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Biomedical subjects

D Ellis

Publications and source records attributed to D Ellis.

At least 145 records · Page 8Linked to original sources

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↗

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↗

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↗

Factors associated with avoidance of severe complications after 25 yr of IDDM. Pittsburgh Epidemiology of Diabetes Complications Study I.

To identify characteristics associated with long-term avoidance of insulin-dependent diabetes mellitus (IDDM) complications, subjects taking part in an epidemiologic natural history study of childhood-onset IDDM, with a duration of disease greater than or equal to 25 yr, were studied. Nineteen percent of 175 subjects had avoided overt nephropathy, definite cardiovascular and peripheral vascular disease, clinical neuropathy, and proliferative retinopathy. Approximately half of the nonrenal complications occurred in the absence of renal disease. Subjects free of these advanced complications were characterized by a longer duration of disease (P less than 0.05), better lipid profile and blood pressure (P less than 0.01), and considerably lower glycosylated hemoglobin levels (P less than 0.001). Health-related behaviors, including recent medical contact, regular glucose monitoring, physical activity in youth, and avoidance of cigarette smoking, did not relate to complication status, although regular (at least weekly) alcohol consumption was more prevalent (P less than 0.05) in those without complications. We conclude that a lower mean glycosylated hemoglobin level is strongly related to the avoidance of all IDDM complications.

Adult↗

Making sense of Chinese walls or how to sort the purchasers from the providers.

One of the odd consequences of the white paper is that until NHS Trusts become the norm, districts have to manage their units but as purchasers must keep their distance. Peter Catchpole, Steven Phoenix, David Ellis and Claire Holloway discuss the various ways in which this might be achieved, and describe the model chosen in Mid Downs HA.

Contract Services↗

Aminoaciduria of phosphate depletion manifests at the renal brush border membrane.

Vitamin-D deficiency is associated with secondary hyperparathyroidism, hypophosphatemia, generalized aminoaciduria, phosphaturia and, late in its course, hypocalcemia. The tubulopathy has been attributed to the elevated levels of circulating parathyroid hormone. To further delineate the mechanisms responsible for aminoaciduria, vitamin-D deficiency and/or phosphate depletion were induced by placing weanling Sprague-Dawley rats on one of the following diets for 5 weeks: (1) control = 0.7% P, 5.5 micrograms % vitamin D; (2) D-P- = 0.1% P, 0 microgram % vitamin D; (3) D+P- = 0.1% P, 5.5 micrograms % vitamin D; (4) D-P+ = 0.3% P, 0 microgram % vitamin D, and (5) D-P++ = 0.7% P, 0 microgram % vitamin D. Short-term P depletion was produced in a group of animals fed D-P++ for 4 weeks, then fed D-P- for another week. To study the effects of acute supplementation with a pharmacological dose of calcitriol on the transport of amino acids by renal brush border membrane vesicles, the latter experimental group received 500 pmol of calcitriol (and is known as the SUPP group), or an equal amount of the vehicle (and is referred to as the ETH group). The uptake of taurine and proline by renal brush border membrane vesicles was blunted by 50 +/- 3 and 40 +/- 5%, respectively, at the peak of the overshoot, in all diets except D-P++. No changes were observed in vesicle size or Vmax.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Obstetric care in rural Missouri: the loss of rural general and family practitioners.

Family and general practitioners have historically provided a substantial portion of obstetric care in rural parts of the United States, including Missouri. The authors surveyed 328 rural general physicians to determine their participation in obstetrics. Their findings show a dramatic loss of physician obstetric services in rural Missouri and suggest that the dilemma is not likely to be easily remedied.

Adult↗

Effects of saponin on contractile force and intracellular ion activities of cardiac tissues.

The effects of the glycoside saponin on ferret ventricular muscle have been investigated. Saponin produced a positive inotropic effect, the extent of which was determined by the bathing calcium concentration. If the bathing calcium concentration is reduced to levels equivalent to those found intracellularly then similar saponin concentrations are able to "skin" the cardiac cells. The effects were further investigated in sheep heart Purkinje fibres. In the presence of normal extracellular calcium concentrations (to prevent skinning), saponin produced increases in sodium activity, decreases in potassium activity but little change in intracellular pH. The decreases of potassium activity were compared to the effects of strophanthidin. The changes in intracellular ion levels were accompanied by the development of a contracture. The effects of saponin could be explained by its interaction with cholesterol in the cell membrane resulting in an increase in membrane permeability to sodium which may be part of a nonspecific increase in membrane permeability.

Animals↗

Cyclic AMP does not alter taurine accumulation by rat renal brush border membrane vesicles.

Secondary hyperparathyroidism has been attributed to be responsible for the generalized aminoaciduria and phosphaturia of vitamin D deficiency. Since PTH acts in the kidney to generate cAMP, we explored the possibility that its synthetic analog, dbcAMP, would alter the renal transport of taurine (an amino acid lost in the urine in vitamin D deficiency) and Pi. Exposure of renal BBMV prepared from normal and vitamin D-calcium-deficient rats to dbcAMP at concentrations ranging between 10(-4) and 10(-7) M did not alter taurine uptake by these vesicles. Higher dbcAMP concentrations blunted uptake, but these concentrations reduced intravesicular volume, thus representing an artifact of osmolarity. Preincubation of BBMV with dbcAMP for times between 0 and 60 min at 0 or 25 degrees C also did not alter taurine accumulation. Hypotonic lysis of BBMV, allowing entry of the cyclic nucleotide, followed by isotonic resealing did not influence taurine uptake. The addition of potassium fluoride (to inhibit phosphodiesterase activity) and ATP (as an energy source) did not alter taurine accumulation at 60 sec. The uptake of Pi, which is influenced by PTH, was decreased by 25% following exposure to dbcAMP on the internal surface of the vesicle. These data indicate that the taurinuria observed in vitamin D deficiency is unlikely to be related to a PTH-induced increase in intracellular cAMP, unlike the changes in Pi transport, which is sensitive to cyclic nucleotides.

Adenosine Triphosphate↗

Mechanisms of hypertension during and after orthotopic liver transplantation in children.

The aim of this study was to assess the hormonal alterations that may mediate the systemic hypertension that develops in patients during the perioperative period of orthotopic liver transplantation. We studied nine pediatric patients without previous hypertension or renal disease during six time points, starting before transplantation and ending at 48 hours after surgery. Hypertension developed in all patients in association with central venous pressures less than 10 mm Hg. Free water clearance was negative in all nine patients. Vasopressin levels increased intraoperatively but fell as hypertension developed. Atrial natriuretic factor levels increased as systemic blood pressure rose. A high level of plasma renin activity was observed in four patients with renal insufficiency. In six patients, postoperative 24-hour urinary norepinephrine excretion was within the normal age-adjusted range. These findings suggest that the combination of cyclosporine, corticosteroids, and, in some patients, an elevated plasma renin activity prevents the kidney from responding to the acute volume and salt overload with an appropriate diuresis and natriuresis, thus leading to systemic hypertension. The treatment of hypertension after liver transplantation may include salt restriction, diuretics, and, in those patients with a low creatinine excretion index, angiotensin coverting enzyme inhibitors.

Adolescent↗

Choice of urine sample predictive of microalbuminuria in patients with insulin-dependent diabetes mellitus.

Twenty-four-hour, four-hour (8 to 12 am), and overnight urine collections were examined for their ability to detect microalbuminuria in 292 patients with insulin-dependent diabetes mellitus (IDDM). Albumin excretion rate (AER) was measured and also estimated from the product of the urinary albumin/creatinine ratio (A/C) and the calculated 24-hour creatinine excretion. The fractional excretion of albumin (FEA) was also determined in aliquots from each urine sample. The correlation coefficients between measured 24-hour AER and estimated AER were 0.940 and 0.956 for four-hour and overnight collections, respectively (significance of each correlation, P less than 0.001). There was no advantage in using the FEA over the A/C ratio in predicting measured AER. Urinary A/C ratios (mg/mg) between 0.03 and 0.31 in the four-hour collections were highly predictive of microalbuminuria and of measured AER in the 24-hour collections: AER24-h (microgram/min/1.73 m2) = 2.74 + 0.870 x A/C4-h (all log10 values). In a subgroup of 175 patients having all three collections validated, 34 (20%) had microalbuminuria defined as AER 20 to 200 micrograms/min/1.73 m2 in at least two of the three samples and 44 (25%) had overt nephropathy (greater than 200 micrograms/min/1.73 m2). The ability of the AER in one urine collection to predict microalbuminuria in at least one of the other two collections was assessed in these 175 patients. Compared with the overnight urine collection, the four-hour collection had greater sensitivity while affording similar specificity and positive predictive value. Based on these data, the A/C ratio from a morning urine sample following initial AM voiding would seem adequate for the detection and monitoring of microalbuminuria in patients with IDDM.

Adult↗

Selective thyromimetics. Cardiac-sparing thyroid hormone analogues containing 3'-arylmethyl substituents.

Introduction of specific arylmethyl groups at the 3'-position of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3), and its known hormonally active derivatives, gives liver-selective, cardiac-sparing thyromimetics, with potential utility as plasma cholesterol lowering agents. Selectivity-conferring 3'-substituents include substituted benzyl, e.g. p-hydroxybenzyl, and heterocyclic methyl, e.g. 2-oxo-1,2-dihydropyrid-5-ylmethyl and 6-oxo-1,6-dihydropyridazin-3-ylmethyl. Correlations between in vivo and in vitro receptor binding affinities show that liver/heart selectivity does not depend on receptor recognition but on penetration or access to receptors in vivo. QSAR studies of the binding data of a series of 20 3'-arylmethyl T3 analogues show that electronegative groups at the para position increase both receptor binding and selectivity in vivo. However, increasing 3'-arylmethyl hydrophobicity increases receptor binding but reduces selectivity. Substitution at ortho and meta positions reduces both binding and selectivity. Replacement of the 3,5-iodo groups by halogen or methyl maintains selectivity, with 3,5-dibromo analogues in particular having increased potency combined with oral bioavailability. Diphenyl thioether derivatives also have improved potency but are less orally active. At the 1-position, the D enantiomer retains selectivity, but removal of the alpha-amino group to give a propionic acid results in loss of selective thyromimetic activity.

Animals↗

In vitro modulation of tubular cyst regression in murine polycystic kidney disease.

Recent studies in a murine model of genetically-determined polycystic kidney disease, the CPK mouse, have suggested that alterations in renal Na-K ATPase activity in concert with tubular epithelial hyperplasia have pathogenic import in proximal tubular cyst formation. In the current study, we therefore studied the relative roles of Na-K ATPase activity, tubular epithelial hyperplasia, and basal lamina alterations during in vitro modulation of proximal tubular cyst regression during serum-free organ culture of newborn CPK kidneys. Under basal in vitro conditions, regression of CPK proximal tubular cysts was demonstrated in association with progressive decreases in Na-K ATPase activity and tubular epithelial hyperplasia. The pattern of proximal tubular cyst regression was modified by: a) Na-K ATPase activity induction with triiodothyronine, which promoted proximal tubular cystogenesis; and b) Na-K ATPase activity inhibition with ouabain, which blocked the effects of T3 on the process of cyst formation. Modulation of proximal tubular cystogenesis by Na-K ATPase induction and inhibition were accomplished without significant changes in proximal tubular epithelial hyperplasia or expression of basal lamina components. We conclude that increased Na pump activity may have a significant role in proximal tubular cyst formation and progressive enlargement in the CPK mouse.

Animals↗

Assessment of AlbuSure and its usefulness in identifying IDDM subjects at increased risk for developing clinical diabetic nephropathy.

This study, which included 154 participants in a 10-yr follow-up study of diabetes complications, was conducted to evaluate AlbuSure (a qualitative test designed to detect urinary albumin concentrations greater than 0.03 g/L) for its ability to discriminate between albumin concentrations above and below the manufacturer's concentration threshold and to identify individuals at increased risk for developing diabetic nephropathy (i.e., those with albumin excretion rate [AER] greater than 0.0288 g/24 h). The reproducibility of AlbuSure results was also evaluated. The results of these evaluations were examined by three different types of urine collections (24 h, overnight, and timed postclinic) and overall. AlbuSure's validity was examined by comparing its results to immunonephelometrically measured concentrations and AER. When compared to albumin concentration, AlbuSure had an overall sensitivity of 81.8%, specificity of 94.8%, and positive predictive value of 90.6%. AlbuSure's sensitivity was lower (71.4%) when compared with AER; however, this was higher than the sensitivity achieved by dipsticks against AER (50.7%). On testing urine samples stored for 3 days at 4 degrees C, AlbuSure results were 100% reproducible after 1 day and had an overall reproducibility of 92% after 3 days. When urine was retested after 3 and 15 mo of storage at -70 degrees C, AlbuSure was greater than or equal to 90% reproducible, with some of the differing results attributable to corresponding changes in albumin concentration. The overnight sample appeared to be the sample of choice for testing with AlbuSure in that it showed excellent reproducibility and the highest sensitivity (compared to both albumin concentration and AER).

Agglutination Tests↗

Male abuse of a married or cohabiting female partner: the application of sociological theory to research findings.

Does women abuse vary with marital status and, if so, why? The primary objectives of this article are to answer these two questions. A review of research findings indicates that men are more likely to beat women they live with than those they have married. The theoretical accounts of Goode and Gelles are used as a starting point for an explanation of this finding. Implicated in this explanation are social factors operating at the level of society (group memberships), a disjunction between patriarchal societal norms and their existential basis in households (employment patterns), relational norms (ambiguity and flexibility), and social and economic costs. These variables influence woman abuse differentials by either increasing the amount of strain/stress or decreasing the likelihood of effective social regulation.

Female↗

Effect of vitamin D deficiency on amino acid excretion in the phosphate-depleted rat.

Vitamin D deficiency is associated with a generalized aminoaciduria which has been shown to be independent of parathyroid hormone (PTH) and urinary cyclic AMP excretion. To further characterize the mechanism underlying the tubulopathy, weanling rats were placed on one of the following diets for 5 weeks: (1) control [0.7% phosphorus (P), 5.5 micrograms % vitamin D]; (2) D-P- (0.1% P, 0 vitamin D); (3) D+P- (0.1% P, 5.5 micrograms % vitamin D); (4) D-P+ (0.3% P, 0 vitamin D); (5) D-P++ (0.7% P, 0 vitamin D). All diets contained 1.2% calcium (Ca). A group of rats raised on D-P++ for 4 weeks were fed D-P- for 7 days after which they received 500 pmol of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; SUPP] or an equal volume of the vehicle (ETH). The above diets resulted in partial vitamin D depletion in that 1,25(OH)2D levels were 50.25-79 pg/ml in the presence of very low 25(OH)D concentrations. Augmentation in the urinary excretion of 6 out of 8 amino acids measured was observed in P depletion irrespective of vitamin D status. For the most part, acute supplementation with 1,25(OH)2D3 did not ameliorate the tubulopathy. Plasma PTH and Ca concentrations remained normal in all diets, except D+P-, where plasma Ca was 15.88 +/- 0.54 mg/dl. P depletion was associated with hypercalciuria, hypophosphatemia, avid reabsorption of P and growth retardation, irrespective of vitamin D status. Using taurine as a representative of the amino affected, there was a strong correlation between urinary taurine on the one hand and dietary P content (r = 0.613), plasma P (r = 0.399) and 1,25(OH)2D levels (r = -0.576) on the other. The present study suggests that the aminoaciduria of vitamin D deficiency is not related to elevated levels of PTH. A similar defect may be produced by P depletion, suggesting the possibility of a common pathway for the effect.

Amino Acids↗

Congenital murine polycystic kidney disease. II. Pathogenesis of tubular cyst formation.

In the current study, the pathogenesis of proximal tubular cyst formation was studied in an animal model of polycystic kidney disease, the CPK mouse. The specific roles of (a) sodium-potassium adenosine triphosphatase (Na-K ATPase) activity, determined by an enzyme-linked kinetic microassay, (b) proximal tubular epithelial hyperplasia, determined by calculation of mitotic indices, and (c) altered proximal tubular basal lamina formation, determined by immunohistological localization of basal lamina glycoproteins, were investigated at progressive developmental stages of CPK proximal tubular cyst formation. Increases in renal Na-K ATPase were present at the earliest fetal stages of proximal tubular cyst formation, and subsequently paralleled the course of proximal tubular cyst progression. Proximal tubular epithelial hyperplasia, although not present at the earliest stages of cyst formation, was a consistent feature of progressive proximal tubular cystic enlargement. Abnormalities in basal lamina glycoprotein expression were not present at any stage of proximal tubular cyst development. We conclude that increased Na-K ATPase and tubular epithelial hyperplasia are significant features of proximal tubular cyst formation in the CPK mouse.

Age Factors↗