PubMed Health⌕ Search

Biomedical subjects

A Gaur

Publications and source records attributed to A Gaur.

At least 19 recordsLinked to original sources
PubMed1992

Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy.

Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system that can be induced in susceptible strains of mice by immunization with myelin basic protein (MBP) or its immunodominant T cell determinants, serves as a model of human multiple sclerosis. Tolerance to MBP in adult mice was induced by intraperitoneal injection of synthetic peptides of immunodominant determinants of MBP and prevented MBP-induced EAE. Furthermore, tolerance-inducing regimens of peptides administered to mice after the disease had begun (10 days after induction with MBP) blocked the progression and decreased the severity of EAE. Peptide-induced tolerance resulted from the induction of anergy in proliferative, antigen-specific T cells.

Animals↗
PubMed1992

Internalization of a major group human rhinovirus does not require cytoplasmic or transmembrane domains of ICAM-1.

Intercellular adhesion molecule-1 (CD54), a cell adhesion molecule and the receptor for the major group of rhinoviruses, is a class 1 membrane protein with five Ig-like domains in its extracellular region, a transmembrane domain, and a short cytoplasmic domain. The amino-terminal domains (D1 and D2) are sufficient for virus binding and the first is most important (1). We have investigated whether other extracellular domains, transmembrane or cytoplasmic domains are required for virus entry as determined by postinfection virion protein biosynthesis. We demonstrate that cytoplasmic, transmembrane, and Ig-like domains 3, 4, and 5 are not essential for rhinovirus entry into transfected COS cells. The efficiency of rhinovirus infection directly correlates with the efficiency of rhinovirus binding and a form of intercellular adhesion molecule-1 that is glycophosphatidyl-inositol anchored, and thus does not extend into the inner leaflet of the membrane bilayer or the cytoplasm efficiently supports virus entry.

Cell Adhesion Molecules↗
PubMed1992

Transferable antibiotic resistance among thermotolerant coliforms from rural drinking water in India.

A total of 231 thermotolerant coliforms was isolated from rural drinking water from four states of India. Of these, 220 isolates were resistant to ampicillin, chloramphemicol, streptomycin and tetracycline. Multiple (MAR), double and single antibiotic resistances were observed in 31.4, 48.6 and 13.7% of the isolates, respectively. Out of 177 antibiotic-resistant isolates examined for transmissibility, only 15.3% were able to transfer their resistances to Escherichia coli K-12 recipient. The resistances were transferred by 32.5% of MAR, 21.9% of double resistant and 7.6% of single resistant isolates. Ampicillin resistance was transferable in 14.69% strains while resistances for the rest of the antibiotics were transferable in less than 4% strains. MAR strains of E. coli and Klebsiella sp. showed highest levels of R-plasmid transfer.

Ampicillin Resistance↗
PubMed1992

Transient achalasia of esophagus in tetanus.

A case with tetanus presenting with progressive dysphagia due to lower esophageal dysfunction is described. A barium swallow at the onset of symptoms showed esophageal dilatation with a smooth tapering at the lower end suggestive of achalasia cardia. The patient recovered from tetanus over the ensuing three weeks; repeat barium swallow at this time was normal, suggesting that esophageal dysfunction was a manifestation of tetanus.

Deglutition Disorders↗
PubMed1992

Prevention of B cell clonal deletion and anergy by activated T cells and their lymphokines.

B cell tolerance is described as the absence of a measurable antibody forming response to an antigenic challenge. The establishment of antigen-specific tolerance requires, by definition, engagement of the B cell antigen-specific receptor. However, only in some circumstances does this engagement lead to tolerance, while in others it produces B cell activation and secretion of immunoglobulins. Several mechanisms occur naturally in vivo abrogating the expression of deleterious autoantibodies and contributing to the state of self-tolerance. In this review, we will examine different ways in which B cell tolerance can be broken, focusing on evidence showing that activated-T cells and/or their lymphokines can prevent B cell clonal deletion and thus have a potential role in the pathogenesis of autoimmune diseases. This approach is based on the well-known association of several lymphokines, such as IL-1, IL-2, IL-4, IL-5, and type I interferons, with autoimmune phenomena in vivo.

Animals↗
PubMed1992

Anti-immunoglobulin treatment of murine B-cell lymphomas induces active transforming growth factor beta but pRB hypophosphorylation is transforming growth factor beta independent.

Cross-linking of B-cell membrane immunoglobulin (Ig) receptors induces growth arrest at G1-S, leading to apoptosis and cell death in the immature lymphomas WEHI-231 and CH31, but not in the CH12 B-cell line. In this system, which has been used as a model for B-cell tolerance, we have established that these lymphomas produce active transforming growth factor beta (TGF-beta) when treated with anti-Ig and that their hierarchy of sensitivity to TGF-beta generally correlates with their growth inhibition by anti-Ig. TGF-beta, in turn, has been shown to interfere with the phosphorylation of the retinoblastoma gene product, pRB. Herein, we also demonstrate that in WEHI-231 B-lymphoma cells treated with anti-Ig for 24 h, the pRB protein is found to be predominantly in the underphosphorylated form, as previously reported for cells arrested by the exogenous addition of TGF-beta. However, neutralizing antibodies to TGF-beta failed to prevent growth inhibition by anti-Ig in WEHI-231 and CH31. When WEHI-231 lymphoma cells were selected for growth in TGF-beta, the majority of the TGF-beta-resistant clones remained sensitive to anti-Ig-mediated growth inhibition. In these clones, the retinoblastoma gene product was found to be in the underphosphorylated form after 24-h treatment with anti-Ig, but not with TGF-beta. These data show that anti-Ig treatment of murine B-cell lymphomas stimulates the production of active TGF-beta but that a TGF-beta-independent pathway may be responsible for the pRB underphosphorylation and cell cycle blockade.

Animals↗
PubMed1991

The T cell receptor repertoire influences V beta element usage in response to myoglobin.

T cell clones recognizing the sperm whale myoglobin (SpWMb) epitope 110-121 in association with H-2d major histocompatibility complex class II molecules display a very limited heterogeneity of T cell receptor (TCR) V beta usage in DBA/2 mice. All clones previously tested used the same V beta 8.2 gene segment and very restricted junctional regions. To investigate the significance of this observation in vivo, we immunized DBA/2 mice with the intact SpW Mb protein or peptide 110-121. Only the V beta 8+ T cells showed any significant response to the 110-121 epitope. The response to peptide 110-121 was then analyzed in mice which, either as a consequence of antibody depletion or through genetic deletion of TCR V beta genes, lacked V beta 8+ peripheral T cells. DBA/2 mice depleted of V beta 8+ T cells by antibody treatment responded poorly to the 110-121 peptide, and only at high antigen concentrations. In contrast, DBA/2V beta a mice (homozygous for a deletion of multiple V beta gene segments including the V beta 8 family) made a response at least as great as that made by DBA/2 mice, even though the DBA/2V beta a mice had a very restricted TCR V beta repertoire compared with DBA/2 mice. Mechanisms which might determine differences in the 110-121 specific response of DBA/2, DBA/2V beta a and F23.1-treated DBA/2 mice are discussed.

Animals↗
PubMed1991

A polyclonal model for B-cell tolerance. II. Linkage between signaling of B-cell egress from G0, class II upregulation and unresponsiveness.

Overnight exposure of adult splenic B cells to anti-Ig, a surrogate for antigen/tolerogen, can result in a hyporesponsive state in terms of antibody synthesis. Since B cells treated with either intact of F(ab')2 fragments of anti-Ig will exit the G0 phase of the cell cycle and enter G1 or S, respectively, we examined which steps in B-cell activation were required for this form of hyporesponsiveness. We found that B-cell hyporesponsiveness could be induced under conditions leading to either abortive or productive B-cell cycle progression, depending on the immunogenic challenge employed. Thus, PMA + ionomycin, concanavalin A, PMA alone, or ionomycin alone induced hyporesponsiveness. Each of these reagents is able to drive B-cell exit from G0 into G1 and cause class II hyperexpression. We next examined the effect of cyclosporin A (CSA), a reagent that blocks anti-Ig but not by PMA-induced class II hyperexpression. Interestingly, CSA only interfered with the induction of B-cell hyporesponsiveness with anti-Ig. These results suggest that upregulation of MHC class II may be coincident with a CSA-sensitive tolerance pathway in B cells stimulated by anti-Ig. Finally, IL-4 pretreatment was found to ablate hyporesponsiveness induced by either intact anti-Ig or PMA. These results parallel the Fc-dependent induction of hyporesponsiveness reported earlier (G. Warner and D. W. Scott, J. Immunol. 146, 2185, 1991). We propose that crosslinking of surface Ig, leading to cell cycle progression out of G0 as well as class II hyperexpression, in the absence of a cognate T cell signal, leads to B-cell hyporesponsiveness.

Animals↗
PubMed1990

Bypass by an alternate 'carrier' of acquired unresponsiveness to hCG upon repeated immunization with tetanus-conjugated vaccine.

We report here the use of an alternative carrier diphtheria toxoid (DT) in human subjects to overcome antigen-specific unresponsiveness upon immunization with a hapten/ligand-carrier conjugate. In the phase I clinical trial of a birth control vaccine using gonadotrophin subunits linked to tetanus toxoid, some of the subjects failed to evoke a booster antibody response to human chorionic gonadotrophin (hCG). Presentation of the ligand on DT instead in subsequent immunizations restored anti-hCG response.

Antibody Formation↗
PubMed1990

Antibiotic resistance of coliforms in drinking water in rural areas.

The antibiotic sensitivity of 197 coliform sp. isolated from drinking water in five rural areas was studied. Twelve strains (6.1%) showed multiple antibiotic resistance, three (1.5%) of which were able to transfer the resistances to an Escherichia coli K-12 recipient. It seems unlikely that the occurrence of transmissible multiple antibiotic resistance among coliforms in drinking water in the areas studied poses a significant public health risk.

Anti-Bacterial Agents↗
PubMed1989

Synergistic activation of granulocyte-macrophage colony-stimulating factor production by IL-1 and IL-2 in murine Th1 cells.

Recent reports indicate that murine CD4+ Th1-type cloned T cells are insensitive to IL-1 because specific IL-1R are not detected on these cells and IL-1 does not modulate proliferative responses. However, we have determined that Th1 clones can respond to IL-1, because they function synergistically with IL-2 to induce granulocyte-macrophage-CSF secretion. This response to IL-1 plus IL-2 could be induced by IL-1 alpha or IL-1 beta and by membrane-bound IL-1 on macrophages. However, IL-1R could not be detected, and Th1 cells did not respond to IL-4 in the presence or absence of IL-1, as measured by either proliferation or granulocyte-macrophage-CSF production. Therefore, IL-1 functioned as a cofactor in Th1 cells stimulated with IL-2, but not with IL-4. A possible mechanism whereby IL-1 activates Th1 cells is discussed.

Animals↗
PubMed1989

Prostaglandin E2-dependent induction of granulocyte-macrophage colony-stimulating factor secretion by cloned murine helper T cells.

PG are known to inhibit T cell proliferation, at least in part by suppressing IL-2 production, but effects of PG on the production of other lymphokines have not been well studied. We have found that PGE2 and PGE1, but not PGF2 alpha, inhibit both proliferation and production of granulocyte-macrophage (GM)-CSF by murine TH clones stimulated with Ag or anti-CD3 antibody. Thus, signals generated via the Ag receptor:CD3 complex were inhibited by PGE. Most interesting, however, was the finding that PGE2 and PGE1 could act synergistically with IL-2 for the induction of GM-CSF in some TH1 clones. Dependence on PGE2 for this response was not found in all clones, as some TH1 cells could produce GM-CSF after IL-2 alone, and some cells did not produce GM-CSF even in the presence of PGE2 and IL-2. These observations indicate that there is a subset of TH1 cells receptive to a stimulating activity of PGE2 in the presence of IL-2. PGE2 is known to elevate cAMP levels in T cells. Therefore, we tested whether other agents known to increase cAMP, such as forskolin and cholera toxin, could act in conjunction with IL-2 to induce GM-CSF secretion. As was found with PGE2, these compounds also induced GM-CSF activity in the presence of IL-2, suggesting a critical role for cAMP in this process. Overall these data indicate that the requirements for activation of GM-CSF secretion vary among individual T cells. Most importantly they provide the first evidence that E-series PG are positive signals for lymphokine induction in certain T cells, whereas simultaneously acting as negative signals limiting proliferation. This result also suggests that treatment with anti-inflammatory drugs that decrease PGE2 concentrations may inhibit lymphokine secretion normally stimulated by this pathway.

Alprostadil↗
PubMed1989

Vaccine for control of fertility.

Birth control vaccines constitute a new category of vaccines. Immunization with the objective of selectively blocking a physiological process differs in many respects from immunizing against pathogens. Conceptually, these widen the orbit of therapeutic intervention by immunological methods. Success recorded in making vaccines regulating fertility offers models to regulate any other physiological process in the body. At a practical level, the task of making such vaccines is beset with inherent difficulties and with new challenges. This article, dedicated to Avrion Mitchison, aims to discuss these problems and to record successes wherever achieved.

Family Planning Services↗
PubMed1989

Antibody response and characteristics of antibodies in women immunized with three contraceptive vaccines inducing antibodies against human chorionic gonadotropin.

Data are presented on antibody titers generated in 88 women immunized with three formulations of antihuman chorionic gonadotropin (hCG) vaccine, namely, beta-hCG (formulation B); beta-hCG associated with alpha-subunit of ovine luteinizing hormone (LH) (formulation A) and beta-hCG + beta-ovine LH (formulation M), each linked to tetanus toxoid and cholera toxin chain B as carriers. Each formulation was tested at two dose levels (100 and 500 micrograms). All women without exception developed anti-hCG antibodies having hCG-binding capacity above 20 ng mL-1 (0.5 nM), a level considered to be the threshold for prevention of pregnancy. Formulations A and B gave relatively better immunogenic response in human subjects than M. In each case, the antibody response was reversible. The mean duration of response above 20 ng was 35 to 37 weeks for formulation A, 34 weeks for B, and 17 to 20 weeks for M. Antibodies induced by three formulations of the vaccine had high-affinity (Ka 10(9)-10(10)M-1) for binding with hCG. They were devoid of cross-reaction with human follicle-stimulating hormone and thyroid-stimulating hormone but, as expected, cross-reacted with human LH. Antibodies were competent to block the hCG induced ovarian hyperemia.

Adult↗
PubMed1988

Use of filter paper discs as substrate for collection and storage of blood samples for screening of anti-tetanus toxoid antibodies.

A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to tetanus in dried blood samples spotted on filter paper discs has been developed. A good correlation was found between the two methods, filter paper disc assay and direct blood assay (r = 0.91). The specificity of the test was determined by a competitive inhibition assay using goat anti-tetanus-toxoid antibodies coupled to horseradish peroxidase. The interassay coefficient of variation is 10-12%. The antibodies were measurable until 4 months of storage of filter paper discs at room temperature (25 degrees C). This procedure is useful for mass screening of anti-tetanus antibodies using dried blood samples on filter paper discs.

Adult↗
PubMed1987

Recent developments in immunocontraception.

The possibility of controlling fertility by antibodies inactivating key reproductive hormones has been amply demonstrated by active and passive immunization in primates. Four birth control vaccines directed against human chorionic gonadotropin are currently in early clinical trials. The nature of these vaccines and the underlying principles are described, as are the available results from clinical studies. The alpha- and beta-subunits of human chorionic gonadotropin and the ovine gonadotropins have been cloned by recombinant deoxyribonucleic acid methods. A new breed of vaccines that combines the genes of gonadotropins linked to hepatitis B surface protein has been developed. The next generation of birth control vaccines is likely to be polyvalent and to have the ability to intercept fertility at more than one point. A number of monoclonal antibodies against human sperm have shown the presence of tissue-specific antigens and the possibility of preventing the fertilization of the egg. Inclusion of more than one carrier in the vaccine increases the percentage of high responders and accords immunoprophylactic benefits against more than one disease. Conjugates have also been developed to obtain high titers of antibodies against gonadotropin-releasing hormone with permissible adjuvants. This vaccine may have therapeutic applications in hormone-dependent cancers and precocious puberty.

Chorionic Gonadotropin↗
PubMed1986

Construction of genomic libraries of mycobacterial origin: identification of recombinants encoding mycobacterial-specific proteins.

A complete genomic library from Mycobacterium vaccae (2785 recombinants) and a partial genomic library of M. leprae and BCG (300 and 1750 clones, respectively) were constructed in the plasmid pBR322. Bam HI was selected as the restriction endonuclease for obtaining DNA cleavage products. Evidence was obtained for limited expression of the cloned mycobacterial DNA inserts in Escherichia coli. A recombinant has been identified which codes for antigen immunoreactive with rabbit anti-M. leprae antibody but not with anti-H37Rv antibody.

Antigens, Bacterial↗