PubMed Health⌕ Search

Biomedical subjects

U Sreenivasan

Publications and source records attributed to U Sreenivasan.

11 recordsLinked to original sources
PubMed1993

Synthesis and dopamine receptor modulating activity of lactam conformationally constrained analogues of Pro-Leu-Gly-NH2.

A series of analogues of the potent analogue of Pro-Leu-Gly-NH2 (PLG), 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1-pyrrolidineacet amide (2) were synthesized in which the (R)-gamma-lactam residue of 2 was replaced with a (R)-beta-lactam, (R)-aminosuccinimide, (R)-cycloseryl, (R)-delta-lactam, (R)-epsilon-lactam, or (S)-epsilon-lactam residue to give analogues 3-8, respectively. These substitutions were made so as to vary the psi 2 torsion angle. The analogues were tested for their ability to enhance the binding of the dopamine receptor agonist ADTN to the dopamine receptor. Analogues 3-6 and 8 exhibited dose-response curves that were bell-shaped in nature with the maximum effect occurring at a concentration of 1 microM. Analogue 7 was inactive. Analogues 3 and 4 were found to be as effective as PLG, while analogues 5, 6, and 8 appeared to be more effective than PLG in terms of enhancing the binding of ADTN to dopamine receptors. The activity of analogues 3-6 and 8 with their psi 2 angles in the vicinity of that observed in a type II beta-turn is consistent with the hypothesis that this type of turn is the bioactive conformation of PLG.

Amino Acid Sequence↗
PubMed1992

Buried water in homologous serine proteases.

Buried water molecules in the structurally homologous family of eukaryotic serine proteases were examined to determine whether buried waters and their protein environments are conserved in these proteins. We found 16 equivalent water sites conserved in trypsin/ogen, chymotrypsin/ogen, elastase, kallikrein, thrombin, rat tonin and rat mast cell protease, and 5 additional water sites in enzymes which share the primary specificity of trypsin. Based on an alignment of 30 serine protease sequences, it appears that the protein environments of these 21 conserved buried waters are highly conserved. The protein environments of buried waters are comprised primarily of atoms from highly conserved residues or main chain atoms from nonconserved residues. In one instance, the protein environment of a water is conserved even in the presence of an unlikely Pro/Ala substitution. We also note 3 instances in which a histidine side chain substitutes for water, suggesting that the structural role of water at these sites is satisfied by the presence of an alternative hydrogen bonding partner. Buried waters appear to be integral structural components of these proteins and should be incorporated into protein structures predicted on the basis of sequence homology to this family, including the catalytic domains of coagulation proteases.

Animals↗
PubMed1987

Epilepsy-aphasia syndrome in children: an unusual presentation to psychiatry.

This paper describes the psychiatric and clinical manifestations of the epilepsy-aphasia syndrome which occurs in children. In 1957, Landau and Kleffner reported the development of receptive and expressive aphasia at 5 to 6 years of age, in six children with normal language development at that time. Since this first report, further accounts of acquired language disabilities associated with EEG abnormalities have appeared. However, the clinical syndrome remains ill defined and its pathophysiology is poorly understood. There are no reported cases of this syndrome presenting initially to psychiatry. This paper reports a child who presented to psychiatry with severe aggression associated with the clinical syndrome of epilepsy-aphasia. The discussion examines the relationships between the aggressive behavior and the EEG findings and aphasia.

Aphasia↗
PubMed1984

Anorexia nervosa associated with energy-wasting disorders.

Some patients with anorexia nervosa and energy-wasting disorders have been found to be able to use their illness to lose weight. This paper presents two patients with diabetes mellitus and one with ulcerative colitis in whom the illness was complicated by anorexia nervosa.

Adolescent↗
PubMed1978

Anorexia nervosa in boys.

The literature on primary anorexia nervosa in the male is reviewed and the case histories of 3 new patients are reported. Most surveys comment on the rarity of the syndrome in the male, with the sex ratio in the range of 1 in 10 to 1 in 20. The patients reported here had certain features in common. All the mothers and fathers were overweight, but obesity was marked only in the fathers, who also showed moderate to severe degrees of alcoholism. The mothers were oversensitive, insecure individuals, and the marriages suffered in proportion to the severity of the husband's alcoholism. Preoccupation with food was observed on home visits. There was overt mutual hostility between each father and anorexic son; the boys showed pronounced obsessional traits in their personalities. Dieting in order to ameliorate real or feared obesity was a first step in the development of the syndrome in each boy. In the past 3 years an equal number of boys and girls (new patients) have been referred for treatment in the psychiatric unit. Speculative reasons for this are discussed.

Adolescent↗
PubMedDate not supplied

Simulated dipeptide recognition by vancomycin.

The antimicrobial activity of vancomycin and related glycopeptide antibiotics is due to stereospecific recognition of polypeptide components in bacterial cell walls. To better understand how these antibiotics recognize polypeptide determinants, we have developed dynamic models of the complexes formed by the vancomycin aglycon and two different dipeptide ligands, Ac-D-ala-D-ala and Ac-D-ala-gly. Molecular dynamics simulations of the two complexes, initially conditioned with distance constraints derived from two-dimensional nuclear magnetic resonance (NMR) studies, are conformationally stable and propagate in a manner consistent with the NMR-derived constraints after the constraints are removed. Free energy calculations accurately predict the relative binding affinity of these two complexes and help validate the simulation models for detailed structural analysis. Although the two ligands adopt similar conformations when bound to the antibiotic, there are clear differences in the configuration of intermolecular hydrogen bonds, the overall shape of the antibiotic, and other structural features of the two complexes. This analysis illustrates how complex structural and dynamic factors interrelate and contribute to differences in binding affinity.

Anti-Bacterial Agents↗
PubMedDate not supplied

Encopresis in Hirschsprung's disease: a report on two cases.

Two patients with persistent severe encopresis after surgery for Hirschsprung's disease were treated with a token economy type of behavior modification therapy. After eight weeks there was very marked improvement, which persisted after discharge home without relapse after four and eight months respectively.

Behavior Therapy↗