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Biomedical subjects

K Sundaram

Publications and source records attributed to K Sundaram.

At least 73 records · Page 4Linked to original sources

Suppression of skin allograft rejection by post-transplantation administration of specific anti-lymphocyte serum.

An heterologous anti-lymphocyte serum ALS(I-GR), was raised in rabbits by immunization with draining lymph node cells of AKR mice which had rejected DBA/2 skin allografts. Treatment of AKR mice with this ALS on the 4th day after DBA/2 skin grafting, significantly prolonged the survival of the graft in comparison with that in allografted mice treated with normal rabbit serum. In contrast, ALS prepared against unsensitized lymph node cells was found to be ineffective when administered after transplantation. A further prolongation of allograft survival was obtained when ALS(I-GR) was administered to recipients on days +4 and +7. ALS(I-GR) seemed to specifically suppress the rejection of DBA/2, but not of C57 BL/6 skin grafts. The suppressive action of ALS(I-GR) was not due to cross reactive (anti-DBA) antibodies and was probably directed against idiotypic determinants on antigen-stimulated cells.

Animals↗

Electrokinetic status of the subpopulations of lymph node cells in contact-sensitized CBA mice.

Electrokinetic behaviour of LNC and their subpopulations from CBA mice contact-sensitized with dinitrofluorobenzene and oxazolone were studied. The sensitized LNC showed a significant reduction of mean EPM on the days of maximum DH response. Histogram analysis revealed that LNC of unsensitized as well as contact-sensitized mice were heterogeneous populations. While the LNC of unsensitized mice resolved into two subpopulations, sensitized LNC resolved into three distinct subpopulations. The emergence of a new populations with mean EPM intermediate between those of low and high mobility lymphocytes was a consequence of contact sensitization. Enriched subpopulations were also obtained by nylon adherence-dependent and surface marker-dependent procedures. histograms of these subpopulations revealed that in the mice sensitized to DNFB and oxazolone both T and B cells were electrokinetically altered and were heterogeneous in the distribution of their EPM. These findings are similar to the earlier observations on EPM of LNC in allograft-sensitized mice.

Animals↗

Lactic dehydrogenase isozyme distributions in lymphocytes from normal and leukemic mice.

LDH isozyme distributions were studied in the thymocytes of normal and spontaneously leukemic mice. In the normal animals, H:M ratios were found to be higher for more mature cells of adult animals than for less mature thymocytes of the neonates. However, thymocytes from leukemic animals bearing mature phenotype displayed very low values of H:M ratios. From these results, the relationship between the changes in LDH-isozyme distributions in AKR thymocytes and their progressive maturation appears to be equivocal. Alterations in isozyme distribution patterns, reflecting a decrease in H:M ratios, on the other hand, appears to be a characteristic feature of terminal stages of this murine leukemia.

Animals↗

Isolation and characterization of the two subpopulations of cells with different lethalities from Zajdela ascitic hepatoma.

Two distinct subpopulations of cells, light (L-cells) and heavy (H-cells), have been isolated and characterized from a rat ascitic tumor, the Zajdela ascitic hepatoma. These two populations have been separated by Percoll density gradient centrifugation and studied by flow cytofluorimetry. The two populations, in addition to their difference in buoyant densities, show characteristically different profiles for DNA and RNA contents, nonspecific esterase activity, and surface amino group distribution. The DNA distribution in the two types of cells clearly shows that the H-cells are rapidly proliferating while the L-cells are quiescent. Studies on the two groups of cells after colchicine treatment also confirm this conclusion. The H-cell induced tumors kill the host animals rapidly while the L-cell induced tumors regress in about 3 months. The H- and L-cells from the Zajdela tumor form a convenient experimental system to study the marked difference in the progression of tumors induced by these cells, possible differences in gene expression in regressing and nonregressing tumors and the interactions between the subpopulations with a view to delineate molecular events governing tumor progression and tumor heterogeneity.

Animals↗

Species differences in the sensitivity to a GnRH antagonist.

The effects of the potent GnRH antagonist [Ac-D-NAL(2)1, 4F-D-Phe2, D-Trp3, D-Arg6]-GnRH (GnRH-A), on ovulation in mature rats and rabbits and on serum LH and FSH levels in ovariectomized rats, rabbits and mice were investigated. Dose-response studies showed that 1 microgram (4 micrograms/kg) of GnRH-A was sufficient to inhibit ovulation completely in cycling rats, while 500 micrograms (135 micrograms/kg) were required to inhibit mating induced ovulation in 8 of 11 rabbits. Two of the 3 rabbits which ovulated in spite of the antagonist treatment had delayed LH surges. The mean LH peak of these 3 rabbits was significantly (p less than 0.001) lower than that of controls. Pituitary response to GnRH-A, as measured by plasma gonadotropin levels following GnRH-A treatment in ovariectomized rabbits, rats and mice showed highest sensitivity of the rat to the inhibitory effects of the antagonist. Serum FSH levels were slightly suppressed in rats, but remained undiminished in rabbits and mice. The difference in the response of the three species to the antipituitary effects of GnRH-A is most likely due to differences in the affinity of the pituitary GnRH receptor to the antagonist.

Animals↗

Studies on germinal effects of quercetin, a naturally occurring flavonoid.

Quercetin (3,3',4',5,7-pentahydroxyflavone) is one of the most widely occurring flavonoids ingested by man in food. It has been shown to be mutagenic in prokaryotes as well as in in vitro mammalian cell lines. In view of the unavoidability of ingesting it via a normal diet, there is a need to assess the potential genetic risk to man, due to flavonoid ingestion, using whole animal assays. Dominant lethal studies have been carried out in adult Swiss male mice and Wistar male rats to investigate the germinal effects of quercetin. Adult Swiss males were treated with 200, 300 or 400 mg/kg of quercetin dissolved in 60% dimethyl sulfoxide, intraperitoneally. In the rat study, 200 and 300 mg/kg of quercetin were used. Individually caged males were paired with untreated females for a week and six sequential matings were carried out. Two independent experiments in mice and a single experiment in rats constituted the study. Females were evaluated for inducted dominant lethality during the midterm of pregnancy. At 200 mg/kg dose of quercetin, there were no significant differences between control and the test group in pregnancy, total or live implantations in mice or rats during the whole test period that could be attributed to the flavonoid exposure. In mice at 300 and 400 mg/kg of quercetin, there was a profound reduction in fertility of the males during all six matings. The number of total and live implantations also decreased, particularly at the 400 mg/kg dose, although the sample size was too small to be statistically significant. Contrary to this, the rat study did not show any impairment of fertility, nor was there any substantial suppression of total and live implantations at the highest (300 mg/kg) dose tested. There were no significant differences between control and treated groups with regard to the number of dead implantations at any dosage level at any stage of the study in mice and rats. Thus, no post-implantation losses--a reliable measure of dominant lethal mutations--were induced by quercetin in mice or rats. The loss of fertility could be due to germinal cytotoxicity, oligospermia or impairment of fertilizing ability of the treated animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Species differences in the sensitivity to GnRH analogs.

The effects of several GnRH agonists and antagonists with high biological activity, have been investigated in rats, mice, rabbits and monkeys. Striking differences exist in the response of different species to the antigonadal and antipituitary effects of these peptides. Of all the animals studied, the rat is the most sensitive. The magnitude of the response to GnRH agonists seems to depend on the sensitivity of the pituitary and the presence of GnRH receptors in the target organs. Findings from animal models require careful interpretation before predictions can be made regarding their possible effects in the human.

Animals↗

Use of LHRH agonists and antagonists in male contraception: a review.

Agonists and antagonists of LHRH have been shown to inhibit testicular function in animals and are considered to offer potential for nonsteroidal contraception. In men, they offer one of the few promising approaches to reversible suppression of spermatogenesis. They do, however, also depress testosterone synthesis, thus causing loss of libido, necessitating the administration of supplemental androgens.

Animals↗

Species differences in the sensitivity to the antitesticular effects of [Ac-D-NAL(2)1, 4FD-Phe2, D-Trp3,D-Arg6]-LHRH, a potent LHRH antagonist.

The antigonadal effects of [Ac-D-NAL(2)1, 4FD-Phe2, D-TRP3, D-Arg6]-LHRH (LHRH-A), a potent antagonist of LHRH, were investigated in rats and rabbits. Rats and rabbits were given LHRH-A (1250 micrograms/kg) daily for 15 days. Some animals were killed on day 16 (24 h after the last treatment) while others were mated. In the male rats serum LH and testosterone levels as well as the weights of sexual organs were significantly reduced. Mating behavior and fertility that were suppressed by the end of treatment returned to normal by 7 weeks after last treatment. In contrast to rats, the testicular function and fertility of rabbits appeared unaffected by LHRH-A treatment. The difference in the response between rats and rabbits led us to compare the response of rats and mice. Male rats and mice were given LHRH-A (1450 micrograms/kg) daily for 5 days and killed on day 6. In rats LHRH-A caused a 93% decrease in serum T and 88% decrease in in vitro testicular T production. In mice, however, the Leydig cell function remained unaffected when examined 24 h after the last dose of LHRH-A. To explain the differences between the effects of LHRH-A on rats, rabbits and mice, the acute effect of this peptide on serum T levels was investigated in these species. Administration of a single dose of LHRH-A (1250 micrograms/kg) led to a rapid decrease in serum T that was sustained for 24 h in rats. In rabbits and mice, however, the same dose of LHRH-A caused only a transient decrease in serum T. Male rhesus monkeys treated with LHRH-A (1000 micrograms/kg) also showed a transient decrease in serum T concentrations. It is concluded that there are considerable species differences in the sensitivity to the antigonadal effects of LHRH-A.

Animals↗

[Ac-D-NAL(2)1,4FD-Phe2,D-Trp3,D-Arg6]-LHRH, a potent antagonist of LHRH, produces transient edema and behavioral changes in rats.

Acute toxicity studies of [Ac-D-NAL(2)1,4FD-Phe2,D-Trp3,D-Arg6]-LHRH (LHRH-A), a potent antagonist of LHRH were performed. Subcutaneous administration of this peptide to rats induced transient edema of the face and extremities. This effect was maximal 3-5 h after peptide administration and subsided by 24 h. These effects were not seen with an LHRH agonist or two other antagonists. This side effects of LHRH-A was peculiar to rats and not observed in mice, rabbits and rhesus monkeys. Intravenous administration led within minutes to depression of spontaneous activity in rats and monkeys. We conclude that some LHRH antagonists produce species specific effects on vascular permeability and spontaneous activity.

Animals↗

Enhanced host resistance to transplantable murine lymphosarcoma in Swiss mice by combined immunostimulation with BCG and polyinosinic-polycytidylic acid.

Combined immunostimulation with BCG and double-stranded polyinosinic-polycytidylic acid (poly I . poly C) was more effective than single-modality immunostimulation in suppressing tumor growth in inbred Swiss mice. BCG sensitization followed by administration of poly I . poly C on the day of tumor cell injection significantly prolonged the survival period against parental lymphosarcoma (LS) and its ascites variant (LS-A). BCG and poly I . poly C given together on the day of tumor cell injection suppressed only LS-A and not LS. BCG or poly I . poly C given alone did not result in tumor cures. Silica injection given 2 days before poly I . poly C injection completely abrogated the antitumor effect of sequential treatment with BCG and poly I . poly C. Silica treatment given on and beyond the day of poly I . poly C injection did not abrogate the antitumor effect. This observation indicated that intact macrophage effector function was essential at the time of tumor cell inoculation to obtain an effective antitumor action.

Adjuvants, Immunologic↗

Ovulation inhibition in the pregnant mare's serum gonadotropin-treated immature rat: a bioassay for luteinizing hormone-releasing hormone antagonists.

A convenient method for evaluating the biological activity of luteinizing hormone-releasing hormone (LHRH) antagonists was devised. Pregnant mare's serum gonadotropin (PMSG) treatment of immature rats is known to stimulate follicular growth and estrogen production, that in turn stimulates the release of LHRH which triggers an ovulatory discharge of luteinizing hormone (LH) from the pituitary. The present bioassay of the antagonists is based on the inhibition of ovulation in the PMSG-treated rats. Twenty-eight-day-old Sprague Dawley rats maintained under a light period of 12 h/day (lights on at 0630 h) were given 10 IU of PMSG s.c. at 0930 h. On Day 30 of age the antagonist was given s.c. at 1430 h. The rats were killed on the following morning and the oviducts examined for the presence of ova. In addition, the antagonists were compared in their ability to inhibit serum testosterone levels in adult male rats. In the PMSG-treated rats the order of ovulation-inhibiting potency of the following antagonists was: [Ac-D-NAL(2)1,4FD-Phe2,D-Trp3,D-Arg6]-LHRH (LHRH-1) greater than [Ac-delta 3 Pro1,4FD-Phe2,D-NAL(2)3.6]-LHRH (LHRH-2) greater than [Ac-delta 3 Pro1,4FD-Phe2,D-Trp3,6]-LHRH (LHRH-3). The order of potency was confirmed by their antitesticular effects in adult male rats.

Animals↗

Antibodies against the beta-subunit of ovine luteinizing hormone can decrease the clearance of human chorionic gonadotropin in rhesus monkeys.

Contraceptive vaccines based on active immunization against gonadotropic hormones are being investigated in humans and other primates. Immunization against the beta-subunit of ovine luteinizing hormone (oLH beta) reduces fertility in rhesus monkeys by inducing inadequate luteal phases and preventing corpus luteum rescue by rhesus chorionic gonadotropin (rhCG). These effects result from the cross-reactions of the oLH beta-antibodies with rhCG and rhLH. We used human CG (hCG), which also cross-reacts strongly with anti-oLH beta to examine how the circulating oLH beta-antibodies affect the metabolic clearance rates (MCR) of hCG in rhesus monkeys. 125I-hCG was injected into four nonimmunized and seven immunized monkeys and blood was collected at frequent intervals over 7 days. Total and immunoprecipitable radioactivity did not differ significantly, suggesting that the radioactivity in the plasma consisted almost entirely of 125I-hCG. This was confirmed by column chromatography. The MCR (mean +/- SE) was significantly lower (p less than 0.001) in six immunized monkeys (0.35 +/- 0.06 liters/day) as compared to controls (1.19 +/- 0.09 liters/day). The hCG disappearance curve in control monkeys was best described by a two-compartmental system (slow and fast) while an additional third (intermediate) compartment of distribution was typical for immunized animals. The half-lives of hCG for the two exponentials corresponding to the slow and fast components of distribution were not significantly different between the two groups. One immunized monkey had a MCR (1.44 liters/day) that was much greater than the MCR of the other six.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of an LHRH agonist on pituitary and testicular function in rhesus monkeys.

Male rhesus monkeys were given 100 micrograms [(imBzl)-D-His6,Pro9-NEt]-LHRH (LHRH-A), a potent LHRH agonist, s.c. daily for 40 weeks. The first dose of LHRH-A caused acute increases (2-4 h after injection) in serum LH (50-fold), FSH (2 X 5-fold) and testosterone (15-fold) concentrations. Chronic treatment led to a 95% decrease in LH and FSH responses. In spite of a marked decrease in LH response the effect on testosterone response was less evident. Administration of 50 i.u. hCG to control and LHRH-A-treated animals showed that the testicular steroidogenic response was unimpaired by the chronic treatment. Evaluation of the electroejaculated semen at regular intervals showed that there was no consistent reduction in the sperm count of LHRH-A-treated monkeys. Testicular biopsies showed that normal spermatogenesis was occurring in all treated animals, but testicular volume was significantly decreased. These results suggest that, in rhesus monkeys, the pituitary is more susceptible to desensitization by chronic LHRH agonist treatment than are the testes, and that LHRH agonists do not have direct antitesticular effect in rhesus monkeys.

Animals↗

The subpopulations of lymph node cells from allograft-sensitized AKR mice.

Electrokinetic behaviour of skin allograft-sensitized LNC and their subpopulations from AKR mice were studied. Sensitized LNC showed a significant reduction in the mean EPM in the post-transplantation period. Histogram analysis of both unsensitized and sensitized LNC of AKR mice showed a heterogeneous population. This heterogeneity in the lymph node cells was more pronounced in the case of sensitized cells. While unsensitized cells resolved into two subpopulations, sensitized LNC resolved into three distinct subpopulations. The emergence of a new population in the case of sensitized cells may be a consequence of allograft sensitization. Subpopulations of unsensitized and sensitized LNC were also obtained by surface marker dependent and differential adherence to nylon wool procedures. Histograms of these subpopulations showed heterogeneity, indicating that both T and B lymphocytes are affected by allograft sensitization. These findings were further confirmed by interacting the subpopulations with specific HCA antigen.

Animals↗

Specificity of spatial clustering of amino acid residues as an evolutionary trend in proteins.

Three-dimensional structures of cytochrome c and myoglobin molecules together with amino acid substitution data on these proteins from a close range of taxa highlight an interesting evolutionary trend. Assuming three-dimensional structures of homologous proteins to be largely similar, the distribution of amino acid residue types around one another was studied. The application of information theory to three dimensional arrangement of amino acid residues revealed that in general, the higher the taxonomic order, the more specific is the clustering of residue types with one another.

Amino Acid Sequence↗