Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 109 records · Page 6Linked to original sources

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

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↗

PubMed1991

Occupational health and the environment in an urban slum in India.

The Indo-Dutch Environmental & Sanitary Engineering Project under the Ganga action Plan in Kanpur and Mirzapur is being executed within the Indo-Dutch bilateral development cooperation framework. The project aims to integrate physical, social and health related improvements. It is expected that the development approach and methodology can be replicated in other urban settlements in India. The project is being supplemented by a training and institutional strengthening programme to facilitate the transfer of new technologies and improvement of operation and maintenance of the new facilities. The project is also aimed at the improvement of the living conditions of the population, by installing drinking water and drainage systems. A socio-economic unit in the project supports the technical interventions by enhancing the community to participate in project activities. The Occupational Health Programme in Jajmau, an industrial slum of Kanpur, aims to improve the working conditions of tannery workers. Four hundred and ninety-seven tannery workers and 80 employees not engaged in leather work, from 20 tanneries, were interviewed and underwent physical examination. The mean age of tannery workers was 32 years, about half of them recently migrated to Kanpur. The majority of the workers are illiterate, have temporary jobs and 85% have a monthly income between 300 and 600 Rs. Occupational morbidity was 28.2%. Regular meetings with tannery owners, the training of tannery workers in first aid, and support for the installation of safety and health councils in tanneries are the main programme activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Disappearance of a cerebral aneurysm--an unusual angiographic event.

Spontaneous thrombosis of cerebral aneurysms demonstrated by angiography is infrequent. This article describes angiographically documented spontaneous thrombosis of an intracranial aneurysm at the posterior cerebral-posterior communicating artery junction in a 40-year-old woman. The initial angiogram done on 16th day after an episode of subarachnoid haemorrhage showed a medium sized aneurysm. Subsequent angiograms done on 30th, 40th and 60th day failed to demonstrate the aneurysm. The factors leading to this rare event remain obscure.

Adult↗

PubMed1991

Metabolism of benzo[a]pyrene and persistence of DNA adducts in the brown bullhead (Ictalurus nebulosus).

1. The in vitro metabolism of [3H]benzo[a]pyrene (BP) and [14C]benzo[a]pyrene-7,8-dihydrodiol (BP-7,8-diol) by liver of brown bullhead (Ictalurus nebulosus) was characterized, as was the formation and persistence of BP-DNA adducts in vivo. 2. Compared to rat liver microsomes, bullhead liver microsomes produced relatively larger amounts of BP-7,8-diol (predominantly the [-] enantiomer) and smaller amounts of of BP-7,8-diol (predominantly the [-] enantiomer) and smaller amounts of BP-4,5-diol. 3. BP phase I metabolites were efficiently converted by freshly isolated bullhead hepatocytes to conjugates, predominantly glucuronides. 4. BP-7,8-diol was metabolized by hepatocytes 4-fold more rapidly than was BP and was converted to approximately equal amounts of glucuronides, glutathione conjugates and sulfates. 5. BP-DNA adducts formed in bullhead liver with a lag time of several days and maximum adduct formation at 25-30 days. The major adduct was anti-BPDE-deoxyguanosine.

Animals↗

PubMed1991

A new model of nephrolithiasis involving tubular dysfunction/injury.

To better understand the pathogenesis of nephrolithiasis, we developed a new animal model that closely mimics human calcium oxalate stone disease. Rats were treated with a regimen that combines moderate hyperoxaluria (produced by 10 days of feeding with 3% ammonium oxalate) with mild proximal tubular injury/dysfunction (produced by 8 daily injections of gentamicin sulfate -40 mg./kg.). This combined treatment caused a marked increase in the incidence of calcium oxalate crystals and stones over that seen in animals treated with oxalate or gentamicin alone. Using a semiquantitative scoring system for estimating the abundance of crystals in coronal sections of kidneys, we found that 63% of animals receiving gentamicin plus oxalate showed "moderate" numbers of crystal, as compared to 8% of animals receiving oxalate alone; and the majority of the crystals occurred in the papilla, a pattern similar to that seen in human stone disease. Untreated rats and rats treated with gentamicin alone did not exhibit calcium oxalate crystals or stones. Despite the abundance of crystals and stones, animals receiving gentamicin plus oxalate retained relatively normal renal function as judged by creatinine clearance. Thus, the model has several advantages over preexisting models of nephrolithiasis. Crystal and stone deposition develop rapidly (within 14 days). The pattern of deposition resembles that seen in human stone disease and renal function remains relatively normal. These findings indicate that this model of nephrolithiasis may prove useful for studies of the pathogenesis of stone disease. Moreover, they suggest that renal tubular injury and/or dysfunction may produce conditions conducive to the formation and growth of calcium oxalate stones.

Animals↗

PubMed1991

Oxalate transport in renal tubular cells from normal and stone-forming animals.

To investigate the cellular mechanism(s) underlying kidney stone disease, we examined oxalate uptake in suspensions of renal cortical and papillary cells derived from control and stone-forming animals. In control animals, both cortical and papillary cells exhibited a time-dependent accumulation of oxalate. This uptake was mediated both by passive diffusion and by one or more transport processes sensitive to the anion transport inhibitor, DIDS. Oxalate uptake was also markedly sensitive to extracellular pH, showing increased uptake at acidic pH outside (pHo) (6.0), and reduced uptake at alkaline pHo (8.0). In renal tubular cells from stone-forming animals, oxalate uptake was markedly altered. Uptake was significantly reduced in cortical cells, whereas it was significantly stimulated in papillary cells from the same animals. Since the observed changes in oxalate handling occurred only in stone-forming animals, it is possible that alterations in renal cell oxalate transport contribute to calcium oxalate stone formation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1991

Expression of growth factor receptors in human brain tumours.

The expression of the EGF receptor, c-erbB-2 and PDGF receptor proteins has been studied in a series of human brain tumour biopsies and cell lines. Western blotting was used to determine the amount of protein present and their intrinsic and ligand promoted enzyme activities were studied by immunoprecipitation followed by autophosphorylation. EGF receptors were found to be expressed at very high levels in 40% of primary tumour biopsies, but at uniformly low levels in tumour derived cell lines. The c-erbB-2 protein was not detected in tumour biopsies, but was present at variable, but low levels in extracts of tumour cell lines. PDGF receptors were also found at moderate to low levels in both primary tumours and cell lines. The EGF receptor gene was amplified in four out of 14 primary tumours and this generally correlated with high levels of protein expression. The c-erbB-2 gene was not amplified. Employing the polymerase chain reaction and sequence specific oligonucleotides as probes there was no evidence of mutations in the c-erbB-2 gene transmembrane region. These results suggest that alterations of expression of the EGF receptor may play a role in human brain tumours. There was however no evidence for aberrant expression of the c-erbB-2 protein. Additional experiments are required to assess the influence of PDGF receptor expression in brain tumour cells.

Brain Neoplasms↗

PubMed1991

Structural and dynamic aspects of non-intercalative (1:1) binding of a thiazole-lexitropsin to the decadeoxyribonucleotide d-[CGCAATTGCG]2: An 1H-NMR and molecular modeling study.

The location, orientation and dynamics of a thiazole-containing analogue of distamycin 1 bound to the decadeoxyribonucleotide d-[CGCAATTGCG]2 have been studied by non-exchangable and imino proton NMR resonances of the 1:1 complex. Using NOE difference, COSY and NOESY experiments, lexitropsin (1) was located in the minor groove of DNA at 5'-CAAT sequence. This was concluded by an intermolecular NOE between the ligand and a minor groove A4H2 proton. The NOE cross-correlations in the NOESY map confirmed that the DNA decamer duplex in the 1:1 complex remains in a right-handed B-conformation similar to that in the free decamer. Experiments on non-exchangeable and exchangeable proton NMR resonances placed the N-formylamino terminus of drug 1 on the 5'-C3 nucleotide, while the rest of the molecule extends onto the 5'-AAT sequence. The structural evidence for sequence preferential binding at 5'CAAT rather than 5'AATT suggests this reflects an attempt on the part of the sterically demanding inward directed sulfur of the thiazole to minimize compression by moving part of the molecule to the somewhat wider CG base site. The lack of evidence for a 2:1 drug:DNA complex, in contrast to distamycin, is in accord with this interpretation. The lexitropsin 1 was found to be in an exchange between the equivalent 5'-CAAT sites at a rate of approximately 35S-1 with a delta G degree of 65 +/- 5 kJ mol-1 at 303 K. The experimental data suggests a slide-swing mechanism for this exchange process.

Base Sequence↗