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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 595 records · Page 33Linked to original sources
PubMed1999

Effects of epinephrine and amrinone on contractility and cyclic adenosine monophosphate generation of tumor necrosis factor alpha-exposed cardiac myocytes.

OBJECTIVE: This study utilized an in vitro neonatal rat cardiac myocyte assay to evaluate potential differences in the response of TNF-alpha-exposed myocytes to stimulation with the adrenergic agent, epinephrine, and the phosphodiesterase III inhibitor, amrinone. DESIGN: Contractility was assessed by measuring the maximum extent of the contraction of electrically paced neonatal rat cardiac myocytes in tissue culture using a closed-loop video tracking system. Myocytes were incubated in control or media containing TNF-alpha (50 ng/mL) for 20 mins and were then stimulated with increasing concentrations of either epinephrine (0.1 to 100 ng/mL) for 15 mins or amrinone lactate (0.25 to 10 microg/mL) for 20 mins. MEASUREMENTS AND MAIN RESULTS: Compared with control myocytes, TNF-alpha-exposed myocytes stimulated with increasing concentrations of epinephrine demonstrated a decreased peak augmentation of contractility (p<.0001 analysis of variance). This decrease was paralleled by a decrease in epinephrine-stimulated generation of cyclic AMP, as measured by enzyme-linked immunoassay (p = .05 polynomial regression). In contrast, increasing concentrations of amrinone produced increased peak augmentation of contractility (p = .003 analysis of variance) in TNF-alpha-exposed cardiac myocytes (relative to controls). However, this increase was not reflected by increased amrinone-stimulated generation of cyclic AMP relative to control myocytes not exposed to TNF-alpha (p = NS polynomial regression). CONCLUSIONS: Our data suggest that TNF-alpha induces a defect in beta-adrenergic signal transduction and catecholamine-stimulated contractility in neonatal rat cardiac myocytes. In addition, TNF-alpha augments the inotropic response of myocardial tissue to phosphodiesterase inhibitors through a mechanism independent of cyclic AMP generation. Phosphodiesterase inhibitors such as amrinone may be found to exert significant inotropic effects in catecholamine-refractory septic shock with myocardial depression and other conditions of inflammatory myocardial dysfunction.

Amrinone↗
PubMed1999

Myocardial kinetics of 99m technetium-Q agents: studies in isolated cardiac myocyte, isolated perfused rat heart, and canine regional myocardial ischemia models.

OBJECTIVE: Based on reports of high cellular uptake and low plasma binding of nonreducible mixed ligand Tc(III) cations (Q complexes) and high linear uptake versus blood flow of 99mTc-Q3 in canine hearts, the authors hypothesized that the two Q complexes, 99mTc-Q63 and 99mTc-Q64, would have high cell uptake and better differentiation between ischemic and nonischemic myocardium compared with other 99mTc-based compounds. METHODS: Uptake and retention kinetics of 99mTc-Q63 and 99mTc-Q64 were measured in isolated rat cardiac myocytes, isolated perfused rat hearts, and intact canines and compared with previously reported Q-based compounds, a clinically available 99mTc perfusion agent (sestamibi), and 201Tl. RESULTS: Uptake of Q63, Q64, and sestamibi by isolated cardiac myocytes was similar. Maximum extraction (Emax) of Q64 by isolated perfused rat hearts was greatest among the 99mTc agents (P < 0.02), but net extraction (Enet) of Q64 was not different from Q63 or sestamibi 3 minutes after tracer injection. By 15 minutes, 201Tl Enet was lower than Q63, Q64, and sestamibi (P < 0.05). Among 99mTc agents, the uptake versus flow of Q3, Q63, and Q64 by canine heart was superior to Q12 and sestamibi (P < 0.05). CONCLUSIONS: The activity of Q63 and Q64 in the myocardium is related to actual myocardial blood flow over a broad, clinically relevant range of flows. The ischemic-to-normal zone activity distributions of Q63 and Q64 approximate actual flow in a manner more like that of 201Tl than sestamibi or Q12. These results provide a rational foundation in support of further evaluation of Q63 and Q64 in humans.

Acute Disease↗
PubMed1999

Closed reduction of posterior dislocation of the elbow: a simple technique.

A simple technique is described for closed reduction of posterior dislocation of the elbow in the supine position without anesthesia or the help of an assistant. The main feature of this technique is gentle disengagement of the coronoid process from the lower humerus and control over the olecranon during reduction. There is less likelihood of soft tissue damage by avoiding traction and hyperextension. This technique is safe, simple, and easily learned and has a high success rate.

Humans↗
PubMed1999

Leukoderma following occupational allergic contact dermatitis.

We describe 2 cases of occupational allergic contact dermatitis followed by leukoderma. The 1st case was a 49-year-old wood machinist who developed leukoderma in areas of contact dermatitis involving his lips, neck, hands and forearms and was found to be allergic to colophony and pine sawdust on patch testing. The 2nd case involved a 44-year-old man who worked as an epoxy applicator in a ceramics factory. He developed depigmentation in areas of contact dermatitis involving his face, hands, forearms, back, thighs and legs and was found on patch testing to be allergic to epoxy resin. The appearance of contact leukoderma may be indistinguishable from idiopathic vitiligo. However the prognosis for repigmentation may be better in contact leukoderma than in idiopathic vitiligo.

Adult↗
PubMed1999

Neural spectrum: palisaded encapsulated neuroma and verocay body poor dermal schwannoma.

We examined 25 palisaded encapsulated neuromas (PEN) of the skin and used peripherin antibody as an immunohistochemical label for axons. Quantitative analysis of the axon to schwann cell nuclear ratio for each PEN was determined by examining cross-sectioned neuroid fascicles. This revealed that 120 of the 253 cross-sectioned fascicles in PEN lacked axon and only 5% of the fascicles had an axon to schwann cell nuclear ratio greater than 1:2. In contrast, all fascicles in 40 dermal nerves adjacent to PENs as well as 35 traumatic neuromas in surgical scars had an axon to schwann cell nuclear ratio of at least 1:2 and the majority a ratio of 1:1 or higher. These results suggest that there is a spectrum between PENs which are axon rich to a form of schwannoma with an identical histopathology which lacks significant axonal content and that not all PENs are true neuromas.

Adult↗
PubMed1999

Role of secondary structure in discrimination between constitutive and inducible activators.

We have examined structural differences between the proto-oncogene c-Myb and the cyclic AMP-responsive factor CREB that underlie their constitutive or signal-dependent activation properties. Both proteins stimulate gene expression via activating regions that articulate with a shallow hydrophobic groove in the KIX domain of the coactivator CREB-binding protein (CBP). Three hydrophobic residues in c-Myb that are conserved in CREB function importantly in cellular gene activation and in complex formation with KIX. These hydrophobic residues are assembled on one face of an amphipathic helix in both proteins, and mutations that disrupt c-Myb or CREB helicity in this region block interaction of either factor with KIX. Binding of the helical c-Myb domain to KIX is accompanied by a substantial increase in entropy that compensates for the comparatively low enthalpy of complex formation. By contrast, binding of CREB to KIX entails a large entropy cost due to a random coil-to-helix transition in CREB that accompanies complex formation. These results indicate that the constitutive and inducible activation properties of c-Myb and CREB reflect secondary structural characteristics of their corresponding activating regions that influence the thermodynamics of formation of a complex with CBP.

Amino Acid Sequence↗
PubMed1999

Safety and effectiveness of BCG vaccination in preterm babies.

AIM: To assess the cell mediated immune response to BCG vaccine in preterm babies. METHODS: Sixty two consecutive preterm babies born at < 35 weeks of gestation were randomly allocated into two groups. Babies in group A were vaccinated early at 34-35 weeks and group B were vaccinated late at 38-40 weeks of postconceptional age. The two groups were similar in terms of: gestational age (mean (SD) 33.1 (1. 1) and 33 (1.2) weeks, respectively); birthweight 1583 (204) and 1546 (218) g; neonatal problems; socioeconomic status; and postnatal weight gain. The cell mediated immune response to BCG was assessed using the Mantoux test and the lymphocyte migration inhibition test (LMIT) 6-8 weeks after BCG vaccination. Induration of >5 mm after the Mantoux test was taken as a positive response. RESULTS: There was no significant difference in the tuberculin conversion rates (80% and 80.7%, respectively), positive LMIT (86.6% and 90.3%, respectively), or BCG scar (90.0% and 87.1%, respectively) among the two groups. CONCLUSIONS: Prematurity seems to be an unlikely cause for poor vaccine uptake. Preterm babies can be effectively vaccinated with BCG at 34-35 weeks of postconceptional age, the normal time of discharge in a developing country.

BCG Vaccine↗
PubMed1999

Plant retrotransposons.

Retrotransposons are mobile genetic elements that transpose through reverse transcription of an RNA intermediate. Retrotransposons are ubiquitous in plants and play a major role in plant gene and genome evolution. In many cases, retrotransposons comprise over 50% of nuclear DNA content, a situation that can arise in just a few million years. Plant retrotransposons are structurally and functionally similar to the retrotransposons and retroviruses that are found in other eukaryotic organisms. However, there are important differences in the genomic organization of retrotransposons in plants compared to some other eukaryotes, including their often-high copy numbers, their extensively heterogeneous populations, and their chromosomal dispersion patterns. Recent studies are providing valuable insights into the mechanisms involved in regulating the expression and transposition of retrotransposons. This review describes the structure, genomic organization, expression, regulation, and evolution of retrotransposons, and discusses both their contributions to plant genome evolution and their use as genetic tools in plant biology.

Evolution, Molecular↗
PubMed1999

Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility.

Previous studies have demonstrated the existence of a circulating myocardial depressant substance during human septic shock. We have recently identified this substance as a synergistic combination of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). This study utilized an in vitro cardiac myocyte assay to evaluate the potential mechanistic role of nitric oxide (NO) and cGMP in depression of myocyte contractility induced by TNF-alpha, IL-1beta, TNF-alpha + IL-1beta (at low concentrations), and human septic shock serum (HSS). TNF-alpha, IL-1beta, TNF-alpha + IL-1beta, and each of 5 sera from patients with acute septic shock caused depression of both maximum extent and peak velocity of cardiac myocyte shortening and an increase in intracellular cGMP concentration during 30 min of exposure (minimum P < 0.01). NO synthetase (NOS) and guanylate cyclase inhibitors such as N-methyl-L-arginine (L-NMA) and methylene blue prevented these effects; an excess of L-arginine with L-NMA restored them (minimum P < 0.01). In contrast, D-arginine failed to reestablish cytokine-induced myocyte depression and cGMP accumulation prevented by L-NMA. Exposure of myocytes to TNF-alpha, IL-1beta, or TNF-alpha + IL-1beta produced a concentration-dependent increase in intracellular cGMP that paralleled the depression of cardiac myocyte contractility (minimum P < 0.001). In addition, TNF-alpha, IL-1beta, TNF-alpha + IL-1beta, or HSS application to cardiac myocytes resulted in increased NO gas generation, which was inhibited by L-NMA (minimum P < 0.01). Furthermore, unstimulated cardiac myocytes were shown to harbor constitutive but not inducible NOS activity. These data suggest that the sequential generation of NO by a constitutive NOS and cGMP by guanylate cyclase represents an important mechanism of cardiac myocyte depression by TNF-alpha, IL-1beta, TNF-alpha + IL-1beta, and the myocardial depressant substance(s) of septic shock.

Animals↗
PubMed1999

Serial segmental bronchoalveolar lavage in individual rats.

Bronchoalveolar lavage (BAL) is a well-characterized technique for analysis of cellular constituents of the airways and air spaces, but whole lung lavage requires that the animal be euthanized. We describe a technique of segmental BAL in rats that allows serial measurements of inflammation. A tracheal tube was placed, under direct visualization, in lightly anesthetized animals, and a catheter was passed through the tracheal tube and advanced to a wedge position. Five 0.1-ml volumes of buffer solution were instilled and then withdrawn with gentle suction. In normal rats, the percentages of neutrophils, eosinophils, and mononuclear cells had a high level of agreement in the segmental samples compared with those obtained subsequently by whole lung lavage. In rats with acute pulmonary inflammation, the differential leukocyte counts from segmental samples exhibited patterns of change that differed from those of whole lung lavage; however, most segmental samples were obtained from the left lung base so that regional variability could be minimized in serial studies. Lung mechanics and airway inflammation were not affected by repeated segmental BALs done 2 wk apart.

Aging↗
PubMed1999

Role of C/A polymorphism at -20 on the expression of human angiotensinogen gene.

-Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive hormones, angiotensin II. Human angiotensinogen gene contains a C/A polymorphism at -20 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at -20, this sequence binds to the estrogen receptor. We also show that transcriptional activity of reporter constructs containing human angiotensinogen gene promoter with nucleoside A at -20 is increased on cotransfection of an expression vector containing human estrogen receptor-alpha coding sequence in human hepatoma cells (HepG2) followed by estrogen treatment. On the other hand, adenoviral major late transcription factor binds preferentially to this region of the promoter when nucleoside C is present at -20. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at -20 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at -20. Our data suggest that C/A polymorphism at -20 may modulate the expression of human angiotensinogen gene in a sex-specific manner.

Adenoviridae↗
PubMed1999

Prevention of chronic postbronchiolitis airway sequelae with IFN-gamma treatment in rats.

After viral bronchiolitis at an early age, Brown Norway (BN) rats develop chronic airway dysfunction consisting of inflammation, remodeling, episodic reversible obstruction, and hyperresponsiveness. We hypothesized that supplementation of interferon gamma (IFN-gamma) during viral illness would alter the inflammatory response and attenuate the postviral sequelae. Weanling rats were treated daily with aerosolized interferon gamma (IFN-gamma), from 2 d prior through 7 d after inoculation, and compared with saline-treated infected rats and with noninfected control rats. The IFN-gamma treatment had no significant effect on viral titers, growth retardation, or total bronchoalveolar leukocytes, but there was a slight decrease in lung interleukin-4 (IL-4) mRNA (p = 0.015) during the first week. Despite having minimal effects on the acute illness, the IFN-gamma had marked effects on postviral sequelae, the IFN-gamma group having less bronchiolar inflammation (p = 0.025) and fibrosis (p = 0.01), and lacking abnormalities in pulmonary resistance (p = 0.028) and dynamic compliance (p = 0.006) compared with the untreated postviral group. We conclude that IFN-gamma modulated the inflammatory response to viral illness, such that acute airway injury did not evolve into chronic airway dysfunction. If similar processes contribute to the development of human asthma, it may be possible to interrupt the progression of airway dysfunction with an early immunomodulatory intervention.

Airway Resistance↗