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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 703 records · Page 39Linked to original sources
PubMed1996

Lipid prodrugs of phosphonoacids: greatly enhanced antiviral activity of 1-O-octadecyl-sn-glycero-3-phosphonoformate in HIV-1, HSV-1 and HCMV-infected cells, in vitro.

Phosphonoformate (PFA) effectively inhibits viral polymerases but is relatively ineffective in virus-infected cells in tissue culture. A lipid prodrug of phosphonoformate was synthesized by coupling the phosphonate residue of phosphonoformate to the sn-3 hydroxyl of 1-O-octadecyl-sn-glycerol. This prodrug, 1-O-octadecyl-sn-glycero-3-phosphonoformate (ODG-PFA), was 93-fold more active than phosphonoformate in cells infected with the AD169 strain of cytomegalovirus (CMV), and 111-147-fold more active in cells infected with three human clinical isolates of CMV. The compound was also 44-fold more active in human immunodeficiency virus-1 (HIV-1) infected cells and 43-fold more active in cells infected with herpes simplex virus (HSV). Studies of the mechanisms of increased antiviral activity indicate that 1-O-octadecyl-sn-glycero-3-[14C]phosphonoformate is taken up more extensively than the free drug by the host MRC-5 human lung fibroblasts. Intracellular enzymes convert 1-O-octadecyl-sn-glycero-3-phosphonoformate to phosphonoformate. This conversion does not occur in the tissue culture medium containing fetal bovine serum (FBS) or in MRC-5-conditioned medium. In view of its greatly increased in vitro potency and selectivity, 1-O-octadecyl-sn-glycero-3-phosphonoformate may be useful in treating viral diseases.

Anti-HIV Agents↗
PubMed1996

Doramectin systemic activity against cattle grubs, Hypoderma lineatum and H. bovis (Diptera: Oestridae), and cattle lice, bovicola bovis (Mallophaga: Trichodectidae), Linognathus vituli and Solenopotes capillatus (Anoplura: Linognathidae), and Haematopinus eurysternus (Anoplura: Haematopinidae), in Wyoming.

Seven individual trials were conducted in Wyoming to evaluate the therapeutic efficacy of doramectin administered subcutaneously at a dosage of 200 micrograms kg-1 against multiple, natural infestations of cattle grubs or cattle lice. Insect species present and the number of trials that included each species were: Hypoderma lineatum, 2; Hypoderma bovis. 1; Bovicola bovis, 5; Haematopinus eurysternus, 1; Linognathus vituli, 5; and Solenopotes capillatus, 3. Examinations for lice were performed prior to treatment and either weekly or bi-weekly thereafter for 28 days. Examinations for cattle warbles were performed either weekly or every 4 to 5 weeks from time of first appearance through last appearance in the backs of the cattle. No H. lineatum, H. bovis, H. eurysternus, L. vituli, or S. capillatus were found on doramectin-treated animals at any time following treatment. By 28 days following treatment, the number of B. bovis was reduced between 58 and 98%. Treatments applied later in the season, i.e. in March, were more efficacious against B. bovis than those applied in January or February.

Animals↗
PubMed1996

Global aphasia due to thalamic hemorrhage: a case report and review of the literature.

A 55-year-old patient was admitted with weakness in the right extremities and with significant language deficits. Both computed tomography (CT) and positron-emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose were done within 1 month and repeated at 10 months after onset. Language evaluation was done using parts of the Western Aphasia Battery (WAB) and the Boston Diagnostic Aphasia Examination (BDAE) at 1 month after admission, at 3 months, and at 10 months. The initial CT scan revealed hemorrhage in the left thalamus with edema surrounding the hemorrhage. A follow-up CT scan after 10 months showed an old hemorrhage in the left thalamus with no new lesions. The initial PET scan revealed hypometabolism in the left thalamus, and a repeat PET scan at 10 months showed reduced uptake in the left frontal, left parietal, and left temporal cortex. An initial language evaluation showed impaired auditory and reading comprehension, poor verbal expression, impaired repetition, and difficulty with naming and with sentence completion. The patient was diagnosed with global aphasia. Follow-up language evaluation at 3 months and 10 months showed only minimal improvement in his communication. Global aphasia due to lesions in the thalamic region is rare and the prognosis is poor.

Aphasia↗
PubMed1996

Modulating L-type calcium current affects discontinuous cardiac action potential conduction.

We have used pairs of cardiac cells (i.e., one real guinea pig ventricular cell and a real-time simulation of a numerical model of a guinea pig ventricular cell) to evaluate the effects on action potential conduction of a variable coupling conductance in combination with agents that either increase or decrease the magnitude of the L-type calcium current. For the cell pairs studied, we applied a direct repetitive stimulation to the real cell, making it the "leader" cell of the cell pair. We have demonstrated that significant delays in action potential conduction for a cell pair can occur either with a decreased value of coupling conductance or with an asymmetry in size such that the follower cell is larger than the leader cell. In both conditions we have shown that isoproterenol, applied to the real cell at very low concentrations, can reversibly decrease the critical coupling conductance (below which action potential conduction fails) for a cell pair with fixed cell sizes, or, for a fixed value of coupling conductance, increase the maximum allowable asymmetry in cell size for successful conduction. For either of these effects, we were able to show that treatment of the real cell with BayK 8644, which more specifically increases the magnitude of the L-type calcium current, was able to mimic the actions of isoproterenol. Treatment of the leader cell of the cell pair (the real cell) with nifedipine, which selectively lowers the magnitude of the L-type calcium current, had effects opposite those of isoproterenol or BayK 8644. The actions of nifedipine, isoproterenol, and BayK 8644 are all limited to conditions in which the conduction delay is on the order of 5 ms or more, whether this delay is caused by limited coupling conductance or by asymmetry in size of the cells. This limitation is consistent with the time course of the L-type calcium current and suggests that the effects of calcium channel blockers or beta-adrenergic blocking drugs, in addition to being selective for regions of the heart that depend on the L-type calcium current for the upstroke of the action potential, would also be somewhat selective for regions of the heart that have discontinuous conduction, either normally or because of some pathological condition.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Action potential conduction between a ventricular cell model and an isolated ventricular cell.

We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded real cell action potentials was quite good, and the strength-duration curves for the real cells and for the LR model cell were in general correspondence. The experimental protocol allowed us to modify the effective size of either the simulation model or the real cell. 1) When we normalized real cell size to LR model cell size, required conductance for propagation between model cell and real cell was greater than that found for conduction between two LR model cells (5.4 nS), with a greater disparity when we stimulated the LR model cell (8.3 +/- 0.6 nS) than when we stimulated the real cell (7.0 +/- 0.2 nS). 2) Electrical loading of the action potential waveform was greater for real cell than for LR model cell even when real cell size was normalized to be equal to that of LR model cell. 3) When the size of the follower cell was doubled, required conductance for propagation was dramatically increased; but this increase was greatest for conduction from real cell to LR model cell, less for conduction from LR model cell to real cell, and least for conduction from LR model cell to LR model cell. The introduction of this "model clamp" technique allows testing of proposed membrane models of cardiac cells in terms of their source-sink behavior under conditions of extreme coupling by examining the symmetry of conduction of a cell pair composed of a model cell and a real cardiac cell. We have focused our experimental work with this technique on situations of extreme uncoupling that can lead to conduction block. In addition, the analysis of the geometrical factors that determine success or failure of conduction is important in the understanding of the process of discontinuous conduction, which occurs in myocardial infarction.

Action Potentials↗
PubMed1996

Oxidative stress-mediated neurotoxicity of cadmium.

Young albino rats were administered cadmium i.p. (0.4 mg/kg body weight) for a period of 30 days and membrane fluidity, intracellular calcium level, MDA level, phospholipids, (phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, phosphatidylserine and sphingomyelin) and reduced glutathione were studied in olfactory bulb, cerebellum and rest of brain. A decrease in membrane fluidity was observed in all the brain regions studied, maximum being in olfactory bulb (21%). Intracellular calcium (Ca+2)i level was increased significantly in olfactory bulb (150%) followed by rest of brain (98%) and cerebellum (71%) in Cd-exposed rats in comparison with controls. A significant decrease in phosphatidylcholine (27%) and phosphatidylethanolamine (22%) was observed in olfactory bulb, while other phospholipids remained unaffected. TBA reactivity was increased in olfactory bulb (77%), cerebellum (35%) and rest of brain (27%). Reduced glutathione level was also decreased in different brain regions. The results suggest that the effect of cadmium in brain is region-specific and most pronounced in olfactory bulb.

Acetates↗
PubMed1996

Post-natal depression in an urban area of Portugal: comparison of childbearing women and matched controls.

The point prevalence of depression measured on one occasion between 2 and 5 months after childbirth was estimated to be 13.1% in 352 mothers living in urban Portugal; the criterion was a score of 13 or more on a translated version of the Edinburgh Post-natal Depression Scale (EPDS). More detailed comparisons were made between a subgroup of 118 mothers and 118 matched controls who had not borne a child in the previous 2 years. Post-natal women were twice as likely as non-childbearing controls to meet the EPDS criterion for depression In comparison with controls, they were also more severely depressed as judged by their total scores on another questionnaire, the Zung Scale. Comparisons of individual symptom scores (Zung Scale) showed that childbearing women, as a whole, reported more somatic symptoms than controls, but when only those women judged to be depressed or dysphoric by the EPDS were compared, this difference disappeared. Stepwise logistic analyses of symptoms contributing to the categorization of a 'case' of post-natal versus non-post- natal depression did not reveal any very clear divergences in self-reported psychopathology. In childbearing women, two factors were found significantly to contribute to higher depression scores; women with more children and those from lower socio-economic groups were most at risk.

Adult↗
PubMed1996

Membrane characterization of amastigote-like forms of Leishmania donovani.

During in vitro transformation, Leishmania donovani promastigotes converted into amastigote-like forms and underwent several changes in membrane parameters. They exhibited significantly increased microviscosity comparable to true amastigotes. Activities of several functionally important membrane bound enzymes were also altered, thereby indicating a change in their orientation. Peanut agglutinin was found to be specific for agglutination of stationary phase promastigotes whereas wheat-germ agglutinin was specific for the amastigote-like forms as well as for pure amastigotes, implying the presence of specific glycoconjugates on the parasite surface.

Animals↗
PubMed1996

Conjunctival impression cytology with transfer (CICT) to detect pre-clinical vitamin A deficiency among slum children in India.

In order to establish a method usable in the field for diagnosis of pre-clinical vitamin A deficiency, conjunctival impression cytology with transfer (CICT) was used in 200 normal slum children aged 6-120 months in Chandigarh, India. Conjunctival impressions taken on cellulose acetate paper were transferred to glass slides which were fixed in ethanol and stained with alcian blue and carbol fuchsin. Sixty samples of cellulose acetate paper were preserved after transfer of impression and were stained later. Transfer was complete in forty-eight samples and in the other twelve it was incomplete. Conjunctival impressions on paper and slide of these twelve cases were comparable. At a plasma retinol concentration of < 0.70 mumol/l measured by HPLC the sensitivity, specificity and positive predictive values of CICT were 90.59%, 100% and 100% respectively. Compared with conventional conjunctival impression cytology, CICT is less time consuming, cheaper and comparable in validity. It is thus more suitable than the conventional method for mass screening.

Child↗
PubMed1996

Effect of individual and multiple antioxidant vitamins on growth and morphology of human nontumorigenic and tumorigenic parotid acinar cells in culture.

The effects of individual and multiple antioxidant vitamins on growth and morphology of human nontumorigenic (2HPC8) and tumorigenic (2HP1G) parotid acinar cells in culture have not been investigated. Our study showed that tumorigenic acinar cells were more sensitive than nontumorigenic acinar cells to individual vitamins such as vitamin C, beta-carotene (BC), d-alpha-tocopheryl succinate (alpha-TS), and retinoic acid (RA) and a mixture of four vitamins (vitamin C, BC, alpha-TS, and RA). The effect of individual vitamins on tumorigenic acinar cells depended on the dose and the type of vitamins. Vitamin C at a low concentration stimulated growth, but at a high concentration it inhibited growth. BC was most effective in reducing growth, and it alone caused extensive morphological changes in tumorigenic acinar cells. A mixture of four vitamins at appropriate doses was more effective than a mixture of two or three vitamins at the same doses in reducing the growth of tumorigenic acinar cells. The extent of growth inhibition depended on the dose and the type of vitamins. Our results suggest that the use of multiple antioxidant vitamins is essential for a maximal reduction in cancer incidence among a high-risk population. The use of one or two vitamins may be ineffective or even harmful.

Antioxidants↗
PubMed1996

Separation of 7-methyl- and 7-(2-hydroxyethyl)-guanine adducts in human DNA samples using a combination of TLC and HPLC.

We have used a combination of thin-layer chromatography (TLC) and high pressure liquid chromatography (HPLC) to achieve separation of 32P-postlabelled 7-methylguanine and 7-(2-hydroxyethyl)-guanine adducts. The level of these two adducts was determined in human total white blood cells (mean values 0.7 to 1.5 adducts per 10(7) normal nucleotides) and isolated lymphocytes (mean values 1.1 to 12 adducts per 10(7) normal nucleotides). The separation of these two adducts revealed that the level of 7-(2-hydroxyethyl)-guanine was twice the level of 7-methylguanine adducts in total white blood cells, whereas, in isolated lymphocytes it was at least four times more than the 7-methylguanine adduct. The combined level of these two adducts in the lymphocytes of non-smokers was 1.1 to 8.4 adducts per 10(7) normal nucleotides and in the lymphocytes of smokers, the level was 5.6 to 12 adducts per 10(7) normal nucleotides. We also report detection of three unidentified adducts in the samples analysed, and at least one of these adducts seemed to be related to smoking. The chromatographic behaviour and depurination at neutral pH indicated the probable 7-alkylguanine or 3-alkyladenine nature of these unidentified adducts.

Chromatography, High Pressure Liquid↗
PubMed1996

7-Alkylguanine adducts of styrene oxide determined by 32P-postlabeling in DNA and human embryonal lung fibroblasts (HEL).

The modified 32P-postlabeling method was used for the detection of N-7-(2-hydroxy-phenylethyl) guanine adducts in DNA and human embryonal lung (HEL) cells treated in vitro with styrene oxide (SO). The total recovery of 7-alkylguanine adducts of styrene oxide in DNA analysed by 32P-postlabeling assay was 4.1 +/- 0.6%. The disappearance of 7-alkyldeoxyguanosine monophosphate adducts from SO-modified DNA at 37 degrees C showed a half-life of 19 h. The levels of 7-alkylguanine DNA adducts and single-strand breaks (SSBs) in DNA were determined in HEL cells treated with SO for 3 and 18 h. In the 3 h treatment there was a concentration-dependent increase of both 7-alkylguanine adducts and SSBs in DNA (r = 0.98, P = 0.012 and r = 0.99, P = 0.003, respectively). We found a significant correlation between 7-alkylguanine DNA adducts and SSBs in DNA (r = 0.98, P = 0.011). In HEL cells approximately 3-fold higher levels of both 7-alkylguanine DNA adducts and SSB in DNA were found after the SO (100 microM) treatment for 3 h than after the treatment for 18 h. A significant concentration-dependent increase was found only for SSB ( r = 0.95, P = 0.024) in the 18 h treatment with SO. There was no significant correlation between 7-alkylguanine adducts and SSBs (r = 0.72, P = 0.15). Our data suggest relatively fast removal of both 7-alkylguanine adducts of SO and DNA SSBs.

Autoradiography↗
PubMed1996

32P-postlabelling of diastereomeric 7-alkylguanine adducts of butadiene monoepoxide.

The reaction of 3,4-epoxy-1-butene (BMO) with deoxyguanosine-3'-monophosphate (3'-dGMP) resulted in the formation of two pairs of diastereomeric 7-alkyl-3'-dGMP derivatives corresponding to two isomers C¿-1 and C¿-2. The T4 polynucleotide kinase-mediated phosphorylation with [gamma-32P]-ATP showed preferential labelling of diastereo- mers of the C¿-1 isomer. The diastereomers 1 and 2 of the C¿-1 isomer had labelling efficiencies of 42%. However, the labelling efficiencies of diastereomers 3 and 4 of the C¿-2 isomer were 11 and 10%, respectively. The 32P-postlabelling of BMO-modified DNA yielded four isomers in the ratio of 4:4:1:1 with overall recoveries being 14%. The two isomers had a half-life of 270 min (C¿-1 isomer) and 300 min (C¿-2 isomer) which is in accordance with the stability predicted by other similar adduct experiments. The molecular modelling experiments showed more pronounced restricted rotation of butadiene residue in C¿-2 isomers due to steric interaction between butadiene residue at N-7 and O(6) atom of guanine than in C¿-1 isomer. The butadiene residue also leads to steric overcrowding at 3'-phosphate in C¿-2 isomer which probably restricts the access to the active site of T4 polynucleotide kinase.

Animals↗
PubMed1996

Statistical choropleth cartography in epidemiology.

BACKGROUND: The potential of maps in the study of regional variation and similarity in health and in understanding the underlying processes is being increasingly realized. It has thus become important that more care is exercised in drawing health maps and the subjective elements are minimized. Conventional choropleth maps based on qualitative data are mostly arbitrary with regard to the number of categories and the cutoff points. This can lead to substantially different pictures based on the same data set. METHODS: We suggest use of cluster methods to discover 'natural' groups of data points which to a large extent are suggested by the data themselves. These methods can determine not only the cutoff points but also the number of categories required to depict the variability in the data. The methods have natural extension to the multivariate set-up and thus can provide the strategy to construct integrated maps based on the simultaneous consideration of several variables. Since different cluster methods can yield different grouping we propose a simple method to identify cutoffs common to a majority of the methods. RESULTS: The details of the methods are explained on two real data sets. One is the indicators of mortality before one year of age in India and the other is years of life lost due to premature mortality in different countries. The maps obtained are compared with the conventional maps. CONCLUSION: The cutoff points obtained by a majority of cluster methods deserve attention for obtaining natural groups for choroplethic depiction. Maps based on such cutoffs seem to have promise for increasing the accuracy in perception and cognition of regional variation.

Analysis of Variance↗
PubMed1996

Review of G and P typing results from a global collection of rotavirus strains: implications for vaccine development.

Candidate rotavirus vaccines have been prepared with reassortant strains specifically to protect against the 4 major rotavirus G serotypes (G1 -4). Many studies using P (VP4) genotyping methods have indicated that, worldwide, rotavirus strains of the 4 common G serotypes are each associated with 1 P genotype: GI, G3, and G4 are associated with P[8], and G2 is associated with P[4]. In contrast, G and P genotyping of rotavirus in specimens from India revealed that a high percentage of the childhood diarrhea strains belong to genotype P[6], and the most common strain had an unusual G serotype, G9. Similarly, in all regions surveyed in Brazil, apparent reassortants of genotype P[8], G5 were found in children with gastroenteritis. These studies indicate that while rotavirus strains have limited diversity in many settings, reassortment between common and uncommon serotypes or animal strains can arise in some settings and, thus, lead to unusual diversity.

Child↗
PubMed1996

Abnormalities of the vitamin D receptor in uraemia.

The 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) receptor mediates many of the actions of 1,25(OH)2D3 in cells of target tissues. Abnormalities in vitamin D receptor concentration and regulation exist in tissues of subjects with chronic renal failure and end-stage renal disease. There is evidence that inhibitors of vitamin D receptor-1,25(OH)2D3 binding and 1,25(OH)2D3 action are present in dialysates and sera of individuals with end-stage renal disease. The biological significance of decreased vitamin D receptor number and altered vitamin D receptor regulation in uraemia is unclear at present as responses to 1,25(OH)2D3 in uraemia have not been systematically compared with responses in normal subjects.

Calcitriol↗
PubMed1996

Endoscopic correction of vesicoureteral reflux secondary to posterior urethral valves.

PURPOSE: We review our experience with children with high grade vesicoureteral reflux secondary to posterior urethral valves treated endoscopically with subureteral polytetrafluoroethylene (Teflon) injection. MATERIALS AND METHODS: Between 1985 and 1994, 54 infants and children were diagnosed with posterior urethral valves of whom 38 (70%) had vesicoureteral reflux. In 9 patients reflux resolved after valve ablation. Seven patients underwent nephroureterectomy for nonfunctioning kidneys and in 2 reflux was treated with continuous chemoprophylaxis. The remaining 20 patients underwent an antireflux procedure, including reimplantation of the ureters in 5 and subureteral polytetrafluoroethylene injection in 15. Of the 15 patients who underwent injection 6 had unilateral and 9 had bilateral vesicoureteral reflux. According to the international classification reflux was grade IV in 6 ureters and grade V in 18. Patient age at injection ranged from 8 months to 6 years (mean 2.2 years). RESULTS: Reflux was eliminated in 17 ureters after a single subureteral polytetrafluoroethylene injection. Five ureters required 2 injections and 2 ureters required 3 to correct reflux. Followup of the 15 patients ranges from 1 to 10 years. Followup voiding cystography in the 15 patients (24 ureters) showed no evidence of recurrence of reflux. No clinically untoward effects were noted in these children from the use of polytetrafluoroethylene as an injectable material. CONCLUSIONS: Subureteral polytetrafluoroethylene injection is a simple and effective endoscopic alternative to open surgery for the management of high grade vesicoureteral reflux secondary to posterior urethral valves.

Child↗