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Biomedical subjects

S Arora

Publications and source records attributed to S Arora.

At least 91 records · Page 5Linked to original sources
PubMed1998

Reactive hyperemic response of the brachial artery: comparison of proximal and distal occlusion.

RATIONALE AND OBJECTIVES: The authors compared the postocclusion hyperemic responses of the brachial artery after occluding blood flow proximal to and distal to the studied area. MATERIALS AND METHODS: Response of the brachial artery to hypoxia was evaluated with duplex Doppler ultrasound in 13 healthy subjects. A pneumatic tourniquet was first positioned 2-5 cm superior to the left elbow, proximal to the area of artery studied. Two hours later the response was remeasured with the tourniquet positioned 2-5 cm inferior to the elbow, distal to the artery studied. Arterial diameter, mean and peak flow velocities, and heart rate were assessed. RESULTS: No significant differences were observed between measurements of baseline and postischemic arterial diameter, percentage diameter change, baseline mean arterial blood flow velocity, baseline peak arterial blood flow velocity, or postischemic heart rate obtained with proximal occlusion of the artery and those obtained with distal occlusion. In contrast, mean and peak postischemic arterial blood flow velocity and preocclusion heart rate were higher in measurements made during proximal artery occlusion. Significant correlation was found between measurements of percentage change in artery diameter obtained with proximal artery occlusion and those obtained with distal occlusion (r = 0.611, P < .05). CONCLUSION: There are no major differences in postischemic changes in brachial artery diameter related to reactive hyperemia between blood flow occlusion applied proximal and distal to the studied area. However, there are significant differences in the mean and peak systolic velocities. Either occlusion site can be used for clinical studies if arterial diameter change is monitored, but if velocity measurements are being compared, a single occlusion site should be chosen.

Adult↗
PubMed1998

Management of presumed intraocular tuberculosis: possible role of the polymerase chain reaction.

PURPOSE: A highly selective technique of polymerase chain reaction (PCR) was performed for detection of Mycobacterium tuberculosis from aqueous samples of 45 patients to evaluate its role in initiating antituberculosis treatment in patients with presumed intraocular tuberculosis. METHODS: Forty-five patients were divided into three groups. Group I included 17 patients of presumed intraocular tuberculosis, group II 13 disease controls and group III had 15 normal controls. Patients with positive PCR were offered antituberculosis chemotherapy and followed up for a minimum of 18 months. RESULTS: Ten patients in group I, 3 in group II and none in group III were positive for Mycobacterium tuberculosis by PCR. Ten patients with positive PCR for Mycobacterium tuberculosis (8 in group I and 2 in group II) were treated with antituberculosis chemotherapy and all showed resolution of inflammation without any recurrence over 18 months of follow-up. Two PCR positive patients treated with steroids alone, however, did not show complete resolution and had recurrent attacks. CONCLUSION: These results suggest that antituberculosis treatment in PCR positive patients leads to resolution of inflammation and elimination of recurrences, most likely by eliminating Mycobacterium tuberculosis from the intraocular tissues.

Adolescent↗
PubMed1998

A proteinase K inhibitor using alpha,beta-unsaturated (dehydro) residues: a presumptive model.

Enzymes of the subtilisin family, of which proteinase K is a member, have been studied extensively on account of their numerous biological applications. Specific inhibitors of the proteinases are of immense importance in regulating their activity so as to protect the cells against uncontrolled proteolysis. Using the specific design principles of peptides containing dehydro-Alanine (deltaAla), generated by our theoretical calculations, we present here the design of an inhibitor of proteinase K. Energy minimization and molecular modeling of the interaction of the designed tetrapeptide with the recognition site of proteinase K indicate that it is an effective inhibitor.

Binding Sites↗
PubMed1998

Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps.

BACKGROUND: Estimates of habitual dietary folate intake are known to be imprecisely correlated with systemic measures of folate status. Furthermore, measurements of blood folate concentrations may not accurately reflect the concentration of folate in tissues of interest. This issue is important for assessing folate status in the colorectal mucosa because low dietary intake or blood concentrations of folate are associated with an increased risk of colorectal neoplasia. OBJECTIVE: We examined whether conventional measures of folate in blood and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflected folate concentrations in human colonic mucosa obtained by endoscopic biopsy. DESIGN: In 30 persons with colorectal polyps, blood samples were taken and biopsies of normal rectosigmoid mucosa performed at the time of colonoscopic polypectomy. Serum, red blood cell, and colonic mucosal folate and serum homocysteine concentrations were measured. RESULTS: Serum and red blood cell folate and serum homocysteine concentrations accurately reflected colonic mucosal folate concentrations; among these, serum homocysteine correlated best with mucosal concentrations. Folate concentrations in the normal rectosigmoid mucosa were significantly lower in persons with adenomatous polyps than in those with hyperplastic polyps (P=0.04). Conventional measures of systemic folate status were not significantly lower in those with adenomas, although serum homocysteine was mildly elevated (P=0.04). CONCLUSIONS: Our data underscore the ability of systemic measures of folate status, particularly serum homocysteine, to reflect folate concentrations in the colonic mucosa. Nevertheless, future studies that examine the ability of folate to modulate colorectal carcinogenesis may benefit from direct measurement of folate in the colon.

Adenoma↗
PubMed1998

Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy.

OBJECTIVE: We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects. RESEARCH DESIGN AND METHODS: We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44 degrees C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response). RESULTS: The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 +/- 4 vs. 55 +/- 10 [mean +/- SEM]; P < 0.01)], the non-neuropathic group (33 +/- 6 vs. 88 +/- 14; P < 0.01), and the control subjects (43 +/- 6 vs. 93 +/- 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 +/- 0.24; non-neuropathic group, 2.55 +/- 0.35; and control subjects, 2.11 +/- 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 +/- 0.27; non-neuropathic group, 2.08 +/- 0.33; and control subjects, 2.77 +/- 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups. CONCLUSIONS: In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.

Adult↗
PubMed1998

Effect of growth hormone on fibrinolytic system in rat.

Growth hormone deficiency (GHD) is associated as a risk factor in increased mortality from cardiovascular diseases. Abnormal lipid profile and increased levels of plasminogen activator inhibitor (PAI) and fibrinogen have been noted in GHD patients. Present study was carried out to investigate the effect of growth hormone (GH) on plasminogen activator (PA) activity in heart, levels of PA, PAI, glucose and fibrinogen in plasma and serum lipid profile. Rats were injected 125 mU GH kg-1 body weight subcutaneously daily for one week. PA activity was significantly higher in the heart of GH treated rats as compared to controls. GH treatment decreased plasma glucose and fibrinogen levels significantly. No significant differences were seen in PA, PAI in plasma, triglycerides and total cholesterol in serum of the two groups of rats. A significant increase in high density lipoprotein cholesterol (HDL) occurred in GH treated group resulting into a decrease in LDL/HDL ratio. The results indicate that GH may be beneficial in cardiovascular diseases as it decreases the levels of plasma fibrinogen and increases the level of HDL in blood and also increases the level of PA in heart.

Animals↗
PubMed1997

RNA base-amino acid interaction strengths derived from structures and sequences.

We investigate RNA base-amino acid interactions by counting their contacts in structures and their implicit contacts in various functional sequences where the structures can be assumed to be preserved. These frequencies are cast into equations to extract relative interaction energetics. Previously we used this approach in considering the major groove interactions of DNA, and here we apply it to the more diverse interactions observed in RNA. Structures considered are the three different tRNA synthetase complexes, the U1A spliceosomal protein with an RNA hairpin and the BIV TAR-Tat complex. We use binding data for the base frequencies for the seryl, aspartyl and glutaminyl tRNA-synthetase and U1 RNA-protein complexes. We compare with the previously reported DNA major groove peptide contacts the results for atoms of RNA bases, usually in the major groove. There are strong similarities between the rank orders of interacting bases in the DNA and the RNA cases. The apparent strongest RNA interaction observed is between arginine and guanine which was also one of the strongest DNA interactions. The similar data for base atomic interactions, whether base paired or not, support the importance of strong atomic interactions over local structure considerations, such as groove width and alpha-helicity.

Amino Acid Sequence↗
PubMed1997

Lower extremity macrovascular disease in diabetes.

Lower extremity macrovascular disease is more common and progresses more rapidly in the presence of diabetes and has a characteristic peritibial distribution with sparing of the foot arteries. The biology of the diabetic foot is compromised, thereby making it more susceptible to injury. Hence, compromises in perfusion have a greater significance, warranting an aggressive approach to revascularization.

Arterial Occlusive Diseases↗
PubMed1997

Accuracy of self-reported educational attainment among diverse patient populations: a preliminary investigation.

Despite speculation concerning the accuracy of self-reported information, particularly from certain patient populations, many neuropsychologists continue to estimate premorbid intellectual functioning on the basis of self-reported educational attainment. This study examined 116 individuals with diverse diagnoses [i.e., alcoholism, posttraumatic stress disorder (PTSD), schizophrenia or schizoaffective, and dementia] to determine the accuracy of their self-reported high school educational attainment. Results suggest that at least half of all participants were inaccurate as defined by discrepancies between actual and estimated GPA greater than.5 on a traditional 4-point grading scale. Most patients were inaccurate in the direction of overestimating their educational attainment. Patients diagnosed with alcoholism and PTSD were significantly less accurate in recalling their educational history when compared to a group of normal-control subjects. Several subjects, whose records could not be verified, were found to have not attended high school as they had claimed. These results underscore the potential inaccuracy that exists when estimating premorbid intelligence using self-reported information.

Journal Article↗
PubMed1997

Human lymphocyte cytochrome P450 2E1, a putative marker for alcohol-mediated changes in hepatic chlorzoxazone activity.

Cytochrome P450 (CYP) 2E1 is implicated in a variety of chemically initiated hepatotoxicities, including alcoholic liver disease. These pathological conditions arise from increased production of reactive intermediates caused by elevated enzyme concentrations. Thus, the ability to detect enhanced CYP2E1 levels would aid in identifying individuals at high risk for xenobiotic-promoted liver injury. With this in mind, the present investigation assessed in vivo chlorzoxazone metabolism and compared pharmacokinetic parameters with CYP2E1 expression in blood. Twenty-two subjects were recruited and divided into two groups, control subjects and alcohol abusers, based on responses to two screening questionnaires. Those individuals with higher survey scores, i.e. those who consumed alcohol more frequently, exhibited higher rates of chlorzoxazone metabolism. Indeed, a correlation (r = 0.66, p < 0.01) was obtained when scores were compared with the pharmacokinetic parameter AUC for chlorzoxazone. Lymphocyte microsomes isolated from blood samples obtained from these same individuals were subjected to immunoblot analyses to detect CYP2E1 levels. That lymphocytes contained CYP2E1 was confirmed by reverse transcription-polymerase chain reaction and sequence analysis of the cDNA. Quantification of immunoreactive bands revealed that levels of this P450 were 2.3-fold higher in alcoholics than in control subjects. This increase in lymphocyte CYP2E1 content in alcoholic subjects coincided with a 2.1-fold increase in chlorzoxazone clearance and a 2-fold decrease in the AUC for chlorzoxazone. Importantly, a correlation (r = 0.62, p < 0.01) was observed between CYP2E1 content in lymphocytes and chlorzoxazone clearance rates. Thus, monitoring lymphocyte CYP2E1 expression may provide a substitute for estimating hepatic activity of this P450.

Adult↗
PubMed1997

High prevalence of p53 gene alterations and protein overexpression in human esophageal cancer: correlation with dietary risk factors in India.

Epidemiological studies have demonstrated an association between human esophageal cancer and dietary/nutritional risk factors in developing countries. We examined the expression of p53 protein in 51 cases of esophageal squamous cell carcinomas (ESCCs) and paired normal esophageal tissues by immunohistochemistry. Alterations in the tumor suppressor gene p53 (exons 5-8) were analyzed in 51 cases of ESCC and paired normal tissues by PCR and single-strand conformation polymorphism. p53 protein expression was correlated with major dietary risk factors and common carcinogens identified in India. Immunohistochemical analysis of frozen esophageal tissue sections using anti-p53 monoclonal antibody (D0-1) showed overexpression of the protein in the nuclei of epithelial cells in 39 of 51 (76%) cases. The histopathologically proven normal esophageal tissue sections taken from a distant site from esophageal cancer patients did not show any detectable level of p53 immunoreactivity. The PCR-single-strand conformation polymorphism analysis showed a mobility shift in 37 of 51 (72%) ESCCs. Intake of chilies was positively associated with p53 protein expression (P < 0. 01) in the esophageal cancerous lesions. Our results suggest that p53 alterations are frequent events in esophageal oncogenesis in the Indian population, which has dietary habits that are considerably different from those of the Western population.

Adult↗
PubMed1996

The effect of orlistat, an inhibitor of dietary fat absorption, on the pharmacokinetics of beta-carotene in healthy volunteers.

To assess the influence of orlistat, a lipase inhibitor, on the absorption of beta-carotene, an open-label, parallel, placebo-controlled, randomized, two-way crossover study was performed in 48 healthy volunteers between the ages of 19 and 58 years. Each subject received a single oral dose of 0, 30, 60, or 120 mg beta-carotene (12 subjects per dose level) on the fourth day of treatment with orlistat (120 mg) or placebo 3 times a day for 6 days. The treatments were separated by a washout period of at least 5 weeks. Serial blood samples were collected before and at appropriate intervals after administration of beta-carotene to determine plasma concentrations of unchanged beta-carotene. Short-term (3 to 6 days) treatment with orlistat did not alter endogenous profiles of beta-carotene in plasma. When beta-carotene was given during orlistat treatment, its absorption was reduced by approximately one-third. This reduction was consistent for all three dose levels of beta-carotene studied; however, the results for the 30-mg dose level were subject to greater variability, particularly for area under the concentration-time curve (AUC). It was concluded that two thirds of a supplemental dose of beta-carotene will be absorbed during orlistat treatment; this may be sufficient to achieve physiologic levels of beta-carotene with an appropriate dose of beta-carotene, should supplementation be needed in obese patients who have developed beta-carotene deficiency during therapy with orlistat.

Absorption↗
PubMed1996

The design of an inhibitor using alpha, beta-dehydro residues.

X-ray crystallography and NMR spectroscopic studies on peptides containing alpha, beta-unsaturated (dehydro) residues have indicated that the steric effects caused by the dehydro residue are strong and predictable, and such residues can be used to generate specific peptide structures. In particular, dehydro-Alanine (delta Ala) is found to adopt an extended conformation and also induces a definite conformation in the neighboring saturated residue. In order to design a sequence that would fold into a known three-dimensional structure, we have undertaken a systematic theoretical study of the preferred conformations of tetrapeptide sequences of the type N-Ac-delta Ala-X-delta Ala-NHCH3 (x = Gly, L-Ala, L-Val, L-Leu, L-Lys, L-Arg, L-Phe). The methodology and parameters used have been standardized against sequences with known crystal structures. In all the sequences a consistent folding pattern is observed in which the delta Ala residues are in an extended conformation with phi approximately 140 degrees and psi approximately -40 degrees. The results are used to predict a sequence which has a structure very similar to that of the binding loop region of the bovine pancreatic trypsin inhibitor (BPTI).

Alanine↗