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Biomedical subjects

N Kumar

Publications and source records attributed to N Kumar.

At least 19 recordsLinked to original sources

Structure of RG-12561 dichloromethane solvate and a diastereomer.

(III): [4 alpha,6 beta(E)]-(+-)-6-(2-[2-(4-Fluoro-3-methylphenyl)- 4,4,6,6-tetramethyl-1-cyclohexen-1-yl]ethenyl)-4-hydroxytetrahy dro pyran-2-one (RG-12561) dichloromethane solvate, 2C24H31FO3.CH2-Cl2, Mr = 857.94, triclinic, Pl, a = 11.7413 (5), b = 13.0279 (5), c = 16.2332 (9) A, alpha = 99.456 (4), beta = 94.217 (4), gamma = 101.893 (4) degrees, V = 2381.9 (4) A3, Z = 4 [four molecules of (III)+two molecules of solvent per unit cell], Dx = 1.195 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 16.69 cm-1, F(000) = 912, T = 293 K, final R = 0.053, wR = 0.060 for 4031 reflections with I greater than 3 sigma(I). (IV): [4 beta,6 alpha(E)]-(+-)-6-(2-[2- (4-Fluoro-3-methylphenyl)-4,4,6,6-tetramethyl-1-cyclo-hexen-1-yl]e thenyl)-4- hydroxytetrahydropyran-2-one, C24H31FO3, Mr = 386.51, triclinic, Pl, a = 6.054 (2), b = 12.931 (2), c = 14.838 (3) A, alpha = 67.70 (2), beta = 85.75 (2), gamma = 82.85 (2) degrees, V = 1066.0 (8) A3, Z = 2, Dx = 1.203 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 6.86 cm-1, F(000) = 414, T = 293 K, final R = 0.073, wR = 0.081 for 1588 reflections with I greater than 3 sigma(I). (III) is a potent HMG-CoA reductase inhibitor and has the potential to function as a superior hypocholesterolemic agent; (IV) lacks this activity. (III) and (IV) have different conformations and molecular-model calculations suggest that crystal-packing effects are primarily responsible for the overall conformation of (IV). The principal intermolecular contacts are hydrogen bonds of the type O-H...O = C.

Anticholesteremic Agents

New surgical technique for type B aortic interruption.

Restoring continuity of the aortic arch in aortic interruption continues to be a problem in terms of both surgical technique and long-term results. We report here a surgical technique using the left subclavian artery along with an aberrant right subclavian artery to form a conduit in a patient with type B interruption, to reestablish aortic continuity.

Aorta, Thoracic

Sleep deprivation in human males and its effect on SCE rates in chromosomes--a preliminary study.

The present preliminary study on 5 healthy volunteers deprived of sleep for a day showed a considerable increase in sister-chromatid exchange (SCE) rate in the chromosomes after sleep deprivation. Although the rate of increase varied between the studied subjects, interestingly the 5% plasma from a volunteer with a statistically significant increase after sleep deprivation, when supplemented to cell cultures from an age-matched normal subject, induced high SCEs. This suggests the presence/absence of some factor(s) in plasma samples of subjects showing high SCEs after sleep deprivation, playing a role in the induction of high SCEs in normal cells exposed to the samples in vitro. The present study also suggests that there could be categories which may or may not respond to sleep deprivation with high SCE induction and their plasma supplemented to normal cell culture in turn may or may not induce high SCEs. Nevertheless, the pathophysiological role of high SCEs induced by sleep deprivation in some cases remains intriguing and unresolved and needs further extensive study.

Adult

Further characterization of interactions between gamete surface antigens of Plasmodium falciparum.

Target antigens of malaria transmission blocking immunity include a complex of 3 gamete surface proteins of 230-kDa and 48/45-kDa glycoproteins. Previous studies have shown that epitopes recognized by blocking antibodies are conformational (reduction sensitive) in nature. Studies were conducted to characterize the interactions between the target antigens and role of disulfide groups in the formation of the complex. Treatment of detergent extracts of gametes with chaotropic agents and extremes of pH resulted in dissociation of the complex. The interaction between the 3 proteins was also perturbed when the extract was incubated in the presence of antibodies against the 230-kDa protein but not against the 48/45-kDa doublet. Chemical modifications of disulfide and sulfhydryl groups in the target antigens, otherwise inaccessible either in the total extract or after phase separation in Triton X-114, required prior denaturation of antigens.

Animals

Total cavopulmonary connection for right ventricular endomyocardial fibrosis.

Endomyocardial fibrosis is an endemic problem in tropical countries and is characterised by ventricular cavity obliteration, decreased ventricular compliance, and atrioventricular valve regurgitation. We report on a patient with right ventricular endomyocardial fibrosis resulting in obliteration of the cavity and tricuspid regurgitation treated successfully by total cavopulmonary connection and exclusion of the right ventricle.

Adult

The structure of celiprolol.

The crystal structure and nuclear magnetic resonance (NMR) spectra and assignments of celiprolol, N'-[3-acetyl-4[3-[N-t-butylamino-2-hydroxypropoxy]phenyl]-N,N- diethylurea, are reported. Celiprolol crystallizes in the monoclinic space group, P2(1)/a, with a = 9.081(2), b = 13.800(4), and c = 17.471(5) A and beta = 95.04(2)degrees. Structure was solved by direct methods; structure refinement to R of 0.058. Intermolecular hydrogen-bonding in the crystal is discussed. The 1H, 13C, and two-dimensional (2D) NMR spectra of the hydrochloride have been obtained and definitive signal assignments made.

Adrenergic beta-Antagonists

The biological activity of 7 alpha-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone.

Based on the premise that testosterone, but not 7 alpha-methyl-androgens, is reduced at the 5 alpha-position in the prostate and seminal vesicles, the differential bioactivities of these androgens were investigated in castrated rats. The ability of 7 alpha-methyl-19-nortestosterone acetate (MENT) to increase the weights of ventral prostate and seminal vesicles of castrated rats was four times higher than that of testosterone, while its effect on the weights of bulbocavernosus plus levator ani muscles (muscle), was 10 times that of testosterone. MENT was also approximately 12 times more potent than testosterone in the suppression of serum gonadotropin levels. A dose of testosterone that maintains serum gonadotropin levels and muscle mass also maintains prostate and seminal vesicle weights in castrated rats. By contrast, a dose of MENT that maintains muscle and gonadotropins does not maintain prostate and seminal vesicles. The action of other 7 alpha-methylated androgens were similar to that of MENT. The importance of 5 alpha reductase in the differential action of testosterone and MENT on prostate was confirmed by using a 5 alpha-reductase inhibitor. The activity of testosterone was significantly suppressed in the ventral prostate and seminal vesicles but not on muscle by the 5 alpha-reductase inhibitor (N,N-diethyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide). The enzyme inhibitor, however, had no influence on the activity of MENT on either tissue. In contrast, cyproterone acetate, an antiandrogen that competitively binds to the androgen receptors, inhibited the action of MENT and of testosterone on the prostate as well as on the muscle. In conclusion, these observations show that 7 alpha-methylated androgens can maintain muscle mass and normal gonadotropin levels in androgen deficient rats without hyperstimulating the prostate. These findings suggest that 7 alpha-methylated androgens may offer some health benefits to men who require androgen treatment.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Financing long-term care: a practical mix of public and private.

Congress is considering proposals to improve its financing of long-term care. The key issue is whether it should support a social insurance program or a program targeted to a population group defined by income and assets. Social insurance is expensive, costing between $15 and $20 billion. For the most part, it provides benefits--primarily asset protection--to middle- and upper-income individuals. An improved Medicaid program, costing about $8 billion, benefits lower-income individuals but does not protect those with higher incomes. These two options cannot be viewed independently from trends in the private market. Sales of private long-term care policies have grown and between 30 percent and 40 percent of the elderly can be considered potential buyers. If private alternatives are available for those individuals who need asset protection, the case for a more targeted public approach--along with reliance on the private sector--becomes more compelling. Congress should consider a program that enhances Medicaid; improves consumer education; assists states in regulating long-term care policies, so as to enhance consumer protection and confidence; and clarifies taxes on long-term care insurance to encourage workers and the elderly to protect themselves against catastrophic expenses.

Aged

Recognition of Plasmodium falciparum asexual stage antigens by antibodies in sera from people exposed to Plasmodium vivax.

An analysis of Plasmodium falciparum antigen-specific antibodies was performed on 44 serum samples from Guatemala, a region endemic for P. vivax. Most sera showed positive reactivity to P. falciparum asexual stage antigens by indirect immunofluorescent assay, enzyme-linked immunosorbent assay, and immunoprecipitation analysis using biosynthetically labeled parasites. Although several antigens were recognized by these sera, proteins with molecular weights of 195 kD, 140 kD, and in the range of 70-80 kD were strongly recognized by many of the sera studied. No such reactivity was observed for any of the surface antigens in the male and female gametes and zygotes of P. falciparum. These studies suggest that P. vivax and P. falciparum, two major human parasites, may share certain epitopes in several antigens of immunologic significance.

Adolescent

Interrelationship between ovine follicular fluid inhibin and serum albumin.

Ovine follicular fluid inhibin (oFF-I) as isolated in this laboratory, proved to be a monomeric protein (M(r).65 kDa). It was found to share very many of the physico-chemical characteristics of ovine serum albumin (oSA)-such as molecular size, iso-electric point, N-terminal aminoacid, finger-print patterns following enzymatic or cyanogen bromide cleavage, as well as binding of estradiol-17 beta and tryptophan. Furthermore, an antiserum containing polyclonal antibodies to oSA showed perfect cross-reaction with oFF-I. Nevertheless, oFF-I is distinct and different from oSA, as would be evident from the data reported here. Of the two proteins, oFF-I alone is capable of suppressing pituitary FSH output in a dose-dependent manner. Secondly, an antiserum containing polyclonal antibodies against Fraction-S2, a partially purified, biologically active fragment (M(r): 30-40 kDa)-derived from oFF-I, cross-reacted with the 65 kDa inhibin, but did not recognize oSA. Finally, the CD-spectra of the two proteins, when examined as a function of pH, show characteristic differences.

Animals

Solitary rectal ulcer syndrome.

Solitary rectal ulcer syndrome (SRUS) clinically presents with rectal bleed. Twenty three cases of SRUS are described highlighting that it is a distinct clinicopathological entity which can be diagnosed in the presence of typical clinical features, sigmoidoscopic findings and histopathological appearance of mucosal biopsy.

Adolescent