The formation of elastic fibers in livers with massive hepatic necrosis.
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Biomedical subjects
Publications and source records attributed to M A Gerber.
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Characteristic alterations of marker enzymes and tumor-associated antigens have been detected in the preneoplastic lesions of experimental hepatocarcinogenesis. An identical pattern of enzyme activity (increased gammaglutamyl transferase, loss of glucose-6-phosphatase, and canalicular adenosine triphosphatase) was demonstrated in a case of nodular "regenerative" hyperplasia of liver. The lack of marker antigens (alphafetoprotein, carcinoembryonic antigen, alpha 1-antitrypsin) in the hyperplastic nodules in this patient may be related to the discontinuation of oral contraceptive steroids four years earlier. The phenotypic changes of enzyme activity suggest that nodular "regenerative" hyperplasia of the liver in man is preneoplastic.
Febrile seizures are a common pediatric problem, yet there is a great deal of disagreement about the appropriate diagnostic evaluation of a child with this disorder. We reviewed the routine diagnostic tests performed on 100 consecutive children admitted with their first "simple" febrile seizure. The studies performed included lumbar puncture, measurement of blood glucose, serum calcium, serum electrolytes, and BUN levels, blood cell count, urinalysis, skull roentgenograms, and EEG. Though resulting in a significant expense, these routine investigations proved to be of little diagnostic value. Based on this experience and a review of the current literature, we concluded that diagnostic procedures should be performed only when specifically called for by the patient's condition or medical history.
Hepatic neoplasms and peliosis are known to occur in women taking contraceptives orally. We observed hyperplasia of hepatocytes combined with hypertrophy of sinusoidal lining cells and sinusoidal dilatation with progression to peliosis in the liver of a patient who had been taking such contraceptives for 10 years. These changes resembled the precursor stage in the development of hepatic angiosarcoma induced by vinyl chloride, Thorotrast, and arsenic. In users of orally administered contraceptives these findings may precede the development of hepatocellular neoplasms.
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Hepatocytes with orcein-positive ground-glass cytoplasm have been shown to contain abundant hepatitis B surface antigen in the cisternae of excess smooth endoplasmic reticulum. Hepatocytes with similar cytoplasmic changes that did not react with orcein were observed in 26.5% of 49 cases of cirrhosis. These cells exhibited granular, deeply eosinophilic cytoplasm that stained with phosphotungstic acid-hematoxylin and contained numerous densely packed mitochondria as demonstrated by electron microscopy. Therefore, these cells were designated hepatic oncocytes. They were detected predominantly in cases of established cirrhosis, unrelated to etiology. Hepatic oncocytes may form nodular aggregates, but they did not show evidence of regeneration. The nature and pathogenesis of these cells remain unclear. Because of similar appearance, histochemical stains may be necessary to distinguish ground-glass hepatocytes from hepatic oncocytes.
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Receptor sites for polymerized human serum albumin (pHSA) on the envelope of hepatitis B virus (hepatitis B surface antigen) and antibodies to pHSA in sera of patients with liver disease were differentiated by an indirect fluorescent antibody method. Analysis of the specificities of pHSA receptors and antibodies to pHSA by hemagglutination inhibition suggested that pHSA receptors reacted with a species-specific site on pHSA, whereas "autoantibodies" to pHSA cross-reacted with pHSA from different species. These human antibodies inhibited the binding of hepatitis B surface antigen-associated receptors to pHSA.
Several investigators reported that sera from patients with liver disease react with polymerized human serum albumin. This reactivity may be mediated by antibodies to polymerized albumin or polymerized albumin receptor sites on HBsAg. We tested sera from 114 patients with a variety of liver diseases by techniques which differentiate polymerized albumin binding activity mediated by HBsAg-associated receptors from that due to immunoglobulins. Total polymerized albumin binding activity was detected by passive hemagglutination of polymerized albumin-coated red blood cells, in 62.3% of patients with liver disease. The specificity for polymerized albumin was proven by hemagglutination inhibition of 18 sera using polymeric, monomeric, and native albumin as inhibiting antigens. Indirect immunofluorescence of polymerized albumin coated red blood cells after incubation with serum revealed that antibodies, HBsAg or both mediated polymerized albumin binding. The predominant immunoglobulin class with polymerized albumin binding activity was IgG in sera from patients with chronic active hepatitis and alcoholic liver disease, and IgM in acute viral hepatitis, chronic persistent hepatitis, and primary biliary cirrhosis. HBsAg-mediated polymerized albumin binding activity was frequently associated with antibodies to polymerized albumin. The attachment of hepatitis B virus to hepatocytes may be facilitated by polymerized albumin via polymerized albumin receptors. Antibodies to polymerized albumin may interfere with this binding and may result in reduced infectivity.
PLC/PRF/5, a tissue culture cell line derived from a human hepatocellular carcinoma and producing hepatitis B surface antigen (HBsAg), was studied by immune and enzyme histochemical techniques. HBsAg was demonstrated in the cytoplasm and on the surface of tumor cells. The percentage of HBsAg-positive cells in subculture increased with time until almost all cells expressed HBsAg when the monolayer reached confluence. Similar patterns were found for alpha 1-anti-trypsin and carcino-embryonic antigen, whereas alpha-fetoprotein was observed only in small foci of cells. Hepatitis B core antigen and albumin were not detected. gamma-Glutamyl transferase activity was markedly increased in the tumor cells, whereas adenosine triphosphatase and glucose-6-phosphatase activities were not demonstrable. Patterns of antigenic expression and enzyme phenotype of PLC/PRF/5 cells show remarkable resemblance to those observed in vivo in human hepatocellular carcinoma. Therefore, this cell line may be a useful model to study the control and modulation of both oncofetal antigens and HBsAg.
The human hepatocellular carcinoma cell line PLC/PRF/5, which synthesizes and secretes hepatitis B surface antigen, was grown under optimal conditions in tissue culture, using Eagle's minimal essential medium supplemented with 10% fetal bovine serum and 10(-11) M triiodothyronine on collagen rafts. Injection s.c. of the PLC/PRF/5 cell line into athymic BALB/c nude mice resulted in the growth of a well-circumscribed, moderately differentiated hepatocellular carcinoma. The intervals until tumor appearance and tumor "take" rates were dependent on inoculum dose. Four to 5 x 10(6) cells induced tumor growth in 29% of 14 injected mice within 29 to 40 days, while 7 to 13 X 10(6) cells induced tumors in all 15 mice within 10 to 12 days after inoculation. Hepatitis B surface antigen was detected in the nude mouse serum and tumor tissue, and its concentration roughly correlated with tumor weight. A low level of antibody against hepatitis B surface antigen was detected in five tumor-bearing animals, as well as in one mouse which did not produce a tumor. Hepatitis B core antigen and its antibody and hepatitis B e antigen and its antibody were not detected in 26 mice, using immunohistochemical and radioimmunoassay methods. alpha-Fetoprotein, carcinoembryonic antigen, and alpha-antitrypsin were detected in nude mice tumors, using the peroxidase-antiperoxidase technique. Finally, hepatitis B virus DNA, identified in the nude mouse tumor by molecular hybridization techniques, was compared to PLC/PRF/5 cell line hepatitis B virus DNA.
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Liver-specific protein (LSP) prepared by standard methods from five normal human livers showed significant variations in terms of quantitative yield, lipid/protein ratio and migration characteristics of different components on SDS-polyacrylamide gel electrophoresis. This heterogeneity is probably related to varying amounts of different molecular species in the LSP preparations. Delipidation and re-chromatography of the LSP preparation appeared to result in relative enrichment of apo-LSP which showed immunological identity with LSP. Rabbit antiserum to LSP gave a precipitin line of identity with standard antisera to human LSP (anti-LSP) from two other laboratories. After extensive absorption, anti-LSP showed selective reactivity with a surface membrane antigen on a human hepatocellular carcinoma cell line (PLC/PRF/5) that exhibits functional and morphological characteristics of differentiated hepatocytes. The antiserum did not react with cell lines derived from other organs as determined by the indirect fluorescent antibody technique. The surface staining of viable PLC/PRF/5 cells was eliminated by absorption with LSP and apo-LSP, but not with the equivalent kidney fractions. These findings support the concept of a liver-specific antigen and suggest that the PLC/PRF/5 cell line may serve as a source of homogeneous LSP.
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The eyes of a 53-year-old woman with K light chain macroglobulinemia were studied histopathologically. Retinal hemorrhages were observed on gross examination. Microscopic examination disclosed eosinophilic, PAS-positive deposits in cystoid spaces within the outer plexiform layer, in the inner retina, and about photoreceptors. Immunofluorescent studies showed that the deposits contained IgM. Aneurysmal dilations of small retina vessels were demonstrated as well.
Progressive multifocal leukoencephalopathy and malignant lymphoma of the brain were noted at postmortem examination in a 68-year-old white woman who was treated with immunosuppressive agents after renal transplantation. The two diseases are not uncommon in patients with immunodeficiency, but their occurrence in the same patient is extremely rare. This association suggests the oncogenicity of papova viruses in man. However, no papovavirus was demonstrated in the tumor by electron microscopy and immunohistochemical staining. The immunohistochemical staining of routine histology sections for the common antigen of polyomaviruses by the peroxidase anti-peroxidase technique is shown to be simple and specific for the detection of polyomaviruses in the demyelinated areas of progressive multifocal leukoencephalopathy.
The immunologic responses to streptolysin O and streptococcal deoxyribonuclease B were evaluated in children with group A streptococci recovered from the upper respiratory tract to re-examine the hypothesis that a limited capacity to respond to group A streptococcal infection may explain the rare occurrence of acute rheumatic fever in very young children. ASO and anti-DNase B titers were determined on serial bleedings from a total of 301 individuals (52 less than or equal to 3 years; 249 older than 3 years). Very young children with group A streptococcal upper respiratory tract infections had an immunologic response to SO greater than the response in older children as reflected by the magnitude of the antibody rise, and comparable to the ASO response in older children as measured by the percentage showing a significant titer rise. Similar analyses of the anti-DNase B responses showed the response in young children to be comparable to those of the older group. Clinical manifestations of group A streptococcal upper respiratory tract infection in very young children differ from those observed in older children and have not changed significantly in the past several decades. These data suggest that the infrequent occurrence of acute rheumatic fever in very young children is not due to a difference in antibody response to streptolysin O or streptococcal DNase B.
Two patients experienced acute transient hepatic and renal failure following ingestion of substantial but less than the usually toxic doses of acetaminophen, in both cases associated with heavy acute alcohol intake. One patient developed transient clinical features of chronic active liver disease one month later. Liver biopsy specimens from both patients taken after the acute episodes revealed, in addition to the well recognized centrilobular hepatic injury of acetaminophen, unusual portal tract lesions, which resembled chronic active hepatitis in one case. In some patients therapeutic doses of acetaminophen, if taken together with alcohol, may produce acute and chronic liver disease.