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Biomedical subjects

E F Williams

Publications and source records attributed to E F Williams.

At least 19 recordsLinked to original sources
PubMed1998

Plasma 25-hydroxyvitamin D concentrations are inversely associated with blood pressure of Dahl salt-sensitive rats.

Dietary salt is a contributing factor to the development of hypertension in individuals who are salt-sensitive. The vitamin D endocrine system has been reported to modulate vascular structure and function. Since elderly hypertensive females with low plasma renin activity, typical of salt-sensitivity, had significantly lower 25-hydroxyvitamin D concentrations compared with normotensive elderly and young females, we have used Dahl salt-sensitive and salt-resistant rats fed high (80 g/kg diet) and low (3 g/kg diet) salt diets as models to examine the relationship between salt-sensitivity and 25-hydroxyvitamin D, the precursor of the hormonal form of vitamin D, 1,25-dihydroxyvitamin D. Plasma 25-hydroxyvitamin D concentrations of salt-resistant rats were unaffected by a high salt diet, but plasma 25-hydroxyvitamin D concentrations of salt-sensitive rats were significantly reduced within three weeks to lower than 25%. There was a negative association between plasma 25-hydroxyvitamin D concentrations of salt-sensitive rats and the number of days that the rats were fed a high salt diet (r = -0.98, P < 0.02) and a positive association between blood pressure and the number of days that the rats were fed a high salt diet (r = 0.97, P < 0.05). An inverse relationship was found between plasma 25-hydroxyvitamin D concentrations and blood pressure (r = -0.99, P < 0.01). Spontaneously hypertensive rats did not have low plasma 25-hydroxyvitamin D concentrations, suggesting that reduction of plasma 25-hydroxyvitamin D concentration might be specific to salt-induced hypertension.

Animals↗
PubMed1998

Exogenous 25-hydroxycholecalciferol does not attenuate salt-induced hypertension.

We have reported that an inverse relationship exists between blood pressure and plasma concentration of 25-hydroxyvitamin D, the precursor of the hormonal form of vitamin D, for Dahl salt-sensitive rats fed a high salt diet. Plasma 25-hydroxyvitamin D concentrations decreased with time on the diet, as blood pressure increased. Experiments were conducted to determine whether the blood pressure increase of salt-sensitive rats fed a high salt diet could be attenuated by exogenous 25-hydroxycholecalciferol. Dahl salt-sensitive rats were fed a high salt diet and administered exogenous 25-hydroxycholecalciferol via subcutaneously implanted Alzet pumps. Exogenous 25-hydroxycholecalciferol (various doses from 28 to 80 microg/kg body weight-day) had no significant effect on the blood pressure of vitamin D-replete rats fed a high salt diet for 15 days. When exogenous 25-hydroxycholecalciferol (28 and 60 microg/day-kg body weight) was administered to vitamin D-depleted salt-sensitive rats, plasma 25-hydroxyvitamin D concentrations of the rats fed a low salt diet (26 +/- 2 and 59 +/- 6 nM) were proportional to the 25-hydroxycholecalciferol concentration in the pumps. Plasma 25-hydroxyvitamin D concentrations of the rats fed a high salt diet (18 +/- 1 and 23 +/- 3 nM) were not proportional to the 25-hydroxycholecalciferol concentration in the pumps, but were inversely proportional to the blood pressure of the rats. These data indicate no ameliorating effect of exogenous 25-hydroxycholecalciferol on salt-induced hypertension, but accelerated metabolism and/or clearance of 25-hydroxycholecalciferol in salt-induced hypertension.

Animals↗
PubMed1997

Tissue response to suture materials implanted subcutaneously in a rabbit model.

We compared the tissue response to a nonabsorbable monofilamented suture made of expanded polytetrafluoroethylene (ePTFE), which has recently been introduced for use in plastic surgery, with the response to 10 other commercially available absorbable sutures and nonabsorbable monofilamented and multifilamented sutures. The sutures were used to secure a patch of ePTFE implanted in the dorsum of adult New Zealand White rabbits. At 30, 60, and 120 days after implantation, the tissue response to the sutures was assessed with respect to the number of foreign-body giant cells present, the thickness of the fibrous capsule that developed, and the general inflammatory response (n = 4 for each suture for each time period). Analysis of variance revealed that specific suture type was significantly associated with foreign-body giant cell count and fibrous capsule thickness. Tevdek had a significantly higher value for mean number of foreign-body giant cells. Silk and Tevdek had significantly thicker fibrous capsules, and ePTFE suture had a significantly thinner capsule. Absorbable sutures and nonabsorbable multifilamented sutures evoked a more extensive tissue response than monofilamented sutures; the differences between nonabsorbable monofilamented and nonabsorbable multifilamented sutures were significant for capsule thickness. In general, suture made of ePTFE produced a minimal tissue response. It should be a good choice for use in facial plastic surgery, in which excellent functional and aesthetic results are critical.

Animals↗
PubMed1997

Plasticity of cardiovascular nucleoside transporters following chronic dipyridamole treatment.

Dipyridamole (37.5 mg/kg, s.c., b.i.d.), a potent inhibitor of nucleoside transport, was administered to guinea pigs for 14 days in order to investigate the effects of: 1) chronic dipyridamole treatment on [3H]nitrobenzylthioinosine ([3H]NBMPR) binding: 2) chronically released endogenous adenosine on adenosine A1 and A2 receptors. Comparisons of the binding capacities (Bmax) and equilibrium dissociation constants (Kd) in vehicle-treated (VTA) and dipyridamole-treated animals (DTA), revealed a 100 percent increase in Kd of [3H]NBMPR binding in the kidney of DTA but not in heart or brain. There were no changes in adenosine A1 or A2 receptor activities in kidney and brain as measured by [3H]R-phenylisopropyladenosine and [3H]5'-N-ethyl-carboxamidoadenosine binding, respectively. The data suggest that cardiac and central nucleoside transporters may be either less susceptible to chronic dipyridamole administration or have a different adaptive mechanism. Also, endogenous adenosine, which may be chronically released upon dipyridamole treatment, has no effect on adenosine receptors.

Adenosine↗
PubMed1996

Modified Bernard-Burow cheek advancement and cross-lip flap for total lip reconstruction.

Subtotal lip reconstruction can be performed using local flaps such as the cross-lip flap or fan flap. Total lip reconstructive efforts usually are suboptimal in providing an adequate oral sphincter, an acceptable aesthetic result, or both. For total upper, lower, or extensive combined soft-tissue defects that include both lips, traditional methods of reconstruction include the use of regional flaps. More contemporary reconstructive efforts emphasize staged reconstruction with local tissue flaps using "like" tissue in a sequential fashion to achieve a successful outcome. We describe the reconstruction of total upper, lower, or extensive combined defects and report on 7 cases using a 2-staged method of reconstruction based on the modifications of the Bernard-Burow and Abbe flaps. The principle of esthetic units an intact modiolus and oral sphincter are emphasized to ensure excellent aesthetic and functional results.

Aged↗
PubMed1996

Chronic dipyridamole administration downregulates [3H]nitrobenzylthioinosine binding site affinity in guinea pig kidney but not heart and brain.

Specific binding of the nucleoside transporter probe, [3H]nitrobenzylthioinosine, ([3H]NBMPR) was measured in washed guinea pig cardiac, renal and forebrain membranes after 14 days of treatment with dipyridamole (37.5 mg/kg, s.c., b.i.d.) or vehicle. When compared to values in vehicle-treated animals, a 100 percent increase in equilibrium dissociation constant (Kd) was observed in the kidney of dipyridamole-treated animals (0.51 +/- 0.04 to 1.0 +/- 0.06, p < 0.01). The maximal binding capacity (Bmax) was unaltered. No changes were observed in the heart or forebrain. The increase in Kd suggests that chronic dipyridamole treatment decreases the apparent binding affinity of NBMPR for kidney nucleoside transporters. Cardiac and brain nucleoside transporters may be either less susceptible to chronic dipyridamole administration or have a different adaptive mechanism.

Animals↗
PubMed1996

Comparison of nucleoside transport binding sites in rabbit iris-ciliary body and cultured rabbit nonpigmented ciliary epithelial cells.

The iris-ciliary body (ICB) is a site of action for topically applied antiglaucoma drugs. Moreover, adenosine has been implicated as a modulator of aqueous humor dynamics. The present study compares the binding of the nucleoside transporter probe, [3H]nitrobenzylthioinosine ([3H]NBMPR), to homogenates prepared from rabbit ICB and a cultured rabbit nonpigmented ciliary epithelial cell line (NPE) to determine whether NPE can be used as an experimental model to study the nucleoside transporter. Linear transformation of the saturation binding data revealed that [3H]NBMPR binds to a homogeneous population of binding sites with similar binding affinities (Kd = 0.3 +/- 0.1 and 0.6 +/- 0.1 nM in NPE and ICB, respectively). However, the maximal binding capacity in NPE (Bmax = 288 +/- 54 fmol/mg protein) was significantly higher than that in ICB (Bmax = 154 +/- 17 fmol/mg protein). Selected inhibitors of the nucleoside transport system and structural analogs of adenosine inhibited the binding in both homogenate preparations with a similar rank order of potency: NBMPR > DPY > CV-1808 > CHA > R-PIA > S-PIA > 2-CADO > NECA. The results suggest that NPE is a useful model which could be used for characterizing the nucleoside transporter in ICB and for the screening of nucleoside transport inhibitors as potential antiglaucoma drugs.

Adenosine↗
PubMed1996

Effects of MaxEPA on salt-induced hypertension: relationship to [3H]nitrobenzylthioinosine binding sites.

We investigated the effects of dietary MaxEPA (a major source of eicosapentaenoic acid in fish oil) supplementation on blood pressure (BP) responses and heart rate (HR) of Dahl salt-sensitive (SS) rats fed low (0.4% NaCl) and high (8.0% NaCl) sodium diets. During a four week treatment period, BP remained normotensive in rats on low salt diet but was significantly elevated in those on high salt diet, causing 50% mortality. MaxEPA diminished the BP elevation and prevented the high salt-induced mortality. HR was not affected by either salt diet alone but was reduced in the presence of MaxEPA. At the end of the treatment period, the distribution of [3H]nitrobenzylthioinosine ([3H]NBMPR) binding, a putative marker of adenosine transport and metabolism, was estimated in selected rat tissues in order to evaluate the role of the purinergic system in the BP lowering effect of MaxEPA. Maximal [3H]NBMPR binding capacity (Bmax) in the kidney and platelets were 39% and 82% lower, respectively, in rats on high salt diet than in those on low salt diet. MaxEPA significantly blunted the decrease in Bmax in the kidney but not in platelets and increased Bmax in heart (48%) of low salt group. There were no changes in dissociation constants (Kd). The results suggest that MaxEPA can attenuate salt-induced hypertension, reduce salt-induced mortality and protect the integrity of kidney NBMPR binding sites in salt-induced hypertension.

Affinity Labels↗
PubMed1996

Radioreceptor characterization of cardiovascular nucleoside transporters.

The nucleoside transport system (NTS), an integral part of the adenosine inactivation mechanism, is physiologically significant in adenosine-mediated autoregulation of cardiovascular function. Radioreceptor approaches have been employed in the characterization of nucleoside transporters as potential targets in the therapy of cardiovascular diseases. Unanswered questions that are being addressed relate to their pharmacological regulation and their involvement in the pathogenesis of disease states. A brief overview of the characterization of nucleoside transporters in the cardiovascular system is presented and discussed in terms of their relevance to cardiovascular function.

Animals↗
PubMed1994

Nucleoside transport sites in a cultured human retinal cell line established by SV-40 T antigen gene.

Adenosine, an important neuromodulatory compound in the brain and retina, is a potent vasodilator in most vascular beds throughout the body. Its actions are potentiated by inhibitors of nucleoside transport into cells. Knowledge of the existence of specific adenosine uptake systems in mammalian retina and the inhibition of the uptake by nitrobenzylthioinosine (NBMPR), a potent inhibitor of nucleoside transport, raises the possibility that the associated nucleoside transport system may be of pharmacological importance in retinal function. We have characterized the binding of the nucleoside transporter probe, [3H]NBMPR, to a cultured human retinal cell line established by transfection of SV-40 T antigen plasmid-DNA. The binding was specific, saturable and reversible. Scatchard analysis of the saturation data revealed that NBMPR binds to a homogeneous population of high affinity binding sites (KD = 0.65 +/- 0.22 nM; Bmax = 466 +/- 157 fmol/mg protein) characteristically similar to the binding sites in human retinal tissue (KD = 0.32 +/- 0.01 nM; Bmax = 292 +/- 41 fmol/mg protein). Selected compounds inhibited the binding in the cell line and retinal tissue with the same rank order of potency, suggesting that the transporters in the cell line and retinal tissue are similar. The data showed that the cell line is a useful model for the study of nucleoside transporter function in human retina.

Adenosine↗
PubMed1992

Cation regulation of guinea pig cardiac nitrobenzylthioinosine binding sites.

The effects of several ions on [3H]NBMPR specific binding were characterized in guinea pig cardiac membranes. Binding of [3H]NBMPR was enhanced by Mg2+ Ca2+, Na+ and K+ but inhibited by Mn2+, Cu2+ and Zn2+. The effects of Cu2+ and Zn2+ were observed in micromolar concentrations while the effects of the other cations were observed between 1 and 300 mM. The anions tested had no significant effect on the binding. Scatchard analyses of the [3H]NBMPR saturation equilibrium data showed that the enhancement by Na+ and Mg2+ was due to an increase in the number of binding sites number with no change in apparent affinity. The inhibition of the binding by Cu2+ and Zn2+ was due to a decrease in both the apparent affinity and the number of binding sites. The regulation by cations imply that [3H]NBMPR binding sites are physiological receptors that may be involved in postreceptor coupling.

Animals↗
PubMed1991

The effects of adenotonsillectomy on growth in young children.

A history of poor weight gain can often be elicited in young children with chronic upper airway obstruction resulting from adenotonsillar hypertrophy. A series of 41 consecutive children under 3 years of age, who underwent inpatient adenotonsillectomy, were reviewed for changes in weight and height. Thirty-seven patients had adequate long-term follow-up. Of these, many had dramatic improvements in growth after adenotonsillectomy. Indications for surgery in this group were recurrent infection in three patients (7%), unilateral tonsillar mass in one patient (3%), and upper airway obstruction in 37 patients (90%). A clear history of sleep apnea was elicited in 59%. At the time of surgery, 19 of 41 patients (46%) were of the fifth percentile or lower for age-corrected weight. The inpatient hospital stay averaged 3.2 days. The postoperative complication rate was 27%, with postoperative stridor as the most common complication. After surgery, 28 children (75%) showed a change to a higher percentile for weight. Twenty-four (65%) had percentile changes of 15% or more. This change is significant according to results of the Wilcoxon signed-rank test (p less than 0.001). We conclude that a relationship exists between improved growth rate and adenotonsillectomy in our study group. The rapid improvement in growth appears to be most obvious in children with upper airway obstruction resulting from adenotonsillar hypertrophy. Upper airway obstruction (including andenotonsillar hypertrophy) should be suspected as a possible cause in the workup of children with suboptimum growth.

Adenoidectomy↗
PubMed1990

Changes in renal, platelet and cardiac nitrobenzylthioinosine binding in spontaneously hypertensive rats.

In an attempt to investigate the role of nucleoside transporter function in the hypertensive state, we have compared the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR), a nucleoside transporter probe, in membranes prepared from platelet, renal, pulmonary, cardiac and brain tissues of spontaneously hypertensive rats (SHR) to those of age-matched Wistar-Kyoto (WKY) controls. At 4 weeks of age, [( 3H]NBMPR) binding sites (Bmax) increased in the kidney of SHR but decreased in platelets, whereas no changes were found in the heart, lung or brain. At 18 weeks of age, [3H]NBMPR binding sites (Bmax) remained increased in the kidney and decreased in platelets with no changes in the other tissues. The only change in apparent binding affinity (KD) was an increase in the heart of SHR at 4 weeks. Age-dependent decreases were also observed in the heart and platelets of both SHR and WKY at 18 weeks. The results indicate that the changes in binding characteristics may be due to a combination of the pharmacodynamic differences between the strains, age, as well as to the pathogenesis of hypertension. Consequently, it cannot be concluded that the altered binding characteristics are the result of the elevated blood pressure.

Affinity Labels↗
PubMed1985

Affinity of calcium channel inhibitors, benzodiazepines, and other vasoactive compounds for the nucleoside transport system.

There is evidence to suggest that several different groups of drugs including the so-called coronary vasodilators, benzodiazepines, and calcium channel inhibitors may owe their vasoactivity, in part, to the potentiation of the vasorelaxant effects of endogenous adenosine. To measure the affinity of some of these agents for the membrane-located nucleoside transport system, competition binding assays have been performed using the high-affinity radioligand [3H]nitrobenzylthioinosine (NBMPR). Experiments were performed on human erythrocytes and cardiac membranes from guinea pigs and rats. Recognized nucleoside transport inhibitors had high affinity (less than 50 nM) for NBMPR recognition sites associated with the nucleoside transporter complex in human erythrocytes, whereas calcium channel inhibitors and benzodiazepines had predominantly low affinity (greater than 1 microM). Although some recognized transport inhibitors, such as dipyridamole, show marked differences in affinity for NBMPR sites in guinea pig and rat tissues, benzodiazepines and calcium channel blockers displayed no such species selectivity and had low affinity (greater than 1 microM) for NBMPR sites in both guinea pig and rat cardiac membranes. Consequently, it is unlikely that agents such as benzodiazepines and calcium channel inhibitors cause significant inhibition of adenosine transport, and hence potentiate adenosine actions, at the concentrations required to induce effects through occupation of their respective, specific high-affinity sites.

Animals↗
PubMed1984

Nucleoside transport in heart: species differences in nitrobenzylthioinosine binding, adenosine accumulation, and drug-induced potentiation of adenosine action.

The site-specific binding of the potent and selective nucleoside transport inhibitor, [3H]nitrobenzylthioinosine (NBMPR), to the nucleoside transport system of cardiac membranes of several species was investigated. The affinity of [3H]NBMPR for these sites ranged from 0.03 nM in rat to 0.78 nM in dog. The maximal binding capacity of cardiac membranes for [3H]NBMPR was also species dependent and was greatest in bovine and guinea pig heart (2551 and 1700 fmol/mg protein, respectively) and least in rat (195 fmol/mg protein). The affinities of recognized nucleoside transport inhibitors and benzodiazepines for these transport inhibitory sites in guinea pig and rat heart were estimated by studying the inhibition of the site-specific binding of [3H]NBMPR in competition experiments. These values were compared with their inhibitory effects on the transporter-dependent accumulation of [3H]adenosine in guinea pig and rat cardiac muscle segments and with their ability to potentiate the negative inotropic action of adenosine in electrically driven guinea pig and rat left atria. In guinea pig heart, the recognized nucleoside transport inhibitors and benzodiazepines had an order of affinity (dilazep greater than hydroxynitrobenzylthioguanosine greater than dipyridamole greater than hexobendine much greater than lidoflazine much greater than flunitrazepam greater than diazepam greater than lorazepam greater than flurazepam) for the NBMPR site which was similar to those for the inhibition of [3H]adenosine accumulation and for potentiation of adenosine action. In contrast, in rat heart, where the maximal binding capacity of [3H]NBMPR was lower (eightfold), the nucleoside transporter dependent accumulation of [3H]adenosine was also lower (sixfold) and the negative inotropic action of adenosine was not significantly potentiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1983

Saturable, high affinity binding of the nucleoside transport inhibitor, nitrobenzylthioinosine, to guinea pig cardiac membranes.

The site-specific binding of the potent nucleoside transport inhibitor, [3H]nitrobenzylthioinosine ([3H]NBMPR), to guinea pig cardiac membranes was rapid, reversible and saturable. [3H]NBMPR bound with high affinity to a single class of sites at which the KD was 0.23 +/- 0.07 nM and which had a Bmax of 1700 +/- 290 fmol/mg protein. Several recognized nucleoside transport inhibitors and benzodiazepines inhibited the binding of [3H]NBMPR with an order of potency similar to that observed for the inhibition of the binding of [3H]NBMPR to human erythrocytes and guinea pig synaptosomes.

Animals↗
PubMed1982

An in vitro binding assay which differentiates benzodiazepine 'agonists' and 'antagonists'.

An in vitro test which discriminates benzodiazepine "agonists' and 'antagonists' has been developed by exploiting the apparent differences in modulation of the benzodiazepine receptor by these classes of compounds. In the presence of 10 microM GABA, the potency of benzodiazepine 'agonists' (i.e., compounds which bind to the benzodiazepine receptor with a relatively high affinity and share pharmacologic properties with benzodiazepines) to displace [3H]3-carboethoxy-beta-carboline is significantly increased. In contrast, the potency of benzodiazepine 'antagonists' (compounds which have been demonstrated to antagonize some of the pharmacologic actions of benzodiazepines) is not altered by GABA. Several chemically diverse classes of compound have been examined in this test, and within the limited number of compounds examined, this test accurately predicts 'agonist' and 'antagonist' actions in vivo.

Animals↗