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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

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

Diabetic RBC-induced oxidant stress leads to transendothelial migration of monocyte-like HL-60 cells.

Red blood cells (RBC) from patients with diabetes mellitus exhibit an increased propensity to adhere to cultured human umbilical vein endothelial cells (HUVEC) as a result of interaction of advanced glycation end products with their counter receptors, contributing to the pathogenesis of vascular complications. We determined whether the interaction of diabetic RBC with HUVEC induced cellular oxidant stress that would culminate in adherence and diapedesis of monocytes, these being initiating events in endothelial injury and atherogenesis. We show that the adherence of diabetic RBC (2% hematocrit), but not normal RBC, to HUVEC results in a fourfold increase in the production of lipid peroxides. Furthermore, diabetic RBC-induced oxidant stress causes a sixfold increase in platelet endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation and doubles transendothelial migration of monocyte-like HL-60 cells; both are blocked by antioxidants and protein kinase C (PKC) inhibitors. Our results show that the adherence of diabetic RBC to endothelial cells initiates a cascade of cellular events resulting in PKC activation, causing PECAM-1 phosphorylation and concomitant transendothelial migration of monocytes. The increased diapedesis of monocytes, brought about by the interaction of diabetic RBC across vascular endothelium, may play an important role in accelerated atherosclerosis and cardiovascular disease in diabetics.

Antioxidants↗
PubMed1997

Geographic variation in the utilization and choice of procedures for treating coronary artery disease in New York State. Ischaemic Heart Disease Patient Outcomes Research Team (PORT).

OBJECTIVES: To examine geographical variations in rates of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in New York State, and to examine variations in the choice between these two procedures. METHODS: A retrospective analysis of data from the New York registries for CABG and angioplasty was conducted. Rates were compared for 12 different regions of the state to assess geographic variations. To assess variations in the choice of procedure, frequencies of each procedure by region were compared with expected frequencies obtained by a logistic regression model that related procedure performance to various patient risk factors. RESULTS: There was more than a three-fold variation in age/sex adjusted CABG rates and more than a two-fold variation in age/sex adjusted angioplasty rates among regions. The regional percentages of patients undergoing CABG rather than PTCA ranged from 49% to 70%, and most of the disparity was not related to patient risk factors. Instead, the disparity was largely a result of differences in racial composition and the hospitalization rate for myocardial infarctions. CONCLUSIONS: There is considerable regional variation in New York in the tendency to use aggressive cardiac procedures and in the choice of which procedure to use, and these differences are mostly unrelated to patient need.

Age Distribution↗
PubMed1997

Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation.

OBJECTIVE: To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-one patients with symptoms and signs of peripheral neuropathy were randomized to the electrotherapy or sham treatment (control) group. The electrostimulation was given by a portable unit (H-Wave machine) than generated a biphasic, exponentially decaying waveform (pulse width 4 ms, 25-35 V, > or = 2 Hz). Patients treated each of their lower extremities for 30 min daily for 4 weeks at home. Nine patients from the sham-treatment group participated for a second period, during which all of them received the active electrotherapy. Patient's degree of pain and discomfort was graded on a scale of 0 to 5. RESULTS: In the sham-treated group (n = 13), the neuropathic symptoms improved in five (38%) patients, and the pain score declined from 2.92 +/- 0.13 to 2.38 +/- 0.26 (P < 0.04), suggesting a procedure-related placebo effect. In the electrotherapy group (n = 18), symptomatic improvement was seen in 15 (83%) cases, 3 of which were completely asymptomatic; the pain score declined from 3.17 +/- 0.12 to 1.44 +/- 0.25 (P < 0.01) and the posttreatment pain scores were considerably lower (P < 0.03), indicating a substantial treatment effect over and above any placebo influence. Patients in the electrotherapy group reported greater reduction in symptoms (52 +/- 7% vs. 27 +/- 10% in control subjects, P < 0.05) on an analog scale. Moreover, the electrotherapy decreased pain scores (from 3.0 +/- 0.62 to 1.56 +/- 0.32, P < 0.02) in nine patients who had received sham treatment earlier. CONCLUSIONS: A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy. This novel modality offers a potential non-pharmacological treatment option.

Adult↗
PubMed1997

Lispro analog for treatment of generalized allergy to human insulin.

OBJECTIVE: To evaluate the clinical usefulness of the human insulin analog lispro in a patient with generalized allergy to human insulin. RESEARCH DESIGN AND METHODS: A 34-year-old obese female patient developed systemic allergic reactions to human insulin but tolerated insulin lispro. Sequential analyses of the anti-insulin IgE and IgG immunoglobulins were performed. RESULTS: On intradermal test, the lispro insulin produced a 50% less intense wheal-flare response, compared with human insulin, which was presumed to be due to lispro's molecular form. The intradermal reactivity to both human and lispro insulins decreased with time and disappeared by week 25. 125I-labeled lispro and human insulin binding antibody titers of both the IgE and IgG immunoglobulins were high initially, but decreased progressively, becoming very low by the end of 1 year. In in vitro immunoassay, the lispro and human insulins show a complete cross-reactivity. CONCLUSIONS: Lispro may be useful for the management of allergy to human insulin. This analog of human insulin appears to have a reduced immunogenic potency.

Adult↗
PubMed1997

Calcium modulatory properties of O,O-diphenyl O-N-cyclooctyl phosphoramidate [corrected] isolated from Ptychodiscus brevis in rat atria and smooth muscle.

Calcium modulatory activity of a marine toxin has been studied employing in vitro preparations. The toxin induced contracture in rat diaphragm was not modified by denervation, d-tubocurarine and tetrodotoxin (TTX). In contrast, varying concentrations of calcium, EGTA and ryanodine inhibited the contracture significantly. The toxin produced a series of repeating contractions in vas deferens. Experiments with TTX, adrenoceptor blockers and other agents exclude a release of neuromediators or direct stimulation of post synaptic receptors to account for the rhythmic effect in vas deferens. The dependence of rhythmicity on external Ca2+ concentration and inhibiting effect of Mn2+, ryanodine and nifedipine indicate a direct activation of voltage-sensitive calcium channel. The toxin also evoked a similar pattern of response in paced atria mediated through Ca2+ influx.

Animals↗
PubMed1997

Central noradrenergic & dopaminergic modulation of brewer's yeast-induced inflammation & nociception in rats.

The possibility of central noradrenergic and dopaminergic modulation of Brewer's yeast-induced peripheral inflammation was investigated in rats. Centrally administered noradrenaline (NA), amphetamine, which liberates NA and dopamine in the central nervous system and L-dopa, the precursor of dopamine significantly suppressed paw oedema. Conversely, the beta-adrenoceptor blocker, propranolol, catecholaminergic neuron degenerator, 6-hydroxydopamine (6-OHDA), dopaminergic antagonist, haloperidol and dopamine synthesis inhibitor, alpha-methyl para tyrosine (AMPT) augmented paw oedema. In addition, 6-OHDA and haloperidol produced significant reduction in pain threshold. The results of this study indicate that central NA and dopamine exert inhibitory effects on Brewer's yeast-induced peripheral inflammation.

Amphetamine↗
PubMed1997

Cardiovascular effects of an organophosphate toxin isolated from Ptychodiscus brevis.

The dose-dependent hypotensive and bradycardic effects induced by an ichthyotoxic organophosphate compound isolated from the marine dinoflagellate Ptychodiscus brevis were studied. These effects were not antagonized by atropine, but potentiated by alpha-adrenoceptor blocker and hexamethonium. The toxin abolished the vasopressor effect elicited by phenylephrine, indicating an alpha-adrenergic blocking activity. The cardiovascular depressor responses were antagonized by tetraethylammonium while blockade of cholinergic and histaminergic receptors or inhibition of prostaglandin synthesis failed to modify these effects. The results indicate that the cardiovascular depressor effects of the toxin are probably mediated through alpha-adrenergic and ganglionic blockade accompanied by modulation of potassium channel activity.

Adrenergic alpha-Antagonists↗
PubMed1997

Role of the interstitial cells of Cajal in the control of gut motility.

BACKGROUND: The interstitial cells of Cajal (ICCs) are a population of cells in the gastrointestinal tract which have a role in the control of gut motility. METHOD: A comprehensive review of the scientific literature was undertaken to assess current understanding of the morphology, structure, identification, distribution, development and function of these cells. RESULTS AND CONCLUSIONS: ICCs have an important role in the control of gut motility. Experimental evidence from animal studies suggests roles as pacemakers and coordinators of gut motor activity, and as intermediaries in the neural control of motility. With an increasing understanding of the distribution and behaviour of these cells in the healthy or diseased human gastrointestinal tract, there is the potential to develop novel therapeutic approaches to diseases that have gut dysmotility as a contributory factor.

Digestive System↗
PubMed1997

Platelet aggregation and lipid profile in offsprings of young ischemics.

OBJECTIVE: To study the platelet aggregation and lipid profile in offsprings of young ischemic parents. DESIGN: Cross sectional. SETTING: Hospital based. METHODS: 40 adults under 45 years of age with proven CHD and their 50 offsprings comprised the study group. In the control group, 40 age matched adults with normal maximal treadmill test and their 50 off springs were included. All were screened for lipid profile and platelet aggregation. RESULTS: Platelet aggregation was significantly elevated in adults with CHD (44.0 +/- 15.5%) compared to controls (32.22 +/- 9.1%). Children of CHD adults also had significantly elevated aggregation (34.9 +/- 12.5%) compared to control offsprings (27.8 +/- 9.9%). Adult CHD subjects had significantly elevated serum cholesterol, LDL-cholesterol (LDL-C) and atherogenic index compared to control adults. The children in both groups had similar lipid profiles. CONCLUSION: Platelet aggregation is enhanced in offsprings of young ischemics. The potential of this index as a marker for early development of CHD needs to be explored.

Adolescent↗
PubMed1997

Mechanism of cardiotoxicity induced by a marine toxin isolated from Ptychodiscus brevis.

An organophosphate toxin of marine origin isolated from red tide dinoflagellate P. brevis produced a dose-dependent dual effect on rat atria, i.e. positive inotropic effect at low concentrations (2.8 x 10(-8) to 8.4 x 10(-7) M) and negative inotropic and chronotropic responses at an elevated dose (4.8 x 10(-6) to 7.2 x 10(-4) M). The negative chronotropic and inotropic responses of the toxin were potentiated with physostigmine and ouabain whereas antagonized by atropine and hemicholinium-3 pretreatments and those effects remained unaltered by isoproterenol, phenylephrine and ouabain pretreatments. The results indicate that the toxin induced negative inotropic and chronotropic effects are mediated through release of acetylcholine from the nerve endings and consequent activation of muscarinic receptor. In atria exposed to guanethidine, bretylium, propranolol and tyramine tachyphylaxis, the positive inotropic response of the toxin was not modified. However, the response was antagonized by EGTA, nifedipine, ryanodine, calcium-free ringer and potentiated with caffeine and amiloride pretreatments. The results suggest that the positive inotropic effect of the toxin is mediated through Ca2+ influx and impairment of Na+/Ca2+ exchange process.

Animals↗
PubMed1997

Adriamycin depresses in vivo and in vitro phosphatidylethanolamine N-methylation in rat heart sarcolemma.

Adriamycin, an effective anticancer chemotherapeutic agent, causes an insidious and delayed cardiotoxicity. Different subcellular abnormalities including calcium transport changes in the sarcolemma (SL) as well as downregulation of the adrenergic system have been shown to be associated with the development of this cardiomyopathy. Since both of these activities are influenced by phospholipid methylation, effects of adriamycin on the three catalytic sites of SL phosphatidylethanolamine N-methyltransferase were examined. Rats were administered with a cumulative dose of adriamycin (15 mg/kg) over 2 weeks and examined after 3 weeks. Vehicle injected animals served as controls. Dyspnea, high mortality rate, ascites and decrease in aortic and left ventricular systolic pressure, as well as increase in left ventricular end diastolic pressure were seen in the adriamycin group. Myocardial cell damage typical of adriamycin cardiomyopathy, i.e. sarcotubular swelling, vacuolization and myofibrillar drop-out, was also apparent. Total methyl group incorporation into SL phosphatidylethanolamine using radiolabeled S-adenosyl-L-methionine as the donor was significantly depressed in the 3 week group at catalytic sites II and III. Decreased production of methylated intermediates, phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine as well as phosphatidylcholine (PC) was seen. Depression of phosphatidylethanolamine N-methylation was also noticed when SL, isolated from untreated hearts, was exposed in vitro to different concentrations (10, 100 and 1000 microM) of adriamycin. Inhibition of phosphatidylethanolamine N-methylation appears to be mediated by adriamycin-induced increase in the oxidative stress and may contribute in the pathogenesis of subcellular changes associated with this cardiomyopathy.

Analysis of Variance↗
PubMed1997

Neural networks for signal processing applications: ECG classification.

QRS complexes were classified using a Multi Layer Perceptron (MLP) using a modified version of the original Backpropagation (BP) algorithm. The input to the network were bitmaps of the QRS complexes represented in the form of a 20 x 20 matrix. A number of hidden layers (and neurons in each hidden layer) were experimented upon to observe the rate at which the network converged. Larger Networks were observed to find the minimum on the error curve with ease. Increasing the network size beyond a certain size did not improve the performance rate, rather it decreased the performance rate. It is evident that there exists an optimal neural network architecture for every given problem. The weights change rules in Backpropagation algorithm were modified to include a variation of the relationship between momentum and learning rate to observe any increase in network's performance rate. A learning rate adaptation factor was introduced into the learning algorithm to decrease the network's chances of missing a minimum on the error curve. The network was found to perform extremely well with the modified version of the algorithm. The network converged after only 9000 learning cycles when compared to 14,000 cycles with the original algorithm.

Algorithms↗
PubMed1997

Conjunctival impression cytology in xerophthalmia among rural children.

The advent of Conjunctival Impression Cytology (CIC) has opened a new chapter in the detection of Vitamin A deficiency as it is a simplified field technique. The need for such a technique was of paramount importance in India where as estimated 5 to 7 percent children suffer from eye signs of Vitamin A deficiency. In the present study the results of clinical evaluation of apparently healthy children and those having clinical sings and symptoms of Vitamin A deficiency have been compared with CIC results. Serum Vitamin A levels have also been estimated wherever possible. The findings indicate that CIC results are superior to the clinical assessment and it is suggested that CIC can be used as screening tool for children of school going age (and earlier) for early detection and correction of Vitamin A deficiency.

Child↗
PubMed1996

A 43 kDa DNA binding protein from the pea chloroplast interacts with and stimulates the cognate DNA polymerase.

A DNA binding protein with DNA polymerase 'accessory activity' has been identified and purified to apparent homogeneity from pea chloroplasts. This protein consists of a single subunit of 43 kDa and binds to DNA regardless of its base sequence and topology. It increases cognate DNA polymerase-primase activity in a dose dependent manner. Using solid phase protein-protein interaction trapping and co-immunoprecipitation techniques, the purified protein was found to associate with the chloroplast DNA polymerase. The chloroplast DNA polymerase also binds directly to the radioiodinated 43 kDa protein. The specific interaction between 43 kDa protein and chloroplast DNA polymerase results in the synthesis of longer DNA chains. The 43 kDa protein, present abundantly in the pea chloroplast, appears to increase processivity of the chloroplast DNA polymerase and may play an important role in the replication of pea chloroplast DNA.

Antibodies↗
PubMed1996

Audit of sphincter repair. Factors associated with poor outcome.

PURPOSE: This study was designed to critically analyze the outcome of sphincter repair and, if possible, to identify high-risk factors. METHODS: Clinical and physiologic assessment was made of all sphincter repairs (42 patients) performed in one unit by two surgeons during five years. RESULTS: Forty-two patients (10 men, 32 women) underwent sphincter repair. Only three of five men with anterior defects of the anorectum from perineal trauma were rendered continent. Only three of five men with defects from fistula operations became continent, but one improved by later graciloplasty. All six women with fistula-related injuries eventually achieved continence, but two required repeat sphincter repairs because of early breakdown from sepsis. The worst results were in 26 women with third-degree obstetric injuries, of whom 11 remain incontinent; poor results in this group were associated with gross perineal descent, obesity, and age older than 50 years; two or more of these factors indicated a poor outcome. Preoperative anorectal physiology did not identify a poor-risk group. CONCLUSIONS: Poor results were identified in women with anterior defects from obstetric trauma, especially if they were obese, older than 50 years of age, and had perineal descent.

Adult↗