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D Shouval

Publications and source records attributed to D Shouval.

At least 73 records · Page 4Linked to original sources
PubMed1996

Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine containing Pre S antigens: a preliminary report.

A new vaccine against hepatitis B virus (HBV) infection, produced in mammalian Chinese hamster ovary (CHO) cells, contains the small(s), middle (Pre S2) and large (Pre S1) surface proteins of HBV. Three injections of a 5-micrograms or 10-micrograms dose were administered intramuscularly (i.m.) at 0, 1 and 6 months to a group of 105 young adults, who were monitored for a period of 6 months after the third injection. Seroconversion rates were 100% after the second injection of the 5-micrograms or 10-micrograms dose. Geometric mean titres of HBsAb at 1 month after the third injection were 12,156 mIU ml-1 and 13,482 mIU ml-1 in those receiving the 5-micrograms and 10-micrograms dose respectively. The vaccine was well tolerated with no significant adverse events. These preliminary results suggest that the Pre S-s recombinant vaccine, produced in mammalian cells, is highly immunogenic, leading to 100% seroconversion in the population tested after injection of only two doses of 5 micrograms.

Adolescent↗
PubMed1996

Mononeuritis multiplex: a rare complication of acute hepatitis A.

A 28-year-old man suffered from acute severe hepatitis A virus infection, documented by serologic diagnosis. During the clinical and enzymatic recovery phase, mononeuritis multiplex that involved the left ulnar and right lateral cutaneous nerves developed. It presented by sensorimotor disturbances in left arm and right thigh. Mononeuritis multiplex has been frequently described in patients with chronic hepatitis B, either isolated or associated with periarteritis nodosa. However, it has not been reported in association with hepatitis A infection.

Adult↗
PubMed1996

Esophageal malignancy after liver transplantation in a patient with Barrett's esophagus.

Patients undergoing liver transplantation are predisposed to develop extrahepatic malignancies. It is also known that patients with predisposed conditions, such as Barrett's esophagus, have higher rates of esophageal carcinoma. We present here a patient who underwent liver transplantation, had Barrett's esophagus, and developed esophageal malignancy a short time after transplantation. Liver transplantation may be associated with acceleration of the precancerous condition and the development of malignancies.

Adenocarcinoma↗
PubMed1995

Hepatitis C-associated cryoglobulinemia after liver transplantation.

Mixed cryoglobulinemia is well known to be associated with hepatitis C virus (HCV) infection. We report two cases in which cryoglobulinemia appeared or became grossly exacerbated after orthotopic liver transplantation. In both cases, there was co-appearance of cryoglobulinemia with the reinfection of the grafted liver with HCV. It is postulated that the cryoglobulinemia might be related to secondary HCV infection in these patients.

Adult↗
PubMed1995

p53 expression in patients with cirrhosis with and without hepatocellular carcinoma.

BACKGROUND: Mutated p53 acts as a dominant oncogene, whereas the wild type (wt) p53 gene product suppresses cell growth. Abnormalities in the p53 gene are reported in more than 50% of malignant tumors. Recently, an allelic loss of chromosome 17p, where the p53 gene is located, was found to be more frequent in hepatocellular carcinoma (HCC) cell lines and human tumors. In addition, in half of the cases of HCC from endemic areas for hepatitis B virus and aflatoxin, a hot spot point mutation at codon 249 was detected, as previously reported. Missense mutations in p53, mdm-2 complex formation, and other unknown mechanisms may lead to stabilization of the gene product, thus rendering it detectable by immunohistochemistry. METHODS: To assess the relationship between p53 status at a premalignant stage and in HCC, the authors studied the immunohistologic expression of p53 in HCC and in the adjacent nontumorous resected liver tissue, using monoclonal antibody to wt and mutated p53. RESULTS: Twelve of the 14 patients with liver tumors had HCC. Of the 12 patients with HCC and underlying cirrhosis, 8 (67%) had increased p53 expression in HCC cells. Eight of the 12 patients with p53-positive HCC cells had p53 overexpression in the nontumorous hepatocytes within regenerative nodules adjacent to HCC tissue. Three of 21 cirrhotic livers without a detectable tumor had increased p53 expression in the regenerative nodules. None of the 12 patients with chronic active hepatitis without cirrhosis or the 13 with a normal liver histology had increased p53 expression. CONCLUSION: p53 overexpression in some cirrhotic livers and in nontumorous livers of patients with HCC may indicate a normal p53 gene response to cellular stress or, alternatively, to an abnormally or mutated p53 gene, and could occur before the development of HCC.

Adolescent↗
PubMed1995

Hepatitis A virus and polymerase chain reaction amplification: methodology and results.

Hepatitis A infection among patients receiving solvent/detergent inactivated factor VIII preparations in various locations in Europe have been documented recently. In investigations in Italy, Germany and Ireland, polymerase chain reaction (PCR) amplification was used to detect hepatitis A virus in frozen plasma pools, purified factor VIII, patient sera and samples from animal transmission studies; nucleic acid sequencing was used to clarify and identify the virus responsible based upon genotype analysis. Unique virus strains were found among the cases in Italy and Germany, and identical virus sequences were also found in some factor VIII lots. However, with the exception of the Italian investigation, lack of appropriate samples have precluded the identification of virus in these outbreaks. In addition, animal infectivity studies have not been successful in demonstrating infectivity under laboratory conditions. We discuss the limitations of PCR amplification with respect to detecting virus within these situations, and the necessity for the corresponding epidemiologic investigations.

Animals↗
PubMed1995

Immunization against hepatitis B through adoptive transfer of immunity.

Clearance of hepatitis B virus (HBV) infection requires an effective T-cell-dependent humoral response that is often defective in HBV carriers and in immunosuppressed patients. We have shown in mice and humans that bone marrow (BM)-derived memory cells, capable of producing antibodies to the HBV envelope and nucleocapsid antigens, are transferable from BM donors (BMD) to their recipients. BMD BALB/c mice were immunized with recombinant HBV surface antigen (HBsAg), and BM from anti-HBs-positive donors was transplanted to irradiated recipient mice, who seroconverted to anti-HBs within 30 days of bone marrow transplantation (BMT), and responded to booster vaccination. In a similar manner, 19/26 human BM recipients, who received their HLA-matched BM from BMDs immunized once with HBsAg, seroconverted within several weeks after BMT. Antibodies to HBsAg were also observed in 3 recipients of peripheral blood lymphocytes (PBL) obtained from HLA-matched immunized human donors. Finally, clearance of HBsAg and HBV DNA was observed in an HBsAg carrier with leukemia who received BMT from his HLA-matched anti-HBc+/anti-HBs+ brother. These results indicate that adoptive transfer of immunity to HBV may be achieved through immunization of BM or PBL donors against HBV.

Animals↗
PubMed1995

Specific targeting of adriamycin conjugates with monoclonal antibodies to hepatoma associated antigens to intrahepatic tumors in athymic mice.

Doxorubicin (adriamycin), once considered the treatment of choice for hepatocellular carcinoma (HCC), is known to cause cardiotoxicity and myelotoxicity. To reduce the systemic toxicity of adriamycin by direct delivery of the drug to the tumor site, we established a panel of monoclonal antibodies (MAbs) to hepatoma associated antigens that were conjugated to adriamycin by a dextran bridge. Initially, the efficacy of these conjugates in suppressing tumor growth was assessed using a model of subcutaneous HCC tumors injected in athymic mice. In the second stage of the study, we tested these conjugates in an experimental model in which human HCC was transplanted intrahepatically by intrasplenic injection, thus providing the tumor cells with growth factors and an adequate cellular matrix, similar to the natural microenvironment of HCC. Anti-tumoral therapy resulted in lower serum alpha-fetoprotein (AFP) levels in two of three experimental groups treated with different specific conjugates as compared with control mice treated with the individual components. Efficacy of targeting was enhanced using the intrahepatic model system for propagation of HCC and was demonstrated by fluorescence of adriamycin and MAb in tumor tissue and absence of this fluorescence in healthy liver tissue surrounding the tumor. Reduction of systemic toxicity was shown by the absence of adriamycin fluorescence in myocardial tissue in conjugate-treated mice, whereas in all other treatment groups, including mice treated with a mixture of adriamycin and specific MAb, there was strong myocardial fluorescence of adriamycin.

Animals↗
PubMed1995

Successful immunization of autologous bone marrow transplantation recipients against hepatitis B virus by active vaccination.

Patients undergoing autologous bone marrow transplantation (BMT) are severely immunosuppressed. These patients are exposed to various infections agents due to delayed and efficient reconstitution of their immune system. Forty-eight patients with hemato-oncological malignancies were immunized against hepatitis B virus (HBV) following autologous BMT. Twenty one were vaccinated more than 10 days before BMT, 17 on days 1-9 before and 10 day after BMT. Thirty three patients (68.7%) seroconverted within 40 days after autologous BMT after receiving one dose of the vaccine before autologous BMT with a relatively low level of anti-HBs, whereas in 11 no anti-HBV antibodies could be detected. Nineteen patients remained seropositive but in 11 the seroconversion was only transient no correlation was found between permanent or transient seroconversion and basic disease, conditioning regimens, post-transplant therapy, immunotherapy and day of vaccination in relation to autologous and day of vaccination in relation to autologous BMT. Active HBV immunization of patients with malignancy undergoing autologous BMT is feasible and levels of antibodies, although low, are above the conventional protective titers. Therefore active immunization of some patients may reduce hepatitis-related complications in the setting of autologous BMT.

Adolescent↗
PubMed1994

Improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis B vaccine containing pre-S1 and pre-S2 antigens as compared with conventional yeast-derived vaccines.

The widely used hepatitis B virus (HBV) vaccines consist of the small hepatitis B surface (SHBs) protein produced in transfected yeast cells. The frequency of non-responders, especially among immunocompromised patients, has increased the demand for a more immunogenic vaccine. We evaluated the immunogenicity of recombinant HBs 20 nm particles secreted by transfected Chinese hamster ovary (CHO) cells, Bio-Hep-B (BioTechnology General Ltd, Israel), and compared it with yeast-derived vaccines. The CHO-derived vaccine contains the small hepatitis B surface antigen (SHBs protein) as the major component, as well as the middle HBs (MHBs, pre-S2) and the large HBs (LHBs, pre-S1) antigens. Nine groups of ten female Balb/c mice, 4-6 weeks old, were injected once intraperitoneally (i.p.) with 0.09, 0.27 or 0.81 micrograms of each of three vaccines: Bio-Hep-B or two conventional yeast-derived recombinant vaccines, Engerix-B (SmithKline Beecham, Belgium) and H-B-Vax II (Merck, Sharp & Dohme, USA) containing only non-glycosylated SHBs antigen. After 30 days, 40% of the mice injected with 0.09 microgram Bio-Hep-B had seroconverted, but none of the mice receiving the same dose of the other vaccines. The immunogenic dose in 50% of the mice at day 14 after injection was 0.13 microgram for Bio-Hep-B, but over 0.81 microgram for the other two vaccines. Mice of the strain B10/M (which are unresponsive to SHBs and MHBs antigens at the T-cell level) developed 100-fold higher anti-HBs titres after immunization with 1 microgram of Bio-Hep-B i.p., as compared with mice receiving the same amount of yeast-derived HBsAg vaccines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Enhancement of HBsAg detection in serum of patients with chronic liver disease following removal of circulating immune complexes.

Patients with chronic liver disease and hepatocellular carcinoma may lack serological evidence of previous hepatitis B virus infection. The purpose of the present study was to test the hypothesis that circulating immune complexes may interfere with the detection of low levels of HBsAg in such patients. Sera from 190 patients were initially screened for the presence of circulating immune complexes. Patients belonged to three clinical categories: asymptomatic HBsAg carriers (50 patients), chronic liver disease (30 patients) and hepatocellular carcinoma (110 patients). Forty-one of the group of 190 patients (21%) were positive for circulating immune complexes. Sera from 21 patients were selected for further evaluation. The sera of 13 chronic liver disease or hepatocellular carcinoma patients (HBsAg negative, hepatitis B virus-DNA negative, with or without evidence of previous hepatitis B virus infection) and eight HBsAg positive carriers (four asymptomatic, three with chronic liver disease and one with hepatocellular carcinoma) were passed through a Clq affinity column (first column) to remove circulating immune complexes. Unbound material was then passed through a monoclonal IgG2a anti-HBs affinity column (second column). Unbound material (following both columns) contained free HBsAg, as determined by monocolonal radio-immunoassay, in eight patients in whom HBsAg had been undetectable in the original serum. Removal of circulating immune complexes from the serum of the three HBsAg positive patients with chronic liver disease also caused a significant increase in measurable circulating HBsAg compared with the original serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Exposure to hepatitis B and C and to HTLV-1 and 2 among Israeli drug abusers in Jerusalem.

The incidence of exposure to hepatitis B (HBV) and C (HCV) viruses and to that of HTLV 1 and 2 were investigated in a group of 181 illicit drug users attending a drug rehabilitation centre in Jerusalem. In this predominantly male group, 28% were intravenous drug abusers (IVDAs) and 72% non-IVDAs; 92% of the individuals were of Middle Eastern descent (of which 40% were of a Moroccan descent). Antibodies to hepatitis C virus (anti-HCV) were found in 54% of the IVDAs compared with 4.5% in the non-IVDAs (p < 0.001), indicating the presence of a significant reservoir of HCV among this IVDA group. Evidence for previous hepatitis B (HBV) infection was found in 26% of the IVDAs and 33% of the non-IVDAs (p = NS) with no HbSAg positivity. The similar prevalence of previous HBV infection in both drug abuser groups, which was also observed when the groups were analysed according to their ethnic origin, suggests that a vertical transmission of HBV rather than an exclusive association with intravenous drug abuse may have been the source of exposure to HBV. HTLV-1 rates were 2% among IVDAs and 0% among non-IVDAs (p = NS). No serologic evidence for HTLV-2 was detected in this cohort. The present study supports previous observations in other countries and indicates the exceptionally high prevalence of HCV infection among Israeli i.v. drug abusers. It also suggests that using HBV seropositivity as an indicator for needle exchange among drug abusers may be of limited value in geographic areas where vertical transmission of HBV is common. HCV antibodies might become more suitable markers for this purpose.

Adult↗
PubMed1994

Development of antibodies to hepatitis B virus surface antigen in bone marrow transplant recipient following treatment with peripheral blood lymphocytes from immunized donors.

Bone marrow transplantation (BMT) recipients are immunosuppressed and are at risk for contracting severe infections. Recently, adoptive transfer of immunity against hepatitis B virus (HBV) was documented in BMT recipients receiving bone marrow from 'naturally' HBV-infected individuals who recovered spontaneously, or those transplanted with bone marrow cells obtained from actively immunized donors. Furthermore, reconstitution of the immune system in a BMT recipient who was a hepatitis surface antigen (HBsAg)+/HBV DNA+ carrier with HBV immune bone marrow cells led to clearance of the replicating virus, presumably through adoptive cell-mediated immunotherapy. We report three cases of induction of immunity to HBV by selective adoptive transfer by i.v. injection of peripheral blood lymphocytes (PBL) obtained from BMT donors who were actively immunized against HBV after harvesting of bone marrow. All three BMT recipients developed anti-HBs antibodies. In one BMT case in whom antibodies to HBsAg developed following adoptive transfer of immune PBL, a mild booster effect was documented in the BMT recipient upon immunization with a recombinant hepatitis B vaccine. The two remaining patients lost their antibodies to HBsAg in association with relapse of leukaemia. This immune manipulation may open the door to evaluation of adoptive transfer of immunity to HBV through selective transplantation of HBV immune lymphocytes in selected patients such as those with persistent HBV infection, as well as liver transplant recipients who require protection of the graft against HBV re-infection.

Adolescent↗
PubMed1994

Sequence variability of hepatitis A virus and factor VIII associated hepatitis A infections in hemophilia patients in Europe. An update.

Outbreaks and sporadic cases of hepatitis A have been observed in 4 European countries in hemophilia patients receiving factor VIII preparations. PCR amplification of potential hepatitis A virus (HAV) nucleic acid present in plasma pools, purified factor VIII and acute-phase sera from infected individuals has been performed and the nucleic acid sequence determined for those samples that resulted in a positive PCR product. HAV sequences were detected in the serum of 2 German patients, but not in the factor VIII lots administered to these individuals. Screening of plasma pools and the corresponding 5 lots of factor VIII associated with the outbreak in Ireland did not reveal any HAV sequences. In contrast, a study of samples from Italy detected HAV sequences in 5 of 12 lots and in 2 hemophilia patients who developed hepatitis A. These data suggest that implicated factor VIII preparations might have been involved in the outbreaks of HAV infection among Italian hemophiliacs. However, no molecular evidence was obtained for a similar association in Germany or Ireland. The preliminary data from these two investigations must be verified by animal inoculation studies and supported by epidemiologic analysis.

Base Sequence↗
PubMed1994

Chronic hepatitis C virus infection with exposure to hepatitis B virus.

The prevalence of hepatitis C virus (HCV) infection in patients with chronic liver disease (CLD) in Israel has not yet been reported. A retrospective analysis was performed on the first 92 consecutive patients referred to our Liver Unit with serologically confirmed antibodies to hepatitis C virus (anti-HCV) who had evidence for chronic hepatitis, cirrhosis, and hepatocellular carcinoma. We compared 31 patients who were anti-HCV positive with 61 patients who had evidence for both previous or present infection with hepatitis B virus (HBV) as well as HCV. Dual infection was significantly more prevalent in Jewish patients of non-Ashkenazi origin, who were also characterized by higher rates of portal hypertension manifested by ascites, bleeding esophageal varices as well as hepatic encephalopathy and spontaneous bacterial peritonitis. We conclude that dual infection of HBV and HCV was found in 66% of patients with anti-HCV positive liver disease in Jerusalem, and that these patients develop more serious complications than CLD patients with anti-HCV alone.

Adolescent↗