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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 1,207 records · Page 67Linked to original sources

Role of male behavior in cervical carcinogenesis among women with one lifetime sexual partner.

BACKGROUND: The role of male behavior in the genesis of cervical cancer was examined. In India, where the incidence of cervical cancer is among the highest in the world, promiscuity among women is virtually unknown. In this study, the authors investigated the role of male behavior in cervical carcinogenesis among Indian women who had one lifetime sexual partner. METHODS: A case-control study was used. RESULTS: Premarital sexual relationships (relative risk [RR], 1.9; confidence interval, 1.2-3.2) and extramarital sexual relationships (RR, 2.7; confidence interval, 1.5-4.9) of husbands were risk factors. When husbands had sexual relationships both before and during the marriage, their wives' risk of getting cervical cancer increased by 6.9 (CI, 2.3-20.7). Risk also increased with husbands having three or more extramarital sexual partners (RR, 3.05; CI, 1.25-12.6). Sexual contact with prostitutes before or after marriage, however, did not increase the risk. History of sexually transmitted disease before marriage (RR, 2.9) or after marriage (RR, 5.9) was an important risk factor, which persisted after controlling for other factors. Sexual abstinence for 40 or more days after a wife's giving birth or having an abortion provided protection. Sex with uncircumcised men or men circumcised after age 1 year increased the risk of cervical cancer (RR, 4.1). Bidi smoking (bidi is a cheap smoking stick of 4-8 cm, consisting of a rolled piece of dried temburni leaf [Diospyres melanoxylon] containing 0.15-0.25 g of coarsely ground tobacco) for more than 20 years was a significant risk factor (RR = 2.4), whereas cigarette smoking was not a risk factor. CONCLUSIONS: Male sexual partners play a role in cervical carcinogenesis.

Adult↗

Modulation of benzene induced toxicity by protein A.

Administration of benzene (i.p. 1.0 mL/kg body weight) for 3 consecutive days produced leucopenia and lymphocytopenia in female albino rats. In addition, the total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly (P < 0.001) increased. Low molecular weight (LMW) bleomycin-detectable iron accumulated only in bone marrow. Prior administration of Protein A (PA), a multipotent immunostimulant and interferon inducer (60 micrograms/kg body weight, i.v. twice weekly for 2 weeks), ameliorated most of the adverse effects of benzene. PA restored the changes in hepatic histological architecture, reversed leucopenia and superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content of bone marrow were normalized. Isozymes of glutathione-S-transferase (alpha, pi, mu) which decreased following benzene exposure increased in PA pretreated benzene exposed rats. This study suggests that pretreatment with PA modulates the toxicity of benzene.

Animals↗

Regional cerebral glucose metabolism in late-life depression and Alzheimer disease: a preliminary positron emission tomography study.

Eight subjects with late-life depression, eight subjects with probable Alzheimer disease, and eight healthy age-matched controls were studied using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in the resting state with their eyes open and ears unoccluded. The depressed subjects showed widespread reductions in the regional cerebral metabolic rate for glucose in most major neocortical, subcortical, and paralimbic regions that were significantly different from control values (P < 0.01). The metabolic decrements in the depressed group were comparable in magnitude to those seen in the Alzheimer disease group. These data demonstrate widespread nonfocal decline in glucose metabolism in late-life depression that is comparable to the hypometabolism seen in Alzheimer disease. These findings have pathophysiological implications in major depressive disorder in the elderly.

Aged↗

Mapping of nucleic acid binding in proteolytic domains of HIV-1 reverse transcriptase.

Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) and its domain fragments were used to map nucleic acid binding sites within the enzyme. Discrete domain fragments were produced after the digestion of three forms of RT (p66, p66/p51 heterodimer, and p51) with V8 protease or trypsin, and the primary structure of each domain fragment was mapped by both immunoblotting and N-terminal amino acid sequence analysis. These domain fragments represent N-terminal, middle, or C-terminal regions of RT. Using Northwestern or Southwestern blotting assays, the domain fragments were evaluated for nucleic acid binding. In this technique, RT proteins are electroblotted onto the membrane and renatured after SDS-PAGE; the proteins are then probed with the primer analogues 32P-labeled d(T)16 or 32P-labeled tRNA(Lys,3). A V8 protease domain fragment spanning residues 195 to approximately 300 (p12), which was found earlier to be UV cross-linked to the primer in intact RT [Sobol et al. (1991) Biochemistry 30, 10623-10631], showed binding to both nucleic acid probes. We first localized nucleic acid binding in p66 to an N-terminal domain fragment of residues 1 approximately equal to 300. By contrast, a C-terminal domain fragment termed p30(303 approximately equal to 560) did not show nucleic acid binding. To investigate the role of the region just N-terminal to residue 303, an expression vector named pRC-35 encoding residues 273-560 was constructed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

The minus 35-recognition region of Escherichia coli sigma 70 is inessential for initiation of transcription at an "extended minus 10" promoter.

It is known that Escherichia coli promoters having the major minus 10 consensus sequence TATAAT, but lacking significant resemblance to consensus in the minus 35 region, allow transcriptional initiation in vivo and in vitro if they have an additional TGn motif immediately upstream of minus 10. To determine whether region 4.2 of sigma 70, whose normal role is sequence recognition at minus 35, is unnecessary for initiation of transcription at such "extended minus 10" promoters, we modified the sigma 70 gene so as to generate a carboxy-truncated polypeptide lacking the last 84 amino acids and therefore missing region 4.2. Our results show that both the intact and truncated sigma 70 allow purified RNA polymerase to initiate efficiently and specifically at an extended minus 10 promoter, whereas only the intact sigma 70 permits efficient initiation at normal promoters (defined by minus 35 and minus 10 hexamer sequences).

Bacterial Proteins↗

Balloon pulmonary valvoplasty: factors determining short- and long-term results.

Balloon pulmonary valvoplasty was performed in 139 patients (age 2-44 years) with pulmonary valve stenosis. The right ventricular peak systolic pressure decreased from 137.1 +/- 46.8 mmHg to 76 +/- 51.3 mmHg (P < 0.001) and the right ventricle to pulmonary artery peak systolic gradient decreased from 116.3 +/- 49 mmHg to 54.4 +/- 51.9 mmHg (p < 0.001). There was no significant change in systemic artery systolic pressure. The right ventricular peak systolic pressure to systemic artery systolic pressure ratio decreased from 1.13 +/- 0.41 to 0.63 +/- 0.42 (P < 0.001). Patients with incomplete immediate relief of obstruction (right ventricle to pulmonary artery peak systolic gradient > 35 mmHg) had higher pre-dilatation right ventricular peak systolic pressure (161.1 +/- 45.3 mmHg vs. 93.9 +/- 38.8 mmHg, P < 0.001) and higher right ventricular peak systolic pressure to systemic artery systolic pressure ratio (1.31 +/- 0.42 vs 0.98 +/- 0.33, P < 0.001) pre-dilatation and were older (17.2 +/- 8.6 years vs. 12.8 +/- 9.7 years, P < 0.01). The residual right ventricle to pulmonary artery peak systolic gradients in the majority of patients were infundibular, which regressed at follow up even in patients who did not receive long-term oral beta blockers. Follow up catheterisation in 79 patients after 13 +/- 8.7 months showed a further fall in right ventricular peak systolic-pressure (P < 0.001) and right ventricle-to-pulmonary artery peak systolic gradient (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pattern of cardiac malformation in oculoauriculovertebral spectrum.

The reported prevalence of congenital heart defects (CHD) in the oculoauriculovertebral "spectrum" (OAVS) is 5-58%. This variability is mainly due to differences in the diagnostic criteria used, and to ascertainment bias introduced by selection of patients from different specialty databases. Two-thirds of the cardiac anomalies reported are either tetralogy of Fallot (TOF) or ventricular septal defect (VSD). We found a CHD frequency of 19% in a series of 32 patients identified either through a genetic or autopsy database. The cardiac lesions were much more varied and complex than previously reported and included asplenia syndrome, ventricular inversion associated with double outlet right ventricle, pulmonary atresia with VSD, double outlet right ventricle, and infradiaphragmatic total anomalous pulmonary venous connection. Pulmonary and renal abnormalities were more common in OAVS patients with CHD than in those where the heart was normal.

Canada↗

The dysfunction of coagulation factor VIIPadua results from substitution of arginine-304 by glutamine.

This study addresses whether a mutation in the factor VIIPadua gene could explain the reduced activity of the inherited variant protein. All nine exons of the normal and Padua factor VII gene were amplified using the polymerase chain reaction, cloned into pUC19 and sequenced. A point mutation (G to A at nucleotide position 10828) was found which results in the substitution of a glutamine (CAG) for arginine (CGG) at amino acid position 304. This substitution creates a PvuII restriction site useful in screening for the defect and in demonstrating homozygosity. This substitution involves an arginine residue in the catalytic domain within a Leu*****Pro******Cys motif which occurs in conserved region 5 in up to 16 coagulation and other serine proteinases. On the basis of conformational homology among serine proteinases, it is suggested that the observed amino acid substitution in factor VIIPadua could cause structural changes affecting its activation and/or catalytic activity.

Amino Acid Sequence↗

Concurrence of supravalvular aortic stenosis and peripheral pulmonary stenosis in three generations of a family: a form of arterial dysplasia.

Isolated supravalvular aortic stenosis (SVAS) commonly is an autosomal dominant trait; it may also occur in the Williams syndrome (WS). While peripheral pulmonary stenosis (PPS) can occur in the same individual with familial isolated SVAS, concurrence of these lesions in different relatives of a family is uncommon. We describe five affected individuals in one family; three had isolated SVAS, one had isolated PPS, and one had SVAS and PPS. Based on this family and review of literature, we suggest that SVAS is a form of arterial dysplasia encompassing PPS in its spectrum. It is developmentally distinct from other left heart obstructive lesions that are hypothesized to be related to blood flow abnormalities in the developing embryo. We also conclude that the clinical disorder in this family represents one that is distinct from WS.

Abnormalities, Multiple↗

Mammalian heterogeneous ribonucleoprotein A1 and its constituent domains. Nucleic acid interaction, structural stability and self-association.

With a view toward further understanding the structure-function relationships of the eukaryotic heterogeneous ribonucleoprotein (hnRNP) A1, and in particular its multiplicity of nucleic acid-interactive domains, we have studied the nucleic acid binding properties of the globular N-domain (UP1) and sequence-repetitive, flexible C-domain, the thermal denaturation of UP1 and the concomitant effects of binding polynucleotide, and the self-associative properties of the full-length protein. Utilizing protein tryptophan fluorescence as a probe, polynucleotide binding was shown to stabilize UP1 against thermal unfolding. The denaturation profile of UP1-poly(thymidylic acid) complexes was biphasic, suggesting that unfolding of the two subdomains of UP1 can occur independently. This is in agreement with a previously proposed structure in which only one of the two UP1 subdomains binds the nucleic acid. The subdomains of UP1 can be prepared by controlled proteolysis of A1, further indicating that these two globular segments within A1 are connected by an exposed, flexible linkage. Circular dichroism measurements on UP1 confirm previous data that this portion of A1 binds single-stranded nucleic acids non-co-operatively. UP1 clearly shows a preference for single-stranded nucleic acids with a 2'-OH, since its affinity for poly(U) is three times higher than for poly(dU), and five times higher than its affinity for poly(2'-OCH3U). The nucleic acid-interactive properties of the C-domain were further examined by preparing a synthetic peptide polymer (M(r) approximately 12,000) containing about seven repeats of a 16-residue sequence, GNFGGGRGGNYGGSRG, which in turn comprises two copies of the C-terminal consensus, GN(F/Y)GG(G/S)RG. The polymer of this sequence exhibited significant affinity for the fluorescent polyribonucleotide, poly(ethenoadenylic acid), binding stoichiometrically at < or = 0.2 M-Na+. Complex formation was accompanied by an increase in aggregate formation, as indicated by the appearance of scattering. For purposes of comparison, the data were analyzed via the linear co-operative model of McGhee and von Hippel, though this model may not be fully descriptive of the protein-nucleic acid complex(es) formed in this case. In contrast to the non-co-operative binding mode of the UP1 domain, the C-polymer exhibited moderate co-operativity, comparable to that seen with full-length A1. Although addition of sufficient NaCl reversed the interaction, a sigmoidal binding isotherm could still be observed (with sufficient added polymer) at 0.8 M-NaCl. This suggests that non-electrostatic interactions contribute significantly to the free energy of binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Intragastric bile acid and symptoms in patients with an intrathoracic stomach after oesophagectomy.

Bile acid concentration and symptoms were evaluated in 24 patients after total oesophagectomy and gastric pull-up. Patients were randomly allocated to receive pyloroplasty or not. After operation all were followed for a minimum of 6 months. Bile acid concentration in the gastric juice was estimated. The mean(s.d.) bile acid concentration 6 months after surgery was similar in patients with and without pyloroplasty (34.9(30.1) and 25.0(24.2) mg/dl respectively). Postprandial discomfort and bilious eructations were the two most commonly observed symptoms in both groups. Other features noted were vomiting, anaemia and anorexia. These did not however seem to be related to intragastric bile acid concentration of individual patients in either group and occurred irrespective of whether pyloroplasty was performed or not.

Adolescent↗

Successful aortic balloon valvuloplasty in critical aortic stenosis with shock.

Emergency balloon valvuloplasty was performed in a 42 year old male with critical aortic stenosis, severe congestive heart failure, and shock. Hemodynamic and clinical improvement occurred and he underwent elective aortic valve replacement. Balloon aortic valvuloplasty may provide a "bridge" to aortic valve replacement in patients with critical aortic stenosis and shock.

Adult↗

Sonourethrography in the evaluation of anterior urethral strictures: correlation with radiographic urethrography.

A total of 30 patients with suspected urethral strictures underwent sonographic and roentgenographic urethrograms. Two patients showed a normal anterior urethra in the sonourethrogram; 29 strictures were diagnosed in the remaining 28 patients, 1 patient showing strictures at two different sites. Sonourethrography was an accurate predictor of stricture length, retrograde urethrography underestimating the stricture length in most of the cases. Periurethral structures, including the urethral wall, corpus spongiosum, corpora cavernosa, bulb, and external urinary sphincter, were seen clearly with sonourethrography. Periurethral fibrosis was seen in 16 patients and graded as mild (n = 5), moderate (n = 2) or severe (n = 9), depending on the depth of involvement of the corpus spongiosum. Sonourethrography was unsatisfactory in the evaluation of membranous strictures, failing to visualize the proximal limit of the stricture.

Adult↗

Aspergillus fumigatus antigen induced eosinophilia in mice is abrogated by anti-IL-5 antibody.

A murine model of allergic bronchopulmonary aspergillosis (ABPA), developed by exposure to Aspergillus fumigatus antigens, demonstrated eosinophilia of peripheral blood (PB), bone marrow (BM), and lung. The eosinophilia was abrogated by monoclonal anti-interleukin-5 (IL-5) antibody (TRFK-5) and not by an isotype control antibody (GL 113). Eosinophils in PB were enumerated from stained smears and their relative increase or decrease in cells from BM and lung was determined by an eosinophil peroxidase (EPO) assay (measured in optical density). Intraperitoneal injection of TRFK-5 in mice exposed to A. fumigatus antigen produced a significant reduction in eosinophils (PB 6.6 +/- 1.14% vs. 3.8 +/- 0.8%, P < .01) and EPO production in BM (0.935 +/- 0.03 vs. 0.615 +/- 0.02, P < .001). A similar reduction in EPO production in the lung (0.691 +/- 0.12 vs. 0.495 +/- 0.05, not significant) was also reflected in the histopathology for the different groups of mice. These findings confirming the role of IL-5 in eosinophilia, although not surprising, are significant in elucidating the immunopathogenesis of ABPA in the murine model. We conclude that in this model, eosinophilia may be due largely to the Th2 cytokine -IL-5 induced by A. fumigatus antigens.

Animals↗

Serologic markers of viral hepatitis A, B, C, and D in patients with hemophilia.

Forty-one patients with hemophilia A were studied for the prevalence of serological markers for hepatitis A, hepatitis B, hepatitis C (non-A and non-B hepatitis), and delta hepatitis (hepatitis D). Ten of 41 (24.4%) patients demonstrated hepatitis A antibody and 31 of 41 (75.6%) patients had a serologic marker for previous hepatitis B infection; four of these 31 patients (13%) also demonstrated antibody to delta agent (hepatitis D). Thirty-seven of 41 (90.2%) patients demonstrated antibody for hepatitis C. Nine of 31 (29%) patients with a hepatitis B marker (no hepatitis B vaccinees) were negative for anti-HBc but positive for anti-HBs; all of these nine patients were HIV antibody positive, although they had no overt immunodeficiency. Twenty-six of 41 (63.5%) patients were HIV antibody positive. Of HIV antibody positive patients, 27%, 88%, and 100% demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C, respectively. Of HIV antibody negative patients; 20%, 53%, and 73% of the patients demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C infections, respectively. The difference between HIV antibody positive and HIV antibody negative groups was not significant for hepatitis A but was significant for hepatitis B (P < 0.001) and hepatitis C (P < .001). Of the 31 patients with a hepatitis B serologic marker, all had antibody to hepatitis C. Of 10 patients, without a hepatitis B serologic marker, only 6 (60%) had antibody to hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Gas chromatographic-mass spectrometric assay of tissue malondialdehyde, 4-hydroxynonenal, and other aldehydes after their reduction to stable alcohols.

Measurement of specific aldehydes such as malondialdehyde, hexanal, or 4-hydroxynonenal provides a method to evaluate the extent of lipid peroxidation. However, assay of aldehydes is complicated by their high reactivity toward other molecules and their chemical instability. In the proposed method, aldehydes are reduced to stable alcohols. Except for malondialdehyde, this is readily accomplished under neutral conditions at room temperature or at 4 degrees C with either sodium borodeuteride (NaB2H4) or sodium borohydride (NaBH4). Complete reduction of malondialdehyde requires a more powerful reducing agent, borane trimethylamine. After ether extraction and evaporation of the organic phase, the alcohols are converted to t-butyldimethylsilyl ethers and analyzed by selected ion monitoring gas chromatography-mass spectrometry in the positive chemical ionization mode for malondialdehyde and 4-hydroxynonenal and electron impact mode for all other aldehydes. Quantitation is achieved using internal standards of 1,3-[2H8]propanediol for MDA, of 4-[2-2H]hydroxynonenal for 4-hydroxynonenal, and of the corresponding saturated per-deuterated alcohols for all saturated aldehydes, for example and [2H13]hexanol for hexanal. Saturated per-deuterated alcohols also serve as external standards for their unsaturated aldehydes with same chain length. The detection limit for individual aldehydes is 0.5 nmol in a given sample. In addition to being highly sensitive and selective, the present method allows one to verify the identity of each aldehyde by observing a mass shift when aldehydes are reduced with either NaB2H4 or NaBH4. The usefulness of our method is demonstrated by measuring aldehyde accumulation in autoxidized arachidonic acid solutions and in heart homogenates before and after induction of peroxidation.

Alcohols↗

Specific amplification of Aspergillus fumigatus DNA by polymerase chain reaction.

We have developed a specific and sensitive method to detect the human pathogen Aspergillus fumigatus by polymerase chain reaction (PCR) with an objective of detecting the organism in peripheral blood and urine which can be obtained by non-invasive procedures. A pair of oligonucleotide primers for PCR were designed based on the published partial protein sequences of an 18 KD IgE-binding protein of A. fumigatus Asp f1 and the ribotoxins mitogillin and restrictocin of A. restrictus, and alpha-sarcin of A. giganteus. The primers were specific in amplifying an expected 315 bp region of the homologous genes in A. fumigatus and A. restrictus but not in A. giganteus. Also, there was no amplification of human DNA or DNA of A. flavus, A. niger, A. fischeri, Penicillium sp., Candida albicans and Pneumocystis carinii. The sensitivity of the PCR detection of A. fumigatus DNA is about 20 pg on an ethidium bromide gel and 0.6 pg by Southern analysis using a 32P-labelled internal oligonucleotide. In preliminary analysis of 13 urine specimens of patients suspected of invasive aspergillosis (IA), two were PCR positive, one of whom died of IA with brain lesion. Further analyses of both urine and blood specimens of IA are in progress to determine the comparative utility of PCR over the conventional antigen tests.

Aspergillus↗