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Biomedical subjects

V Sharma

Publications and source records attributed to V Sharma.

At least 181 records · Page 10Linked to original sources
PubMed1997

Bipolar depression: treatment options.

OBJECTIVE: To review studies on treatments for bipolar depression and make recommendations for practising clinicians treating patients with bipolar depression. METHOD: Studies that examined various treatments for bipolar depression were evaluated and rated for evidence of efficacy using Periodic Health Examination criteria. The rating for classification of recommendation for an intervention was made taking both the efficacy and the side effects into consideration. RESULTS: Mood stabilizers, cyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and electroconvulsive therapy (ECT) are all effective in treating bipolar depression. Almost all antidepressant treatments with the exception of mood stabilizers have been reported to induce a manic-hypomanic switch and rapid cycling. CONCLUSIONS: Mood stabilizers, lithium in particular, are recommended as the first-line treatment. Addition of a second mood stabilizer or a cyclic antidepressant would be an appropriate next step. Newer agents such as lamotrigine offer considerable promise in treating bipolar depressed patients.

Antidepressive Agents↗
PubMed1997

Continuation and prophylactic treatment of bipolar disorder.

OBJECTIVES: To summarize the evidence for efficacy from published literature of biological treatments in the continuation and maintenance phases of bipolar disorder, as well as the recommendations about different treatment options made by the working group within the Bipolar Sub-Committee of the Canadian Network for Mood and Anxiety Treatments (CANMAT). METHODS: A review of relevant published literature and proceedings of international conferences was conducted. The quality of evidence was assessed and classified according to the Periodic Health Examination criteria. Treatment recommendations of the working group were based on quality of evidence, a consensus of expert views, and the opinions of psychiatrists and family physicians from across Canada. RESULTS: There is overwhelming evidence for the efficacy of lithium in the prophylaxis of bipolar disorder. The evidence for carbamazepine is less robust. There are no published double-blind studies with adequate numbers of subjects treated with divalproex sodium. CONCLUSIONS: During and at the end of the continuation phase it is recommended that mood stabilizers should remain the mainstay of therapy and that other treatments should be gradually discontinued or maintained only if there is valid reason to do so. Efficacious maintenance treatment can reduce morbidity and mortality significantly and improve patients' quality of life.

Algorithms↗
PubMed1997

Tuberculous duodenal obstruction--a case report.

Proximal duodenal obstruction due to tuberculosis can masquarade as duodenal ulcer. Although commonest cause of duodenal obstruction is ulcer, other causes must be considered, particularly tuberculosis which is common in tropics.

Adult↗
PubMed1996

Identification of a new member of the MNP transcription factor family in differentiated HL60 cells.

MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem cells and modulate inflammatory responses. It is also an inhibitor of HIV replication in CD8+ T-cells, MIP-1 alpha is expressed in transformed B cells and can also be induced during cellular activation of CD4+ T-cells and monocytes. We have previously identified a new transcription factor family (the MNP family) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cells strongly express only MNP-2. In this communication we show evidence identifying a new member of the MNP transcription family, MNP-3, in PMA differentiated HL60 cells.

Base Sequence↗
PubMed1996

Effects of multidrug resistance (MDR1) P-glycoprotein expression levels and coordination metal on the cytotoxic potency of multidentate (N4O2) (ethylenediamine)bis[propyl(R-benzylimino)]metal(III) cations.

Enhanced mitochondrial transmembrane potentials in tumor cells have been proposed to confer tumor-selective-targeting properties to modestly lipophilic monocationic compounds. To explore the potential cytotoxic activity of lipophilic cationic metallopharmaceuticals containing a highly flexible hexadentate N4O2 Schiff-base phenolic ligand, we first synthesized precursors H3Mabi (1) and H3DMabi (2) by condensation of an appropriate linear tetraamine with substituted salicylaldehydes. The desired N4O2 ligands, (ethylenediamine)-N,N'-bis[propyl[(2-hydroxy-3-methoxybenzyl)imino]] and (ethylenediamine)-N,N'-bis[propyl[2-hydroxy-4,6-dimethoxybenzyl)-imino]] (R-ENBPI), were obtained by cleavage of the imidazolidine ring, and their corresponding monocationic complexes were produced by reaction with appropriate hydrated salts or acetylacetonates of Al(III), Fe(III), Ga(III), and In(III). All complexes were stable to neutral hydrolysis. In human epidermal carcinoma KB-3-1 cells, cytotoxic potencies of racemic mixtures of these complexes were in the low micromolar range and, for a given ligand, depended on the identity of the coordinating central metal. The active 4,6-dimethoxy-ENBPI complexes were more potent than their 3-methoxy analogs, while the free ligands and metal(III) ions showed little or no cytotoxic activity. Furthermore, in colchicine-selected KB-8-5 multidrug resistant (MDR) cells, modest cellular expression of human MDR1 P-glycoprotein conferred protection from the cytotoxic activities of Al(III), Fe(III), and Ga(III) R-ENBPI complexes indicating that these complexes were recognized as transport substrates by the P-glycoprotein efflux transporter. However, the cytotoxic activities of the corresponding In(III) complexes, while among the lowest in potencies, were also not altered by expression of MDR1 P-glycoprotein. Thus, for the Group III elements, human cells were capable of distinguishing R-ENBPI complexes formed of the same ligands with different metals. Furthermore, selected R-ENBPI metal(III) complexes may be useful as novel anticancer metallopharmaceuticals.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Imparting exquisite specificity to peanut agglutinin for the tumor-associated Thomsen-Friedenreich antigen by redesign of its combining site.

Lectins from legumes constitute one of the most thoroughly studied families of proteins, yet the absence of a rigorous framework to explain their carbohydrate binding specificities appears to have prevented a rational approach to alter their ligand binding activity. Studies reported here deal with the redesign of the recognition propensity of peanut agglutinin (PNA), an important member of the family. PNA is extensively used as a tool for recognition of the tumor-associated Thomsen-Friedenrich antigen (T-antigen; Galbeta1-3GalNAc) on the surfaces of malignant cells and immature thymocytes. PNA also recognizes N-acetyllactosamine (LacNAc; Galbeta1-4GlcNAc), which is present at the termini of several cell-surface glycoproteins. The crystal structure of the PNA-lactose complex revealed, in addition to the expected interactions with the residues constituting the binding site, the presence of leucine 212 at a position close enough to be in steric contact with the acetamido group on LacNAc. We report here two leucine mutants, one to asparagine (L212N) and the other to alanine (L212A), that exhibit distinct preference for T-antigen and N-acetyllactosamine, respectively. Carbohydrate binding studies reveal that mutant L212N does not recognize LacNAc at high concentrations, thus making it an exquisitely specific cell-surface marker compared with its wild-type counterpart.

Antigens, Neoplasm↗
PubMed1996

Cloning and sequencing of winged bean (Psophocarpus tetragonolobus) basic agglutinin (WBA I): presence of second glycosylation site and its implications in quaternary structure.

We report cloning of the DNA encoding winged bean basic agglutinin (WBA I). Using oligonucleotide primers corresponding to N- and C-termini of the mature lectin, the complete coding sequence for WBA I could be amplified from genomic DNA. DNA sequence determination by the chain termination method revealed the absence of any intervening sequences in the gene. The DNA deduced amino acid sequence of WBA I displayed some differences with its primary structure established previously by chemical means. Comparison of the sequence of WBA I with that of other legume lectins highlighted several interesting features, including the existence of the largest specificity determining loop which might account for its oligosaccharide-binding specificity and the presence of an additional N-glycosylation site. These data also throw some light on the relationship between the primary structure of the protein and its probable mode of dimerization.

Amino Acid Sequence↗
PubMed1996

HIV-1 tat induces the expression of a new hematopoietic cell-specific transcription factor and downregulates MIP-1 alpha gene expression in activated T-cells.

MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem cells and modulate inflammatory responses. It is also an inhibitor of HIV replication in CD8+ T-cells. The expression of MIP-1 alpha is induced during cellular activation of CD4+ T-cells and monocytes. It is also expressed in transformed B-cells. We have previously identified a new transcription factor family (the MNP family) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation and in transformed B cells. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cells strongly express only MNP-2. Recently, we reported that HIV-1 tat downregulates MIP-1 alpha expression in Jurkat T-cells. In this report we show induction of MNP-1 in Jurkat T-cells expressing HIV-1 tat. Expression of neither HTLV-1 tax in Jurkat T-cells nor EBV in B-cells had any effect on MNP-1 or MNP-2 expression, showing that the effect is specific for HIV-1 tat. We propose that HIV-1 tat may inhibit MIP-1 alpha expression by inducing MNP-1 expression in T-cells, probably by either competing with MNP-2 for binding to the MIP-1 alpha promoter or by sequestering it into inactive forms.

B-Lymphocytes↗
PubMed1996

IL-12 expression in AIDS-related lymphoma B cell lines.

IL-12 is a 70-kDa heterodimer formed by the 40-kDa heavy chain (p40) and the 35-kDa light chain (p35). Twenty-five Burkitt's lymphoma cell lines (CL) and seven normal lymphoblastoid B CL were studied. The Burkitt's CL included AIDS-associated B CL (AABCL) (7 EBV+/2 EBV-) and non-AABCL (8 EBV+/8 EBV-). Reverse transcription-PCR detected p40 in EBV+ AABCL (7 of 7), EBV+ non-AABCL (3 of 8), and normal lymphoblastoid B CL (6 of 6) but not in EBV- CL (0 of 10). p35 mRNA was detected in 30 of 30 CL. Constitutive secretion of p40 was found in 7 of 7 EBV+ AABCL (range, 341-18,086 pg/ml) and p70 in 3 of 7 EBV+ AABCL (range, 25-197 pg/ml), but in only 1 of 8 EBV+ non-AABCL and 0 of 7 normal lymphoblastoid CL. PMA stimulated p40 secretion in 7 of 7 EBV+ AABCL and p70 secretion in 5 of 7 EBV+ AABCL. PMA also triggered p40 and p70 secretion in 2 EBV+ non-AABCL and in 3 of 7 normal lymphoblastoid CL. No IL-12 secretion was detected in 10 EBV- CL, including EBV- AABCL. The CL produced IL-10, a known inhibitor of IL-12, but anti-IL-10 Abs did not neutralize IL-12. Similarly, neutralizing anti-IFN gamma Abs or IFN gamma did not affect B cell IL-12. For IL-12R studies, reverse transcription-PCR and 125I-IL-12 binding assays were performed. Although all CL tested showed mRNA accumulation for one of the IL-12R components, IL-12 binding sites were detected in only 1 of 30 CL. Our data suggest that: 1) AABCL constitutively secrete large amounts of IL-12, contrasting with low IL-12 production by HIV-1 infected PBMC; 2) lack of IL-12 expression in EBV- AABCL suggests that in vivo exposure of B cells to HIV-1 only does not induce IL-12 secretion and that both HIV-1 and EBV are required; 3) the autocrine-negative effect of IL-10 on IL-12 in monocytes and the enhancing effect of IFN gamma on IL-12 secretion do not apply to B cells derived from AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Menaquinone (vitamin K2) biosynthesis: localization and characterization of the menE gene from Escherichia coli.

In Escherichia coli, the biosynthesis of the electron carrier menaquinone (vitamin K2) involves at least seven identified enzymatic activities, five of which are encoded in the men cluster. One of these, the conversion of o-succinylbenzoic acid to 1,4-dihydroxy-2-naphthoic acid, requires the formation of o-succinylbenzoyl-CoA (OSB-CoA) as an intermediate. Formation of the intermediate is mediated by OSB-CoA synthetase encoded by the menE locus known to be located either 5' of menB, or 3' of menC. A DNA fragment overlapping the 3' end of menC in shown by enzymatic complementation to elevate OSB-CoA synthetase activity. Nucleotide sequence analysis of the fragment identified a 1.355-kb open reading frame (ORF) which, when deleted at either the 5' or 3' end, failed to generate increased enzymatic activity. The ORF is preceded by a consensus ribosome-binding site, but no apparent sigma-70 promoter. An oppositely transcribed unidentified gene cluster follows the menE ORF. The region 5' of menB contains an an additional ORF of unknown function (orf241) and establishes the order of genes in the men cluster as menD, orf241, menB, menC and menE. All loci are transcribed counter-clockwise.

Acyl Coenzyme A↗
PubMed1996

The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients.

We report the clinical and neuropathologic phenotypes associated with two different missense mutations in the presenilin 1 (PS-1) gene in Japanese patients with early-onset familial Alzheimer's disease (FAD). In the AM/JPN1 pedigree a missense mutation (C-->T) was found at nucleotide 1102, which is predicted to cause an alanine-to-valine missense substitution at codon 260. In this family, the disease had a mean age of onset of 40.3 years and an indolent course (range, 8-19 years). Neuropathologic studies in 3 members of this pedigree showed widespread senile plaques, neurofibrillary tangles, and neuronal loss, as well as abundant perivascular subpial amyloid deposits in the Virchow-Robin spaces and the presence of Pick-like intraneuronal inclusions in the dentate gyrus. In the second pedigree, transmitting a C-->T nucleotide substitution at position 1027, leading to the missense mutation of alanine to valine at codon 285, the disease had a later onset (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes associated with other missense mutations in exon 9 of PS-1 reveals no clinical or pathological phenotype, which uniquely distinguishes Alzheimer's disease associated with PS-1 mutations from other forms of early-onset FAD, implying that direct mutation screening is required to identify these cases.

Adult↗
PubMed1996

Wide range in age of onset for chromosome 1--related familial Alzheimer's disease.

Mutations in three different genes on chromosomes 1, 14, and 21 cause autosomal dominant forms of familial Alzheimer's disease (FAD). Most result in an early-onset phenotype. However, several kindreds of Volga German ancestry have the same chromosome 1 gene mutation and demonstrate a relatively older mean age of onset and include individuals with late age of onset. In these families, the mean age of onset is 54.9 +/- 8.4 years (range, 40-75 years), mean age at death is 65.9 +/- 10.2 years (range, 43-88 years), and mean disease duration is 11.3 +/- 4.6 years (range, 5-23 years). This contrasts with a group of 7 families with chromosome 14 mutations in which the mean age of onset is 44.8 +/- 4.8 years (range, 30-55 years), mean age at death is 52.6 +/- 5.7 years (range, 39-65 years), and mean disease duration is 7.6 +/- 3.2 years (range, 2-17 years). (All means are significantly different in the 2 groups of families, p < 0.005.) In the chromosome 1 families, 7 persons (16%) had an age of onset at or older than 65 years and 22 (54%) survived to age 65 or older versus none in the chromosome 14 families. An example of probable nonpenetrance of disease at age 89 was also found in a chromosome 1 kindred. It is concluded that, unlike the chromosome 14 gene, mutations in the chromosome 1 FAD gene may result in individuals with a late age of onset overlapping with the more common sporadic form of the disease occurring in the general population. In light of the great variability in age of onset in persons with identical mutations, study of the genetic and environmental factors contributing to delayed onset of disease in chromosomal 1 FAD kindreds will be an important area for further investigation. Apolipoprotein E genotype may be one such factor that plays a partial role in this variability.

Adult↗
PubMed1996

Longitudinal epidemiological study of coronary heart disease in a rural population of Kheda district, Gujarat, India.

The present study was undertaken to determine the incidence and related risk factors for coronary heart diseases and hypertension in the rural population of Kheda district, Gujarat (India). The observations from the first five years of this ongoing project (May 1987-May 1992) are described in this paper. Out of an initial sample of 750 individuals in the age group 30-62 years, who were selected by stratified random sampling, 714 persons (males = 429; females = 285) were actually studied, after excluding those suffering from coronary heart diseases (CHD). Initially, all the included subjects were examined clinically and appropriate laboratory investigations were done. A detailed socio-economic history was also obtained. Subsequently all of them were followed up and biannual clinical and laboratory investigations were performed. Cases of CHD were diagnosed according to the recommendations of the New York Heart Association. The overall five-year incidence of CHD was 25.17 per thousand persons. The incidence in males was 3 times higher than in females. More males suffered from myocardial infarction (MI), while in the females the incidence of sudden death was higher (33.3%). The average yearly mortality rate due to CHD was 2.46 per thousand persons. CHD was significantly associated with increased blood pressure (both diastolic and systolic), smoking, and family history of heart disease, and was weakly associated with body weight (p = 0.06).

Adult↗
PubMed1996

Poloxamer 188 decreases susceptibility of artificial lipid membranes to electroporation.

The effect of a nontoxic, nonionic block co-polymeric surface active agent, poloxamer 188, on electroporation of artificial lipid membranes made of azolectin, was investigated. Two different experimental protocols were used in our study: charge pulse and voltage clamp. For the charge pulse protocol, membranes were pulsed with a 10-micronsecond rectangular voltage waveform, after which membrane voltage decay was observed through an external 1-M omega resistance. For the voltage clamp protocol the membranes were pulsed with a waveform that consisted of an initial 10-microsecond rectangular phase, followed by a negative sloped ramp that decayed to zero in the subsequent 500 microseconds. Several parameters characterizing the electroporation process were measured and compared for the control membranes and membranes treated with 1.0 mM poloxamer 188. For both the charge pulse and voltage clamp experiments, the threshold voltage (amplitude of initial rectangular phase) and latency time (time elapsed between the end of rectangular phase and the onset of membrane electroporation) were measured. Membrane conductance (measured 200 microseconds after the initial rectangular phase) and rise time (tr; the time required for the porated membrane to reach a certain conductance value) were also determined for the voltage clamp experiments, and postelectroporation time constant (PE tau; the time constant for transmembrane voltage decay after onset of electroporation) for the charge pulse experiments. The charge pulse experiments were performed on 23 membranes with 10 control and 13 poloxamer-treated membranes, and voltage pulse experiments on 49 membranes with 26 control and 23 poloxamer-treated membranes. For both charge pulse and voltage clamp experiments, poloxamer 188-treated membranes exhibited a statistically higher threshold voltage (p = 0.1 and p = 0.06, respectively), and longer latency time (p = 0.04 and p = 0.05, respectively). Also, poloxamer 188-treated membranes were found to have a relatively lower conductance (p = 0.001), longer time required for the porated membrane to reach a certain conductance value (p = 0.05), and longer postelectroporation time constant (p = 0.005). Furthermore, addition of poloxamer 188 was found to reduce the membrane capacitance by approximately 4-8% in 5 min. These findings suggest that poloxamer 188 adsorbs into the lipid bilayers, thereby decreasing their susceptibility to electroporation.

Electric Conductivity↗
PubMed1996

A prospective outcome study of patients with clot in an ulcer and the effect of irrigation.

BACKGROUND: The proper management of patients with clots in an ulcer base has not been clearly defined by prospective studies. Variable prevalence and rebleeding rates may be explained by differing degrees of vigor used to clear the clot, as removal may reveal other stigmata. We prospectively assessed the natural histories of patients with clots after vigorous irrigation, employing a management strategy of endoscopic therapy for patients with high-risk stigmata and observation of those with clots resistant to washing or low-risk findings. METHODS: Forty-six patients with upper gastrointestinal bleeding found to have a clot in an ulcer had irrigation with a 3.2 mm bipolar probe for up to 5 minutes. Stigmata after washing were recorded; endoscopic therapy was given for active bleeding that persisted > or = 5 min or for nonbleeding visible vessels. Patients were observed in the hospital for > or = 3 days. RESULTS: Findings revealed after irrigation were adherent clot, 26 (57%); clean base, 1 (2%); flat spot, 5 (11%); nonbleeding visible vessel, 7 (13%); oozing, 6 (13%); and spurting, 1 (2%). Two of the 26 (8%) with adherent clots after washing rebled; endoscopic therapy resulted in no further bleeding. One of the 14 (7%) with active bleeding or visible vessels treated with hemostatic therapy rebled; repeat endoscopic therapy resulted in no further bleeding. No deaths occurred. CONCLUSIONS: Irrigation appears to be useful in patients with upper gastrointestinal bleeding who have ulcers with clots. The endoscopic findings present after washing can be used to dictate the appropriate management at initial endoscopy. Application of hemostatic therapy in patients with active bleeding or nonbleeding visible vessels and observation of patients with other stigmata, including clots resistant to washing, resulted in an excellent outcome.

Blood Coagulation↗
PubMed1996

The influence of size or number of biopsies on rapid urease test results: a prospective evaluation.

BACKGROUND: The optimal number or size of endoscopic biopsies for use in rapid urease testing has not been established. Postulating that increasing the amount of tissue sampled would improve diagnostic yield and hasten development of a positive test, we compared urease testing with one regular biopsy, two regular biopsies, and one "jumbo" forceps biopsy. METHODS: One hundred fifty patients undergoing endoscopy had three sets of prepyloric biopsies placed in a CLOtest: one regular forceps biopsy, two regular forceps biopsy, and one large-channel jumbo forceps biopsy. Biopsies were then taken for two independent histologic examinations. Disagreements were resolved by another examiner. RESULTS: Eighty-nine patients (59%) had Helicobacter pylori infection by histology; interobserver agreement was 90% with kappa = 0.78. The mean time to a positive test was 5.3 +/- 0.9 hours for one regular biopsy, 3.2 +/- 0.7 hours for two regular biopsies, and 3.8 +/- 0.8 hours for one jumbo biopsy (p < 0.01 for two regular, one jumbo vs. one regular biopsy). Compared to one regular biopsy, the urease test was positive at least 30 minutes earlier in 56% of the patients with two regular biopsies and 54% with one jumbo biopsy. Sensitivities for one regular versus two regular biopsies were 1 hour, 19% versus 33% (p = 0.059); 2 hours, 38% versus 49% (p = 0.17); 3 hours, 48% versus 60% (p = 0.18); and 24 hours, 75% versus 79% (p > 0.20). CONCLUSIONS: Doubling the amount of tissue in the CLOtest hastens the development of a positive test by approximately 1 1/2 to 2 hours; tests become positive at least 30 minutes earlier in over 50% of the patients. Low cost, ease, and excellent specificity make the rapid urease test a valuable diagnostic tool. Nevertheless, if used as a "rapid" diagnostic test (read within 3 hours of biopsy), it is associated with a false negative rate of approximately 40%.

Adult↗
PubMed1996

A novel mode of carbohydrate recognition in jacalin, a Moraceae plant lectin with a beta-prism fold.

Jacalin, a tetrameric two-chain lectin (66,000 Mr) from jackfruit seeds, is highly specific for the tumour associated T-antigenic disaccharide. The crystal structure of jacalin with methyl-alpha-D-galactose reveals that each subunit has a three-fold symmetric beta-prism fold made up of three four-stranded beta-sheets. The lectin exhibits a novel carbohydrate-binding site involving the N terminus of the alpha-chain which is generated through a post-translational modification involving proteolysis, the first known instance where such a modification has been used to confer carbohydrate specificity. This new lectin fold may be characteristic of the Moraceae plant family. The structure provides an explanation for the relative affinities of the lectin for galactose derivatives and provides insights into the structural basis of its T-antigen specificity.

Amino Acid Sequence↗