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Biomedical subjects

J Patel

Publications and source records attributed to J Patel.

At least 235 records · Page 13Linked to original sources
PubMed1983

Adenosine uptake inhibitors potentiate the sedative effects of adenosine.

A major action of adenosine is the induction of profound behavioral inactivity. 6-(4-Nitrobenzyl)-thioinosine (NBI) and 6-(2-hydroxy-5-nitrobenzyl)-thioguanosine (NBG) have been shown to inhibit adenosine uptake. To investigate the possible synergism between exogenous ligand and reuptake inhibition, mice were treated with NBI or NBG + adenosine. NBI and NBG potentiated the effects of adenosine at doses which did not in themselves induce behavioral inactivity. These behavioral results support the proposed role of NBI and NBG as adenosine uptake site blockers which increase synaptic concentrations of adenosine and postsynaptic responses to adenosine in vivo.

Adenosine↗
PubMed1983

Chronic caffeine consumption increases the number of brain adenosine receptors.

Caffeine, a potent central stimulant, is known to competitively inhibit the specific binding of both adenosine and benzodiazepine receptor ligands to brain membranes in vitro. In mice receiving a diet containing non-toxic doses of caffeine (200 or 400 mg/kg diet) for periods up to 40 days, a dose-related increase in the number of binding sites for [3H]-CHA and [3H] DPX was observed in whole brain membranes without modifications of the receptors' affinity. Furthermore, a transitory increase in the number of [3H]-DZP binding sites was observed. These preliminary data seem to confirm the involvement of the adenosine receptors in the mode of action of caffeine and may be relevant to the development of both tolerance and dependence to some of the central effects of this compound.

Adenosine↗
PubMed1983

Attenuation of alcohol drinking in tetrahydroisoquinoline-treated rats by morphine and naltrexone.

In rats of either the Sprague-Dawley or Long-Evans strain, either tetrahydroisoquinoline (THP) was infused chronically ICV, or one of three protoberberine (PBN) compounds was administered subcutaneously at birth. When the animals were 120-180 days of age, a constant concentration of alcohol was offered simultaneously with water to those rats which demonstrated a clear-cut preference for alcohol. This concentration was selected on the basis of an alcohol preference screen. After alcohol intakes had stabilized, naltrexone was injected subcutaneously in a dose of either 1.0 or 5.0 mg/kg twice a day for three consecutive days. The higher dose (10.0 mg/kg total) of naltrexone suppressed the voluntary intake of alcohol by 26%, whereas the lower dose (2.0 mg/kg total) attenuated alcohol drinking by 14%. Both doses of naltrexone reduced food intake but did not appreciably affect water intake or body weight. When morphine was injected according to the same regimen in a dose of 10.0 or 2.5 mg/kg twice per day, a 49% reduction in alcohol intake was produced by the higher dose and a 32% decline followed the lower dose. Although morphine attenuated food intake, neither water intake nor body weight was affected. Saline control injections administered twice daily in the same way failed to alter any of the intake measures or body weight. These findings indicate that the long-lasting opiate antagonist naltrexone attenuates the voluntary consumption of alcohol in a manner similar to that produced by naloxone. The present results are discussed in terms of the evidence that an opiate agonist and antagonist may exert their actions by different mechanisms in the brain, possibly through separate subpopulations of opiate receptors.

Alcohol Drinking↗
PubMed1983

Differential binding properties of adenosine receptor agonists and antagonists in brain.

The binding properties of N6-cyclohexyl [3H]adenosine ( [3H]CHA) and 1,3-diethyl-8-[3H]phenylxanthine ( [3H]DPX) in rat forebrain membrane are compared. The kinetic parameters of binding for each ligand are quite distinct, with [3H]CHA displaying two populations of binding sites (KD = 0.4 +/- 0.05 nM and 4.2 +/- 0.3 nM; Bmax = 159 +/- 17 and 326 +/- 21 fmol/mg protein), whereas [3H]DPX yielded monophasic Scatchard plots (KD = 13.9 +/- 1.1 nM; Bmax = 634 +/- 27 fmol/mg protein). The metals copper, zinc, and cadmium are potent inhibitors of [3H]CHA binding, with respective IC50 concentrations of 36 microM, 250 microM, and 70 microM. Copper is a much less potent inhibitor of [3H]DPX binding (IC50 = 350 microM). The inhibitory effect of copper on both [3H]CHA and [3H]DPX binding is apparently irreversible, as membranes pretreated with copper cannot be washed free of its inhibitory effect. The inhibitory effect of both copper and zinc on [3H]CHA binding was reversed by the guanine nucleotide Gpp(NH)p. [3H]DPX binding is only partially inhibited by zinc and cadmium (60% of specific binding remains unaffected), suggesting that this adenosine receptor ligand binds to two separate sites. Guanine nucleotides had no effect on the inhibition of [3H]DPX binding by either copper or zinc. Differential thermal and proteolytic denaturation profiles are also observed for [3H]CHA and [3H]DPX binding, with the former ligand binding site being more labile in both cases. Stereospecificity is observed in the inhibition of both [3H]CHA and [3H]DPX binding, with L-N-phenylisopropyladenosine (PIA) being 50-fold more potent than D-PIA in both cases. Evidence is therefore provided that adenosine receptor agonists and antagonists have markedly different binding properties to brain adenosine receptors.

Adenosine↗
PubMed1983

S-100-mediated inhibition of brain protein phosphorylation.

The effects of the glial-specific, calcium-binding, S-100 protein on brain membrane and supernatant protein phosphorylation were assessed. S-100 concentrations as low as 5 micrograms/ml caused a marked inhibition of the phosphorylation of a soluble brain protein having a molecular weight of 73,000 daltons (73K). This protein was designated the S-100 protein-modulated phosphoprotein (SMP). Half-maximal inhibition of the phosphorylation of SMP by S-100 was obtained at concentrations of 12 micrograms/ml (0.57 microM). The inhibition of SMP phosphorylation by S-100 was calcium-dependent, with a calculated calcium Ka of 2.0 +/- 0.3 microM. SMP phosphorylation was also inhibited by calmodulin, but only partially and with a much lower potency. The inhibition of SMP phosphorylation by S-100 was not inhibited by fluphenazine, whereas the effect of calmodulin was. SMP was found in many brain areas, with the highest levels seen in the corpus callosum. Various peripheral tissues, such as kidney; liver; and pineal, pituitary, and adrenal glands, did not contain detectable SMP levels. At higher S-100 concentrations, greater than 10 micrograms/ml, the phosphorylation of several other soluble proteins was markedly inhibited. These proteins have molecular weights of 56K, 50K, and 47K. The phosphorylation of these proteins was enhanced by calmodulin. These data suggest that the S-100 protein may function to modulate the phosphorylation of brain proteins in a manner analogous to (although in a reciprocal fashion) that of calmodulin.

Animals↗
PubMed1983

Evaluation of latex-Rickettsia rickettsii test for Rocky Mountain spotted fever in 11 laboratories.

A latex-Rickettsia rickettsii test for detection of antibodies to Rocky Mountain spotted fever (RMSF) was evaluated during the 1980 RMSF season in 11 laboratories in nine states where the disease is endemic. In a double-blind study, all sera submitted to each laboratory for RMSF testing were also examined by the latex-R. rickettsii test. A portion of each specimen was then sent to the New York State laboratory for testing by latex-R. rickettsii and by the reference microimmunofluorescence test. Results were exchanged at the end of the examination period. At the usual ratio of reactive to nonreactive sera encountered in a diagnostic laboratory on a day-to-day basis, the efficiency of the latex-R. rickettsii test relative to microimmunofluorescence was 96.79% for New York and 93.30% for the collaborating laboratories. Both the latex and microimmunofluorescence tests detected antibodies to RMSF within 7 to 9 days of onset. With the latex-R. rickettsii test--but not necessarily with microimmunofluorescence--a high titer (greater than or equal to 128) on a single serum was diagnostic of active RMSF. Changes in serum titer for patients with multiple sera were similar for both tests. The test detects rickettsial antibodies in patients with active infection, but in most cases it does not detect antibody in patients with past infection. Test reactivity could not be uniquely linked to a particular immunoglobulin class.

Antibodies, Bacterial↗
PubMed1983

Prediction of adult height from height and bone age in childhood. A new system of equations (TW Mark II) based on a sample including very tall and very short children.

A new series of equations is presented for predicting the adult height of a child given present height and bone age. These equations (TW height prediction, Mark II) which replace the ones given in 1975 (TW height prediction, Mark I) are based on larger numbers of normal children, and more importantly on a sample that includes, for the first time, numbers of very tall, very short, and very growth-delayed children. In addition, equations are given for use when the increment of height or bone age, or both, over the previous year is known. These variates improve the prediction at most ages over 8 years in girls and 11 years in boys. The previously given parental allowance has been dropped. Typically 95% of the predictions lie within +/- 8 cm of the real value for boys aged 10 years, falling to +/- 6 cm for boys aged 15 years, or +/- 4 cm if their previous height increment is known. For premenarcheal girls the predictions lie within about +/- 6 cm at age 8 years; a figure which diminishes little till 13 years unless height and bone age increments are known, when it reaches +/- 4 cm at 13 years. For postmenarcheal girls the predictions are substantially more accurate.

Adolescent↗
PubMed1983

Cranial computed tomography and real-time sonography in full-term neonates and infants.

The results of cranial ultrasonography (US) and computed tomography (CT) were compared in 52 full-term neonates and young infants. The chief indications for examination included: increasing head size, dysmorphic features, myelomeningocele, inflammatory disease, and asphyxia. Disorders detected included hydrocephalus, parenchymal abnormalities, intracranial hemorrhage, extraparenchymal fluid collections, and vascular and other developmental malformations. Hydrocephalus and subdural collections were seen in patients referred for all clinical indications, whereas diffuse parenchymal abnormalities, subarachnoid hemorrhage, and intraventricular hemorrhage occurred primarily in patients with hypoxia. CT and US essentially were equivalent in detecting hydrocephalus, moderate to large intraventricular hemorrhages or subdural collections, and large focal parenchymal lesions, although CT was somewhat better in determining the level and cause of obstruction in patients with hydrocephalus and characterizing parenchymal abnormalities. CT was more sensitive than ultrasound in detecting subarachnoid hemorrhage (100% vs. 0%), diffuse parenchymal abnormality (100% vs. 33%), and small intraventricular hemorrhages (100% vs. 0%) but these lesions often were not clinically significant. The results suggest that US should be used as the primary neuroradiological examination in term infants; CT probably should be reserved for further investigation after US in those patients with a history of hypoxia and progressive clinical deterioration.

Brain↗
PubMed1982

Specific calcium antagonist binding sites in brain.

The binding of the calcium antagonist [3H] nitrendipine ([3H] NDP) to brain and heart is described and the brain site is characterized. The binding is saturable, specific and of very high affinity with KD values of 0.16 nM in brain and 0.21 nM in heart. Our kinetic results are similar to those recently reported by two other groups (1, 2), indicating a saturable, high affinity binding site in brain. In brain the binding sites are enriched in crude nuclear and synaptosomal fractions. The highest levels of binding are seen in the hippocampus, caudate and cerebral cortex with much lower levels in the cerebellum and pons. Calcium has a marked stimulatory effect on [3H] NDP binding at 10(-4) M. Addition of 0.5 mM CaCl2 to EDTA treated membranes nearly doubles the number of binding sites. Of the many drugs and neurotransmitters tested only other calcium antagonists, i.e. verapamil, inhibit binding (IC50 = 250 nM). The inhibition of [3H] NDP binding by verapamil is apparently non-competitive and not complete, suggesting that [3H] NDP binds to several sites, only some of which are inhibited by verapamil. The [3H] NDP binding site is probably a protein since it is very sensitive to trypsin, heat and sulfhydryl reagents.

Animals↗
PubMed1982

Differential effects of GABA on peripheral and central type benzodiazepine binding sites in brain.

The binding of the clinically inactive benzodiazepine [3H]RO-5-4864 to brain membranes was investigated. The peripheral type benzodiazepine binding site was demonstrated in brain with an apparent Kd of 1.6 nM and a Bmax of 20 fmol/mg protein. Monophasic Scatchard plots indicate a homogenous population of a high affinity sites. The major inhibitory transmitter GABA, has no effect on [3H]RO-5-4864 binding to extensively wash brain membranes. The peripheral type benzodiazepine binding site found in brain is therefore not modulated GABA.

Animals↗
PubMed1982

Effects of caffeine and theophylline on adenosine and benzodiazepine receptors in human brain.

The binding of various adenosine receptor ligands and of [3H]diazepam, as well as their inhibition of methylxanthines, have been studied in human brain cerebral cortex membranes. Caffeine and theophylline competitively inhibit binding of [3H]cyclohexyladenosine, [3H]diethylphenylxanthine, [3H]phenylisopropyladenosine and [3H]diazepam. Both caffeine and theophylline are more potent as inhibitors of adenosine receptor ligand binding compared to [3H]diazepam binding. Theophylline was more potent than caffeine in its ability to compete with adenosine receptor ligand binding while the reverse was true for [3H]diazepam binding. The meaning of these results for the mode of action of methylxantine is discussed.

Adenosine↗