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Biomedical subjects

Z Schaff

Publications and source records attributed to Z Schaff.

At least 91 records · Page 5Linked to original sources

Retrovirus-like particles in hepatocytes of patients with transfusion-acquired non-A, non-B hepatitis.

Retrovirus-like particles 60-85 nm in diameter were observed in the cytoplasm of hepatocytes in liver biopsies obtained during the acute and chronic phases of non-A, non-B hepatitis (NANBH) in three patients with transfusion-acquired disease. The particles appeared in dilated endoplasmic reticulum cisternae as well as in enlarged Golgi vesicles. No such particles were seen in hepatocytes in liver biopsies similarly obtained during the acute or chronic phases of NANBH from 11 additional patients with NANBH who did not acquire their disease following blood transfusion. Particle-associated reverse transcriptase activity (peak activity at a density of 1.14 gm/ml) was present in the sera of all three "particle-positive" patients and also in 42% of the "particle-negative" patients. The retrovirus-like particles described here were apparently unrelated to the previously described human T cell lymphocytotropic retroviruses (HTLV), since none of the 14 patients studied had antibodies in their serum directed against antigens of any of the three known HTLVs.

Adult↗

Interferon-induced modulation of human ras oncogene expression.

Treatment of NIH 3T3 cells with interferon (IFN) after transfection with human bladder carcinoma EJ/T24 c-Ha-ras1 oncogene DNA caused inhibition of ras-induced cell transformation. Furthermore, the effect of IFN on oncogene expression in an established tumor line was studied. A tumor line of NIH 3T3 (RS485) was transformed by human c-Ha-ras1 activated by a viral long terminal repeat. Treatment of the tumor cells with IFN was associated with a progressive appearance of reverted, flat colonies which exhibited a normal phenotype with respect to morphology and growth. The revertants were well spread, contact inhibited cells; they did not grow in soft agar and were not tumorigenic in nude mice. Revertants retained their normal phenotype, although they contained transfecting human c-Ha-ras1 DNA; but, they produced significantly decreased levels of the onc-encoded protein p21 and c-Ha-ras1 mRNA as compared to RS485 cells.

Animals↗

Biological and morphological characteristics of phenotypic revertants appearing in interferon-treated mouse cells transformed by a human oncogene.

Phenotypic revertants appearing in interferon-treated mouse cells that had been transformed by an activated human c-Ha-ras1 oncogene (cell line RS485) were tested for several biological properties. The cloned revertants regained the growth characteristics of the untransformed parental NIH 3T3 cell line; unlike RS485 cells the revertants failed to form colonies in soft agar or to form rapidly growing tumors in nude mice. Animals inoculated with RS485 cells developed tumors within one week. In contrast, revertant clonal line 4C3 failed to form tumors four months after transplantation. Revertant 4C8 cells were tumorigenic; however, the developing tumors had increased latency, slower growth rate, and remained smaller than tumors of RS485 cells. Histopathological analysis revealed that revertant-associated fibrosarcomas were less anaplastic, less cellular and had relatively infrequent mitotic figures as compared to fibrosarcomas of RS485 cells. The result suggest the IFN-induced revertants exhibit a significantly less malignant phenotype than their parental transformed cells and that the biological differences are maintained after IFN treatment is discontinued.

Animals↗

Ultrastructural and cytochemical study of hepatocytes and lymphocytes during experimental non-A, non-B infections in chimpanzees.

A human agent of non-A, non-B hepatitis (Inoculum I) was transmitted to chimpanzees and alterations in liver and lymphocytes were studied by electron microscopy and by cytochemical techniques during the acute phase of the disease. Three types of cytoplasmic alterations, consisting of a membraneous and an amorphous part were observed in the hepatocytes. The density of the amorphous constituent decreased after treatment with pronase, but not after treatment with ribonuclease (RNase) or deoxyribonuclease (DNase). The wall of C-III, but not C-II had fibrils with a periodicity the contrast of which markedly increased after pronase treatment. Cytochemical data suggest that the inclusions (C-I-III) represent a cellular reaction to the infectious agent rather than the virus itself. Intranuclear vermicular inclusions (INI) were observed in hepatocytes and lymphocytes as well, mainly in degenerating cells. Tubuloreticular inclusions (TRS) did not appear in circulating lymphocytes during acute infection; however, they could be induced by human alpha interferon treatment in vitro. Increased numbers of lymphocytes with parallel tubular arrays (PTA) were noted at the peak of serum aminotransferase elevations. The latter two alterations (TRS and PTA) most likely represent immunologic reactions of the host to the infectious agent.

Animals↗

Ultrastructural alterations in serial liver biopsy specimens from chimpanzees experimentally infected with a human non-A, non-B hepatitis agent.

Four chimpanzees experimentally infected with an agent of human non-A, non-B hepatitis were studied to determine the sequence of ultrastructural alterations in hepatocytes during infection. Three of the four types of cytoplasmic alterations previously described in association with non-A, non-B hepatitis were observed in the hepatocytes. Sponge-like cytoplasmic inclusions (designated C-I) were detected at or near the time of peak serum aminotransferase elevations in two of the four chimpanzees. Undulating membranes (designated C-II) were observed in all four chimpanzees, at the time of the first elevation of serum aminotransferase levels. Cytoplasmic tubules (designated C-III) were first observed four, eight, and twelve weeks, respectively, after inoculation in three of the chimpanzees. Four weeks after the peak of serum aminotransferase elevations, cytoplasmic alterations could no longer be detected in hepatocytes of the four chimpanzees. Intranuclear inclusions consisting of 20-27 nm granules and vermicular particles were observed in hepatocytes from preinoculation liver biopsy specimens, as well as biopsies obtained during non-A, non-B hepatitis. The number of these particles was greatest near the time of peak elevation of serum aminotransferase levels, however. Tubulo-crystalline inclusions were noted as well in the endothelial cells from both preinoculated and infected chimpanzees. Cytoplasmic alterations in hepatocytes of chimpanzees experimentally infected with an agent of non-A, non-B hepatitis appear characteristic of infection with this agent. In contrast, intranuclear particles were not specifically related to the non-A, non-B hepatitis infection.

Animals↗

D-galactosamine-induced liver injury in immunosuppressed mice.

Thymectomized DBA/2 mice, irradiated with 720 rad/min and reconstituted with syngeneic bone marrow, were treated i.p. with 1 g/kg body weight D-galactosamine-HCl (DGA). Light and electron microscopic changes characteristic of the toxic effect of the agent, such as hepatocellular cytoplasmic inclusions and unicellular necrosis, could be observed but no inflammatory reaction was detectable in the liver. The phagocytic activity of Kupffer cells proved to be unchanged in immunosuppressed animals. Liver regeneration following DGA injury took place in 120 hours exactly as in animals having an intact immune system. The experiments suggested that T-lymphocytes participate in the development of DGA-hepatitis and their absence does not influence the restoration of liver injury. The experimental system described seems to be suitable for separating primary and secondary events and also for studying the role of the immune system in toxic liver injury.

Animals↗

Polarization colours of collagen fibres: a sign of collagen production activity in fibrotic processes.

The maturation process of collagen fibres was investigated by the picro-sirius red/polarization light technique in experimental wound healing, in allyl-alcohol induced subacute and chronic liver fibrosis and in human biopsy material. Evidence was obtained that collagen fibres undergo a rapid maturation in fibrotic processes; the intensity of their birefringence increases and, at the same time, their polarization colour changes. Newly formed collagen fibres appear on the 4-6 mum thick sections in green polarization colour. Later, in a more mature stage, they became yellow, orange or red under crossed polaroids. The findings suggest that the simple picro-sirius red/polarizing light technique may be useful to form an opinion about the activity of the fibrotic process.

Animals↗

HBsAg-like structures in immunosuppressed mice inoculated with human hepatitis B virus.

Thymectomised and irradiated DBA/2 mice were injected intraperitoneally with human serum containing high titer of HBsAg, and were positive for HBsAg. Through the entire experiment neither degenerative and inflammatory lesions nor hepatitis B virus antigens could be detected in the liver of these animals by histomorphology and immunofluorescence, respectively. The sera of all these mice were negative for HBsAg by radioimmunoassay. By electron microscopy, however, increasing amounts of filaments and round particles measuring 20-22 nm in diameter could be observed in the endoplasmic reticulum of the mouse hepatocytes from the 8th day following injection. From the 90th day after inoculation the number of the filaments increased in an extreme degree. After fixation with KMnO4 and EDTA preferential staining, the filaments proved to be highly electrondense. According to the authors the filaments observed in mouse livers are lipoproteins produced by the hepatocytes in response to HBV inoculation. The appearance of the filaments is HBsAg-like, though their immunological characteristics become modified.

Animals↗