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Biomedical subjects

R K Sharma

Publications and source records attributed to R K Sharma.

At least 433 records · Page 24Linked to original sources

On the mechanism of interaction between calmodulin and calmodulin-dependent proteins.

Molecular and kinetic studies of the interaction between calmodulin and calmodulin-dependent proteins have been reviewed. Several calmodulin-dependent proteins have been purified to homogeneity and characterized in terms of subunit structure in recent years. The results indicate that these proteins do not contain a common subunit as the basis of calmodulin binding. A monoclonal antibody capable of interacting with several calmodulin-dependent proteins has been obtained, suggesting that these proteins contain common structure. It seems that hybridoma technology may be used for probing calmodulin-binding domains in the calmodulin-dependent proteins. Using a fluorescent-labelled cyclic nucleotide phosphodiesterase, the interaction between calmodulin and the enzyme in the absence of Ca2+ can be demonstrated, and the equilibrium constant of the reaction can be determined. The study further defines the multiple interactions in the activation of the cyclic nucleotide phosphodiesterase by Ca2+ and calmodulin. Previous kinetic results along with the present results are summarized and used to elucidate the regulatory significance of the multiple Ca2+-binding of calmodulin.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Ionization processes of some harmala alkaloids.

The ionization and UV-visible spectral properties of some harmala alkaloids have been investigated spectrophotometrically. Harmaline and harmine were found to have pKa values of 9.55 +/- 0.04 and 7.45 +/- 0.03, respectively. The ionization of harmalol was characterized by two processes which could be spectrophotometrically isolated from one another, allowing pKa values of 8.62 +/- 0.15 and 11.30 +/- 0.23 to be determined. The lower of these was ascribed to the phenolic group and the higher to the enamino site. Support for this assignment lay in the yellow color (lambda max 433 nm) at intermediate pH values, which was typical of a formally neutral quinone-methide structure. For harmol, pKa values of 7.90 and 9.47, reported at 21 degrees by Perrin [N.Z.J. Sci. Technol. 388:688-694 (1957)], were reassigned with the lower value reflecting phenolic ionization, as opposed to the original literature assignment. Partition coefficients at pH 7.4 (n-heptane/water) were determined. The comparative pharmacology of these alkaloids is discussed and related to both their pKa values and the relative stability of the neutral quinone-methide structure.

Alkaloids↗

Polyamines inhibit the protein kinase 380--catalyzed phosphorylation of eukaryotic initiation factor 2 alpha.

Polyamines putrescine, spermidine, and spermine specifically inhibit the PK 380--catalyzed phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha). Since te PK 380--dependent phosphorylation of eIF-2 alpha inhibits the initiation or protein synthesis, the possibility exists that the polyamines enhance protein synthesis by inhibiting the phosphorylation of eIF-2 alpha by PK 380.

Adrenal Cortex↗

Spectrum of rapidly progressive (crescentic) glomerulonephritis in northern India.

36 consecutive patients whose biopsies showed significant extracapillary proliferation in the face of rapidly declining renal function were reviewed between 1967 and 1979. About 30% of the patients belonged to the pediatric age group with a male:female ratio of 2.5:1. Oliguria/anuria, hematuria, and progressive renal insufficiency were present in all cases. There was evidence of 9 cases being poststreptococcal, 2 SLE, 1 Henoch-Schönlein purpura, 2 possibly viral and 1 staphylococcal. Histologically, 29 cases had more than 60% crescents, 5 between 50 and 60% and 2 cases a little less than 50%. 28 cases were fatal in less than 10 months. 2 were lost of follow-up. 6 survivors with reversal of renal functions had 3 common factors to note, namely an antecedent disease, less crescents both in number and size, accompanied by fewer interstitial changes and early treatment. Rebiopsy in 2 survivors showed regression of histologic severity.

Adolescent↗

Relationship of calcium and membrane guanylate cyclase in adrenocorticotropin-induced steroidogenesis.

Chlorpromazine, when incubated with isolated adrenal cells, inhibited the ACTH-stimulated formation of cGMP and corticosterone production. It also inhibited the ACTH-stimulated membrane guanylate cyclase, but did not affect the binding of ACTH to the membrane receptors. cGMP-induced steroidogenesis was not affected by the drug. These data indicate that chlorpromazine interferes with adrenal steroid metabolism at a site between the hormone receptor and guanylate cyclase and also show that guanylate cyclase is composed of separate receptor and catalytic components. Furthermore, based on the premise that chlorpromazine exerts its inhibitory action by blocking the binding of a calcium receptor protein, such as calmodulin, to the receptor-coupled guanylate cyclase, it is proposed that the interaction of calcium, presumably through a calcium-binding protein, is essential for ACTH-dependent guanylate cyclase.

Adrenal Gland Neoplasms↗