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Biomedical subjects

D Shouval

Publications and source records attributed to D Shouval.

At least 127 records · Page 7Linked to original sources
PubMed1989

Improvement of immune-complex nephritis associated with hepatitis B surface antigen excess.

A case of hypocomplementemic membranoproliferative glomerulonephritis was studied during remission of nephrosis induced by high doses of corticosteroids. Hepatitis B surface antigen (HBsAg) and immune complexes were detected in serum and glomeruli. Anti-hepatitis-B surface antibody, undetectable in serum by conventional radioimmunoassays was identified in circulating immune complexes (CIC). On two occasions, improvement in renal function coincided paradoxically with an extreme increase in serum HBsAg levels as well as with marked elevation of CIC. We suggest that, as previously observed in animal models of glomerulonephritis, extreme antigen excess may inhibit glomerular deposition of immune complexes.

Antigen-Antibody Complex↗
PubMed1988

Erythropoietin-induced polycythemia in athymic mice following transplantation of a human renal carcinoma cell line.

An established cloned human renal carcinoma line RC-1, which has been continuously maintained in culture for several years and which produces erythropoietin, was injected s.c. into BALB/c athymic mice and produced tumors. Tumorigenicity was directly correlated with the number of RC-1 cells inoculated. Tumor cell histology resembled the original patient-derived tumor. Tumor-bearing mice developed hepatosplenomegaly and significant reticulocytosis with elevated hemoglobin and hematocrit values that were proportional to tumor mass. In addition, red cell mass and blood volume of nude mice increased over 100% as compared to control mice or to animals bearing nonrelevant neoplasms. Large amounts of immunoreactive erythropoietin could be extracted from the nude mouse RC-1 tumors. These results indicate that the RC-1 cell line is tumorigenic and produces biologically active erythropoietin in vivo in athymic mouse hosts, thus providing a reproducible model to study ectopic erythropoietin production and its regulation in vivo.

Animals↗
PubMed1988

An acupuncture-associated outbreak of hepatitis B in Jerusalem.

Two clusters of between five and eleven cases of hepatitis B associated with acupuncture treatment by a physician occurred in Jerusalem in late 1986. The origin of the outbreak is believed to have been an Ethiopian immigrant surgical patient, a known HBsAg carrier, who infected an operating room nurse during a surgical procedure. This is the first recorded instance of transmission of HBV from an Ethiopian immigrant to the local Israeli population. We reiterate the need for the enforcement of correct sterilization techniques in all skin-piercing settings, a step which in many countries will require the licensing of a variety of occupations not presently covered by health regulations.

Acupuncture Therapy↗
PubMed1988

Comparative morphology and tumourigenicity of human hepatocellular carcinoma cell lines in athymic rats and mice.

Four human hepatoma cell lines PLC/PRF/5, Hep G2, Sk-Hep 1 and Mahlavu were inoculated subcutaneously into athymic Balb/c nude mice and N/NIH outbred nude rats, producing well encapsulated tumours. The 4 hepatoma tumour types in the athymic rodents differ morphologically. PLC/PRF/5 and Hep G2 cells are well differentiated polygonal cells which resemble normal hepatocytes. Tumour arrangement is characterized by solid masses and trabeculae while stromal support is minimal. In contrast, Mahlavu and Sk-Hep 1 tumours have a sarcomatous appearance and consist of spindle shaped cells arranged in solid masses with a rich stromal support. Tumourigenicity of hepatoma cells in the athymic rodents was dependent on injected cell type, inoculation density, relative immunocompetence of the host and the species of animals used. In nude mice, Sk-Hep 1 cells were the most tumourigenic, while Hep G2 cells were tumourigenic only at very high inoculation densities. In nude rats, which were more resistant to tumour formation, PLC/PRF/5 cells were the most tumourigenic. Pre-treatment of athymic mice and rats with total body irradiation resulted in enhanced tumourigenicity for all hepatoma cell lines tested. This was manifested as increased "take" rates, a decreased latency from tumour cell injection to tumour detection, increased tumour weight, and for PLC/PRF/5 cells an increased invasiveness to adjacent body cavities. Furthermore, following irradiation, the minimal number of injected cells required to produce subcutaneous tumours was markedly reduced in both animal species, regardless of tumour cell type. The protocols described enable the reproducible growth of human hepatoma tumours in athymic rodents.

Animals↗
PubMed1988

Sublines of the Burkitt line Daudi, selected on the basis of reactivity with soybean agglutinin, differ in tumorigenicity in athymic mice.

Two subpopulations were isolated on the basis of soybean agglutinin (SBA) binding, from the human Burkitt lymphoma line Daudi. The low- and high-binder sublines maintained this characteristic in continuous passages. Their surface marker profiles, antibodies, scanning electron microscope (SEM), cytochemical reactions and binding of other lectins (concanavalin A and wheatgerm agglutinin) were not different. They differed, however, in growth potential in athymic mice. The low-binder subline had lower frequency of takes, tumor weight and volume, and did not metastasize as compared to the high-binder subline. However, the reaction with F-SBA of all the tumor cells examined was strong (greater than 70%), indicating in vivo selection and tumor development of high binder cells.

Animals↗
PubMed1988

Doxorubicin conjugates of monoclonal antibodies to hepatoma-associated antigens.

A panel of six murine monoclonal antibodies against hepatocellular carcinoma-associated antigens, reactive with PLC/PRF/5 human hepatoma cells, was conjugated to Adriamycin (doxorubicin) via a dextran bridge. This library of antibodies includes three monoclonal antibodies against hepatitis B virus surface antigen, one anti-alpha-fetoprotein, and two other IgG2a antibodies against PLC/PRF/5 hepatoma-associated antigens. The use of dextran for conjugation of Adriamycin to antibodies enabled a 5- to 10-fold amplification of the number of drug molecules linked to antibody. Conjugation of Adriamycin to dextran caused an occasional reduction in the pharmacologic activity of dextran-Adriamycin in [3H]thymidine incorporation assays in hepatoma cells as compared to nonconjugated Adriamycin. This loss of anticellular activity was partially compensated for by conjugation of specific antibodies to the dextran-Adriamycin conjugate. Conjugated compounds completely retained their binding activity to purified hepatitis B virus surface antigen and alpha-fetoprotein fixed to a solid matrix as compared to binding of homologous nonconjugated antibodies. However, some reduction of the binding activity to intact hepatoma cells was observed in three of six conjugates. Binding activity to hepatoma cells and, as a consequence, suppression of tumor cell DNA synthesis by the various conjugates was enhanced as compared to the same effect in treated colorectal carcinoma cells that do not express the relevant hepatoma-associated proteins. Furthermore, two conjugates containing nonspecific antibodies did not bind to hepatoma cells and caused minimal suppression of DNA synthesis. These results suggest that this panel of monoclonal antibody-dextran-Adriamycin conjugates was effective in suppression of PLC/PRF/5 cell growth in vitro.

Animals↗
PubMed1988

Measles: clinical and laboratory observations in young adults during an epidemic.

We describe the spectrum of clinical and laboratory findings in 130 young nonvaccinated adults who had measles during an epidemic, and give special emphasis to liver involvement. The data from these cases are compared to those of other selected groups of hospitalized young adults. Since measles seems to cause severe morbidity in adults, active measures should be taken to identify and vaccinate vulnerable nonimmunized individuals.

Acute Disease↗
PubMed1988

Pathophysiological changes associated with increasing grade of hepatic encephalopathy.

The pathophysiological changes occurring with increasing grade of encephalopathy were examined in 93 consecutive episodes in 44 patients with liver cirrhosis (37 posthepatic). The incidence of gastrointestinal bleeding and leukocytosis increased significantly when the grade advanced from 1 to 5. The following variables showed a trend for change that did not reach statistical significance: rising serum bilirubin, SGOT, and BUN levels; decreasing serum sodium and chloride levels; and increased incidence of infection. The mean values of the following variables were significantly different in 25 fatal episodes and 68 survivors, implicating a bad prognosis: high serum bilirubin, alkaline phosphatase, and BUN levels; low serum albumin, sodium, and chloride levels; and a higher incidence of severe infections (sepsis, infected ascitic fluid). Because increasing grade of encephalopathy is the most important factor in determining the prognosis of hepatic encephalopathy (mortality 0, 10, 5, 19, and 85 percent in grades 1 to 5, respectively), more efforts should be made to understand and prevent the pathophysiological changes associated with advancing grades of encephalopathy.

Acute Disease↗
PubMed1988

Delta virus infection in Jerusalem.

The role of hepatitis delta virus (HDV) infection was analyzed retrospectively in a highly selected population of 76 patients who were hospitalized in Jerusalem for hepatitis B surface antigen positive for chronic active hepatitis and cirrhosis. Of 25 patients in whom serum and liver tissue were available, 5 patients (20%) showed evidence for HDV infection using a serum anti-HDV IgG radioimmunoassay; in one of them, HDV was also detected in nuclei of infected hepatocytes by immunofluorescence (IF). When only serum was tested, 12 of 45 patients (27%) were anti-HDV IgG positive. The use of IF alone had a very low yield of HDV detection. All HDV-positive patients with available serum had superinfection with the delta agent as confirmed by a negative anti-HBc IgM assay. The majority of HDV-positive patients were immigrants from Rumanian or Middle Eastern and Mediterranean origin. The mean age of delta-positive patients was 10 years lower at clinical presentation as compared with HDV-negative patients. HDV-positive patients had a higher mortality as compared with the HDV-negative group. In conclusion, HDV infection is prevalent among Israeli patients with chronic liver disease and persistent hepatitis B virus infection and leads to a significant morbidity and mortality.

Adolescent↗
PubMed1987

Clofibrate does not induce peroxisomal proliferation in human hepatoma cell lines PLC/PRF/5 and SK-HEP-1.

The potential of fibrate drugs to induce peroxisomal proliferation in human liver cells was evaluated in athymic nude mice transplanted with human hepatoma cells and treated by clofibrate in vivo as well as in cultured human hepatoma cells in the presence of fibrate drugs added to the culture medium. Clofibrate did not induce peroxisomal activities and neither acted as a peroxisomal proliferator in human PLC/PRF/5 or SK-HEP-1 heterotransplants under conditions of induction of peroxisomal activities in the host rodent liver. Similarly, clofibric acid or bezafibrate did not induce peroxisomal activities in cultured human PLC/PRF/5 or SK-HEP-1 cells under conditions of induction of peroxisomal activities in cultured primary rat liver cells. The lack of response of the human cells to peroxisomal proliferators of the fibrate type may indicate a species specificity with respect to induction of peroxisomal activities by xenobiotic peroxisomal proliferators.

Carcinoma, Hepatocellular↗
PubMed1987

Stimulation by cAMP of erythropoietin secretion by an established human renal carcinoma cell line.

We used our recently reported stable, transformed human renal carcinoma cell line as a model system to study the role of 3',5'-adenosine monophosphate (cAMP) in erythropoietin secretion. The erythropoietin produced by these cells is both biologically active and immunologically cross-reactive with purified native human hormone in our radioimmunoassay. Erythropoietin release by these renal carcinoma cells appears to be stimulated by cAMP as well as by the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (MIX). The response to cAMP involves a rapid and enhanced release of hormone, which occurred within 30 minutes of exposure of the cells to the effector and continued for at least 4 hours. Intracellular erythropoietin was higher in the control cultures than in the cells treated with cAMP, suggesting that cAMP stimulates the release of a storage pool of hormone. The ability of cAMP and MIX to elicit the release of erythropoietin suggests that a cAMP-mediated mechanism is involved in the release of this hormone.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Nodular regenerative hyperplasia with portal hypertension in a patient with myasthenia gravis.

Nodular regenerative hyperplasia of the liver is a rare cause of portal hypertension and bleeding esophageal varices, occurring mainly in association with collagen vascular diseases. The patient described herein had both myasthenia gravis and nodular regenerative hyperplasia. To the best of our knowledge, this is the first report of this association.

Esophageal and Gastric Varices↗
PubMed1986

Conjugates between monoclonal antibodies to HBsAg and cytosine arabinoside.

Chemotherapeutic agents such as cytosine arabinoside (ARA-C) and adenine arabinoside (ARA-A) have been shown to eliminate or suppress replication of some DNA viruses. These effects were however associated with systemic side-effects to the treated hosts. We are currently exploring a strategy to construct conjugates between these antiviral agents and monoclonal antibodies directed against viral surface proteins. Such conjugates should enable specific delivery of the antiviral agents to their preferred site of action. In the present study, monoclonal antibodies to hepatitis B virus surface antigen (HBsAg) of the IgG2a and IgM isotypes were conjugated to ARA-C via a dextran bridge. The use of dextran enables the binding of a high number of drug molecules to the antibody with minimal loss of activity. Briefly, partially oxidized dextran was coupled to ARA-C and then to monoclonal anti-HBs. Following the conjugation process, the IgG2a anti-HBs-(dex)-ARA-C conjugate retained its capacity to bind to HBsAg fixed to a solid matrix as compared to non-conjugated homologous antibodies. Conjugates between ARA-C and IgM anti-HBs lost a significant degree of their binding activity to purified HBsAg. However, conjugates containing anti-HBs of both isotypes bound specifically to PLC/PRF/5 human hepatoma cells that express HBsAg on their cell surface. Conjugates containing non relevant monoclonal antibodies did not bind to target cells. Pharmacologic activity of the various compounds was assessed by an [3H]thymidine incorporation assay in hepatoma cells in culture. IgM and IgG2a containing conjugates caused suppression of [3H]thymidine incorporation into PLC/PRF/5 cells. This effect was more pronounced for conjugates containing monoclonal IgM anti-HBs.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1986

Detection of alpha-foetoprotein messenger RNA in human hepatocellular carcinoma and hepatoblastoma tissue.

Alpha-foetoprotein (AFP) synthesis, although repressed in normal adults, is increased in the majority of patients with hepatocellular carcinoma (HCC). We have investigated whether active transcription of the AFP gene may explain raised serum AFP concentrations in patients with HCC and hepatoblastoma by assaying human tumour and non-neoplastic tissue by molecular hybridization for the presence of mRNA encoding AFP. Ten operative HCC and six autopsy HCC specimens, two HCC cell lines, and one hepatoblastoma specimen were examined. Total cellular RNA and poly-(A)+ RNA were extracted and AFP mRNA sequences sought by dot-blot and Northern blot hybridisation to a human cDNA AFP probe. Cellular AFP was localised by avidin-biotin staining. AFP mRNA was detected in 8/10 operative specimens, as well as PLC/PRF/5 nude mouse tumours. Weaker hybridization was detected in 4/6 autopsy specimens. Signals of comparable intensity to that in operative tumours were detected in non-neoplastic tissue of 6 patients. AFP mRNA from nude mouse tumours migrated as a 20S discrete band on agarose gel electrophoresis, whereas a more complex hybridization pattern was evident in human tumours. Positive cytoplasmic immuno-staining for AFP was observed in 4 tumours and 2 corresponding non-neoplastic specimens and in a HCC cell line. In non-neoplastic liver, AFP was localised in cells that appeared dysplastic. Thus steady-state levels of AFP mRNA are detectable in human HCC tissue and surrounding non-neoplastic liver. These findings may prove pertinent to an understanding of the genetic expression of AFP in malignant hepatocytes, and the sequence of events leading to uncontrolled cellular proliferation.

Carcinoma, Hepatocellular↗