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Biomedical subjects

D Shouval

Publications and source records attributed to D Shouval.

At least 55 records · Page 3Linked to original sources
PubMed1999

Antigen-specific B and T cells in human/mouse radiation chimera following immunization in vivo.

Adoptive transfer of human peripheral blood mononuclear cells (PBMC) into mice with severe combined immunodeficiency (SCID) or into lethally irradiated BALB/c mice radioprotected with SCID bone marrow, leads to marked engraftment of human T and B cells. In such chimeras, human serum antibody responses can be stimulated readily by vaccination with recall antigens, but the detection of antigen-specific functional T or B cells has been extremely difficult. In the present study, we were able to detect by Elispot analysis high frequencies of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-gamma (IFN-gamma) or interleukin-4 (IL-4)-secreting T cells in peritoneum and spleen of human/BALB/c chimeric mice during the first 3 weeks after PBMC transfer. Moreover, specific memory responses were elicited by vaccination with tetanus toxoid (TT) or hepatitis B virus (HBV) surface (HBs) antigen of chimeric mice transplanted with PBMC derived from TT- or HBV-immune donors. Substantially higher TT-specific B-cell frequencies were found during the first 3 weeks after vaccination in mice challenged with the specific antigen compared to the levels found in control animals. High numbers of TT-specific IFN-gamma-secreting T cells persisted in the peritoneum of vaccinated, but not of unvaccinated, animals during the entire observation period, but only low numbers of specific IL-4-secreting T cells were found in vaccinated mice. Similar results were achieved following vaccination with HBs antigen of chimeric mice, transplanted with PBMC of HBV immunized donors. Thus, TT or HBsAg-specific antibody responses in our model correlate closely with the existence of specific IFN-gamma-secreting T helper 1/0 cells. Furthermore, these results show that adoptive transfer of human PBMC into lethally irradiated mice provides an efficient approach to generate specific B-cell fusion partners for the production of human monoclonal antibodies and specific T-cell lines for adoptive cell therapy of malignant or infectious diseases.

Adoptive Transfer↗
PubMed1999

Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.

A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.

Adolescent↗
PubMed1998

Psychological distress in patients with chronic, nonalcoholic, uncomplicated liver disease.

To study whether the presence of significant disease in a major organ, possibly with minimal or no clinical symptoms, would be associated with psychological disturbance, 80 subjects suffering from chronic hepatitis or cirrhosis, of nonalcoholic etiology were interviewed. Of these, 64 had either minimal or no physical symptoms. Patients completed the Brief Symptom Inventory (BSI) and the Impact of Event Scale (IES), questionnaires, which measure symptoms of psychological distress. It was found that 50% of the liver subjects were defined as cases by the BSI criteria including 15% who were defined as severe cases. There were no gender differences. Forty-five percent of asymptomatic liver subjects were defined as cases. Psychological distress was significantly pronounced in subjects with less than 12 years of education. This study points to a significant incidence of psychological distress, even in clinically asymptomatic subjects, suffering from chronic, nonalcoholic, uncomplicated liver disease.

Adult↗
PubMed1998

Hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is one of the world's most common malignancies. The aims of the present paper are to review data on (1) epidemiology and screening programmes for the early detection of the tumour and (2) advances in the diagnostic imaging and management. METHODS: Relevant English language articles, published between January 1985 and December 1997, were reviewed. Articles were identified through Medline search, using the key words 'hepatocellular carcinoma'. Articles cited in the bibliographies of these articles were searched manually. RESULTS: Hepatocellular carcinoma has a heterogeneous geographical distribution. Although its risk factors have been identified, the efficacy of screening programmes remains uncertain. Imaging has improved substantially with the recent application of dual-phase helical computed tomography and magnetic resonance imaging employing specific contrast agents. The comparative efficacy of conservative therapy and surgical resection is uncertain, since well controlled trials are lacking. CONCLUSION: Hepatocellular carcinoma is commonly a problem of two diseases, the malignancy itself and cirrhosis. This renders treatment rarely curative, even when surgical resection can be applied in a technically successful sense. Liver transplantation could be a definitive treatment but this is plagued by limited donor resources.

Carcinoma, Hepatocellular↗
PubMed1998

Vaccines for prevention of viral hepatitis.

At the end of the 20th century active immunization against hepatitis A and B has been introduced into routine medical practice. Therefore, patients at risk, and especially those with coagulation disorders, should be immunized at the earliest age possible. In contrast, development of an efficacious vaccine against hepatitis C remains an important goal for the next decade.

Blood Coagulation Disorders↗
PubMed1998

Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera: the Trimera system.

An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested.

Amino Acid Sequence↗
PubMed1997

Suppression of human hepatoma in mice through adoptive transfer of immunity to the hepatitis B surface antigen.

BACKGROUND/AIMS: Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) has previously been shown to occur in mice and humans through transplantation of bone marrow cells from donors immunized against HBsAg (anti-HBs) to non-immune recipients. In the present study we evaluated the effect of adoptive transfer of immunity to HBsAg on the growth of HbsAg-secreting hepatocellular carcinoma (HCC) xenografts in athymic mice. METHODS: Immunocompetent mice were immunized with recombinant HBsAg. Bone marrow cells from anti-HBs+ mice were injected intravenously to irradiated athymic Balb/c mice which had been previously transplanted subcutaneously with Hep3B human hepatoma cells. Treatment groups included mice receiving bone marrow transplantation from HBV-immunized (anti-HBs positive) and non-immunized (anti-HBs negative) donors. RESULTS: At 9 weeks post bone marrow transplantation, tumor volume and serum alpha-fetoprotein levels in athymic mice receiving HBV-immune bone marrow cells were 11.5 mm3 and 363 ng/ml, respectively, as compared to 1579 mm3 and 19,000 ng/ml, in recipients of non-immune bone marrow transplantation (p<0.005). T-cell depletion of antiHBs+ immune bone marrow prior to transplantation decreased the anti-tumor effect but did not abolish it. A mild nonspecific, bone marrow-derived, graft versus tumor effect was observed in mice transplanted with human hepatoma cells that do not express HBsAg. CONCLUSIONS: Adoptive transfer of immunity to HBV facilitates suppression of experimental human HCC expressing HBsAg. This effect is the result of a combination of specific anti-viral surface antigen effect and a nonspecific graft versus tumor effect.

Adoptive Transfer↗
PubMed1997

Comparison of methods for extraction of nucleic acid from hemolytic serum for PCR amplification of hepatitis B virus DNA sequences.

The sensitivity of PCR for the amplification of target nucleic acid sequences in clinical diagnostics may often be reduced due to the presence of inhibitory factors. Hemolytic serum contains a number of PCR inhibitors, one of which is hemin. In this study we have found that conventional methods of DNA extraction were not sufficient for the removal of PCR-inhibitory compounds in hemolytic serum. We have therefore compared the efficiency of several commercial and noncommercial methods of nucleic acid purification from hemolytic serum samples prior to PCR amplification. Separation with the QIAamp HCV kit, dialysis with Millipore filters, and bovine serum albumin absorption were all found to be suitable extraction methods for eliminating inhibitors from hemolytic serum for PCR amplification. Using these methods we were able to detect very low levels of hepatitis B virus DNA in hemolytic serum.

Animals↗
PubMed1997

Hepatitis C-associated cryoglobulinemia presenting with pericardial effusion.

A 54-yr-old man underwent orthotopic liver transplantation for cirrhosis caused by hepatitis C virus and associated with cryoglobulinemia and proteinuria. Four months after transplantation, the patient was reinfected with hepatitis C virus and cryoglobulinemia recurred, accompanied by increasing proteinuria, ascites, and pleural and pericardial effusion. Serum cryoglobulins and pleural and pericardial effusion disappeared rapidly following treatment with ribavirin, whereas proteinuria remain unchanged. We believe that pericardial effusion is an unusual presentation of hepatitis C virus-associated cryoglobulinemia.

Cryoglobulinemia↗
PubMed1996

Beneficial effect of ribavirin on hepatitis C-associated cryoglobulinemia after liver transplantation.

Mixed cryoglobulinemia is a well-known complication after hepatitis C virus (HCV) infection. We report five cases in which cryoglobulinemia appeared or grossly exacerbated following orthotopic liver transplantation (OLT). Cryoglobulinemia and the associated clinical symptoms resolved or improved in two patients treated with ribavirin after liver transplantation, while plasmapheresis was ineffective in another patient. The mechanism involved in induction of cryoglobulinemia after liver transplantation is unknown. However, the effect of antiviral therapy observed in these patients suggests a correlation between cryoglobulinemia, HCV replication, and possibly hepatocellular disease activity. A larger-scale study is warranted to test the effect of ribavirin on post-OLT HCV-associated cryoglobulinemia.

Adult↗