Search PubMed⌕ Search

Biomedical subjects

I Sarov

Publications and source records attributed to I Sarov.

At least 55 records · Page 3Linked to original sources

Inhibition of Chlamydia trachomatis growth in endometrial cells by copper: possible relevance for the use of the copper IUD.

There is agreement that the relative risk of developing pelvic inflammatory disease (PID) increases among women who use the intrauterine contraceptive device (IUD). The role of Chlamydia in causing PID among IUD users is not clear. The present study demonstrates that Chlamydia trachomatis growth can be inhibited in cultured human endometrial cells by copper ions at concentrations known to be released by the copper IUDs. More than 98% inhibition was produced with 10(-5) and 10(-6) M of copper. Both C. trachomatis serovar E and a lymphogranuloma venereum Chlamydia serovar L2 (LGV) were inhibited by the copper ions. Although the mechanism of the inhibition is not known, the continuous presence of the copper ions during and after adherence appeared to be necessary for maximal effect. If such inhibition occurs in vivo, it is possible that copper ions released from the copper-containing IUD may partially protect against chlamydial infection.

Cells, Cultured↗

Effect of Chlamydia trachomatis infection on ciliary activity in single cells from cultures of human nasal polyps.

We have tested the hypothesis that the ciliary activity of epithelial cells from human nasal polyps is altered after infection with Chlamydia trachomatis. Ciliated epithelial cells from human nasal polyps were cultured and infected with C. trachomatis. The measurement of ciliary beating was based on a technique which enables one to monitor a fraction of a single ciliated cell. A marked decrease of ciliary beating frequency versus time was observed 24 h after infection with C. trachomatis. About 50% of the cilia of infected cells were paralysed 48 h post-infection. The potential effect of C. trachomatis infection on the physiological functions dependent on cilia is discussed.

Cell Movement↗

The persistence of Chlamydia trachomatis elementary body cell walls in human polymorphonuclear leucocytes and induction of a chemiluminescent response.

Human polymorphonuclear leucocytes (HPMN) were incubated with [35S]methionine-labelled Chlamydia trachomatis (serovar L2/434/Bu) elementary bodies (EB) and EB cell walls. No net loss in the TCA-precipitable radioactivity was observed over 24 h in the HPMN that had taken up EB cell walls. SDS-polyacrylamide gel electrophoresis of the labelled C. trachomatis EB and EB cell wall proteins extracted from the HPMN at 2 and 24 h after infection demonstrated the persistence of most of the chlamydial cell wall polypeptides. Analysis of extracts of the HPMN that had taken up either EB or EB cell walls on Urografin density gradients at 2 and 24 h after infection, and electron microscopic observations on fractions representing the peaks, demonstrated the persistence of the EB cell walls in the HPMN. Electron microscopic observations of HPMN that had taken up EB or EB cell walls demonstrated EB cell walls in the HPMN phagosomes at 24 h after infection. The HPMN exposed to EB and EB cell walls of C. trachomatis gave chemiluminescent (CL) responses with peaks respectively 12 and 7 times greater than the peak value of the control. The significance of the persistence of the EB cell wall polypeptides and cell walls in the HPMN and activation of the HPMN to produce oxygen radicals (i.e. a CL response), and its possible relation to rheumatic diseases, is discussed.

Cell Wall↗

Inhibition of growth of Chlamydia trachomatis by the calcium antagonist verapamil.

Treatment of BGM (African Green Monkey kidney) cells with the calcium antagonist Verapamil resulted in a reduced yield of chlamydial infectious particles. The inhibitory effect was concentration-dependent, the maximal effect being achieved at 200 microM-Verapamil, which produced a 99.99% reduction of infectious particle yield. Electron microscopy showed that control Chlamydia trachomatis-infected BGM cells contained typical large inclusions in which most of the particles were elementary bodies, whereas Verapamil-treated infected cells contained small inclusions consisting predominantly of reticulate bodies. The findings indicate a possible therapeutic use of this calcium antagonist as an anti-chlamydial drug.

Animals↗

Reversion of the antichlamydial effect of tumor necrosis factor by tryptophan and antibodies to beta interferon.

Human recombinant tumor necrosis factor-alpha (TNF-alpha) inhibited the growth of Chlamydia trachomatis (L2/434/Bu) in HEp-2 cells. The effect was synergistic with that of gamma interferon (IFN-gamma). TNF-induced resistance to chlamydiae could be blocked with cycloheximide, suggesting that it involves the function of some induced proteins. Tryptophan degradation was enhanced in the TNF-treated cells and was much further increased when the cells were treated with both TNF and IFN-gamma at concentrations at which IFN-gamma by itself had very little effect. Antibodies to IFN-beta blocked the augmentation of tryptophan degradation by TNF and decreased but did not fully eliminate the antichlamydial effect of TNF. Increased concentration of tryptophan in the growth medium (greater than 100 micrograms/ml) resulted in reversion of the antichlamydial effect of TNF. This study suggests that the inhibition of chlamydial growth by TNF is mediated partly through an autocrine function of IFN-beta which, in synergism with TNF, enhances the activity of a tryptophan-degrading enzyme(s) and partly by some other activities of TNF which can be blocked by tryptophan.

Cell Line↗

Detecting Chlamydia trachomatis in men with urethritis: serology v isolation in cell culture.

The accuracy of single serovar (L2) inclusion immunoperoxidase assay (IPA) to show serum IgG and IgA antibodies specific to chlamydiae was compared with culture for Chlamydia trachomatis to diagnose chlamydial infection in 73 men with acute urethritis. C trachomatis only was isolated from 18 (25%), Neisseria gonorrhoeae only from 17 (23%), and both organisms from six (8%). Thus 24 (33%) yielded chlamydiae. Assays based on IgG antibodies to chlamydiae at a titre of 1/64 or more showed high sensitivity (96%) and a good negative predictive value (80%), but low specificity (13%) and agreement (48%) compared with culture. IgG antibodies to chlamydiae at a titre of 1/128 or more showed lower sensitivity (75%) but higher specificity (72%), negative predictive value (79%), and agreement (73%). IgA antibodies to chlamydiae at a titre of 1/8 or more showed a sensitivity of 88%, specificity of 72%, negative predictive value of 88%, and agreement of 79%. An appreciable (fourfold or more) decrease in IgA and IgG titres was observed in most (10) of the 15 men from whom second blood samples were obtained one to two years after treatment. Measuring specific IgA and IgG antibodies to chlamydiae by IPA may serve as a useful complementary test for diagnosing and following up patients with urethritis.

Adolescent↗

A cluster of cases of spotted fever in a kibbutz in southern Israel.

During the 3-year period 1984-1986, 13 cases of spotted fever were clinically diagnosed and serologically confirmed among the 341 residents of an agricultural settlement in the Negev desert in southern Israel (attack rate 3.8%, expected attack rate 0.13%). The disease was observed more frequently during the warmer months, with a peak in June. Nine cases were children and adolescents and 4 were adults (attack rate 6.2% and 2.0% respectively; p less than 0.05). The clinical and laboratory findings were consistent with a multisystem involvement. A "tache noire" was not observed in any case. Four cases required hospitalization for complications including severe toxicity, intractable vomiting, thrombophlebitis and hyponatremia. Three of the hospitalized patients were adults and only one was a youngster. All patients recovered. The geographic distribution of the cases showed a clustering in the marginal area of residency: 8 cases occurred among the 121 residents of this area (6.6%), vs. only 5 cases among the 220 residents of the central area (2.3%) (p less than 0.05). This finding suggests that in endemic areas, the inhabitants of the interface between man's habitat and a wild ecological niche have a higher risk of acquiring spotted fever.

Adolescent↗

Placebo-controlled trial of topical interferon in labial and genital herpes.

The efficacy of topical interferon-beta (IFN-beta) treatment was assessed in 25 patients with herpes of the lips or genitals who completed a 2-year follow-up in a double-blind placebo-controlled trial. IFN-beta gel (10(5) U/g) 4 times daily (about 2 x 10(4) U) applied locally during eruptions (about 10 days) reduced the mean number of recurrences (p less than 0.007) and the duration of eruptions (p less than 0.007): in the placebo group these indices did not change significantly. Reduction of symptoms and severity was noted in 11 of 12 patients on IFN-beta and in only 1 on placebo. No important side-effects were recorded. Topical IFN-beta may therefore be advantageous as a time-limited local treatment of recurrent herpes simplex virus infections of the genitals and lips.

Administration, Topical↗

Prevalence of CMV antibodies among women of childbearing age in different social environments in southern Israel.

The prevalence rate of IgG antibodies to cytomegalovirus (CMV) was determined in a sample of 567 women of childbearing age in the southern part of Israel by the immunoperoxidase assay to membrane antigen (IPAMA) technique. Urban Jewish women of Afro-Asian origin showed significantly higher rates of seropositivity than urban Jewish women of European-American origin (80% vs 65%, respectively, P less than 0.001), closely resembling the level of CMV seropositivity found in Afro-Asian and European-American countries in the same age and sex population groups. The Bedouin women showed slightly lower rates of CMV seropositivity (75%) than Jewish women of Afro-Asian origin. Particularly high rates of CMV seropositivity were detected in women who live in a kibbutz environment: 96% in women of Afro-Asian origin and 80% in women of Euro-American origin. Multiple discriminant analysis also singles out the kibbutz environment as a major contributor to the variance between the groups tested (P less than 0.003).

Adult↗

Chlamydia specific IgG and IgA antibodies in women with obstructive infertility as determined by immunoblotting and immunoperoxidase assays.

The prevalence rate of IgG and IgA antibodies to Chlamydia was analyzed in 50 women with laparoscopy-verified tubal infertility and in 50 age-matched control women by single serovar (L2) inclusion immunoperoxidase assay (IPA) and by immunoblotting technique (IB). Women with tubal infertility had significantly (p less than 0.001) elevated IPA Chlamydia IgG antibody titer greater than or equal to 128 and greater than or equal to 256 than controls (64% vs 16%. Odds ratios = 9.3 and 50% vs 10%, Odds ratio = 9 respectively). The prevalence rate of IPA IgA antibody titer (greater than or equal to 16) to Chlamydia was also significantly higher (p less than 0.001) in women with tubal infertility than controls (48% vs 8%, Odds ratio = 10.6). Antibodies to at least 19 chlamydial structural polypeptides ranging in molecular weight from 30 kD to 204 kD, were detected by the IB technique in the IPA seropositive sera. Antibodies to 57-60 kD were detectable in almost all the IPA IgG and IgA seropositive sera. The prevalence rate of IgG antibody to 57 kD-60 kD was significantly higher in women with obstructive infertility than healthy woman (84% vs. 56% p less than 0.01; Odds ratio = 3.8). More significantly, higher differences to 57-60 kD polypeptide were found in the case of IgA between the infertile women and controls (52% vs. 10%, p less than 0.001; Odds ratio = 9.7). The significance of IPA and IB technique for screening of infertile women is discussed.

Adult↗

Serum-specific antibodies for Chlamydia trachomatis in premature contractions.

A case-control study was undertaken to examine the possible morbidity associated with Chlamydia trachomatis in 28 pregnant women having idiopathic premature contractions, in 35 healthy preterm pregnant women, and in 43 healthy pregnant women at term. Serum C. trachomatis IgG- and IgA-specific antibodies were determined by the single serovar inclusion immunoperoxidase assay. There were no significant differences in the prevalence rate of elevated C. trachomatis IgG-specific antibodies (titer greater than or equal to 1:128) between pregnant women suffering from idiopathic premature contractions as compared with healthy preterm and term pregnant women (11%, 28%, and 26%, respectively). The known prevalence rate in a normal healthy population is 23%. The prevalence rate of elevated C. trachomatis IgA-specific antibodies (titer greater than or equal to 1:16) was significantly lower in the pregnant women with idiopathic premature contractions as compared with the healthy preterm and term pregnant women (0%, 20%, and 17%, respectively; p less than 0.002 and p less than 0.012). These findings do not support the assumption that C. trachomatis has a role in premature contractions.

Adult↗

Inhibition of CMV replication in human fibroblasts by human monocyte-derived macrophages: implication for CMV persistent infection.

The effect of monocytes (M) and monocyte-derived macrophages (MdM) on cytomegalovirus (CMV) replication in human fibroblasts (HF) was studied by one step growth experiments, plaque formation and dot hybridization with a labeled CMV DNA probe. HF were infected with CMV at multiplicities of infection (mol) of 0.001 to 1. After virus adsorption, M or MdM were added at an effector target ratio of 2:1. MdM reduced both infectious viral yield and the quantity of viral DNA and inhibited viral plaque formation. M, however, affected these parameters to a lesser extent. Electron microscopic studies showed that MdM treated CMF-infected HF, 4 days pi, contained only a few capsids in their nuclei and many vacuoles in their cytoplasm as compared to CMV infected HF (control). A reduction of CMV DNA inhibition was observed upon incubation of the infected HF cells with MdM separated from the infected cells by a membrane. Addition of tumor necrosis factor (TNF) antibody to CMV-infected HF incubated with MdM either in direct contact or separated by a membrane from the infected cells reduced the inhibition of CMV-DNA production. The results of this study suggest that MdM may modulate CMV replication in vivo and may also have a role in CMV persistence or chronic infection.

Cytomegalovirus↗

Induction of DNA strand scissions in HeLa cells by human polymorphonuclear leucocytes activated by Chlamydia trachomatis elementary bodies.

Incubation of human polymorphonuclear leucocytes (HPMN) with Chlamydia trachomatis elementary bodies (EB) or phorbol 12-myristate 13-acetate (PMA) resulted in the production of superoxide anions (.O2-) and hydrogen peroxide (H2O2). Exposure of HeLa cells to EB- or PMA-activated HPMN and to EB alone, for 2 h, resulted in the formation of DNA strand scissions (nicks) in the HeLa cells. The nicks were visualized by incorporation of biotin 11-dUTP with its detection by streptavidin-peroxidase, and quantified by using [3H]dCTP in the in situ nuclear nick-translation reaction. Catalase, and to a lesser extent superoxide dismutase, reduced the amount of nicks induced by the EB- or PMA-activated HPMN. The possible relationship between the activity of PMN in chlamydial infections and the development of chronic diseases is discussed.

Catalase↗

Inhibition of Chlamydia trachomatis replication in HEp-2 cells by human monocyte-derived macrophages.

Monocytes (M) and macrophages are important components of the immune response to foreign agents. Using an in vitro system, we studied the influence of human M and M-derived macrophages (MdM) on the replication of Chlamydia trachomatis (L2/434) in HEp-2 cells. M or MdM were added to infected cells at a ratio of 4:1, and the resultant chlamydial yield was evaluated in one-step growth experiments. Chlamydial DNA production was evaluated by dot hybridization. Both M and MdM reduced chlamydial yield and DNA production, but the reductions caused by MdM were more pronounced. Electron microscopy showed that while control HEp-2 cells at 48 h postinfection contained large inclusions in which most particles were elementary bodies, the infected HEp-2 cells exposed to MdM contained small vacuoles with abnormal reticulate bodies and very few typical elementary bodies. Separation of the MdM from the HEp-2 cells by a membrane reduced the inhibitory effect of the MdM relative to that of MdM in direct contact with the infected cells. Addition of tumor necrosis factor antibodies to C. trachomatis-infected HEp-2 cells exposed to MdM (either in direct contact or separated by a membrane from the infected cells) reduced the inhibition of chlamydial DNA production. These data suggest the possibility that MdM may modulate C. trachomatis replication in vivo.

Cell Line↗

Inhibition of Chlamydia trachomatis growth by recombinant tumor necrosis factor.

Purified human recombinant tumor necrosis factor (rTNF) alpha inhibited the growth of Chlamydia trachomatis (L2/434/Bu) in HEp-2 cell cultures. The inhibition of C. trachomatis yield could be achieved even when the rTNF alpha (200 ng/ml) was added up to 12 h after infection. The effect of rTNF alpha on chlamydial infection was synergistic with that of gamma interferon.

Carcinoma↗