Biomedical subjects

A Gaur

Publications and source records attributed to A Gaur.

69 records · Page 4Linked to original sources

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↗

PubMed1984

Effects on pregnancy in mice of passive immunization against ovine LH and human chorionic gonadotrophin.

Mice given daily i.p. injections of immunoglobulins against ovine LH on Days 3-7 of pregnancy were devoid of implantation sites on Day 8 whereas mice treated with antibodies to hCG had embryos of normal number and appearance on Day 8. These antibody treatments reduced the mean +/- s.d. serum progesterone concentrations from 65.4 +/- 15.3 ng/ml (control globulins) to 8.6 +/- 4.9 ng/ml (anti-LH) and 9.2 +/- 3.1 ng/ml (anti-hCG) on Day 8 and had no differential effect on serum oestrogen levels on Day 4. However, the mice treated with anti-hCG did not litter; resorption of the embryos took place between Days 10 and 14 of pregnancy. Indirect immunofluorescence and quantitative immunoenzymic assays showed the presence of anti-ovine LH and anti-hCG reacting antigens in the mouse feto-placental unit. On Day 6, the values of reacting antigens (mean +/- s.d. absorbance units/10 micron section of embryo) were 0.050 +/- 0.002 with control globulins, 0.059 +/- 0.002 with anti-hCG-Ig and 0.196 +/- 0.018 with anti-LH-Ig; the corresponding values on Day 12 were 0.075 +/- 0.009, 0.402 +/- 0.02 and 0.416 +/- 0.015. The quantitative disposition of the reacting antigens to the two types of anti-gonadotrophins seems to bear a temporal relationship to their respective antifertility action. The pregnancy terminating action of immunoglobulins to ovine LH (Days 6, 7 & 8) and hCG (Days 8, 9 & 10) was counteracted by administration of 2 mg medroxyprogesterone acetate on Days 6, 9 and 12, indicating the importance of progesterone in the maintenance of pregnancy in the mouse.

Animals↗

PubMed1983