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Biomedical subjects

M A Gerber

Publications and source records attributed to M A Gerber.

At least 199 records · Page 11Linked to original sources

Morphometric study of hepatocytes containing hepatitis B surface antigen.

The development of hepatocellular carcinoma (HCC) is probably related to infection with hepatitis B virus (HBV). Hepatocytes in livers of patients with HCC have been reported to show putative preneoplastic changes such as hyperplasia, dysplasia, or adenomatous regeneration. To determine quantitatively whether these morphologic changes are associated with HBV-infected cells, the authors performed morphometry of hepatitis B surface antigen (HBsAg)-positive hepatocytes in the nontumorous portion of 10 livers with HCC and in 10 livers without HCC. The diameter of nuclei and cytoplasm of HBsAg-positive hepatocytes was measured after demonstration of HBsAg by the peroxidase-antiperoxidase method. As controls, HBsAg-negative hepatocytes in the same liver sections were measured as well as hepatocytes of 20 age-matched HBsAg-negative patients with normal liver or alcoholic cirrhosis. HBsAg-positive hepatocytes exhibited significantly larger nuclei and a higher nucleocytoplasmic ratio than control hepatocytes. In addition, HBsAg-positive cells were often arranged in foci that consisted of two cell populations: hypertrophic (enlarged nuclei and nucleocytoplasmic ratio) and hyperplastic (two-cell-thick plates of small cells with a high nucleocytoplasmic ratio). While precancerous cells have been difficult to identify, these morphologic changes are frequently associated with the development of malignant neoplasia.

Carcinoma, Hepatocellular↗

Albumin binding sites of human hepatocytes.

Recent studies of hepatitis B virus suggest that polymeric human serum albumin may facilitate the attachment of the virus via albumin receptors to hepatocytes during the infectious process. If this hypothesis is correct, hepatocytes should express binding sites for polymeric albumin. We employed the red blood cell adherence test using albumin-coated red blood cells as indicator cells on frozen sections of normal human livers to demonstrate these binding sites. Hepatocytes showed binding activity for both polymeric and monomeric albumin from different species. The receptor-ligand interaction was temperature and pH dependent, Ca++ independent and not altered by mercaptoethanol treatment. The binding activity was sensitive to neuraminidase and pronase, but resistant to trypsin, lipase and collagenase digestion. These findings suggest that human hepatocytes display species-non-specific albumin binding sites, which are glycoproteins.

Animals↗

Immunohistochemical study of delta antigen in an American metropolitan population.

Delta antigen, a transmissible agent associated with hepatitis B virus, has been detected primarily in Italian patients. The preservation of delta-antigen in formalin-fixed, paraffin-embedded liver tissue enabled us to study the prevalence of this agent in our material. Using the peroxidase-antiperoxidase method, delta-antigen was found in 2 of 65 consecutive biopsy specimens of patients with HBsAg-positive liver disease. In addition, delta-antigen was demonstrated in 2 of 14 autopsy specimens from HBsAg-positive patients. Of the delta-antigen-positive patients, one was Italian, one was a polytransfused American-born Italian and two were American homosexuals. All four delta-Ag-positive patients had chronic active hepatitis. In one patient, the agent persisted for 5 years while chronic active hepatitis reverted to chronic persistent hepatitis during prednisone therapy. These findings suggest that transmission of delta-antigen follows that of hepatitis B virus infection, although it is relatively uncommon in New York City.

Biopsy↗

Physicochemical and immunohistological studies of a sulfobromophthalein- and bilirubin-binding protein from rat liver plasma membranes.

Affinity chromatography over bilirubinagarose and sulfobromophthalein (BSP)-agarose was used to isolate two proteins, with high affinities for bilirubin and BSP, respectively, from Triton X-100-solubilized rat liver plasma membranes. The protein eluted from either affinity column migrated as a single band of approximately 55,000 D on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, and either protein cochromatographed with both [14C]bilirubin and [35S]BSP on Sephadex G-75. On gradient gels without reduction or SDS, or on Sephadex G-150, the native BSP-binding protein had an estimated molecular mass of approximately 100,000 D. After incubation with SDS, an additional Sephadex G-150 peak of molecular mass of 56,000 D was observed. Both, the 100,000- and 56,000-D G-150 peaks cochromatographed with [35S]BSP. The native protein had an isoelectric point of 3.5, stained with periodic acid-Schiff but not Sudan black, and contained 4 mol of sialic acid per mol of protein. A rabbit antibody to the BSP-binding protein gave a line of identity with both the BSP- and bilirubin-binding antigens, and inhibited the binding of [14C]bilirubin and [35S]BSP, but not [14C]oleate or [14C]taurocholate, to rat liver plasma membranes. Immunohistochemical studies revealed the presence of the antigen on all surface domains of rat hepatocytes, but not on other cell populations from normal rat liver. It was not found in other organs. These data are compatible with the hypothesis that a specific liver cell plasma membrane protein mediates the hepatocytic sequestration of bilirubin and BSP.

Animals↗

Sterilization of infant formula.

A survey of 237 pediatricians currently practicing in Connecticut revealed that 97 (41%) recommend routine sterilization of infant formula for a mean of 4.4 months. Eight bottles of proprietary formula were prepared in a controlled manner: four utilizing the "terminal heating method" of sterilization and four utilizing the "clean method" without sterilization. While the "terminal heating method" resulted in less bacterial contamination, three of the bottles prepared by the "clean method" had negative coliform counts and the other bottle had a minimal count. Ten bottles prepared without sterilization were randomly selected from mothers who had brought their infants for well-child care. With the exception of a small inoculum of enterotoxin-producing Staphylococcus aureus in one bottle, no enteropathogens were identified. The implications of this study for the routine preparation of infant formula are discussed.

Food Handling↗

Phenotypic characterization of hepatic proliferation. Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver.

Different forms of hepatocellular proliferation are seen in fetal livers, massive hepatic necrosis, and nodular transformation (nodular regenerative hyperplasia) of the liver. In an attempt to characterize the proliferating cells in these conditions, we studied the expression of several antigens by immunohistochemical methods. Alpha-fetoprotein (AFP), alpha 1-antitrypsin (AAT), a hepatocellular export protein, carcinoembryonic antigen (CEA), a marker of bile duct epithelial cells, and hepatitis B virus antigens (HBsAg, HBcAg), were localized by the peroxidase-antiperoxidase method in 11 fetal livers, 10 cases of nodular transformation, and 7 cases of massive hepatic necrosis. AFP was the most prevalent antigen in fetal hepatocytes. Many hyperplastic hepatocytes in nodular transformation contained AAT, but not oncofetal antigens, supporting the differentiated hepatocellular nature of these cells. A similar staining pattern was seen in two-cell-thick plates of hepatocytes in massive hepatic necrosis. In contrast, the ductlike structures at the periphery of necrotic lobules contained both AAT and CEA, suggesting that these cells exhibit features of hepatocytes and bile duct epithelial cells. Therefore, the appropriate term for these regenerating cells appears to be "ductular" or "biliary hepatocytes".

Adult↗

Kaposi's sarcoma in a young homosexual man. Association with angiofollicular lymphoid hyperplasia and a malignant lymphoproliferative disorder.

Recent reports have described an unexpected number of cases of a virulent form of a Kaposi's sarcoma (KS) as well as acquired immunodeficiency in young homosexual men. A 31-year-old man initially had a benign disorder, angiofollicular lymphoid hyperplasia. Kaposi's sarcoma then developed, and he died of a malignant lymphoproliferative disorder. We believe that this is unique among the recently described cases of KS in homosexual men because of the occurrence of this second malignancy. It may be that similar cases will be recognized in this population.

Adult↗

Nodular regenerative hyperplasia of the liver in a patient with diabetes mellitus.

Diffuse nodular regenerative hyperplasia of the liver (NRH) is a rare cause of portal hypertension. It is characterized by diffuse nodularity of the liver without cirrhosis. NRH is usually associated with other diseases, most commonly Felty's syndrome. A case is reported in which maturity-onset diabetes mellitus was accompanied by elevated serum insulin levels. Hepatotrophic hormones such as insulin or glucagon may play a role in the development of some cases of NRH.

Biopsy↗

Liquid crystal forehead temperature strips. A clinical appraisal.

We recently compared two brands of liquid crystal temperature strips, designed for application to the forehead, Clinitemp and Fever Scan, with recently calibrated rectal and oral glass thermometers in 134 children. The Clinitemp identified as febrile nine (28%) of 33 children who had fever verified by a glass thermometer. Five of seven children less than 2 years of age with rectal temperatures of 38.9 degree C or higher were identified as afebrile by the Clinitemp. The Fever Scan identified as febrile 26 (79%) of 33 children who had fever verified by a glass thermometer. One of six children less than 2 years of age with rectal temperatures of 38.9 degree C or higher was identified as afebrile by the Fever Scan. Parents who rely on these strips to identify a fever in their children may be misled by an erroneous afebrile reading.

Adolescent↗

Ultrastructural analysis of hepatitis B surface antigen production in vitro.

Recently several continuous cell lines (among these PLC/PRF/5 cells) producing hepatitis B surface antigen (HBsAg) were established from human hepatocellular carcinomas. The cultured cells provide the first opportunity to study HBsAg synthesis and secretion in vitro. HBsAg, but not HBcAg, was localized by the fluorescent antibody technique in the cytoplasm and on the surface of the cultured cells. Under the electron microscope, th PLC/PRF/5 cells displayed morphologic characteristics of both hepatocytes and hepatocellular carcinoma cells. However, 22-nm. spherical or filamentous HBsAg particles were not seen in the cells, although spherical HBsAg particles were observed in the supernatant culture media. Therefore, the indirect immunoperoxidase technique was used to demonstrate HBsAg at the ultrastructural level. Electron-dense reaction product was detected along the nuclear envelope, on rough-surfaced endoplasmic reticulum, and in cisternae of endoplasmic reticulum. These findings suggest that HBsAg is synthesized on rough-surfaced endoplasmic reticulum and transferred into endoplasmic cisternae for processing and secretion. This mode of HBsAg production is identical with that observed in hepatocytes of patients infected with hepatitis B virus. The absence of detectable intracellular HBsAg particles suggests that the cultured cells secrete the particles very rapidly or that they may have a defect in intracisternal packaging of HBsAg into particles.

Adult↗

Patterns of renal injury in systemic lupus erythematosus: light and immunofluorescence microscopic observations.

Light and immunofluorescent microscopic patterns of lupus nephritis in 203 biopsies, 1 nephrectomy, and 20 autopsies from 179 patients were analyzed. The latest World Health Organization (WHO) classification was used. Seventy patients had diffuse lupus nephritis, 43 mesangial, 19 membranous, 19 focal, and 16 minimal change; 2 patients had advanced sclerosing nephritis. Nine patients were difficult to classify by light microscopy, but 3 of these could be classified with the help of immunofluorescence microscopy. Strict definition, especially of category III (focal and segmental lupus nephritis) is important, since this lesion has a tendency to heal, and patients with few immune deposits outside the segmental lesions have a rather good prognosis. Category V (membranous lupus nephritis) should probably be limited to membranous lesions with pure subepithelial deposits or with subepithelial and mesangial deposits, while membranous changes associated with diffuse or focal proliferative lesions are better classified as Category IV (diffuse lupus nephritis). It was observed that steroid treatment reduces the amount of deposits, especially those in the subendothelial and mesangial locations. The amount of proliferation is also reduced, but in a considerable proportion of cases, it is replaced by sclerosis. Therefore, interpretation of biopsy patterns must take prior therapy into consideration. Immunofluorescence findings in the glomeruli correlated quite well with light microscopic patterns. Active interstitial inflammation, which is most common in diffuse lupus nephritis, was only observed in the presence of tubulointerstitial immune deposits. Acute arteritis was much more common in autopsy than in biopsy specimens pointing to its ominous nature. It was concluded that combined examination of biopsies by light and immunofluorescence microscopy as well as electron microscopy, and strict categorization of lesions are valuable diagnostic and prognostic aids. Their usefulness is considerably enhanced if certain clinical data, such as prior therapy are taken into consideration.

Antigen-Antibody Complex↗