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Biomedical subjects

N Garg

Publications and source records attributed to N Garg.

At least 19 recordsLinked to original sources
PubMed2001

Ultrastructure of the fresh water cyanobacterium Anabaena variabilis SPU 003 and its application for oxygen-free hydrogen production.

Photoproduction of hydrogen has been studied as one of the ways to produce a clean, renewable energy source. Ultrastructure of the selected strain Anabaena variabilis SPU 003, a heterocystous cyanobacterium, has been done to understand the cell structure. The organism was found to be essentially a dark hydrogen producer. While pH had no significant effect on hydrogen production, optimum temperature was found to be 30 degrees C. Various sugars increased the production of hydrogen while the presence of various nitrogen sources inhibits the production. The production of hydrogen is highly sensitive to salinity and micronutrients.

Anabaena↗
PubMed2001

Beneficial effects of nicorandil versus enalapril in chronic rheumatic severe mitral regurgitation: six months follow up echocardiographic study.

BACKGROUND AND AIM OF THE STUDY: It is possible that vasodilator therapy may retard left ventricular (LV) dilatation and functional deterioration in chronic mitral regurgitation (MR). The study objectives were to evaluate comparatively the efficacy of nicorandil (a new, balanced vasodilator) and enalapril therapy on LV volume, mass and function in mildly symptomatic, chronic rheumatic severe MR. METHODS: Eighty-seven mildly symptomatic rheumatic patients with severe MR were enrolled in this prospective, randomized study. All patients underwent serial echocardiography study at entry, and again at six months. Eighty patients completed the study. RESULTS: At six months, the nicorandil and enalapril patient groups each had a significant reduction in LV end-systolic volume index (57.4 +/- 24.8 versus 43.2 +/- 20.7 ml/m2, p = 0.003; 50.0 +/- 19.0 versus 40.4 +/- 14.2 ml/m2, p = 0.006, respectively) and LV mass index (218.0 +/- 88.0 versus 188.0 +/- 76.0 g/m2, p = 0.05; 217.2 +/- 48.0 versus 186.2 +/- 45.0 g/m2, p = 0.002 respectively). Both nicorandil and enalapril caused significant improvement in ejection fraction (63.8 +/- 7.0 versus 71.0 +/- 6.7%, p <0.0001; 63.2 +/- 6.9 versus 67.5 +/- 6.4%, p = 0.002, respectively) and a reduction in LV end-systolic stress (152.9 +/- 29.0 versus 126.0 +/- 25.0 dyne/cm2, p = 0.001; 150.0 +/- 30.2 versus 138.0 +/- 29.0 dyne/cm2, p = 0.002, respectively). However, nicorandil caused a greater reduction in absolute LV end-systolic volume index (13.3 +/- 10.1 versus 9.6 +/- 5.9 ml/m2, p = 0.02), and a greater improvement in absolute ejection fraction (7.2 +/- 4.7 versus 4.2 +/- 2.6%, p = 0.0005) than enalapril. CONCLUSION: It is concluded that nicorandil is equivalent to enalapril in improving LV volume, mass, end-systolic stress and ejection fraction in mildly symptomatic chronic rheumatic severe mitral regurgitation over a period of six months.

Adolescent↗
PubMed2000

Primary congenital anomalies of the coronary arteries: a coronary: arteriographic study.

Geographic variations in the incidence of different congenital coronary anomalies are well known, but infrequently studied in the Indian population. Among 4,100 adult patients who underwent diagnostic coronary arteriography, 39 (0.95%) patients (34 males, 5 females) had one or more anomalous coronary arteries. Their mean age was 46.4 +/- 8.2 years (range, 26-68 years). Thirty-five (89.74%) had anomalies of origin and distribution, while the remaining four (10.25%) had coronary artery fistulae. Right coronary artery was the commonest anomalous vessel, involved in 19 (48.74%) patients. It was originating from the left sinus of Valsalva in 15 and from the non-facing aortic sinus in four patients. Anomalous left circumflex artery was the second commonest anomaly, seen in 14 (35.89%) patients. Anomalous left anterior descending artery and anomalous left coronary artery from pulmonary artery were seen in one patient each. Among patients with coronary fistulae, two had fistulae between the left anterior descending artery and the main pulmonary artery, one between the conal artery and the right atrium, while the fourth patient had fistulae from the right coronary as well as from the left anterior descending artery to the left atrium. Atherosclerotic plaques in the anomalous arteries were seen in only 13 (33.33%) patients, much less than the overall incidence of coronary artery disease in patients with congenital coronary anomalies in this series (66.66%). In four (10.25%) patients, only the anomalous vessels were involved in coronary artery disease. Thus, in a small subgroup there does not appear to be an increased risk for development of atherosclerotic coronary artery disease in anomalous coronary arteries. Recognition of coronary anomalies is important in patients undergoing coronary arteriography, coronary interventions and cardiac surgery. Variations in the frequency of primary congenital coronary anomalies may possibly have a genetic background.

Adult↗
PubMed2000

Characterization of the extracellular polysaccharide produced by a marine cyanobacterium, Cyanothece sp. ATCC 51142, and its exploitation toward metal removal from solutions.

Cyanobacterium, Cyanothece sp. ATCC 51142 produces an exopolysaccharide at a high level. Physical analysis of the exopolysaccharide (EPS), such as nuclear magnetic resonance, infrared spectrum, were done to determine its possible structure. Thermal gravimetric analysis, differential scanning calorimeter, and differential thermal analysis of the polymer were done to find out the thermal behavior. Calcium content within the sample was found out. Some of the physicochemical properties, such as relative viscosity, specific viscosity, and intrinsic viscosity of the EPS were studied under different conditions. The phenomenon of gel formation by the EPS was investigated for its potential application in metal removal from solutions.

Calcium↗
PubMed2000

Hypoglycaemic neuropathy: a case report.

A 53 years old male, a known case of ankylosing spondylitis having recurrent attacks of hypoglycaemia, developed symmetrical distal sensorimotor neuropathy. The neuropathy was axonal with secondary demyelination. Evidence of vasculopathy was also noted on histopathology of the nerve. Serum C-peptide level was low, a feature reported with autoimmune hypoglycaemia with antireceptor antibodies. The patient showed spontaneous recovery.

Capillaries↗
PubMed1999

Design and fast synthesis of C-terminal duplicated potent C(2)-symmetric P1/P1'-modified HIV-1 protease inhibitors.

An analysis of the X-ray structure of a complex of HIV-1 protease with a linear C(2)-symmetric C-terminal duplicated inhibitor guided the selection of a series of diverse target compounds. These were synthesized with the objective to identify suitable P1/P1' substituents to provide inhibitors with improved antiviral activity. Groups with various physical properties were attached to the para-positions of the P1/P1' benzyloxy groups in the parent inhibitor. A p-bromobenzyloxy compound, prepared in only three steps from commercially available starting materials, was utilized as a common precursor in all reactions. The subsequent coupling reactions were completed within a few minutes and relied on palladium catalysis and flash heating with microwave irradiation. All of the compounds synthesized exhibited good inhibitory potency in the protease assay, with K(i) values ranging from 0.09 to 3.8 nM. A 30-fold improvement of the antiviral effect in cell culture, compared to the parent compound, was achieved with four of the inhibitors. The differences in K(i) values were not correlated to the differences in antiviral effect, efficiency against mutant virus, or reduced potency in the presence of human serum. The poorest enzyme inhibitors in fact belong to the group with the best antiviral effect. The binding features of two structurally related inhibitors, cocrystallized with HIV-1 protease, are discussed with special emphasis on the interaction at the enzyme/water phase.

Animals↗
PubMed1999

Roles of free GPIs in amastigotes of Leishmania.

Glycosylated phosphatidylinositols (GPIs) are abundant cell surface molecules of the Leishmania. Amastigote-specific GPIs AmGPI-Y and AmGPI-Z, both ethanolamine (EtN)-containing glycolipids, were identified in Leishmania amazonensis. A paucity of GPI-anchored proteins in amastigotes of L. amazonensis made the kinetoplastid suitable for evaluating the importance of free (i.e. unconjugated to protein or polysaccharide) GPIs. A strain deficient in both AmGPI-Y and AmGPI-Z was produced by stable transfection of wild-type Leishmania with a GPI-phospholipase C gene. Phosphatidylinositol deficiency was not detected in the transfectants. GPI-deficient promastigotes infected murine macrophages in vitro and differentiated into amastigotes whose growth was arrested within the host cells. Cytostasis of amastigotes was also observed during axenic culture of GPI-deficient parasites. In a hamster model of leishmaniasis, GPI-deficient promastigotes produced smaller lesions with 20-fold fewer amastigotes than infections with control parasites. Together, these observations indicate that EtN-GPIs may be essential for amastigote viability, replication, and/or virulence. Implicit in these observations is the notion that drugs targeted against the GPI biosynthetic pathway might be of value in the management of human leishmaniasis.

Animals↗
PubMed1999

Prediction of preterm delivery with transvaginal ultrasonography of the cervix in patients with high-risk pregnancies: does cerclage prevent prematurity?

OBJECTIVES: We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes. STUDY DESIGN: Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospectively from 14 weeks' to 23 weeks 6 days' gestation with transvaginal ultrasonography of the cervix. The subgroup of patients with either a cervical length of <25 mm or funneling of >25% or both was offered McDonald salvage cerclage, which was performed at the discretion of the patient and the obstetrician. The 2 groups (with and without cerclage) were compared for the primary outcome of preterm delivery at <35 weeks' gestation. RESULTS: One hundred sixty-eight women were followed, including 97 (58%) with >/=1 prior 14- to 34-week preterm deliveries. Of 63 (37. 5%) patients identified as having cervical changes, 23 (37%) had preterm delivery; of 105 patients with no cervical changes, 8 (8%) had preterm delivery (relative risk, 4.8; 95% confidence interval, 2. 3-10.1). The sensitivity, specificity, and positive and negative predictive values of either a short cervix of <25 mm or funneling of >25% or both were 74%, 70%, 37%, and 92%, respectively. Of 63 pregnancies in which there were cervical changes, 39 underwent cerclage and 24 did not. These 2 groups were similar for demographic characteristics, risk factors, and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes (18.3 vs 21.2 weeks' gestation in the groups with and without cerclage, respectively; P <.001). Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage (odds ratio, 1.1; 95% confidence interval, 0.3-4.6). Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage, which was similar for all characteristics studied. The incidence of preterm delivery remained similar (27% vs 23%, respectively; P =.7), as did days from cervical changes to delivery (111 vs 96, respectively; P =.2). CONCLUSIONS: Transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation is a good predictor of preterm delivery in high-risk pregnancies. Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography.

Cervix Uteri↗
PubMed1999

Effect of gender, treatment site and psychiatric comorbidity on quality of life outcome in substance dependence.

Patients receiving treatment for substance dependence frequently endorse high rates of psychological impairment and other measures of reduced quality of life. We conducted a baseline and six-month follow-up study of a series of one hundred and three unselected patients receiving treatment for a substance abuse or dependence problem. Women and patients requiring in-patient detoxification demonstrated the most psychological impairment at baseline, as measured by the mental component summary of the SF-36. Inpatient site of treatment was associated with continued psychological impairment six months following treatment. More aggressive psychiatric and psychological interventions may be indicated for women and for inpatient substance dependence populations.

Adult↗
PubMed1999

Function of the central domain of streptokinase in substrate plasminogen docking and processing revealed by site-directed mutagenesis.

The possible role of the central beta-domain (residues 151-287) of streptokinase (SK) was probed by site-specifically altering two charged residues at a time to alanines in a region (residues 230-290) previously identified by Peptide Walking to play a key role in plasminogen (PG) activation. These mutants were then screened for altered ability to activate equimolar "partner" human PG, or altered interaction with substrate PG resulting in an overall compromised capability for substrate PG processing. Of the eight initial alanine-linker mutants of SK, one mutant, viz. SK(KK256.257AA) (SK-D1), showed a roughly 20-fold reduction in PG activator activity in comparison to wild-type SK expressed in Escherichia coli (nSK). Five other mutants were as active as nSK, with two [SK(RE248.249AA) and SK(EK281.282AA), referred to as SK(C) and SK(H), respectively] showing specific activities approximately one-half and two-thirds, respectively, that of nSK. Unlike SK(C) and SK(H), however, SK(D1) showed an extended initial delay in the kinetics of PG activation. These features were drastically accentuated when the charges on the two Lys residues at positions 256 and 257 of nSK were reversed, to obtain SK(KK256.257EE) [SK(D2)]. This mutant showed a PG activator activity approximately 10-fold less than that of SK(D1). Remarkably, inclusion of small amounts of human plasmin (PN) in the PG activation reactions of SK(D2) resulted in a dramatic, PN dose-dependent rejuvenation of its PG activation capability, indicating that it required pre-existing PN to form a functional activator since it could not effect active site exposure in partner PG on its own, a conclusion further confirmed by its inability to show a "burst" of p-nitrophenol release in the presence of equimolar human PG and p-nitrophenyl guanidino benzoate. The steady-state kinetic parameters for HPG activation of its 1:1 complex with human PN revealed that although it could form a highly functional activator once "supplied" with a mature active site, the Km for PG was increased nearly eightfold in comparison to that of nSK-PN. SK mutants carrying simultaneous two- and three-site charge-cluster alterations, viz., SK(RE24249AA:EK281.282AA) [SK(CH)], SK(EK272.273AA;EK281.282AA) [SK(FH)], and SK(RE248.249AA;EK272.273AA:EK281.282AA+ ++) [SK(CFH)], showed additive/synergistic influence of multiple charge-cluster mutations on HPG activation when compared to the respective "single-site" mutants, with the "triple-site" mutant [SK(CFH)] showing absolutely no detectable HPG activation ability. Nevertheless, like the other constructs, the double- and triple-charge cluster mutants retained a native like affinity for complexation with partner PG. Their overall structure also, as judged by far-ultraviolet circular dichroism, was closely similar to that of nSK. These results provide the first experimental evidence for a direct assistance by the SK beta-domain in the docking and processing of substrate PG by the activator complex, a facet not readily evident probably because of the flexibility of this domain in the recent X-ray crystal structure of the SK-plasmin light chain complex.

Amino Acid Sequence↗
PubMed1998

Pressure zone used and the occurrence of mitral regurgitation in Inoue balloon mitral commissurotomy.

Mitral regurgitation (MR) is a known complication of Inoue balloon mitral commissurotomy (BMC) and has been variously ascribed to the presence of severe subvalvular pathology (SVP), preexisting MR, calcification, or oversizing. The pressure zone used--with the low pressure zone (LPZ) the lower half of the spectrum of sizes available out of a single balloon, and the high pressure zone (HPZ) the upper two levels, i.e., within 2 mm of its maximum size--could have a bearing on the occurrence of MR, but has not been studied before. We analysed 251 consecutive patients (mean age 28.6 + 9.7 years), undergoing BMC from October 1993 onwards, with pliable, non-calcific, splittable (bilateral dark zones present) valves with not more than trivial MR (1 + in grades of 1-4). Balloon sizing was done with standard formula using height with stepwise dilatation starting 2 mm below the reference size. Thirty-two patients additionally had severe SVP. Patients were divided into two groups, HPZ-BMC and LPZ-BMC, depending upon the final balloon size needed for a successful result. Incidence of MR (2+ or more) was significantly lower in the LPZ BMC (18%) vs. HPZ BMC (32.2%) (P < 0.05). Moderate to severe MR (3+/4+) was also less in LPZ BMC (2.8%) vs. HPZ BMC (8.2%) (P < 0.05). Amongst patients with severe SVP, 3/15 (20%) developed MR in the LPZ-BMC group (all mild only) as against 8/17 (42%) (P < 0.05) in the HPZ-BMC group with half of them having moderate to severe MR. In 54 patients where the reference size had to be exceeded, no patient (0/8) developed MR as long as the higher size was in the LPZ of the particular balloon used as compared to 17/46 (36.9%) who developed MR when the size used fell in the HPZ. We conclude that the pressure zone used has a strong bearing on the occurrence of MR in Inoue BMC and that a low-pressure strategy could avoid MR.

Adult↗
PubMed1998

Vaccination with trypomastigote surface antigen 1-encoding plasmid DNA confers protection against lethal Trypanosoma cruzi infection.

DNA vaccination was evaluated with the experimental murine model of Trypanosoma cruzi infection as a means to induce antiparasite protective immunity, and the trypomastigote surface antigen 1 (TSA-1), a target of anti-T. cruzi antibody and major histocompatibility complex (MHC) class I-restricted CD8(+) cytotoxic T-lymphocyte (CTL) responses, was used as the model antigen. Following the intramuscular immunization of H-2(b) and H-2(d) mice with a plasmid DNA encoding an N-terminally truncated TSA-1 lacking or containing the C-terminal nonapeptide tandem repeats, the antibody level, CTL response, and protection against challenge with T. cruzi were assessed. In H-2(b) mice, antiparasite antibodies were induced only by immunization with the DNA construct encoding TSA-1 containing the C-terminal repeats. However, both DNA constructs were efficient in eliciting long-lasting CTL responses against the protective H-2Kb-restricted TSA-1515-522 epitope. In H-2(d) mice, inoculation with either of the two TSA-1-expressing vectors effectively generated antiparasite antibodies and primed CTLs that lysed T. cruzi-infected cells in an antigen-specific, MHC class I-restricted, and CD8(+)-T-cell-dependent manner. When TSA-1 DNA-vaccinated animals were challenged with T. cruzi, 14 of 22 (64%) H-2(b) and 16 of 18 (89%) H-2(d) mice survived the infection. The ability to induce significant murine anti-T. cruzi protective immunity by immunization with plasmid DNA expressing TSA-1 provides the basis for the application of this technology in the design of optimal DNA multicomponent anti-T. cruzi vaccines which may ultimately be used for the prevention or treatment of Chagas' disease.

Animals↗
PubMed1997

Proteins with glycosylphosphatidylinositol (GPI) signal sequences have divergent fates during a GPI deficiency. GPIs are essential for nuclear division in Trypanosoma cruzi.

Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell surface proteins of several major protozoan parasites of humans, including Trypanosoma cruzi, the causative agent of Chagas' disease. To investigate the general role of GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression of T. brucei GPI-phospholipase C. Putative protein-GPI intermediates were depleted, causing the biochemical equivalent of a dominant-negative loss of function mutation in the GPI pathway. Cell surface expression of major GPI-anchored proteins was diminished in GPI-deficient T. cruzi. Four proteins that are normally GPI-anchored in T. cruzi exhibited different fates during the GPI shortage; Ssp-4 and p75 were secreted prematurely, while protease gp50/55 and p60 were degraded intracellularly. These observations demonstrate that secretion and intracellular degradation of GPI-anchored proteins may occur in the same genetic background during a GPI deficiency. We postulate that the interaction between a protein-GPI transamidase and the COOH-terminal GPI signal sequence plays a pivotal role in determining the fate of these proteins. At a nonpermissive GPI deficiency, T. cruzi amastigotes inside mammalian cells replicated their single kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs appear to be essential for nuclear division, but not for mitochondrial duplication.

Animals↗