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K Namboodiri

Publications and source records attributed to K Namboodiri.

At least 19 recordsLinked to original sources
PubMed1997

Decavanadate possesses alpha-adrenergic agonist activity and a structural motif common with trans-beta form of noradrenaline.

Decavanadate, an inorganic polymer of vanadate, produced contraction of rat aortic rings at a relatively high concentration compared to phenylephrine, an agonist of alpha-adrenergic receptor. This effect was blocked by two known alpha-adrenergic receptor antagonists, prazosin and phenoxybenzamine. Decavanadate, formed by possible dimerization of V5 under acid conditions, possessed a structural feature of two pairs of unshared oxygen atoms at a distance of 3.12 A, not found in its constituents of V4 or V5. A structural motif of O..O..O using such oxygen atoms is recognized in decavanadate. This matches with a similar motif of N..O..O that uses the essential amino and hydroxyl groups of the side-chain and the m-hydroxyl group in trans-beta form of noradrenaline. The interaction of such a structural motif with the membrane receptor is likely to be the basis of the unusual noradrenaline-mimic action of decavanadate.

Adrenergic alpha-Agonists↗
PubMed1994

Calcium ionophore, A23187 and its amino acid complexes: spectroscopic and molecular modeling studies.

The circular dichroism, fluorescence, Nuclear Magnetic Resonance and BLM conductance studies indicate that A23187 forms a stable complex with amino acids at low ionophore concentrations (< 10(-4)M). However, A23187 prefers to be in a dimeric structure with no significant binding to amino acids, at concentrations higher than 10(-4)M. It was also observed that at lower concentrations, at which the amino acids bind to the ionophore, the affinity for calcium ions was several orders of magnitude lower than that at higher ionophore concentrations. We have also conducted molecular modeling studies to examine the structure of the A23187 dimer and its amino acid complexes. The results of these modeling studies strongly support our experimental results and validate the formation of a hydrogen bonded and energetically stable A23187 dimer and its amino acid complexes.

Amino Acids↗
PubMed1991

PRENRL_3D: a computer program for an automatic creation of NRL_3D, protein sequence-structure database, from the Protein Data Bank.

Recently, we have developed a sequence-structure database of protein information, NRL_3D, that is extracted from the Protein Data Bank (PDB) of the Brookhaven National Laboratory. NRL_3D provides a vehicle for the retrieval of the three-dimensional coordinates of protein fragments as identified by sequence properties. These data are formulated to allow access by standard sequence analysis programs such as those provided by the Protein Identification Resource (PIR). Because the PDB is updated four times per year, semimanual construction of NRL_3D in coordination with these updates becomes a time-consuming and inefficient task. Hence, we have developed a computer program (PRENRL_3D) in the "C" computer language that automatically extracts NRL_3D from the PDB. Although the program was developed in a VAX/VMS environment, care was taken to ensure its portability to other computer systems. Customized versions of the NRL_3D database can be created from the PDB entry files using various options available in PRENRL_3D, such as selection of entries determined at high resolution and with low R-value. The program has been developed modularly and it contains a number of generalized procedures for manipulating various information in the PDB.

Amino Acid Sequence↗
PubMed1990

Novel [(diazomethyl)carbonyl]-1,2,3,4-tetrahydronaphthalene derivatives as potential photoaffinity ligands for the 5-HT1A receptor.

The photolabile (diazomethyl)carbonyl function was introduced into the 8-position of 2-(N,N-di-n-propyl-amino)-1,2,3,4-tetrahydronaphthalene in three ways, resulting in the ether 8-[[(diazomethyl)carbonyl]methoxy]-2-(N,N-di-n-propylamino)-1,2,3,4- tetrahydronaphthalene (2), the ester 8-(diazoacetoxy)-2-(N,N-di-n-propyl-amino)-1,2,3,4- tetrahydronaphthalene (3), and the ketone 8-[(diazomethyl)carbonyl]-2-(N,N-di-n-propylamino)- 1,2,3,4-tetrahydronaphthalene (4). Specific binding of these compounds at the 5-hydroxytryptamine1A sites in rat brain membranes labeled with 1 nM [3H]-8-hydroxy-2-(N,N-di-n-propylamino)- 1,2,3,4-tetrahydronaphthalene (8-OH-DPAT) showed IC50 values of ca. 75, 125, and 25 nM, respectively, for the three compounds. Photolysis of methanolic solutions of 2-4 in the absence of receptor proteins lead in each case to an abundance of Wolff-rearranged products. In the case of ether 2, subsequent beta-elimination to 8-OH-DPAT removed this compound from serious consideration as a photoaffinity ligand. Ester 3 and ketone 4 were photolysed in vitro. Whereas ester 3 was ineffective in decreasing the specific binding of [3H]-8-OH-DPAT, ketone 4 decreased 40% of the specific binding of [3H]-8-OH-DPAT in the presence (but not the absence) of ultraviolet light. Thus this ketone emerges from these studies as a good candidate for a photoaffinity label for the 5-hydroxytrypatamine1A receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

NRL-3D: a sequence-structure database derived from the protein data bank (PDB) and searchable within the PIR environment.

The protein identification resource (PIR) and the Brookhaven National Laboratory protein data bank (PDB) are well-known databases for primary sequences and three-dimensional structures of proteins, respectively. Lesk et al, have compared the primary sequences in these two databases and concluded that the sequences in them are not redundant. Moreover, PIR programs can not be used directly on PDB files to access primary sequences because the FORMATS of these two data bases are different. We have developed a sequence-structure database, called NRL-3D, from the sequences, chain identification and the residue numbers of proteins in the PDB. This new database is designed such that it can be used in conjunction with PIR programs to search and extract sequences of interest and the corresponding three-dimensional coordinates from the structures in PDB.

Amino Acid Sequence↗
PubMed1987

Toward a unified approach to expounding demographic indices.

"Based on the notion that duration of occupancy of a demographic state is a random variable and defining demographic behaviours in terms of hazard rates or transitional intensities, this review paper shows that a framework of piecewise exponentials can provide a unified approach in expounding demographic indices." The primary focus is on mortality.

Behavior↗
PubMed1984

The Collaborative Lipid Research Clinics Program Family Study: detection of major genes influencing lipid levels by examination of heterogeneity of familial variances.

Age, sex-adjusted, and transformed lipid and lipoprotein data on over 1,200 white North American sibships in the Collaborative Lipid Research Clinics Family Study were analyzed for possible major genes causing high or low levels of these traits. The sibships were stratified on the basis of parents' trait values, and within-sibship variance in the high (or low) families was compared to that in the normal families via an F-test. The null hypothesis of multifactorial transmission was strongly rejected for low LDL, low total cholesterol, and high HDL families. An analysis of spouse-pair variance gave similar results. This may reflect the presence of dominant genes for hyperalpha- and hypobetalipoproteinemia. There was weaker evidence for single genes causing hyperbetalipoproteinemia. There was no evidence for major genes influencing triglyceride levels. Methodological issues with significant bearing on these results and those of other studies are discussed.

Biometry↗
PubMed1983

Familial aggregation of lipids and lipoproteins and early identification of dyslipoproteinemia. The Collaborative Lipid Research Clinics Family Study.

We examined the hypothesis that familial aggregation of lipids and lipoproteins facilitates within-family identification and hyperlipoproteinemia. We studied 841 offspring and 1,236 siblings of normocholesterolemic probands, 833 offspring and 1,194 siblings of hypercholesterolemic probands, 806 offspring and 1,099 siblings of normotriglyceridemic probands, and 877 offspring and 1,108 siblings of hypertriglyceridemic probands in the Lipid Research Clinics Collaborative Family Study Program. As the categorization of probands' hypercholesterolemia or hypertriglyceridemia increased from sporadic, to persistent, to severe, the percentage of hypercholesterolemic or hypertriglyceridemic offspring and siblings increased. Close sibling and parent-offspring lipid and lipoprotein risk factor associations in hypercholesterolemic and hypertriglyceridemic family units during and after the period of shared common-household environment facilitate within-family identification of dyslipoproteinemia and suggest potential sharing of coronary heart disease risk.

Cholesterol↗
PubMed1981

Genetic transmission of serum IgE Levels.

Genetic aspects of IgE levels were studied in three large pedigrees, many of whose members had atopic sensitivities to ragweed. Data on 184 persons (80 M, 104 F) were analyzed by the methods of Elston and Stewart after logarithmic transformation and appropriate adjustment for sex and age effects. Several modes of transmission were fitted to the data. The environmental model (of equal transmission frequency for all genotypes) clearly did not fit the data (chi 2 23.03, df 3); this suggested a strong hereditary involvement in IgE distribution. High IgE levels being determined by a dominant allele gave the best fit among the hypotheses examined in pooled data. Under a pure polygenic model, the estimated heritability was 49.5%. Using a mixed model of major gene and polygenic transmission (in an analysis which approximates, but is biased toward inflating the major gene component) polygenic inheritance was found to be 11%, but has no significant improvement over the major gene model. When families are analyzed separately, there was evidence of significant heterogeneity among families. The genetic picture was blurred, with one family favoring recessive inheritance of high IgE levels, one with no clear mode, and the third leaning slightly in favor of dominant inheritance. This suggests that the mechanism is not as simple as was thought and that there may be either two alleles or one gene involved in the determination of IgE levels. The findings are consistent with IgE levels being genetically determined with heritability estimated to be about 50%.

Adolescent↗
PubMed1980

A family with hereditary ataxia: HLA typing.

In a previously unreported family with olivopontocerebellar atrophy, the kindred contained over 600 individuals in five generations. Of 83 offsping of affected individuals who over over 38.8 years of age (the mean age of the onset of disease in this family), 47 had ataxia; there was autosomal dominant transmission. Clinical findings included lower bulbar palsies, hyperreflexia, ataxia, incoordination, scanning and explosive speech, and, in some, slow motor-nerve conduction velocities. There was cortical and cerebellar atrophy of pontine nuclei, inferior olives, and XII nuclei, and loss of Purkinje cells in the cerebellum. Seventy-three individuals of the III and IV generations were typed for HLA histocompatibility antigens. A maximum lod score of 1.97 was found at male recombination fraction 0.18 and female recombination fraction 0.36. When the lod score values reported in other studies were combined with the values in this family, the maximum lod score was found to be 4.681 at a recombination frequency of 0.22.

Adult↗