Nurith Vardinon

Prevalence and clinical features of dementia associated with the antiphospholipid syndrome and circulating anticoagulants.

The increasing prevalence with age of antiphospholipid antibodies (aPL), of dementia and of stroke complicates the study of a causal relationship between antiphospholipid syndrome (APS) and dementia. Prolonged aPTT due to circulating anticoagulants (CAC) may serve as a more specific laboratory marker of APS. In a hospital-based study, we examined all patients with CAC and included 23 who fulfilled standard criteria for primary APS. These patients were assessed for dementia, vascular brain disease, autoimmune disease activity and dementia risk factors. Among CAC-positive APS patients, 13 of the 23 (56%) were demented and these were significantly older (mean age+/-S.E., 68+/-3 years) than the nondemented APS group (n=10, 51+/-4 years; p<0.01, Students t-test). The demented patients had significantly more pathology on computerized brain tomography (CT) and electroencephalography (EEG) studies but six of them had no clinical or CT evidence of vascular brain disease. Erythrocyte sedimentation rate was significantly lower in the dementia group, in which there was also a significant negative correlation between levels of aPL and age. CAC-positive APS patients seem to be at risk for developing dementia with age, suggesting a pathogenic role for prolonged exposure to elevated aPL.

Molecular epidemiology of HIV in Israel.

The aim of this study was to identify the HIV types and subtypes prevalent in Israel among different populations in terms of risk or geographic origin of the HIV infection. A total of 149 blood samples were collected from HIV-positive persons from different risk groups for HIV infection who were living in Israel. HIV subtyping was performed by a V3-based peptide enzyme immunoassay, supplemented by direct sequencing of polymerase chain reaction products from the V3 region. Multiple HIV-1 subtypes were shown to circulate in Israel; whereas most of the infections among Israelis and Palestinians were of subtype B, infections among the large Ethiopian population in Israel were caused by HIV-1 subtype C. Occasionally, we found HIV-1 subtypes A and D and a putative B/C recombinant. No HIV-2 infection was identified. Sequence comparisons and phylogenetic tree analyses point at multiple introductions of HIV into the country. The presence of mainly two different HIV-1 subtypes, B and C, in two separated populations in Israel may result in two distinct epidemiologic patterns among HIV-infected individuals in Israel. Subtype C infection among the Ethiopians in Israel opens new research avenues toward better understanding the natural history of infection with HIV-1 subtype C in Ethiopians living in a Western society compared with those living in Ethiopia.

Anti–HIV indeterminate Western blot in dialysis patients: A long-term follow-up

In a group of 520 patients undergoing chronic hemodialysis, 23 (4. 4%) were enzyme immunoassay (EIA) positive for human immunodeficiency virus (HIV) and indeterminate by Western blot (IWB) analysis. The antibodies were mostly directed against p24 and p55 antigens. A comparison between hemodialysis patients with and without IWB showed significant differences between the two groups with respect to number of units of blood transfused, history of renal transplant rejection, and Rh status. No significant differences were observed with respect to ethnic group, nature of renal disease, duration of hemodialysis, associated diseases, and ABO blood group. The HIV IWB phenomenon may represent abnormal immune reactivity as a result of transplantation antigens and/or autoantibody formation. Five-year follow-up of the HIV EIA-positive IWB patients showed that none had seroconverted to HIV-positive status.

Cytomegalovirus retinitis in patients with AIDS in Europe

The incidence of cytomegalovirus (CMV) retinitis and risk factors associated with the condition were studied in patients with the acquired immune deficiency syndrome (AIDS) in a multicenter retrospective cohort study of 6458 patients from 52 centers in 17 countries in Europe. Cytomegalovirus retinitis was diagnosed in 154 patients (2.4%) at the time of AIDS diagnosis, the probability of this diagnosis being significantly higher for those with CD4+ cell counts of <100/mm3 (3.4%) than with counts of 100–200/mm3 (1.3%) or >200/mm3 (0.8%). The rate of developing CMV retinitis after AIDS diagnosis was 9.4 per 100 patient years of follow-up. Multivariate analysis showed that risk behavior was significantly associated with the risk of developing CMV retinitis: lower for intravenous drug users [relative risk (RR) 0.47] and those engaged in “other risk behavior” (RR 0.58) than for homosexual men. The risk of developing CMV retinitis after AIDS diagnosis was significantly associated with CD4+ cell count at the time of AIDS diagnosis: for counts <100/mm3 (RR 2.90) and from 100 to 200/mm3 (RR 2.13), there was a higher risk than for counts > 200/mm3. Patients withPneumocystis carinii pneumonia, toxoplasmosis, or extraocular CMV infection at time of AIDS diagnosis exhibited an increased risk of developing CMV retinitis. Patients treated with zidovudine exhibited an increased rate of CMV retinitis: RR was 1.75 during and 2.87 after the second year of treatment as compared to those who had not received zidovudine. Median survival after CMV retinitis at time of AIDS diagnosis was eight months.

Increased intracellular macrophage inflammatory protein-1β correlates with advanced HIV disease

The objective of this study was to correlate between macrophage inflammatory protein-1beta (MIP1beta) and viral loads in untreated, HIV-infected individuals. For that purpose, HIV-positive patients were tested for number of copies of HIV-RNA in plasma and for intracellular MIP1beta in freshly explanted CD8 and CD4 lymphocytes and monocytes. Results demonstrate that the levels of MIP1beta in the various cell populations were significantly higher in the HIV group than in age-matched healthy individuals. Moreover, patients with low CD4 cell counts (<500/microl) and relatively high viral loads exhibited much higher levels of intracellular MIP1beta than patients with lower viral loads and CD4 counts >500/microl. We conclude therefore that although MIP1beta is induced in the various cell populations as a result of HIV infection in vivo, a high intracellular level of MIP1beta appears to be linked to a deterioration in the immune status of the patients.

Suppressive Action of Candida albicans on the Immune Response in Mice

This study was carried out to determine whether Candida albicans infection has a suppressive effect on the immune response in mice and, if so, whether the suppressive effect influences the response towards T-dependent or T-independent antigens. ICR mice were injected with SRBC with or without C. albicans, or with bacterial LPS with or without C. albicans. The immune response of the mice towards SRBC or towards the LPS was compared by the assay for PFC, hemagglutination and hemolysis tests. The results showed a decrease in the number of PFC in spleens of mice inoculated with SRBC and C. albicans as compared to mice inoculated with SRBC alone, but no decrease in animals injected with LPS and C. albicans as compared to those immunized with LPS alone. No significant differences in the titers of hemagglutinins and hemolysins in sera of mice inoculated with SRBC or with SRBC and C. albicans were observed. C. albicans infection had no effect at all on the hemagglutinins and hemolysins titers in sera of mice inoculated with LPS. These data indicate that C. albicans affects the early phase of the immune response primarily towards T dependent antigens.

Influence of the synthetic pentapeptide LAsp-Ser-Asp-Pro-Arg on the direct and indirect mast cell degranulation induced by reaginic antibodies.

The Prausnitz-Kustner (PK) reaction in man is a known method for proving the presence of reagin IgE antibodies towards various allergens (7). During recent years a method has been devised for detection of IgE-type antibodies in •vitro either in human patients or experimental animals. This method is based on mast cell degranulation test in a direct way by using cells from the sensitized individual (9,11) or in the indirect form by employing normal rat mast cells (8,10,11). It was claimed recently (3) that a synthetic pentapeptide can inhibit the PK reaction and that this effect is due to similarity in structure with the specific IgE binding site for the mast cells (2). The amino acid sequence of the pentapeptide is L^sp-Ser-Asp-Pro-Arg (3). The present work was started in order to find out whether the synthetic pentapeptide can also inhibit the in vitro mast cell degranulation characteristic for the reaction between suitable antigen and IgE bound to mast cells. For this pur-

MAST CELL SENSITIZING ANTIBODY (MCSAb) RESPONSE IN EXPERIMENTAL CANDIDIASIS: CHROMATOGRAPHIC STUDIES

A single dose of the yeast-like fungus Candida albicans (CA), mixed with Complete Freunds Adjuvant (CFA), and inoculated into guinea-pig foot-pads, provoked the productions of homologous mast cell sensitizing antibodies (MCSAb) present in the psiI-globulin fraction only, and of agglutinins localized in the same fraction. Heterologous MCSAb and skin-sensitizing antibodies detectable by passive cutaneous anaphylaxis (PCA) were constantly absent. These facts are in contradiction to results of previous experiments performed with other antigens; which after similar inoculation elicited production of heterologous MCSAb attaching themselves on rat mast cells (MC) and present in the psi2 fast moving globulin, homologous MCSAb localized in the psiI-globulin and in the psi2 fast moving globulin, and PCA antibodies. The immunogenicity of CA is discussed.

Human milk anti-E. coli antibodies: relationship to maternal parity.

Fifty samples of human milk obtained on the third day after delivery were analysed for antibody titers against E. coli antigens, using the passive haemagglutination test (PHA). Antigens were prepared from two “enteropathogenic” E. coli strains (0111:B4 and 0.26:B6) and one “saprophitic” strain (088) by two methods of extraction for each bacterial strain: 1. with water at 100°C, and 2. with veronal buffer, pH 8.4. The milk samples were classified into three groups: after the first parturition [17], after the second parturition [14], and after the third or subsequent parturition [19]. The mean antibody titer was highest in the first group and lowest in the third group. The immunoglobulins in the milk samples, characterized by the radial immunodiffusion test, were found to be IgA and IgM. The concentration of IgA was relatively higher than that of IgM in all the groups; no IgG was detected. The third group showed the lowest concentrations of immunoglobulins. In an attempt to characterize the type of anti-E. coli antibodies, several samples were fractionated on DEAE-cellulose. Using the PHA test, it was possible to demonstrate that only the IgA fraction contained E. coli antibodies. These results suggest that the anti-E. coli antibodies in human milk are mianly of the IgA type and that a decrease of immunoglobulin concentration can be observed after three or more parturitions.

Antigenic Relationships between Candida albicans and Various Yeasts as Reflected by Immunoglobulin-Class Specificity

A group of guinea pigs was inoculated into the foot pads with a single dose of Candida albicans in complete Freunds adjuvant, while another group was similarly inoculated once in the foot pads but also several times intramuscularly, with Candida alone. All guinea pigs were bled at different intervals after immunization and sera were separated chromatographically into IgG and IgM fractions. In order to study the antigenic relationships as reflected by immunoglobulin-class specificity, IgG and IgM fractions and whole sera obtained from guinea pigs differently immunized, were tested for the presence of agglutinins against C. albicans, six other species of Candida, and species of the ascosporogenous genera Saccharomyces, Kluyveromyces and Schizosaccharomyces. The results show that (1) only IgG fractions of the different sera prepared contained the specific anti-C. albicans antibodies; (2) IgG and IgM fractions of the sera obtained from a single inoculation did not reveal a specific pattern expressing antigenic relationships of the yeast studied, and (3) the IgM fractions of the sera obtained from several inoculations had a more homogenous pattern of reactivity, since mainly these contained the agglutinins against the ascosporogenous yeast species.