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Biomedical subjects

J M Smith

Publications and source records attributed to J M Smith.

At least 19 recordsLinked to original sources
PubMed1992

Venous leg ulcers: a prognostic index to predict time to healing.

OBJECTIVE: To evaluate the prognostic factors in uncomplicated venous leg ulcer healing. DESIGN: Randomised parallel group controlled trial with subjects stratified by initial ulcer diameter and four months' maximum duration of follow up. SETTING: Assessment at Northwick Park Hospital vascular unit with community based treatment. PATIENTS: 200 patients with clinical and objective evidence of uncomplicated venous leg ulceration and an initial ulcer diameter > 2 cm. MAIN OUTCOME MEASURE: Time to complete healing of the ulcer. RESULTS: In the presence of graduated compression healing occurred more rapidly in patients with a smaller initial ulcer area (relative risk of healing 1.92 associated with halving of ulcer area (95% confidence interval 1.58 to 2.33)), shorter duration of ulceration (relative risk 1.35 associated with halving duration (1.17 to 1.56)), younger age (relative risk 1.34 associated with 10 year decrease (1.12 to 1.59)), and no deep vein involvement (relative risk 1.8 (1.19 to 2.78)). CONCLUSION: These prognostic factors used in a simple scoring system predict time to healing.

Aged↗
PubMed1992

Contempo '92.

Explore the source record for details and available documents.

Forecasting↗
PubMed1992

Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway.

Aminoimidazole riobnucleotide carboxylase, the sixth step in the purine biosynthetic pathway, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to carboxyaminoimidazole ribonucleotide (CAIR). The gene products of the purE and purK genes (PurE and PurK, respectively) thought to be responsible for this activity have been overexpressed and the proteins purified to homogeneity. PurE separates from PurK in the first ammonium sulfate fractionation during the purification. No evidence for association of the two gene products under a variety of conditions using a variety of methods could be obtained. To facilitate the assay for CAIR production, the purC gene product, 5-aminoimidazole-4-N-succinylcarboxamide ribonucleotide (SAICAR) synthetase has also been overexpressed and purified to homogeneity. The activities of PurE, PurK, and PurE.PurK have been investigated. PurE alone is capable of catalyzing the conversion of AIR to CAIR 1 million times faster than the nonenzymatic rate. The Km for HCO3- in the PurE-dependent reaction is 110 mM! PurK possesses an ATPase activity that is dependent on the presence of AIR. No bicarbonate dependence on this reaction could be demonstrated (less than 100 microM), and AIR is not carboxylated during the hydrolysis of ATP. Incubation of a 1:1 mixture of PurE and PurK at low concentrations of bicarbonate (less than 100 microM) revealed that CAIR is produced but requires the stoichiometric conversion of ATP to ADP and Pi. No dependence on the concentration of HCO3- could be demonstrated. A new energy requirement in the purine biosynthetic pathway has been established.

Adenosine Triphosphatases↗
PubMed1992

Mechanisms of inactivation of Schistosoma mansoni and mammalian glutathione S-transferase activity by the antischistosomal drug oltipraz.

Glutathione S-transferase (GST) purified from Schistosoma mansoni or human placenta was inhibited by the antischistosomal drug oltipraz (OPZ) in a time- and concentration-dependent manner. Inhibition of placenta GST was complete at a low concentration of drug, whereas that of parasite GST was incomplete and relatively high amounts of OPZ were needed to reach 50% inhibition. Complete reactivation of GST from placenta was achieved with dithiothreitol (DTT) and other sulfhydryl-containing compounds, while the inactivation of parasite GST was irreversible. The oxy-derivative of OPZ (RP 36,642), in which the thione sulfur is replaced with oxygen, did not inhibit GST activity. There were no differences between OPZ and RP 36,642 in their patterns of binding to the hydrophobic non-substrate site of GST. GST from the placenta incorporated much higher levels of [14C]N-ethylmaleimide compared to schistosome GST. The incorporation of [14C]N-ethylmaleimide by GST was inhibited by OPZ but not by RP 36,642. Yeast and S. mansoni hexokinases were similarly inhibited by OPZ but not by RP 36,642. Both hexokinase preparations recovered their activity following incubation with DTT. These data suggest that the inactivation of these enzymes by OPZ is a result of its interaction with their SH groups. Thus, the antischistosomal activity of OPZ may be accounted for by its interaction with the SH groups of macromolecules in general.

Animals↗
PubMed1992

Induction of glutathione S-transferase isoenzymes in mouse liver by 5-(2-pyrazynl)-4-methyl-1,2-dithiole-3-thione (oltipraz).

Treatment of mice with a single dose of oltipraz (OPZ) at 200 mg/kg led to a significant (P less than 0.05) increase in hepatic cytosolic glutathione S-transferase (GST) activity and content. GST activity monitored with 1,2-dichloro-4-nitrobenzene was increased 3.8-fold 3 days after treatment, suggesting the induction of mu class isoenzymes. Ethacrynic acid, a marker for pi class isoforms, showed only a slight increase in GST activity while no induction was observed with cumene hydroperoxide, an indicator for the alpha class. The increase in mu class isoenzymes was further confirmed by separation of the mouse liver affinity purified GST by chromatofocusing and also by resolving the GST subunits by reverse-phase high performance liquid chromatographic procedures. Therefore, OPZ induces mainly the mu class isoenzymes in mouse hepatic tissues.

Animals↗
PubMed1992

Characterization of the upp gene encoding uracil phosphoribosyltransferase of Escherichia coli K12.

The upp gene coding for uracil phosphoribosyltransferase was subcloned on a 5-kb EcoRI restriction fragment along with the purMN operon. By a combination of complementation, deletion and minicell analyses, the upp gene was located adjacent to and divergently transcribed from the purMN operon. All three gene products could be identified in minicell extracts. The cloned upp gene shows an elevated expression upon uracil starvation. The nucleotide sequence and transcription start of the gene were determined. The sequence yields an open reading frame of 624 nucleotides encoding a protein of 22.5 kDa which is in agreement with the previously determined subunit Mr of the purified enzyme. A putative 5-phosphoribosyl-alpha-1-diphosphate (PRPP) binding site has been identified which is similar to the PRPP binding site of the yeast uracil phosphoribosyltransferase.

Amino Acid Sequence↗
PubMed1992

Foot currents and ankle SARs induced by dielectric heaters.

Data are presented on ankle-specific SARs and foot currents as a function of strengths of radio-frequency electromagnetic fields encountered by operators of dielectric heaters. The determination of foot currents was based on near-field exposures in which reactive coupling dominates, and which can result in substantial SARs in exposed workers. The operators were located less than one wavelength from--usually within one meter of--the dielectric heaters, which generated fields at frequencies from 6.5 to 65 MHz. At distances normally assumed by workers, maximal strengths of electric fields ranged from 10(4) to 2.4 x 10(6) V2/m2; maximal strengths of magnetic fields ranged from 5.0 x 10(-3) to 33.3 A2/m2. Currents through both feet to ground were measured while operators stood where they normally worked. Maximal currents ranged from 3 to 617 mA, rms. Nearly 27 percent of the dielectric heaters induced foot currents that exceeded the 200-mA limit that has been proposed for a new ANSI C95.1 standard. Twenty percent of the heaters induced foot currents that exceeded 350 mA. SARs in ankles were calculated from foot currents, and they approximated 5 W/kg at 100 mA, 29 W/kg at 250 mA, and 57 W/kg at 350 mA. The maximal SAR in the ankle was approximately 176 W/kg at 617 mA.

Ankle↗
PubMed1992

Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species.

The two pathogenic species of Neisseria, N. meningitidis and N. gonorrhoeae, have evolved resistance to penicillin by alterations in chromosomal genes encoding the high molecular weight penicillin-binding proteins, or PBPs. The PBP 2 gene (penA) has been sequenced from over 20 Neisseria isolates, including susceptible and resistant strains of the two pathogenic species, and five human commensal species. The genes from penicillin-susceptible strains of N. meningitidis and N. gonorrhoeae are very uniform, whereas those from penicillin-resistant strains consist of a mosaic of regions resembling those in susceptible strains of the same species, interspersed with regions resembling those in one, or in some cases, two of the commensal species. The mosaic structure is interpreted as having arisen from the horizontal transfer, by genetic transformation, of blocks of DNA, usually of a few hundred base pairs. The commensal species identified as donors in these interspecies recombinational events (N. flavescens and N. cinerea) are intrinsically more resistant to penicillin than typical isolates of the pathogenic species. Transformation has apparently provided N. meningitidis and N. gonorrhoeae with a mechanism by which they can obtain increased resistance to penicillin by replacing their penA genes (or the relevant parts of them) with the penA genes of related species that fortuitously produce forms of PBP 2 that are less susceptible to inhibition by the antibiotic. The ends of the diverged blocks of DNA in the penA genes of different penicillin-resistant strains are located at the same position more often than would be the case if they represent independent crossovers at random points along the gene. Some of these common crossover points may represent common ancestry, but reasons are given for thinking that some may represent independent events occurring at recombinational hotspots.

Base Sequence↗
PubMed1992

Analyzing the mosaic structure of genes.

Some genes in prokaryotes consist of a mosaic of regions derived from different ancestors by horizontal gene transfer. A method is described for demonstrating the statistical significance of such mosaic structure and for locating the crossover points separating different regions.

Chi-Square Distribution↗
PubMed1992

Effects of dietary fish oil on myocardial ischemic/reperfusion injury of Wistar Kyoto and stroke-prone spontaneously hypertensive rats.

The purpose of the present study was to determine whether 15 weeks of dietary fish oil supplementation to Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SP-SHR) would alter cardiac contractile performance. Isolated perfused working hearts were used to determine the effects of varying left atrial filling pressures on cardiac pump output and pressure development. In addition, the ability of these hearts to recover cardiac output after a 60-minute period of low-flow ischemia followed by 30 minutes of reperfusion was assessed. Myocardial high-energy phosphate levels and long-chain acylcarnitine content were measured. Fish oil supplementation had no effect on indirect tail-cuff systolic blood pressure of WKY rats, but produced a small decrease in systolic blood pressure of SP-SHR. In response to varying left atrial filling pressures, hearts from WKY rats and SP-SHR exhibited no major differences in aortic flow, left intraventricular diastolic pressure, systolic pressure, positive and negative rate of pressure change per unit of time (dP/dt), or relaxation time; however, coronary flow values were lower in SP-SHR groups relative to respective WKY groups. Fish oil supplementation had no effect on these cardiac parameters. When these hearts were subjected to ischemia and reperfusion, the recovery of cardiac contractile performance was significantly improved in fish oil-fed WKY and SP-SHR groups, compared with their corn oil-fed counterparts. There were no differences in the recovery of the above cardiac hemodynamic parameters between corn oil-fed WKY and SP-SHR. These results provide further support to the hypothesis that dietary fish oil can significantly reduce the mortality risk from cardiovascular disease.

Animals↗
PubMed1992

Environmental concern and cooperative-competitive behavior in a simulated commons dilemma.

Commons-dilemma simulation games are designed to examine behavior associated with preservation and destruction of slowly regenerating natural resources. In Experiment 1, 120 introductory psychology students in the United States were assigned to high- or low-environmental-concern conditions based on a median split of their scores from a pretest. They then played either a points game, in which they selected numerical points from a slowly regenerating pool, or a tree game, in which they harvested trees from a jointly managed forest. After the game, subjects were asked to sign a petition for an environmental cause, to participate in a litter pick-up, and to participate in a recycling drive. Neither environmental concern nor proenvironmental behaviors were related to commons dilemma performance. In Experiment 2, 57 other introductory psychology students were assessed on environmental concern and Machiavellian personality, size of other players' harvesting choices, and other players' altruistic choices, all correlated with subjects' outcomes in the game. Overall, cooperation and competition were more important than environmental concern in predicting behavior in the commons dilemma simulation game.

Adult↗
PubMed1992

Effects of dietary fish oil on Rb+ efflux from aorta of stroke prone spontaneously hypertensive rats.

The effect of fish oil on potassium efflux and basal tension in aortas from stroke prone spontaneously hypertensive rats (SHRSP) was evaluated. Four-week-old male Wistar-Kyoto rats (WKY) and SHRSP were divided into two groups: one received a 5% corn oil diet; the other a 5% menhaden oil diet. After 15 weeks, mean systolic blood pressure (mm Hg) was reduced in SHRSP-fish (202 +/- 5) compared to SHRSP-corn (227 +/- 4). Systolic pressure of WKY-fish (146 +/- 3) was not different from WKY-corn (151 +/- 4). Potassium efflux was evaluated with the isotope 86Rb. Basal 86Rb efflux from aorta of SHRSP-corn was evaluated compared to WKY-corn. Diltiazem or sodium nitroprusside decreased 86Rb efflux and basal tension in SHRSP. Basal 86Rb efflux, tension, and the magnitude of this diltiazem- or nitroprusside-induced inhibition were decreased in SHRSP-fish. At maximal diltiazem or nitroprusside concentration, 86Rb efflux from both SHRSP dietary groups was similar but still greater than control aorta. The IC50 values for diltiazem or nitroprusside effects on 86Rb efflux and tension were not altered by diet in SHRSP. Qualitatively similar changes in basal 86Rb efflux and tension were noted in WKY-fish compared to WKY-corn. These experiments demonstrate that dietary fish oil supplementation decreased calcium-sensitive 86Rb efflux and basal tension in vascular smooth muscle and suggest that these changes may contribute to the concomitant antihypertensive effect of dietary fish oil in SHRSP.

Animals↗
PubMed1992

Local activation variability during monomorphic ventricular tachycardia in the dog.

OBJECTIVE: The aim was to determine the beat to beat variability in local activation time during sustained monomorphic ventricular tachycardia in a canine model of experimental myocardial infarction. METHODS: A digital template matching algorithm was developed for detecting subtle beat to beat variability in local activation timing at each of multiple ventricular sites. Ten electrically induced sustained ventricular tachycardia episodes, mean cycle length 211 (SD 40) ms, were endocardially and epicardially mapped in mongrel dogs weighing 15-20 kg. Digitised data were analysed for beat to beat local activation time variability. Similar data recorded during ventricular pacing at comparable rates and during sinus rhythm served as controls. RESULTS: The overall mean variability of local activation time for all 10 ventricular tachycardias was 3.2(1.6) ms, range 1.8(1.1) ms to 4.7(2.8) ms, in contrast to the overall mean variability of 0.2(0.4) ms (p = 0.0001) for ventricular pacing and 0.7(0.6) ms (p = 0.0001) for sinus rhythm. Oscillations in local activation time manifested alternans type periodicity during seven of 10 ventricular tachycardias independent of any alternans in local electrogram morphology. CONCLUSIONS: During sustained, monomorphic ventricular tachycardia, beat to beat variability and alternans type oscillations in local activation time are common and may be an intrinsic property of re-entry since they are negligibly small during ventricular pacing.

Animals↗
PubMed1992

Reduced synthesis of tissue plasminogen activator by vascular endothelium during acute myocardial infarction.

We measured levels of tissue plasminogen activator (t-PA) antigen in 100 patients within six hours of the onset of acute myocardial infarction, in 34 patients with chronic angina but no recent infarction, and in 36 normal subjects. We also assayed von Willebrand factor in the acute patients and in the normal subjects. Measurements were repeated in 40 acute patients at three weeks after myocardial infarction. Although resting levels of t-PA antigen were not significantly different from normal during myocardial infarction, the capacity of the vascular endothelium to release t-PA after five minutes of venous occlusion was impaired (p less than 0.01). The acute phase vessel wall release of von Willebrand factor was increased during acute infarction (p less than 0.01). We conclude that impairment of t-PA production is associated with acute coronary thrombosis, although it is not possible to differentiate between a causative role or a secondary response due to exhaustion of the t-PA producing mechanism.

Adult↗