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Biomedical subjects

H Paul

Publications and source records attributed to H Paul.

At least 37 records · Page 2Linked to original sources
PubMed1996

The beta-adrenergic receptor is a substrate for the insulin receptor tyrosine kinase.

G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on beta-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of beta 2-adrenergic receptors. Phosphorylation of tyrosyl residues 350/354 of beta 2-adrenergic receptors is obligatory for counter-regulation by insulin (Karoor, V., Baltensperger, K., Paul, H., Czech, M., and Malbon, C. C. (1995) J. Biol. Chem. 270, 25305-25308), suggesting the hypothesis that G-protein-linked receptors themselves may act as substrates for the insulin receptor and other growth factor receptors. This hypothesis was evaluated directly using recombinant human insulin receptor, hamster beta 2-adrenergic receptor, and an vitro reconstitution and phosphorylation assay. Insulin is shown to stimulate insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor. Phosphoamino acid analysis establishes that insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor in vitro is confined to phosphotyrosine. High pressure liquid chromatography and two-dimensional mapping reveal insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor at residues Tyr132/Tyr141, Tyr350/Tyr354, and Tyr364, known sites of phosphorylation in response to insulin in vivo. Insulin-like growth factor-I receptor as well as the insulin receptor displays the capacity to phosphorylate the beta 2-adrenergic receptor in vitro, establishing a new paradigm, i.e. G-protein-linked receptors acting as substrates for intrinsic tyrosine kinase growth factor receptors.

Amino Acid Sequence↗
PubMed1996

Correlates of vascular access and nonvascular access-related hospitalizations in hemodialysis patients.

Four hundred and thirty randomly selected hemodialysis patients, aged 20 years and over, were studied to identify risk factors for vascular access and nonvascular access-related hospitalizations in the immediately preceding 1 year. Risk estimates for hospitalization were assessed using a multinominal logistic analysis model. We measured functional status, utilizing a 14-point Karnofsky scale, and in a separate analysis of covariance, in which Karnofsky score was the outcome, we examined the relationships of age, gender, ethnicity, renal diagnosis, and hospitalization. Individual comparisons were adjusted for multiple comparison bias by Tukey's Honest Difference method. There were a total of 508 hospitalizations of which 322 (63%) lasted > or = 1 week. Two hundred and sixty (60%) patients were hospitalized at least once; 105 (24.4%) for access problems only, 115 (27%) for a nonaccess problem only, and 40 for access and nonaccess-related problems. Access-related problems, accounted for 48% of all hospitalizations. The risk of hemodialysis vascular access morbidity was increased in women (p < 0.028) and white (p < 0.048) hemodialysis patients. Neither diabetic nor elderly hemodialysis patients were at greater risk for access hospitalization than their respective counterparts, though a greater proportion of the access hospitalizations in the elderly (> or = 64 years) lasted > or = 1 week (p < 0.0006). More access-related hospitalizations in blacks (64.5%), lasted for > or = 1 week than in whites (40.6%) (p < 0.001). Hispanics (p < 0.043), whites (p < 0.002), and the older patients (p < 0.054) were at greater risk for nonaccess hospitalization than blacks and younger patients, respectively. Even after adjusting for age, race, and diabetes, each decrease of one unit in the modified Karnofsky score was associated with a 3-4% increased risk for all types of hospitalization (p < 0.001)--poor functional status is associated with increased risk for all hospitalizations. We conclude that the risk for hemodialysis vascular access morbidity is increased in women and white hemodialysis patients. Poor functional status is associated with increased risk for all hospitalizations.

Adult↗
PubMed1995

Phosphorylation of tyrosyl residues 350/354 of the beta-adrenergic receptor is obligatory for counterregulatory effects of insulin.

Insulin stimulates a loss of function and increased phosphotyrosine content of the beta 2-adrenergic receptor in intact cells, raising the possibility that the beta 2-receptor itself is a substrate for the insulin receptor tyrosine kinase. Phosphorylation of synthetic peptides corresponding to cytoplasmic domains of the beta 2-adrenergic receptor by the insulin receptor in vitro and peptide mapping of the beta 2-adrenergic receptor phosphorylated in vivo in cells stimulated by insulin reveal tyrosyl residues 350/354 and 364 in the cytoplasmic, C-terminal region of the beta 2-adrenergic receptor as primary targets. Mutation of tyrosyl residues 350, 354 (double mutation) to phenylalanine abolishes the ability of insulin to counterregulate beta-agonist stimulation of cyclic AMP accumulation. Phenylalanine substitution of tyrosyl reside 364, in contrast, abolishes beta-adrenergic stimulation itself.

Amino Acid Sequence↗
PubMed1995

[Bipolar dislocation of the first metatarsal bone].

Simultaneous dislocation of the first cuneometatarsal joint and metatarsophalangeal joint is a rare injury. The case of a 22-year-old man is reported, but no previous cases have been reported in the literature. The treatment by closed reduction and pinning was very classical. Occasionally the reducibility of the metatarsophalangeal joint may be made more difficult by the interposition of a sesamoid bone. The simultaneous dislocation occurred because the injury was very severe. After 2 years, the function and mobility of the toe were normal, but radiographs revealed modifications of the Lisfranc joint.

Adult↗
PubMed1994

In vitro and in vivo genotoxicity evaluation of hormonal drugs. II. Dexamethasone.

Genotoxicity evaluation of a widely used glucocorticoid medicine, dexamethasone, was undertaken using in vitro and in vivo assays. Analyses of chromosomal aberrations, sister-chromatid exchanges (SCEs) in human lymphocytes and micronuclei and SCEs in mouse bone marrow showed the drug to be capable of attacking the genetic material. However, the Ames/Salmonella assay, both with and without S9 mix, did not show any increase in His+ revertants.

Animals↗
PubMed1994

In situ localisation of beet necrotic yellow vein virus (BNYVV) in rootlets of susceptible and resistant beet plants.

Mechanisms of resistance to beet necrotic yellow vein virus (BNYVV) were studied by comparing the multiplication and distribution of BNYVV in root tissue of some beet accessions. Seedlings were infected either by soil containing resting spores of Polymyxa betae with BNYVV, or by a viruliferous zoospore suspension. With both inoculation methods high virus concentrations were obtained in rootlets of the susceptible cultivar 'Regina'. Using infested soil, low virus concentrations were found in the partially resistant cultivar 'Rima' and in the resistant accessions Holly and WB42. When a zoospore suspension was used, similar virus concentrations occurred in 'Rima' and Holly as in 'Regina', while a low virus concentration was found in WB42. By in situ localisation studies, using immunogold-silver labelling, virus was detected in 'Regina' after infection by soil or a zoospore suspension, but it could only be detected in the resistant accessions after infection by a zoospore suspension. In rootlets of 'Regina', 'Rima' and Holly, virus was found in the epidermis, cortex parenchyma, endodermis, and interstitial parenchyma, but in general not inside the vascular tissue. In WB42 the virus, occurring in small aggregates, seemed to be restricted to the epidermis and some cortex parenchyma cells. Comparing both the multiplication and distribution of BNYVV in rootlets of the accessions studied, it is concluded that the virus resistance mechanism in 'Rima' and Holly is different from that in WB42.

Immunohistochemistry↗
PubMed1994

Pervasive failed rehabilitation in center-based maintenance hemodialysis patients.

At its inception in 1972, the end-stage renal disease (ESRD) program was conceived with a set of assumptions about cost, rate of growth, and treatment outcomes in its client population. Despite the potential to correct anemia with recombinant erythropoietin (EPO) introduced in 1987 and improved survival, the level of physical activity among some segments of the hemodialysis population remains suboptimal. This study was undertaken, among other reasons, to identify correlates of poor functional status as measured by a modified Karnofsky scale. Using a modified Karnofsky scale, we measured the functional status of 430 patients who had been treated by hemodialysis for at least 1 year and some of whom were also receiving concomitant treatment with EPO. Patients studied were randomly selected from eight dialysis units in urban New York and suburban New Jersey. A Karnofsky score of less than 70 indicated frank disability--the subject was unable to perform routine living chores without assistance. In addition, current vocational activity was ascertained, and comorbid conditions were quantified. The necessity for wheelchair dependence was noted for each patient. The mean age (+/- SD) of the study population was 56 +/- 14 years (range, 21 to 92 years). Subjects had been on maintenance hemodialysis for 4.09 +/- 3.8 years (range, 1 to 23 years). The study group included 215 men and 215 women, of whom 65% were black, 27% white, 6% Hispanic, and 2% Asian; 36.5% had diabetes mellitus. Although 376 members (87%) of the study group were under treatment with EPO, the mean hematocrit of the study population was only 29% +/- 4.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1993

Blood-ocular barrier permeability and electroretinogram after intravitreal silicone oils of varying composition.

Silicone oils, used as long-term retinal tamponades, cause retinal toxicity that may be related to certain ingredients. Specific additives, proven to increase corneal endothelial permeability, were added to a purified oil, and placed into the vitreous of rabbits to assess their effects on the retina. Oils were exchanged for vitreous at constant intraocular pressure to 1 ml oil volume. Blood-ocular barrier permeability was measured with fluorophotometry after intravenous dye, and retinal function was measured using dark-adapted electroretinography (ERG). Each parameter was determined at eight week intervals: this periodicity was chosen to allow any toxicity to develop based upon prior data in the literature. The fluorescein concentration in different ocular compartments indicated an increased aqueous humor fluorescein concentration after pure oil (a non-statistically significant 50% increase) or oil plus long chain additive (a significant 240% increase). After oil plus a linear series of compounds both aqueous humor (2000%) and anterior vitreous fluorescence (8000%) was statistically significantly increased, indicating a breakdown of the blood-aqueous barrier. The height of the b-wave of the ERG was unaffected by any oil in the presence or absence of additive. Overt changes were minimal with oil alone, increased with oil containing linear chain additive, and were extensive with oil with long chain additive.

Animals↗