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Biomedical subjects

I Sarov

Publications and source records attributed to I Sarov.

At least 19 recordsLinked to original sources

The long term follow-up of asymptomatic women with Chlamydia trachomatis.

A community oriented intervention program was initiated in 1985 in 12 rural communities in southern Israel to identify and treat women of reproductive age with markers of Chlamydia trachomatis (CT) infection. Among 860 women tested, 21 (2.4%) had CT IgG antibody titers greater than or equal to 128, or CT IgA antibody titers greater than or equal to 16, and 9 of these women had positive cultures for CT. The 21 women, as well as their male partners, received specific anti-CT treatment, and were followed up for 5 years to assess obstetric complications, and to evaluate the effectiveness of treatment. In 9 women positive cultures became negative. In 13 out of the 17 cases with sequential follow-up a four fold decrease in IgG specific antibody titers was observed. Yet, in all but two of the cases, IgA specific antibody titers remained greater than or equal to 16.

Adult

Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates.

We conducted a prospective randomized double blind study to determine: (1) the safety and immunogenicity of live oral tetravalent human-rhesus rotavirus reassortant vaccine in neonates; and (2) whether a second dose at the age of 6 to 8 weeks enhances the immunogenicity. Two hundred forty healthy neonates were enrolled and received vaccine (183) or placebo (57) on the second day of life. At the age of 6 to 8 weeks 133 received placebo and 88 received a second dose of vaccine. Medical events were noted within 10 days from vaccine administration in 6 of 183 (3.3%) vaccine recipients vs. 0 of 57 placebo recipients (P = 0.34) after the first dose and in 8 of 88 (9%) vs. 4 of 133 (3%) after the second dose (P = 0.069); none was severe and all were of short duration. Seroresponse of any type (detectable IgA or 4-fold increase of titer to rhesus rotavirus was 9% for the placebo, vs. 52 and 46% for those who received one and two doses of vaccine, respectively. However, neutralizing antibodies against human serotypes 1, 2 and 3 were not raised successfully in vaccinated infants when compared with placebo recipients. The same pattern was found when geometric mean titers were compared. Vaccine take was better when cord blood titers were low. At the age of 1 year the vaccinees had more often high titers for antirhesus rotavirus antibodies (> 640) than the placebo recipients (49% vs. 0%; P < 0.001). NO difference was found between the groups in neutralizing antibodies to human serotypes 1, 2 and 3 rotavirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Herpes simplex virus and cytomegalovirus in the serum of schizophrenic patients versus other psychosis and normal controls.

One hundred and thirty eight subjects were examined for presence of antibodies by immunoperidose assay (IPA). The frequency of Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) antibody of 48 schizophrenic inpatients was compared to 48 inpatients with other psychosis and to 48 staff controls. No differences were found between schizophrenic and control groups.

Antibodies, Viral

Comparison of structural polypeptides, detected by immunoblotting technique, in the sera of spotted fever group rickettsia positive cases--symptomatic versus asymptomatic.

In an attempt to characterize the nature of symptomatic versus asymptomatic spotted fever group rickettsia (SFGR) infection, the immune response to R. conorii (boutonneuse fever) structural polypeptides was studied by Western-blot immunoassay. Sera from immunoperoxidase assay (IPA), SFGR seropositive (titre greater than or equal to 80) individuals, symptomatic and asymptomatic and from SFGR seronegative (IPA titre less than 80) individuals living in a kibbutz community in the desert region of Southern Israel were examined by immunoblot. This community suffered from a very high morbidity rate due to SFGR (21-fold higher than the national reported average). The entire community (n-326) has been followed-up since 1985, with serial serum samples being examined for specific IgG antibodies by IPA. The intensity of the immunoblot reaction correlated with specific IgG antibody titres as determined by IPA. This correlation was also observed between the decrease in the IgG titre and the strength of the antibody-antigen reaction by immunoblot over time for a given individual. IPA seropositive sera from asymptomatic as well as symptomatic spotted fever cases reacted to 8 individual polypeptides. In both cases antibodies to 22 kD, 24 kD, 26 kD, 28 kD, 30 kD, 32 kD, 34 kD, and 37 kD were found. In the IPA seronegative sera, antibodies to polypeptides in the range of 24 kD to 32 kD were not detected. The lack of detectable differences by immunoblotting between SFGR symptomatic vs, asymptomatic cases might be explained by other aspects of the immune response of each infected individual, and/or it is possible that virulent and non-virulent antigenically closely related SFGR strains infected symptomatic vs. asymptomatic individuals.

Bacterial Proteins

[Antinuclear antibodies in IgA nephropathy, as well as mesangiocapillary and membranous glomerulonephritis].

IgA nephropathy, assumed to be a form of chronic immune complex glomerulonephritis, has sometimes been associated with various autoimmune diseases and autoimmune phenomena including autoantibody production. The present study was aimed at thoroughly investigating the frequency of autoantibodies against five common nuclear autoantigens in 59 patients with IgA nephropathy and in 48 patients with other immune complex glomerulonephritides (24 patients with membranous and 24 with mesangio-capillary glomerulonephritis) and in 30 healthy controls. The incidence of raised autoantibody titres (greater than or equal to 2 SD of the average of controls) in IgA NP was not found to be significantly different from the incidence of other immune complex glomerulonephritis groups. In none of the subjects was a titer above 3 SD of the average of controls found. Although IgA NP is thought to be an immune mediated disease, on the basis of our study it is not associated with a statistically significant incidence of raised antinuclear antibodies.

Antibodies, Antinuclear

Cytomegalovirus IgG and IgA serum antibodies in a study of HIV infection and HIV related diseases in homosexual men.

The significance of serum IgG and IgA antibodies to cytomegalovirus (CMV) at various stages of human immune deficiency virus (HIV) infection was studied in 175 homosexual men. Sera were obtained from 123 HIV seropositives [41 asymptomatic, 29 with lymphadenopathy associated syndrome (LAS), 22 with AIDS related complex (ARC), and 31 AIDS patients], 17 HIV seroconverters, and 35 HIV asymptomatic seronegatives. The sera were tested blindly for CMV IgA and IgG antibodies using the immunoperoxidase assay (IPA) and CMV infected human embryo cells. Cross-sectional analysis of CMV IgG antibodies at a titer of greater than or equal to 20 showed 87% and 100% prevalence in the HIV seronegative groups and in the HIV seropositive groups, respectively (P less than 0.05). CMV IgG antibodies at a titer of greater than or equal to 80 were present in significantly higher proportions among the HIV seropositive subjects of the various groups as compared with the HIV seronegative homosexual men. However, in the HIV seronegatives who later seroconverted to HIV, a significantly higher prevalence of CMV antibodies (35%) was detected before HIV seroconversion, as compared with the persistently HIV seronegative subjects (14.3%) (P less than 0.05). The HIV seronegatives pre-HIV seroconversion also exhibited a significantly higher geometric mean titer (GMT) of CMV IgG antibodies (62.17 +/- 0.64) as compared with the persistently HIV seronegatives (34.0 +/- 0.6) (P = 0.03). Significantly higher GMTs of CMV IgG antibodies were detected in all the HIV seropositive groups as compared with the persistently HIV seronegative group. CMV IgG antibodies were not detected in the HIV seronegative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Implications for persistent chlamydial infections of phagocyte-microorganism interplay.

In vitro models of Chlamydia trachomatis inhibition by cytokines, human-monocyte derived macrophages (HMDM) and human polymorphonuclear leukocytes (HPMN) are discussed in an attempt to delineate the molecular basis of parasite-host cell interplay in persistent and chronic chlamydial infection. Interferon gamma (IFN) has been found to reversibly inhibit chlamydial growth at an early stage in the replicative cycle, while tumor necrosis factor (TNF) has a more profound effect on chlamydial growth resulting in production of aberrant reticulate bodies and enhancement of production of prostaglandin E2 (PGE2). Chlamydia trachomatis (serovar L2) replicate in HMDM while serovar K has been found to be restricted in these cells. Chlamydiae are killed by HPMN but the cell walls persist undegraded, inducing production of oxygen radicals which can be demonstrated to induce DNA strand scissions in HeLa target cells. Evidence is accumulating that chlamydia specific serum IgA antibodies may serve as a noninvasive serological marker for diagnosis of a number of acute and persistent Chlamydia trachomatis infections.

Chlamydia Infections

Immunoglobulins A, G, and M to cytomegalovirus during recurrent infection in recipients of allogeneic bone marrow transplantation.

Occurrence and significance of specific IgA and IgM to cytomegalovirus (CMV) in recurrent CMV infection was evaluated in 21 allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) recipients who had been previously CMV seropositive. Of 17 patients with CMV infection, viruria was detected in 94%, CMV-specific IgA in 88% and IgM in 76%, and a fourfold rise in IgG in 65%. The median time between BMT and detection of viruria was 69 days, of IgA 70, of IgM 62, and of IgG 88 days. The IgM and IgA responses lasted for 14 and 30 days (median time), whereas high IgG titers persisted. Twelve patients developed CMV disease; in these the appearance of viruria, IgA, and IgM preceded the rise of IgG (P less than .02). CMV-specific IgA and IgM are valuable diagnostic tools in BMT recipients with recurrent CMV infection.

Adolescent

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

Western blot analysis of immune response to Legionella bozemanii antigens.

The immune response to individual major antigens of Legionella bozemanii was studied in 67 sera from 26 inpatients with febrile disease using immunoblotting techniques. All the patients had fever of unknown origin and showed strong serological reactions to L bozemanii that cross-reacted with Rickettsia typhi, as determined by a standard indirect microimmunofluorescence assay. Sera analysed by western blotting reacted with 12-14 molecular components of L bozemanii with apparent molecular weights ranging from 14,000 to 94,000 daltons. These reactions compared well with a reference system using antisera of rabbits immunised with the same strain of Legionella. The three major cross-reactive components of R typhi were polypeptide antigens of 94,000, 67,000 and 43,000 daltons. It is concluded that western blotting can help in the differential diagnosis of patients with fever of unknown origin whose sera cross-react to L bozemanii and R typhi.

Adult

Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity.

Immunological cross-reactivity between tumor necrosis factor (TNF) binding proteins which are present in human urine (designated TBPI and TBPII) and two molecular species of the cell surface receptors for TNF is demonstrated. The two TNF receptors are shown to be immunologically distinct, to differ in molecular weight (58,000 and 73,000), and to be expressed differentially in different cells. It is further shown that polyclonal antibodies against one of the TNF binding proteins (TBPI) display, by virtue of their ability to bind the TNF receptor, activities which are very similar to those of TNF. These antibodies are cytotoxic to cells which are sensitive to TNF toxicity, induce resistance to TNF toxicity, enhance the incorporation of thymidine into normal fibroblasts, inhibit the growth of chlamydiae, and induce the synthesis of prostaglandin E2. Monovalent F(ab) fragments of the polyclonal antibodies lack TNF-like activities, but acquire them upon cross-linking with anti-F(ab)2 antibodies, suggesting that the ability of the anti-TBPI antibodies to mimic TNF correlates with their ability to cross-link the TNF receptors. This notion was further supported by data obtained in a comparative study of the TNF-like cytotoxicity of a panel of monoclonal antibodies against TBPI. The induction of TNF-like effects by antibodies to a TNF receptor suggests that TNF is not directly involved in intracellular signalling. Rather, it is the receptors to this cytokine which, when properly triggered in a process which appears to involve clustering of these receptors, transduce the signal for response to TNF into the cell's interior.

Animals

Cloning, characterization and sequence of a novel 59-kDa protein of Chlamydia trachomatis.

Chlamydia trachomatis (Ct) serovar L2 DNA was partially digested with BamHI, ligated with plasmid vector pBR325 and used to transform Escherichia coli JMB83. Recombinant colonies were screened for their ability to synthesize chlamydial (chl) proteins by dot immunoblot and by in vitro transcription translation assays. A clone, B1, expressing a 59-kDa protein was further characterized, and the encoding gene was subcloned in the expression vector, pKK223-3, containing the tac promoter. Elevated levels of the 59-kDa protein were produced in E. coli in the presence of the lac inducer, IPTG. Sequencing identified one long open reading frame encoding a polypeptide of 59,075 Da (59 kDa). The partially purified 59-kDa protein was recognized by sera from patients with chl infections as shown in immunoblotting. In addition, the 59-kDa protein was located in the sarcosyl-soluble fraction of chl lysates. When used as a DNA probe in dot hybridization assays, the clone encoding the 59-kDa protein showed high homology to all serovars of Ct and four strains of Chlamydia psittaci. The cloned 59-kDa protein is neither related to the 60-kDa heat-shock protein found in many strains of bacteria, nor to the Cys-rich sarcosylinsoluble protein described in other studies of chlamydia.

Amino Acid Sequence

Chlamydial IgG and IgA in serum and follicular fluid among patients undergoing in vitro fertilisation.

The point prevalence of IgG and IgA antibodies to Chlamydia was analyzed in serum and follicular fluid in 63 patients undergoing in vitro fertilisation (IVF) in comparison to sera of 298 healthy women by the single serovar (L2) inclusion immunoperoxidase assay (IPA). The presence of specific IgG and IgA to Chlamydia in follicular fluid was demonstrated. No statistical association was found between the presence of specific Chlamydia IgG and IgA in serum and follicular fluid to oocyte fertilization. The positive predictive value for mechanical infertility of Chlamydia IgG at titers of greater than or equal to 128 and IgA titers at greater than or equal to 16 was 91 and 92%, respectively, in this high-risk group for mechanical infertility. Multiple regression analysis singled out Chlamydia IgG levels as a major contributor to the variance between the groups of infertile patients.

Adolescent

Serum IgG and IgA antibodies specific to Epstein-Barr virus capsid antigen in a longitudinal study of human immunodeficiency virus infection and disease progression in homosexual men.

A longitudinal study of serum IgG and IgA antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) was carried out in 218 homosexual men at various stages of human immunodeficiency virus (HIV) infection. The serum samples tested were obtained from the following groups: 24 HIV seroconverters, 41 persistently HIV-seropositive asymptomatic individuals, 22 seropositives who developed AIDS-related complex (ARC), 29 HIV seropositives who developed lymphadenopathy syndrome (LAS), 35 HIV seronegatives with LAS, 36 asymptomatic HIV seronegatives, and 31 AIDS patients. Blind-tested samples were titrated for IgG and IgA EBV-VCA antibodies by immunoperoxidase assay (IPA). Cross-sectional analysis indicated that all HIV-seropositive subjects exhibited significantly elevated EBV IgG and IgA antibody titers compared with HIV-seronegative subjects. The proportions with EBV-VCA IgA antibodies at a titer of greater than or equal to 128 rose during the course of HIV infection and progression of the disease: 8% in HIV seronegatives, 11% in HIV seronegatives with LAS, 25% in HIV seronegatives prior to HIV seroconversion, 44% in asymptomatic HIV seropositives, 34% in LAS, 50% in ARC, and 58% in AIDS patients. An increase in EBV-VCA IgG and IgA titers was detected following HIV seroconversion and in samples obtained 6 months before disease progression to LAS. These data suggest the possible involvement of EBV in the natural history of HIV infection and disease progression. The possibility that EBV-VCA IgA antibody levels would be of value in prediction of progression of HIV-related illness is discussed.

AIDS-Related Complex

Rotavirus diarrhea in Jewish and Bedouin children in the Negev region of Israel: epidemiology, clinical aspects and possible role of malnutrition in severity of illness.

We conducted a 1-year prospective study in the Negev region of southern Israel to determine the epidemiologic and clinical patterns of rotavirus diarrhea. A total of 605 patients were studied, 392 Bedouins and 213 Jews, 441 of whom had diarrhea (449 episodes) and 164 did not. Rotavirus was the most common organism detected in children with diarrhea (63 of 444; 14%) but was rarely found in controls (3 of 163; 2%) (P less than 0.001). In 22% (12 of 54) of the rotavirus-positive patients, at least one other organism was also detected. The rate of rotavirus detection decreased as age increased, from 18% in the first year to 8% in the third year of life. Hospitalization with rotavirus diarrhea occurred more frequently in the summer. However, during winter, when diarrhea was less prevalent in the community, the proportion of cases associated with rotavirus was higher. Compared with controls, malnourished children were more likely to be hospitalized. However, rotavirus was detected in similar proportions among well-nourished and malnourished cases with diarrhea. The most prevalent rotavirus serotype was type 1 (in 69%), followed by types 4 and 2 (18 and 13%, respectively). We estimated that during the study period, approximately 2% of all Bedouin infants vs. only 0.2% of Jewish infants were hospitalized with rotavirus disease in their first year of life. Clinical signs and symptoms and stool appearance were not useful in predicting rotavirus detection. Malnutrition seems to be an important indicator of disease severity, which may explain why the toll of rotavirus-associated morbidity and mortality is particularly high among children in developing countries.

Acute Disease

Leishmania major: inhibition of the chemiluminescent response of human polymorphonuclear leukocytes by promastigotes and their excreted factors.

The effect of various leishmanial preparations on the chemiluminescent response (CR) of human polymorphonuclear leukocytes (PMN) was studied. Almost no CR was observed with PMN stimulated with either Leishmania promastigotes or their excreted factors (EFs). Promastigotes added to PMN stimulated with phorbol myristate acetate (PMA), at a proportion of 20 to 1, respectively inhibited approximately 80-83% of the CR activity. Leishmanial promastigotes, whether live or dead, infective or non-infective as well as whole parasite homogenates, soluble and insoluble fractions, all decreased the CR of the PMN (PMN-CR). A similar effect was also observed with leishmanial EFs. The degree of inhibition was dose dependent and increasing the amount of EFs in the reaction mixture resulted in decrease of the PMN-CR. More than 80% of the total activity of the PMN-CR was inhibited by 500 micrograms EFs added at zero time to the reaction mixture. The inhibition of PMN-CR obtained from a patient suffering from a chronic infection caused by L. major was not significantly different from that observed with PMN from normal donors. The present study suggests that the PMN-CR is impaired by the Leishmania parasites and their EFs and thus may allow a greater survival of the parasites within these cells.

Animals

Tumor necrosis factor alpha and prostaglandin E2 production by human monocyte-derived macrophages infected with spotted fever group rickettsiae.

Infection of macrophages by intracellular parasites might modulate production of tumor necrosis factor (TNF) and prostaglandin E2 (PGE2), which, in turn, might have a profound effect on the outcome of the infection in vivo. In this study we examined in an in vitro system, the rickettsial yield in human monocyte-derived macrophages (MdM) and the PGE2 and TNF production by MdM infected with Rickettsia conorii RC, Casablanca strain) or Israeli spotted fever (ISF, G-212 strain). TNF and PGE2 were determined in the media of MdM infected with RC or ISF. TNF reached maximum levels 24 h post-infection and then declined, while PGE2 levels increased continuously during the infection up to 96 h post-infection. Addition of dexamethasone inhibited both TNF and PGE2 production and enhanced rickettsial yield in MdM. Inhibition of PGE2 production by indomethacin resulted in increased production of TNF from rickettsial-infected MdM, while addition of PGE2 caused partial inhibition of TNF production from infected MdM.

Dexamethasone