The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Robert R Maronpot - One of the best experts on this subject based on the ideXlab platform.
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prediction of rodent carcinogenesis an evaluation of prechronic liver lesions as forecasters of liver tumors in ntp carcinogenicity studies
Toxicologic Pathology, 2004Co-Authors: D G Allen, G Pearse, Joseph K Haseman, Robert R MaronpotAbstract:The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity (or lack of carcinogenicity). Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice (83 compounds) and rats (87 compounds) was assessed. These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular Cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increase dl iver weight. Our results indicate that pooling 3 of these prechronic data points (hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular Cytomegaly) can be very predictive of carcinogenicity in the 2-year study ( p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted ( p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential.
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prediction of rodent carcinogenesis an evaluation of prechronic liver lesions as forecasters of liver tumors in ntp carcinogenicity studies
Toxicologic Pathology, 2004Co-Authors: D G Allen, G Pearse, Joseph K Haseman, Robert R MaronpotAbstract:The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity (or lack of carcinogenicity) are assessed. Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice (83 compounds) and rats (87 compounds). These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular Cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increased liver weight. Our results indicate that pooling 3 of these prechronic data points (hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular Cytomegaly) can be very predictive of carcinogenicity in the 2-year study (p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted (p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential.
Dorota Nowakowska - One of the best experts on this subject based on the ideXlab platform.
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TLR9 2848 GA Heterozygotic Status Possibly Predisposes Fetuses and Newborns to Congenital Infection with Human Cytomegalovirus
2015Co-Authors: Wioletta Wujcicka, Edyta Paradowska, Mirosława Studzińska, Zuzanna Gaj, Jan Wilczyński, Zbigniew Leśnikowski, Dorota NowakowskaAbstract:BackgroundSome single nucleotide polymorphisms (SNP), located in Toll-like receptor (TLR) genes, were reported to be associated with human cytomegalovirus (HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4 and TLR9 genes with the occurrence of congenital Cytomegaly, based on available samples.MethodsReported case-control study included both HCMV infected and non-infected fetuses and newborns. The specimens were classified to the molecular analyses, based on serological features of the recent infection and HCMV DNAemia in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was assessed for the identified genotypes. The linkage disequilibrium was also estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and congenital Cytomegaly development was estimated, using a logistic regression model.ResultsHardy Weinberg equilibrium was observed for almost all SNPs, both infected and non-infected patients, with exception of TLR4 896 A>G polymorphism in the control group (P≤0.050). TLR4 896 A>G and 1196 C>T SNPs were found in linkage disequilibrium in both study groups (P≤0.050). The CC genotype at TLR4 1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated with HCMV infection (P≤0.050). The risk of congenital Cytomegaly was higher in heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the reported locus (OR 4.81; P≤0.050). The GC haplotype at TLR4 SNPs and GCA variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection (P≤0.0001). The ACA variants were more frequent among fetuses and neonates with symptomatic, rather than asymptomatic Cytomegaly (P≤0.0001).ConclusionsTLR4 and TLR9 polymorphisms may contribute to the development of congenital infection with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly predisposes to HCMV infection, increasing the risk of congenital Cytomegaly development.
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TLR9 2848 GA heterozygotic status possibly predisposes fetuses and newborns to congenital infection with human cytomegalovirus.
Public Library of Science (PLoS), 2024Co-Authors: Wioletta Wujcicka, Edyta Paradowska, Mirosława Studzińska, Zuzanna Gaj, Jan Wilczyński, Zbigniew Leśnikowski, Dorota NowakowskaAbstract:Some single nucleotide polymorphisms (SNP), located in Toll-like receptor (TLR) genes, were reported to be associated with human cytomegalovirus (HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4 and TLR9 genes with the occurrence of congenital Cytomegaly, based on available samples.Reported case-control study included both HCMV infected and non-infected fetuses and newborns. The specimens were classified to the molecular analyses, based on serological features of the recent infection and HCMV DNAemia in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was assessed for the identified genotypes. The linkage disequilibrium was also estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and congenital Cytomegaly development was estimated, using a logistic regression model.Hardy Weinberg equilibrium was observed for almost all SNPs, both infected and non-infected patients, with exception of TLR4 896 A>G polymorphism in the control group (P≤0.050). TLR4 896 A>G and 1196 C>T SNPs were found in linkage disequilibrium in both study groups (P≤0.050). The CC genotype at TLR4 1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated with HCMV infection (P≤0.050). The risk of congenital Cytomegaly was higher in heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the reported locus (OR 4.81; P≤0.050). The GC haplotype at TLR4 SNPs and GCA variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection (P≤0.0001). The ACA variants were more frequent among fetuses and neonates with symptomatic, rather than asymptomatic Cytomegaly (P≤0.0001).TLR4 and TLR9 polymorphisms may contribute to the development of congenital infection with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly predisposes to HCMV infection, increasing the risk of congenital Cytomegaly development
François Davodeau - One of the best experts on this subject based on the ideXlab platform.
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Grade of activity-related renal histological features.
2016Co-Authors: Laëtitia Dorso, Edith Bigot-corbel, Jérôme Abadie, Maya Diab, Sébastien Gouard, Frank Bruchertseifer, Alfred Morgenstern, Catherine Maurel, Michel Chérel, François DavodeauAbstract:Activity-related increases in (A) Cytomegaly/karyomegaly, (B) proteinaceous casts and (C) glomerulosclerosis, of control mice (n = 8), mice injected with 3.7 MBq (n = 5), 7.4 MBq (n = 8) and 11.1 MBq (n = 6). Histological features were graded as follows: 0 (absent), 1 (moderate), 2 (marked) and 3 (severe). Histological grade occurrences in the different groups were compared using Fisher’s exact test. P values ≤0.05 were considered significant.
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Grade of activity-related hepatic histological features.
2016Co-Authors: Laëtitia Dorso, Edith Bigot-corbel, Jérôme Abadie, Maya Diab, Sébastien Gouard, Frank Bruchertseifer, Alfred Morgenstern, Catherine Maurel, Michel Chérel, François DavodeauAbstract:Activity-related increases in (A) Cytomegaly/karyomegaly, (B) intranuclear cytoplasmic inclusion, and (C) inflammation/fibrosis of control mice (n = 10), mice injected with 3.7 MBq (n = 5), 7.4MBq (n = 8) and 11.1 MBq (n = 6). Histological features were graded on histological slides as follows: 0 (absent), 1 (moderate), 2 (marked) and 3 (severe). Histological grade occurrences in the different groups were compared using Fisher’s exact test. P values ≤0.05 were considered significant.
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Liver histology of control and 213Bi-BSA injected mice.
2016Co-Authors: Laëtitia Dorso, Edith Bigot-corbel, Jérôme Abadie, Maya Diab, Sébastien Gouard, Frank Bruchertseifer, Alfred Morgenstern, Catherine Maurel, Michel Chérel, François DavodeauAbstract:(A) Control liver, 26 weeks post-injection, (B) livers of mice 26 weeks after injection of 3.7 MBq 213Bi-BSA, and (C, D, E, F) livers of mice 26 weeks after injection of 11.1 MBq 213Bi-BSA. Livers of mice injected with 3.7 MBq 213Bi-BSA do not show any significant histological injury. Livers of mice injected with 11.1 MBq 213Bi-BSA show extramedullary haematopoiesis (C, arrow), isolated necrosis (D, arrow), karyomegaly (Ka), Cytomegaly (Cy) and intranuclear acidophilic cytoplasmic invagination (INCI) (E). Inflammation and fibrosis are rarely observed (F, arrow). Haematoxylin-Eosin-Saffron (bar = 100 μm).
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Kidney histology of control and 213Bi-BSA injected mice.
2016Co-Authors: Laëtitia Dorso, Edith Bigot-corbel, Jérôme Abadie, Maya Diab, Sébastien Gouard, Frank Bruchertseifer, Alfred Morgenstern, Catherine Maurel, Michel Chérel, François DavodeauAbstract:Comparison between kidneys of (A, D, G) control animals, (B, E, H) kidneys of mice 35 weeks after injection of 3.7 MBq of 213Bi-BSA, (C and I) 26 weeks after injection of 11.1 MBq of 213Bi-BSA and (F) 35 weeks after injection of 7.4 MBq of 213Bi-BSA. Control kidneys, Haematoxylin-Eosin-Saffron (A), Periodic Acid Schiff (D), and Masson’s Trichrome (G). Kidneys of mice injected with 3.7 MBq 213Bi-BSA do not show any significant histological injury (B (HES), E (PAS) and H (MT)). Kidneys of mice injected with 11.1 or 7.4 MBq 213Bi-BSA show basophilic tubules, karyomegaly and Cytomegaly (C, arrow) (HES), proteinaceous casts (F, arrow), (PAS), and glomerulosclerosis (I, arrow) (MT) (bar = 100 μm).
D G Allen - One of the best experts on this subject based on the ideXlab platform.
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prediction of rodent carcinogenesis an evaluation of prechronic liver lesions as forecasters of liver tumors in ntp carcinogenicity studies
Toxicologic Pathology, 2004Co-Authors: D G Allen, G Pearse, Joseph K Haseman, Robert R MaronpotAbstract:The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity (or lack of carcinogenicity). Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice (83 compounds) and rats (87 compounds) was assessed. These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular Cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increase dl iver weight. Our results indicate that pooling 3 of these prechronic data points (hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular Cytomegaly) can be very predictive of carcinogenicity in the 2-year study ( p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted ( p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential.
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prediction of rodent carcinogenesis an evaluation of prechronic liver lesions as forecasters of liver tumors in ntp carcinogenicity studies
Toxicologic Pathology, 2004Co-Authors: D G Allen, G Pearse, Joseph K Haseman, Robert R MaronpotAbstract:The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity (or lack of carcinogenicity) are assessed. Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice (83 compounds) and rats (87 compounds). These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular Cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increased liver weight. Our results indicate that pooling 3 of these prechronic data points (hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular Cytomegaly) can be very predictive of carcinogenicity in the 2-year study (p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted (p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential.
John M Russell - One of the best experts on this subject based on the ideXlab platform.
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Running Title: Role of iron in Cytomegaly Address Correspondence to:
2013Co-Authors: William E Crowe, Lilia M Maglova, Prem Ponka, John M Russell, Ph. DAbstract:A hallmark of human cytomegalovirus (HCMV) infection is the characteristic enlargement of the host cells (Cytomegaly). Since iron (Fe) is required for cell growth and Fe chelators will inhibit viral replication, we investigated the effects of HCMV infection on Fe homeostasis in MRC-5 fibroblasts. Using the metallo-sensitive fluorophore calcein and the Fe chelator salicylaldehyde isonicotinoyl hydrazone (SIH), the labile iron pool (LIP) in mock-infected cells was determined to be 1.04±0.05 µM. Twenty-four hours post infection (h.p.i.), the size of the LIP was nearly doubled. Since Cytomegaly occurs between 24 and 96 h.p.i., access to this larger LIP could be expected to facilitate enlargement to ~375 % of the initial cell size. The ability of Fe chelation (SIH, 100 µM) to limit enlargement to ~180%, confirms that the LIP plays a major role in Cytomegaly. The effect of SIH chelation on the mitochondrial membrane potential ( M) and morphology was studied using the mitochondrial voltage-sensitive dye, JC-1. The mitochondria in mock-infected cells were heterogeneous with a broad distribution of M and thread-like. In contrast, the mitochondria of HCMV-infected cells had a more depolarized M distributed over a narrow range and were grain-like in appearance. However, the HCMV-induced alteration i
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the sodium potassium chloride cotransporter human cytomegalovirus and the cell cycle
Physiology and Pathology of Chloride Transporters and Channels in the Nervous System#R##N#From Molecules to Diseases, 2009Co-Authors: John M RussellAbstract:This chapter defines the basics and pathology of human cytomegalovirus (HCMV) infection. HCMV infection is widespread, affecting 50–90% of the adult population. It has the potential to be deadly under certain conditions. The most obvious morphological characteristic of infection with this pathogen is cell swelling, termed Cytomegaly, a 2–3-fold enlargement of the host cell. It is this cell enlargement feature that led to the original interest in the possible role of NKCC in the HCMV infection cycle. The virus is spread by contact with body fluids such as blood, saliva, semen, tears, breast milk and vaginal secretions. HCMV, a beta-herpes virus, is an opportunistic virus like other members of the Herpes family. Following the primary infection, it remains latent, hidden in cells of the salivary glands, kidneys, bone cells as well as in blood cells such as lymphocytes and macrophages.
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human cytomegalovirus induced host cell enlargement is iron dependent
American Journal of Physiology-cell Physiology, 2004Co-Authors: William E Crowe, Lilia M Maglova, Prem Ponka, John M RussellAbstract:A hallmark of human cytomegalovirus (HCMV) infection is the characteristic enlargement of the host cells (i.e., Cytomegaly). Because iron (Fe) is required for cell growth and Fe chelators inhibit v...
