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Biomedical subjects

Z Handzel

Publications and source records attributed to Z Handzel.

13 recordsLinked to original sources
PubMed1999

Identification of a subset of common variable immunodeficiency patients with impaired B-cell protein tyrosine phosphorylation.

The mechanisms responsible for common variable immunodeficiency syndrome (CVID) are as yet unknown. In the present study, we show that the B-cell dysfunction in a subset of CVID patients is caused by defective protein tyrosine phosphorylation (PTP). We demonstrated that the PTP level and immunoglobulin (Ig) secretion malfunctions can be successfully repaired when normal plasma membrane components are implanted into these patients' B cells. Stimulation of CVID patients' peripheral blood mononucleated cells with anti-Ig antibody revealed that 7 of 11 patients had lower PTP levels than those found in the normal donor cells. Plasma membrane implantation to the cells of these patients resulted in elevated PTP levels which reached normal levels upon stimulation with anti-human Ig antibody. The results revealed two distinct groups of CVID patients. The first group included patients whose B cells expressed low PTP levels after Ig stimulation. In these patients the plasma membrane implantation restored the normal PTP level as well as the ability to secrete IgM and/or IgG after B-cell stimulation. In the second group, patients whose B cells expressed a normal PTP level after Ig stimulation, with no restoration of their ability to secrete Ig upon plasma membrane implantation and lipopolysaccharide stimulation. We conclude that the first group has an early signal transduction defect located in the B-cell plasma membrane, while in the second group the defect is located elsewhere.

Adult↗
PubMed1991

Sequential serological studies of homosexual men with and without HIV infection. Epstein-Barr virus activation preceding and following HIV seroconversion.

Viral cofactors may be important in the pathogenesis of HIV infection and the development of AIDS, but their role is still imperfectly understood. Sequential serological studies were performed in a cohort of 100 homosexual men and 70 matched healthy controls over a mean period of 4 years. Of the patients, 18 were found to be HIV+ on admission to the study and 15 seroconverted to HIV+ during the follow up (seroconversion group). Serum antibodies of both IgG and IgA isotypes against Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were determined. IgG antibodies indicate past infection, while a marked increase in IgG titre or a positive IgA titre were taken to indicate active infection or reactivated latent infection. EBV and CMV infections were about two to four times more prevalent in the homosexual men both HIV- and HIV+, compared with controls. Active infections were increased in the homosexual men and particularly in the HIV+ patients. The seroconversion group revealed activation of both EBV and CMV following HIV infection. When the antibody profile of seroconverting patients at the time preceding seroconversion was compared with a matched group of 39 homosexual men who remained HIV-, no change was found in CMV antibodies, but four out of 15 (26.6%) of the patients had high titres of anti-EBV IgA preceding seroconversion, as compared with only one out of 39 (2.6%) of HIV- homosexual men (P less than 0.05). This suggests a role for EBV reactivation in the pathogenesis of HIV infection in some patients.

Antibodies, Viral↗
PubMed1988

Immune changes in male homosexuals--predisposing factors for HIV seroconversion.

Israel is still a low incidence country for AIDS and thus the temporal relationships between various cofactors and HIV infection can be more easily determined. We have studied a cohort of 243 asymptomatic male homosexuals (MHS) during the last 4 years. At the beginning of the study, 40% had significant decreases in the peripheral blood lymphoid populations, signs for reactivation of CMV and EBV infections, and elevated serum levels of interferon. There was no difference in the prevalence of these immune derangements between seropositive and seronegative individuals. In the course of 4 years' follow-up, the prevalence of these immune derangements has remained the same though being significantly more severe in the HIV seropositive subjects. HIV seroconversion did not exceed 8% (about 2% annually) and was related to the immune impairments found when first seen at the beginning of the study. The results suggest that immune impairments are common among asymptomatic MHS, precede HIV infection, and probably contribute to the increased risk for AIDS among male homosexuals.

Antibodies, Viral↗
PubMed1979

Thymic deficiency in Down's syndrome.

Children with Down's syndrome (DS) often have small and abnormal thymuses, with lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation--a picture resembling thymic involution. Besides this, they have markedly enlarged Hassall's corpuscles, some surrounded by a sheath of lymphocytes. Patients with DS are known to have increased numbers of respiratory infections; they also have a higher incidence of lymphatic leukemia than do individuals who do not have DS. Studies of cell-mediated (thymic-dependent) immunity demonstrate that children with DS have both diminished numbers of T cells as well as functional deficiency of these cells.

Child↗