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Biomedical subjects

A Singh

Publications and source records attributed to A Singh.

At least 271 records · Page 15Linked to original sources

Prevalence of hypertension in chronic cocaine users.

The association of cocaine and acute hypertension is well known; however, cocaine use has not generally been linked to chronic hypertension. We hypothesized that chronic use of cocaine over time would increase the prevalence of hypertension and that cocaine induced vasoconstriction would result in urine protein leakage, manifested by microalbuminuria. Therefore, we studied a population of predominantly black male patients admitted for addiction treatment whose drug of dependence was cocaine. A urine toxicology screen was considered positive if cocaine was detected within 24 h prior to or during admission to the hospital. A total of 301 patients with normal renal function were observed over their 2 week hospitalization. The majority (62%) of the patients were normotensive regardless of the status of their initial urine toxicology screen. Twenty percent of the population had acutely elevated blood pressure that normalized within 1 day, whereas 18% had blood pressure chronically >140/90 mm Hg (chronic hypertension). Levels of systolic and diastolic blood pressures were examined at age deciles and compared to the NHANES III (Third National Health and Nutrition Examination Survey) data for a predominantly black population. There was no significant difference in blood pressure with age in the cocaine users compared to the NHANES groups. Random urine samples were screened for the presence of microalbuminuria and no significant elevation was detected in any of the samples tested. We conclude that chronic cocaine use is associated with acute but not chronic hypertension in middle-aged black males. Cocaine use does not cause microalbuminuria.

Adult↗

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part I: Dioxygenated 4-methyl coumarins as superb antioxidant and radical scavenging agents.

Twenty-three 4-methylcoumarins bearing different functionalities have been examined for the first time for their effect on NADPH-catalysed liver-microsomal lipid peroxidation with a view to establish structure-activity relationship. Dihydroxy- and diacetoxy-4-methylcoumarins produced dramatic inhibition of lipid peroxidation. 7,8-Diacetoxy-4-methylcoumarin and 7,8-dihydroxy-4-methylcoumarin were found to possess superb antioxidant and radical scavenging activities.

Animals↗

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part II: Mechanism-based inhibition of rat liver microsome-mediated aflatoxin B1-DNA binding by the candidate antimutagen 7,8-diacetoxy-4-methylcoumarin.

7,8-Diacetoxy-4-methylcoumarin (DAMC), with no prerequisite for oxidative biotransformation has been reported to produce suicide inactivation of microsomal cytochrome P-450-catalysed formation of aflatoxin B1-8,9-oxide that binds to DNA. Parenteral administration of DAMC to rats caused significant inhibition of AFB1 binding to hepatic DNA in vivo as well as AFB1-induced micronuclei formation in bone marrow cells. These results highlight the antimutagenic potential of DAMC.

7-Alkoxycoumarin O-Dealkylase↗

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 3: A novel mechanism for the inhibition of biological membrane lipid peroxidation by dioxygenated 4-methylcoumarins mediated by the formation of a stable ADP-Fe-inhibitor mixed ligand complex.

7,8-Dihydroxy-4-methylcoumarin (DHMC) and 7,8-diacetoxy-4-methylcoumarin (DAMC) have been reported to effectively inhibit in-vivo lipid peroxidation in rat tissues induced by CCl4 and paraquat. DHMC was found to readily impart green colour to the lipid peroxidation incubation mixture containing ADP and Fe3+, whereas DAMC formed green complex only upon incubation with liver microsomes, confirming our earlier observation that liver microsomal deacetylase hydrolyses DAMC to DHMC. Sensitive pH metric technique revealed the formation of ADP-Fe-DHMC ternary complex with highest stability, while Fe-DHMC and ADP-DHMC had negligible stabilities concluding that ADP-perferryl ion formation is prevented by DHMC resulting in the production of stable ternary mixed ligand complex (ADP-Fe-DHMC), thereby inhibiting the formation of O2-, and eventually other reactive oxygen species (ROS) responsible for membrane lipid peroxidation.

Adenosine Diphosphate↗

Drug resistance in Leishmania: similarities and differences to other organisms.

The main line of defense available against parasitic protozoa is chemotherapy. Drug resistance has emerged however, as a primary obstacle to the successful treatment and control of parasitic diseases. Leishmania spp., the causative agents of leishmaniasis, have served as a useful model for studying mechanisms of drug resistance in vitro. Antimonials and amphotericin B are the first line drugs to treat Leishmania followed by pentamidine and a number of other drugs. Parasites resistant against all these classes of drugs have been selected under laboratory conditions. A multiplicity of resistance mechanisms has been detected, the most prevalent being gene amplification and transport mutations. With the tools now available, it should be possible to elucidate the mechanisms that govern drug resistance in field isolates and develop more effective chemotherapeutic agents.

Journal Article↗

Biochemical control of breast aromatase.

Aromatase activity is increased in breast tumors and it is possible that this results from stimulation by cytokines and/or prostaglandin E2 (PGE2) which regulate the activity of this enzyme. As different promoters can be used to control aromatase gene expression in normal and malignant breast tissues, which are regulated by different factors, we are currently investigating the relative roles of cytokines and PGE2 in controlling breast tumor aromatase activity. No significant effect of PGE2 on aromatase activity in MCF-7 breast cancer cells has so far been detected. However, preliminary evidence was obtained, from co-cultures of MCF-7 cells and breast tumor-derived fibroblasts, that MCF-7 cells secrete a factor, possibly a cytokine, which can act in a paracrine manner to enhance aromatase activity in stromal cells. Understanding the complex regulation of aromatase activity in breast tumors could lead to novel therapies for specifically inhibiting tumor estrogen synthesis.

Aromatase↗

Haematological and biochemical studies on experimental Theileria annulata infection in crossbred calves.

Administration of ground-up tick tissue stabilate (0.75 tick equivalent) by the subcutaneous route to crossbred calves aged 1 week to 1 month led to the development of acute theileriosis. Haematological studies revealed significant progressive decreases in haemoglobin concentration, packed cell volume and red blood cell count, whereas the total leukocyte count showed an initial non-significant leukocytosis followed by a significant leukopenia. Analysis of serum revealed significant increases in levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase and gamma-glutamyltransferase, and in the concentrations of uric acid, blood urea nitrogen and bilirubin. The concentrations of total protein, albumin, glucose, cholesterol and calcium showed non-significant decreases, while phosphorus decreased significantly during the terminal stages of the disease.

Alanine Transaminase↗

Death domain receptors and their role in cell demise.

Apoptotic signals are transduced by five death domain-containing receptors--TNFR1, Fas, DR3, DR4, and DR5--by binding to their ligands. The intracellular portion of all these receptors contains a region, approximately 80 amino acids long, referred to as the "death domain" (DD). On activation by its ligand, the DD recruits various proteins that mediate cell death. These proteins, in turn, recruit other proteins via their DDs or death effector domains (DED). The actual destruction of the cell, however, is accomplished by serial activation of a family of proteases referred to as caspases. Cell death is, in part, regulated by transmembrane decoy receptors that contain either none of or only part of the DD. This article briefly reviews what is known about the receptors and other proteins involved in apoptosis. In addition, because numerous proteins that mediate apoptosis have been discovered independently and simultaneously and thus are known by many different names, a comprehensive cross-referenced list of these proteins is provided.

Amino Acid Sequence↗

Improved survival in patients with advanced colorectal carcinoma failing 5-fluorouracil who received irinotecan hydrochloride and have high intratumor C-fos expression.

This study determines the prognostic role of c-fos protein expression in patients with colon cancer who previously failed therapy with 5-fluorouracil (5-FU). Patients with advanced colorectal who were refractory to 5-FU therapy received irinotecan (CPT-11) by a 90-minute intravenous infusion at a dose of 125 mg/m2 weekly for four weeks followed by a 2-week rest period were eligible for oncogene assessment. C-fos protein expression was evaluated using archival formalin-fixed, paraffin-embedded tumor tissue, and an automated immunoperoxidase histochemical technique. Thirty-five patients were found to have > 25% positive c-fos activity. Nine patients had no detectable c-fos expression. Characteristics of patient subgroups were not different, however, the median survival of patients with elevated c-fos expression from the time of treatment with CPT-11 was 436 days, whereas patients with no detectable c-fos expression had a median survival of 365 days (p = 0.045). C-fos exhibits a casual role in the initiation of apoptosis and is implicated in differentiation and proliferation. It has been shown to correlate with poor survival in breast cancer, but improved survival in patients with astrocytic glioma. In this analysis, there is a suggestion that elevated c-fos expression is a good prognostic marker for patients with refractory colorectal carcinoma.

Adult↗

Mycoplasma pulmonis inhibits electrogenic ion transport across murine tracheal epithelial cell monolayers.

Murine chronic respiratory disease is characterized by persistent colonization of tracheal and bronchial epithelial cell surfaces by Mycoplasma pulmonis, submucosal and intraluminal immune and inflammatory cells, and altered airway activity. To determine the direct effect of M. pulmonis upon transepithelial ion transport in the absence of immune and inflammatory cell responses, primary mouse tracheal epithelial cell monolayers (MTEs) were apically infected and assayed in Ussing chambers. M. pulmonis-infected MTEs, but not those infected with a nonmurine mycoplasma, demonstrated reductions in amiloride-sensitive Na+ absorption, cyclic AMP, and cholinergic-stimulated Cl- secretion and transepithelial resistance. These effects were shown to require interaction of viable organisms with the apical surface of the monolayer and to be dependent upon organism number and duration of infection. Altered transport due to M. pulmonis was not merely a result of epithelial cell death as evidenced by the following: (i) active transport of Na+ and Cl-, albeit at reduced rates; (ii) normal cell morphology, including intact tight junctions, as demonstrated by electron microscopy; (iii) maintenance of a mean transepithelial resistance of 440 omega/cm2; and (iv) lack of leakage of fluid from the basolateral to the apical surface of the monolayer. Alteration in epithelial ion transport in vitro is consistent with impaired pulmonary clearance and altered airway function in M. pulmonis-infected animals. Furthermore, the ability of M. pulmonis to alter transport without killing the host cell may explain its successful parasitism and long-term persistence in the host. Further study of the MTE-M. pulmonis model should elucidate the molecular mechanisms which mediate this reduction in transepithelial ion transport.

Amiloride↗

Evaluation of the abbott LCx assay for detection of Neisseria gonorrhoeae in endocervical swab specimens from females.

The Abbott LCx Neisseria gonorrhoeae assay (Abbott Laboratories, Abbott Park, Ill.) uses a ligase chain reaction (LCR) amplification in the LCx probe system for detection of a specific nucleotide sequence in the Opa-encoding gene of N. gonorrhoeae. We evaluated the LCx assay in a comparison with conventional culture employing modified Thayer-Martin media for the detection of N. gonorrhoeae from female endocervical specimens obtained from patients attending a sexually transmitted disease clinic. Discordantly LCR-positive and culture-negative specimens were further evaluated by testing with another LCR assay which used an N. gonorrhoeae-specific pilin probe. Specimens positive by both LCR assays were considered confirmed LCx-positive specimens. A specimen was considered to contain N. gonorrhoeae when it was either culture positive or culture negative and confirmed LCx positive. A total of 403 female endocervical specimens were evaluated. The prevalence of N. gonorrhoeae in this population was 8.7%. The sensitivity and specificity of the LCx assay were 94.3 and 99.4%, and those of culture were 77.1 and 100%, respectively. The Abbott LCx assay is a rapid, sensitive method for detection of N. gonorrhoeae in female endocervical specimens.

Cervix Uteri↗

Determinants of entry cofactor utilization and tropism in a dualtropic human immunodeficiency virus type 1 primary isolate.

Human immunodeficiency virus type 1 strain 89.6 is a dualtropic isolate that replicates in macrophages and transformed T cells, and its envelope mediates CD4-dependent fusion and entry with CCR5, CXCR-4, and CCR3. To map determinants of cofactor utilization by 89.6 and determine the relationship between cofactor use and tropism, we analyzed recombinants generated between 89.6 and T-cell-tropic (HXB) or macrophage-tropic (JRFL) strains. These chimeras showed that regions of 89.6 env outside V3 through V5 determine CXCR-4 utilization and T-cell line tropism as well as CCR5 utilization and macrophage tropism. However, the 89.6 env V3 domain also conferred on HXB the ability to use CCR5 for fusion and entry but not the ability to establish productive macrophage infection. CCR3 use was conferred on HXB by 89.6 env V3 or V3 through V5 sequences. While replacement of the 89.6 V3 through V5 region with HXB sequences abrogated CCR3 utilization, replacement of V3 or V4 through V5 separately did not. Thus, CCR3 use is determined by sequences within V3 through V5 and most likely can be conferred by either the V3 or the V4 through V5 domains. These results indicate that cofactor utilization and tropism in this dualtropic isolate are determined by complex interactions among multiple env segments, that distinct regions of the Env glycoprotein may be important for utilization of different chemokine receptors, and that determinants in addition to cofactor usage participate in postentry stages in the virus replication cycle that contribute to target cell tropism.

Cell Fusion↗

Can total urinary protein measurements predict microalbuminuria?

We re-addressed the question of whether routine total urinary protein determinations can be used to predict the presence of microalbuminuria by studying 61 patients who attended a diabetic clinic and tested negative or had one positive protein by dipstick. Total urinary protein was measured by the Biorad dye-binding method in undialyzed urine (UND), in dialyzed urine (DIAL), and in dialyzed urine in which albumin and globulins were separated, measured separately with albumin and globulin standards and the results added together to obtain total urinary protein (A + G). The results were compared with albumin measurements obtained by radioimmunoassay (RIA). Compared to DIAL, urinary protein measurements were 43% higher with A + G and 22% higher with UND. Microalbuminuria correlated moderately with UND (r =0.81) and better with the other methods (r=0.87 for DIAL, r=0.91 for A + G). None of the methods predicted microalbuminuria reliably. Taking a protein-to-creatinine ratio of 0.15 and an albumin-to-creatinine ratio of 0.03 as upper limits of normal, we found that UND had a 72% positive predictive value (28% false positives) and 85 % negative predictive value (15% false negatives). DIAL had 90% positive predictive value (10% false positives) and 78% negative predictive value (22% false negatives). A + G had 65% positive predictive value (35% false positives) but 91% negative predictive value (9% false negatives). A + G, which uses the correct standards, would be the most suitable method for screening, having the least number of false negatives, but has more false positives because it is more sensitive. In practice, most routine chemical laboratories find it expedient to use only UND, but physicians interpreting the results of this method should be aware of its limitations.

Albuminuria↗

The importance of lesion location in poststroke depression: a critical review.

BACKGROUND: Mood disorder may be a specific complication of stroke. An earlier finding of an association between left anterior lesions and poststroke depression stimulated interest in the significance of stroke lesion characteristics. Subsequent research efforts, however, often failed to replicate this finding. OBJECTIVE: This paper represents a critical appraisal of hemispheric lesion localization studies by computed tomography (CT) scanning in poststroke depression. METHOD: Systematic selection of original studies involved a Medline search and a review of the bibliographies of retrieved articles for additional references. Two sets of inclusion criteria were independently applied to the studies by 2 observers blind to authorship, affiliation, and journal name. Studies that satisfied minimum inclusion criteria, as determined by consensus, were included in the review. RESULTS: Twenty-six original articles were retrieved by the search. Thirteen studies satisfied all or nearly all of the minimum criteria for inclusion. Six of those studies found no difference between right- and left-hemisphere lesions leading to depression. Two studies found right-sided lesions more likely to be associated with depression, while 4 studies found depression to be associated more often with left-sided lesions. One study matched subjects with and without depression for lesion location and size to identify nonlesion risk factors. All studies suffered from methodological limitations, and no studies were completely comparable with respect to sample, timing and analysis of CT scan, and psychiatric evaluation. CONCLUSION: Based on a systematic review of the present literature, any definitive statements regarding stroke lesion location and risk for depression are not yet substantiated. The authors suggest methodologies for future localization studies of poststroke depression.

Aged↗

High intensity exercise promotes escape of adrenocorticotropin and cortisol from suppression by dexamethasone: sexually dimorphic responses.

Exercise promotes escape of ACTH and cortisol from suppression by dexamethasone (DEX) in some healthy men and women. To determine whether stimulus strength, diurnal rhythmicity, or gender influences neuroendocrine escape during DEX suppression, we studied men (n = 5) and women (n = 5) during high intensity exercise tests after taking 4 mg DEX: two tests (one at 90% and one at 100% of maximal aerobic capacity) were conducted in the morning and two were performed in the afternoon on nonconsecutive days. Plasma ACTH and cortisol showed significantly greater increases with the 100% compared to the 90% intensity exercise (ACTH: 90%, 2 +/- 0.4; 100%, 3 +/- 0.5 pmol/L; cortisol: 90%, 53 +/- 5.3; 100% 93 +/- 23.6 nmol/L). Plasma cortisol responses were significantly higher in women than in men (P < 0.01). Plasma arginine vasopressin (AVP) exhibited significant intensity-dependent increases, with higher responses in women than men (P < 0.01). In conclusion, despite high dose glucocorticoid pretreatment, intense exercise can override the glucocorticoid negative feedback of hypothalamic-pituitary-adrenal activation in most normal men and women. This ability to override cortisol negative feedback inhibition may relate to the magnitude of the AVP response, the potency/specificity of the stressor to elicit a CRH/AVP response, and/or the sensitivity of the glucocorticoid negative feedback system at the time of the stress.

Adrenocorticotropic Hormone↗

Sequential analysis of the lipid profile of children post-renal transplantation.

Persistent hyperlipidemia and hypercholesterolemia post-transplantation are risk factors for accelerated atherosclerosis. To evaluate the natural history of lipid abnormalities in children post-transplantation, this study utilized a cohort of 29 patients who were all treated with the same three- drug maintenance immunosuppression (cyclosporine, azathioprine, and prednisone) and whose dosing regimen was rigidly controlled. Fasting blood samples were taken monthly to determine lipid profiles measuring total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), very low density lipoprotein cholesterol (VLDL), and levels of lipoprotein (a) (LP(a)). A mean value was determined for each of five time periods: 0-3 months, 3-6 months, 6-9 months, 9-12 months and 12-15 months post-transplant. A single specimen of fasting lipid profile was drawn from 21 non-immunosuppressed children attending an ambulatory pediatric clinic and used as control. Despite significant reductions in the cyclosporine and prednisone doses post-transplantation, significant reduction in any of the lipid parameters was only noted after the first year. Reductions in the HDL fraction and in the TG level were noted during the 12-15 month period, however the values obtained in the patient population were significantly elevated for CHOL, TG, LDL and VLDL compared to controls. This study, using a fixed protocol, suggests that the lipid profile should be measured at one year post-transplant in all transplant patients, and if subsequent follow-up continues to exhibit abnormally elevated levels of CHOL and LDL, interventional therapy should be considered.

Adolescent↗

Diagnostic yield in computed tomography guided stereotactic biopsies.

Fifty three patients underwent computerised tomography (CT) guided stereotactic biopsies from different CT defined zones of attenuation with the Leksell stereotactic apparatus from October 1993 through January 1995. Multiple lesions were seen in 16 cases and 3 of them had multiple rim enhancing lesions. Astrocytoma was the most common histological diagnosis and thalamus was the commonest site of these tumours. The overall positivity rate was 98.2%. Positive yield from the centre of the lesion, peripheral and perilesional areas was 92.1%, 54.7% and 17.6%, respectively. The definite pathological diagnosis was made in 81.1% of cases. Post-operative neurological worsening was seen in 6 patients, of which 2 recovered without any surgical treatment, in 1 patient ventriculo-peritoneal shunt was done post-biopsy whereas in another evacuation of hamatoma was done which relieved headache and vomiting while 2 patients (3.7%) died.

Adolescent↗

Interaction of PCB congeners and 2,3,7,8-TCDD in the rat liver: an electron microscope study.

Polyhalogenated aromatic compounds such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins continue to be environmental contaminants because of their bioaccumulation in the food chain and resistance to biodegradation. This study was undertaken to determine if WHO-IPCS PCB congeners or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually or their coadministration in rats produced morphological alterations in the liver. Groups (N = 5) of female Sprague Dawley rats received TCDD (0, 2.5, 25, 250, 1,000 ng/kg bw/day) or PCB (0, 2, 20 micrograms/kg bw/day) either alone, or each dose of PCB coadministered with that of TCDD. The test substances were dissolved in corn oil and given by gavage at 0.2 ml/100 g bw/day for 28 days. At the end of the experiment the rats were killed and liver samples were prepared for transmission electron microscopy. Electron micrographs of the liver from animals of the control groups revealed characteristic normal hepatocyte architecture. An increase in smooth endoplasmic reticulum (SER) profiles and a corresponding decrease in the profiles of rough endoplasmic reticulum (RER) proportional to the increased doses of the compounds was revealed in the micrographs. Coadministration of PCBs and TCDD induced greater SER proliferation and a greater decrease in the number of RER profiles compared to either compound administered individually. The PCBs and TCDD at the doses used apparently interacted to induce hepatic ultrastructural alterations. These changes may represent an attempt by the organism to metabolize and neutralize the effects of xenobiotics.

Animals↗