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J Green

Publications and source records attributed to J Green.

At least 451 records · Page 25Linked to original sources
PubMed1990

X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor.

The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-psi[CH(OH)CH2N]-Pro-Ile-Val-OMe; the Ki is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-A resolution by using restrained least squares with rms deviations in bond lengths of 0.02 A and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365.

Amino Acid Sequence↗
PubMed1990

Cytosolic pH regulation in osteoblasts. Regulation of anion exchange by intracellular pH and Ca2+ ions.

Measurements of cytosolic pH (pHi) 36Cl fluxes and free cytosolic Ca2+ concentration ([Ca2+]i) were performed in the clonal osteosarcoma cell line UMR-106 to characterize the kinetic properties of Cl-/HCO3- (OH-) exchange and its regulation by pHi and [Ca2+]i. Suspending cells in Cl(-)-free medium resulted in rapid cytosolic alkalinization from pHi 7.05 to approximately 7.42. Subsequently, the cytosol acidified to pHi 7.31. Extracellular HCO3- increased the rate and extent of cytosolic alkalinization and prevented the secondary acidification. Suspending alkalinized and Cl(-)-depleted cells in Cl(-)-containing solutions resulted in cytosolic acidification. All these pHi changes were inhibited by 4',4',-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) and H2DIDS, and were not affected by manipulation of the membrane potential. The pattern of extracellular Cl- dependency of the exchange process suggests that Cl- ions interact with a single saturable external site and HCO3- (OH-) complete with Cl- for binding to this site. The dependencies of both net anion exchange and Cl- self-exchange fluxes on pHi did not follow simple saturation kinetics. These findings suggest that the anion exchanger is regulated by intracellular HCO3- (OH-). A rise in [Ca2+]i, whether induced by stimulation of protein kinase C-activated Ca2+ channels, Ca2+ ionophore, or depolarization of the plasma membrane, resulted in cytosolic acidification with subsequent recovery from acidification. The Ca2+-activated acidification required the presence of Cl- in the medium, could be blocked by DIDS, and H2DIDS and was independent of the membrane potential. The subsequent recovery from acidification was absolutely dependent on the initial acidification, required the presence of Na+ in the medium, and was blocked by amiloride. Activation of protein kinase C without a change in [Ca2+]i did not alter pHi. Likewise, in H2DIDS-treated cells and in the absence of Cl-, an increase in [Ca2+]i did not activate the Na+/H+ exchanger in UMR-106 cells. These findings indicate that an increase in [Ca2+]i was sufficient to activate the Cl-/HCO3- exchanger, which results in the acidification of the cytosol. The accumulated H+ in the cytosol activated the Na+/H+ exchanger. Kinetic analysis of the anion exchange showed that at saturating intracellular OH-, a [Ca2+]i increase did not modify the properties of the extracellular site. A rise in [Ca2+]i increased the apparent affinity for intracellular OH- (or HCO3-) of both net anion and Cl- self exchange. These results indicate that [Ca2+]i modifies the interaction of intracellular OH- (or HCO3-) with the proposed regulatory site of the anion exchanger in UMR-106 cells.

Animals↗
PubMed1990

Eating and its relationships with subjective alertness and sleep in narcoleptic subjects living without temporal cues.

The sleep and meal patterns of normal subjects appear to be governed by a common timing mechanism. To investigate whether the postulated mechanism may be disordered in narcolepsy, a disorder of sleep timing, we analyzed the sleep, eating, and subjective alertness of six narcoleptic subjects and seven normal controls while they lived in a temporal isolation laboratory. When subjects were free to eat and sleep whenever they chose ("free-running"), the meal patterns and nutrient intakes of the free-running narcoleptic subjects and controls were similar; no evidence of an eating disorder intrinsic to narcolepsy was found. When meals were offered on a 24-h schedule, narcoleptic subjects ate more frequently than did the controls. In two of three narcoleptic subjects whose free-running biological days markedly lengthened, intermeal intervals lengthened proportionately. This was evidence that the timing of sleep (bed-dark) periods and meals was indeed governed by a common mechanism. Meal onsets of narcoleptic subjects were preceded by a 90-min period of decreased napping and, when meals were scheduled, by increased subjective alertness. They were followed by a 150-min period of increased napping and decreased subjective alertness. Postprandial deactivation was not found in controls. The deactivation could not be explained by a post-absorptive effect of food, since the contents of meals that were followed by naps did not differ from those that were not followed by naps. While a preabsorptive effect of meals has not been ruled out, we suggest that postmeal deactivation may be evidence that the mechanism that times sleep periods and meals also modulates the temporal pattern of narcoleptic naps.

Adult↗
PubMed1990

The bottom line.

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Accounting↗
PubMed1990

Phobic anxiety and clumsiness in a 10-year-old girl.

During assessment of a girl with a long-standing phobic state, it was found that she also had previously unrecognised perceptuo-motor problems, which were associated with continuing problems in balance and spatial awareness. Her phobia improved after a desensitisation programme, but the physical disorder persisted, despite physiotherapy. The authors conclude that the girl's phobic anxiety may have had its origin in her experience of the perceptual disorder during development.

Child↗
PubMed1990

Responses of single phrenic motoneurons to altered ventilatory drives in anesthetized dogs.

We studied the effects of altered ventilatory drives on the activity of the whole phrenic nerve and single phrenic motoneurons in dogs anesthetized with alpha-chloralose and paralyzed with gallamine triethiodide. Single phrenic motoneurons were classified as either late-onset or early-onset motoneurons (LOM and EOM, respectively), depending on the time of onset of their activity during inspiration. Increase in ventilatory drive was induced by altering chemical drive with changes in arterial blood gases and also by altering the vagal afferent contribution to ventilatory drive. The latter was accomplished by inducing pulmonary gas embolism (PGE) during hyperoxia. Whole phrenic nerve activity was increased by both types of increase in ventilatory drive. In both cases, changes in the firing pattern of LOMs and EOMs were responsible for the increased phrenic output. The changes in post-PGE firing pattern of the LOMs generally consisted of a shift in the time of onset to an earlier point in inspiration and an increase in the number of spikes per inspiratory cycle. Vagotomy abolished the difference between the contributions of LOMs and EOMs to the phrenic response to PGE. Data from dogs studied while they were breathing spontaneously were qualitatively the same as those from the paralyzed animals, indicating no major role for phasic volume feedback in these responses. Our data regarding altered chemical drive are similar to those reported earlier in other species, whereas those regarding PGE demonstrate that vagally mediated increases in ventilatory drive affect both LOMs and EOMs, although LOMs are affected to a greater degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1990

Progressive aphasia: a precursor of global dementia?

We studied 8 subjects longitudinally in whom isolated language dysfunction had developed gradually at a mean age of 62.8 years. The language deficits initially displayed by the subjects were characteristic of the syndrome of "progressive aphasia without dementia." By 5 years after onset of progressive aphasia, however, 7 of the 8 subjects additionally had developed mild dementia as diagnosed by clinical means, and the remaining subject demonstrated declining performance in both verbal and nonverbal psychometric measures. Thus, generalized cognitive impairment occurred in all. Neuropathologic evidence of a diffuse dementing disorder was present in the 2 subjects studied postmortem. One had Alzheimer's disease with disproportionate involvement of the left inferior parietal cortex, and the other displayed widespread neocortical neuronal loss and microvacuolation in the absence of specific histopathologic markers. In this series, progressive aphasia was a precursor of global dementia.

Aged↗
PubMed1990

Ouham-Pendè: a new endemic goiter area in Centro-African Republic (C.A.R.). Preliminary observations on school children.

In this work, the Authors make several epidemiological observations and report a series of biohumoral data relative to a new endemic goiter area in the north-western region of the Centro-African Republic (CAR). In this province whose chief-town is Bocaranga, living conditions are very poor and primitive, manioca being the staple food. The survey was carried out in 11 rural schools and in 2 schools in the chief-town; 4009 subjects were examined; 2839 were males, 1170 females. The goiter prevalence observed in the whole sample population was 79.75%. The prevalence for each step of the grading were: 34.6% for 1a; 32.9% for 1b; and 11.8% for 2. In the schools of the chief town the goiter prevalence was found to be significantly lower than in the rural schools (71.9% versus 83.6% with P less than 0.01). Being the goitrous F/M ratio equal to 1.041, the goiter prevalences and gradings in females were higher and more severe than in males. After calculating these differences by means of the cumulated frequencies and the Kolmogorov Smirnov test, they were found to be significant. In 45 goitrous subjects, high TSH (7.19 microU/ml +/- 5.1), T3 (1.65 ng/ml +/- 0.56), and TG serum levels (410 ng/ml +/- 280) were found; however, low normal levels were observed for rT3 (8.97 ng/dl +/- 7.5) and fT4 (0.50 ng/ml +/- 0.51). In 42 casual urine samples, iodine excretion was 23.2 micrograms/l +/- 12.8; thyocianate excretion was 9.72 mg/l +/- 6 with a I/SCN ratio = 2.38.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Ouham-Pendé: a new endemic goiter area in the Centroafrican Republic (CAR): epidemiological survey on 7621 subjects.

The authors report epidemiological observations about a new endemic goiter area in the North western region of the Centro-African Republic (CAR). The research was carried out in 7 quarters of the chief-town (Bocaranga) and in 8 rural villages; 7621 people were examined by the same three of the present Authors who filled in a sample individual form (proposed by WHO) with the generalities and the goiter grading. The data were analyzed according to sex, age and place of residence by means of the common position parameters and the cumulative frequencies, taking into account the goiter grading of each group. The goiter prevalences observed in the rural areas varied from 70.9% (males) to 82.6% (females), whereas in the chief-town they varied from 29.3% (males) to 57.9% (females). Neurological and myxedematous cretins were seen to constitute 3.4% of the visited population. The M/F goitrous ratio was near unity under the age of 6; above this age, females are more widely and severely affected than males. An important fall in goiter prevalence was observed in adult males after the age of 16. The gradings observed in the rural villages, in both females and males of different ages (0-5; 6-15; 16-45; greater than 45 ys.) were significantly more severe than those observed in the chief town (P less than 0.01). The results obtained confirm those of a preliminary survey which the Authors previously carried out on a sample of school children living in the same region of CAR.

Adolescent↗
PubMed1990

Profile of bronchospastic disease in Puerto Rican patients in New York City. A possible relationship to alpha 1-antitrypsin variants.

A high prevalence of asthmalike symptoms was noted among patients of Puerto Rican descent attending Beth Israel and North Central Bronx Medical Centers in New York City, as compared with other ethnic groups. An evaluation of family and medical histories, pulmonary function data, and alpha 1-antitrypsin phenotypes was undertaken in such Puerto Rican patients and control subjects without asthma. The patients showed a higher proportion of MS and MV phenotypes. All the patients in both MM and variant phenotype groups, with the exception of four MM patients, had features indicative of asthma, with labile airway obstruction, and elevated serum immunoglobulin E and eosinophil levels. The latter was significantly higher in the patients with variant phenotypes than in MM patients. Patients with alpha 1-antitrypsin variants also had much shorter smoking histories as compared with the MM group, and all reported histories of asthma in first-degree relatives, as compared with 66% among the MM patients. We conclude that there is an increased incidence of asthma among Puerto Ricans in New York City, and that the antitrypsin variant phenotypes (specifically S and V) play a role in this incidence and its expression.

Asthma↗
PubMed1989

Classification of prostaglandin receptors based on coupling to signal transduction systems.

A wide spectrum of prostaglandins (PG) stimulate both the production of cyclic AMP and an increase in free cytosolic Ca2+ concentration [( Ca2+]i) in the osteogenic osteosarcoma cell line, UMR-106-01, which has characteristics compatible with osteoblasts. Using PG-stimulated determinations of the second messengers cyclic AMP and [Ca2+]i, a method for classification of PG receptors is presented. UMR-106-01 cells demonstrate three subclasses of PG receptors. One receptor interacts with PGF2 alpha, PGD2, and thromboxane B2 (TxB2) to increase [Ca2+]i. A second receptor binds PGE2, PGE1, PGI2, PGA2 and 6-oxo-PGF1 alpha to increase [Ca2+]i by stimulation of a second separate phospholipase C pool. A third receptor accepts PGE2, PGE1, PGA2, PGI2 and to a lesser extent PGF2 alpha, PGD2 and TxB2 to increase cyclic AMP. Such a classification system may be applicable to other cells responding to multiple PGs by inducing changes in cellular second messengers.

Adenylyl Cyclases↗
PubMed1989

Substrate specificity of soluble methane monooxygenase. Mechanistic implications.

Following the example set by studies of the mechanistic aspects of the substrate specificity of various cytochrome P-450 enzymes, we have undertaken a parallel investigation of the soluble methane monooxygenase from Methylococcus capsulatus (Bath). Soluble methane monooxygenase is a multicomponent enzyme with a broad substrate specificity. Using substrates previously tested with cytochrome P-450 enzymes and using purified enzyme preparations, this work indicates that soluble methane monooxygenase has a similar oxidative reaction mechanism to cytochrome P-450 enzymes. The evidence suggests that soluble methane monooxygenase oxidizes substrates via a nonconcerted reaction mechanism (hydrogen abstraction preceding hydroxylation) with radical or carbocation intermediates. Aromatic hydroxylation proceeds by epoxidation followed by an NIH shift.

Alkanes↗
PubMed1989

A stitch in time.

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Community Mental Health Services↗