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Biomedical subjects

H Kaur

Publications and source records attributed to H Kaur.

At least 19 recordsLinked to original sources
PubMed1996

Do human atherosclerotic lesions contain nitrotyrosine?

Nitrotyrosine has been widely used as a marker of peroxynitrite formation in normal and diseased tissues. However, studies of normal human aortic intima and atherosclerotic lesions at various stages of development failed to reveal its presence except in a very few specimens of both normal and diseased tissues. The techniques used to detect nitrotyrosine-HPLC with photodiode array detection and Western blotting- were able to identify nitrotyrosine after chemical nitration. Hence peroxynitrite may not be as important in the initiation of atherosclerosis as has commonly been proposed.

Antibody Specificity↗
PubMed1996

Measurement of oxidized and methylated DNA bases by HPLC with electrochemical detection.

Oxidative DNA damage is thought to be an important contributor to cancer development and to be affected by dietary constituents, so its accurate measurement is important. DNA methylation is recognized as an important mechanism affecting gene expression. In the present paper we describe an HPLC-with-electrochemical-detection procedure that allows rapid and sensitive measurement of four oxidized (2,6-diamino-4-hydroxy-5-formamidopyrimidine, 5-hydroxyuracil, 8-hydroxyguanine, 8-hydroxyadenine) and three methylated (7-methylguanine, 1-methylguanine, O6-methylguanine) bases in acid hydrolysates of DNA. Guanine was also detected, but was clearly separated from the other bases.

Chromatography, High Pressure Liquid↗
PubMed1996

Mutational studies of conserved residues in the dimer interface of nerve growth factor.

An understanding of the structure-function relationship of nerve growth factor (NGF) requires precise knowledge of all the residues and regions that participate in NGF receptor binding, receptor activation, and biological activity. Seven recombinant human NGF mutants having alanine substituted for residues located either in the NGF dimer interface or beta-strand region were studied to determine the role of each amino acid residue in NGF biological activity. F86A, T91A, R100A, and R103A remained nearly full active with 61, 120, 91, and 73% of wild-type activity, respectively, in the PC12 cell bioassay. Hydrophobic core and dimer interface residues Y52, F53, and F54 were studied in more detail. Y52A and F54A were expressed in very low levels, suggesting that these two residues may be important for protein stability. Y52A retained full biological activity (91%). F53A had a 20- and 70-fold reduction in biological activity and TrkA phosphorylation, respectively, with only a 5- to 10-fold effect on TrkA binding and no effect on low-affinity receptor binding. F54A had significantly decreased TrkA phosphorylation and biological activity (40-fold). The results suggest that F53 and F54 may play a structural role in TrkA receptor activation subsequent to binding.

Animals↗
PubMed1996

Studies on activation and inhibition of cathepsin B from buffalo liver.

Cathepsin B (EC 3.4.22.1) was purified from buffalo liver. The enzyme activity against alpha-benzoyl-DL-arginine-naphthylamine (BANA) was substantially reduced by heat (above 37 degrees C) and by nondenaturing concentrations of urea (3 M) and guanidine hydrochloride (1 M). Cathepsin B was significantly activated by 1.5 mM EDTA alone. The activation of the enzyme was further enhanced in the presence of thiol compounds, e.g., cysteine thioglycolic acid, 2,3-dimercapto-1-propenol, and dithioerythritol (DTE). The minimum concentration of the thiol compound required for optimal activation of cathepsin B was found to be lowest (0.2 mM) for DTE. The BANA hydrolyzing activity of cathepsin B was substantially reduced by Cu2+ (20-200 microM) and Ca2+ (30-250 mM) as well as by thiol blocking reagents, e.g., iodoacetate, 5,5'-dithiobis(2-nitro-benzoic acid) (DTNB), and p-hydroxymercuribenzoate (pHMB). The enzyme activity was completely abolished when the molar ratio of the reagent: cathepsin B was close to 1. The number of free sulfhydryl groups in cathepsin B was determined to be 2 by titration against DTNB and pHMB. Modification of one free thiol group of cathepsin B resulted in complete loss of BANA hydrolyzing activity.

Animals↗
PubMed1996

Acute respiratory tract infection: a community-based intervention study in Malaysia.

A community-based intervention trial was conducted in Kelantan, Malaysia with the aim of reducing severe acute respiratory tract (ARI) infection in children. Interventions included health education of mothers on childhood pneumonia and training of health staff on case management. In a house-to-house survey 1382 and 1107 children less than 5 years of age in the intervention and control areas, respectively, were followed up every 2 weeks over a 62-week period. The reduction in the incidence of severe ARI cases in the intervention area was significantly greater than in the control area (P < 0.05). The ARI mortality rates were low in both the intervention and control areas ( < 0.1%). Our results indicate that with relatively inexpensive methods and simple interventions, reduction of severe ARI may be effectively achieved. This has important implications for an ARI control programme in Malaysia and other developing countries.

Acute Disease↗
PubMed1996

Protection against peroxynitrite dependent tyrosine nitration and alpha 1-antiproteinase inactivation by some anti-inflammatory drugs and by the antibiotic tetracycline.

OBJECTIVE: To examine in vitro the ability of several drugs to protect against deleterious effects of peroxynitrite, a cytotoxic agent formed by reaction of nitric oxide with superoxide radical, that may be generated in the rheumatoid joint and could cause joint damage. METHODS: The ability of several drugs to protect against such possible toxic actions of peroxynitrite as inactivation of alpha 1-antiproteinase and nitration of tyrosine was evaluated. RESULTS: Most non-steroidal anti-inflammatory drugs were moderately (indomethacin, diclofenac, naproxen, tolmetin) or only weakly (sulindac, ibuprofen, aurothioglucose, flurbiprofen, sulphasalazine, salicylate, penicillamine disulphide) effective in preventing tyrosine nitration and alpha 1-antiproteinase inactivation by peroxynitrite, but 5-aminosalicylate and penicillamine were much more effective, as was the antibiotic tetracycline (but not ampicillin). Phenylbutazone and flufenamic acid protected effectively against tyrosine nitration, but could not be tested in the alpha 1-antiproteinase system. The analgesic paracetamol was highly protective in both assay systems. CONCLUSION: Many drugs used in the treatment of rheumatoid arthritis are unlikely to act by scavenging peroxynitrite. The feasibility of peroxynitrite scavenging as a mechanism of penicillamine, 5-aminosalicylate, and paracetamol action in vivo is discussed.

Acetaminophen↗
PubMed1996

Partial purification and characterization of cyclic adenosine monophosphate dependent protein kinase from mycobacterium smegmatis.

Adenosine 3' 5'-monophosphate (cyclic AMP) - dependent protein kinase was purified about 42 fold from the M. smegmatis by ammonium sulphate fractionation followed by DEAE-cellulose and phosphocellulose column chromatography. SDS-PAGE revealed two prominent bands, with molecular masses of 55 KDa and 58 KDa. The enzyme preferentially utilized phosvitin and Histones as exogenous phosphate acceptor. Mg2+ ions were essential for enzyme activity, other metal ions like Ca2+, Zn2+, Co2+ and Mn2+, could not substitute for Mg2+. Inhibition of enzyme activity by thiol reagents, 5-5'-dithio bis (2-nitrobenzoic acid) and N-ethylmaleimide suggest that the cystein residues in the protein kinase might be located at or near the active site of the enzyme.

Amino Acid Sequence↗
PubMed1995

DNA damage and cancer: measurement and mechanism.

There is currently great interest in the possible role of reactive nitrogen species and reactive oxygen species in causing DNA damage that leads to cancer. It appears likely that certain reactive oxygen species can act as complete carcinogens. However, the development of human cancer will depend on other factors such as the extent of DNA damage, antioxidant levels and DNA repair systems. The true picture will only be seen if we have reliable and sensitive techniques for the measurement of DNA damage. In this article we outline various methods for measuring DNA damage base, with special emphasis on HPLC and GC-MS based systems.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Role of cyclic adenosine monophosphate in phospholipid synthesis in Mycobacterium smegmatis ATCC 607.

The present study was undertaken to examine the influence of intracellular levels of cyclic AMP on phospholipid synthesis in Mycobacterium smegmatis ATCC 607. The cyclic AMP levels were modulated by growing cells in the presence of activator (forskolin) and inhibitor (atropine) of adenylate cyclase, the synthesizing enzyme of cyclic AMP. Forskolin-grown cells exhibited a 1.4-fold increase in the level of cAMP while a similar decrease (1.8-fold) was seen with atropine-grown cells. These altered levels of cAMP in turn affected the total content, composition and synthesis of phospholipids. Total phospholipid content increased and decreased in cells grown in the presence of forskolin and atropine, respectively. These observations were further supported by alterations in [14C]acetate incorporation as well as in activities of glycerol kinase and glycerol-3-phosphate acyltransferase, the key enzymes of phospholipid synthesis. Protein phosphorylation mechanism seems to be involved in phospholipid metabolism as the activities of protein kinase increased and decreased in cells grown in forskolin or atropine cells. Our results demonstrate a correlation between phospholipid synthesis and intracellular levels of cAMP in M. smegmatis.

Adenylyl Cyclase Inhibitors↗
PubMed1995

Effect of the hydrophilic alpha-tocopherol analog MDL 74,405 on detection of hydroxyl radicals in stunned myocardium in dogs.

We have previously shown in dogs that the hydrophilic alpha-tocopherol analog, MDL 74,405, attenuates postischemic myocardial dysfunction ("stunning") and generation of free radicals as assessed with the spin trap alpha-phenyl N-tert-butyl nitrone (PBN). However, we could not discern whether this drug acts on primary radicals (such as hydroxyl radical [.OH]) or on secondary radicals. The goal of this study was to directly determine whether the beneficial effects of MDL 74,405 result from actions against .OH. Open-chest dogs undergoing a 15-minute coronary artery occlusion and 3 hours of reperfusion received an intravenous infusion of either saline solution (control group, n = 7) or MDL 74,405 (n = 6) starting 30 minutes before coronary occlusion and ending 60 minutes after reflow at a dose of 0.3 mg/kg/hr. Formation of .OH was estimated by the technique of aromatic hydroxylation of phenylalanine. Phenylalanine was infused intravenously, and the plasma concentrations of the hydroxylated products ortho-, meta-, and para-tyrosines (o-, m-, and p-tyr) in the coronary venous effluent and in the arterial blood were measured with high-performance liquid chromatography. In the control group a dramatic increase in the myocardial release of o-, m-, and p-tyr was observed immediately after reperfusion; the release of tyrosines peaked at 1 minute of reflow and continued up to 10 minutes after reperfusion. MDL 74,405 abolished the release of o-tyr throughout the first 10 minutes of reperfusion but had a less pronounced effect on the production of m- and p-tyr. These results demonstrate that MDL 74,405 is effective in inhibiting .OH-initiated reactions in the postischemic stunned myocardium in the dog, suggesting that the anti-.OH action of MDL 74,405 is an important mechanism of action of this antioxidant.

Animals↗
PubMed1995

Addition of immunotherapy with Mycobacterium w vaccine to multi-drug therapy benefits multibacillary leprosy patients.

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w, was given in addition to standard chemotherapy (multidrug therapy (MDT)) to 93 multibacillary (MB) leprosy patients. One hundred and seven patients with similar types of disease served as controls and received MDT + placebo injections. The study was a double-blind randomised trial. On opening the codes, results obtained were in concordance with those in a single-blind trial which has been extensively reported. Bacteriological clearances were significantly more rapid in vaccinated patients (p < 0.03). Thirty-five LL or BL patients with a high bacterial index (BI) of 6 were completely cleared of acid-fast bacilli (AFB) after eight doses of vaccine. Only 8 patients in the control group became bacteriologically negative in the same time period. They all had BIs < 4. Associated with decreasing BI was accelerated clinical regression of lesions after vaccination and lepromin conversion rates of 100% for BB, 71% for BL and 70% for LL. A significant number of immunised patients showed histological improvement (p < 0.004). Thirty-six showed a complete disappearance of dermal granulomas and a picture of non-specific infiltration. The vaccine did not precipitate neuritis or deformities; episodes were noted in vaccinated patients as were incidences of Type 2 reaction. The overall improvement was reflected by a shorter duration of treatment and faster release of vaccinated patients.

Bacterial Vaccines↗
PubMed1995

Rifamycins: strain improvement program.

Rifamycins are primarily produced by Gram-positive bacterium Amycolatopsis mediterranei, which belongs to the order Actinomycetales. These antibiotics, apart from their application against pathogens of tuberculosis and leprosy, have also been found to be effective against several other pathogens including Mycobacterium avium and Pneumococcus. Because of the importance of rifamycin, the producer strain A. mediterranei has been genetically manipulated since 1957 in order to develop a strain that can either produce larger amounts of rifamycin or derivatives of rifamycin. In this article, the importance of the producer strain, traditional methods (mutations and recombination) of strain improvement, their limitations, and the development of a cloning vector and transformation methods that have made recombinant DNA techniques accessible for genetic manipulations of A mediterranei are discussed.

Actinobacteria↗
PubMed1995

Importance of dynamic assessment of the soft tissues in the sonographic diagnosis of echogenic superficial abscesses.

Superficial abscesses evaluated by ultrasonography may occasionally be isoechoic relative to the surrounding inflamed tissues and without mass effect, preventing diagnosis by morphologic criteria alone. We present a simple and effective method to detect such abscesses. In three cases, gentle repetitive pressure of the inflamed tissue revealed the liquefied nature of abscesses that otherwise would have been overlooked.

Abscess↗
PubMed1995

Ascaris and Trichuris do not contribute to growth retardation in primary school children.

To access the effectiveness of the treatment of soil-transmitted helminthiasis (STH) on the growth of primary school children, 353 children were block stratified to receive either mebendazole plus pyrantel oxantel pamoate every three months or a placebo. The children were followed for two years with 89% completing the trial. Follow-up stools indicated that the treatment was efficacious for ascariasis and trichuriasis. There was virtually no hookworm infection. The children were malnourished as measured by the number below -2 SD of height and weight standards. There was no difference in height or weight between the treatment and control groups by sex initially or at the end of two years of follow-up. The treatment of Ascaris and Trichuris had no effect on growth parameters. The effect of STH on growth may be mediated through hookworm infections.

Ascariasis↗
PubMed1995

Predictive utility of clinical and stool parameters in bacterial diarrhoea in children.

A prospective one year study was conducted on children between the ages of 1 month to 5 years hospitalised in the pediatric ward of Christian Medical College, Ludhiana, with the aim of determining the predictive utility of certain clinical and stool parameters in diagnosing bacterial diarrhoea. Among the 204 children enrolled in the study, fever was observed in 40% in both the culture positive and negative groups. Clinical features such as abdominal distension, vomiting and oliguria although had low positive predictive values, their negative predictive values were high. Among the stool parameters, watery consistency and pus cells > 5 HPF were significantly more often observed in culture positive cases. The presence of mucus and pus cells > 5 HPF had good sensitivity (70-80%) but poor specificity (27-40%), while the reverse was true of blood (sensitivity 23%, specificity 89%). Again the positive predictive values were uniformly low while the negative ones were high. In conclusion the clinical and stool parameters were found to be more useful by their absence than by their presence in excluding a positive stool culture.

Bacterial Infections↗
PubMed1994

Intense oxidative DNA damage promoted by L-dopa and its metabolites. Implications for neurodegenerative disease.

Oxidative DNA damage can cause mutation and cell death. We show that L-DOPA, dopamine and 3-O-methyl-DOPA cause extensive oxidative DNA damage in the presence of H2O2 and traces of copper ions. 8-Hydroxyguanine is the major product. Iron ions were much less effective and manganese ions did not catalyse DNA damage. We propose that copper ion release, in the presence of L-DOPA and its metabolites, may be an important mechanism of neurotoxicity, e.g. in Parkinson's disease and amyotrophic lateral sclerosis.

Brain Chemistry↗