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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,585 records · Page 88Linked to original sources
PubMed1991

Evidence for domain organization within the 61-kDa calmodulin-dependent cyclic nucleotide phosphodiesterase from bovine brain.

The complete amino acid sequence of the 61-kDa calmodulin-dependent, cyclic nucleotide phosphodiesterase (CaM-PDE) from bovine brain has been determined. The native protein is a homodimer of N alpha-acetylated, 529-residue polypeptide chains, each of which has a calculated molecular weight of 60,755. The structural organization of this CaM-PDE has been investigated with use of limited proteolysis and synthetic peptide analogues. A site capable of interacting with CaM has been identified, and the position of the catalytic domain has been mapped. A fully active, CaM-independent fragment (Mr = 36,000), produced by limited tryptic cleavage in the absence of CaM, represents a functional catalytic domain. N-Terminal sequence and size indicate that this 36-kDa fragment is comprised of residues 136 to approximately 450 of the CaM-PDE. This catalytic domain encompasses a approximately 250 residue sequence that is conserved among PDE isozymes of diverse size, phylogeny, and function. CaM-PDE and its PDE homologues comprise a unique family of proteins, each having a catalytic domain that evolved from a common progenitor. A search of the sequence for potential CaM-binding sites revealed only one 15-residue segment with both a net positive charge and the ability to form an amphiphilic alpha-helix. Peptide analogues that include this amphiphilic segment were synthesized. Each was found to inhibit the CaM-dependent activation of the enzyme and to bind directly to CaM with high affinity in a calcium-dependent manner. This site is among the sequences cleaved from a 45-kDa chymotryptic fragment that has the complete catalytic domain but no longer binds CaM. These results indicate that residues located between position 23 and 41 of the native enzyme contribute significantly to the binding of CaM although the involvement of residues from additional sites is not excluded.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Amino acid sequence of nitrite reductase: a copper protein from Achromobacter cycloclastes.

The amino acid sequence of the copper-containing nitrite reductase (EC 1.7.99.3) from Achromobacter cycloclastes strain IAM 1013 has been determined by using peptides derived from digestion with Achromobacter protease I (Lys), Staphylococcus aureus V8 protease (Glu), cyanogen bromide, and BNPS-skatole in acetic acid. The subunit contains 340 amino acids. The identity of the first seven amino acids is tentative. The sequence has been instrumental in the X-ray structure determination of this molecule; in conjunction with the X-ray structure, ligands to a type I copper atom and a type II copper atom (one of each per subunit) have been identified. Comparison of the sequence to those of multi-copper oxidases such as ascorbate oxidase, laccase, and ceruloplasmin [Messerschmidt, A., & Huber, R. (1990) Eur. J. Biochem. 187, 341-352] reveals that each of two domains seen in the X-ray structure is similar to the oxidases and also to the small blue copper-containing proteins such as plastocyanin. The combination of sequence and structural similarity to ascorbate oxidase and sequence similarity to ceruloplasmin leads to a plausible model for the domain structure of ceruloplasmin.

Alcaligenes↗
PubMed1991

Adenine photodimerization in deoxyadenylate sequences: elucidation of the mechanism through structural studies of a major d(ApA) photoproduct.

The mechanism of the photodimerization of adjacent adenine bases on the same strand of DNA has been elucidated by determining the structure of one of the two major photoproducts that are formed by UV irradiation of the deoxydinucleoside monophosphate d(ApA). The photoproduct, denoted d(ApA)*, corresponds to a species of adenine photodimer first described by Pörschke (Pörschke, D. (1973) J.Am.Chem.Soc. 95, 8440-8446). From a detailed examination of its chemical and spectroscopic properties, including comparisons with the model compound N-cyano-N1-(1-methylimidazol-5-yl)formamidine, it is deduced that d(ApA)* contains a deoxyadenosine unit covalently linked through its C(8) position to C(4) of an imidazole N(1) deoxyribonucleoside moiety bearing an N-cyanoformamidino substituent at C(5). On treatment with acid, d(ApA)* is degraded with high specificity to 8-(5-amino-imidazol-4-yl)adenine whose identity has been confirmed by independent chemical synthesis. It is concluded that the primary event in adenine photodimerization entails photoaddition of the N(7)-C(8) double bond of the 5'-adenine across the C(6) and C(5) positions of the 3'-adenine. The azetidine species thus generated acts as a common precursor to both types of d(ApA) photoproduct which are formed from it by competing modes of azetidine ring fission.

Adenine↗
PubMed1991

Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein.

The circumsporozoite (CS) protein has been the target for development of malaria sporozoite vaccines for a decade. However, immunization with subunit vaccines based on the CS protein has never given the complete protection found after immunization with irradiated sporozoites. BALB/c mice immunized with irradiated Plasmodium yoelii sporozoites produced antibodies and cytotoxic T cells against a 140-kilodalton protein, sporozoite surface protein 2 (SSP2). Mice immunized with P815 cells that had been transfected with either SSP2 or CS genes were partially protected, and those immunized with a mixture of SSP2 and CS transfectants were completely protected against malaria. These studies emphasize the importance of vaccine delivery systems in achieving protection and define a multi-antigen sporozoite vaccine.

Animals↗
PubMed1991

Water supplementation in exclusively breastfed infants during summer in the tropics.

This study was designed to determine the need for water supplementation to maintain water homoeostasis in exclusively breastfed infants during summer in a tropical country. A prestudy questionnaire revealed that 97% of 34 nurses and 63% of 70 doctors advocated such supplementation. 45 healthy, male, exclusively breastfed babies, aged 1-4 months, were recruited from a well-baby clinic. 9 who had never received supplemental water plus a random selection of 14 others were allocated to group I (breastmilk only); the remaining 22 infants were allocated to group II (breastmilk plus supplemental fluid according to the mother's usual practice). The babies were studied at the hospital for 8 h; breastmilk intake was measured by weighing the infant before and after each feed, water intake by calibrated bottles, and urine output by accurate collection and measurement. The maximum room temperatures were 34-41 degrees C and relative humidities 9-60% (below 50% in all but 3 infants). In group II the mean water intake was 11% (95% confidence interval 7-16%) of the total fluid intake. Both breastmilk intake (274 vs 210 ml) and total fluid intake (274 vs 233 ml) were higher in group I than in group II (p = 0.003, p = 0.073, respectively), after adjustment for age, weight, length, room temperature, and humidity. However, there were no significant differences between the groups in urine output, urine or serum osmolality, weight change, or rectal temperature whether or not the factors adjusted for included total fluid intake. Thus, exclusively breastfed infants do not need supplemental water to maintain water homoeostasis; a reduced breastmilk intake is a potential disadvantage of this practice.

Attitude of Health Personnel↗
PubMed1991

Recoverin: a calcium sensitive activator of retinal rod guanylate cyclase.

Vertebrate retinal photoreceptors recover from photoexcitation-induced hydrolysis of guanosine 3', 5'-monophosphate (cyclic GMP) by resynthesizing cyclic GMP, which reopens cation channels that have been closed by light. Activation of guanylate cyclase by light-induced depletion of cytosolic calcium is a key event in this recovery process. This cyclase has now been shown to be regulated by a 23-kilodalton calcium binding protein. The protein is present in both rod and cone photoreceptors and was named recoverin because it promotes recovery of the dark state. The amino acid sequence of recoverin exhibits three potential calcium binding sites (EF hands). That recoverin binds calcium was confirmed with calcium-45 and by observing calcium-induced changes in its tryptophan fluorescence. Recoverin activated guanylate cyclase when free calcium was lowered from 450 to 40 nM, an effect that was blocked by an antibody to recoverin. Thus, guanylate cyclase in retinal rods is stimulated during recovery by the calcium-free form of recoverin. A comparison of recoverin with other calcium binding proteins reveals that it may represent, along with the protein visinin, a family of proteins that are regulated by submicromolar calcium concentrations.

Amino Acid Sequence↗
PubMed1991

Rat mast cell carboxypeptidase: amino acid sequence and evidence of enzyme activity within mast cell granules.

The amino acid sequence of rat mast cell carboxypeptidase has been determined. The major form has 308 residues; a minor form has an additional (glutamyl) residue at the amino terminus that may indicate an alternate cleavage site during zymogen activation. The enzyme is homologous to pancreatic carboxypeptidases A and B, with conservation of the functional amino acid residues of the active site. The putative substrate binding site resembles that of carboxypeptidase A, although other structural features bear more similarity to carboxypeptidase B. Mast cell carboxypeptidase retains enzymatic activity toward a peptide substrate (angiotensin I) while bound within the granular matrix of the rat connective tissue mast cells. Evidence is presented to suggest that a cluster of positively charged lysyl and arginyl residues binds the enzyme to the negatively charged heparin of the granular matrix but leaves the active site exposed to bind and cleave peptide substrates.

Amino Acid Sequence↗
PubMed1991

Comparison of lisinopril versus atenolol for mild to moderate essential hypertension.

The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension. After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol. Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. No important changes in hematologic and biochemical profiles were seen with either drug. Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group. Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension.

Antihypertensive Agents↗
PubMed1991

Genetic linkage studies of autosomal dominant polycystic kidney disease: search for the second gene in a large Sicilian family.

Polycystic kidney disease (PKD) is a common autosomal dominant genetic disorder caused by mutation in at least two different gene loci. The PKD1 gene has been localized on the short arm of chromosome 16. The location of a second genetic locus in the human genome is not yet known. A large PKD kindred, unlinked to chromosome 16, with over 250 members was studied using both DNA and classical markers. In total, 29 informative marker loci on 11 autosomes have been analyzed for linkage with PKD. The data significantly exclude the linkage with disease locus from 17 marker loci and show no evidence of close linkage with the other loci.

Female↗
PubMed1991

Which 3-ribofuranosyl-substituted purine 5'-phosphates undergo template-directed oligomerization?

We have studied the oligomerization reactions of the 2-methylimidazolide derivatives of 3-isoisoguanosine 5'-phosphate (2) and 3-isoxanthosine 5'-phosphate (5) in the presence of a variety of homopolynucleotide templates. In no case did we observe a substantial template-facilitated production of long oligomers. Polyuridylic acid directed the synthesis of low molecular-weight products from both monomers. Polycytidylic acid, polyadenylic acid, polyinosinic acid, and polyguanylic acid were ineffective as templates in the systems that we investigated.

Chromatography, High Pressure Liquid↗
PubMed1991

Effect of automobile exhaust on the distribution of trace elements and its modulation following Fe, Cu, and Zn supplementation.

The effect of automobile exhaust on the distribution of trace elements with special reference to Pb and its modulation following Cu, Zn, and Fe supplementation, in mouse organs, has been studied using Energy Dispersive X-ray Fluorescence technique. Seven elements, namely K, Fe, Cu, Zn, Br, Rb, and Pb, were detected in all the organs. The maximum concentration of Pb was found in lungs followed by that in liver and kidney. The effect of automobile exhaust was found to be significant on the concentrations of Fe and Pb; their concentrations were found to increase in all the organs. However, the concentrations of Cu and Zn were found to be decreased significantly in the liver. In the animals given Fe, Cu, or Zn supplementation along with motor exhaust, the percentage change in the concentration of Pb in lungs was decreased, and that of Fe was increased significantly. In kidney, no significant change was observed for the animals given Cu and Zn, whereas for animals given Fe, the level of Pb decreased significantly. In liver, the reduction in the level of Zn in the exhaust-exposed animals was made up and the level of Pb was reduced following Zn supplementation. These results clearly indicate that Fe and Zn play an important role in Pb metabolism and tend to lower the absorption of Pb. The effect of Fe is more pronounced than that of Zn, whereas the effect of Cu seems to be insignificant.

Administration, Inhalation↗
PubMed1991

Arm lift strength in work space.

This study was conducted to determine arm strength values for isometric and isokinetic efforts around the human trunk. Thirty-eight normal young adults (20 male and 18 female) performed a total of 19 tasks. These consisted of one self-selected optimum posture with upright stance and elbows bent at 90 degrees , designated as standard posture for isometric test. In addition, isometric testing was done sagittally symmetrical 30 degrees and 60 degrees lateral planes at half-, three-quarters- and full-reach distances at knuckle height. The isokinetic tests were done between knuckle height and shoulder height in postures identical to isometric tests. The sequence of these tasks was randomised. The peak strength in standard posture was invariably lower than the peak strength at half-reach in isometric condition in all three planes for both sexes with the exception of one condition among females (60 degrees lateral plane, half-reach isometric). Peak and average arm lift strengths of males were significantly higher than those of females (p < 0.01) and ranged between 44% and 71%. For both sexes isometric strength was significantly higher than isokinetic strength (p < 0.01). The peak and average strengths in the sagittal plane were invariably higher than those of asymmetric postures, with one exception among females. With increasing reach distance the strength declined significantly for all conditions among both genders (p < 0.01). The ANOVA showed that the gender, mode of lifting, postural symmetry and reach of lifting, in addition to affecting the peak and average strength individually (p < 0.01), had significant 2-way and 3-way interactions (p < 0.01). All strength values were inter-correlated (p < 0.01). The regressions predicting peak and average strengths from anthropometric characteristics and sagittal plane strengths accounted for 63% to 89% of all variance and were highly significant (p < 0.01).

Journal Article↗
PubMed1991

Interaction of bovine neutrophils in Pasteurella haemolytica mediated damage to pulmonary endothelial cells.

The purpose of these studies was to determine mechanisms of pulmonary tissue damage mediated by Pasteurella haemolytica and interaction with bovine neutrophils. Bovine pulmonary artery endothelial cell monolayers were treated with various combinations of P. haemolytica factors including bacterial culture supernatant (CS) and purified LPS, with and without bovine neutrophils. Damage to endothelial cells was monitored by 51Cr release, cell detachment rate, and morphological changes. At 5 h post-treatment (PT) bacterial factors produced very little toxic change in cells, however, by 22 h PT both crude leukotoxin and LPS caused high levels of cytotoxicity and detachment. Neutrophils did not augment toxicity mediated by LPS, but actually protected endothelial cells from low levels of LPS. When the LPS component of CS was neutralized with polymyxin B, leukotoxin mediated neutrophil killing resulted in extensive endothelial cell damage. These results suggest that LPS may directly injure endothelial cells and this toxic effect may be reduced by neutrophils. However, neutrophil killing by leukotoxin may also contribute to endothelial cell damage in the absence of LPS.

Animals↗
PubMed1991

Semmes-Weinstein monofilaments: a simple, effective and inexpensive screening device for identifying diabetic patients at risk of foot ulceration.

Both vibration perception threshold (VPT) by biothesiometry and pressure perception using Semmes-Weinstein monofilaments (filaments) have been proposed to identify diabetic patients at risk of foot ulceration. The two methods were compared in 182 subjects attending a national patients conference. Both measures were made over the great toe. Filaments of three calibres were used: 4.17, 5.07 and 6.10 bending with 1, 10 and 75 g force, respectively. Pressure perception was normal (4.17) in 122 patients (group 1) whereas in 45 patients it was grade 5.07 (group 2) and 6.10 or greater in 15 (group 3). The corresponding mean VPT (+/- SD) for the three groups were 10.6 (+/- 6.7), 22.8 (+/- 12.7) and 32 (+/- 14.3), respectively. The mean VPT for the 3 groups were significantly different (P less than 0.001). The filaments were more sensitive (100%) but less specific (77.7%) in identifying patients who had foot ulcers compared to biothesiometry which was less sensitive (78.6%) but more specific (93.4%). The filaments are therefore reliable and may be superior to biothesiometry in screening for patients at risk of foot ulceration since sensitivity is the more important parameter. In addition, they are inexpensive (12 pounds) compared to the biothesiometer (400 pounds) and are simple and easy to use.

Adult↗