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Biomedical subjects

E Ben-Porath

Publications and source records attributed to E Ben-Porath.

At least 37 records · Page 2Linked to original sources
PubMed1985

Antigenic characterization of human hepatocellular carcinoma. Development of in vitro and in vivo immunoassays that use monoclonal antibodies.

Several libraries of monoclonal antibodies have been produced by immunization of Balb/c mice with single cell suspensions of nontrypsin-treated human hepatocellular carcinoma cell (HCC) lines in order to study the antigenic properties of transformed hepatocytes. The antibodies were characterized with regards to specificity for hepatoma-associated antigens and their capability for use as reagents in radioimmunoassays (RIAs) and tumor localization in vivo. Three such antibodies namely, P215457, PM4E9917, P232524 of the IgG2a, IgG2a, and IgG1 isotypes, respectively, not only recognized separate and distinct antigenic determinants on four human hepatoma cell lines but also reacted with epitopes present on chemically induced rat hepatoma cell lines. In contrast, only 1 of 38 other human malignant and transformed cell lines demonstrated reactivity with the three antibodies; normal human tissues were also found to be unreactive. Monoclonal antibody P215457 densely stained the plasma membrane by indirect immunofluorescence, showed rapid binding activity to HCC cells in suspension, and precipitated a 50,000-mol wt cell surface protein; antibody PM4E9917 also stained the plasma membrane and precipitated a 65,000-mol wt protein, whereas P232534 recognized cytoplasmic antigenic determinants. With these antibodies "simultaneous sandwich" RIAs were established that detect soluble hepatoma-associated antigens in culture supernatants. Finally, the Fab fragment of P215457 was found to be useful in tumor localization in vivo. This antibody fragment when labeled with 131I was shown to localize by radionuclide-imaging studies in human hepatoma grown in nude mice. Thus, these investigations demonstrate that monoclonal antibodies may be produced against epitopes that reside almost exclusively on transformed hepatocytes and such antibodies may be successfully employed in the development of in vitro and in vivo immunoassays.

Animals↗
PubMed1985

Structural analysis of hepatitis B surface antigen by monoclonal antibodies.

A method has been developed for the analysis of hepatitis B surface antigen (HBsAg) antigenic structure at the molecular level that creates "fingerprints" or "signatures" of various hepatitis B viral (HBV) strains. This technique employs high affinity IgM and IgG monoclonal antibodies (anti-HBs) directed against distinct and separate determinants on HBsAg. In performing this antigenic structural analysis, separate binding curves for different monoclonal anti-HBs are generated by measuring immunoreactivity in serial dilutions of HBsAg-positive serum by radioimmunoassay. Since the HBsAg concentration in serum is unknown, the binding profiles of groups of samples are aligned by an iterative least-squares procedure to generate the numerical signature characteristic of the viral strain. The numerical signatures are then displayed on a computer-graphic plot. The signature profiles of HBsAg subtypes are a true reflection of their antigenic structure, and in vertical and horizontal transmission studies the molecular characteristics of the viral epitopes are conserved. By signature analysis we found substantial antigenic heterogeneity among the ayw3 strain both in the U.S. and France, as well as in populations of the Far East and Africa. Populations in Ethiopia, Gambia, and the Philippines were infected with two antigenically distinct HBV strains. In some newly identified HBV strains, it was found that epitopes identified by some monoclonal antibodies were absent or substantially reduced, which suggested that a genetic mutation may have occurred. Thus this study suggests that there is far more antigenic heterogeneity in HBV than previously recognized. These variants are antigenically distinct from each other at the epitope level, and were heretofore unrecognized by polyvalent anti-HBsAg antibodies.

Adult↗
PubMed1983

Epstein-Barr virus and infectious mononucleosis in children.

The presence of IgG antibodies to Epstein-Barr virus (EBV) has been investigated in two groups of children aged 3 to 35 months. The test group consisted of 31 children from an institution in which a high incidence of suspected infectious mononucleosis (IMN) was found. The control group comprised 54 children, aged 1 to 26 months, with noninfectious diseases. In the test group, 29 of the 31 children were positive for IgG anti-EBV antibodies in the serum, whereas only 5 children were positive in the control group. None of the children in the test group had detectable heterophile antibodies, and most of them did not show the typical symptoms of IMN. The reliability of diagnosing IMN in early childhood, by means of detection of anti-EBV serum antibody levels, is discussed.

Age Factors↗
PubMed1983

Ethnic differences in the incidence of postnecrotic cirrhosis in Israel: correlation with hepatitis B virus serological markers.

While immigrants from Morocco and Romania make up 7 and 6%, respectively, of the Israeli population, one-third of all postnecrotic cirrhosis patients come from Morocco and another third from Romania. The rate of hepatitis B virus (HBV) infection, as expressed by serum hepatitis B surface antigen, anti-HBs, and anti-HBc, was compared in immigrant patients with postnecrotic cirrhosis and in age and sex matched controls from the same countries. Among 19 Moroccan immigrants with postnecrotic cirrhosis 74% showed evidence of HBV infection. This was not significantly different from the prevalence of HBV infection (64%) in a matched control group of 61 Moroccan individuals. In the 26 Romanian cirrhotics, however, a significantly higher prevalance of HBV infection than in the 60 matched controls was observed (54 and 23%, respectively, p less than 0.01). The difference was detected only when anti-HBc was looked for in addition to hepatitis B surface antigen and anti-HBs. These results indicate that: 1) HBV infection and postnecrotic cirrhosis are associated in Romanian immigrants to Israel. 2) Association between HBV infection and cirrhosis in Moroccan immigrants cannot be shown because of the high infection rate in the control population. 3) Anti-HBc is often the only marker of HBV infection in cirrhotic patients, and should be examined in addition to hepatitis B surface antigen and anti-HBs in order to get meaningful results.

Adult↗
PubMed1981

A controlled trial with inactivated poliovaccine.

A trail with inactivated polio vaccine (IPV) was carried out, aiming at the earliest possible vaccination of young infants from rural settlements, before their exposure to type 1 wild poliovirus, highly prevalent in the environment. One hundred and fifteen infants were primed at the age of 2 and 3 1/2 months with the quadruple antigen DPT-polio. When 10 months old, 61 were boosted with the same antigen, and 54 with TOPV associated with DTP. Another 53 babies fed with TOPV at 2, 4, 6 and 12 months were used as a control. One dose of IPV produced antibody to polio type 1 in 83% of babies. With two doses of IPV a 100% response was obtained. Six months after the second dose, a small decrease in the percentage of infants wih detectable antibody to type 1 was observed, but at one month after the booster a highly significant anamnestic response was achieved. The results with IPV compared favorably with the immune response of infants given TOPV. Details on the results of the field trial will be presented, and field implementations of IPV will be discussed.

Clinical Trials as Topic↗
PubMed1976

Nonsuppressible insulin-like activity and thyroid hormones: major pituitary-dependent sulfation factors for chick embryo cartilage.

Serum from hypothyroid hypophysectomized rats did not stimulate sulfation or incorporation of amino acids into chick embryo sterna. When such rats were treated for a short time with growth hormone (somatotropin), their serum stimulated incorporation both of sulfate and of amino acids. The different actions of the two types of sera were not due to changes in thyroid state. The results support the existence in serum of a sulfation factor for chick embryo cartilage that is dependent upon growth hormone. Highly purified preparations of nonsuppressible insulin-like activity from human serum stimulated incorporation of amino acids, and of uridine into RNA, in chick embryo sterna in vitro; chondrocytes prepared from this tissue had specific high-affinity binding sites for this insulin-like activity. However, sulfate incorporation was stimulated very little, unless serum from hypothyroid hypophysectomized rats was also present. When L-3,5,3'-triiodothyronine was added as well, the stimulation was enhanced further. From these and other experiments, we conclude that (i) nonsuppressible insulin-like activity or a closely related peptide is the growth-hormone-dependent growth and sulfation factor for chick embryo cartilage: (ii) a second, unidentified factor must be present for the insulin-like activity to stimulate sulfation; and (iii) stimulation of sulfation by thyroid hormones in vitro is additive to that of nonsuppressible insulin-like activity.

Animals↗
PubMed1976

Rubella antibodies in women of childbearing age during an epidemic and the two years thereafter.

An epidemic of rubella started in the south of Israel late in 1971, and reached the north of the country in the spring of 1972. Between April 1972 and April 1975, 14,149 women of childbearing age from Haifa and the north of Israel were examined for rubella antibodies by hemagglutination inhibition (HI) and complement fixation (CF) tests. During the year of the epidemic, CF antibody titers of greater than or equal 16 were found in 9.3% of cases with HI antibody titers of 64, in 37.7% of cases with HI titers of 128, and in 71.7% of cases with HI titers of greater than or equal 256. Two years later there were no women with CF antibody titers of greater than or equal 16 among those with HI titers of 64, and the percentage with CF antibody titers of greater than or equal 16 had decreased to 4.3% among women with HI titers of 128 and to 38.7% among those with HI antibody titers of greater than or equal 256. These results show that the determination of CF antibody titers may be useful in the serodiagnosis of recent rubella infection, especially diring an epidemic occurring several years after a previous one. The epidemic hardly altered the percentage of women susceptible to rubella. Although vaccination of 12-year-old girs was introduced in Israel in 1972, careful surveillance of women of childbearing age still remains necessary for detection and vaccination of susceptible nonpregnant women.

Adult↗
PubMedDate not supplied

Clinical significance of enhanced detection of HBsAg by a monoclonal radioimmunoassay.

We assessed the significance of the enhanced detection by monoclonal radioimmunoassay (M-RIA) of HBsAg in serum of patients with hepatitis B virus (HBV) infection. In acute HBV infection, the M-RIA detected HBsAg in the blood for a far longer period of time than previously recognized. In some patients, the "window phase" of HBV infection (defined as the presence of anti-HBc and the lack of detectable HBsAg and anti-HBs) was shortened or completely eliminated. Furthermore, 26% of individuals with anti-HBc as the only serologic marker of recent or past HBV infection were reactive only in the M-RIA. Analysis of patients tested for HBsAg because of suspected underlying liver disease revealed additional HBsAg-positive sera, unrecognized by polyvalent RIA, thus adding important information in the immunodiagnosis of HBV infection. The enhanced performance of the monoclonal RIA compared to conventional polyvalent RIA was due in part to the increased sensitivity of the assay and the observation that M-RIA may detect "hidden" HBV antigens in immune complexes.

Antibodies, Monoclonal↗
PubMedDate not supplied

Hepatitis B virus infection and liver disease in Ethiopian immigrants to Israel.

We assessed infection with hepatitis B virus in 357 Ethiopians who immigrated to Israel. Hepatitis B virus infection, as measured by the presence in the serum of HBsAg, anti-HBs, or anti-HBc, started at an early age (35% at the age of 1 to 4 years) and reached an overall rate of 98% in individuals over 40 years old. A high rate of HBsAg antigenemia in the young age group (19% at the age of 1 to 8 years) was associated with HBeAg and serum hepatitis B virus DNA. However, hepatitis B virus DNA was rarely detected in HBsAg-positive serum of older individuals who were anti-HBe-positive. No hepatitis B virus DNA sequences were detected in the serum of individuals who had anti-HBs. Despite the extremely high rate of hepatitis B virus infection that occurred at an early age, no clinical evidence of chronic liver disease in this population was detected.

Adolescent↗
PubMedDate not supplied

Improved detection of hepatitis B surface antigen (HBsAg) in blood donors by monoclonal radioimmunoassay.

We evaluated the performance of a monoclonal radioimmunoassay (M-RIA) with enhanced sensitivity and high specificity for hepatitis B surface antigen (HBsAg) in blood donors. The results were compared to a conventional RIA that used polyvalent antibodies (P-RIA). Analysis of 6409 American blood donors not reactive by P-RIA revealed an additional 1.4 HBsAg-positive donors per 1000 by M-RIA, or an approximate 60 percent, improvement in HBsAg detection rate. Furthermore, in 995 Israeli blood donors negative by P-RIA, 11 additional HbsAg-positive donors were identified. The 55 percent improvement in detection rate was similar to that observed with American blood donors. Since several of the newly identified HBsAg-positive blood donors had antibodies to the core antigen (anti-HBc) as the only serologic evidence of recent or past hepatitis B exposure, we studied an additional 68 anti-HBc-positive individuals with the M-RIA. It was found that 26 percent (18/68) reacted only by M-RIA and not by P-RIA. These findings suggest that there are blood donors with HBsAg undetectable by P-RIA.

Antibodies, Monoclonal↗
PubMedDate not supplied

Comparison of inactivated poliovirus vaccine and oral poliovirus vaccine programs in Israel.

In spite of high vaccination coverage, paralytic poliomyelitis still occurs in Israel, either in sporadic form in the urban area or in small outbreaks in the rural, non-Jewish segment. At high risk are mainly very young infants, not yet protected by poliovirus vaccine and children who have failed to seroconvert after a full course of oral poliovirus vaccine ( OPV ). In these circumstances, a new program for vaccination of young infants early in life with a quadruple vaccine containing inactivated poliovirus vaccine (IPV) and diphtheria, tetanus, and pertussis vaccines (DTP) has been tested. Administration of two doses of IPV up to the age of three and one-half months followed by a booster at the age of 10 months has produced a very satisfactory antibody response (100% seroconversion and high geometric mean titers of antibody to the three antigens), which has occurred early in life and persisted up to two years after booster. This response was similar to that observed after four doses of trivalent OPV ( TOPV ) reinforced with one dose of monovalent type 1 OPV . Two doses of the quadruple vaccine have also induced an antibody response to pertussis antigen in greater than 90% of the infants. After booster, a greater than 99% conversion rate has been recorded, which has remained unchanged at one year of follow-up. The above data have led to the modification of the poliovirus vaccination schedule in the areas at risk.

Antibodies, Viral↗