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Biomedical subjects

M A Gerber

Publications and source records attributed to M A Gerber.

At least 73 records · Page 4Linked to original sources
PubMed1995

Morphometric and immunohistochemical characterization of human liver regeneration.

Regeneration in human liver is characterized in part by the formation of ductular structures, so-called ductular hepatocytes in massive hepatic necrosis and bile ductules in mechanical biliary obstruction. In an attempt to characterize the liver regenerative process, we performed image analysis and immunohistochemical staining of the ductular structures in these well defined human liver disorders, 13 cases of massive hepatic necrosis and 9 cases of mechanical biliary obstruction. The proliferation index was determined and the expression of several antigens was localized by immunohistochemical staining using antibodies to alpha-fetoprotein, alpha-1-antitrypsin, albumin, and cytokeratin 19. The ductular structures in adult human liver were compared with the developing ductal plates in 11 fetal livers, ranging in age from 9 to 36 weeks of gestation. Image analysis demonstrated that the mean total area, mean nuclear area, and mean cell size of ductular hepatocytes were significantly larger than those of bile ductules (p < 0.05). The proliferation index of ductular hepatocytes and bile ductules was significantly higher than that of hepatocytes of normal livers (p < 0.02). Bile ducts, bile ductules in mechanical biliary obstruction, ductular hepatocytes in massive hepatic necrosis, and the ductal plate cells in fetal liver showed strong staining for cytokeratin 19, which characterizes intermediate filaments associated with bile duct epithelial cells. Albumin, a liver-specific protein, and alpha-1-antitrypsin, a protease inhibitor, were strongly expressed in ductal plate cells of fetal liver, hepatocytes, and ductular hepatocytes, whereas bile duct cells and bile ductules were negative for albumin. In summary, ductular hepatocytes demonstrate morphometric and immunophenotypic features of both hepatocytes and biliary epithelial cells, whereas bile ductules share characteristics primarily with fetal ductal plates and mature bile ducts. These findings suggest that ductular hepatocytes in massive hepatic necrosis may serve as bipotential progenitor cells, and bile ductules in mechanical biliary obstruction are related to ductal plates of fetal liver.

Aging↗
PubMed1995

Pathobiology of hepatitis C.

Hepatitis C virus (HCV) represents the major etiologic agent of non-A, non-B hepatitis. The pathological changes in hepatitis C are characterized by the histologic triad of lymphoid aggregates in portal tracts, epithelial damage of small bile ducts, and micro- and macro-vesicular steatosis. HCV antigens are demonstrable in the cytoplasm of infected hepatocytes by immunohistochemical staining with mono- or polyclonal antibodies, particularly when frozen tissues are employed. Detection of HCV RNA sequences in fixed liver tissues by in situ hybridization appears to be a more sensitive method than immunohistochemical staining. These studies are important to determine the viral load and expression pattern of HCV in the infected liver. The mechanism of hepatocyte and bile duct injury in HCV infection appears to be related to the host immune response to the virus, although direct viral cytopathogenicity may also pay a role.

Bile Ducts↗
PubMed1994

Expression of hepatitis C virus in hepatocellular carcinoma.

BACKGROUND: Epidemiologic studies have suggested a strong association between chronic hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). To investigate the possible role of HCV in the pathobiology of HCC, the authors studied the expression of HCV in 10 cases of HCC with chronic HCV infection. METHODS: The core, envelope, and nonstructural (NS) 3 and 5 proteins were localized in liver and tumor tissues by the immunoperoxidase technique using mouse monoclonal antibodies to recombinant proteins or synthetic peptide of HCV. In addition, the positive and negative strands of HCV RNA were detected in the tissues by strand-specific reverse transcription/double polymerase chain reaction using primers for the 5'-nontranslated region. RESULTS: The HCV proteins were expressed in three of nine HCC specimens tested (the core protein in three HCC, the envelope, NS3 and NS5 proteins in one HCC) and in two of nine nontumorous liver specimens adjacent to the HCC (the core protein in two specimens, envelope, NS3 and NS5 proteins in one specimen). Positive-stranded HCV RNA was detected in all tumorous and nontumorous specimens except in one tumor. Negative-stranded HCV RNA was found in six of nine HCC tested and in all nontumorous livers. CONCLUSIONS: These findings suggest that HCV persists in hepatocytes during malignant transformation, although secondary infection of tumor cells by HCV cannot be excluded. Some HCC appear to support replication and expression of HCV.

Adult↗
PubMed1994

Conservation of hepatitis C virus 5' untranslated sequences in hepatocellular carcinoma and the surrounding liver.

Persistent infection by hepatitis C virus is a major risk factor for the development of hepatocellular carcinoma, but the mechanism of hepatocarcinogenesis is unknown. To study the association of hepatitis C virus with hepatocellular carcinoma, we sequenced part of the 5' untranslated region of hepatitis C virus from the tumor tissue and the surrounding nontumorous liver of three patients with hepatocellular carcinoma. No sequence differences between tumor-derived and liver-derived hepatitis C virus isolates were detected. The conservation of the 5' untranslated region of hepatitis C virus--not only in infected hepatocytes, but also in neoplastic cells--suggests that the regulatory elements at the 5' terminus of the viral genome play an important role in the pathobiology of hepatitis C virus.

Base Sequence↗
PubMed1994

Genomic and replicative hepatitis C virus RNA sequences and histologic activity in chronic hepatitis C.

Hepatitis C virus (HCV) frequently leads to chronic hepatitis, cirrhosis, and hepatocellular carcinoma, but the mechanism of liver injury is unknown. To determine whether replication of HCV is related to liver damage, we studied 17 liver biopsy specimens (six anti-HCV-positive chronic persistent hepatitis specimens, seven anti-HCV-positive chronic active hepatitis specimens, and four anti-HCV-negative controls) by reverse transcription followed by double polymerase chain reaction for the 5' nontranslated regions of the genomic and replicative strands of HCV. The histologic activity index as well as lymphoid aggregates in portal tracts, bile duct damage, and fatty change were assessed semiquantitatively. There was a statistically significant correlation between the presence of HCV RNA sequences in liver tissue and anti-HCV antibody in serum (P < .005). No correlation was detected between the histologic activity index or any individual histologic parameters and the presence of genomic or replicative strands of HCV. These findings suggest that a direct viropathic effect is less important than other mechanisms, such as the host immune response, in the pathogenesis of hepatocyte and bile duct injury in chronic hepatitis.

Adult↗
PubMed1994

Quantitative polymerase chain reaction for hepatitis B virus DNA.

To monitor and compare the effect of drugs on hepatitis B virus (HBV) replication in hepatitis patients, an accurate quantitative method with high sensitivity is needed. Polymerase chain reaction (PCR) is the most sensitive method for the detection of HBV DNA, but because of sample to sample variability in amplification efficiency, the quantification of target nucleic acids by conventional PCR is inaccurate. Therefore, we developed a competitive PCR method with an internal standard which uses the same primers as the target HBV DNA. The standard was generated from the HBV S gene by PCR site-directed mutagenesis and differed from the native S gene by a single base which introduced an internal restriction enzyme site. For practical application, this method was used to quantitate the effect of the carbocyclic analogue 2'-deoxyguanosine (2'-CDG) on HBV DNA replication in 2.2.15 cells, an HBV transfected HepG2 cell line. A decrease of HBV DNA level in the attomole range was demonstrated by the assay in the media of 2.2.15 cells treated with 2'-CDG. The results were verified by conventional HBV DNA slot blot analysis followed by densitometric scanning. Competitive PCR proved to be a sensitive, accurate and reliable method for HBV quantitation.

Antiviral Agents↗
PubMed1994

Childhood neurologic disorders and Lyme disease during pregnancy.

To determine the prevalence of clinically significant nervous system disease attributable to transplacental transmission of Borrelia burgdorferi, we surveyed neurologists in areas of the United States in which Lyme disease is endemic (i.e., Massachusetts, Rhode Island, Connecticut, New York, New Jersey, Wisconsin, and Minnesota). Overall, 162 of the 176 (92%) pediatric neurologists contacted responded to the survey with a range of 90-100% in the different geographic areas. One pediatric neurologist was following 3 children who were labeled as having "congenital Lyme disease," but none of the 3 met our case definition. None of the other pediatric neurologists surveyed had ever seen a child whose mother had been diagnosed as having Lyme disease during pregnancy. Similarly, none of the 37 adult neurologists in Connecticut surveyed had ever seen a child whose mother had been diagnosed as having had Lyme disease during pregnancy. We conclude that congenital neuroborreliosis is either not occurring or is occurring at an extremely low rate in areas endemic for Lyme disease.

Adult↗
PubMed1994

Is there recurrence of primary biliary cirrhosis after liver transplantation? A clinicopathologic study in long-term survivors.

Liver transplantation has been accepted as a successful therapeutic tool for irreversible liver diseases such as primary biliary cirrhosis. However, removal of the diseased liver may not eliminate this autoimmune disease, and recurrence of primary biliary cirrhosis in the liver graft has been reported as early as within the first posttransplant year. We studied whether or not primary biliary cirrhosis recurs after liver transplantation in follow-up biopsies of 19 primary biliary cirrhosis patients. Biopsies of 14 non-primary biliary cirrhosis patients served as controls. The median follow-up period was 5 years (range 1-11 years). Both groups of patients were selected according to strict criteria which excluded pre- and posttransplant diseases which could mimic primary biliary cirrhosis. The follow-up biopsies were taken according to a protocol at yearly intervals. Established histologic criteria for primary biliary cirrhosis were assessed semi-quantitatively in 119 biopsies in a coded fashion. A longitudinal study was performed after decoding the biopsies, to document the course of morphological changes in time per patient. In addition to data on liver tests and immunosuppression, anti-mitochondrial antibodies including the primary biliary cirrhosis specific subtypes (anti-PDH-E2 and BCKD-E2) were determined in freeze-stored serum samples. The biopsies showed a striking concordance between the primary biliary cirrhosis and non-primary biliary cirrhosis groups and few overt histologic abnormalities. There was no significant difference in liver-test results and immunosuppression. Overall anti-mitochondrial antibodies remained present in decreased titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The risk of acquiring Lyme disease or babesiosis from a blood transfusion.

To determine the risk of acquiring Lyme disease or babesiosis from blood transfusion, serum was collected before and 6 weeks after patients received multiple transfusions during cardiothoracic surgery and antibodies to Borrelia burgdorferi and Babesia microti were measured. Of 155 subjects, 149 received 601 total units of packed red blood cells (PRBC) and 48 received 371 total units of platelets. No patient developed clinical or serologic evidence of Lyme disease; 1 (who received 5 units of PRBC) developed clinical and serologic evidence of babesiosis. The risk of acquiring Lyme disease from a transfused unit of PRBC was 0 (95% confidence interval [CI], 0-0.5%) and from a transfused unit of platelets was 0 (95% CI, 0-0.8%); the same risks for babesiosis were 0.17% (95% CI, 0.004%-0.9%) and 0 (95% CI, 0-0.8%), respectively. The risk of acquiring either Lyme disease or babesiosis from a blood transfusion in Connecticut is very low.

Aged↗
PubMed1994

Pathology of hepatitis C.

The basic morphological patterns of acute or chronic viral hepatitides are very similar, irrespective of the causative hepatitis viruses A, B, C, D or E. In addition, however, acute and chronic hepatitis C shows characteristic, although not pathognomonic histological changes. These consist of lymphoid aggregates in portal tracts, sometimes with germinal centers, damage of bile duct epithelium, and micro- or macrovesicular steatosis of hepatocytes. A combination of two of these three characteristic alterations is seen in over half of the patients with chronic hepatitis C and is helpful in the histological diagnosis of the disease.

Acute Disease↗
PubMed1994

Primary vs metastatic hepatic carcinoma. An immunohistochemical study of 34 cases.

The distinction between primary and metastatic hepatic epithelial malignant neoplasms can often be difficult if histologic features alone are used. The purpose of this study was to determine whether certain immunohistochemical markers could be used to aid in the diagnosis. The cases that were studied included 14 hepatocellular carcinomas, 10 cholangiocarcinomas, and seven metastatic adenocarcinomas; three cases of poorly differentiated carcinoma (not otherwise specified) were also studied. The antibodies that were chosen included alpha-fetoprotein, alpha 1-antitrypsin, monoclonal carcinoembryonic antigen, Leu-M1, B72.3, factor XIIIa, and Le(x). We found that the cases of hepatocellular carcinoma displayed cytoplasmic reactivity for alpha 1-antitrypsin, alpha-fetoprotein, and factor XIIIa. The cases of cholangiocarcinoma showed membranous and cytoplasmic reactivity for Le(x) but only cytoplasmic reactivity for Leu-M1 and B72.3, whereas the opposite pattern of staining was found in cases of metastatic adenocarcinoma. We conclude that immunohistochemical studies can be useful in the distinction of primary vs metastatic hepatic malignant neoplasms and recommend a panel of alpha 1-antitrypsin, alpha-fetoprotein, Leu-M1, B72.3, factor XIIIa, and Le(x).

Adenocarcinoma↗