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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 361 records · Page 20Linked to original sources
PubMed1993

Comparative study of bioavailabilities and pharmacokinetics of clindamycin in healthy volunteers and patients with AIDS.

The absolute oral bioavailability and pharmacokinetics of clindamycin administered to 16 healthy volunteers and 16 patients with AIDS were compared. Clindamycin was given intravenously (i.v.) (Cleocin phosphate) at a dose of 600 mg as a 25-min infusion and orally (Cleocin hydrochloride) by use of a crossover design in both study groups. Plasma samples were analyzed by gas-liquid chromatography. Plasma drug clearance and volume of distribution at the steady state following the i.v. dose differed between study groups. The clearances were 0.27 +/- 0.06 liter/h/kg in healthy volunteers and 0.21 +/- 0.06 liter/h/kg in AIDS patients (P = 0.014; Mann-Whitney U test); the volumes of distribution at the steady state were 0.79 +/- 0.13 and 0.66 +/- 0.12 liter/kg in healthy volunteers and AIDS patients, respectively (P = 0.005). The elimination half-life did not differ between the two groups. The bioavailability of clindamycin capsules in AIDS patients was approximately 1.5 times that in healthy volunteers (0.53 +/- 0.14 versus 0.75 +/- 0.20; P = 0.002). Peak concentrations following the oral dose were higher in AIDS patients as well (7.7 +/- 2.5 versus 5.3 +/- 1.0 mg/liter; P = 0.0008). Three AIDS patients experienced severe diarrhea following the oral dose; four patients had mild diarrhea following the i.v. dose. No adverse effects were reported by the healthy volunteers. The pharmacokinetic parameters observed in this study for AIDS patients may be useful for the consideration of clindamycin dosage regimens in patients treated for toxoplasmic encephalitis. These findings suggest that the effect of AIDS on drug disposition deserves further investigation, particularly for orally administered drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Brain lactate and pH dissociation in edema: 1H- and 31P-NMR in collagenase-induced hemorrhage in rats.

Brain edema has been shown to increase brain lactate, but the effect on pH is unclear. We used in vivo nuclear magnetic resonance (NMR) spectroscopy to measure lactate and pH in a region of brain edema. Ninety-five anesthetized rats underwent proton and 31P-NMR spectroscopy with a 7-T 89-mm vertical bore spectrometer, using a surface coil over the edematous regions and distant from a hemorrhage produced by the injection of bacterial collagenase. Brain water content was measured from multiple regions after the NMR measurements in all rats. Lactate was significantly increased 4 h after the hemorrhage and remained elevated for 48 h, but brain pH was unaffected. The increase in lactate correlated (P < 0.01) with the increase in water content in the measured region. We conclude that lactate and pH are dissociated in a region of primarily vasogenic edema.

Animals↗
PubMed1993

Differential effects of the optical isomers of EMD 53998 on contraction and cytoplasmic Ca2+ in isolated ferret cardiac muscle.

EMD 53998 (a thiadiazinone) is a novel inotropic substance that increases the Ca2+ sensitivity of the myofilaments in skinned cardiac fibers and has been found to have similar effects in intact cardiac muscle. However, the compound also possesses the ability to inhibit phosphodiesterase III, indicating that its actions in intact cardiac muscle are likely to be complex. The present study was carried out to investigate the possibility that the optical isomers of EMD 53998--(+)EMD 57033 and (-)EMD 57439--which have recently been shown to possess a separation of sensitization and phosphodiesterase inhibition in subcellular preparations, might also demonstrate this separation of activities in intact cardiac muscle. The experiments were performed on isolated ferret papillary muscles, which were contracting isometrically. In some preparations, the photoprotein aequorin was injected into superficial cells to measure intracellular Ca2+ as well as force. (+)EMD 57033 caused a substantial positive inotropic effect that was associated with prolongation of the twitch, reduction in the amplitude of the Ca2+ transient, and abbreviation of the Ca2+ transient. This is the profile expected of a Ca(2+)-sensitizing compound. Conversely, (-)EMD 57439 caused a less marked positive inotropic effect that was associated with an abbreviation of the twitch, an increase in the amplitude of the Ca2+ transient, and an abbreviation of the Ca2+ transient. This is the profile expected of an agent producing its inotropic effect by increasing cAMP (e.g., phosphodiesterase inhibition). The results indicate that the optical isomers of EMD 53998 possess a remarkable separation of Ca(2+)-sensitizing and phosphodiesterase-inhibiting activities in intact cardiac muscle. These actions were additive and could account for the effects observed with EMD 53998. (+)EMD 57033 appears to be the first inotropic agent that acts predominantly by increasing myofilament calcium sensitivity.

Animals↗
PubMed1993

Markets, budgets, and health care cost control.

Health care cost control is often debated in terms of markets versus bureaucracies. Market restraints are limited in practice by the goal of providing access to care. Therefore, effective cost control requires budgeting. Experience from budgeting for other services should put health care cost control in perspective: The goal should not be rational and efficient allocations, merely better ones. The important choice is not between markets and bureaucracy, but rather which decisions should be made by physicians and which by budgeters, and how to ensure that professional judgment is applied where most important.

Budgets↗
PubMed1993

Effects of ethanol on carbohydrate metabolism in the elderly.

We have previously reported that in young men, ethanol caused acute insulin resistance, but compensatory insulin secretion prevented deterioration of glucose tolerance (1). In this study, we tested the hypothesis that elderly men, because of their pre-existing insulin resistance and compromised insulin secretory capacity, may experience worsening of their glucose tolerance after ethanol. Nine elderly men (65.7 +/- 0.8 yr, BMI 25.8 +/- 1.4 kg/m2) received ethanol (13 mmol/kg for 30 min i.v.) or saline followed 30 min later by i.v. glucose (2.8 mmol/kg for 5 min). To determine the mechanism of the ethanol effect, six of the men underwent euglycemic-hyperinsulinemic (approximately 350 pM) clamping with simultaneous infusion of ethanol or saline. Muscle biopsies were obtained before and 1 and 4 h after insulin infusion. In all nine men, glucose concentrations after i.v. glucose were higher after ethanol than after saline, whereas insulin was the same and glucose tolerance decreased by 23% (Kg 2.41 +/- 0.2 vs. 1.86 +/- 0.1%/min, P < 0.01). Ethanol reduced insulin-stimulated glucose uptake from 40.6 +/- 3.1 to 25.6 +/- 1.9 mumol.kg-1.min-1 (-37%, P < 0.05), glucose oxidation from 11.7 +/- 1.1 to 7.0 +/- 0.7 mumol.kg-1.min-1 (-33%, P < 0.01), and glucose storage from 28.7 +/- 2.4 to 18.6 +/- 1.7 mumol.kg-1.min-1 (-35%, P < 0.01). Ethanol increased muscle lactate concentration from 0.49 +/- 0.14 to 1.99 +/- 0.99 mumol/mg protein (P < 0.05), but had no effects on muscle concentration of free glucose, G-6-P, and citrate concentrations, nor did it affect muscle GS activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Purification and initial characterization of peptidyl-tRNA hydrolase from rabbit reticulocytes.

We have identified an activity in rabbit reticulocyte lysate as peptidyl-tRNA hydrolase, based upon its ability to hydrolyze native reticulocyte peptidyl-tRNA, isolated from polyribosomes, and N-acylaminoacyl-tRNA, and its inability to hydrolyze aminoacyl-tRNA, precisely the same substrate specificity previously reported for peptidyl-tRNA hydrolase from bacteria or yeast. The physiological role of the reticulocyte enzyme may be to hydrolyze and recycle peptidyl-tRNA that has dissociated prematurely from elongating ribosomes, as suggested for the bacterial and yeast enzymes, since reticulocyte peptidyl-tRNA hydrolase is completely incapable of hydrolyzing peptidyl-tRNA that is still bound to polyribosomes. We have purified reticulocyte peptidyl-tRNA hydrolase over 5,000-fold from the postribosomal supernatant with a yield of 14%. The purified product shows a 72-kDa band upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis that has co-purified with enzyme activity and comprises about 90% of the total stained protein, strongly suggesting that the 72-kDa protein is the enzyme. Sucrose density gradient analysis indicates an apparent molecular mass for the native enzyme of 65 kDa, implying that it is a single polypeptide chain. The enzyme is almost completely inactive in the absence of a divalent cation: Mg2+ (1-2 mM) promotes activity best, Mn2+ is partly effective, and Ca2+ and spermidine are ineffective. The hydrolase shows a Km of 0.60 microM and Vmax of 7.1 nmol/min/mg with reticulocyte peptidyl-tRNA, a Km of 60 nM and Vmax of 14 nmol/min/mg with Escherichia coli fMet-tRNA(fMet), and a Km of 100 nM and Vmax of 2.2 nmol/min/mg with yeast N-acetyl-Phe-tRNA(Phe). The enzyme has a pH optimum of 7.0-7.25, it is inactivated by heat (60 degrees C for 5 min), and its activity is almost completely inhibited by pretreatment with N-ethylmaleimide or incubation with 20 mM phosphate. The fact that the enzyme hydrolyzes E. coli but not yeast or reticulocyte fMet-tRNA(fMet) may be explained, at least in part, by structural similarities between prokaryotic tRNA(fMet) and eukaryotic elongator tRNA that are not shared by eukaryotic tRNA(fMet).

Animals↗
PubMed1992

The site of hydrolysis by rabbit reticulocyte peptidyl-tRNA hydrolase is the 3'-AMP terminus of susceptible tRNA substrates.

The preceding paper (Gross, M., Starn, T.K., Rundquist, C., Crow, P., White, J., Olin, A., and Wagner, T. (1992) J. Biol. Chem. 267, 2073-2079) reported the purification and partial characterization of rabbit reticulocyte peptidyl-tRNA hydrolase. In this article we demonstrate that, unlike bacterial and yeast peptidyl-tRNA hydrolase which act by deacylation, the reticulocyte enzyme hydrolyzes N-acylaminoacyl-tRNA to N-acylaminoacyl-AMP. Reticulocyte lysate has a separate enzyme, that we have isolated and termed aminoacyl-AMP deacylase, which hydrolyzes N-acylaminoacyl-AMP and aminoacyl-AMP, recycling the amino acid and nucleotide components. The action of this enzyme is relatively specific for the N-acylaminoacyl-AMP generated by peptidyl-tRNA hydrolase, since it is much less active with N-acylaminoacyl-adenosine and inactive with N-acylaminoacyl-ACCAC, N-acylaminoacyl-tRNA, or aminoacyl-tRNA. The tRNA product of peptidyl-tRNA hydrolase action is tRNA missing only its 3'-AMP terminus (tRNA(c-c)), since reaminoacylation requires tRNA nucleotidyltransferase but not CTP. The 3' exonucleolytic action of reticulocyte peptidyl-tRNA hydrolase is specific to susceptible tRNA substrates, since it does not hydrolyze CACCA, CACCA-N-acylamino acid, polyuridylic acid, or the 3' polyadenylate tail of globin mRNA, and, since its ability to hydrolyze Escherichia coli f[3H]Met-tRNA(fMet) is not reduced by excess 5 S or 28 S ribosomal RNA and is reduced only slightly by excess tRNA(c-c). Reticulocyte peptidyl-tRNA hydrolase also hydrolyzes th 3'-AMP terminus of deacylated tRNA. This property may explain why the 3'-terminal AMP of tRNA undergoes turnover in reticulocytes and reticulocyte lysate, since we find that such turnover in gel-filtered reticulocyte lysate is increased under conditions where aminoacylation is reduced.

Adenosine Monophosphate↗
PubMed1992

The acidic transcriptional activator GAL-VP16 acts on preformed template-committed complexes.

The action of the chimeric acidic transcriptional activator GAL-VP16 has been investigated by performing a series of kinetic experiments using the detergent Sarkosyl as well as monoclonal antibodies which specifically inhibit GAL-VP16 DNA binding and transcriptional activation. GAL-VP16 binds to recognition site rapidly, remains bound after transcriptional initiation and is required to maintain stimulated levels of reinitiation. GAL-VP16 action, which appears to result in an increase in the number of preinitiation complexes formed, occurs after the formation of template-committed complexes composed of promoter-bound TFIIA (STF) and a partially purified TFIID fraction conferring GAL-VP16 responsiveness on a reconstituted basal transcription system. This TFIID fraction cannot be replaced by TFIIB or cloned TFIID. Our results suggest that GAL-VP16 activates step(s) in preinitiation complex assembly occurring after TFIID has bound.

Antibodies, Monoclonal↗
PubMed1992

Variation in the composition of the venom from a single specimen of Pseudonaja textilis (common brown snake) over one year.

Venom was collected over a 12-month period from a single specimen of Pseudonaja textilis. No trends in the weight of venom extracted or protein content were noted. Amidolytic activity, coagulant and esterolytic activity showed a decrease over the summer months, while a rise in phosphodiesterase and 5' nucleotidase activity was noted at this time. Precipitin lines developed against the venoms by brown snake antivenom showed variability over the 12-month period. Gel filtration and SDS-polyacrylamide gel electrophoresis profiles showed quantitative and minor qualitative differences; however, the variation noted in the activities of these venoms was not predictable from these profiles.

Animals↗
PubMed1992

Novel translocation (2;4) with consistent involvement of 2p23 in acute nonlymphocytic leukemia (M2).

A translocation involving the short arm of chromosome 2 and the long arm of chromosome 4 is described in three patients, all of whom had acute nonlymphocytic leukemia (M2). One patient had M2 de novo, one progressed from refractory anemia with excess blasts in transformation to M2 over a 4-month period, and one had had sideroblastic anemia 30 years prior to development of M2. In all three patients, the translocation involved the breakpoint p23 on chromosome 2, but the breakpoints on chromosome 4 varied between q25, q31, and q35. Translocations specifically involving 2p23 have not previously been described in leukemia, but more cases are required to identify a specific association with either the FAB type or prognosis.

Adult↗
PubMed1992

Extracellular: intracellular and subcellular concentration gradients of thiols.

Chinese hamster V79 cells in Eagle's minimum essential medium in vitro at room temperature were incubated with the aminothiol, WR-1065, or glutathione (GSH) at extracellular concentrations of approximately 1 mmol dm-3. Average intracellular concentrations of GSH, cysteine, and WR-1065 were measured by high performance liquid chromatography, and the effective reducing environment near DNA probed by staining the cells with acridine orange (AO) and measuring the delayed fluorescence. Exposure to either thiol resulted in a rapid, 10-fold increase in average intracellular cysteine concentrations (to about 1 mmol dm-3). Adding extracellular GSH after prior depletion of GSH by treatment with L-buthionine sulfoximine (BSO) did not restore intracellular GSH, but intracellular cysteine was elevated 10-fold. These results are ascribed to thiol/disulfide exchange with cystine in the medium. WR-1065 slowly concentrated intracellularly to approximately 160% of the extracellular concentration. Chemical conjugation of GSH in cells decreased the reducing environment near DNA, but BSO treatment altered the uptake of AO. The electrostatic attraction of WR-1065 toward isolated DNA was markedly affected by ionic strength.

Animals↗
PubMed1992

Correlation of the radiosensitization potency afforded by nitroacridine intercalators with their electron scavenging efficiency in DNA.

Nitracrine (1-NC) and its nitro-positional analogues are electron-affinic DNA intercalating compounds that act as hypoxic cell radiosensitizers in cell culture, but are too rapidly metabolized to provide radiosensitization in vivo. We have explored the electron-trapping efficiencies of nitroacridines to see if such compounds can scavenge radicals formed in irradiated DNA and if the efficiency of such trapping is related to their radiosensitization properties. We have shown that a correlation does indeed exist as 1-NC, the most potent radiosensitizer, scavenges approximately 45% of the migrating electrons (formed by attachment of eaq- to the DNA) compared with approximately 4% for 4-NC, the least efficient radiosensitizer. The quenching of the delayed fluorescence from acridine orange bound to DNA was also used to probe intracellular uptake and association with DNA. The results are in accord with earlier measurements of average uptake and a suggestion that intercalators which form DNA complexes with short residence times will be preferable to highly bound agents as radiosensitizers. Since 1-NC possesses the smallest association constant with DNA of the four compounds, it is suggested that its high radiosensitization potency may well be related to it being able to interact with more radical sites on the DNA than the other analogues, in addition to its capture of migrating electrons in DNA.

Animals↗
PubMed1992

Genes necessary for directed axonal elongation or fasciculation in C. elegans.

The outgrowth of single axons through different cellular environments requires distinct sets of genes in the nematode C. elegans. Three genes are required for the pioneering circumferential outgrowth of identified motor neuron axons between the lateral hypodermal cell membrane and the basal lamina. Three other genes are required for the longitudinal outgrowth of these axons along preexisting axon bundles as well as for the fasciculation of axons within these neuron bundles. Five additional genes are required for circumferential outgrowth, longitudinal outgrowth, and fasciculation; mutations in three of these genes disrupt axon ultrastructure, suggesting that they function in axon formation rather than in axon guidance.

Animals↗
PubMed1992

Ineffective staff, ineffective supervision, or ineffective administration? Why some nursing homes fail to provide adequate care.

This study involved 530 nursing staff working in 25 for-profit and nonprofit nursing homes, two of which failed to meet resident care standards required for state recertification. Staff members' job attitudes, opinions regarding elderly residents, and perceptions of the organization climate varied between the successful for-profit and non-profit homes. The organization climate in the failed homes was significantly different from the climate in either the successful for-profit or successful nonprofit homes.

Attitude of Health Personnel↗
PubMed1992

Cognitive bias in the articulated thoughts of depressed and nondepressed psychiatric patients.

Beck's cognitive theory of depression postulates several types of cognitive bias among depressed patients. Empirical studies supporting this hypothesis have usually used questionnaire "endorsement" measures of cognition, which may suggest responses to subjects. We used the articulated thoughts during simulated situations (ATSS) method of cognitive assessment in comparing cognitive processes of 15 outpatients with major depression with those of 15 nondepressed psychiatric outpatients in three simulated situations. Depressed patients exceeded nondepressed patients in cognitive bias only in the negative (not the neutral or positive) simulated situation. Discussion centered on the possible utility of ATSS for research on cognition in stressful situations.

Cognition↗