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Biomedical subjects

M A Gerber

Publications and source records attributed to M A Gerber.

At least 235 records · Page 13Linked to original sources

Chronic hepatitis in chimpanzee carriers of hepatitis B virus: morphologic, immunologic, and viral DNA studies.

Years after infection with hepatitis B virus, chimpanzees may have manifestations of the carrier state as described in man. In addition to serologic evidence for persistent viral infection, percutaneous liver biopsy specimens showed hepatitis B virus surface antigen in the cytoplasm and hepatitis B virus core antigen in the nucleus. Four carrier animals had portal inflammatory reaction as seen in human chronic persistent hepatitis. Viral DNA was demonstrated in nucleic acid extracts of liver biopsy specimens by molecular hybridization to cloned plasmic pA01 containing hepatitis B virus DNA sequences. Although a viral molecule of length greater than the putative virus was identified, it did not appear to represent integration of viral DNA into the host genome. The chimpanzee model may serve as a means to study the mechanism of hepatitis B viral persistence and progression to chronic liver disease.

Animals↗

Ground-glass cells in hepatocellular carcinoma.

Hematoxylin and eosin-stained sections representing ten cases of hepatocellular carcinoma showed many tumor cells with ground-glass cytoplasm identical to that found in hepatocytes containing hepatitis B surface antigen (HBsAg). However, the aldehyde fuchsin stain was negative, as were the were the immunoperoxisidase stains for HBsAg and core antigen (HBcAg). Electron microscopically, the ground-glass appearance corresponded to the presence of non-membrane-bound amorphous or fibrillar inclusions. Immunohistochemically, the ground-glass material reacted with antiserum to human fibrinogen, suggesting synthesis of this protein by the carcinoma cells. Although the ground-glass appearance in hepatocellular carcinomas may sometimes be associated with HBsAg, special stains or technics are necessary to confirm its presence.

Adolescent↗

Risk of bacteremia after endotracheal intubation for general anesthesia.

Blood cultures were obtained before and after endotracheal intubation to assess the risk of bacteremia associated with this procedure and to evaluate the need for prophylactic antibiotics to prevent bacterial endocarditis in patients with structural heart disease requiring general anesthesia. Blood cultures were obtained immediately before intubation and two and ten minutes after intubation in 50 individuals without evidence of structural heart disease who required general anesthesia for elective surgery. Of 32 who had orotracheal intubation, only one demonstrated postintubation bacteremia; of 18 individuals who had nasotracheal intubation, none had evidence of bacteremia. These data suggest that in healthy individuals undergoing endotracheal intubation under direct vision the risk of bacteremia is quite small (about 2%).

Adolescent↗

Enzyme patterns in human hepatocellular carcinoma.

Characteristic enzyme alterations have been demonstrated during the stages of experimental hepatocarcinogenesis in rats. The activity of gamma-glutamyl transpeptidase (GGTPase) in hyperplastic and neoplastic hepatocytes is usually increased, whereas that of canalicular adenosine triphosphatase (ATPase) and of glucose-6-phosphatase (G6Pase) is more variable. The activities of these marker enzymes were studied by histochemical techniques in 10 human hepatocellular carcinomas (HCCs), 1 liver cell adenoma, and 1 cholangiocarcinoma of liver. In 9 cases, the nontumorous liver was also examined. All HCCs, but not the liver cell adenoma, displayed enzyme patterns that differed from normal. GGTPase activity was markedly increased in 8 HCCs, whereas the activities of G6Pase and ATPase were lost in 6 and 8 HCCs, respectively. These enzyme alterations occurred as 5 of 7 possible combinations, resulting in significant heterogeneity of enzyme phenotypes, similar to that in experimental hepatocarcinogenesis.

Adenoma, Bile Duct↗

Immunohistochemical demonstration of common antigen of polyomaviruses in routine histologic tissue sections of animals and man.

All polyomaviruses have a common antigen, which is located on the major capsid polypeptide (VPI). This antigen was demonstrated in routine histologic sections of formalin-fixed paraffin-embedded tissues by the peroxidase-antiperoxidase technic. Antiserum to the common determinant reacted with JC virus in oligodendrocytes of a patient who had progressive multifocal leukoencephalopathy, BK virus in bladder epithelium of a renal transplant patient, and K virus in endothelial cells of mouse lung. This method may be applicable to the screening of tissues for all polyomaviruses in diagnostic and investigative pathology.

Adult↗

Enzyme-linked immunosorbent assay of antibodies in human sera to streptococcal DNase B.

An ELISA method for determining the streptococcal anti--DNase B titers in human sera is presented. The details of this technique, a method for converting A493 readings into titers, and a standardization procedure are discussed. Anti--DNase B titers of 20 sera determined by ELISA were compared with titers determined by the microtechnique. A correlation coefficient of 0.96 between the two methods was obtained. The reproducibility of the ELISA method was established by comparing titers obtained from two separate determinations on the 20 sera. Twenty-four pairs of acute and convalescent sera were assayed for anti--DNase B titers by both ELISA and microtechnique to compare the ability of the two techniques to identify significant titer rises. The ELISA was as specific and possibly more sensitive than the microtechnique in identifying significant anti--DNase B titer rises. This ELISA method is simple and rapid and has the potential for automation.

Adolescent↗

Caroli's disease: a rarely recognized entity.

Caroli's disease, well known in the European literature, has been recognized infrequently in this country. The disease is characterized by cystic dilation of intrahepatic bile ducts and is complicated by formation of gallstones, cholangitis, and hepatic abscesses. Surgical intervention and therapy with antibiotics is often unsuccessful and Gram-negative septicemia is a common cause of death. Cysts may be present in other organs, such as kidney, pancreas, and spleen, and may be helpful in the early diagnosis of this rare disease.

Bile Duct Diseases↗

Antibodies to ribosomes in chronic active hepatitis.

A recently developed Farr-type radioimmunoassay for the detection of antibodies to tritium-labeled HeLa cell cytoplasmic ribosomes was evaluated as a serologic test in a variety of liver diseases. Ribosomal antibodies were detected in the sera of 31.4% of 70 patients with chronic active hepatitis (CAH) and primary biliary cirrhosis compared with only 4.2% of patients with chronic persistent hepatitis, acute viral hepatitis, alcoholic liver disease, and miscellaneous liver diseases (X2 = 17.89, P less than 0.001). The level of ribosomal binding activity was also significantly higher in sera of patients with CAH and primary biliary cirrhosis (15.4% vs 6.5%; t = 5.61, P less than 0.001). The antibodies were observed almost exclusively in HBsAg-negative CAH with autoimmune features and infrequently at lower titer in HBsAg-positive CAH or CAH without HBsAg or autoantibodies. Inhibition experiments with purified ribosomal RNA suggested that the ribosomal antibodies are in part reactive with ribosomal RNA. Ribosomal antibodies appear to represent another example of the exaggerated immune response associated with CAH and primary biliary cirrhosis.

Autoantibodies↗

Distribution of five antigens in hepatocellular carcinoma.

A variety of antigens may be detected in the serum of patients with hepatocellular carcinoma (HCC). The incidence and distribution of five antigens in 37 HCC and their relation to each other in a given tumor was examined by the peroxidase-antiperoxidase technique using formalin-fixed paraffin-embedded tissues. alpha 1-Antitrypsin was frequently expressed in HCC (73 per cent of cases), whereas alpha-fetoprotein and carcinoembryonic antigen were less common. HBsAg, but not HBcAg, was observed in tumor cells in seven of nine HCC from HBsAg-positive patients. In 20 HCC (54 per cent), two or more antigens, most frequently alpha 1-antitrypsin and alpha-fetoprotein, were detected. Double staining for simultaneous localization of two antigens in the same tissue section revealed that different antigens were usually present in different tumor cells, although some cells displayed two antigens simultaneously. These findings suggest that hepatocellular carcinoma cells are functionally heterogeneous, even if they appear histologically monomorphic.

Antigens, Neoplasm↗

Carcinoembryonic antigen in normal and diseased liver tissue.

Many reports have demonstrated an elevation of circulating carcinoembryonic antigen (CEA) in the majority of patients with alcoholic liver disease and, less frequently, in patients with nonalcoholic liver disease. Several explanations for this finding have been proposed, eg, increased production or release of CEA by the damaged liver, decreased hepatic metabolism, or diminished excretion of CEA of extrahepatic origin. In an attempt to clarify the mechanism of CEA elevation in liver disease, we have compared the CEA plasma level as measured by radioimmunoassay with CEA demonstrable in liver tissue by the indirect fluorescent antibody technique in 7 patients without significant changes in the liver biopsy specimen, 23 patients with alcoholic liver disease, and 16 patients with miscellaneous liver diseases such as acute or chronic nonalcoholic hepatitis or extrahepatic biliary obstruction. The mean CEA plasma level in patients with alcoholic liver disease was significantly higher than in patients with nonalcoholic liver disease (8.8 +/- 9.5 vs 2.7 +/- 2.5 ng/ml; P less than 0.02). In normal liver tissue, CEA was observed in the apical cytoplasm and along the luminal surface of bile duct epithelial cells, suggesting that under normal conditions CEA accumulates in and is excreted by bile ducts. In patients with alcoholic hepatitis and/or cirrhosis there was marked bile ductular proliferation and prominent cytoplasmic CEA-specific staining and both were associated with elevated CEA plasma levels in more than 80% of cases. In the group of miscellaneous liver diseases, bile ductule counts and CEA-specific staining did not correlate with CEA plasma levels. These observations suggest that proliferating bile ductules contribute to elevated plasma CEA in alcoholic patients.

Carcinoembryonic Antigen↗

Ultrastructural localization of mitochondrial and ribosomal antigens by peroxidase-labeled human antibodies.

Immunohistochemical techniques have facilitated the detection of a variety of antibodies to different cells and tissues in patients with chronic active liver disease; however, the ultrastructural localization of the antigenic binding sites, particularly of mitochondrial antibody, has been controversial. Therefore, we have employed direct immunoelectron microscopy to compare the reactivity of mitochondrial antibody with that of ribosomal antibody using gastric and renal tissues as substrates. Mitochondrial antibodies from three patients with primary biliary cirrhosis and from one patient with chronic active hepatitis reacted with the inner membrane and cristae of all mitochondria in different cells, whereas a ribosomal antibody from a patient with ovarian carcinoma bound to the rough endoplasmic reticulum, and possibly free ribosomes and polysomes, of all cells observed. Identification and characterization of these antibodies is needed for the differential diagnosis of chronic active liver disease.

Antibodies↗

Radioimmunoassay for antibodies to cytoplasmic ribosomes in human serum.

A radioimmunoassay for the detection of antibodies in human serum to tritium-labeled HeLa cell cytoplasmic ribosomes was developed with the use of Macaloid for the inhibition of endogenous ribonuclease activity. Antibodies were observed in the serum of patients with systemic lupus erythematosus in high incidence and titer. Patients with rheumatoid arthritis and chronic active hepatitis manifested a lower incidence and titer of antibodies to ribosomes, whereas serums from normal individuals and from patients with sarcoidosis, chronic glomerulonephritis, and malignant tumors showed no significant reactivity with cytoplasmic ribosomes. Maximum inhibition of the reaction was achieved with unlabeled HeLa cell ribosomes or rat liver ribosomes and partial inhibition by purified ribosomal RNA.

Animals↗