Search PubMed⌕ Search

Biomedical subjects

K Sundaram

Publications and source records attributed to K Sundaram.

At least 91 records · Page 5Linked to original sources
PubMed1983

Information contained in protein shapes.

The sequence of local conformations at C alpha atoms of a protein has been considered as an informational message string. The total self information contents and self information per letter have been evaluated for 83 globular proteins whose structures are known from X-ray crystallography. The derived information contents provide a method of quantitating structural specificity of proteins. This method of analysis enables repeating, intricate structural features to be recognized. Among the globular proteins whose structures have been solved, high potential iron protein stands out with the largest three-letter dependence.

Mathematics↗
PubMed1983

Structural conservation in globular proteins.

Some well sequenced classes of homologous proteins have been analysed in the light of their representative tertiary structures to reveal the nature of structural conservation during protein evolution. Within 'the sphere of influence' around conserved residue sites preferential association of other conservative sites has been observed to be a feature of natural selection valid for all residue types. An information theory approach evolved to examine residue variability reveals that even some non-conservative sites scaffold clusters of high biochemical specificity and intermediate folding units.

Amino Acid Sequence↗
PubMed1983

Mice are insensitive to the antitesticular effects of luteinizing hormone-releasing hormone agonists.

Treatment of male rats with [(imBzl)-D-His6, Pro9-NEt]LHRH or [D-Trp6,Pro9-NEt]LHRH, potent agonists of LHRH, led to a marked decrease in serum testosterone levels and a reduction in testicular LH receptor concentration. Similar treatment of mice showed that they were resistant to the antitesticular effects of the LHRH agonists. To further explore the differences between rats and mice, the direct antitesticular effects of these peptides were investigated in hypophysectomized animals. Hypophysectomized rats and mice were given ovine FSH (50 micrograms), with or without a LHRH agonist (10 micrograms), daily for 5 days. On day 6, the testicular steroidogenic response to hCG was studied. In these studies the in vivo as well as the in vitro steroidogenic response of rat testes to hCG were inhibited by the LHRH analogs. In contrast, pretreatment of mice with the LHRH analogs did not affect their testicular steroidogenic response. Binding studies with the [125I]LHRH analog demonstrated receptors for this peptide on Leydig cells from adult rats. Receptors for LHRH were not, however, detectable on murine Leydig cells. These results suggest that one of the reasons for the lack of an antitesticular effect of LHRH agonists in mice may be due to the inability of these peptides to have a direct effect on testes and may relate to a lack of LHRH receptors.

Animals↗
PubMed1982

A program to calculate non-bonded interaction energy in biomolecular aggregates.

This paper describes a program to calculate intermolecular as well as intramolecular electronic potential energy resulting from non-bonded interactions. The underlying theory is obtained by the application of Rayleigh-Schroedinger perturbation theory to non-overlap regions of a molecular system. The rigorous theoretical expressions for the energy terms are simplified by approximations consistent with those commonly employed in semi-empirical molecular orbital theories. The program is particularly suited for the study of biomolecular assemblies, and in situations where insight into contributions to total energy from various component interaction types is desired. The inclusion of the non-additive dispersion effects in this approach makes it especially interesting for the study of cooperative phenomena in the light of a recent finding [1].

Computers↗
PubMed1982

Impaired steroidogenesis in the luteal phase of the reproductive cycle and during pregnancy in rhesus monkeys immunized with the beta-subunit of ovine luteinizing hormone.

Monkeys immunized with the beta-subunit of ovine luteinizing hormone (oLH beta) develop antibodies which cross react with rhesus chorionic gonadotropin (rhCG) and luteinizing hormone (rhLH). Immunization causes shortened menstrual cycles and reduced fertility. Fertility can be restored by administration of medroxyprogesterone acetate (MPA) during the first 5 weeks of pregnancy. In the present study, we have measured the effects of circulating oLH beta-antibodies on peripheral estradiol, progesterone and 17 alpha OH-progesterone (17OH-P) concentrations throughout the menstrual cycle and during gestation in monkeys which became pregnant following MPA-treatment. Progesterone concentrations were markedly reduced during the luteal phase in cycling animals and the luteal phase of the cycle was significantly shorter as compared to non-immunized controls. Concentrations of estradiol and 17OH-P in the peripheral circulation were not affected by the oLH beta-antibodies. In immunized monkeys which became pregnant following MPA-treatment, progesterone and 17OH-P levels were consistently lower and estradiol concentrations were increased during the second and third trimesters. Our results show that circulating antibodies to oLH beta have multiple endocrinological effects. Corpus luteum function is impaired in cycling monkeys and during the early part of pregnancy. In addition, the pattern of steroid secretion remains abnormal in pregnant monkeys even after the luteal-placental shift.

Animals↗
PubMed1982

Characterization of anti oLH beta-antibodies acting as contraceptives in rhesus monkeys. I. In vitro binding properties.

Female monkeys actively immunized with oLHbeta are infertile when circulation antibody titers become sufficiently high to bind 30% of an iodinated hCG standard. We report here the extensive characterization of the oLHbeta antibodies. Their binding affinity and capacity for human and rhesus gonadotropins were determined. The affinity was high (Ka - 10(9) M-1) and was similar for high, medium and low titer antisera. In contrast, the binding capacity for hCG correlated well with antibody titers (n = 18, r = 0.888, P less than 0.001) and ranged from 0.09 to 8.3 x 10(-7)M. Column chromatographic analysis showed that anti-oLHbeta was mostly IgG. A temporal increase of affinity ('maturation') after booster was absent in the majority of monkeys. Cross-reaction between hCG and hLH as well as rhCG and rhLH was high. The latter, however, did not interfere with regular cycles and ovulation, suggesting that oLHbeta may be a useful antigen for human contraception.

Animals↗
PubMed1982

Direct inhibition of testicular steroidogenesis and gonadotrophin receptor levels by [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH, potent agonists of GnRH.

The effects of [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH on testicular function in rats was evaluated. In adult rats the administration of 0.01, 0.1 or 10 micrograms of either agonist induced rapid increases in serum LH, FSH and testosterone (T) levels which started to decline within several hours. Both agonists caused a decrease in testicular LH and FSH receptor concentrations. The testicular FSH receptor concentration started to decline earlier than the LH receptor concentration but, both reached their lowest levels by day 2 after the administration of the agonists. The recovery of FSH receptor content was slower than that of LH. The extrapituitary effects of the 2 agonists were investigated in immature hypophysectomized animals. Administration of hCG (5 IU daily) to hypophysectomized rats for 5 days caused an increase in serum T levels. Concomitant administration of either of the agonists (10 micrograms) inhibited the steroidogenic action of hCG. Administration of the agonists alone caused a reduction in testicular LH receptor concentration in hypophysectomized rats. Treatment of the hypophysectomized rats for 0-4 days suggested that the direct antitesticular action of the agonists requires 1-2 days to become evident.

Animals↗
PubMed1982

Inhibition of pituitary-testicular function with [D-Trp6] luteinizing hormone-releasing hormone in rhesus monkeys.

The effect of [D-Trp6]LHRH, a potent agonist of LHRH, on pituitary-testicular responses was investigated in male rhesus monkeys. Acute administration of 5, 25, or 500 micrograms [D-Trp6]LHRH produced dose-related increases in serum testosterone and bioassayable LH levels. The administration of 500 micrograms [D-Trp6]LHRH twice weekly for 12 weeks led to a 75% decrease in the LH responses to successive doses of this peptide; testosterone responses in these animals were unchanged, however. The lack of any change in the motility or sperm number in semen obtained by electroejaculation suggested that there was no effect on spermatogenesis during the twice weekly administration. These animals were then treated with [D-Trp6]LHRH (500 micrograms daily) for 16 weeks. This caused dramatic decreases in the LH responses to the agonist in all four animals. The testosterone response was reduced in two and abolished in two animals. These latter two animals also lost their electroejaculatory response. During the recovery period following the cessation of treatment, these two animals produced ejaculates with no sperm, indicating that a transient period of azoospermia was achieved. The results of these studies suggest that 1) the responsiveness of the pituitary is more susceptible to desensitization by [D-Trp6]LHRH than that of the testes; and 2) even though chronic administration of [D-Trp6]LHRH suppressed the pituitary-Leydig cell axis in all monkeys, seminiferous tubular function was reduced only in those animals with very low androgen levels.

Androgens↗
PubMed1982

The status of concanavalin A receptors on the lymphocytes of leukemic AKR mice: inhibition of redistribution by high concentrations of the lectin.

Cell-electrophoretic and fluorescence microscopic investigations were carried out on the interaction of concanavalin A with the splenic lymphocytes of normal and spontaneously leukemic AKR mice. The normal splenic lymphocytes (NSL) showed a biphasic profile of electrophoretic mobility (EPM) as a function of the concentration of Con A, under capping conditions. The mean EPM of NSL increased at low concentrations of the lectin and was reduced below that of untreated cells at higher (greater than or equal to 15 micrograms/ml) concentrations of the lectin. The leukemic cells (LSL) also showed enhancement in EPM at low concentrations of Con A. At high concentrations of the same, however, the mean EPM of LSL was the same as that of untreated cells. In the case of NSL the reduction in EPM at high concentration of Con A is known to be brought about by post-redistributional binding of excess lectin to new receptor sites which emerge after capping of the first type of receptors. Similar investigations of the electrokinetic characteristics of Con A-receptor interaction on leukemic cells revealed that only a single type of receptor was present on LSL. These receptors were inducible to redistribution at low concentrations of Con A. High concentrations of the lectin, however, inhibited the redistribution of the receptors to Con A on LSL. This was confirmed when LSL treated with high concentrations of Con A were relieved from this inhibition by moderate concentrations of alpha-methyl glucoside, which dissociates cell bound Con A. Very low or very high concentrations of alpha-MG were ineffective. The receptors to Con A on LSL were thus behaviorally distinguishable from those on NSL. These data clearly demonstrate that the malignant transformation in AKR mice is also associated with alterations in the properties of receptors to a multivalent ligand Con A.

Animals↗
PubMed1982

Amino acid residues at conservative sites in proteins.

In the process of protein evolution, amino acid residues at certain sites are fixed by natural selection, indicating that such residues are important structurally and functionally. Analysis has revealed some useful observations concerning their specificity contributions. Physicochemical and conformational characteristics of amino acid residues do not seem to fully explain their occurrence probability at the conservative sites. The relative preferences of residues at these sites could be important in the control of biochemical specificity.

Amino Acids↗
PubMed1981

Theoretical studies on tricyclic antidepressants: III. Analysis of stereospecificity.

By dynamic simulation of molecular structures in a digital computer, search was made for all possible ways of superposing a phenyl ring of a tricyclic antidepressant on the phenyl ring of norepinephrine. Using all available structure activity data and deductive reasoning, attempt was then made to reject all but one superposition. A significant outcome was information regarding 2-hydroxydesipramine. Although manifestly inactive when administered, this drug is likely to be potent if delivered at the neuronal site of action. From the chosen superposition a dihydroxy derivative is predicted to be even more potent if it can be endogenously generated or suitably modified to enable delivery at the site of action. Among the various superpositions obtained, it was indirectly possible to make a Monte Carlo type of conformational analysis on the side chain of norepinephrine. Previous conformational studies on norepinephrine are reviewed in this context.

Antidepressive Agents, Tricyclic↗
PubMed1981

Theoretical studies on tricyclic antidepressants. IV. Probable submolecular topographic structures of the "amine pump" receptor.

A probable structure for the best tricyclic antidepressant with respect to inhibition of reuptake of norepinephrine into peripheral adrenergic nerve terminals has been reported. Using tha result as indicating the particular conformation in which the tricyclic antidepressant is likely to mimic the biogenic amine at the membrane "pump" receptor site, the topography of the receptor surface has been worked out by simulating space-filling models of the best inhibitors of the two types in the superposed state. With appropriate computer graphic facilities such surfaces can be used to screen other untested molecules and to predict their activity.

Animals↗