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Biomedical subjects

M Verma

Publications and source records attributed to M Verma.

At least 91 records · Page 5Linked to original sources

Neutrophil leukotriene generation increases after cardiopulmonary bypass.

BACKGROUND: Leukotriene B4 has been shown to play a role in the systemic inflammatory response after cardiopulmonary bypass in experimental animal models; however, the importance of this mediator in human beings undergoing cardiac operations has not been established. METHODS: The neutrophils of ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were studied for their ability to generate leukotrienes at the time of the induction of anesthesia, the institution of cardiopulmonary bypass, the removal of the aortic crossclamp, at the end of the operation, on admission to the intensive care unit, and on postoperative days 1 and 2 RESULTS: After cardiopulmonary bypass, the generation of chemotactic leukotrienes rose significantly and remained elevated on the first postoperative day compared with prebypass values (prebypass 133.8 +/- 10.7 versus postbypass 192.7 +/- 19.2 [p < 0.05] and first postoperative day 196.6 +/- 13.8 [p < 0.05]). The increases in plasma complement and lactoferrin levels, although significant, were not sustained. In addition to the neutrophil count, the potential leukotriene and oxygen radical produced was significantly increased, and this increase was correlated with postoperative length of stay. CONCLUSION: These observations support the laboratory data documenting that the rise in leukotriene generation after cardiopulmonary bypass includes human patients.

Aged↗

Triazines as anti-inflammatory agents.

5,6-Diphenyl 1,2,4-triazine-3-thiol (III) was synthesized from alpha-diketone benzyl (II); II in turn was synthesized from benzoin (I). III on reaction with 1-chloro-2,3-epoxy propane yielded 3-[(oxiranyl methyl)thio]-5,6-diphenyl 1,2,4-triazine (IV). IV was converted to 3-[5,6-diphenyl-1,2,4-triazine-3-yl thio]-3-substituted propanols (V) on reaction with aryl amines. These compounds were screened for their anti-inflammatory activity in albino rats with carrageenin induced paw oedema. Two compounds, Ve and Vl, exhibited significant anti-inflammatory activity compared to the standard, phenylbutazone, with high ALD50 values.

Animals↗

Molecular cloning and sequencing of a canine tracheobronchial mucin cDNA containing a cysteine-rich domain.

To date the complete sequence of only one mammalian mucin cDNA, MUC1, has been reported, although several mucin proteins have been partially characterized. Here we report the nucleotide sequence of a canine tracheal mucin cDNA containing two potential translation initiation codons, one translation termination codon and a poly(A) tail. A lambda gt11 cDNA library prepared from canine tracheal epithelial cells was screened with polyclonal anti-apo-canine tracheal mucin antibodies with the aim of obtaining the deduced amino acid sequence of the mucin core protein. Antibody-positive clones containing overlapping inserts of various lengths were purified and used for nucleotide sequencing. Based on the sequencing data, synthetic oligonucleotide primers were constructed and both ends (5' and 3') of the cDNA were determined. The complete sequence was 3.7 kb and included an open reading frame with coding capacity for 1118 aa, two translation initiation ATG codons in context with Kozak consensus sequences, one polyadenylylation site, and a poly(A) stretch. The protein was rich in Thr, Pro, Ser, Gly, and Ala and poor in Tyr, Phe, and Trp. Although tandem repeats of amino acids were absent in the deduced canine tracheal mucin sequence, motifs TPTPTP and TTTTPV appeared 13 and 19 times, respectively. The C-terminal region contained a Cys-rich domain (although a few Cys residues were also present in the middle of the protein) as has been reported for bovine submaxillary mucin, porcine submaxillary mucin, rat intestinal mucin, human intestinal mucin, and frog skin mucin. This suggested that a broad group of mucins contain such a Cys-rich domain whose functional significance is yet to be understood. Three potential N-glycosylation sites were present in canine tracheal mucin and the amino acid sequence showed homology with both human tracheal and intestinal mucins. The N-terminal domain showed more flexibility (probably due to a high number of Pro residues in this region) when analyzed by the University of Wisconsin Genetics Computer Group program package to determine the predicted secondary structure. Evaluation of the transcripts using the canine mucin cDNA as a probe indicated a polydisperse message with total RNA.

Amino Acid Sequence↗

Human lung enolase: cloning and sequencing of cDNA and its inducibility with dexamethasone.

Corticosteroids used orally and intravenously lead to lung diseases and vascular disorder. To investigate whether enolase levels are also changed by treatment with synthetic steroid dexamethasone (as alteration in the enolase levels have been correlated with lung cancer) we performed the following studies. A cDNA library was prepared from poly(A) mRNA extracted from human lung fibroblast cells. cDNA clone HLE1 containing 1.7 kb insert coding for enolase was isolated. Its identity was confirmed by (a) translation of the hybrid selected mRNA and (b) nucleotide sequence analysis of the insert and comparison with known enolase sequences from other species. The lung enolase is coded by a polypeptide of 458 amino acid residues (mr = 49.5 kD). Nucleotide sequencing and derived amino acid sequence data suggest that the cloned enolase is non-neuronal isoform of enolase (NNE). In lung fibroblast cells, dexamethasone caused remarkable increase in the abundance of the enolase mRNA, which was concentration and time dependent. The induction by dexamethasone required de novo RNA synthesis but not de novo protein synthesis.

Amino Acid Sequence↗

Attitudes of medical students towards Objective Structured Clinical Examination (OSCE) in pediatrics.

A standardized Likert type scale containing 10 items was administered to 40 Fourth year medical students to assess their attitudes towards Objective Structured Clinical Examination (OSCE). The overall attitudes were favorable. However, on certain aspects, a near neutral attitude was observed. Remedial changes in the teaching methodology have been undertaken to mould the attitudes favorably as well as to make pediatric teaching more effective.

Attitude↗

C-myc, c-fos, and c-ras coding sequences are conserved from yeast to mammals.

Oncogenes, along with the autocrine secretion growth factors, emerged as a unifying theme in the search for the molecular and cellular basis of malignant transformation. To investigate whether some of the oncogene coding sequences are phylogenetically conserved, we performed hybridization experiments using well characterized c-myc, c-fos and c-ras oncogene probes to establish the sequence divergence in the genomes of different organisms. Our results indicate the c-myc, c-fos, and c-ras coding sequences exist in human, cow, monkey, rabbit, chicken, and yeast genomes. To the best of our knowledge this is the first report wherein a correlation among species in the oncogenes coding region has been established. The evolutionary implication of the present studies is discussed.

Animals↗

Antipyrine congeners as antidepressant agents.

1-(N-Antipyrinylglycyl)-3-arylideneamino)-2-thiobarbituric acids (III) were synthesized from 1-arylidene-4-(N-antipyrinyl glycyl)-3-thiosemicarbazones (II). Compounds II in turn were prepared from 4-amino antipyrine. Compounds III were finally converted into 1-(N-antipyrinylglycyl)-3-[(3'-chloro-4-aryl)azitidinyl]-2-t hiobarbituric acids (IV). 4-Aminoantipyrine was also treated with different N-protected amino acids in the presence of N,N'-dicyclohexylcarbodiimide to yield N-(antipyrinylcarbamoyl) substituted alkyl benzamides (V); their debenzoylation yielded 2-(amino-N-antipyrinyl) substituted acetamides (VI). The compounds were screened for their antidepressant activity. Compounds IIId, Va and Vb exhibited activity better than imipramine with less toxicity (ALD50 > 1000 mg/kg).

Amphetamine↗

Experiences with objective structured clinical examination (OSCE) as a tool for formative evaluation in pediatrics.

Mean scores obtained at objective structured clinical examination (OSCE) and clinical case (CC), by 4 groups of 15 students each were compared. The range of dispersion was more with OSCE as compared to CC. There was no correlation between the scores obtained at OSCE and CC. It is suggested that OSCE can be employed for evaluation of specific clinical skills; however, for comprehensive evaluation, a combination of OSCE and CC should be used.

Clinical Competence↗

Thiazolidinone congeners as central nervous system active agents.

3-(Benzylidene amino)-2-imino-4-thiazolidinones (IIa-c) synthesized by cyclization of substituted thiosemicarbazones (Ia-c) were converted into 2-amino-3-(substituted benzylamino)-4-thiazolidinones (IIIa-c), 2-imino-3-(alpha-aryl azo benzylidene) amino-4-thiazolidinones (IVa-f) and 2-(2-amino-4-oxo-3-thiazolidinyl)-3-aryl-4-isothiazolidinones (VIa-c), IVa-f were finally converted into 5-(arylamino methyl)-2-imino-3-(alpha-aryl azobenzylidene)-amino-4-thiazolidinones (Va-l). These compounds III, V and VI were evaluated for their monoamine oxidase (MAO) inhibitory activity in vitro and various CNS activities in vivo. Some of the compounds exhibited promising CNS activity.

Amphetamine↗

Attitudes of medical students towards IAP Pediatric Quiz.

Attitudes of medical students towards IAP Pediatrics Quiz were assessed, using a 5 point pre-tested, standardized Likert type scale, developed in our own department. Students had a favorable attitude towards the Quiz and felt that it helps them in the study of Pediatrics, but they are not able to devote sufficient time for preparations because of their preoccupation with other major subjects. The attitudes demonstrated a decline towards unfavorableness when comparison was made between the scores of third year and final year medical students. The difference was statistically significant (p < 0.05). It is suggested that the timing of the Quiz should be changed, so that it doesn't coincide with final professional examinations. This will make it more popular besides generating interest of medical students in Pediatric. Giving more weightage to Pediatrics in university examinations is also re-emphasized as a means of making students more interested in pediatrics.

Attitude↗

Microwave induced alteration in the neuron specific enolase gene expression.

Exposure of pNGE7, a recombinant clone containing the coding and regulatory sequences for the expression of neuron specific enolase gene, cells to electromagnetic radiations (915 MHz, 16 Hz AM, SAR 0.05 mW/kg) resulted in the elevation of neuron specific enolase (NSE), a diagnostic marker for neuron and lung cancer. Using ion-exchange chromatography we separated the neuron specific enolase activity from the non-neuronal enolase (NNE) activity and observed an alteration in the expression of neuron specific enolase and non-neuronal enolase. The clinical applications of the present studies have been discussed.

Base Sequence↗

Liposome-mediated modulation of multidrug resistance in human HL-60 leukemia cells.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in cancer treatment. Resistance of cultured tumor cells to major classes of cytotoxic drugs is frequently due to expression of a plasma membrane P-glycoprotein encoded by MDR genes. We have demonstrated that liposome-encapsulated doxorubicin is more toxic than the free drug and that it modulates MDR in Chinese hamster LZ cells and human colon cancer cells. PURPOSE: To investigate further the association between expression of P-glycoprotein and modulation of MDR by liposome-encapsulated doxorubicin, we studied vincristine-resistant HL-60/VCR leukemia cells, which express P-glycoprotein, and doxorubicin-resistant HL-60/ADR leukemia cells, which do not. METHODS: Cells were exposed to various concentrations of free doxorubicin and liposome-encapsulated doxorubicin. The cellular content of doxorubicin was determined by fluorescence analysis, and cytotoxicity was determined by cell growth inhibition. Photoaffinity-labeling studies of P-glycoprotein binding were performed on HL-60/VCR and HL-60/ADR cells and KB-GSV2 cells transfected with the MDR1 gene (also known as PGY1). RESULTS: The concentrations that caused 50% inhibition of growth (IC50) for free doxorubicin in HL-60, HL-60/ADR, and HL-60/VCR cells were 30 nM, 9 microM, and 0.9 microM, respectively. The values for liposome-encapsulated doxorubicin in parental HL-60 cells and HL-60/ADR cells were 20 nM and 9 microM, respectively, indicating little or no sensitization. In contrast, HL-60/VCR cells were fivefold more sensitive to liposome-encapsulated doxorubicin than to free doxorubicin, and IC50 was reduced to 0.17 microM. In HL-60 cells exposed to liposome-encapsulated doxorubicin, intracellular doxorubicin accumulation was less than that seen with free drug. In contrast, in HL-60/VCR cells, accumulation was twofold to threefold higher than that with free doxorubicin. Liposome-encapsulated doxorubicin completely inhibited the photoaffinity labeling of P-glycoprotein by azidopine in membrane vesicles of HL-60/VCR cells, with a potency comparable to that of azidopine, suggesting that circumvention of MDR by liposomes is related to their specific interaction with P-glycoprotein. The studies with KB-GSV2 cells indicated that blank liposomes can directly inhibit photoaffinity labeling of P-glycoprotein. CONCLUSIONS: These results demonstrate the effectiveness of liposome-encapsulated doxorubicin in overcoming resistance in the multidrug-resistant phenotype of HL-60/VCR cells by direct interaction with P-glycoprotein. Furthermore, they indicate that liposome-encapsulated doxorubicin may be an effective treatment for human cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Decreased access to medical care for girls in Punjab, India: the roles of age, religion, and distance.

Risk factors that increase the likelihood of discrimination against girls in India have not been well studied. In this study of hospitalized children in Punjab, India, girls were less likely to be in the newborn or infant age groups, to be of the Sikh religion, or to come from far away than were boys. These differences suggest that these factors are significant risk factors for denied access to medical care for girls living in Punjab, India.

Adolescent↗

Analytical procedures for a cryptic messenger RNA that mediates translational control of prostaglandin synthase by glucocorticoids.

Expression of the enzyme prostaglandin H synthase in cultured vascular smooth muscle cells required epidermal growth factor (EGF) and type beta transforming growth factor (TGF-beta) and was inhibited by cycloheximide but not actinomycin D. Preincubation with the glucocorticoid dexamethasone (0.5 microM) blocked the EGF-induced expression of prostaglandin H (PGH) synthase. Following dexamethasone addition, levels of hybridizable mRNA for PG synthase were reduced by over 90% within 1 h. After dexamethasone was removed, PG synthase mRNA recovered within 3 h by a process that was not inhibited by actinomycin D. These observations, together with other findings, suggested that the mRNA was being converted into some nonextractable and nontranslated form, probably by binding of a glucocorticoid-induced protein to the conserved 3' untranslated region. In order to investigate further the nature of this phenomenon, seven different literature procedures were evaluated for extracting and determining the PG synthase mRNA. Five of the seven procedures failed to detect hybridizable PG synthase mRNA in glucocorticoid-treated cells. Two procedures, however, recovered mRNA in both glucocorticoid-treated and control cells. A comparison of the protocols indicated that only those methods that incorporate a cationic detergent (sodium N-lauroylsarcosine), instead of anionic detergents in the lysis or homogenization buffers, successfully extract the glucocorticoid-suppressed PG synthase mRNA. Based upon these results two procedures are described, one that optimizes the extraction and determination of the glucocorticoid-suppressed (cryptic) form of the mRNA, and another which optimizes the analysis of normal mRNA without extracting the cryptic form. The results indicate that translational control of PG synthase by glucocorticoids is regulated by converting the mRNA into a cryptic form that is more firmly tissue bound than normal mRNA.

Animals↗