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Biomedical subjects

D Stone

Publications and source records attributed to D Stone.

At least 37 records · Page 2Linked to original sources
PubMed1989

Switching of Candida albicans during successive episodes of recurrent vaginitis.

Strain relatedness and switching were monitored in Candida albicans strains isolated from different body locations through three episodes of recurrent vulvovaginal candidiasis separated by two treatment-latency periods in a single patient. Strain relatedness was assessed by comparing Southern blot hybridization patterns with the relatively immobile mid-repeat sequence Ca3. The following conclusions are demonstrated. (i) Three different strains of C. albicans colonized the mouth, the area under the breasts, and the vulvovaginal, anal, and rectal regions, respectively, at the time of the first infection. (ii) The same strain of C. albicans was responsible for the three vaginal infections. (iii) Switching of colony phenotype occurred with each new vaginal infection. (iv) Enrichment of drug-resistant switch phenotypes (assessed in vitro) was unlikely the basis for the changes in the switch phenotypes of the strain found in the vulvovaginal, anal, and rectal areas after treatment of the first infection with clotrimazole. (v) The same strain of C. albicans was responsible for the recurrent increases in mouth colonization and was distinct from the recurrent vaginal strain. The results of this case study demonstrate the need for further detailed analyses of full-body mycofloras, strain relatedness, switching repertoires, and changes in drug susceptibility during successive episodes of recurrent vulvovaginal candidiasis.

Antifungal Agents↗
PubMed1989

The glutathione status of perfused rat hearts subjected to hypoxia and reoxygenation: the oxygen paradox.

Langendorff perfused rat hearts were subjected to 30 min hypoxia followed by 20 min reoxygenation and the levels of the oxidised and reduced forms of glutathione measured. No change in the concentration of oxidised glutathione was detected in reoxygenated hearts when compared to normoxic controls. In contrast hearts exposed to oxidative stress in the form of H2O2 showed elevated levels of both oxidised glutathione (GSSG) and the glutathione-protein mixed disulphide. These results suggest that if oxidants do contribute to cell damage on reoxygenation of the hypoxic myocardium then their action is local and not through overwhelming of the cells antioxidant defences.

Animals↗
PubMed1989

Oxygen and reperfusion damage: an overview.

The ischaemic myocardium shows a number of distinct oxygen dependent responses to reperfusion. In the case of myocardial stunning and reperfusion arrhythmias there appears to be a beneficial effect of scavenging radicals in the extracellular space. This result is supported by the finding that free radicals can be detected extracellularly after reperfusion. The source of these oxidants and site of action is as yet unclear. In contrast hypoxic myocytes shown an oxygen dependent Ca2+ uptake on reoxygenation which is not affected by externally applied antioxidants. This Ca2+ uptake may in turn lead to the cell lysis characteristic of the oxygen paradox in the perfused heart. As yet there is no compelling evidence to suggest that this aspect of reperfusion damage is due to oxidative stress. It appears more likely that mitochondrial electron transport and ion movement play a central role. In the open chested dog model of ischaemia reperfusion, in which the volume of infarcted tissue is measured, considerable evidence suggests that oxidants derived from activated neutrophils contribute to cell death. This is not however the sole mechanism for cell damage in this model since an inhibitor of mitochondrial Ca2+ uptake, ruthenium red, can improve recovery after reperfusion. We conclude that a number of mechanisms may contribute to the observed oxygen dependent dysfunctions which occur on reperfusion of ischaemic tissue.

Animals↗
PubMed1988

A comparative study of the cardiovascular and biochemical actions of the imidazo [4,5b] pyridine sulmazole and an imidazo [4,5c] pyridine analogue, BW A746C.

1. BW A746C is a chemical analogue of the imidazo [4,5b] pyridine, sulmazole (AR-L115 BS). Like sulmazole, BW A746C possesses positive inotropic and vasodilator activity in vivo. 2. In anaesthetized guinea-pigs, dogs and primates, a bolus i.v. injection of BW A746C, (0.001-1.0 mg kg-1) caused a significant, dose-related increase in ventricular dP/dt, and reduction in diastolic blood pressure, with small increases in heart rate. In these species, a significantly higher dose of BW A746C was required to lower blood pressure by 30% from basal, than was needed to raise ventricular dP/dt by 50% over basal. 3. In anaesthetized guinea-pigs and dogs, bolus i.v. injections of sulmazole (0.1-10.0 mg kg-1) caused similar effects to those observed with BW A746C. In these species, however, there was no significant difference between the dose of sulmazole required to lower blood pressure by 30% from basal and that required to raise ventricular dP/dt by 50%. 4. In conscious dogs, i.v. infusion of BW A746C (to a total dose of 0.3 mg kg-1) caused a significant increase in ventricular dP/dt, but no significant change in either diastolic blood pressure or heart rate. 5. In cell-free biochemical assays, there were no clear differences between the observed activities of BW A746C and sulmazole. Both compounds are cyclic nucleotide phosphodiesterase inhibitors with similar potencies and selectivities for the Type III enzyme (IC50 BW A746C = 3.0 +/- 0.5 X 10(-5) M, sulmazole 5.0 +/- 1.9 X 10(-5) M). The compounds had little or no effects on sarcolemmal Na+/K+-ATPase, Ca2+ ATPase or Na+/Ca2+ exchange, and sulmazole, but not BW A746C, had a small, stimulatory effect on myofibrillar ATPase. 6. In anaesthetized guinea-pigs and dogs, BW A746C was significantly more potent as a positive inotrope than sulmazole. In contrast with sulmazole, BW A746C produced its inotropic effects at significantly lower doses than those required to reduce diastolic blood pressure. This was also apparent from the results obtained in the anaesthetised primates and the conscious dogs. It was therefore concluded that the inotropic/vasodilator profile of BW A746C favours its positive inotrope activity. This profile cannot be explained on the basis of any biochemical differences from sulmazole.

Animals↗
PubMed1988

Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria.

Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells.

Achlorhydria↗
PubMed1987

Epidemiology of intraocular pressure in a population screened for glaucoma.

This study evaluated the association between intraocular pressure and various sociodemographic characteristics, ocular findings, and cardiovascular risk factors in a population screened for glaucoma. A total of 2594 subjects older than 40 years residing in three urban areas of southern Israel participated. Of those screened 6.1% had a raised intraocular pressure (IOP greater than or equal to 21). The mean IOP increased with age, was higher among persons born in Africa or Asia than those born in Europe or America, higher among myopes than hypermetropes and among those with an enlarged cup-disc ratio (CDR). Analysis of variance tests indicated that refractive status, CDR, age, country of birth, and diabetes were each independently associated with IOP. In addition, associations between raised intraocular pressure and age, country of birth, myopia, CDR, diabetes, and glaucoma in the family were found.

Adult↗
PubMed1986

The impact of prenatal care on the outcome of pregnancy.

In a 12-months' prospective project all women delivering at the Soroka Medical Center, Beer-Sheba, Israel, were studied with regard to the type of prenatal care (P.C.) and the outcome of pregnancy. The Soroka Medical Center is the sole medical facility providing obstetric and neonatal services to the 300,000 inhabitants of the region. Prenatal care is delivered by a uniform network of 70 community-based stations. The availability, type and quality of services were uniform for all women and were not altered throughout the study period. The project encompassed 7308 deliveries. 2154 Bedouin women were excluded in order to avoid possible bias due to cultural and genetic characteristics. Data regarding 5154 Jewish women were analysed. Perinatal mortality was inversely proportional to the number of prenatal contacts. The uncorrected mortality rates were 12.7% in women entirely lacking P.C. and 6.2%, 1.9% and 1.0% in patients who had 1-6, 7-10 and 11 or more prenatal contacts respectively. The low-birthweight rate was significantly increased in women lacking prenatal care (22.8%) or having rudimentary care (17.4%) as compared to those who had 11 or more prenatal contacts with medical personnel (5.9%). Prenatal care reduced neonatal morbidity as expressed by the length of hospitalization, the frequency of infants with multiple diagnoses and the incidence of specific pathologies such as respiratory distress syndrome, light for dates and asphyxia. The incidence of some complications of pregnancy (abruptio placentae, premature labor, PROM) was significantly increased in women lacking P.C. or having inadequate P.C. (1-6 prenatal contacts). Moreover, lack of prenatal care was clearly connected with high-risk delivery, thus increasing the danger to the baby. It is suggested that many adverse effects of various socio-economic, genetic and general health factors may be diminished by proper prenatal care coupled with adequate obstetric and neonatal services.

Adult↗
PubMed1979

Porcine liver dihydrofolate reductase. Purification, properties, and amino acid sequence.

Porcine liver dihydrofolate reductase has been purified 18,000-fold to homogeneity. The properties of the purified enzyme were compared to those of dihydrofolate reductase from L1210 cells, the only mammalian reductase for which complete amino acid sequence data are available. The enzymes are very similar when compared on the basis of mechanism and kinetic constants, molecular weights, isoelectric points, and stimulation by salt. A comparison of the amino acid sequences of both enzymes shows an overall identity of 89%. Thus, the similarities seen in inhibitor-binding profiles of mammalian enzymes reflect the close relationship of these enzymes at the molecular level.

Amino Acid Sequence↗
PubMed1979

The amino acid sequence of the trimethoprim-resistant dihydrofolate reductase specified in Escherichia coli by R-plasmid R67.

The amino acid sequence of a trimethoprim-resistant dihydrofolate reductase (EC 1.5.1.3) specified by the R-plasmid R67 is described. The sequence was deduced from automatic and manual sequence analysis of the intact protein, the fragments produced by cyanogen bromide cleavage, and peptides derived from the largest cyanogen bromide fragment by digestion with trypsin, Staphylococcus aureus V8 proteus, chymotrypsin, and Lysobacter enzymogenes alpha-lytic protease. The complete sequence comprises 78 residues in a single polypeptide chain of molecular weight 8444. No evidence of heterogeneity was obtained, indicating that all subunits of the native enzyme are identical. Comparison of the sequence with that of all known dihydrofolate reductases shows no significant sequence homology.

Amino Acid Sequence↗
PubMed1979

R plasmid dihydrofolate reductase with subunit structure.

Dihydrofolate reductase, specified by the type II plasmid of a trimethoprim-resistant Escherichia coli, was purified 40-fold to homogeneity using a combination of gel filtration, DEAE-Sephacel chromatography, and hydrophobic chromatography. The final product shows a single protein band on polyacrylamide gel electrophoresis and has a specific activity of 1.0 unit/mg. The molecular weight of the purified enzyme is 36,000 as determined both by gel filtration and Ferguson analysis of polyacrylamide gel electrophoresis. In contrast, a single polypeptide with a molecular weight of 8,500 was observed on sodium dodecyl sulfate-gel electrophoresis. These experiments suggest that, unlike any bacteria or vertebrate dihydrofolate reductase previously examined, the type II R plasmid reductase is a tetramer composed of four identical subunits. A partial amino acid sequence determination shows no heterogeneity of the subunits and also no clear homology with any reductase sequence previously reported.

Amino Acid Sequence↗
PubMed1979

The amino acid sequence of dihydrofolate reductase from the mouse lymphoma L1210.

The determination of the amino acid sequence of the dihydrofolate reductase (EC 1.5.1.3) from cells of the mouse lymphoma L1210 is described. The protein was cleaved by cyanogen bromide to produce the six fragments CB1 (residues 1 to 14), CB2 (residues 15 to 52), CB3 (residues 53 to 111), CB4 (residues 115 to 125), CB5 (residues 126 to 139), and CB6 (residues 140 to 186). One of the fragments, CB2, contained an internal homoserine derived from a methionine which was not cleaved by cyanogen bromide. The amino acid sequences and order of the cyanogen bromide fragments were determined by a combination of automatic and manual sequence analyses of the fragments and small peptides from tryptic, thermolytic, and Staphylococcus aureus protease digestions. The complete sequence comprises 186 residues in a single polypeptide chain of molecular weight 21,458. Comparison of the sequence of the L1210 dihydrofolate reductase with the sequences of the enzymes from Streptococcus faecium, escherichia coli RT500, and Lactobacillus casei indicates that all enzymes show some homology, which is strongest in the regions forming the substrate binding cleft.

Amino Acid Sequence↗
PubMed1978

The amino acid sequence of rabbit skeletal alpha-tropomyosin. The NH2-terminal half and complete sequence.

The amino acid sequence of the large cyanogen bromide fragment (residues 11 to 127) derived from the NH2-terminal half of alpha-tropomyosin has been determined. This was achieved by automatic sequence analysis of the whole fragment as well as manual sequencing of fragments derived from tryptic digestion of the maleylated fragment and thermolytic, Myxobacter 495 alpha-lytic and Staphylococcus aureus protease digestion of the unmodified fragment. Methionine-containing overlap peptides have been isolated from tryptic digests of the maleylated protein as well as from S. aureus protease digests of the unmodified protein. Coupled with previously published information on the small cyanogen bromide fragments and methionine sequences of tropomyosin, these analyses have permitted the completion of the primary structure of the protein. The complete sequence differs by only 1 residue (Gln-24 instead of Glu-24) from that previously reported. Analysis of the sequence by several authors has permitted rational explanations for the stabilization of its coiled-coil structure, for the existence of its two chains in a nonstaggered arrangement, for a head-to-tail overlap of molecular ends of 8 to 9 residues, for the existence of 14 actin-binding sites on each tropomyosin molecule, and a suggestion for the site of binding of troponin-T.

Amino Acid Sequence↗
PubMed1978

Suicide potential and behavior in children ages 4 to 12.

From a population of 662 children 12 years of age and under, seen at the UCLA Neuropsychiatric Institute, during the years 1970 to 1974, 34 severely depressed children were identified who were also self-abusive and/or suicidal. Case study revealed fragmented, pathological homes, where the children's affect disorders and behaviors were symptomatic of acute family breakdown, marital disharmony, and observed and experienced violence, both verbal and physical. Follow-up on all available children, at least three years posttreatment, revealed that no child had committed suicide. Treatment evaluation by the parents was highly positive, with the great majority of children showing fair to good recovery and adjustment.

Behavior Therapy↗