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Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 469 records · Page 26Linked to original sources
PubMed1994

Antianginal and anti-ischemic efficacy of immediate-release nisoldipine in chronic stable angina pectoris.

A double-blind, randomized, placebo-controlled, crossover study tested peak and trough efficacy of immediate-release nisoldipine (20 mg twice daily) added to existent beta-adrenergic blocking therapy. Patients were randomized with a history of chronic stable angina, while receiving a stable regimen of a beta-blocking agent, with exercise test-induced angina in association with 1 mm horizontal or downsloping ST-segment depression and exercise test reproducibility of +/- 15%. Ambulatory electrocardiographic monitoring (48-hour) was performed at 3 of 5 centers (44 patients). Efficacy was achieved in 53 patients (26 taking immediate-release nisoldipine/placebo in sequence and 27 taking placebo/immediate-release nisoldipine in sequence). Total exercise time increased compared with placebo at peak, but only a trend was seen at trough. Time to 1 mm ST-segment depression at peak and trough and ambulatory electrocardiographic parameters were also improved. Adverse effects were mild. This trial confirms that immediate-release nisoldipine when added to existent beta-blocker therapy is an active antianginal and anti-ischemic agent, but that the immediate-release formulation loses its antianginal effect at the end of its dosing interval (9 to 14 hours). This drug is therefore being examined in a new extended-release formulation (Coat-Core).

Adrenergic beta-Antagonists↗
PubMed1994

BCG immunotherapy prevents recurrence of diabetes in islet grafts transplanted into spontaneously diabetic NOD mice.

Islet transplantation can provide a therapeutic option for patients who suffer from type 1 diabetes mellitus, especially if current aggressive immunosuppression could be eliminated. In vitro immunomodulation has achieved this goal for islet allografts--however, strategies must be developed to prevent B cell lysis secondary to the chronic autoimmune process of diabetes. Previously, we have found that adjuvant therapy with CFA was effective in preventing the onset of diabetes and the recurrence of B cell lysis post-islet transplantation. In this study we evaluated the efficacy of BCG, a more clinically relevant immunoadjuvant, to prevent recurrent autoimmune damage to islets grafted into diabetic NOD mice. Highly purified islets were isolated from either 5-7-week-old prediabetic NOD mice or 5-8-week-old CBA/J mice using standard islet isolation techniques. Four hundred purified islets were transplanted into the kidney capsule of diabetic NOD recipients. A single dose of BCG was administered in recipients of syngeneic (gp 1) and allogeneic islets (gp 2). In gp 1, 8 of 10 BCG-treated syngeneic recipients remained normoglycemic for > 100 days posttransplant. In untreated recipients of syngeneic islets (gp 3) the graft failed at 19 days (n = 16) (P value, gp 1 vs. gp 3 < 0.001). In untreated allograft recipients, islet grafts functioned for 11 days (n = 8), which did not differ significantly (P = NS) from the BCG-treated allografts (gp 4) (14 days, n = 7). In 6 mice with long-term graft function, a second syngeneic graft implanted into the contralateral kidney maintained normoglycemia for 50 days following the removal of the first islet graft. Histological examination of the grafts from gp 1 mice showed granulated B cells with periinsular lymphocytes, while those of the control animals showed lytic B cells and marked lymphocytic infiltration. We conclude that adjuvant therapy with a single dose of BCG can prevent the recurrent autoimmune insulitis, but not allograft rejection in islets transplanted into NOD mice, and that a state of unresponsiveness is induced to allow acceptance of a second syngeneic graft. These data suggest that adjuvant therapy may be useful to sustain the function of transplanted islets in the type 1 diabetic.

Animals↗
PubMed1994

Cloning of Giardia lamblia heat shock protein HSP70 homologs: implications regarding origin of eukaryotic cells and of endoplasmic reticulum.

The genes for two different 70-kDa heat shock protein (HSP70) homologs have been cloned and sequenced from the protozoan Giardia lamblia. On the basis of their sequence features, one of these genes corresponds to the cytoplasmic form of HSP70. The second gene, on the basis of its characteristic N-terminal hydrophobic signal sequence and C-terminal endoplasmic reticulum (ER) retention sequence (Lys-Asp-Glu-Leu), is the equivalent of ER-resident GRP78 or the Bip family of proteins. Phylogenetic trees based on HSP70 sequences show that G. lamblia homologs show the deepest divergence among eukaryotic species. The identification of a GRP78 or Bip homolog in G. lamblia strongly suggests the existence of ER in this ancient eukaryote. Detailed phylogenetic analyses of HSP70 sequences by boot-strap neighbor-joining and maximum-parsimony methods show that the cytoplasmic and ER homologs form distinct subfamilies that evolved from a common eukaryotic ancestor by gene duplication that occurred very early in the evolution of eukaryotic cells. It is postulated that because of the essential "molecular chaperone" function of these proteins in translocation of other proteins across membranes, duplication of their genes accompanied the evolution of ER or nucleus in the eukaryotic cell ancestor. The presence in all eukaryotic cytoplasmic HSP70 homologs (including the cognate, heat-induced, and ER forms) of a number of autapomorphic sequence signatures that are not present in any prokaryotic or organellar homologs provides strong evidence regarding the monophyletic nature of eukaryotic lineage. Further, all eukaryotic HSP70 homologs share in common with the Gram-negative group of eubacteria a number of sequence features that are not present in any archaebacterium or Gram-positive bacterium, indicating their evolution from this group of organisms. Some implications of these findings regarding the evolution of eukaryotic cells and ER are discussed.

Amino Acid Sequence↗
PubMed1994

Atrioventricular valve orifice areas in normal subjects: determination by cross-sectional and Doppler echocardiography.

Mitral and tricuspid valve orifice areas were determined in 78 healthy subjects (age range, 2 months-50 years; mean, 20 +/- 13 years; 43 male, 35 female; body surface area, 0.25-1.9 m2; mean, 1.24 +/- 0.45 m2) by a combined echo-Doppler approach to establish normal values and their relationship with body surface area. Mitral valve orifice area by direct planimetry (3.37 +/- 1.13 cm2; range, 0.52-5.6 cm2) and by continuity equation (3.62 +/- 1.08 cm2; range, 0.66-5.4 cm2) were similar (r = 0.85, P < 0.0001). Tricuspid valve orifice area (4.07 +/- 1.5 cm2; range 0.62-7.2 cm2) by continuity equation had a close correlation with mitral valve orifice area (r = 0.76, P < 0.001). Mitral and tricuspid valve orifice areas were significantly correlated to body surface area (r = 0.85 and 0.77, respectively), left and right ventricular outflow tract diameters (r = 0.90 and 0.79, respectively) and age (r = 0.70 and 0.61, respectively). These data provide normal values for atrioventricular valve orifice areas in normal subjects with a wide range of body surface area and support the practice of indexing valve area by body surface area.

Adolescent↗
PubMed1994

Up-regulation of the MHC class II molecules on B cells by peptide ligands.

MHC class I and class II molecules present peptide Ag to T lymphocytes. Peptides are critical in class I heavy chain folding and/or stable association with beta 2m. A recent study suggests the role of peptide Ag binding for MHC class II alpha- and beta-chain heterodimers to enter into a compact state and allow their transport to the cell surface. We have investigated the effect of peptide ligands on the expression of MHC class II I-A(d) molecules on the B cell hybridoma, TA3. These cells, when cultured in vitro, gradually lost the surface expression of I-A(d) molecules. Incubation with peptides, having high affinity for binding to intact I-A(d) molecules, significantly increased the surface expression of I-A(d) in less than 24 h. The ability of peptides to induce increased expression of I-A(d) correlated with the affinity of peptide to intact I-A(d), and an I-Ak-restricted peptide did not have an effect on I-A(d) expression. The effect could be reversed after the removal of the peptide Ag. Based on our studies with inhibitors of protein synthesis and intracellular transport, the mechanism for up-regulation of I-A(d) expression by peptides seems to involve intracellular pathway but appears not to require new protein synthesis or transport from ER. Our results suggest that the decrease in surface expression of I-A(d) on TA3 cells may result from their failure to generate or to be saturated with naturally processed peptide ligands. Thus peptide ligands are evidently important in regulating surface expression of MHC class II molecules and their recognition by T lymphocytes.

Amino Acid Sequence↗
PubMed1994

Novel cAMP PDE III inhibitors: imidazo[4,5-b]pyridin-2(3H)-ones and thiazolo[4,5-b]pyridin-2(3H)-ones and their analogs.

The transformation of milrinone to 1,3-dihydro-5-methyl-6-(4-pyridinyl)-2H-imidazo[4,5-b]pyridin-2-one (13a), 5-methyl-6-(4-pyridinyl)thiazolo[4,5-b]pyridin-2(3H)-one (51), and 7-methyl-6-(4-pyridinyl)-1,8-naphthyridin-2(1H)-one (22) resulted in very potent cAMP PDE III inhibitors with in vitro activity in the nanomolar range. 1,3-Dihydro-2H-imidazo[4,5-b]pyridin-2-ones 13 were prepared from 2-aminopyridine-3-carboxylic acids (7, 10) via Curtius rearrangement. 1,8-Naphthyridin-2(1H)-one 22 and the corresponding 3,4-dihydro derivative 28 were prepared from 5-bromo-2-methyl[3,4'-bipyridin]-6-amine (21) and 5-bromo-2-methyl[3,4-bipyridin]-6(1H)-one (24), respectively, via Heck reaction. Thiazolo[4,5-b]pyridin-2(3H)-ones 35 were prepared from 6-bromo[3,4'-bipyridin]-6-amines 30 and 32 via a four-step sequence. Treatment of 6-amino-2-methyl[3,4'-bipyridine]-5-thiol (59) with ethyl bromoacetate and ethyl bromodifluoroacetate gave pyridothiazinones 60 and 61, respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Posttraumatic paroxysmal nocturnal hemidystonia.

The term "nocturnal paroxysmal dystonia" has been used to describe patients who display paroxysmal episodes of dystonic-dyskinetic movements arising during nonrapid eye movement sleep, in particular stages 2-3 (Lugaresi E, Cirignotta F. Hypnogenic paroxysmal dystonia: epileptic seizure or a new syndrome. Sleep 1981;4: 129-138). The pathogenesis of these attacks has remained controversial. We describe a patient with posttraumatic paroxysmal nocturnal hemidystonia. Acetazolamide led to improvement.

Acetazolamide↗
PubMed1994

Lewis rat T cells can reutilize, process, and present myelin basic protein to antigen-specific T cell lines.

MHC class-II-negative astrocytes prevented from intracellular antigen (Ag) processing induce myelin basic protein (MBP)-specific short-term T cell lines to proliferate. This process results from the ability of the T cells themselves to take up, process, and present Ag to each other. The Ag-presenting function of the T cells occurred in the absence of any conventional antigen-presenting cell (APC), was independent of their T cell receptor specificity, was sensitive to chloroquine, and was prevented by anti-class-II MHC antibody. Both native and HPLC-purified MBP were effective in stimulating T cell lines, and there was no obvious benefit in using either enzymatically digested or synthetic peptide preparations of the Ag. Furthermore, the Ag-presenting T cells could take up, reutilize, and re-present Ag adsorbed to the surface of histoincompatible astrocytes. Responding T cells activated by Ag-presenting T cells in the absence of other conventional APC were fully encephalitogenic upon transfer to syngeneic recipients. These results have relevance for understanding pathogenetic mechanisms in T cell-mediated autoimmunity in the central nervous system.

Amino Acid Sequence↗
PubMed1994

Estimation of unmeasured particulate air pollution data for an epidemiological study of daily respiratory morbidity.

The standard approach to government-mandated aerometric monitoring of airborne particulates across North America is to sample every sixth day year round. However, such data are inadequate for epidemiological studies which aim to examine daily time series relationships of particulate air pollution to respiratory health responses. The aim of the present study was to estimate missing daily particulate matter < or = 2.5 and < or = 10 microns in aerometric diameter (PM2.5 and PM10) and sulfate (SO4(2-) to a degree sufficiently accurate and reliable to allow the use of these estimates, along with the measured data, in an investigation of the relationship of air pollution to respiratory hospital admissions in Montreal during the 1980s. Prediction equations were developed for May through October periods using available daily levels of predictor variables which included: relative humidity-corrected light extinction coefficient (bext) derived from airport visual range sightings, coefficient of haze (COH), SO2, NOx, CO, O3, wind speed, wind direction, barometric pressure (BP), temperature, relative humidity, and total precipitation. Three fourths of the available gravimetric particulate data were used to develop prediction models, while the remaining fourth was used to test the reliability of the model (holdout data). All final models explained over 70% of the variability in the particulate air pollutants and were reliable when tested against the holdout data. The strongest (P < 0.001) and most consistent predictors were bext, COH, and O3 measured on the same day as the particulate, and BP lagged 1 day in the past. Other selected variables were same day NOx, BP, and minimum temperature. Although the present approach to the estimation of missing particulate air pollution may increase the level of exposure misclassification, it does allow for the use of existing network databases in epidemiological studies of daily air pollution health effects even though particulate data is only measured on certain days.

Air Pollutants↗
PubMed1994

Physiochemical characteristics of flours of faba bean as influenced by processing methods.

Wet- and dry-processing with and without heating treatments were used to dehull faba beans for preparation of flours from the cotyledons. Flour qualities were assessed by levels of tannin and trypsin inhibitor and other measures of proximate composition. High roasting temperature and shorter process time that improved the recovered cotyledon yields were verified significant by path analysis methodologies. In turn, the higher cotyledon recoveries correlated with higher protein levels and inversely with the measured tannin levels. Ash reductions were correlated to the wet processing options in hull removal while reductions in the insoluble dietary fiber were notably influenced by level of heating temperatures applied. Trypsin inhibitor levels ranged from 42 to 56% of the original with reductions tied to applications of wet and/or heat processing in each case improved by increased durations and temperatures of treatments.

Chemical Phenomena↗
PubMed1994

Histochemical/histoenzymic studies in broiler chicks fed aflatoxin, ochratoxin and inoculated with inclusion body hepatitis virus singly and in concurrence.

The effect of feeding mycotoxins, i.e. aflatoxin B1 (1.25 ppm from 3 to 38 days of age) and ochratoxin A (0.5 ppm from 3 to 38 days of age) along with inclusion body hepatitis virus (IBHV) inoculation (at 10 days of age) singly and in combination was studied in broiler chicks. Birds in combined treatment groups, i.e. aflatoxin fed and virus inoculated and ochratoxin fed and virus inoculated, showed more changes in activities of phosphatases (AKPase, ATPase, G-6-Pase and ACPase) in liver and kidney tissues than their respective individual treatment groups with a few exceptions. Reduction in the activities of oxido-reductases in liver and kidney tissues were almost comparable in different treatment groups. The increase in muco-polysaccharides reaction was more marked in both the combined treatment groups than the single treatment groups. Intensity of lipid reaction was more in ochratoxin virus combination group than either alone.

Acid Phosphatase↗
PubMed1994

Impact of lead pollution on the status of other trace metals in blood and alterations in hepatic functions.

Lead pollution and its impact on the status of four other trace elements--Fe, Zn, Br, and Rb--have been studied in the whole blood samples of different population groups employing energy dispersive X-ray fluorescence technique. These population groups included normal, automobile workers and lead battery manufacturers. The maximum increase in the concentration of trace elements in the blood samples of automobile workers and battery manufacturers was observed for Pb, when compared with normal Pb-B levels. The effect of lead pollution had significantly reduced Zn levels in automobile workers. Fe-B levels in automobile workers had been found to be reduced significantly as compared to control, whereas in battery workers the reduction was not significant. The concentration of Br was greatly enhanced in the blood samples of automobile workers, whereas Rb-B levels were significantly higher in both the automobile and battery workers. Oral administration of lead acetate (100 mg/kg body wt) to experimental rats significantly decreased the activities of hepatic transaminases after 3 and 4 mo of treatment, whereas the activity of hepatic alkaline phosphatase decreased significantly after 4 mo of treatment. It is concluded from this study that higher Pb-B levels greatly influence the levels of other trace elements in human blood samples and also the activities of hepatic transaminases as well as alkaline phosphatase in experimental rats.

Administration, Oral↗
PubMed1994

Biokinetics of iodine-131 in rat thyroid following lead and lithium supplementation.

The impact of lead as an environmental pollutant on the I-131 uptake and retention in rat thyroid was assayed alone and in combination with lithium treatment. Lead treatment significantly stimulated the 2- and 24-h uptake of I-131 in the thyroid, and the 24-h uptake showed the maximum stimulation after 3 mo of lead treatment. On the contrary, lithium supplementation reduced the uptake significantly and the maximum decrease was noticed after 2 mo of lithium administration. Further, simultaneous lead and lithium treatment resulted in more pronounced increase in the uptake of I-131 by the thyroid, which was maximum after 3 mo of combined treatment. The thyroid biological half-life of I-131 (Tbiol) was found to be increased significantly following lead and lithium treatments when given separately. Interestingly, combined lead and lithium treatment given up to 2 mo further prolonged the Tbiol of I-131, thus reflecting its increased retention.

Animals↗
PubMed1994

Arterial oxygen desaturation during peripheral venous cannulation in children.

Arterial oxygen saturation (SpO2) was measured to determine oxygen desaturation during peripheral venous cannulation prior to induction of anaesthesia in 40 consecutive patients in each of the three age groups; Group I: 1-4 mo, Group II: 4-12 mo, Group III: 12-24 mo. Following premedication with oral trimeprazine tartarate 3 mg.kg-1, one to two hours before operation, baseline SpO2 was noted with child breathing room air. Continuous monitoring during peripheral venous cannulation was done and maximum decrease and duration of SpO2 < 90% was noted. Decreases in mean SpO2, 3.2 +/- 1.4 in Group I, 2.6 +/- 2.0 in Group II and 1.7 +/- 1.9 in Group III, were observed (P < 0.001). Desaturation > or = 4% was noted in 17 patients in Group I, ten patients in Group II and six patients in Group III. Two children, one each in Groups I and II, experienced SpO2 < 90% for 30 sec and 80 sec respectively. We conclude that clinically undiagnosed desaturation occurs during peripheral venous cannulation in healthy children. The authors suggest that continuous monitoring of SpO2 using pulse oximetry should be performed routinely during peripheral venous cannulation.

Anesthesia, General↗
PubMed1994

Road traffic fatalities in Delhi: causes, injury patterns, and incidence of preventable deaths.

India reported nearly 50,000 traffic accident deaths in 1989. Yet, literature addressing the causes, timing, and preventability of these deaths is sparse. We undertook an autopsy study of road traffic fatalities in South Delhi to determine the injury patterns and incidence of deaths that could be prevented by optimal utilization of available medical resources. Among the 177 autopsies reviewed, neurological injury caused death in 60% of patients and hemorrhagic shock in 25%. Twenty-three percent of the deaths were felt to be preventable, 41% possibly preventable, and the rest not preventable. The majority of preventable deaths resulted from a failure to diagnose or treat a treatable injury. Adherence to establish principles in the hospital management of intracavitory hemorrhage could have salvaged 70% of preventable deaths.

Abbreviated Injury Scale↗
PubMed1994

Effect of anti-interferon-gamma monoclonal antibody treatment on the development of experimental allergic encephalomyelitis in resistant mouse strains.

Immunization with myelin basic protein (MBP) in complete Freund's adjuvant failed to induce experimental allergic encephalomyelitis (EAE) in six resistant mouse strains studied: A/J, BALB/c C3H/HeJ, AKR, NZW and DBA/2. However, treatment of challenged mice with anti-interferon-gamma (IFN-gamma) monoclonal antibody (mAb) induced severe EAE in mice of all strains except AKR. Furthermore, anti-IFN-gamma mAb treatment led to increased disease incidence and severity in BALB/c mice challenged with the MBP peptide87-103, known to be encephalitogenic for the susceptible SJL strain. In three strains tested, anti-IFN-gamma mAb enhanced passively induced EAE in the A/J and C3H/HeJ but not in the BALB/c mice. All mice with clinically overt EAE had widespread histological lesions characterized by mononuclear cell infiltrates and focal demyelination. The results indicate that resistant strains are genetically capable of developing EAE, and that IFN-gamma can contribute to disease resistance.

Animals↗