Biomedical subjects
Publications and source records attributed to R Gupta.
We report the case of a 40-yr-old man who presented with recurrent hemorrhage of the upper GI tract who was found to have hepatic artery pseudoaneurysm and amebic liver abscess. Our patient is unique in having hepatic artery pseudoaneurysm and amebic liver abscess diagnosed simultaneously, the association of which has not been previously described.
The status of tuberculin skin sensitivity tests was evaluated in 87 medical students. It was found that Mantoux test has less significant role to play in the vaccinated individuals and in the population at high risk of exposure. Hence this test is to be supplemented with clinical manifestations and other investigations to establish the final diagnosis of tuberculosis.
We report a woman with intestinal lymphangiectasia whose symptoms were wrongly attributed to pregnancy; the diagnosis was made in the postpartum period. She also developed alopecia and herpes zoster.
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Distribution of the enzymes of glycolytic and pentose phosphate pathways were studied in cytosolic and leucoplastic fractions of the developing seeds of Brassica. Leucoplasts were isolated using a discontinuous percoll gradient. Intactness of leucoplasts was checked by ADP-glucose pyrophosphorylase assay in presence and absence of triton X-100. No contamination by microbodies, mitochondria and cytosol was observed as assessed by measuring the activities of marker enzymes. The recovery, latency and specific activity of each enzyme in different fractions were compared. The leucoplastic fraction contained complete set of the enzymes of glycolytic and pentose phosphate pathways, indicating that the two subcellular compartments metabolize carbon independently by these pathways. However, the enzymes showed higher activities in cytosolic fraction as compared to those in the leucoplasts, suggesting the need for exchange of metabolites in the two compartments through various translocators, for acting in cooperation to produce energy, reducing power and carbon skeletons for different biosynthetic activities in the non-photosynthetic plastids. Based on these compartmentation studies, a model for carbon flow for fatty acid synthesis in leucoplasts of developing Brassica seeds has been proposed.
Truncal obesity judged by increased waist-hip ratio (WHR) is an important risk factor for atherosclerosis. One of the mechanisms postulated by which truncal obesity increases coronary risk is high blood pressure (BP). Studies of correlation of WHR with systolic and diastolic BP have shown conflicting results. A study on 443 persons (250 males, 193 females) for WHR measurement during a comprehensive cardiovascular survey in an urban population of Rajasthan was undertaken. The mean WHR in males was 0.90 +/- 0.07 and in females 0.87 +/- 0.08. The median value was 0.91 in males and 0.88 in females. Correlational analysis of WHR with anthropometric and clinical parameters showed that in males there was a positive relationship of WHR with weight (r = 0.11), body mass index (r = 0.13) and systolic (r = 0.11) and diastolic BP (r = 0.11) but not with age and height. In females no significant relationship was seen with these variables. When classified according to the US Fifth Joint National Committee (JNC-V) recommendations for diagnosis of truncal obesity (WHR males > 0.95, females > 0.85) it was seen in 42 (17%) males and 131 (68%) females. Sub-analysis of these two groups showed that mean values of systolic and diastolic BP were not significantly different in truncally obese subjects. However, stratified analysis after classifying WHR in four groups (WHR < 0.85, 0.85-0.89, 0.90-0.95 and > 0.95) showed that in males there was a significantly rising trend of weight, body mass index, systolic and diastolic BP with increasing WHR. WHR of > or = 0.85 was associated with higher systolic and diastolic BP.
The efficacy of topical ketorolac 0.5% in treatment of vernal keratoconjunctivitis (VKC) was evaluated in a randomised double-blind prospective trial in 21 patients. Ketorolac treated eyes showed 50.7% reduction in main symptoms of itching compared to 33.3% relief in placebo treated eyes after 2 weeks of treatment (p < 0.01). Photophobia, ropy discharge, and conjunctival injection also lessened by 39.9%, 31.6%, and 39.1%, respectively, in ketorolac treated eyes compared to 23.8%, 17.3%, and 20.3% in placebo group. Transient stinging sensation was observed in 3 (14.3%) patients on ketorolac therapy. This study shows efficacy of ketorolac 0.5% solution in controlling symptoms in VKC.
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Lipoprotein (a) [Lp(a)] levels have been correlated with angiographically defined coronary artery disease (CAD). Pattern of Lp(a) distribution in various racial groups is different. To study this relationship in Indian patients, plasma levels of Lp(a) and other lipid values were assessed in 101 patients undergoing coronary arteriography. Lp(a) concentration was higher in CAD group (n = 77) compared to normal coronary artery group (n = 24) (26.83 +/- 22.09 mg/dl vs. 15.07 +/- 14.61 mg/dl, P < 0.05). Lp(a) values had graded association with CAD. In Lp(a) quartile of < 5 mg/dl, 66.7% patients had CAD; in Lp(a) quartile of 5-25 mg/dl, 69.0% had CAD; Lp(a) quartile of 26-75 mg/dl, 87.5% had CAD; and in Lp(a) quartile of > or = 76 mg/dl, all patients had CAD. High density lipoprotein (HDL) cholesterol was higher in the normal coronary artery group as compared to CAD group (45.25 +/- 8.26 mg/dl vs. 41.83 +/- 16.47 mg/dl; NS). In HDL quartile of < 35 mg/l, 88.9% patients had angiographically defined CAD. Plasma values of total cholesterol, triglycerides (TG), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), low density lipoprotein (LDL) cholesterol, LDL/HDL cholesterol ratio and Apo A1/B ratio were not significantly different in the groups with normal coronary arteries and CAD. Our results indicate that the measurement of Lp(a) provides a better marker for predicting the presence of angiographically defined CAD as compared to traditional measures.
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We measured the ability of sphingomyelin (SPM) to inhibit phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] hydrolysis catalyzed by human phospholipase C-delta 1 (PLC-delta 1) in model membranes and detergent phospholipid mixed micelles. SPM strongly inhibited PLC-delta 1 catalytic activity measured in large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine (PC), PI(4,5)P2, and SPM from brain or egg. At 37 or 45 degrees C, the rate of PI(4,5)P2 hydrolysis in PC/SPM/PI(4,5)P2 vesicles (15:80:5 mol:mol) was less than 25% of that observed in PC/PI(4,5)P2 vesicles (95:5). By contrast, catalysis was only weakly inhibited by equivalent concentrations of the SPM analog, 3-deoxy-2-O-stearoyl-SPM, which lacks hydrogen bond-donating groups at the C-3 and C-2 positions of the sphingolipid backbone. Inhibition by SPM was not observed in detergent/phospholipid mixed micelles. The binding affinity of PLC-delta 1 for vesicles containing PC and PI(4,5)P2 was slightly diminished by inclusion of SPM in the lipid mixture, but not enough to account for the decreased rate of catalysis. We could find no evidence of specific binding of the enzyme to SPM, which argues against a simple negative allosteric mechanism. To understand the cause of inhibition, the effects of SPM and 3-deoxy-2-O-stearoyl-SPM on the bulk properties of the substrate bilayers were examined. Increasing the mole fraction of SPM altered the fluorescence emission spectra of two sets of head group probes, 6-lauronyl(N,N-dimethylamino)naphthalene and N-[5-(dimethylamino)naphthalene-1-sulfonyl]-1,2-dihexadecanoyl-sn- glycero-3-phosphoethanolamine, that are sensitive to water content at the membrane/solution interface. Results obtained with both probes suggested a reduction in hydration with increasing SPM content. Vesicles containing 3-deoxy-2-O-stearoyl-SPM produced intermediate changes. Our results are most consistent with a model in which SPM inhibits PLC by increasing interlipid hydrogen bonding and by decreasing membrane hydration; both factors raise the energy barrier for activation of PLC-delta 1 at the membrane/protein microinterface.
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We have studied the denaturation of metmyoglobin at pH 6.0 and 25 degrees C by urea and guanidine hydrochloride (GdnHCl) which are known to unfold the protein to the same extent. It has been observed that estimates of protein stability (delta G0N-U) from urea-induced and GdnHCl-induced denaturations do not agree with one another; the linear extrapolation method gave delta G0N-U values of 7.59 +/- 0.33 and 5.35 +/- 0.10 kcal mol-1 for urea and GdnHCl denaturations, respectively. Measurements of the effect of the addition of KCl in the concentration range 0.1-1.0 M to urea denaturation have suggested that this disagreement is not due to the nonionic and ionic characters of urea and GdnHCl, respectively. The functional dependence of the free energy change of unfolding (delta GN-U) on [denaturant], the molar concentration of the denaturant, has been investigated for understanding the cause(s) of the disagreement between the two estimates of delta G0N-U of metmyoglobin. For this purpose, we have studied the GdnHCl-induced denaturation of the protein in the presence of different urea concentrations at pH 6.0 and 25 degrees C and vice versa. These measurements yield delta GN-U values in the full concentration range [Ahmad et al. (1994) J. Biochem. 115, 322-327], and these results provide strong evidence that the delta GN-U dependence on [urea] is linear (linear free energy model of denaturation) and the relation between delta GN-U and [GdnHCl] is curved (binding model of denaturation). It has been observed that the extrapolated value of delta GN-U in urea using the linear free energy model becomes identical to the extrapolated value of delta GN-U in GdnHCl using the binding model.
The t(12;21) (p 13; q22) results in the fusion of the TEL gene located on chromosome 12 with the AML1 gene located on the derivative chromosome 21. Because this translocation is difficult to detect using standard cytogenetic techniques, 27 previously karyotyped B-lineage acute lymphoblastic leukemia (ALL) cell lines were evaluated for the presence of the TEL-AML1 fusion using the reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and cDNA sequencing. Six cell lines expressed the TEL-AML1 chimeric transcript by RT-PCR and the t(12;21) was confirmed by FISH analysis with probes for TEL, AML1, and chromosome 12. While only one of the 6 cell lines with the t(12;21) lost the der(12)t(12;21)-encoded AML1-TEL fusion transcript, 4 cell lines lacked expression of the nontranslocated allele of TEL and 5 cell lines lacked expression of CDKN2. Moreover, in 2 patients (1 with the TEL-AML1 transcript and 1 without), TEL expression was lost with disease progression; le, TEL was expressed in the initial cell lines (established at diagnosis or first relapse) whereas TEL was not expressed in the cell lines established from these patients in late-stage disease. These data show the coexistence of multiple genetic defects in childhood B-lineage ALL Cell lines with t(12;21) will facilitate the study of TEL-AML1 and AML1-TEL fusion proteins as well as TEL and CDKN2 gene inactivation in leukemia transformation and progression.
The growth of Mycobacterium microti was inhibited within J774A.1 macrophage cells activated with either interferon-gamma or tumor necrosis factor-alpha. Activation with interferon-gamma or tumor necrosis factor-alpha alone did not stimulate the production of nitrite in J774A.1 cells. Interferon-gamma but not tumor necrosis factor-alpha increased the production of hydrogen peroxide in a concentration dependent manner but scavengers of reactive oxygen species did not influence the growth inhibiting effect of interferon-gamma within J774A.1 cells. Both interferon-gamma and tumor necrosis factor-alpha enhanced the fusion of M. microti containing phagosomes with lysosomes and the ultimate degradation of bacteria. Our results showed that growth inhibition of M. microti within interferon-gamma or tumor necrosis factor-alpha stimulated J774A.1 cells was independent of reactive oxygen intermediate and reactive nitrogen intermediate production.
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Contact between a transcriptional activator and one or more components of the RNA polymerase II transcription initiation machinery is generally believed important for activators to function. Several different molecular targets have been suggested for direct contact by herpes simplex virus virion protein VP16, including the general initiation factor TFIIB. In this report we have used several strategies to critically assess this interaction between VP16 and TFIIB. Affinity columns of VP16 bound TFIIB activity from HeLa cell extracts and the binding was reduced by mutations in the activation domain of VP16. In assays of direct binding, VP16 bound recombinant human TFIIB but not Drosophila or yeast TFIIB. Unlike binding from an extract, however, we found that the interaction between VP16 and recombinant human TFIIB was not affected by mutations in VP16 that reduce transactivation. Point mutations within human TFIIB that reduce transactivation by VP16 have been shown to reduce VP16 binding, but we show here that these same mutations critically affect both the important TBP-TFIIB interaction and the ability of TFIIB to support activator-independent basal transcription in vitro. Taken together our results suggest more evidence is needed to support the notion that TFIIB is a functionally important target for the activator VP16.