Search PubMed⌕ Search

Biomedical subjects

D Ellis

Publications and source records attributed to D Ellis.

At least 127 records · Page 7Linked to original sources
PubMed1992

Intracellular pH changes induced by hypoxia and anoxia in isolated sheep heart Purkinje fibres.

The effects were studied of hypoxia on intracellular ion activities in sheep heart Purkinje fibres. The intracellular pH (pHi), surface pH (pHs), intracellular potassium activity (aki), and intracellular sodium activity (aNai) of the cells were recorded using liquid ion exchanger-filled microelectrodes. Various methods of inhibiting oxidative phosphorylation were compared for their effect on pHi. These methods were the use of hypoxia, anoxia or NaCN (2 mM). Hypoxia was produced by degassing solutions under reduced pressure then bubbling with 100% nitrogen gas. Anoxia was produced in a similar manner but with the addition of the reducing agent sodium dithionite (0.5 mM) to remove all traces of oxygen from the solutions. Anoxia caused the most marked changes. Concentration of sodium dithionite between 0.1 and 1 mM produced similar maximum rates of acidification. High concentrations (5 or 20 mM) could produce larger intracellular acidifications apparently unrelated to anoxia. The effects of hypoxia and NaCN were similar. Inhibition of Na(+)-H+ exchange with amiloride (1 mM) had little effect on the pH changes produced by hypoxia. Periods of hypoxia exceeding 1 h still resulted in rapid, readily reversible changes in pHi. Hypoxia caused a rise in aNai, the effect being larger in anoxic conditions. The intracellular K+ activity decreased in hypoxia with further decreases in anoxic conditions. The intracellular ion changes produced during hypoxia are discussed in terms of the production of lactic acid by the cells and changes in the ATP supply to the Na(+)-K+ pump.

Adenosine Triphosphate↗
PubMed1992

Virulence, serotype, and molecular characteristics of environmental strains of Cryptococcus neoformans var. gattii.

Four strains of Cryptococcus neoformans var. gattii originating from Eucalyptus camaldulensis, three from Australia and one from San Francisco, were tested for their serotype, virulence for mice, and a number of genetic and molecular characteristics. All were found to be serotype B and showed significantly higher virulence for mice than did the type strains of C. neoformans var. gattii and Filobasidiella neoformans var. bacillispora, which were obtained from human cryptococcosis cases. Electrophoretic karyotypes of the strains from Australia were identical, although they were collected from sites at least 15 to 500 km apart. The electrophoretic karyotype of the strain from San Francisco was the same as that of the Australian isolates except for the mobility of one chromosome. On the contrary, no two isolates of serotype B (of a total of 11) from clinical sources were the same, regardless of their geographic origin. Furthermore, none of the clinical isolates showed a chromosomal banding pattern identical to that of Eucalyptus-originated strains. The Eucalyptus-originated strains failed to form dikaryons when crossed with the tester strains of the two varieties of F. neoformans. Hybridization analysis with a nucleic acid probe (AccuProbe C. neoformans Culture Confirmation Test; Gen-Probe Inc., San Diego, Calif.), however, showed signals of equal intensity for clinical strains and the Eucalyptus-originated strains. Various fungi phylogenetically related to C. neoformans, including a phenol oxidase-positive strain of Cryptococcus laurentii obtained from E. camaldulensis, were negative in the nucleic acid hybridization test. These observations confirm that, in spite of karyotypic differences and the lack of dikaryon formation with the tester strains of F. neoformans, Eucalyptus-originated C. neoformans var. gattii is the same organism as those isolated from cases of human infection. Furthermore, the C. neoformans culture confirmation test using a commercial nucleic acid probe is specific for C. neoformans.

Animals↗
PubMed1992

Potassium supplementation attenuates experimental hypertensive renal injury.

The long-term roles of dietary sodium and potassium on the renal end-organ damage of hypertension were investigated in Wistar-Kyoto (WKY) and in spontaneously hypertensive (SHR) rats. Eight rats from each strain were maintained since 1 month of age on one of four dietary combinations of either low (0.4%) or high (6.0%) NaCl and low (0.51%) or high (7.6%) KCl providing sodium/potassium molar ratios of 1:1, 1:15, 15:1, and 15:15, respectively. Urinary sodium/potassium excretion ratios confirmed the proportion of salts consumed. Systolic blood pressures (SBP) were similar at 5 months of age and at the completion of the study at 9.5 months; SBP was significantly higher in SHR than in WKY rats and was not attenuated by dietary potassium supplementation of a magnitude that raised plasma potassium concentrations. Albumin excretion rate (AER) was also higher in SHR than in WKY rats (P less than 0.0001). In SHR, AER rose further with high sodium intake (P less than 0.035) but, contrary to SBP, was ameliorated by an equimolar addition of potassium (P less than 0.01). Morphologic lesions were generally absent in WKY rats and were more common in SHR as a group (P less than 0.001). In all four SHR groups, the graded histopathologic injury correlated well with measured AER but a major improvement in hypertensive renal lesions occurred largely in the KCl-supplemented, salt-loaded SHR group. These results show a disassociation between the effects of dietary monovalent cations on the level of SBP and their effect on renal injury. Sodium aggravates renal injury and potassium protects against this renal effect of sodium independent of SBP effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1992

Pittsburgh Epidemiology of Diabetes Complications Study. Measuring diabetic neuropathy follow-up study results.

OBJECTIVE: This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospective study. RESEARCH DESIGN AND METHODS: Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing, nerve conduction studies, and clinical examination. RESULTS: Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam approximately 2 yr later, the sensitivity for vibratory thresholds was high (100%). Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline. CONCLUSION: Despite a cross-sectional relationship between the assessment modalities and clinically overt neuropathy at baseline, these follow-up data suggest that the potential for the objective modalities as predictors of clinically diagnosed neuropathy may be limited.

Adult↗
PubMed1992

In-patient treatment of alcohol problems--predicting and preventing relapse.

Seventy-five alcohol-dependent patients (35 males, 40 females) treated by a Minnesota Model in-patient programme were followed up for 1 year. A variety of outcome measures were included, and patients' GPs were also questioned with regard to various aspects of their involvement in treatment for alcohol problems. Males admitted to the programme had a longer history of drinking, consumed more alcohol and showed greater expenditure on alcohol. At 6 months, 66% of males and 45% of females were abstinent; at 1 year, the proportions abstinent were 53% and 39%, respectively. Good outcome for both sexes was associated with attendance of Alcoholics Anonymous meetings. Poor outcome at 1 year was associated with a lack of GP involvement in aftercare and failure to provide alcohol counselling in the community. Females appeared to be particularly disadvantaged by depressive comorbidity. Males showed poorer outcome if they belonged to social class IIIM or lower, were unemployed, or had a family history of alcoholism. It is suggested that closer attention should be paid to monitoring patients' mood state, with appropriate treatment of depression, and that GPs need on-going support and education for helping patients with alcohol problems.

Adult↗
PubMed1991

The role of EGF in testosterone-induced reproductive tract differentiation.

EGF is known to modulate a variety of cellular functions including differentiation. The aim of this investigation was to determine the role of EGF in androgen-induced masculine differentiation. Accordingly, a series of experiments were designed and the results are summarized as described below. (1) We found that the specific deprivation of EGF using anti-EGF serum during the period of masculine differentiation in an organ culture bioassay system resulted in the disintegration of the Wolffian system in a dose-dependent manner. (2) Exogenous EGF supplemented in the above experiment corrected the anti-EGF effect, suggesting a specific role of EGF. (3) Anti-EGF serum was also found to disrupt the differentiation even in the presence of exogenous testosterone, suggesting an effect independent of testosterone synthesis. (4) EGF was found to have a direct masculinizing effect both in vivo and in vitro; however, it was not able to mimic all masculinizing effects of testosterone. The mesonephric segment of the Wolffian duct was retained by EGF in the female fetal tract under in vitro conditions, and under in vivo conditions EGF was able to increase anogenital distance and to induce epididymis in some female fetal mice. (5) We were able to detect an EGF-like material in the fetal genital tract during differentiation and found that the level of this material increased with advancement of differentiation. Thus, it appears from the above results that EGF plays a role in testosterone-induced reproductive tract differentiation.

Animals↗
PubMed1991

Phospholipase-C and Na-K ATPase activation by cyclosporine and FK506 in LLC-PK1, cells. Possible implications in blood pressure regulation.

Enhanced Na+ and water reabsorption by proximal tubular epithelial cells plays an important role in the development of systemic hypertension associated with cyclosporine immunosuppression. Since such Na+ reabsorption is subserved by sodium-potassium adenosine triphosphatase (Na-K ATPase), the current study compared the acute effects of hydrocortisone (H), cyclosporine, and FK506 on cultured LLC-PK1 cell viability and on Na-K ATPase activity. Phospholipase-C (PL-C) activity was also investigated because of its possible regulatory effect on Na-K ATPase activity. Culture medium containing low (5 nM, 4.1 ng/ml) or high (10 nM) concentrations of FK506 plus cyclosporine at 415 microM (500 ng/ml) resulted in cell death, whereas cyclosporine concentrations of 83 microM plus 5 nM or 10 nM FK506, or isolated use of the two drugs at high dosages, did not affect cell viability. As compared with controls, cyclosporine increased Na-K ATPase activity, particularly with addition of H (P less than 0.01). In contrast, FK506 reduced the specific activity of both PL-cyclosporine and Na-K ATPase (P less than 0.001-0.01); addition of H to FK506 resulted in an even greater fall in both the enzyme activities (P less than 0.001). Na-K ATPase activity increased in cell homogenates briefly incubated with cyclosporine in the ATPase reaction mixture (P less than 0.05) while FK506 reduced such enzyme activity (P less than 0.05), suggesting a direct effect of these agents on pump activity. These data in LLC-PK1 cells pocessing proximal tubular epithelial cell characteristics indicate that the combined use of cyclosporine plus FK506 may be very deleterious to viability in such cells. The opposing effects of cyclosporine and FK506 on PL-cyclosporine and Na-K ATPase activities and the possible potentiating effect of H on such responses are speculated to affect Na+ and water homeostasis in a manner that may explain differences in systemic blood pressure due to these agents.

Anti-Bacterial Agents↗
PubMed1990

Anti-masculinizing action of estradiol and cyproterone acetate: regulation of a protein fraction with phospholipase-A2 stimulatory and masculinizing activities.

Recently we have identified a protein fraction (55-63 K) from male and testosterone-exposed female mouse genital tract, which stimulates phospholipase A2 (PLA2) and induces masculine differentiation in an undifferentiated mouse genital explant, suggesting a role of this protein in the action of testosterone. In the current study we have further investigated the role of this protein by determining whether anti-masculinizing agents, namely, estradiol and cyproterone acetate, have any effect on the production of this protein. The results described here indicate that a protein fraction containing PLA2 stimulatory activity was present in both control male and estradiol- or cyproterone acetate-exposed male fetal genital tract. However the specific activity of the PLA2-stimulatory protein was significantly higher in the control males than in the experimental males. We did not find any major difference in the behavior of this protein fraction in various chromatographic steps except that in CM-sepharose column; the PLA2-stimulatory activity from the male preparation was eluted in two overlapping peaks with 0.3 and 0.25 M NaCl and that from the treated males was eluted only with 0.25 M NaCl. The SDS-gel analysis of this protein fraction revealed a doublet band (55 and 63 K) in control samples and primarily a 63 K band in experimental samples. The protein fraction from all these sources showed a significant difference in their biological activity. The control male preparation induced Wolffian duct whereas the estradiol sample was completely ineffective and the cyproterone acetate sample was partially effective in inducing Wolffian duct. Thus, it appears that the protein fraction has a role in the masculinizing action of testosterone.

Animals↗
PubMed1990

Effect of food and antacid on absorption of orally administered ticlopidine hydrochloride.

Ticlopidine is a potent inhibitor of platelet aggregation. Absorption of ticlopidine after oral dosing is rapid and complete. Ticlopidine is extensively metabolized with a relative minor component of unchanged ticlopidine in plasma. The randomized crossover study described here was undertaken to examine the effect of food and antacid on the oral bioavailability of a single dose of ticlopidine (250 mg) in normal volunteers. After postprandial treatment the rate and extent of absorption of ticlopidine was earlier and greater relative to fasting treatment [tmax = 1.71 +/- 0.33 hr (fed) vs 1.92 +/- 0.56 hr (fasting) and AUC0-infinity = 2.164 +/- 0.813 micrograms X hr/mL (fed) vs 1.808 +/- 1.052 micrograms X hr/mL (fasting)]. The oral bioavailability of ticlopidine was increased by 20% when taken after a meal. In contrast, absorption of ticlopidine administered after antacid treatment was approximately 20% lower than under fasting conditions. Administration of ticlopidine with food is recommended to maximize gastrointestinal tolerance.

Administration, Oral↗
PubMed1990

Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II.

The prevalence of and interrelationships among all four major complications of insulin-dependent diabetes mellitus (IDDM) and their risk factors are being examined in a large epidemiologic study of IDDM subjects diagnosed in childhood. This article focuses on the baseline prevalence of complications in the 657 subjects diagnosed between 1950 and 1980 and currently aged 8-48 yr, with a mean duration of 20 yr. In addition to background retinopathy being virtually universal after 20 yr of diabetes, proliferative retinopathy affects 70% of IDDM subjects after 30 yr duration. As with overt nephropathy, prevalence of proliferative retinopathy is marginally higher in females than in males at short durations; the previously reported male excess is limited to the subjects with IDDM of longer duration (greater than or equal to 25 yr). Somewhat different patterns of microalbuminuria are also seen by sex. Males show a threefold increase in prevalence from 10 to 25 yr duration, whereas females show a more constant prevalence across these durations. A further rise in microalbuminuria is seen in males but not females at greater than or equal to 30 yr duration, giving a combined prevalence of microalbuminuria and overt nephropathy at greater than or equal to 30 yr duration of 84% (males) and 59% (females). Distal symmetrical polyneuropathy shows a constant rise with duration and is only marginally higher in men. Prevalence of cardiovascular (coronary and cerebral) disease shows no sex difference, whereas peripheral vascular disease is particularly common in women after 30 yr duration (greater than 30%) compared with men (11%) when determined by ankle/arm blood pressure ratio less than 0.8 at rest or after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗