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O Singh

Publications and source records attributed to O Singh.

At least 37 records · Page 2Linked to original sources
PubMed1993

A birth control vaccine is on the horizon for family planning.

Vaccines for control of fertility are likely to have an important impact on family planning methods. They are designed to act by mobilization of an internal physiological process and do not require external medication on a continuous basis. A number of birth control vaccines are at different stages of development, the most advanced being a vaccine inducing antibodies against human chorionic gonadotrophin (hCG). This vaccine consists of a heterospecies dimer (HSD, beta hCG associated with alpha-subunit of ovine luteinizing hormone, beta hCG:alpha oLH) linked to tetanus toxoid (TT) or diphtheria toxoid (DT) as carriers. The vaccine has recently passed an important milestone; it has completed the first leg of phase II efficacy trials. Women of proven fertility leading active sexual life were protected from becoming pregnant at antibody titres > or = 50 ng of hCG bioneutralization capacity per ml. This vaccine has previously been demonstrated to be reversible in its effect. It is free from any notable side-effects on endocrine, cardiovascular and other body functions. Ovulation was not disturbed and menstrual regularity was maintained. A logistic disadvantage of the present vaccine is the requirement for multiple injections. This is expected to be overcome by encapsulation of the requisite doses of the vaccine in biodegradable microspheres, which could be given at a single contact point for sustained antibody titres lasting over a year. A live recombinant vaccine has also been made that elicits high anti-hCG titres in monkeys for nearly 2 years following primary immunization and a booster at 8-9 months.

Adult↗
PubMed1992

Vaccines for control of fertility and hormone dependent cancers.

Two vaccines, namely one inducing antibodies against hCG and the other against GnRH, are now in clinical trials. The hCG vaccine has entered Phase II clinical trials in three centres in India after successfully completing Phase I clinical studies in several centres in India and in four countries abroad. The vaccine was found to be devoid of side-effects; its effect was reversible. The available data on 179 cycles indicate that the vaccine prevents pregnancy at antibody titres above 50 ng/ml. A genetically engineered version of the vaccine has also been approved for trials in human lung cancer patients of the type which make hCG. hCG is observed to be a growth factor for such tumours. The GnRH vaccine is usable in both males and females as the deca-peptide is common to both sexes. Following suitable experimental and toxicology studies, the vaccine is currently in Phase I/Phase II clinical trials in patients of prostate carcinoma. Where antibody GnRH antibodies were induced, the LH, FSH and testosterone levels declined. This was accompanied by a reduction in prostate specific antigen. Clinical improvement was observed in many cases. The vaccine has also entered Phase I clinical studies in postpartum women, with the objective to extend the lactational amenorrhoea and extend inter-child interval.

Chorionic Gonadotropin↗
PubMed1992

Anti-hCG vaccines are in clinical trials.

Two vaccines inducing antibodies against human chorionic gonadotropin (hCG) have completed Phase I clinical trials, indicating the reversibility and safety of these vaccines. One is currently in Phase II efficacy trials in women in three major centres in India. The available data suggest that the vaccine prevents pregnancy above antibody titres of 50 ng/ml hCG bioneutralization capacity.

Antibodies↗
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↗
PubMed1989

Semisynthetic anti-LHRH vaccine causing atrophy of the prostate.

A modified luteinizing hormone releasing hormone (LHRH) analog (D-lys)6 was synthesized and linked to epsilon-amino caproic acid at the 6th position. The free amino group thus generated was used for conjugation to diphtheria toxoid. Immunogenicity and bioefficacy studies of this conjugate vaccine were carried out in rodents. All immunized animals produced antibodies reactive with native LHRH. A gradual decline in testosterone levels accompanied the rise in anti-LHRH titers. On necropsy, after 10 weeks, a significant reduction in the relative weights of testes and accessory sex organs was noticed. Of particular significance was the marked atrophy of the prostate, indicating a possible therapeutic application of this vaccine in the treatment of androgen-dependent carcinoma of the prostate.

Animals↗
PubMed1989

Stability of an antifertility vaccine consisting of gonadotropin subunits linked to tetanus toxoid.

The shelf life and thermal stability of an antifertility vaccine, in which gonadotropin subunits are linked to carriers such as tetanus toxoid and cholera toxin chain B and has successfully completed phase-I clinical trials at five centres in India, was studied. The vaccine adsorbed on alum was stored at three temperatures, 4 degrees C, room temperature (20-30 degrees C) and at 40 degrees C, for a period of up to 1 year. The human chorionic gonadotropin (hCG) binding capacity of antibodies (peak titres) induced in rodents by the vaccine after 6 months of storage at 40 degrees C and at room temperature were 1430 +/- 201 (mean +/- s.e.m.) and 1291 +/- 152 ng ml-1 respectively as compared to 1075 +/- 185 ng ml-1 for the vaccine stored at 4 degrees C. The difference was not statistically significant. After 12 months of storage, the immunogenic properties of the vaccine were nearly the same irrespective of the temperature at which the vaccine was kept. The findings show that the vaccine adsorbed on alum can withstand storage up to at least one year at room temperature and at 40 degrees C. These observations have implications for the current thoughts on storage of tetanus toxoid and diphtheria toxoid at 4-8 degrees C, the two vaccines widely used in immunoprophylaxis, and suggest that similar investigations on these vaccines as cold chain facilities are not universally available in developing countries.

Animals↗
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

An improved immunogen for anti-human chorionic gonadotropin vaccine eliciting antibodies reactive with a conformation native to the hormone without cross-reaction with human follicle stimulating hormone and human thyroid stimulating hormone.

Beta-subunit of human chorionic gonadotropin (hCG) was associated with alpha-subunit of ovine luteinizing hormone (OLH) to create a heterospecies dimer (HSD) which has a higher steroidogenic potency than the homologous dimer of alpha hCG and beta hCG in the mouse Leydig cell bioassay. The properties and merits of the antibodies induced by this HSD and beta hCG linked to carrier(s) were investigated in rodents and in a subhuman primate species. The antisera had, in both cases, high affinity for binding with hCG (K alpha = 10(9)-10(10) M-1). The mean (+/- S.E.M.) bioneutralization capacity as a percentage of immunoreactivity (determined by radioimmunoassay (RIA)) of the antibodies generated by the HSD-carrier in rats and bonnet monkeys was higher in comparison with those induced by beta hCG linked to carrier (80 +/- 2.3% vs. 63 +/- 1.5% in rats, and 65 +/- 1.9% for HSD vs. 44 +/- 3.7% in monkeys). None of the sera gave any evidence of cross-reactivity with human follicle stimulating hormone (hFSH) and human thyroid stimulating hormone (hTSH).

Animals↗
PubMed1988

Immunological cross-reactivity of antibodies with species chorionic gonadotropin is a critical requirement for efficacy testing of human gonadotropin vaccines in sub-human primates.

A key question in the evaluation of a contraceptive vaccine is its efficacy in the prevention of pregnancy. Primates have been employed for evaluation of the efficacy of candidate vaccines against human chorionic gonadotropin (hCG). Discrepancies have been noted between the immuno-reactive antibody titres (against hCG) determined by RIA and their ability to prevent pregnancy in test animals. To gain further information on factors involved in fertility control, other characteristics of antibodies, such as affinity for hCG, bioneutralization capacities for hCG, hLH and monkey chorionic gonadotropin, have been determined in antisera from ten bonnet monkeys (Macaca radiata) at times when they were infertile and in bleeds preceding conception. The data reported show that the most important correlate for efficacy is the bioneutralization capacity of the antibodies for the species CG; animals became pregnant when the neutralization capacity diminished to low levels (less than 45 IU/l = 5 ng/ml of hCG equivalent). The bioneutralization of heterospecies CG decreased with the increase in affinity for hCG. These findings have implications for the choice and suitability of primate species for the various candidate vaccines being developed. Vaccines inducing highly specific antibodies against hCG, and restricted in their reactivity with primate CG, may not be testable in heterospecies primate models.

Animals↗
PubMed1986

Enhancement of antigonadotropin response to the beta-subunit of ovine luteinizing hormone by carrier conjugation and combination with the beta-subunit of human chorionic gonadotropin.

Previous studies have demonstrated the control of fertility in monkeys on immunization with the beta subunit of ovine luteinizing hormone (beta-oLH) along with Freund's complete adjuvant (CFA). An eventual birth control vaccine would demand immunization without CFA. Beta-oLH linked to tetanus toxoid (TT) adsorbed on alum-induced antibody response in bonnet monkeys with detoxified sodium phthalyl derivative of Salmonella enteritidis lipopolysaccharide added only in the first injection. The antibodies reacted with both LH and human chorionic gonadotropin (hCG). A higher immune response was obtained with the use of a conjugate of beta-oLH and beta-hCG linked to a common carrier (TT) or with a mixture of beta-hCG/TT and beta-oLH/TT. In both cases, the antibodies were of high affinity with Ka ranging from 5 X 10(9) to 6 X 10(10) M-1. The antibodies were devoid of reactivity with human thyroid-stimulating hormone and human follicle-stimulating hormone. Monkeys with titers above 120 ng/ml hCG binding capacity (greater than 60 ng/ml in most cases) were protected from becoming pregnant during repeated mating with males of proven fertility in ovulatory cycles.

Animals↗
PubMed1985

The dominant role of amide group at C-terminus for recognition by antibody in primates against gonadotropin releasing hormone.

A monkey and a baboon immunized with GnRH-tetanus toxoid conjugate developed high anti-GnRH antibody titres which resulted in disruption of cyclicity and low estradiol and progesterone levels indicative of the inhibition of follicular development and ovulation. Sera of both animals reacted with GnRH(NH2) but were devoid of reactivity with peptide sequences, 4-6, 7-10 and 4-10 of GnRH as well as GnRH free acid. Both sera were however reactive with GnRH-Lys-muramyl dipeptide analogue and GnRH-Ala-Ala-Thr-Lys-Pro-Arg-OH. As these compounds differ from GnRH-free acid by the presence of amide linkage at C-terminus of GnRH, these studies point to the importance of the conformation involving amide group at this position for immunoreactivity.

Amino Acid Sequence↗
PubMed1985

Bioeffective monoclonal antibody against the decapeptide gonadotropin-releasing hormone: reacting determinant and action on ovulation and estrus suppression.

A monoclonal antibody generated against the decapeptide gonadotropin-releasing hormone (GnRH) was effective in intercepting the bioactivity of the hormone; it blocked ovulation in rats. The antibody reacted optimally with the native hormone. Substitution of amide at the COOH terminus by a carboxyl group decreased immunoreactivity by a factor of 200. The antibody recognized the amino acid sequences 4-6, 7-10, and 4-10 to a variable degree, which suggests that the epitope has a conformation involving the entire molecule, with the NH2- and COOH-terminal regions probably in proximity. The antibody was also competent to suppress the progression of estrus in dogs, an indication that GnRH may play an inductive role in the reproductive function of dogs.

Animals↗
PubMed1985

Characteristics and bioefficacy of monoclonal antigonadotropin releasing hormone antibody.

Mouse hybrid cell clones secreting antigonadotropin releasing hormone monoclonal antibody were developed by fusion of SP2/O-Ag 1.4 myeloma cells with splenocytes of mouse immunized with gonadotropin releasing hormone (GnRH) tagged to tetanus toxoid. The product of hybrid cell clones obtained as ascites fluid from mouse peritoneal cavity had a titre of 10(6) (30-40% binding of 125I-GnRH) in radioimmunoassay. The antibody was IgG2a and Kappa. The association constant (Ka) of the product of hybrid cell clone P(8)16(62) for binding with GnRH was 1.2 X 10(9) L/mole. The monoclonal antibody (P(8)16(62)) was highly specific for the native GnRH and devoid of reactivity with thyroid releasing hormone as tested in competitive radioimmunoassay. The recognition for GnRH agonists by monoclonal was 387-fold less with D-Ser (But)6 des Gly10 GnRH ethylamide and 608-fold less with Bz1-His6 GnRH. Monoclonal anti-GnRH antibody was competent to neutralize the in vivo bioactivity of the hormone as evident by the block of estrus cycle and termination of pregnancy in mice. Termination of pregnancy in animals receiving anti-GnRH monoclonal could be prevented by administration of progesterone.

Abortion, Induced↗
PubMed1985

Effect of preoperative fasting in children and adults.

This study was carried out to determine the effect of blood sugar level in patients undergoing different operative procedures. Significant fall in blood sugar level has been found in children below the age of 3 years when they were kept fasting for more than 6 hours. Similar study in adults did not show any appreciable fall in blood sugar level with overnight fasting of more than 12 hours. It is concluded that children below the age of 3 years undergoing any operative procedure should not be kept fasting for more than 4 hours.

Adolescent↗
PubMed1985

Evaluation of problems associated with obese patients during general anesthesia.

In the present study, comprising 50 patients, problems faced in obese patients during general anesthesia were evaluated. Difficulty in intubation, diminished cardiopulmonary reserve and the presence of systemic disorders like diabetes, hypertension, ischemic heart disease were observed. In addition there were other problems like difficulty in positioning and shifting the patients, venepuncture, difficult surgical approach inspite of muscular relaxation. It was concluded that anesthetic management of obese patients should be supervised by the senior and experienced anesthesiologist.

Adult↗