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Biomedical subjects

K Sundaram

Publications and source records attributed to K Sundaram.

At least 109 records · Page 6Linked to original sources

Failure of ethanol to induce dominant lethal mutations in Wistar male rats.

2 groups of Wistar male rats (6-7 weeks old) were given ethanol, 15% in drinking water, for 5 days. The level of ethanol was gradually raised to 20 and 30% resp. Both groups received ethanol between 15 and 20% or 15 and 30% continuously during 35 days. Another group was given 30% ethanol for a period of 4 days before mating started. In addition to a control group, which received no treatment, a positive control group of rats exposed to 200 R X-rays, was used. After the treatments, individual males were paired with virgin Wistar females (10-12 weeks) at weekly intervals, and 8 sequential pairings were undertaken. Females were examined for uterine contents and corpora lutea, 10-11 days after their separation from the males. The females mated with irradiated males showed a high incidence of dead implantations and reduction of live implantations. No significant differences in the number of dead, live and total implantations at pre- and/or post-implantation levels were observed among the control and the ethanolic groups, showing that ethanol did not induce any dominant lethal mutations in these Wistar male rats. In the light of studies on alcoholics and other recent data, a need to investigate, independently, the potential mutagenic effects of ethanol and alcoholic beverages is discussed.

Animals↗

The mechanism of action of an antifertility vaccine in the rhesus monkey: reversal of the effects of antisera to the beta-subunit of ovine luteinizing hormone by medroxyprogesterone acetate.

Active immunization of female rhesus monkeys with the beta-subunit of ovine luteinizing hormone )oLH beta) significantly reduced their fertility. To determine whether the major action of the vaccine was interruption of pregnancy, by suppression of "corpus luteum rescue," or inhibition of ovulation, we administered the progestational agent medroxyprogesterone acetate (MPA) from day 4 through day 40 after mating. In the untreated immunized group, the pregnancy rate was significantly below that of control monkeys. MPA treatment restored the fertility rate of immunized animals to that of the control group. These results strongly support the assumption that the antifertility action of antibodies of oLH beta is due to prevention of corpus luteum rescue. Whether the lack of corpus luteum rescue resulted because of neutralization of rhesus monkey chorionic gonadotropin or from a defective corpus luteum, as is found in animals with short luteal phases, cannot be determined from these studies. The successful reversal of the antifertility effect, however, suggests that the circulating antibodies do not interfere with normal ovulation or with the normal development and implantation of the blastocyst.

Animals↗

Lectin potentiation of BCG-contact-mediated antitumor action.

Concanavalin A (Con A) potentiated the BCG-contact-mediated antitumor action when both Con A (10 microgram) and BCG (50 micrograms) were injected with fibrosarcoma cells (5 x 10(4)) into inbred Swiss mice. BCG (50 micrograms) alone had no antitumor effect. The Con A-potentiated BCG-contact-mediated phenomenon was shown to be immunologically mediated, inasmuch as tumors developed in immunosuppressed mice inoculated with tumor cells mixed with Con A and BCG. The same dose of 50 micrograms BCG was effective in controlling the growth of 10(6) fibrosarcoma cells in the presence of Con A. The specific inhibitor of Con A, alpha-methyl D-mannoside, abrogated the potentiation of the BCG effect seen with Con A. Con A also increased the antitumor effect of BCG in sarcoma 180 ascites tumor. Another lectin, peanut agglutinin, also induced an antitumor effect in the presence of BCG only when the tumor cells were treated with Vibrio cholerae neuraminidase.

Animals↗

Observations on the antigenicity and clinical effects of a candidate antipregnancy vaccine: beta-subunit of human chorionic gonadotropin linked to tetanus toxoid.

Observations on the antibody response and clinical effects of injection of purified beta-subunit of human chorionic gonadotropin covalently linked to tetanous toxoid were made in 15 healthy young women who had previously undergone tubal ligation. Antibodies detectable by radioimmunoassay were found in 14 of the women. Clinical surveillance and immunologic, hematologic, and biochemical tests indicated excellent local and systemic tolerance to the antigen. No significant adverse effects on menstrual function, endocrine status, or health were found.

Antibody Formation↗

Theoretical studies on tricyclic antidepressants. I. Molecular structures.

Tricyclic antidepressants are believed to act by inhibiting reuptake of biogenic amines into the presynaptic neuron. This fundamental information can be exploited to characterize the reuptake mechanism in detail and to suggest modifications in drug structure aimed at improving therapeutic value. Knowledge of the three-dimensional geometry of tricyclic antidepressants is a prerequisite for such a research. Hence generation of possible geometries for such structures by theoretical and computer simulation methods has been attempted. Only a limited number of reasonable structures were obtained for most of the molecules, indicating that the obtained structures are likely to be close to actual structures. This has been somewhat substantiated by a study on the structure of imipramine hydrochloride by X-ray crystallographic methods.

Antidepressive Agents, Tricyclic↗

Cytotoxicity of ethyl methanesulfonate in mice spermatogonia.

Enumeration of different types of spermatogonia, following a single i.p. administration of different doses of ethyl methanesulfonate in mice, showed a survival of A1-A4 and in spermatogonia is markedly reduced due to cell killing while the remaining types of spermatogonia were affected marginally. The cell killing effect was dose-dependent, and replenishment of these cells was observed by the end of one cycle of the seminiferous epithelium comprising of 8.5 days.

Animals↗

Computer simulated modeling of biomolecular systems.

This paper describes the algorithm of a program used to simulate three dimensional models of molecules. In addition to open ended molecules the program also enables simulation of structures with constraints in the form of cyclic regions or fixed location of particular atoms. Several molecules can be handled in a single run and each molecule can have any number of contraints. Further, any number of conformations can be obtained for each constrained region. The program can be used for research in several areas of molecular biology, e.g., structure determination, conformational analysis and topographic comparisons.

Chemical Phenomena↗

A computer program for topographic analysis of biomolecular systems.

This program essentially generates a picture of a space filling molecular model. By precise simulation of the intersections between atoms, leaving out the 'hidden line', a good perspective is produced. Additional three dimensional information is provided by simulating reflection spots on the surface. This program has been used to visualise three dimensional surface features of biologically important molecules (e.g., valinomycin). With slight modification the program can be used to visualise enzyme active sites and receptor surfaces. It can also be used to create animated motion pictures of molecular dynamics.

Chemical Phenomena↗

Effects of neonatal thymic exposure to high doses of X-irradiation.

The thymic region of neonatal Swiss mice was exposed to doses varying from 1000 R to 2000 R of X-irradiation. The animals did not show any signs of wasting syndrome up to 6 months after irradiation. At this time hyperplasia of the thymus with an associated lymphocytosis was evident in irradiated animals. Antibody production to sheep red blood cells (SRBC) was not affected. However, at 12 months post-irradiation the animals showed signs of wasting disease with a progressive increase in their numbers at 18 and 24 months of age. The percentage incidence of animals with wasting disease was dose dependent. At this stage in the majority of the animals with the disease the thymus showed varying degrees of atrophy along with splenomegaly. There were no significant differences in the number of lymphocytes but the number of granulocytes showed a substantial increase. This was more evident in animals exposed to 2000 R to the thymic region. Though one observed a lowered ability to form antibodies to bovine serum albumin (BSA) with advancing age, the thymic irradiation did not affect the immune response to BSA even in animals manifesting wasting disease. An interesting observation has been the development of a severe loss of muscle power and tone in the hind limbs in a large majority of animals.

Animals↗

Effects of immunization with the beta-subunit of ovine luteinizing hormone on corpus luteum function in the rhesus monkey.

Rhesus monkeys immunized with the beta-subunit of ovine luteinizing hormone (oLHbeta) developed circulating antibodies which cross-reacted strongly with rhesus monkey chorionic gonadotropin. Normal ovulatory cycles continued, but the fertility of immunized monkeys as compared with that of controls was significantly reduced. Thus, the rhesus monkey represented a useful animal model for the study of certain aspects of an "antifertility vaccine." We investigated the effects of circulating antibodies to oLHbeta on corpus luteum function by measuring production rates (PRs) and peripheral concentrations of progesterone during the luteal phase of the menstrual cycle. Both parameters were significantly lower in immunized animals than in control animals. The length of the menstrual cycle was also significantly reduced. Progesterone PRs were also determined on days 10 and 15 after mating to test the assumption that the antifertility vaccine prevents pregnancy by interfering with "corpus luteum rescue" (the increase in PRs of progesterone usually occurring on day 15 after mating in fertilized animals). PRs increased from days 10 to 15 in pregnant controls, were unchanged in nonpregnant controls, and were significantly lower on day 15 in immunized monkeys as compared with nonpregnant and pregnant controls. These results suggest that "corpus luteum rescue" is suppressed in immunized animals.

Animals↗

Studies on metastases. I. Role of sensitization and immunosuppression.

A normally nonmetastatic tumor metastasized to the regional axillary lymph nodes following severe immunosuppression of inbred Swiss mice. The extent of metastasis was dependent on the severity of lymphocyte depletion and the initial number of tumor cells injected. Sensitization of the host to the tumor was important in prevention of metastasis: Metastasis was induced only if the immunosuppressive treatment occurred within 3 days of tumor inoculation. Antitumor immunity was adoptively transferred by the splenocytes from animals given immunosuppressive treatment with X-rays or hydrocortisone acetate on day 14. Though spleen cells from animals given both immunosuppressants did not have this property, that no metastasis was observed even in doubly immunosuppressed mice indicated sensitization to tumor cells. Lymphocyte number was important also: Injection of splenocytes from normal to tumor-bearing animals significantly reduced the occurrence of metastases.

Animals↗

Suppression of secondary immune response by antilymphocyte serum: time relationship between immunization and administration of antilymphocyte serum.

The effect of antilymphocyte serum (ALS) on the secondary humoral immune response to sheep erythrocytes (SRBC) in rats was studied by the Jerne plaque assay technique. Its effect was also studied on the delayed hypersensitivity (DH) response to SRBC by the foot pad swelling test. ALS(N), which was prepared against lymphocytes from normal rats, had no effect on the secondary humoral and cellular response or on the primary cellular response, when administered postantigenically. ALS(I), which was raised against lymph node cells from SRBC immunized rats produced significant immunosuppression of the secondary response to SRBC when administered either before or after the antigenic injections. In the case of DH, ALS(I) behaved just like ALS(N) having no effect on the secondary response and suppressing the primary only when administered prior to the antigen.

Animals↗

Cell electrophoretic studies on mouse lymphocytes treated with concanavalin A: possible existence of two types of receptors on cell surface.

Concanavalin A (Con A) induced biphasic changes in the electrophoretic mobility (EPM) of splenic lymphocytes of AKR mice. At low concentrations of Con A (2-12.5 mug/ml) there was a significant increase in there was a significant increase in the EPM which could be attributed to the redistribution and endocytosis of Con A receptors. At higher concentrations (greater than or equal to 15.0 mug/ml) a reduction in EPM below that of untreated cells was possibly due to the binding of excess Con A after redistribution. The biphasic profile of EPM was observed only in respect of Con A-treated T lymphocytes. The EPM of B lymphocytes, despite binding of Con A, remained unaltered at all concentrations of Con A. On the basis of these data, the existence of two types of Con A receptors on the cell surface is proposed and their status vis-a-vis the redistribution is discussed.

Animals↗

Time kinetics of the interaction of concanavalin A with splenic lymphocytes of normal AKR mice.

Interaction of concanavalin A (Con A) with splenic lymphocytes of normal AKR mice led to concentration-dependent biphasic changes in electrophoretic mobility. Kinetics of this interaction suggested that at high concentration Con A interacted in two steps. The first step led to redistribution of Con A receptors and increased EPM. In the second step additional receptors to Con A became accessible and their interaction with Con A reduced surface charge density. The kinetic data thus provide additional evidence for the existence of two sets of qualitatively different receptors for Con A on AKR lymphocytes.

Animals↗

Immunogenecity of hapten-protein conjugates in rabbits and monkeys preimmunized against the carrier protein.

The effect of preimmunization with carrier protein on the subsequent response to immunization with hapten-protein conjugate was investigated. Rabbits immunized against bovine serum albumin (BSA) showed a delay in the production of anti-progesterone antibodies upon immunization with progesterone-11-BSA. After a booster injection with P-11-BSA, however, they achieved antiprogesterone levels comparable to those in animals immunized with P-11-BSA only. Similarly, rhesus monkeys preimmunized with tetanus toxoid (TT) showed a delay in the development of anti-hCG titers when immunized with beta-hCG-TT. Here again, after booster immunizations they achieved anti-hCG levels comparable to those of the control animals.

Animals↗