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Biomedical subjects

M Kumar

Publications and source records attributed to M Kumar.

At least 73 records · Page 4Linked to original sources
PubMed1996

Bereavement is associated with time-dependent decrements in cellular immune function in asymptomatic human immunodeficiency virus type 1-seropositive homosexual men.

Seventy-nine human immunodeficiency virus type 1 (HIV-1)-seropositive homosexual men participating in a longitudinal study of HIV-1 infection were assessed twice, 6 months apart, to investigate associations between bereavement and cellular immune function. Subjects were assessed by using a theory-driven model comprising life stressors, social support and coping style, and control variables. Natural killer cell cytotoxicity was decreased among the bereaved at both times. Lymphocyte proliferative response to phytohemagglutinin was decreased among the bereaved at the second time point but not at the first. These functional immune decrements are associated with increased neuroendocrine responses of the sympathetic adrenomeduallary system as well as the limbic-hypothalamic-pituitary-adrenal axis. Implications for differential neuroendocrine responses over time are discussed. Active coping style was independently and positively related to both immune measures. The results imply that a bereavement support group intervention merits investigation for an effect on immunological measures and clinical progression of HIV-1 infection as well as grief resolution.

Adaptation, Psychological↗
PubMed1996

Isolation of an ftsZ homolog from the archaebacterium Halobacterium salinarium: implications for the evolution of FtsZ and tubulin.

We have isolated a homolog of the cell division gene ftsZ from the extremely halophilic archaebacterium Halobacterium salinarium. The predicted protein of 39 kDa is divergent relative to eubacterial homologs, with 32% identity to Escherichia coli FtsZ. No other eubacterial cell division gene homologs were found adjacent to H. salinarium ftsZ. Expression of the ftsZ gene region in H. salinarium induced significant morphological changes leading to the loss of rod shape. Phylogenetic analysis demonstrated that the H. salinarium FtsZ protein is more related to tubulins than are the FtsZ proteins of eubacteria, supporting the hypothesis that FtsZ may have evolved into eukaryotic tubulin.

Amino Acid Sequence↗
PubMed1996

Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.

Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.

Adult↗
PubMed1996

Healing of chronic antral gastritis: effect of sucralfate and colloidal bismuth subcitrate.

BACKGROUND: Colloidal bismuth subcitrate (CBS) causes endoscopic and histological improvement in gastritis and eradication of Helicobacter pylori in patients with non-ulcer dyspepsia (NUD). The effect of sucralfate, a cytoprotective drug, on endoscopic and histologic gastritis and H pylori clearance is not clear. We studied the effect of CBS and sucralfate on these features in patients with NUD. METHODS: Sixty three patients with NUD and H pylori infection were randomized to receive one of the following for four weeks: (i) CBS (240 mg twice daily) (Group 1); (ii) placebo I, similar in size, color and shape to CBS (Group 2); (iii) sucralfate (2.0 g twice daily) (Group 3) and (iv) placebo II, similar to sucralfate (Group 4). Symptoms, endoscopic and histological findings and H pylori status were assessed before and after treatment. RESULTS: Similar symptomatic improvement was observed with each treatment, indicating a placebo effect. Significant endoscopic and histological improvement was observed with CBS only. CBS was better than sucralfate in inducing endoscopic and histological improvement. Clearance rate of H pylori was 46.6% with CBS, 16.6% with its placebo, 33.3% with sucralfate and 13.3% with its placebo. CONCLUSION: CBS is more effective than sucralfate in inducing endoscopic and histologic healing of H pylori-related gastritis among NUD patients.

Adult↗
PubMed1996

Gastrointestinal bleeding in children.

We prospectively evaluated 139 consecutive children presenting to the Sanjay Gandhi Postgraduate Institute of Medical Sciences (Lucknow, India) with gastrointestinal (GI) bleeding from January 1991 to November 1994. Our aims were to find out whether the causes of GI bleeding in a developing country differed from developed countries and how the application of newer diagnostic techniques would help in the diagnosis of GI bleeding. Barium studies, endoscopy, technetium-99m-labelled (erythrocytes and pertechnetate) scans, selective abdominal angiography using a digital subtraction technique and rectal endoscopic ultrasonography were performed. Upper GI bleeding (n = 75) was variceal in 71 (95%) children (extrahepatic portal venous obstruction in 65, cirrhosis in six) and non-variceal in four (5%) cases (Henoch-Schonlein purpura, idiopathic thrombocytopenic purpura, drug-induced gastric erosions and pseudoaneurysm of the gastroduodenal artery due to idiopathic chronic calcific pancreatitis). Causes of lower GI bleeding (n = 64) were colitis (27 cases; 42%), colorectal polyps (26 cases; 41%), enteric fever (n = 3), solitary rectal ulcer (n = 3), portal hypertensive colopathy (n = 2), colonic arteriovenous malformation (n = 1) and internal haemorrhoids (n = 1). One patient remained undiagnosed. Angiography performed in four children was diagnostic in two. In one child with massive lower GI bleeding from portal colopathy, the bleeding site (caecum) was localized by intra-operative colonoscopy, while in the other child with portal colopathy, rectal endoscopic ultrasonography was performed to substantiate the diagnosis. We conclude that the causes of upper GI bleeding in children in developing countries are different from those in developed countries (variceal bleeding due to extrahepatic portal venous obstruction is the most common cause, while peptic ulcer is rare). However, the spectrum of lower GI bleeding is similar to that of developed countries. Application of newer diagnostic techniques is helpful and safe in the identification of the cause of GI bleeding in children.

Child↗
PubMed1996

Immunoproliferative small intestinal disease: a frequently missed diagnosis.

Immunoproliferative small intestinal disease (IPSID) is a poorly recognized cause of malabsorption syndrome in India. Clinicopathological features of five patients with IPSID seen over a two-year period are described. Our data suggest that IPSID is commonly misdiagnosed as intestinal tuberculosis due to lack of awareness and reluctance to obtain small bowel biopsies. Empirical institution of anti-tubercular chemotherapy not only leads to delayed diagnosis but also possibly alters the natural history of the disease, resulting in an intermediate phase of amelioration followed by a terminal phase of lymphomatous transformation. The disease is therefore usually diagnosed at an advanced stage and hence is associated with a relatively poor outcome.

Adult↗
PubMed1996

Synthetic peptides related to laminin pentapeptide (YIGSR) fragment.

The synthetic laminin pentapeptide amide fragment (LF), Tyr-Ile-Gly-Ser-Arg-NH2 corresponding to a part of B1 chain of the glycoprotein, laminin, and six of its analogues having structural modifications at positions 1, 3 and 4 were synthesized by solid phase method employing mainly 9-fluorenylmethoxycarbonyl-amino acid trichlorophenyl esters as coupling agents and Merrifield resin as the solid support. Their biological activities were studied in vivo by lung tumor colonization assay and in vitro by cell adhesion assay. The activity of synthetic LF was found to correlate with the earlier reported results in both in vivo and in vitro assays. Among the analogues made, [Tyr4] LF and [Thr4]LF were found to inhibit the lung tumor colonies more efficiently than LF itself in the in vivo assay whereas [D- Ser4]LF exhibited almost the same inhibition as LF.

Animals↗
PubMed1996

Neonatal cholestasis syndrome: an appraisal at a tertiary center.

OBJECTIVE: To know the magnitude, etiology and clinical profile, the efficacy of various investigations and the outcome in patients with neonatal cholestasis syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants with NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years. SETTING: Tertiary level referral gastroenterology center in North India. METHODS: Liver function tests, urine examination, serum antibodies against Cytomegalovirus (CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done. In appropriate setting, laparotomy and surgical corrections were done for biliary tract disorders. RESULTS: NCS constituted 19% of pediatric liver diseases. Considerable delay in presentation was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0 months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%) infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract infection and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%) were of indeterminate etiology. Liver biopsy was the most accurate (96.4%) investigation in discriminating between EHBA and NH. Of the 18 operated infants with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive (mean follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic. CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian children. (ii) It requires prompt referral, quick investigative approach and targeted management. (iii) Liver biopsy is highly accurate in differentiating EHBA and NH. (iv) infants with EHBA and compensated status of liver should undergo corrective surgery irrespective of age at presentation.

Biliary Atresia↗
PubMed1996

Endoscopic, histologic and microbiologic evaluation of upper abdominal pain with special reference to Helicobacter pylori infection.

OBJECTIVE: To study children with significant upper abdominal pain of unidentifiable etiology and evaluate: (a) the relationship of pain to inflammatory esophago-gastro-duodenal lesions and Helicobacter pylori (HP) infection, and (b) the response to specific therapy. DESIGN: Prospective study. SETTING: Pediatric section of a tertiary referral gastroenterology center. SUBJECTS: Thirty three consecutive children with significant upper abdominal pain [mean age 9.9 +/- 2.7, range 4-15 years; 20 males] were subjected to upper gastrointestinal tract endoscopy and antral mucosal biopsies obtained for rapid urease test (RUT), Gram's staining of impression/crush smears and culture for HP and histologic examination. Patients with HP gastritis were treated with triple therapy, colloidal bismuth subcitrate, amoxycillin and metronidazole, for two weeks. At 8 weeks from the initiation of therapy, patients were re-evaluated for symptoms and HP eradication by repeat endoscopy and antral biopsies. Patients with esophagitis, gastritis and duodenitis without HP infection were treated with ranitidine for 6 weeks. All the patients were followed up for 6 months. RESULTS: Histology revealed antral gastritis in 28/33 (85%) patients. HP infection was present in 12/28 (43%) patients with antral gastritis. Symptomatic improvement with triple therapy was observed in 10/12 (83%) patients with HP gastritis and eradication of HP in 5/7. Improvement on ranitidine therapy was observed in 12/16 (75%) patients with HP negative gastritis. On follow-up, no patient with initial improvement with therapy had relapse of symptoms. CONCLUSION: Symptomatic children with HP related gastritis should be treated with triple therapy and HP negative gastritis with H2-receptor antagonist.

Abdominal Pain↗
PubMed1995

Serotonin uptake and its kinetics in platelets of women with Alzheimer's disease.

The uptake of serotonin (14C-5-hydroxytryptamine, 5HT) in platelets and its kinetic characteristics were investigated in a group of women (n = 20) with probable Alzheimer's Disease (mean age = 76.0, years, SD = 8.27, range = 63-88) and in healthy normal women (n = 18, mean age = 72.6 years, SD = 7.24, range = 61-84). Both the apparent affinity of binding of 5HT to the platelet membrane (Km) and the maximum velocity (Vmax) of the rate of transport of 14C-5HT into platelets were significantly higher in the Alzheimer's Disease group than in the normal comparison group. Initial velocity of 14C-5HT uptake not passive diffusion (nonspecific uptake of 14C-5HT at 4 degrees C) differed significantly in the two groups. Our findings suggest abnormalities in the kinetic mechanisms involved in the uptake of 14C-5HT by platelets in women with Alzheimer's Disease.

Aged↗
PubMed1995

A methylnickel intermediate in a bimetallic mechanism of acetyl-coenzyme A synthesis by anaerobic bacteria.

Resonance Raman (RR) spectroscopy was used to identify a methylnickel adduct (upsilon Ni-C = 422 wave numbers) of carbon monoxide dehydrogenase (CODH) from Clostridium thermoaceticum. Formed at a nickel/iron-sulfur cluster on CODH called center A, the methylnickel species is the precursor of the methyl group of acetyl-coenzyme A in an anaerobic pathway of carbon monoxide or carbon dioxide fixation. Rapid kinetic and RR studies demonstrated that methylation of nickel occurs by heterolysis of the methyl-cobalt bond (upsilon Co-C = 429 wave numbers) of a methylated corrinoid/iron-sulfur protein. In combination with the earlier finding of an iron-carbonyl adduct at center A, detection of the methylnickel intermediate establishes a bimetallic mechanism for acetyl-coenzyme A synthesis.

Acetyl Coenzyme A↗
PubMed1995

The effect of phosphorylation on the antigenic reactivity of p53 in cultured human keratinocytes.

The detection of p53 in human keratinocytes is dependent on the specific anti-p53 monoclonal antibody that is used. Differences in antibody recognition are postulated to be due to the masking or exposure of particular epitopes in different conformations of p53. This study addresses the role of phosphorylation on p53-epitope accessibility in human keratinocytes. Keratinocytes were treated with the phosphatase inhibitor, okadaic acid, to determine the effect of inhibiting cellular phosphatases on p53 phosphorylation and epitope recognition. These studies suggest there is a correlation between the level of p53 phosphorylation and the antigenic reactivity of certain p53 epitopes in human keratinocytes. We also examined the ability of the catalytic subunits of protein phosphatase 1 and 2A to dephosphorylate p53 derived from human keratinocytes in vitro. These data suggest that PP2A may be the phosphatase that acts on p53 in cultured human keratinocytes.

Antibodies, Monoclonal↗
PubMed1995

Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD.

Prominent heightened arousal symptoms and clinical/laboratory findings implicate the central noradrenergic system in posttraumatic stress disorder (PTSD). Heightened arousal frequently manifests in relation to sleep in PTSD. Central noradrenergic systems have a role in regulating arousal levels during sleep. We therefore evaluated noradrenergic production via urinary excretion in relation to sleep/wake activity in PTSD patients and controls. Twenty patients--all Vietnam veterans diagnosed with combat-related PTSD--and eight non-ill, non-combat-exposed controls had overnight sleep studies under medication and substance-free conditions. In association with sleep recording, subjects saved their urine for 24 hours in three 8-hour collections in order to obtain "daytime" (8:00 AM to 4:00 PM, 4:00 PM to MN) and "nocturnal" (MN to 8:00 AM) catecholamine measures. PTSD patients had decreased sleep efficiency relative to controls and increased REM density; 24-hour norepinephrine and MHPG (the more centrally derived metabolite) did not differ between patients and controls. "Nocturnal" excretion of MHPG minus the average of the two "daytime" values was negative in the controls, slightly positive in the patients, and differed significantly between the two groups. "Nocturnal minus daytime" MHPG also correlated negatively with total sleep time in the PTSD patients (R = -.45, p < .05). Our data support a relationship of nondiminished central noradrenergic activity at night, and sleep disturbance, in chronic, combat-related PTSD.

Adult↗
PubMed1995

Mechanism of CO oxidation by carbon monoxide dehydrogenase from Clostridium thermoaceticum and its inhibition by anions.

Carbon monoxide dehydrogenase (CODH) performs two distinct reactions at two different metal centers. The synthesis of acetyl-CoA from a methyl group, CO, and coenzyme A occurs at center A and the oxidation of CO to CO2 occurs at center C. In the work reported here, we have studied the mechanism of CO oxidation by CODH and its inhibition by thiocyanate. Our data are consistent with a ping-pong mechanism. A scheme to explain the first half-reaction was developed that includes binding of water and CO to the oxidized form of center C, deprotonation of coordinated water to yield enzyme-bound hydroxyl, nucleophilic attack on coordinated CO by OH- to form enzyme-bound carboxyl, and deprotonation and decarboxylation to form CO2 and the reduced form of center C. In the second half-reaction, the reduced enzyme is reoxidized by an electron acceptor. CO oxidation was pH dependent. The pH dependence of kcat/Km for CO gave a single pKa of 7.7 and a maximum value at 55 degrees C and high pH of 9.1 x 10(6) M-1 s-1. The pH dependence of kcat followed a two-phase titration curve with pKa values of 7.1 and 9.5 and maximum value of kcat at 55 degrees C and high pH of 3250 s-1 (1310 mumol of CO oxidized min-1 mg-1). The pH dependencies of kcat/Km and kcat are interpreted to reflect the ionization of enzyme-bound water from binary and ternary complexes with center C. Reaction with thiocyanate, azide, or cyanate was found to cause a striking shift in the EPR spectrum of center C from gav = 1.82 (g = 2.01, 1.81, 1.65) to a two-component spectrum with gav = 2.15 (g = 2.34, 2.067, 2.03) and gav = 2.17 (g = 2.34, 2.115, 2.047). Thiocyanate acted as a mixed partial inhibitor with respect to CO. The inhibition constants were pH and temperature dependent. The pH dependencies of the inhibition constants gave pKa values of approximately 7.7. Binding of thiocyanate to the oxidized form of center C appears to be favored by a negative enthalpy that is offset by a decrease in entropy yielding a slightly unfavorable free energy of association.

Aldehyde Oxidoreductases↗
PubMed1995

Structural and electronic factors in heterolytic cleavage: formation of the Co(I) intermediate in the corrinoid/iron-sulfur protein from Clostridium thermoaceticum.

We have completed the first direct structural characterization of an enzyme-bound four-coordinate Co(I) intermediate, in this case for the corrinoid/iron-sulfur protein (C/Fe-SP) from Clostridium thermoaceticum. Extended X-ray absorption fine structure and X-ray edge spectroscopy of the active Co(I) state of the C/Fe-SP indicates a four-coordinate (distorted) square-planar structure where the best fit gives average Co-N(equatorial) distances of 1.87 +/- 0.01 A, corresponding to 4.2 +/- 0.3 ligands. The X-ray edge spectrum of Co(I) C/Fe-SP contains a moderate intensity 1s-4p + "shake-down" (SD) transition and no 1s-3d peak (where SD transitions are indicative of square-planar geometries). X-ray edge results for the methyl-Co(III) form, reported earlier [Wirt, M. D., Kumar, M., Ragsdale, S. W., & Chance, M. R. (1993) J. Am. Chem. Soc. 115, 2146-2150], are consistent with a base-off methylcobamide structure. The absence of a ligated 5-methoxybenzimidazole base in the methyl-Co(III) state is important since the base-off form is predicted to predispose the Co-C bond toward heterolytic cleavage to form the four-coordinate Co(I) species concurrent with methyl transfer. Additionally, we have examined first-derivative X-ray edge spectra of Co(I) C/Fe-SP, relative to edge spectra of a cobalt foil, as an indicator of effective nuclear charge on cobalt. The Co(I) C/Fe-SP edge position at 7720.5 +/- 0.3 eV is less than, but very close to, the value seen for the corresponding free Co(I) cobalamin.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗