyte complexes (COCs). This...Full Text Available
The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles...Full Text Available
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
Stromal cells from DBA/2 mouse bone marrow have been shown to be susceptible to cytotoxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). Treatment with HQ also...Full Text Available
Current information suggests that chemical carcinogenesis is a multistep process with one of the best studied models in this regard being the two-stage carcinogenesis system using mouse skin. The effects of several carcinogens and tumor promoters in various sequences of application were studied to examine the nature of the process. The actions of several tumor inhibitors were compared. (ACR)
We present a drawing package optimised for Feynman diagrams. These can be constructed interactively with a mouse-driven graphical interface or from a script file, more suitable to work with a diagram generator. It provides most features encountered in Feynman diagrams and allows to modify every part of a diagram after its creation. Special attention has been paid to obtain a high quality printout as easily as possible. This package is written in Tcl/Tk and in C. (orig.).
The past three years of work for the Air Force Office of Scientific Research has resulted in the development of a congenic mouse model of JP-8 jet fuel exposure, the role of substance P in the JP-8 jet fuel-induced lung injury process, and development of ...
Cordycepin has been shown to interfere with a myriad of molecular processes from RNA elongation to kinase activity, and prevents numerous inflammatory processes in animal models. Here we show in a mouse...Full Text Available
Two cellular DNA regions representing common domains for proviral DNA integration ( Mlvi -1 and Mlvi -2) have been identified in Moloney murine leukemia virus-induced rat thymic lymphomas. Cellular...Full Text Available
There is significant interest in using computed tomography (CT) for in vivo imaging applications in mouse models of disease. Most commercially available mouse x-ray CT scanners utilize a charge-coupled device (CCD) detector coupled via fibre optic taper to a phosphor screen. However, there has been little research to determine if this is the optimum detector for the specific task of in vivo mouse imaging. To investigate this issue, we have evaluated four detectors, including an amorphous selenium (a-Se) detector, an amorphous silicon (a-Si) detector with a gadolinium oxysulphide (GOS) screen, a CCD with a 3:1 fibre taper and a GOS screen, and a CCD with a 2:1 fibre taper and both GOS and thallium-doped caesium iodide (CsI:Tl) screens. The detectors were evaluated by measuring the modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), stability over multiple exposures, and noise ...
Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of...Full Text Available
4.5S RNA is a group of RNAs 90 to 94 nucleotides long (length polymorphism due to a varying number of UMP residues at the 3' end) that form hydrogen bonds with poly(A)-terminated RNAs isolated from...Full Text Available
Hepatic injury and regeneration of the liver are associated with activation of hepatic stellate cells (HSC). Fibroblast growth factors (FGFs) and their receptors are important regulators of repair in various tissues. HSC express FGFR3IIIc as well as FGFGR4 and different spliced FGFR1IIIc and FGFR2IIIc isoforms which differ in the presence or absence of the acid box and of the first Ig-like domain. Expression of FGF9, known to be capable to activate the HSC FGFR2/3-isoforms, was increased in HSC in liver slice cultures after exposition to carbon tetrachloride, as an acute liver injury model. FGF9 significantly stimulated 3-H thymidine incorporation of hepatocytes, but failed to induce DNA synthesis in HSC despite the fact that FGF9 induced a sustained activation of extracellular signal-related kinases (ERK) 1/2. FGF9 induced an increased phosphorylation of Tyr436 of the fibroblast growth factor receptor substrate (FRS) 2, ...
Twenty-four patients were studied with both /sup 201/Tl-thallus chloride and /sup 99m/Tc-TBI scintigraphy following exercise. Comparison of the two agents in detecting segmental myocardial ischemia and scar was made in 18 patients with evidence of coronary artery disease on /sup 201/Tl-thallous chloride scintigraphy. Agreement between the two studies was observed in 77% (125 of 162) of left ventricular segments, suggesting that /sup 99m/Tc-TBI can be used as a myocardial perfusion agent. Limitations were related to early high background activity from lungs and liver. The high lung activity and early myocardial redistribution within the 1st hour contributed to the failure of /sup 99m/Tc-TBI to detect 16 segmental defects seen in the immediate post-exercise thallous chloride scan. Persistently high liver activity additionally affected accurate interpretation in the left ventricular segments close to the diaphragm. Improvement in the accuracy of ...
High concentrations of toxic chemicals in sediment and white croaker (Genyonemus lineatus), as well as liver diseases (e.g., carcinomas) in this species, were found in the Los Angeles area. The highest concentrations of aromatic hydrocarbons (AHs) in the sediment were in San Pedro Bay, and the highest concentrations of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) derivatives were in sediment from near the White Point sewer outfall. Concentrations of AHs, polychlorobiphenyls (PCBs), and DDT derivatives were generally higher in food organisms from the croaker's stomach than in sediment. Moreover, croaker from San Pedro Bay and White Point were substantially contaminated with DDT derivatives and metabolites of aromatic compounds, compared to croaker from the Hyperion outfall and Dana Point. The evidence suggest that the observed pathological conditions of the liver were associated with exposure of the croaker to toxic chemicals, ...
The authors investigated the effect of T-2 toxin on rat liver mitochondrial protein synthesis. Isolated rat liver mitochondria were supplemented with an S-100 supernatant from rat liver and an external ATP-generating system. An in-vitro assay employing cycloheximide, and inhibitor of cytoplasmic protein synthesis, and chloramphenicol, and inhibitor of mitochondrial protein synthesis, to distinguish mitochondrial protein synthesis from the cytoplasmic process. Amino acid incorporation into mitochondria was dependent on the concentration of mitochondria and was inhibited by chloramphenicol. The rate of uptake of tritium leucine into mitochondrial protein was unaffected by the addition of T-2 toxin and was not a rate-limiting step in incorporation. However, 0.02 micrograms/ml of T-2 toxin decreased the rate of protein synthesis inhibition correlated with the amount of T-2 toxin taken up by the mitochondria. While T-2 toxin is ...
Somatogenic hormones play an important role in regulation of receptors for prolactin (PRL) and estrogen. Plerocercoids of the tapeworm, S. mansonoides produce a factor which mimics some, but not all of the actions reported for GH. Intact female rats were subjected to a constant infusion of plerocercoid growth factor (PGF) via a subcutaneous infection for two weeks to determine if PGF influences receptors for PRL, GH or estradiol. The rate of weight gain in the PGF-treated rats was accelerated in spite of a marked reduction in serum GH. Partially-purified PGF specifically displaced [125I]hGH from rat liver receptors but microsomes prepared from rats treated with PGF specifically bound significantly less [125I]hGH than microsomes from control rats. The reduction in [125I]hGH binding was not due to occupancy or to a change in affinity but to a suppression in receptor concentration. Scatchard analysis of [3H]estradiol binding in rat liver cytosols ...
The primary aim was to evaluate delayed contrast-enhanced MRI in depicting perineural spread of hilar cholangiocarcinoma (CCC) and consequently to determine the capability of MRI/MRCP for staging CCC. Fifteen patients that underwent MRI/MRCP and surgical treatment were retrospectively included. Two radiologists evaluated MR images to assess delayed periductal enhancement, extent of bile duct stenosis, liver parenchymal and vascular involvement and presence of liver atrophy. An agreement between delayed enhancement of the bile duct walls and perineural neoplastic spread showed a very good correlation factor (0.93). The overall accuracy in detecting biliary neoplastic invasion was higher for delayed T1-weighted images (93.3%) than for the MRCP images (80%), and T1-delayed image increased the MR accuracy in assessing the neoplastic resectability (p < 0.05). MRI correctly predicted vascular involvement in 73% and liver ...
Abstract Juvenile cobia (Rachycentron canadum) (100-g) were fed four moist diets (447-476-g-kg-1-dry-wt) where 0, 130, 260 or 390-g-kg-1 of concentrated lizardfish (Saurida undosquamis) silage replaced fresh lizardfish, respectively. Blood and livers were sampled at 0, 6, 12, 24 and 48-h postfeeding at the end of the 3-week experiment. At 6-h postfeeding in all groups, maximum concentrations of most plasma essential amino acids were observed, while significantly lower levels of most non-essential amino acid levels were recorded compared to the other sampled times. At 6 and 12-h after feeding, the concentration of most plasma free amino acid (FAA) increased with an increase in dietary fish silage levels. Most FAA in livers of all groups peaked at 12 and 24-h postfeeding. However, at 48-h po...
The aim of this study was to evaluate the radioprotective effect of turmeric extract (40 mg/kg body weight) and vitamin E (#alpha# - tocopherol acetate, 400 IU/kg body weight) supplementation on lipid peroxidation, reduced glutathione and antioxidant defense enzymes in various organs like liver, kidney and salivary glands at 24 h in adult Swiss mice. "1"3"1Iodine exposure significantly increased lipid peroxidation in kidney and salivary glands in comparison to control animals. Pre supplementation with turmeric extract for 15 days showed significant lowering of lipid peroxidation in kidney. On the other hand vitamin E pre supplementation showed marked reduction in lipid peroxidation in salivary glands. Reduced glutathione levels decreased significantly in liver after radiation exposure. However, pre supplementation with turmeric extract and vitamin E did not improve glutathione levels in liver. In conclusion we have observed ...
Fourteen surgical patients with non-hepatobiliary diseases were studied with "9"9Tc"m EHIDA imaging to evaluate the effect of total parenteral nutrition (TPN) on the hepatobiliary function. The duration of TPN ranged from 6 to 56 days; for 10 of the 14 patients it was between 6 to 10 days. The results showed that: (1) 11 of 14 patients had abnormal scintigraphic features. The most prominent findings were delayed liver excretion and prolonged blood clearance time. This fact suggests that not only the rate of excretion of the bile from the liver is decreased but the uptake ability of the hepatocyte is also impaired. (2) The effect of TPN on liver function is reversible. The authors conclude that in order to prevent irreversible damage of hepatobiliary function caused by TPN, the duration of TPN should not be too long and oral intake of nutrients should be resumed as soon as possible. (author). 9 refs, 3 figs, 3 tabs.
Quantitative hepatic scintiangiography was previously used for evaluating the relative contribution of hepatic arterial and portal venous blood flows to the hepatic circulation. The present study compares 3 different procedures (automatic and manual integration, and slope fitting methods) for analyzing the hepatic time activity curves obtained after bolus i.v. injection of 370 MBq /sup 99m/Tc-diethylentriaminopentacetic acid. Twenty five subjects were studied: Five controls, ten cirrhotics, and ten portal hypertensive patients previously submitted to side to side portacaval anastomosis. The correspondence between results given by the different methods was satisfactory only in shunted patients, and the reproducibility of computed parameters was quite poor for all procedures. Accordingly, none of the methods can be considered as supporting reliable quantitative pathophysiological evaluations. However, the hepatic arterial/portal venous flow ratio was found to be increased in ...
Chicken embryos were x-irradiated in ovo with 5-30 cGy (=priming dose) at the 13th-15th day of development. After 3-48 h, brain- and liver-cell suspensions were x-irradiated in vitro with (challenge) doses of 4-32 Gy. Significantly less radiation damage was observed when the radiation response was measured by scheduled DNA synthesis, nucleoid sedimentation and viscosity of alkaline cell lysates 12-36 h after the priming exposure. In vivo, pre-irradiation with 10 cGy enhanced regeneration as evidenced by the DNA content of chicken embryo brain and liver 24 h following a challenge dose of 4 Gy. From nucleoid sedimentation analyses in brain and liver cells immediately after irradiation with 16 Gy and after a 30-min repair period in the presence of aphidicolin, dideoxythymidine and 3-aminobenzamide or in the absence of these DNA repair inhibitors, it is concluded that a reduction of the initial radiation damage is the dominant ...
Background & AimsMolecular mechanisms underlying alcoholic liver disease (ALD) are still not fully understood. Activating transcription factor-4 (ATF4) is the master coordinator of the integrated stress response (ISR), an adaptive pathway triggered by multiple stressors. which can promote cell death and induce metabolic dysregulation if the stress is intense or prolonged. The aim of this study was to assess the effect of alcohol on the ISR signaling pathway in human liver cells and to define the role of cytochrome P450 2E1 (CYP2E1) in this response. MethodsPrimary cultured human hepatocytes and human HepG2 cells over-expressing CYP2E1 by adenoviral infection were exposed to ethanol (25-100mM) for 8-48h. ResultsEthanol treatment of both liver cells up-regulated ATF4 as well as the pro-survi...
Abstract Toll-like receptor 2 (TLR2) is an immune sensor for gram-positive bacterial cell wall components. Single-nucleotide polymorphisms (SNPs) in the TLR2 gene that impair its function may, therefore, influence the risk and outcomes of gram-positive bacterial infections. In a cohort of 694 liver transplant recipients, we assessed the TLR2 SNP that is translated into an amino acid substitution of arginine for glutamine at position 753 (R753Q), and we found that its presence was associated with the clinical characteristics and outcomes of gram-positive bacterial infections. The proportions of patients with the TLR2 R753Q SNP did not significantly differ between those with gram-positive bacterial infections and those without gram-positive bacterial infections (9.6% versus 9.6%, P = 0.999)....
When labeled cAMP is incubated with isolated mitochondria from rat liver, it penetrates not only through the outer membrane of the mitochondria but also into the mitoplasts, where it is accumulated chiefly in the matrix. Damage to the mitochondrial membrane by freezing-thawing promotes not an influx but an efflux of cAMP out of the mitoplasts. A substantial part of the labeled nucleotide in all the investigated submitochondrial fractions was identified as intact cAMP by the method of thin-layer chromatography. The transport of cAMP into the mitochondria can explain the activation of their functions by the hormones that activate cytoplasmic adenylate cyclase and by extramitochondrial (cytosol) cAMP, as well as the presence of cAMP-dependent protein kinase and cAMP-phosphodiesterase in the mitochondria.
The growing epidemic of juvenile obesity has prompted pediatricians to investigate obesity-related conditions in obese teenagers. We report a clinical case of severe hepatic fibrosis in an adolescent with severe and recent obesity. Because of elevated serum aminotransferase levels, abnormal hepatic ultrasonography and insulin resistance (impaired glucose tolerance), we suspected nonalcoholic steatohepatitis (NASH). Disease activity and fibrosis were confirmed on liver biopsy. Considering the risk of progression toward cirrhosis and its complications, and the pathological liver lesions, we started long-term medical monitoring and drug therapy to control weight loss. At present, although biopsy is the only validated way to establish the diagnosis of NASH, there is no consensus on its indicat...
The purpose of this study was to evaluate the toxicological effects of feeding the oils of Calophyllum inophyllum, Pentaclethra macrophylla and Terminalia catappa to rats. The effects on physical appearance, feed intake, weight gain, plasma and tissue cholesterol and triacyglycerol levels in rats with 5% of the oils in normal rat feed were determined. Weekly monitoring of the rats showed good physical appearance and steady weight gain, with no mortality recorded for the period of the study. Haematological analysis of the rats indicated that they were not anaemic. Histopathotogical examination of the sections of the heart, liver, kidney and spleen revealed moderate (T. catappa oil) to severe fatty change and necrosis in the liver. Glomerulonephrotic changes in the kidneys of rats fed with T...
One hypothesis for the decline of the North American greater (Aythya marila) and lesser (A. affinis) scaup population is that contaminant burdens acquired on wintering or staging areas impair reproduction or cause lethal or sublethal health effects. Recent studies have found increased selenium (Se) concentrations in scaup but have focused on the fall and spring staging periods. From January to March 2006 and December to March 2006 and 2007, we analyzed liver tissues collected from greater scaup wintering in western Lake Ontario for 16 trace elements. We also measured Se concentrations in greater scaup blood and Dreissenid mussel tissue. Se was the only trace element that occurred at increased concentrations (>10??g/g liver dry weight) in a substantial proportion (99%) of greater scaup live...
RIFLE criteria have been used to determine the incidence of acute kidney dysfunction (AKD) after orthotopic liver transplantation (OLT). However, no studies have focused on the incidence of AKD after OLT in patients with normal pre-OLT kidney functions. Using the RIFLE criteria, we determined the incidence and risk factors for AKD after OLT in patients with normal pre-OLT kidney function. We retrospectively analyzed the records of 112 patients who underwent OLT from January 2000 to February 2009 with normal prior kidney function. We investigated three levels of renal dysfunction outlined in the RIFLE criteria: risk (R); injury (I); and failure (F). Preoperative, intraoperative, and postoperative variables were collected. AKD occurred in 64 (57%) OLTs with risk, injury, and failure frequenc...
In this study, we evaluated the hypothesis that long term dietary restriction would have beneficial effects on the oxidative stress and antioxidant enzyme systems in liver, heart and kidney in adult male rats undergoing different intensities of swimming exercise. Sixty male, Sprague-Dawley rats were assigned as either dietary restricted on every other week day (DR) or fed ad libitum (AL) groups, and each group was further subdivided into sedentary, endurance swimming exercise training (submaximal exercise) and exhaustive swimming exercise (maximal exercise) groups. Animals in the submaximal exercise group swam 5 days/week for 8 weeks, while maximal exercise was performed as an acute bout of exercise. In parallel with the increase in the intensity of the exercise, the degree of lipid peroxi...
Hypertension is one of the most important modifiable risk factors for cardiovascular and cerebrovascular diseases. We investigated the potential antihypertensive effect of the purple passion fruit peel (PFP) extract, a mixture of bioflavonoids, phenolic acids, and anthocyanins, in spontaneously hypertensive rats and human. A high-performance liquid chromatography analysis was performed to identify the active ingredients of the PFP extract. In a rat liver toxicity assay, no hepatotoxicity was observed after 9 hours incubation in the presence of PFP extract (20 ?g/mL). The PFP extract also revealed hepatoprotection against chloroform (1 mmol/L)-induced liver injury. In the experimental model, 24 spontaneously hypertensive rats were divided into 3 treatment groups for a period of 8weeks: cont...
A female employee was exposed to lead dust for 8 h daily from 4.5.1982 to 20.5.1982. During this time conception occurred (1st day of last menses 4.5.82). Acute symptoms of lead intoxication were not observed in this subject but were in other employees. Measurements of lead content were started after the end of exposure and continued for 6 months until normal values were obtained. Because of the half-life of nearly 20 days for lead elimination from blood the estimated body burden at the end of exposure was about 1200 ppb. The fetal tissue samples contained between 0.4 (brain) and 7.9 (liver) ..mu..g lead/g dry weight. The fetal lead was mainly stored in bone, blood and liver. From the results given a delayed elimination of fetal lead is suggested.
Aim To determine the fate and clinical implication of large (?2cm), non-hypervascular nodules depicted on magnetic resonance imaging (MRI) in the cirrhotic liver. Materials and methods In 21 patients with cirrhosis (14 hepatitis B, two ethanol abuse, four cryptogenic, one Wilson's disease), 25 large (?2cm in the longest dimension) non-hypervascular nodules were identified on dynamic MRI. The implications for diagnosis of the initial size, contour, and signal characteristics on MRI in addition to patients' age and cause of cirrhosis were assessed in our analysis. Results Twelve (75%) out of 16 lesions were malignant or potentially-malignant from 14 hepatitis B patients, while seven (78%) of the nine lesions from other patients were benign (p=0.016). The mean age of the patients who ha...
Matrine (Mat), a component extracted from Sophora flavescens Ait, has a wide spectrum of pharmacological effects. Glycyrrhizin (Gly), a major active constituent of licorice (Glycyrrhiza glabra) root, has various pharmacological effects. Gly and Mat are ancillary drugs used clinically in China for protection of liver function and treatment of tumors. However, habitual administration of Gly may cause adverse effects marked by the development of pseudohypercorticosteroidism. This work was designed to see whether combination use of Gly and Mat could offer better liver protective and anti-hepatocarcinogenic effects than Gly or Mat alone, and whether it could reduce the adverse effects of Gly alone by acetaminophen-induced hepatotoxicity, diethylnitrosamine-induced hepatocarcinogenesis, inductio...
The activity of tyrosine aminotransferase (TAT) in the liver of mice subjected simultaneously to ionizing radiation and to local inflammatory process showed in the first 24 hours of the experiment statistically significant changes resulting from summation of the harmful effects of both factors. In the second 24-hour period an evident tendency was observed for return of a normal circadian rhythm of the enzyme. This points to presence of an endogenous mechanism of suppression of the manifestations of significant desynchronization of the circadian rhythm. The paper contains also a trial of mathematical analysis of changes in TAT activity in the circadian rhythm, a description and analysis or the suppression process, qualitative and quantitative determination of the phenomenon of cumulation of the effects of powerful stress factors acting on the animal organism. The obtained results were compared with the results of investigations of TAT activity changes obtained in ...
The evaluation of hepatic histology and treatment of hepatitis C virus (HCV)/HIV-coinfected patients is rapidly changing. HCV has become an important cause of mortality in HIV-infected patients. Consequently, assessment of liver histology in all coinfected patients is particularly important. The evaluation of hepatic histology is shifting from reliance on the liver biopsy toward noninvasive modalities. Additionally, the importance of HCV-associated morbidity and mortality in HIV-infected patients has prompted increasing numbers of these patients to be HCV treatment candidates. Prospective trials in coinfected patients have reported lower sustained virologic responses compared to HCV-monoinfected patients. Consequently, the numbers of coinfected nonresponders to pegylated interferon/ribavir...
We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro.
The present study describes pathologic findings and immunohistochemical diagnosis of canine visceral leishmaniasis (CVL) in 22 dogs who died naturally in the Aegean region of Turkey. At necropsy, lymphadenomegaly, hepatosplenomegaly, hepatic, and nephrosclerotic lesions were conspicuous. Histopathologically, chronic inflammatory reactions of the spleen, lymph nodes, bone marrow, liver, and skin were marked findings. Cytological and histological examinations showed macrophages loaded with Leishmania amastigotes in these organs. Immunohistochemistry revealed that immunolabeling of amastigotes and/or parasite antigen, especially in the lymph nodes, spleen, bone marrow, liver, and skin, and occasionally, in the kidneys, intestines and lungs. Our laboratory results showed that immunohistochemis...
"9"9"mTechnetium -heat damaged erythrocyte were used as spleen scanning agents in 12 patients from July, 1985 to April, 1986. We used this scan to evaluate situs inversus, asplenia, accessory spleen, hypersplenism, splenic infarction, tumor staging and evaluation of therapy, especially when the "9"9"mTc-tin colloid scans were not definite for diagnosis. The techniques applied to these scans were in vivo/in vitro-labeling method and heating-method to damage the erythrocytes. Liver-to-spleen uptake ratios were increased upto 100:1 and interference from the left lobe of the liver was eliminated. These scans were helpful to evaluate the spleen. (Author).
Acetaminophen (APAP) overdose, which causes liver injury in animals and humans, activates c-jun N-terminal kinase (JNK). Although it was shown that the JNK inhibitor SP600125 effectively reduced...Full Text Available
The hepatic removal of albumin-bound substances from plasma requires that they dissociate from albumin. Using indirect methods, we and others have proposed that dissociation may be catalyzed by interaction...Full Text Available
IntroductionMustafa Kemal Atatürk, founder of the Turkish Republic, had guarded many German scientists of a Jewish descent before the Second World War. Dr. Rudolf Nissen...Full Text Available
The loss of lead in various kinds of biological materials after drying and ashing is studied by using "2"0"3Pb as tracer which is intravenously injected into mice. The experimental results show that although the oven ashing can be used for determining the lead in samples of lung, kidney, and liver, etc., the oxygen plasma and high pressure digestion are the most suitable methods for the determination of lead in biological materials. (author) 5 refs.; 2 tabs.
The sera of NZB/BL mice have been found to be active in the complement fixation test against isogeneic liver antigens to a higher titre than the sera of CBA, C57BL and DBA/2 mice. Six sera from NZB...Full Text Available
1. Several ring-substituted derivatives of diphenyleneiodonium catalyse the exchange of Cl- and OH- ions across the inner membrane of rat liver mitochondria. They also inhibit state 3 and state 3u oxidations...Full Text Available
Glucose metabolism through glycolysis and hexosamine pathway has been shown to be altered in type 2 diabetes. However, its fate through the pentose phosphate pathway (PPP) is currently unclear....Full Text Available
This case report demonstrates an hepatic amebic abscess by scintigrapy, utilizing a new radiopharmaceutical designed specifically for that purpose. The abscess is delineated as a positive lesion after twenty four hours. The agent, "1"3"1I-labeled bromometronidazole, may prove to be specific for the diagnosis of these abscesses. (orig.).
AimsRosiglitazone and fenofibrate, specific agonists of the peroxisome proliferator activated receptors-γ (PPARγ) and -α (PPARα),...Full Text Available
A small cholangiocarcinoma was detected at autopsy in a patient with thorotrastosis who died from the rupture of esophageal varices at the esophagogastric junction. Prior to the advent of recent diagnostic imaging technique, a correct antemortem diagnosis could only be obtained from tumor markers. However, the tendency for the opacity of the liver to decrease slowly with time and develop uneven trabeculation suggests that small tumors may be difficult to detect against such a non-homogeneous background. (author).
Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic...Full Text Available
Total mercury (THg), methylmercury (MeHg) and 22 other trace elements were measured in ice algae, three species of zooplankton, mixed zooplankton samples, Arctic cod (Boreogadus saida), ringed seals (Phoca hispida) and eight species of seabirds to examine the trophodynamics of these metals in an Arctic marine food web. All samples were collected in 1998 in the Northwater Polynya (NOW) located between Ellesmere Island and Greenland in Baffin Bay. THg and MeHg were found to biomagnify through the NOW food web, based on significant positive relationships between log THg and log MeHg concentrations vs. {delta} {sup 15}N muscle and liver . The slope of these relationships for muscle THg and MeHg concentrations (slope = 0.197 and 0.223, respectively) were similar to those reported for other aquatic food webs. The food web behavior of THg and {delta} {sup 15}N appears constant, regardless of trophic state (eutrophic vs. oligotrophic), latitude (Arctic vs. tropical) or ...
Total mercury (THg), methylmercury (MeHg) and 22 other trace elements were measured in ice algae, three species of zooplankton, mixed zooplankton samples, Arctic cod (Boreogadus saida), ringed seals (Phoca hispida) and eight species of seabirds to examine the trophodynamics of these metals in an Arctic marine food web. All samples were collected in 1998 in the Northwater Polynya (NOW) located between Ellesmere Island and Greenland in Baffin Bay. THg and MeHg were found to biomagnify through the NOW food web, based on significant positive relationships between log THg and log MeHg concentrations vs. #delta# "1"5N muscle and liver . The slope of these relationships for muscle THg and MeHg concentrations (slope = 0.197 and 0.223, respectively) were similar to those reported for other aquatic food webs. The food web behavior of THg and #delta# "1"5N appears constant, regardless of trophic state (eutrophic vs. oligotrophic), latitude (Arctic vs. tropical) or salinity ...
Penetrating liver wounds are related to many causes and rank second after blunt abdominal and liver trauma. In this report are examined the clinical and radiological findings of personal series of patients with penetrating trauma, especially by firearms and stab and cut wounds. It will also tried to define the diagnostic workup of these traumas, which is especially based on CT signs of liver damage and associated changes and which is of basic importance for following treatment, both surgical or conservative. In the last seven years it was retrospectively reviewed 31 cases of penetrating liver trauma. The patients were 19 men and 12 women, ranging in age 18 to 73 (mean 42), with penetrating liver injuries from firearms (16 patients) and stab (9 cases) wounds; 6 patients had injuries from different cases. Abdominal CT was carried out in emergency with the CT Angiography (CTA) ...
Nodular hepatic involvement of multiple myeloma is very rare. We report here on a case of nodular hepatic involvement of multiple myeloma that mimicked intrahepatic cholangiocarcinoma. In patients with multiple myeloma, hepatic involvement of the multiple myeloma might be included in the differential diagnosis of hepatic mass.
The kinetics of lead distribution was studied in suckling and adult rats 8 days after a single intraperitoneal injection of "2"0"3Pb. Marked differences were observed in the kinetics of lead retention and distribution in suckling as compared to adult rats. The rate of "2"0"3Pb disappearance was lower in the whole body, blood and kidneys, but higher in the liver, while the deposition processes predominated in the brain, femur and teeth of sucklings as compared to adult animals. (auth).
Structural and functional alterations in hepatocytes of the European eel, Anguilla anguilla, following a 4-week-exposure to 5, 50, and 250 micrograms/liter dinitro-o-cresol (DNOC) were investigated by means of electron microscopy and biochemistry and compared to liver pathology in eels exposed to the chemical spill into the Rhine river at Basle in November 1986. Whereas phenological parameters (growth, condition factor) are unaffected, ultrastructural and biochemical alterations are detectable at greater than or equal to 50 and 5 micrograms/liter DNOC, respectively. Structural modifications include: rounding-up of the nuclei; fractionation and reduction of the rough endoplasmic reticulum; proliferation of the smooth endoplasmic reticulum (SER), mitochondria, peroxisomes, and lysosomes; bundles of rod-shaped SER profiles; annulate lamellae; membrane whorls within mitochondria; crystallization of the peroxisomal matrix and glycogen bodies; glycogen depletion and ...
We have isolated the human prointerleukin 1 (proIL-1) beta gene from leukocyte and fetal liver libraries. The nucleotide sequence and its gene organization reveals that the proIL-1 beta gene is composed...Full Text Available
The possible genetic (dominant lethal mutations (DLM) and cytogenetic changes in the regenerating liver) and somatic (hematopoietic stem cell changes, growth and nonspecific life time shortening) effects in mice maintained on tritiated water (HTO) over two generations was investigated. Results to date are summarized. (ACR)
1. Amino acid sequences covering the region between residues 173 and 248 [adopting the numbering system proposed by Lai, Nakai & Chang (1974) Science 183, 1204-1206] were derived for trout (Salmo...Full Text Available
The bifunctional rat liver enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (ATP:D-fructose-6-phosphate 2-phosphotransferase/D-fructose-2,6-bisphosphate 2-phosphohydrolase, EC 2.7.1.105/EC...Full Text Available
Pregnant rats were exposed to "8"5Kr for 4-6 hr and sacrificed immediately thereafter. The "8"5Kr concentration in the fetoplacental unit (FPU) was approximately the same at all gestation stages for intact FPU, isolated fetuses or fetal segments, as well as placentas and associated membranes. Maternal tissue concentrations varied over a wide range and only liver and intestine concentrations were relatively similar in both 20-day-gestation (dg) fetuses and adults.
Intrahepatic portosystemic shunts are an anomalous connection between the portal vein and hepatic vein/IVC, which may be either congenital or acquired secondary to liver cirrhosis or portal hypertension. Cases of congenital intrahepatic shunts are usually encountered in children and may spontaneously resolve. We report 5 cases of congenital intrahepatic portosystemic shunts in neonates and an adult
An exhaustive compendium of normal and abnormal imaging is presented. The following systems and procedures are illustrated by over 2800 captioned illustrations: liver, spleen, and hepatobiliary imaging; perfusion and ventilation lung imaging; thyroid imaging; salivary gland imaging; bone imaging; brain imaging; radionuclide cisternography; blood flow studies; gallium imaging; nuclear cardiology; and renal imaging. Not included in the atlas are adrenal imaging procedures and emission computed tomography. (ERB)
The current investigation attempted to confirm the beneficial actions of a chemically characterized Radix Astragali decoction (AM-W) against type 2 diabetic (T2D) Sprague-Dawley (SD) rats. Using a case/control...Full Text Available
Mutations in the mouse formin (Fmn) gene, formerly known as the limb deformity (ld) gene, give rise to recessively inherited limb deformities and renal malformations or aplasia. The Fmn gene encodes many differentially processed transcripts that are expressed in both adult and embryonic tissues. To study the genomic organization of the Fmn locus, we have used Fmn probes to isolate and characterize genomic clones spanning 500 kb. Our analysis of these clones shows that the Fmn gene is composed of at least 24 exons and spans 400 kb. We have identified two novel exons that are expressed in the developing embryonic limb bud as well as adult tissues such as brain and kidney. We have also used a microsatellite polymorphism from within the Fmn gene to map it genetically to a 2.2-cM interval between D2Mit58 and D2Mit103. 36 refs., 6 figs., 1 tab.
The purpose was to study the toxicity of drugs known to generate free radicals on isolated pancreatic islets. The accumulattion of "8"6Rb"+ by mouse pancreatic islets was measured in vitro. Exposing the islets to 6-hydroxydopamine, minhydrin, or phenazine methosulphate + NADH inhibited the Rb"+ uptake, whereas paraquat or acetylphenylhydrazine had no effect. This effect of 6-hydroxydopamine was prevented by either of the hydroxyl radical scavengers, sodium benzoate and mannitol, but not by the non-scavenger,urea; ninhydrin was partially protected against by mannitol but not by benzoate. Protection against 6-hydroxydopamine was also afforded by D-glucose but not by L-glucose or 3-O-methyl-D-glucose; none of the sugars protected against ninhydrin. In damaging islet beta-cells and in being protected against by D-glucose, 6-hydroxydopamine closely resembles the diabetogenic drug, alloxan. It is suggested that protection against alloxan may involve both glucose ...
A rickettsia related to but distinct from the spotted fever agent, Rickettsia rickettsii, has been detected in 167 (18.9%) of 884 Rhipicephalus sanguineus taken off dogs in central and northern Mississippi. The organisms could readily be isolated in male meadow voles (Microtus pennsylvanicus), where it produced massive infections in the tissues of tunica vaginalis. It was practically nonpathogenic for male guinea pigs, although inoculation of these animals with infected tunica vaginalis of voles afforded in 30 of 38 instances solid immunity to challenge with virulent R. rickettsii. The Rhipicephalus rickettsia grew well in monolayers of chicken embryo fibroblast, Vero, mouse L, and HeLa cells. Cytopathogenic effects were minimal unless large concentrations of rickettsiae were used as inocula. It also could be established in embryonated hen eggs but only after injection of massive doses of L cell-propagated organisms. Serological tests (complement fixation, ...
Results reported are for single dose exposures and refer to "6"0Co-#gamma#-irradiation. The RBE determined by V79 cell survival and based on the Do ratio was found to be 1.70#+-#0.4 ranging from 1.5 to 1.8. In the case of the regeneration of mouse jejunal crypts the RBE was calculated at ten cell curvival and was found to be 1.68. The maximum acute mouse skin reaction at a skin score of 2.0 was found to be 2.1 while the average skin reaction was 1.7. Growth retardation of Vicia faba bean roots measured at the level of 50% indicated an average RBE of 3.0 and a range of 2.7 to 3.7. The OER obtained for V79 cell survival was found to be 1.7 to 1.8. Comparison is made with the RBE and OER measurements for the neutron facilities at Clatterbridge, Fermilab and Louvain-la-Neuve which produce neutrons by the same nuclear reaction and whose physical specifications closely resemeble those of the Faure neutrons. This comparison indicates that the Faure ...
The studies reported here used genetic differences in susceptibility of C57BL/6N and C3H/HeN mice and exacerbation of the disease by nitrogen dioxide (NO/sub 2/) as tools in assessing the role of early host responses in the pathogenesis of MRM. The two strains did not differ in susceptibility to infection, but C3H/HeN mice were more susceptible to and had increased severity of lung lesions 14 days after intranasal inoculation as determined by 50% biological endpoints and morphometric analysis of tissues. Exposure to NO/sub 2/ for 4 hours prior to exposure to infectious aerosols exacerbated murine respiratory mycoplasmosis (MRM) by 7 days after exposure in both mouse strains. NO/sub 2/ appeared to affect host lung defense mechanisms responsible for limiting mycoplasmal growth in the lungs. The NO/sub 2/ exposure concentration required for this effect varied with the genetic background of the host, the dose of mycoplasmas administered, and the endpoint measured. ...
Goosecoid is a homeobox gene first isolated from a Xenopus dorsal lip cDNA library. Homologous genes have been isolated from mouse, zebrafish, and chick. In all species examined, the gene is expressed and plays an important role during the process of gastrulation in early embryonic development. The authors report here the cloning of the human goosecoid (GSC) from a genomic library and the sequence of its encoded protein. The genomic organization and protein sequence of the human gene are highly conserved with respect to those of its Xenopus and mouse counterparts: all three genes consist of three exons, with conserved exon-intron boundaries. The sequence of the homeo-domain is 100% conserved in most vertebrates. Using somatic cell hybrid and chromosomal in situ hybridization, the gene was mapped to chromosome 14q32.1. 30 refs., 3 figs., 2 tabs.
Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of ...
Previous behavioral and pharmacological studies have implicated endorphins in radiation-induced locomotor hyperactivity of the C57BL/6J mouse. However, the endogenous opiate(s) responsible for this behavioral change have not been identified. The present study measured beta-endorphin-like immunoreactivity (beta-END-LI) in brain, blood, and combined brain and pituitary samples from irradiated and sham-irradiated C57BL/6J mice. After radiation exposure, levels of beta-END-LI decreased significantly in the brain. A similar, but not statistically significant, decline was measured in combined brain and pituitary samples. Concentrations of blood beta-END-LI were not changed by irradiation. These radiogenic changes in beta-END-LI are in some ways similar to those observed after other stresses. However, radiation-induced locomotor hyperactivity may be mediated more by alterations of beta-END-LI in the brain than in the periphery. Other endogenous opiate systems may also ...
The endothelin-B (ETB) receptor is a G-protein-coupled receptor that binds endothelin ligands and is essential for the development of epidermal melanocytes and enteric neurons. Recent reports indicate that ETB is localized to nuclei in cardiac ventricular myocytes, although it has been thought that ETB is localized mainly on the plasma membrane. It remains unknown, however, whether this unique distribution of ETB occurs in other tissues. To elucidate the subcellular distribution of ETB in the intestine, we performed immunofluorescence of ETB in mouse intestine using a specific antibody. ETB-like immunoreactivity was detected in both the mucosal and muscle layers. In the mucosal layer, villous epithelial cells, stromal cells of the lamina propria, and cryptic cells were immunostained. Subcellularly, ETB is localized mainly to the nuclei of villous epithelial cells. In the muscle layer, immunoreactivity of ETB was localized to the myenteric plexus. These findings ...
We have been investigating radiation-induced neoplastic transformants of C3H 10T1/2 mouse fibroblasts for evidence of heritable changes. C3H 10T1/2 cells were treated with 8 Gy X rays. After approximately 8 weeks of culture, type II/III foci were isolated from the monolayer using cloning rings. Cell lines developed from these foci, and clones established from these cell lines, were examined for DNA content. The isolated focus-derived populations and derived clones often display aneuploidy and/or polyploidization. In one instance a clone (derived from a single cell) displayed multiple polyploidies. During passage the ploidy of many of the anomalous populations gradually reverted to the ploidy of the non-neoplastically transformed state. The morphological features associated with the neoplastic transformation event were nevertheless retained. The results demonstrate that exposure to radiation can induce, in association with morphological neoplastic transformation, a ...
Water and mud samples were collected from canals and rivers which were adjacent to outlets discharging warm water of 3 power plants in Berlin. Downstream samples from 1 bathing resort were also collected. Free living amoebae were isolated from 138 water and 69 mud samples. From these respectively 156 and 73 strains could be cultured and were administered intranasally to mice for pathogenicity tests. Two Acanthamoeba strains from water and 7 from mud could be reisolated from mouse brain and or lungs, although no pathological disorders could be observed. Five Naegleria strains were negative in mouse inoculation tests. Four Acanthamoeba strains which were positive in mice were cultured at + 45 degrees C; no cytopathogenic effects were observed in tissue cultures. Acanthamoeba infective for mice could also be isolated from samples at low water temperatures. Further investigations have to show, whether changes in virulence of amoebic strains are of ...
The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at ...
Thymic epithelial cells (TECs) constitute a major component of the thymic stroma which provides a microenvironment critical for developing thymocytes. We have previously demonstrated that doxycycline (Dox), a tetracycline derivative, enhances the proliferation of the mouse thymic epithelial cell line 1 (MTEC1) via MAPK/ERK signal pathway. Herein we provide evidence that Dox also has profound impact on the cytokine production by MTEC1. Specifically, the expression of IL-6 and GM-CSF, both at mRNA and protein levels, was found to be increased in a time- and dose-dependent manner with the addition of Dox. Western blotting analysis revealed that treatment with Dox-induced phosphorylation of the p65 subunit of NF-kB and ERK. Notably, Dox-induced up-regulation of IL-6 and GM-CSF was largely abol...
WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) has been demonstrated to be cytotoxic to stem spermatogonia in the mouse. Five and 10 injections of 300 mg/kg killed sufficient numbers of stem cells to reduce sperm production 56 days after treatment by 16 and 43%, respectively. Single injections of 300 or 400 mg/kg of WR-2721 given 15 min after irradiation produced negligible toxicity to stem cells as measured by counts of repopulated tubules; 600 mg/kg reduced stem cell survival by 47%. Four daily injections of 300 mg/kg given 4, 3, 2, and 1 days prior to irradiation reduced stem cell survival by about 60%. The cytotoxic effects of WR-2721 on testicular stem cells at least partially explains the reduced protection factors observed in the testis with low doses of radiation and during fractionated treatments involving multiple injections of drug.
The photobiology of mouse melanocyte lines with different pigment genotypes was studied by measuring colony-forming ability after irradiation. The cell lines were wild-type black (melan-a) and the mutants brown (melan-b) and albino (melan-c). Four lamps emitting various UV wavelengths were used. These were germicidal (UVC, 200-280 nm), 82.3% output at 254 nm, TL01 (UVB, 280-320 nm), 64.2% at 310-311 nm, FS20, broadband with peak output at 312 nm and Alisun-S (UVA, 320-400 nm), broadband with peak output at 350-354 nm. Appropriate filtration reduced the contaminating UVC to nonlethal levels for the longer waverange lamps. It is clear from these studies that, in pigment cells, monochromatic results cannot predict polychromatic responses and that cell death from solar irradiations is a complex phenomenon that depends on more than DNA damage. (author).
Lethal yellow (A{sup y}) is a mutation at the mouse agouti locus in chromosome 2 that causes a number of dominant pleiotropic effects, including a completely yellow coat color, obesity, an insulin-resistant type II diabetic condition, and an increased propensity to develop a variety of spontaneous and induced tumors. Additionally, homozygosity for A{sup y} results in preimplantation lethality, which terminates development by the blastocyst stage. The A{sup y} mutation is the result of a 170-kb deletion that removes all but the promoter and noncoding first exon of another gene called Raly, which lies in the same transcriptional orientation as agouti and maps 280 kb proximal to the 3{prime} end of the agouti gene. The authors present a model for the structure of the A{sub y} allele that can explain the dominant pleiotropic effects associated with this mutation, as well as the recessive lethality, which is unrelated to the agouti gene.
The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.
The usefulness of the mouse, rat, and Syrian golden hamster as experimental models for studies of the development of respiratory tract cancer is considered. Three different application methods for examining the effects of environmental chemicals on the respiratory tract in these species are discussed: implantation, intratracheal instillation, and inhalation. The results of various investigations are presented to demonstrate that each particular method has both advantages and disadvantages. The techniques are also considered in comparison with the human situation and in the light of obtaining the most valid data for extrapolation to man. Brief attention is paid to the relevance to respiratory tract carcinogenesis of more recently developed organ and cell culture systems.
This contribution provides an overview and imparts basic knowledge on pertinent technical developments in magnetic resonance imaging (MRI) of the liver: 3D sequences, respiratory triggering, parallel imaging, and 3 Tesla (3T). 3D sequences can be used as T1-weighted (T1w) sequences for analyzing dynamics of contrast enhancement or as T2w sequences for MR cholangiography. Consistent improvements in respiratory triggering make it possible to obtain good image quality on T2w scans even in patients unable to hold their breath. Parallel imaging as a universal technique to accelerate image acquisition is particularly appropriate for MRI of the liver, and it has been shown that the reduced acquisition time is not achieved at the expense of image quality. Further progress in MRI of the liver can be expected with use of the 3T systems, but hitherto irrelevant problems must still be solved. Overall the innovations presented here, ...
Hyaluronate (HA) distribution patterns were examined in the cranial mesenchyme underlying the mesencephalic neural folds of mouse embryos maintained in roller tube culture. Using standard image-processing techniques, the digitized images of Alcian blue-stained or 3H-glucosamine-labeled sections digested with an enzyme specific for HA, were subtracted from adjacent, undigested sections. The resultant difference picture images (DPI) accurately depicted the distribution of stained or labeled HA within the cranial mesenchyme. 3H-glucosamine-labeled HA was distributed uniformly throughout the cranial mesenchyme as 12, 18, and 24 hr of culture. By contrast, the mesenchyme was uniformly stained with Alcian blue at 12 hr, but stain intensity decreased in the central regions of the mesenchyme at 18 and 24 hr. HA distribution patterns were also examined in the cranial mesenchyme of embryos cultured in the presence of diazo-oxo-norleucine (DON), a glutamine analogue that ...
We irradiated proton beams on the ears of rabbits and the Harding-Passey mouse melanoma and observed their morphological change. We used 52 MeV proton beams from the INS-FM cyclotron. We adjusted the energy of the proton beams to be at the plateau part of the Bragg curve, at the half-way point of the Bragg peak, and at the Bragg peak. The amount of radiation was 5000rad in each case. The Harding-Passey mouse melanoma was transplanted into the subcutan of a three week old mouse. In this experiment, we used tumors, the diameter of which grew up to 1.5-2cm in 2-3 weeks after the transplantation. Using the jroscope, we observed both lightly and severely damaged cells. Using proton irradiation with the Bragg peak located at depth of 1mm in the rabbit's ears, we studied the change in the tissue. Irradiated epidermis fell off and was eroded because of radiation damage, but the rear surface of the rabbit's ears ...
The process of mouse skin tumor formation is subdivided into three operational stages. These stages include initiation, promotion and progression. Ionizing radiation has been found to be a weak initiating agent in the production of malignant squamous cell carcinomas, a complete carcinogen and an agent effective in causing tumor progression. Four skin tumor histologies have been seen with ionizing radiation: benign papillomas, squamous (SCC) and basal (BCC) cell carcinomas and fibrosarcomas. Distinct non-ras transforming genes have been detected in radiation initiated SCCs. A benign papilloma cell line (308) was used as a model system to study ionizing radiation induced progression. A variant 308 cell line (308 10 Gy 5) derived by irradiation of the parental 308 cell has been characterized. The 308 10 Gy 5 cells unlike the parental 308 cells from malignant tumors in athymic nude mice upon subcutaneous injection. The variant 308 10 Gy 5 cells unlike the parental ...
A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and conbination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, "3H-thymidine uptake labeling ...
Medical imaging using single gamma-ray-emitting radionuclides typically makes use of parallel hole collimators or pinholes in order to achieve good spatial resolution. However, a tradeoff in sensitivity is inherent in the use of a collimator, and modern preclinical single photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma rays, often less than 0.1%. A system for small animal SPECT imaging which uses no collimators could potentially achieve very high sensitivity-several tens of percent-with reasonably sized detectors. This would allow two significant improvements in preclinical studies: images could be obtained more rapidly, allowing higher throughput for screening applications, or for dynamic processes to be observed with very good time resolution; and images could be obtained with less radioactive tracer, making possible the in vivo imaging of low-capacity receptor systems, aiding research into new tracer compounds, and reducing the cost ...
Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice. TF activity in liver homogenates increased significantly in TF^f^l^o^x^/^f^l^o^x mice treated with ANIT, but not in TF^f^l^o^x^/^f^l^o^x/LysMCre mice (TFD^M^y^e^l^o^i^d mice), which have reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell-specific TF deficiency did not alter expression of the chemokines KC or MIP-2 but redu...
The radioprotective effects of Liv.52 on tissue-reduced glutathione (GSH) levels were studied in rats. Adult female Sprague Dawley rats were exposed to whole body gamma radiation of 4 Gy and 8 Gy. Prior to radiation exposure, Liv.52 was fed, one ml per rat, daily for 15 days. Three days after radiation exposure, reduced glutathione levels in the liver, spleen, kidney and blood were studied. Liv.52 was beneficial in restoring the spleen weight to body weigh t ratio in the animals of the 4 Gy group. In the spleen and liver, Liv.52 helped to restore reduced glutathione in sub-lethally exposed rats. Blood-reduced glutathione was found to be normal in both groups of experimental rats who received Liv.52. The above results exhibit the radioprotective effects of Liv.52 in relation to tissue-reduced glutathione in experimental rats exposed to sub-lethal doses of radiation. (author). 3 tabs., 25 refs.
A new hydroxyiminoamide ligand, 1-(2-nitroimidazole-1-yl)-propanhydroxyiminoamide (N2IPA) was synthesized. The biodistribution of {sup 99m}Tc-N2IPA in mice bearing S180 tumor demonstrated that the complex showed a selective accumulation in tumor and slow clearance from it. The tumor-to-tissue uptake ratios increased with time. At 4 hours after injection, the uptake ratios of tumor to muscle, blood, liver, heart, and lung reached 8.4, 1.5, 0.6, 2.9, and 2.3, respectively. Moreover, the tumor-to-liver uptake ratio steadily increased to 0.9 at 8 hours and 2.3 at 24 hours. The complex showed little uptake and quick clearance in blood, lung and other organs. Compared with other proposed hypoxia-imaging agents, this novel agent has advantages of higher tumor-to-muscle and tumor-to-blood uptake ratios and easier synthesis.
The aim of this study was to evaluate cucurbitacins (Cucs) liver protective activity in vitro and conduct QSAR studies against lipophilicity and ab initio descriptors. Nine Cucs were isolated from Cucurbitaceae plants and eight prepared by C2-alkylation or C16-acylation. Ten Cucs demonstrated protective activity on human hepatocyte-derived HepG2 cells exposed to CCl4 (EC50=2.4-45.3mM) with good margin to toxicity (T/A). All Cucs exhibited anti-proliferative effect on serum-activated rat stellate cells, HSC-T6 (EC50=0.02-4.12mM) with high T/A. While silybin is nontoxic, its protection is lower compared to Cuc D (3), iso-D (4), I (5), B (11), E (12), I-Me (6), L-Me (7), and E-Me (13) on both cell lines. Strong correlations were found for lipophilicity with both protection and toxicity on Hep...
Homology analyses of the protein sequences of chicken liver and rat mammary gland fatty acid synthases were carried out. The amino acid sequences of the chicken and rat enzymes are 67% identical. If conservative substitutions are allowed, 78% of the amino acids are matched. A region of low homologies exists between the functional domains, in particular around amino acid residues 1059-1264 of the chicken enzyme. Homologies between the active sites of chicken and rat and of chicken and yeast enzymes have been analyzed by an alignment method. A high degree of homology exists between the active sites of the chicken and rat enzymes. However, the chicken and yeast enzymes show a lower degree of homology. The DADPH-binding dinucleotide folds of the {beta}-ketoacyl reductase and the enoyl reductase sites were identified by comparison with a known consensus sequence for the DADP- and FAD-binding dinucleotide folds. The active sites of all of the enzymes are primarily in ...
The utilization of 14.6-min "1"0"1Mo and 25-min "1"3"1Te for the determination of molybdenum and tellurium in biological materials by neutron activation analysis is described for the first time. Radioisotopes were separated from the samples activated in a thermal neutron flux of about 10"1"4 n cm"-"2s"-"1. The radiochemical procedure for molybdenum involves extraction of Mo"6"+ from 6 M HCl into diethylether, re-extraction into water, precipitation as oxinate, and measurement of the gamma activity of "1"0"1Tc. The tellurium was separated by reduction to the element with SO_2 in 3 M HCl, dissolution in HNO_3, and reprecipitation as the element for the measurement of radioactivity. The sensitivity was estimated at ca. 10 ng at the level of confidence of 95%. The methods were tested by analyzing NBS-standard Bovine Liver and Orchard Leaves for molybdenum; the concentrations found were 3.2 +- 0.1 #mu#g g"-"1 and 300 +- 60 ng g"-"1, respectively. The tellurium content ...
Rats from an inbred Sprague-Dawley strain were fed semisynthetic diets with a low (0.3 energy percent (en %)), normal (3 en %) or high (10 en %) content of essential fatty acids (EFA) for at least three generations. Twenty-nine- to 33-day-old male rats were given a single intragastric dose of (1-14C)linoleic acid in olive oil, and the respiratory CO2, urine and feces were collected for 46 hours (expt 1) or 20 hours (expt 2). The 14C activity in respiratory CO2, feces, urine and the carcass was determined in both experiments. In experiment 2 it was also measured in samples of the brown fat, liver, adrenals, white fat, skeletal muscles and brain. In both experiments the rats fed the low EFA diet retained significantly more 14C activity than the rats fed the normal or high EFA diets. In all groups the concentration of label was highest in the brown fat and the adrenals, but the above differences among the groups with respect to 14C retention were mainly observed in ...
Persistent hepatitis C virus (HCV) infection affects 170 million people worldwide. Acute HCV infection is often asymptomatic, but many infected individuals develop persistent infections that may lead to development of end-stage liver diseases, including liver cirrhosis and hepatocellular carcinoma. Thus, an HCV vaccine that could significantly lower the chronicity rate would have a major impact on the disease burden. Unfortunately, HCV is a highly mutable virus, and escape mutations can undermine vaccine-induced virus-specific immunity. Also, HCV exists as multiple genotypes, and so genotype-specific vaccines might be required to achieve broad protection. Finally, vaccine development has been hampered by the lack of a small animal model and cell culture systems, but these are currently being established. Despite these obstacles, several vaccine candidates tested in the chimpanzee HCV model have shown some encouraging results.
Summary The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n?=?29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100?mg/m2 on day 1, leucovorin (calcium folinate, CF) 200?mg/m2 on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000?mg/m2 as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.57?months by combination chemothera...
Cholangiocarcinoma may be associated with recurrent pyogenic cholangitis as a complication of longstanding proliferative cholangitis in the presence of intrahepatic stones. Sonographic and CT findings of six patients with cholangiocarcinoma of the liver associated with recurrent pyogenic cholangitis are presented. The cases were among 128 patients who underwent partial resection of the liver because of recurrent pyogenic cholangitis and its complication. On sonogram the mass was depicted in four patients as an ill-defined heterogenously echogenic mass and in one patient as a bulging contour; in the remaining one case the mass was not detected. There were small or large, shadowing or non shadowing stones within the tumor in five cases. In one case, the stone was in the duct proximal to the tumor. On CT scans of four patients, the tumors were depicted as an ill-defined, irregular low attenuation masses with variable contrast enhancement, the ...
Aims: In this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis. Main methods: Human liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2. Key findings: Pa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by inc...
Brain MRI was carried out in patients with chronic liver diseases. No abnormal findings were recognized in patients with chronic viral hepatitis, while 59.2% of cirrhotics showed a symmetrically strong signal in basal ganglia on T1 weighted image in MRI. This finding significantly related with lowered Fischer`s ratio of serum amino acid, increased levels of serum phenylalanine, tyrosine and hyaluronic acid, prolonged prothrombin time and decreased platelet counts in the peripheral blood. Overt hepatic encephalopathy was observed in 6 of 34 patients with the strong signal in MRI during follow-up period, while none of patients without that finding developed hepatic encephalopathy. These results have indicated that the strong signal in basal ganglia on MRI appears in cirrhotic patients with severe liver dysfunction, and it is an useful index in the early diagnosis of latent hepatic encephalopathy. An improvement of this MRI finding was not ...
Background The American Association for the Study of Liver Diseases (AASLD) guidelines recommend that antibiotic prophylaxis should be instituted in any patient with cirrhosis and gastrointestinal hemorrhage, and that oral norfloxacin, intravenous ciprofloxacin, and ceftriaxone are preferable. However, the antimicrobial spectrum of the first generation of cephalosporins (cefazolin) covers a wide range of bacteria species, including community-acquired strains of Escherichia coli and Klebsiella pneumoniae, but their efficacy as prophylactic antibiotics in cirrhotic patients with acute hemorrhage was seldom warranted in the literature. This study aimed to explore the effects of cefazolin on the outcome of cirrhotic patients with acute variceal hemorrhage after endoscopic interventions. Method...
The reactions of native bovine catalase with superoxide and solvated electrons have been investigated using three different methods for generating these reducing substrates: [gamma]-radiolysis of oxygenated or deaerated buffer solutions in the presence of an OH radical scavenger; either xanthine or acetaldehyde with xanthine oxidase; and low-temperature (77 K) [gamma]-radiolysis of buffered ethylene glycol/water solutions with subsequent annealing of samples at 183 K. (Author).
The oral administration of 2,3-dihydroxybenzoic acid (DHB) to rats injected intravenously 1 hr previously with "2"3"9Pu citrate caused an increase in urinary excretion of Pu about 8 times that of animals treated with 0.9% NaCl (controls). Liver retention of Pu was decreased from 18% at 2 days in the control animals to 11% in DHB-treated rats. The skeletal retention was similarly reduced from 56% in the control group to 40% in the DHB-treated animals.
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
The increasing data complexity engendered by the Accelerated Scientific Computing Initiative (ASCI) requires more capability in our scientific visualization software. B Division at Lawrence Livermore National Laboratory (LLNL) addresses these new and changing requirements with MeshTV. We began work on MeshTV around eight years ago, and have progressively refined the software to provide improved scientific analysis and visualization to well over 100 users at Liver-more, Los Alamos, Sandia, and in private industry. (U)
Dietary supplements of about 5 g/kg of a number of amino acids increased tissue lead concentrations in newly weaned rats but decreased them in older rats. The retention of both oral and intraperitoneal lead was affected. The uptake of "2"0"3Pb by tissues was reduced when methionine was given in the diet over a period of 5 weeks or when it or ethionine was given by mouth 24 h before the activity was measured. In the liver the fraction of the total activity found in the nuclei and mitochondria was increased by methionine, but in the kidney only the fraction found in nuclei was increased.
/sup 99m/Tc biliary imaging was performed on a 34-year-old woman who was being investigated for suspected cholelithiasis. A left-sided liver was detected. On subsequent radionuclide imaging, partial visceral situs inversus and asplenia were demonstrated. Extensive roentgenographic investigation, ECG, echocardiogram, and laparotomy confirmed the radionuclide findings. Asplenia syndrome may exist without cardiovascular abnormalities and thus be undiscovered. Radionuclide imaging is important in the diagnosis of this syndrome.
Injection of pregnant rats with monomeric "2"3"9Pu after 9 days of gestation decreased their leukocyte and reticulocyte counts at 5 and 10 days postexposure. Most of the fetal hematologic enumerative values were unaffected by injection of monomeric "2"3"9Pu. There was, however, a major change in the maturation of the cells of the erythroid series, as indicated by a difference in the distribution between cell types. The weight of the yolk sac and fetal liver, and the cellularity of the fetal spleen were decreased.
Variation of CT units, in organs, before and after using contrast enhancing medium was reviewed and personal experience was presented. In the normal brain CT units was little changed by contrast enhancement (CE), whereas remarkable change was observed at lesions. No difference of CT units was observed between the normal liver and hepatomas. The normal kidney had higher CE effect than hypernephromas suggesting an increase of the sensitivity. CE was not found in cysts or necrosis. The changes of CT units in the cases of cerebral diseases are tabled with various contrast medium and scanners.
Studies have shown that CCl_4 administration to rats inhibits endoplasmic reticulum calcium pump activity and reduces the amount of calcium associated with subsequently isolated microsomal subcellular fractions. This report confirms that exposure of isolated hepatocytes to CCl_4 rapidly produces these effects in isolated parenchymal cells and demonstrates that when isolated hepacytes are exposed to CCl_4 calcium is rapidly released from cells. This release can be detected with a calcium ion-selective electrode when cells are incubated in a medium with low extracellular calcium. Calcium released from an intracellular pool(s) may initiate hepatotoxic changes in liver. (author).
A new phenylboric acid derivative entrapped lipiodol (PBAD-lipiodol) was developed as a boron carrier for the boron neutron capture therapy (BNCT) of hepatoma in Taiwan. The biodistribution of both PBAD-lipiodol and BPA-fructose was assayed in GP7TB hepatoma-bearing rat model. The highest uptake of PBAD-lipiodol was found at 2 h post injection. The application of BNCT for the hepatoma treatment in tumor-bearing rats is suggested to be 2-4 h post PBAD-lipiodol injection.
The rate of hepatic cytochrome P450 Cypla1 and Cyp1a2 induction was investigated in C57BL male mice during induction with o-aminoazotoluene (OAT), benzo[a]pyrene (BP) and 1,4-dihydroxyanthraquinone (AQ). The Cypla1 mPNA level determined by quantitative RT-competitive PCR increased more than three orders of magnitude during induction with OAT and BP compared with untreated animals and remained unchanged during induction with AQ. The Cypla2 mRNA level was only 8.5, 18.7 and 1.9 times higher during induction with OAT, BP and AQ respectively than in untreated mice. At the same time 7-Ethoxyresorufin-O-deethylase (EROD) and 7-Methoxyresorufin-O-demethylase (MROD) activities of Cypla were also investigated in liver. The increase of Cypla1 mRNA level correlated with the increase of EROD activity. This suggests involvement of the transcriptional mechanism of the inducibility of this enzyme. In the case of Cypla2 there was insignificant increase of its mRNA level but high ...
Both increased cell proliferation and {open_quotes}altered{close_quotes}CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area of groups of rats, independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CPY gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a unique composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, 3A1, 3A2, and 4A1, which were variably increased or decreased relative to the untreated control livers, depending on the ...
The plerocercoid stage of the tapeworm Spirometra mansonoides produces a functional analog of human growth hormone (hGH). Among the similarities between plerocercoid growth factor (PGF) and hGH is competition for the same receptors on rabbit liver membranes. To take advantage of this characteristic in a purification scheme for PGF, rabbit liver microsomes were solubilized in Triton X-100 and the hGH receptors were purified over an hGH affinity column. The purified receptors from six rabbit livers were coupled to Affi-Gel-10 to create a receptor affinity column which was used to purify PGF. Chromatography of crude PGF over the receptor column resulted in a 1044 fold increase in specific activity. SDS-PAGE in the presence of 2-mercaptoethanol showed that the affinity-purified PGF contained three protein bands with apparent Mrs of 27.5 K, 22 K, and 16.7 K. Injections of the partially-purified PGF into hypophysectomized rats ...
Abstract Unrefined and refined black raspberry seed oils (RSOs) were examined for their lipid-modulating effects in male Syrian hamsters fed high-cholesterol (0.12% g/g), high-fat (9% g/g) diets. Hamsters fed the refined and the unrefined RSO diets had equivalently lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol in comparison with the atherogenic coconut oil diet. The unrefined RSO treatment group did not differ in liver total and esterified cholesterol from the coconut oil-fed control animals, but the refined RSO resulted in significantly elevated liver total and esterified cholesterol concentrations. The unrefined RSO diets significantly lowered plasma triglycerides (46%; P=.0126) in comparison with the coconut oil diet, whereas the refined RSO only tended to lower plasma triglyceride (29%; P=.1630). Liver triglyceride concentrations were lower in the unrefined (46%; P=.0002) and refined ...
Studies have linked cell phone radiation to health problems such as headaches, high blood pressure, cancer and more. There is a latency period for most diseases and it may take years and more studies before the required weight of evidence is established. But the effects are cumulative and precautions should be taken now before it is too late. The aim of the present study was to investigate if supplementation with antioxidants would protect heart and liver tissues from harmful radiation emitted by cell phone. Thirty two male albino rats were randomly divided into four equal groups: I- Control, II- Antioxidants treated group, III- 950 MHz EMR, IV- 950 MHz EMR + antioxidants. A 950 MHz EMR radiation (217-Hz pulse rate, 2-W maximum peak power, SAR Specific Absorption Rate"1.6 W/Kg) was applied to groups III and IV 60 min/day, for 30 days using an experimental exposure device. Antioxidants supplement (Vitamins A, E and C + Se) was administered to rats daily, by gavages, ...
Radioactive phosphorus (P-32) was injected to the chicken in the purpose of determination of the uptake and distribution, as related to sex and hour differences of the various organs of the body. 2..mu..Ci of P-32 were injected to each chicken and the distribution of P-32 was observed at 1 hr, 6 hrs, 12 hrs, 24 hrs and 48 hrs after injection. In this experiment 34 heads of chicken were used (30 chicken for P-32, 4 chicken for control group) and the results obtained as follows: 1. The uptake of P-32 per gram of various organ in g. mm, femur (1 hr), liver, femur, tibia (24 hrs) and tibia (48 hrs) exhibited higher in the male than the female. 2. The uptake of P-32 per gram of various organ in heart, kidney, ovary (1 hr), kidney, brain (24 hrs) and kidney (48 hrs) exhibited higher in the female than the male. 3. The uptake ratio of brain, spleen, g. mm and tibia were increased gradually by the 12 hrs after injection of P-32, but decreased in liver, ...
Embryos of chicken (Gallus domesticus), domestic duck (Anas platyrhynchos), and common eider duck (Somateria mollissima) were exposed in ovo to PCBs and to polycyclic aromatic hydrocarbons. Two coplanar PCBs, 3,3{prime},4,4{prime}-tetrachlorobiphenyl (PCB {number_sign}77) and 3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB {number_sign}126), were considerably more lethal and potent as inducers of 7-ethoxyresorufin O-deethylase (EROD) in chicken embryos (Gallus domesticus) than in embryos of the other two species. In chicken embryos, these compounds caused edema and eye and beak deformities. An artificial mixture of 18 PAHs which all have been detected in environmental samples, was slightly more toxic to embryos of the domestic duck and the common eider duck than to chicken embryos. The most potent compound in the mixture was benzo(k)fluoranthene. When chicken embryo livers were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vitro, EROD was induced by ...
Purpose: To evaluate the results of radiotherapy in cholangiocarcinoma patients managed with various combinations of chemotherapy and surgical resection with selective liver transplantation. Methods and Materials: From January 1990 to December 1995, 61 patients with histologically confirmed biliary duct adenocarcinoma were seen in the Radiation Oncology Department of the University of Pittsburgh. Median follow-up was 22 months (1 to 91 months). The extent of surgery was complete resection in 23 patients (including 17 with orthotopic liver transplant), partial resection in 4, and biopsy in 34. All patients had radiotherapy; median dose was 49.5 Gy. Thirty patients received chemotherapy: 5-fluorouracil (5-FU)-leucovorin with interferon alpha (IFN#alpha#) in 27, and taxol in 3. Results: The median survival was 20 months (95% CI 15-25 months). The 5-year actuarial survival was 23.8 #+-# 6.8%. The only significant variable in multivariate analysis ...
The patients studied were referred for routine abscess localization with indium-111 labelled autologous leukocytes. One series (n=15) was studied at 1 day after reinjection of labelled cells and a second series (n=9) was studied between 4 hours and 4 days after reinjection of labelled cells. The leukocytes were isolated by a gravity sedimentation method and labelled with In-111 oxinate according to Roevekamp and co-workers. The labelled cell suspension administered to the patient contained between 11 and 15 MegaBq (300-400 microCi). The indium-111 concentration in the liver and spleen was quantitated using a scintillation camera and an on-line computer system. Phantom studies were carried out to obtain conversion factors from geometric mean counts to MegaBq of activity for both liver and spleen. Once determined, the amount of activity in liver and spleen was corrected for physical decay of In-111 and expressed as a ...
We labelled Lipiodol with yttrium-90 and analysed the biodistribution in rats after intrahepatic arterial injection. An RP-18 column was used to separate {sup 90}Y from strontium-90. {sup 90}Y was retained on the column, which had been pretreated with yttrium-selective extraction reagent, di(2-ethylhexyl) phosphate, while {sup 90}Sr was washed out. A hexadentate nitrogen-donor chelating ligand N,N,N`,N`-tetrakis(2-benzymidazolylmethyl)-1,2-ethanediamine (EDTB) was synthesized by condensation of 1,2-benzenediamine and ethylene diamine tetra-acetic acid (EDTA). Lipiodol was covalently conjugated with EDTB. The final product was obtained by eluting the retained {sup 90}Y from the RP-18 column with EDTB-Lipiodol. Sixteen male rats (Sprague-Dawley) were sacrificed at 1 h, 24 h, 48 h and 72 h (four rats at each time) after injection of approximately 0.1 mCi {sup 90}Y-Lipiodol via the hepatic artery. Samples of liver, spleen, muscle, lung, kidney, bone, whole blood and ...
An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces ["1"2"5I]hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10"6 cells/tube) were incubated with ["1"2"5I]hGH and increasing concentrations of hGH (ng/ml) or PGF (serial dilutions) for 90 min at 30"0 C. Specific binding (B_0 - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced ["1"2"5I]hGH from human cells in a dose dependent manner (r = 0.98). Based on the IM-9 assay, 1 ml of the PGF had an activity ...
Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection ...
Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection ...
Lipiodol Ultra-Fluid (Lipiodol) is widely applied in the transcatheter arterial embolization (TAE). We studied signal intensity, the T1 relaxation time and the T2 relaxation time of Lipiodol itself using Siemens Magnetom H15-2 T (1.5 Tesla) and Magnetom M10 (1.0 Tesla). Lipiodol showed higher signal intensity than saline solution on the T1-weighted images (short TR, short TE technique in spin echo method). On the T2-weighted images (long TR, long TE technique in spin echo method), Lipiodol showed lower signal intensity than saline solution. The T1 relaxation time of Lipiodol, measured at 1.0 T, was 201 msec and 218 msec at 1.5 T. The T2 relaxation time of Lipiodol, measured at 1.0 T, was 127 msec; and 167 msec at 1.5 T. The signal intensity of Lipiodol at 1.0 T was higher than the intensity at 1.5 T. Shorter T1 relaxation time of Lipiodol at 1.0 T is probably responsible for the higher intensity at 1.0 T. When MRI is performed after TAE with Lipiodol, the signal intensity of Lipiodol ...
Gamma-irradiation of isolated rat liver mitochondria with up to 475 Gy leading to hydrated electrons (G = 1.9, corrected for reaction with solutes), 30 Gy leading to carbohydrate radicals, (G = 5.6), 100 Gy leading to superoxide radicals (G = 6.2), and 130 Gy leading to formate radicals (G = 6.2) showed no effects on the rate of oxygen uptake in various respiratory states, the respiratory control ratio, or the adenosine diphosphate to atomic oxygen ratio. Typical values were 0.020-0.100 nmol O/sub 2/ s/sup -1/ mg protein/sup -1/ for State 1 respiration, 0.25-0.33 nmol O/sub 2/ s/sup -1/ mg protein/sup -1/ for State 4 respiration and 0.65-1.10 nmol O/sub 2/ s/sup -1/ mg protein/sup -1/ for State 3 respiration. Typical respiratory control ratios ranged from 2.0-3.5 for succinate and 4.0-6.5 for a 1:1 glutamate: malate substrate mixture. Adenosine diphosphate to atomic oxygen ratios with succinate as substrate varied from 1.6 to 1.9. In situ and in vitro irradiated ...
A study of mine-waste contamination effects on Methow River habitat on the eastern slopes of the north Cascade Mountains in Washington state, U.S.A., revealed impacts at ecosystem, community, population, individual, tissue, and cellular levels. Ore deposits in the area were mined for gold, silver, copper and zinc until the early 1950's, but the mines are now inactive. An above-and-below-mine approach was used to compare potentially impacted to control sites. The concentrations of eleven trace elements (i.e., Al, As, B, Ba, Cd, Cr, Cu, Mn, Pb, Se, and Zn) in Methow River sediments downstream from the abandoned mine sites were higher than background levels. Exposed trout and caddisfly larvae in the Methow River showed reduced growth compared to controls. Samples of liver from juvenile trout and small intestine from exposed caddisfly larvae were examined for evidence of metal accumulation, cytopathological change, and chemical toxicity. Morphological changes ...
The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in the blood of mice, ...
The authors compared unenhanced and contrast-enhanced fast MRI and Computerized Tomography in the detection of liver metastases. Eleven patients with single or multiple hepatic lesions (42 in all) were submitted to V and magnetic resonance studies; T1- and T2- weighted TSE, T2-weighted TSE with fat suppression, unenhanced breath-hold TFE and early or delayed enhanced breath-hold TFE images were acquired with a 1.5 T superconductive magnet (Philips NT). The quantitative analysis of all magnetic resonance images was performed for contrast/noise ratio (CNR) and number of detected lesions; magnetic resonance and Computerized Tomography images were also compared qualitatively for lesion conspicuity, anatomical structure identification and artifacts. The results were compared with Student's test. Early enhanced breath-hold TFE was statistically superior to T1-weighted TSE (p = .0009), T2-weighted TSE (p = .01) and Computerized Tomography ( p = .0004) for lesion ...
Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many ...
Anti-carcinoembryonic antigen monclonal antibody (MAb) CEA 102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA 102 in colorectal cancers was investigated by autoradiography of sugical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with {sup 131}I-labeled intact CEA 102 or its F(ab'){sub 2}. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of {sup 131}I-labeled CEA 102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the ...
Anti-carcinoembryonic antigen monclonal antibody (MAb) CEA 102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA 102 in colorectal cancers was investigated by autoradiography of sugical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with "1"3"1I-labeled intact CEA 102 or its F(ab')_2. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of "1"3"1I-labeled CEA 102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of ...
In this paper, we propose and implement a website of post-processing system for finite element analysis (WebDFEA). Finite element analysis is a computer-aided engineering tool and is popular for static/dynamic structure analysis. It includes three processing systems where post-processing system is to graphically demonstrate the analysis result of a structure model analyzed by finite element method. WebDFEA performs as a website. It is cross-platform because it can auto-detect a client computer platform and auto-download proper OpenGL API for drawing computer graphics. It can draw precise graphics on webpage which can be free controlled by the mouse as a manner in professional software. A database server is involved to store finite element model data and its analysis result. The graphic use...
Short synthetic single-stranded oligodeoxyribonucleotides (ssODNs) can be used to introduce subtle modifications into the genome of mouse embryonic stem cells (ESCs). We have previously shown that effective application of ssODN-mediated gene targeting in ESC requires (transient) suppression of DNA mismatch repair (MMR). However, whereas transient down-regulation of the mismatch recognition protein MSH2 allowed substitution of 3 or 4 nucleotides, 1 or 2 nucleotide substitutions were still suppressed. We now demonstrate that single- or dinucleotide substitution can effectively be achieved by transient down-regulation of the downstream MMR protein MLH1. By exploiting highly specific real-time PCR, we demonstrate the feasibility of substituting a single basepair in a non-selectable gene. Howev...
Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters and has a wide range of effects on central nervous system. Adolescence is another important developmental period besides the early critical prenatal and neonatal periods. In the present study, we exposed mice to BPA (40, 400 mg/kg/d) between adolescence and young adulthood for 8 weeks and investigated its effects on the non-reproductive behaviors. In open field tests, rearing and grooming sex differences were abolished by BPA exposure. In the elevated plus maze test, the number of open arm entries, the time spent in open arms, and the number of unprotected head dips in the center area were reduced in males but increased in females by BPA at 40 or 400 mg/kg/d, thus eliminating or reversing sex differences in thes...
Fgf receptor 2c (Fgfr2c) was expressed in mature adipocytes of mouse white adipose tissue (WAT). To examine the role of Fgfr2c in mature adipocytes, we generated adipocyte-specific Fgfr2 knockout (Fgfr2 CKO) mice. The hypertrophy impairment of adipocytes in the mesenteric WAT but not in the subcutaneous WAT and decreased plasma free fatty acid (FFA) levels were observed in Fgfr2 CKO mice. Although the expression of genes involved in adipocyte differentiation and lipid metabolism in the mesenteric WAT was essentially unchanged, the expression of uncoupling protein 2 potentially involved in energy dissipation was significantly increased. Among potential Fgf ligands for Fgfr2c, Fgf9 was preferentially expressed in the mesenteric WAT. The present findings indicate that Fgfr2c potentially activ...
The laboratory environment existing outside the test situation itself can have a substantial influence on results of some behavioral tests with mice, and the extent of these influences sometimes depends on genotype. For alcohol research, the principal issue is whether genotype-related ethanol effects will themselves be altered by common variations in the lab environment or instead will be essentially the same across a wide range of lab environments. Data from 20 inbred strains were used to reduce an original battery of seven tests of alcohol intoxication to a compact battery of four tests: the balance beam and grip strength with a 1.25g/kg ethanol dose and the accelerating rotarod and open-field activation tests with 1.75g/kg. The abbreviated battery was then used to study eight inbred str...
Aims: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca^2^+ homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. Main methods: We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-d...
Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A4 (LXA4) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA4, ANXA1, SAA ...
Our understanding of prenatal behavior has been significantly advanced by techniques for direct observation and manipulation of unanesthetized, behaving rodent fetuses with intact umbilical connections to the mother. These techniques involve brief administration of an inhalant anesthesic, enabling spinal transection of the rat or mouse dam, after which procedures can continue with unanesthetized dams and fetuses. Because anesthetics administered to the mother can cross the placental barrier, it is possible that fetuses are anesthetized to varying degrees. We compared in perinatal rats the effects of prenatal maternal exposure to two inhalant anesthetics: ether and isoflurane. Fewer spontaneous fetal movements and first postpartum nipple attachments were observed following maternal exposure...
The findings reported in this study highlight several important features of the development of hematopoietic stem cells after transplantation into irradiated recipients. First, they demonstrate the existence of a class of primitive multipotential stem cells that can function for a significant portion of the lifetime of a mouse (15 mo). In addition, they clearly show that these primitive stem cells can be infected with recombinant retroviruses and thus would be appropriate targets for gene therapy in somatic tissues. Second, our data indicate that the progeny of some, but not all, of the primitive stem cells have fully expanded into the various hematopoietic lineages by 2 mo after reconstitution. Finally, our analysis of the secondary recipients provides strong evidence suggesting that the primitive stem cell population can actually clonally expand. Our current experiments are aimed at determining the extent to which this expansion can occur and whether or not this ...
Many organizations are challenged with the tasks of identifying customer needs and expectations for their products, anticipating future product needs, communicating a future product vision to clients, and designing with today's technology to bring a future vision to successful realization. The design evolution of plant control centres is one aspect of CANDU development that faces such challenges. The Disney Corporation is an example of an organization that has been successful in consistently meeting these challenges for over fifty years; and some of the design practices proven in moviemaking, theme park and resort layout, and vacation experience organization may be helpful and effective when applied in other domains. This paper summarizes the findings from an examination of Disney Corporation design practices, and suggests how some practices could be used to simplify and enhance the design of future CANDU control centres. (author)
Abstract Objectives: This investigation reviewed experimental studies of laser irradiation of wound healing in mice and rats published from 2003 to August 2008, respectively, to assess putative stimulatory effects of this treatment. Background: Animal models, including rodents, attempt to reflect human wound healing and associated problems such as dehiscence, ischemia, ulceration, infection, and scarring. They have played a key role in furthering understanding of underlying mechanisms involved in impaired wound healing, and in testing new therapeutic strategies including laser irradiation. Method: Original research papers investigating effects of laser or monochromatic light therapy on wound healing in mice and rats and published from January 2003 to August 2008 were retrieved from library...
We report for the first time a relationship between the Tpl-2/cot oncogene and Mouse Mammary Tumor Virus (MMTV) associated transformation of mammary gland cells. A sub-genomic library generated from a primary mammary gland tumor yielded a novel MMTV integration site which disrupted the Tpl-2/cot proto-oncogene between exons 7 and 8. Comparison of a cell line derived from normal mammary gland (comma-D) and a cell line established from an MMTV induced mammary tumor (GR) demonstrated similar rearrangements within Tpl-2/cot for the GR cells but not in the comma-D cells. These rearrangements in the cell line were accompanied by an increase in the level of Tpl-2/cot specific mRNA. This data suggests that Tpl-2/cot expression may be important in epithelial cell transformation or tumor progression. PMID:8934549
Sulfur mustard (HD) is an alkylating and cytotoxic chemical warfare agent, which inflicts severe skin toxicity and an inflammatory response. Effective medical countermeasures against HD-caused skin toxicity are lacking due to limited knowledge of related mechanisms, which is mainly attributed to the requirement of more applicable and efficient animal skin toxicity models. Using a less toxic analog of HD, chloroethyl ethyl sulfide (CEES), we identified quantifiable inflammatory biomarkers of CEES-induced skin injury in dose- (0.05-2 mg) and time- (3-168 h) response experiments, and developed a CEES-induced skin toxicity SKH-1 hairless mouse model. Topical CEES treatment at high doses caused a significant dose-dependent increase in skin bi-fold thickness indicating edema. Histopathological e...
The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation...
The ultimate goal of this research is to generate and apply novel technologies to speed completion and integration of the human genome map and sequence with biomedical problems. To do this, techniques were developed and genome-wide resources generated. This includes a genome-wide Mapped and Integrated BAC/PAC Resource that has been used for gene finding, map completion and anchoring, breakpoint definition and sequencing. In the last period of the grant, the Human Mapped BAC/PAC Resource was also applied to determine regions of human variation and to develop a novel paradigm of primate evolution through to humans. Further, in order to more rapidly evaluate animal models of human disease, a BAC Map of the mouse was generated in collaboration with the MTI Genome Center, Dr. Bruce Birren.
Photoacoustic microscopy (PAM) offers label-free, optical absorption contrast. A high-speed, high-resolution PAM system in an inverted microscope configuration with a laser pulse repetition rate of 100,000 Hz and a stationary ultrasonic transducer was built. Four-dimensional in vivo imaging of microcirculation in mouse skin was achieved at 18 three-dimensional volumes per second with repeated two-dimensional raster scans of 100 by 50 points. The corresponding twodimensional B-scan (50 A-lines) frame rate was 1800 Hz, and the one-dimensional A-scan rate was 90,000 Hz. The lateral resolution is 0.23+/-0.03 ?m for Au nano-wire imaging, which is 2.0 times below the diffraction limit.
Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...
Summary Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB r...
Erythroid differentiation regulator (Erdr1) was first discovered in mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression, which has a pro-cancer effect in melanoma. To study the role of Erdr1 as an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify the factors involved in Er...
The effects of dietary plant and yeast cerebroside (glucosylceramide), a major sphingolipid in plants and yeast, on atopic dermatitis (AD) like symptoms were investigated in a mouse model. After 7 wk of feeding with a diet containing maize glucosylceramide, plasma IgE levels became significantly lower and in contrast, the levels of interleukin (IL)-12, which induces cellular immunity, became significantly higher in the AD mice than in the controls. However, the sphingolipid constituents of the skin fraction in the maize glucosylceramide fed group did not contain sphingoid bases of plant origin, such as 8-unsaturated sphingoid bases. The results of the present study indicated that dietary plant glucosylceramide prevented AD-like symptoms in AD model mice via regulation of Th1/Th2 balance. P...
Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. We have created a database of evolutionary conserved regions (ECRs) in vertebrate genomes entitled ECRbase that is constructed from a collection of pairwise vertebrate genome alignments produced by the ECR Browser database. ECRbase features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a collection of promoters in all vertebrate genomes presented in the database. The database also contains a collection of annotated transcription factor binding sites (TFBS) in all ECRs and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and two pufferfish genomes. It is freely accessible at http://ECRbase.dcode.org.
XMRV or xenotropic murine leukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs. Shyh-Ching Lo and Harvey Alter discovered the presence of sequences closely related to XMRV in the blood of 86.5% of patients with CFS [1]. These findings are important because since the initial discovery of XMRV in CFS, several studies have failed to find XMRV in specimens collected from CFS patients. While the current study also did not find XMRV in CFS, Lo et al. did detect sequences that belong to polytropic mouse endogenous retroviruses (PMV), which share considerable similarity with XMRV. Criteria for future studies that will help bring greater clarity to the issue of retroviral sequences in CFS are proposed below. PMID:21994623
Purpose. The paper introduces a novel design of air-core inductive sensors in printed circuit board (PCB) technology for a tongue control system. The tongue control system provides a quadriplegic person with a keyboard and a joystick type of mouse for interaction with a computer or for control of an assistive device. Method. Activation of inductive sensors was performed with a cylindrical, soft ferromagnetic material (activation unit). Comparative analysis of inductive sensors in PCB technology with existing hand-made inductive sensors was performed with respect to inductance, resistance, and sensitivity to activation when the activation unit was placed in the center of the sensor. Optimisation of the activation unit was performed in a finite element model. Results. PCBs with air-core indu...
In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles.
In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles.
Amphiphysin is a protein concentrated in neuronal synapses and peripherally associated with neurotransmitter vesicles. It is expressed in many neurons of the central and peripheral nervous systems, in the adrenal medulla, in the anterior and posterior pituitary, in cell lines of the endocrine pancreas, and in spermatocytes. Its subcellular localization and tissue distribution indicate a potential involvement in mechanisms of regulated exocytosis. A role in the dynamic organization of the membrane-associated cytoskeleton is suggested by structural homology to the products of two yeast genes, RVS161 and RVS167, whose mutation results in an abnormal actin distribution, disturbs budding morphology, and impairs cell entry into stationary phase. Limited stretches of sequence similarity, including an SH3 domain, are also shared with other actin-binding proteins. Amphiphysin is the dominant autoantigen in paraneoplastic Stiff-Man syndrome, a neurological autoimmune disorder characterized by ...
PCR detection of genetic material of the parasites present in faeces may be an alternative for microscopic and serological tests routinely used for diagnosing parasitic enteral infections. However, small amount of target DNA combined with low efficiency of total DNA extraction, and presence of PCR inhibitors in the samples to be amplified, may cause false negative detection results. The aim of this work was to evaluate the impact of DNA isolation procedure used on the amplification of DNA fragments from the genomes of protozoan Cryptosporidium parvum and the nematode Trichinella spiralis. Two methods based on different principles of biological material lysis were evaluated; NucliSENS miniMAG employing simultaneously applied chemical lysis and mechanical disruption or mechanical disruption followed by enzymatic lysis in case of QIAamp DNA Stool Mini Kit. Both of the analyzed systems for nucleic acids purification allowed isolation of DNA from purified Cryptosporidium parvum oocysts and ...
Dose-response studies of the radiosensitivity of spermatogonial stem cells in various epithelial stages after irradiation with graded doses of fission neutrons of 1 MeV mean energy were carried out in the Cpb-N mouse. These studies on the stem cell population in stages IX-XI yielded simple exponential lines characterized by an average D0 value of 0.76 +/- 0.02 Gy. In the subsequent epithelial stages XII-III, a significantly lower D0 value of 0.55 +/- 0.02 Gy was found. In contrast to the curves obtained for stem cells in stages IX-III, the curves obtained in stages IV-VIII indicated the presence of a mixture of radioresistant and radiosensitive stem cells. In stage VII, almost no radioresistant stem cells appeared to be present and a D0 value for the radiosensitive stem cells of 0.22 +/- 0.01 Gy was derived. Previously, data were obtained on the size of colonies (in number of spermatogonia) derived from surviving stem cells. Combining these data with data from the ...
In the bacterial reversion assay with S. typhimurium TA98, TA100, TA1535 and TA1537, gamma irradiated hyaluronic acid (10 and 50 kGy) did not induce a significant increase in the number of revertant colonies in the presence of S9 metabolic activation system. In chromosomal aberration tests with CHO cells, gamma irradiated hyaluronic acid (10 and 50 kGy) did not result in an increase in the frequency of chromosomal aberrations. In vivo mouse micronucleus assay, gamma irradiated hyaluronic acid (10 and 50 kGy) did not show an increase in the frequency of polychromatic erythrocytes with micronuclei. These results indicate that hyaluronic acids irradiated at 10 and 50 kGy did not show any genotoxic effects under these experimental conditions. In order to evaluate their possible subacute toxicity, the male and female of ICR mouse were given to methanol extract of 50 kGy irradiated red ginseng and 20 kGy irradiated water extract of mistletoe for ...
The purpose of this study is to evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and "1"1"1In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/luc mouse xenografts. HT-29 cells stably transfected with plasmid vectors containing luciferase gene (luc) were transplanted subcutaneously into the male NOD/SCID mice. Biodistribution of the drug was performed when tumor size reached 500-600 mm"3. The uptakes of "1"1"1In-VNB-liposome in tumor and normal tissues/organs at various time points postinjection were assayed. Multimodalities, including gamma scintigraphy, bioluminescence imaging (BLI) and whole-body autoradiography (WBAR), were applied for evaluating the therapeutic efficacy when tumor size was about 100 mm"3. The tumor/blood ratios of "1"1"1In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respectively, at 1, 4, 24, 48 and 72 h postinjection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, ...
The sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) #alpha#subunit forms a binding site for #alpha#-bungarotoxin (#alpha#-BTX). Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR #alpha#1 subunits were tested for their ability to bind "1"2"5I-#alpha#-BTX, and differences in #alpha#-BTX affinity were determined by using solution (IC_5_0s) and solid-phase (K_ds) assays. Panels of overlapping peptides corresponding to the complete #alpha#1 subunit of mouse and human were also tested for #alpha#-BTX binding, but other sequence segments forming the #alpha#-BTX site were not consistently detectable. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased #alpha#-BTX binding, whereas ...
Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which ...
A major regulatory element required for expression of the human [alpha]-globin genes is located 40 kb upstream of the embryonic [zeta]-globin gene. To understand how this and other locus control region (LCR) elements contribute to high-level expression in erythroid cells, we have performed high-resolution, in vivo dimethyl sulfate footprinting. In addition, we have modified the dimethyl sulfate-based ligation-mediated polymerase chain reaction in vivo footprinting procedure to permit the assessment of interactions at guanine and adenine residues, rather than guanines alone. In vivo footprinting of the human [alpha]-LCR element carried on chromosome 16 in a mouse erythroleukemia cell environment revealed protein occupancy at GATA-1, AP-1/NF-E2, and CACC/GGTGG motifs, specific differences compared with in vitro protein binding, and distinct changes in one region upon dimethyl sulfoxide-induced cellular maturation. No protein contacts were detected in nonexpressing ...
The detection and quantification of defined reaction products of chemical mutagens and carcinogens (and of many cancer chemotherapeutic agents) with DNA require highly sensitive analytical techniques. The exceptional capability of immunoglobulins to recognize subtle alterations of molecular structure (especially when monoclonal antibodies are used to maximize specificity), outstanding sensitivity of immunoanalysis by high-affinity antibodies, and the fact that radioactively-labelled agents are not required suggest the utility of a radioimmunoassay to recognize and quantitate alkylated DNA products. We have recently developed a set of high-affinity monoclonal antibodies (secreted by mouse x mouse as well as by rat x rat hybridomas; antibody affinity constants, 10"9 to > 10"1"0 lmol) specifically directed against several DNA alkylation products with possible relevance in relation to both mutagenesis and malignant transformation of mammalian ...
Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced /sup 86/Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. /sup 86/Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated /sup 86/Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs adenosine 5'-(beta, gamma-imido)triphosphate ...
Despite extensive clinical use of thallium-201 (/sup 201/Tl) for myocardial imaging, the effect of ischemia on myocardial accumulation and release of /sup 201/Tl independent of flow has not been fully defined. Therefore, myocardial accumulation of /sup 201/Tl in response to ischemic-like myocardial injury was assessed in vitro using the cultured fetal mouse heart preparation. Cultured fetal mouse hearts (n . 311) were subjected to injury simulating ischemia by deprivation of oxygen and oxidizable substrates for periods ranging from 15 minutes to 10 hours. The extent of irreversible injury was determined by the percentage of lactic dehydrogenase (LDH) lost from the hearts to the culture medium during recovery from injury. Injury was essentially reversible at 1 hour of insult. The fraction of /sup 201/Tl content in injured compared with control hearts was not significantly lower after 1 hour of insult. By 3 hours of insult, irreversible injury as ...
Duchenne and Becker muscular dystrophies are caused by defects of dystrophin, which forms a part of the membrane cytoskeleton of specialized cells such as muscle. It has been previously shown that the dystrophin-associated protein A1 (59-kDa DAP) is actually a heterogeneous group of phosphorylated proteins consisting of an acidic ({alpha}-A1) and a distinct basic ({beta}-A1) component. Partial peptide sequence of the A1 complex purified from rabbit muscle permitted the design of oligonucleotide probes that were used to isolate a cDNA for one human isoform of A1. This cDNA encodes a basic A1 isoform that is distinct from the recently described syntrophins in Torpedo and mouse and is expressed in many tissues with at least five distinct mRNA species of 5.9, 4.8, 4.3, 3.1, and 1.5 kb. A comparison of the human cDNA sequence with the GenBank expressed sequence tag (EST) data base has identified a relative from human skeletal muscle, EST25263, which is probably a human ...
The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and retinoic acid receptor beta(2), by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza; 0.25 mg/kg body weight), all-trans retinoic acid (RA; given at 100 microg/kg body weight and 1 mg/kg body weight), and the combination of 5-Aza and the low-dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were done for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. Although all drug treatments limited the increase in the percentage of proliferating cell nuclear antigen-positive ...
To determined precisely a possible connection between the amount of copper in tap-water and the risk of early childhood liver disease, it was attempted through an epidemiological survey, to determine the extent of excessive concentrations of copper in the tap-water of households with copper pipes. Water samples from 956 households were tested for copper, and the state of health of the infants in these households was documented. Infants who had been fed using water with a copper concentration of 0.8 mg/l or more received a paediatric examination with a blood serum analysis to rule out any liver damage. A copper level greater than 0.8 mg/l was found in only 2% of the households examined. Eight infants were examined by a paediatrician and their serum was analysed. These infants had either been breast-fed to the 12th week or had received more than 200 ml of tap water per day during first 12 months. None of the infants examined showed any signs of ...
Hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) is a genetic disorder with autosomal dominance, variable penetrance, and an estimated prevalence of 1/10,000 inhabitants in France. Diagnosis is based on clinical criteria including epistaxis, telangiectasia, visceral manifestations, and familial occurrence. Pulmonary arteriovenous malformations, present in 15-33% of patients, are its primary visceral complications. The disease may be revealed by infectious and ischemic neurological manifestations due to paradoxical embolism. The high frequency of neurologic complications even in asymptomatic patients justifies systematic screening for pulmonary arteriovenous malformations. Treatment of these malformations is based on percutaneous transcatheter coil embolization of the feeding artery. Pulmonary arterial hypertension is rare in this disease. It may be due to systemic arteriovenous shunting in the liver, which increases cardiac output, or be similar to ...
Tungsten, in the form of tungstate, polymerizes with phosphate, and as extensive polymerization occurs, cellular phosphorylation and dephosphorylation reactions may be disrupted, resulting in negative effects on cellular functions. A series of studies were conducted to evaluate the effect of tungsten on several phosphate-dependent intracellular functions, including energy cycling (ATP), regulation of enzyme activity (cytosolic protein tyrosine kinase [cytPTK] and tyrosine phosphatase), and intracellular secondary messengers (cyclic adenosine monophosphate [cAMP]). Rat noncancerous hepatocyte (Clone-9), rat cancerous hepatocyte (H4IIE), and human cancerous hepatocyte (HepG2) cells were exposed to 1-1000 mg/l tungsten (in the form of sodium tungstate) for 24 h, lysed, and analyzed for the ab...
In the present study, chloroform, aqueous, (polyethylene glycol/propylene carbonate) PEG/PC extracts were made from coconut, onion, garlic, fig, date tree, chicory, ananas, and cistrose. These extracts were tested in vivo and in vitro on their anthelmintic activity against cestodes (Hymenolepis diminuta, H. microstoma, Taenia taeniaeformis) and trematodes (Fasciola hepatica, Echinostoma caproni). In all in vitro tests, the target parasites died. It turned out that the treatment of mice and rats with a combination of onion and coconut extracts (with PEG/PC) eliminated all cestodes from their final hosts. In addition, the same composition was effective against the intestinal fluke E. caproni, but not against the liver fluke F. hepatica in the final host, while both worms were killed in vitro...
Purpose - The objective of this study is to examine the effects of pan-frying, boiling and cooking in a microwave on the amount of L-carnitine in meat and to look at its distribution in the surrounding fluid after food processing. Design/methodology/approach - Total carnitine, free carnitine and acylcarnitines were determined in meat samples from beef, pork and poultry (including ostrich) and in a liver sample from beef. The measurements were carried out before and after the specimens were subjected to different heat treatments. A radio-enzymatic assay was used for measurement of L-carnitine. Results are expressed per 100 gram dry matter and per 100 gram wet weight. Findings - Except for pan-frying, virtually no losses of carnitine occurred during the different procedures of heat treatment...
Objective: To investigate the X-ray radiation dose patients dealt with the hepatic intervention. Methods: Thermoluminescence and tissue-equivalent anthropomorphic phantom were used to measure the X-ray radiation dose in patients dealt with the hepatic intervention in 85 patients. Results: The peak skin dose in the patients who accepted hepatic intervention was from 179.95 to 1759.00 mGy, effective dose approached 29.22 mSv (male), 29.27 mSv (female). Conclusion: Hepatic intervention is now regarded as an important therapeutic method for liver cancer. However, the patients were exposed to too much X-ray radiation during interventional procedures. Some more effective protection should be taken to decrease the X-ray radiation dose accepted by patients. (authors)
It is a useful hypothesis to thing of the reaction to protein deprivation as made up of two parts. First there is an initial adaptation involving rapid losses of protein. This is followed by slow continuing depletion. When considering two organ groups, such as the liver and muscle, it appears that the curve of urinary nitrogen excretion reflects the different parts they play in these two phases. The changes in the relative amounts of protein in different organs results in an alteration in the pattern of body protein at the level of the organ, the tissue and the cell. These changes are themselves the result of altered rates of synthesis and breakdown. The questions that must be asked and hopefully will be answered with the help of isotopes, are how these changes are brought about, how they are inter-related and controlled, and what is their significance? This paper contains a discussion of the few results that have been obtained so far. 1 fig.
Purpose: The purpose of this study was to observe the process of fixation in liver specimens non-invasively by means of magnetic resonance. The fixation process of several formaldehyde-containing solutions was monitored with MRI and MRS at two different temperatures. Materials and Methods: Liver specimens were conserved in aqueous fixative solutions containing formaldehyde concentrations of 0.7, 1.8, 4 and 7.2% and at different temperatures of 5 C and 20 C. MRI was performed with T1-, T2- and PD-weighted TSE sequences, a 2D FLASH-sequence with and without magnetization transfer, and a FISP 3D-sequence on a clinical 1.5 Tesla MR whole-body unit, and MRS with {sup 1}H-spectroscopic methods (STEAM-sequence) on a 3 Tesla MR whole-body unit. Results: The diffusion of formaldehyde into the tissue was best identified on PD- and T1-weighted images as a band under the liver surface with increasing thickness, penetrating especially ...
Abstract The heterotetrameric K++-channel KCNQ1/KCNE1 is expressed in heart, skeletal muscle, liver and several epithelia including the renal proximal tubule. In the heart, it contributes to the repolarization of cardiomyocytes. The repolarization is impaired in ischemia. Ischemia stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase, sensing energy depletion and stimulating several cellular mechanisms to enhance energy production and to limit energy utilization. AMPK has previously been shown to downregulate the epithelial Na++ channel ENaC, an effect mediated by the ubiquitin ligase Nedd4-2. The present study explored whether AMPK regulates KCNQ1/KCNE1. To this end, cRNA encoding KCNQ1/KCNE1 was injected into Xenopus oocytes with and without additional injection o...
Two cases of focal nodular hyperplasia (FNH), in which ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MR) studies detected an atypical hemorrhagic pattern associated with an intrahepatic arterio venous malformation (AVM) around the growths, are presented. In both cases, histology demonstrated a very early regenerative stage and necrotic-hemorrhagic areas within the lesions. In these cases, the analysis of radiological findings, surgical specimens and histology seemed to confirm the pathogenetic hypothesis suggested by Wanless: in normal liver parenchyma, a ``blood steal`` phenomenon due to congenital or acquired intrahepatic AVM could cause ischemic damage, appearing as a hemorrhagic necrotic area, the extent of which depends on the degree of residual portal supply. (orig.)
Atrazine is one of the most commonly used herbicides in the United States. While effective on target plants, it has been associated with harmful health effects in non-target organisms such as fish, amphibians and mammals. In this study, growth effects on human liver cells were determined after exposure to increasing concentrations of this herbicide. Growth of immortalized human hepatoma HepG2 cells was inhibited by atrazine concentrations of 625 ppb after 72 h exposure and flow cytometry analysis demonstrated HepG2 cells exposed to 100 ppb atrazine accumulated in S phase after 48 h compared to untreated cells. Expression of cell cycle specific cyclin proteins was altered after atrazine exposure with cyclin E levels significantly decreased after a 24 h exposure and cyclin B levels decreased...
A review is presented of the literature through 1977 on the uses of radioactive lead isotopes in metabolic studies in man, animals, and plants. These studies have been done mainly with the naturally-occurring, long-lived (22-yr half life) "2"1"0Pb, but a few were with 53-hr "2"0"3Pb or 10.6-hr "2"1"2Pb. Such studies have made possible estimates of the metabolic parameters of lead in man and animals, such as intestinal absorption, the ratio of fecal-to-urinary excretion of endogenous lead, residence time of lead in the body and in various organs, and the distribution in the body (skeleton, liver, kidney, and blood). Subsequently, these parameters and data have been used to trace the sources of lead for man, such as those from the atmosphere, food, cigarette smoke, and automobile exhaust.
4-Methylcoumarins that possess two hydroxyl groups ortho to each other in the benzenoid ring have shown to have excellent antioxidant and radical-scavenging properties in different experimental models. Furthermore, they cannot be metabolized by the liver P450 monoxygenases and thus cannot form 3,4-coumarin epoxides, which are believed to be mutagenic. Herein, we present a study on the structure activity relationship of eight synthetic 4-methylcoumarins, carried out by employing a series of different chemical cell-free tests. These compounds were tested by means of three assays involving one redox reaction with the oxidant (DPPH assay, ABTS+ assay and FRAP). Other assays were employed to evaluate the antioxidant properties of the coumarins under investigation against NO, O2- and HClO, which...
Eremostachys laciniata (L) Bunge (family: Lamiaceae alt. Labiatae; subfamily: Lamioideae) is one of the 15 endemic Iranian herbs of the genus Eremostachys. A decoction of the roots and flowers of E. laciniata has traditionally been taken orally for the treatment of allergies, headache and liver diseases. Three antibacterial iridoid glucosides, phloyoside I (1), phlomiol (2) and pulchelloside I (3) have been isolated from the rhizomes of this plant. The structures of these compounds were elucidated unequivocally by a series of 1D and 2D NMR analyses. The antibacterial activity and brine shrimp toxicity of these compounds were assessed using the resazurin microtitre assay and the brine shrimp lethality assay, respectively. All three iridoid glycosides 1-3 exhibited from low to moderate level...
Abstract Alcohol drinking is highly prevalent in many cultures and contributes to the global burden of disease. In fact, it was shown that alcohol constitutes 3.2% of all worldwide deaths in the year 2006 and is linked to more than 60 diseases, including cancers, cardiovascular diseases, liver cirrhosis, neuropsychiatric disorders, injuries and foetal alcohol syndrome. Alcoholism, which has been proven to have a high genetic load, is one potentially fatal consequence of chronic heavy alcohol consumption, and may be regarded as one of the most prevalent neuropsychiatric diseases afflicting our society today. The aim of the integrated genome research network -Genetics of Alcohol Addiction--which is a German inter-/trans-disciplinary life science consortium consisting of molecular biologists,...