PubMed Health⌕ Search

Biomedical subjects

B C Williams

Publications and source records attributed to B C Williams.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cyclic GMP-linked pathway for renin secretion.

The role of cGMP as a second messenger for renin secretion is contentious. This was investigated using a superfused collagenase-dispersed rat kidney cortex cell preparation devoid of indirect influences on renin secretion. Nitroprusside, atriopeptin II and 8-Br-cGMP all increased renin release but the dose-response relationships were biphasic. At low dose ranges there was a positive correlation between increasing drug concentration and renin secretion, but at high drug concentrations, a negative correlation was apparent. Methylene blue, a guanylate cyclase inhibitor, also suppressed baseline renin release at 10(-5) and 10(-6) M, but stimulated release at 10(-3) M. Using mid-range drug concentrations, the cGMP specific phosphodiesterase inhibitor MB22948 potentiated renin release in response to nitroprusside and 8-Br-cGMP. Inhibition of guanylate cyclase with either methylene blue or LY83583 attenuated renin release in response to nitroprusside, but, as expected, had no effect on 8-Br-cGMP induced release. We conclude that, under physiological conditions, cGMP is a stimulatory second messenger for renin release. This activity is mimicked at low dose ranges by 8-Br-cGMP, nitroprusside and atriopeptin II. In response to high doses of these drugs an unknown inhibitory pathway is activated and this opposes, in a dose-related manner, the stimulatory actions of cGMP for renin release.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Primary cultures of bovine inner zone adrenocortical cells secrete cortisol in response to adenosine triphosphate, adenosine diphosphate, and uridine triphosphate via a nucleotide receptor which may be coupled to two signal generation systems.

Cultured inner zone cells isolated from bovine adrenal cortex secreted cortisol in a dose-dependent fashion in response to ATP and ADP. The threshold response was at 10(-6) M ATP, reaching a maximum by 10(-4) M ATP, at which concentration the n-fold relative to basal was 43.8 +/- 22.3 (mean +/- SD, n = 3). The response to 10(-4) M ATP remained linear for up to 2 h, and the cells appeared morphologically normal after removal of the stimulus. Stimulation of cortisol secretion by ATP was evident after 24 h in primary culture and reached a maximum after 48-72 h, thereafter declining. No response was detected in freshly isolated cells. The possibility that added ATP was degraded over the course of the incubation was investigated by separating ATP, ADP, AMP, and adenosine by high resolution anion exchange chromatography after different times of exposure to the cells. Although there was degradation--largely to ADP--about 50% of the ATP remained at 1 h. The potency order of a range of purines was as follows: ATP = ADP > 2-methyl-S-ATP > alpha, beta-methylene ATP = beta, alpha-methylene ATP = AMP. Cells were also responsive to the pyrimidine nucleotide uridine 5'-triphosphate, which was equipotent with ATP. The purinergic antagonist suramin was relatively ineffective. Cells grown in the presence of [3H]inositol (10 microCi/ml) for 48 h (to prelabel the membrane phosphoinositide pool to isotopic equilibrium) showed a time- and dose-dependent increase in [3H]inositol-labeled total phosphoinositols in response to ATP or ADP; the response was linear for at least 60 min. Cells labelled with the Ca2+ indicator fura-2 showed an increase in intracellular calcium in response to 10(-4) M ATP on days 3 and 4 of culture. Basal intracellular Ca2+ was found to be 57.3 +/- 39.3 nmol/liter (mean +/- SD, n = 12 cell suspensions) rising to 171 +/- 84 nmol/liter (mean +/- SD, n = 12 cell suspensions) in response to ATP (10(-4) M). In response to ATP, bovine inner zone cells also demonstrated a dose-dependent increase in intracellular cAMP measured after 1 min stimulation. It was not possible to account for the cAMP response on the basis of conversion of ATP to adenosine, which then acted at an A2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1994

Primary cultures of bovine inner zone adrenocortical cells secrete cortisol in response to adenosine 5'-triphosphate, adenosine 5'-diphosphate, and uridine 5'-triphosphate via a nucleotide receptor that may be coupled to two signal generation systems.

Cultured inner zone cells isolated from bovine adrenal cortex secreted cortisol in a dose-dependent fashion in response to ATP and ADP. The threshold response was at 10(-6) M ATP, reaching a maximum by 10(-4) M ATP, at which concentration the n-fold increase relative to basal was 43.8 +/- 22.3 (mean +/- SD; n = 3). Cells were also responsive to the pyrimidine nucleotide UTP. EC50 values for ATP, ADP, and UTP were 5.83 +/- 3.98 x 10(-6), 13.7 +/- 5.67 x 10(-6), and 7.33 +/- 4.52 x 10(-7) M, respectively (mean +/- SD; n = 3). The response to 10(-4) M ATP was linear for at least 60 min, and the cells appeared morphologically normal after removal of the stimulus. The purinergic antagonist suramin was relatively ineffective. The potency order of a range of purines was as follows: ATP = UTP > ADP > 2-methyl-S-ATP > alpha, beta-methylene ATP = beta, alpha-methylene ATP = AMP. Stimulation of cortisol secretion by ATP was evident after 24 h in primary culture and reached a maximum after 48-72 h, thereafter declining. No response was detected in static incubations of freshly isolated cells. The possibility that added ATP was degraded over the course of the incubation was investigated by separating ATP, ADP, AMP, and adenosine by high resolution anion exchange chromatography after different times of exposure to the cells. Although there was degradation, largely to ADP, about 50% of the ATP remained at 1 h. Cells grown in the presence of [3H]inositol (10 microCi/ml) for 48 h (to prelabel the membrane phosphoinositide pool to isotopic equilibrium) showed a time- and dose-dependent increase in [3H]inositol-labeled total phosphoinositols to ATP or ADP; the response was linear for at least 20 min. Cells labeled with the Ca2+ indicator fura-2 showed an increase in intracellular calcium to 10(-4) M ATP on days 3 and 4 of culture. The basal intracellular Ca2+ concentration was 57.3 +/- 39.3 nmol/liter (mean +/- SD; n = 12 cell suspensions), rising to 171 +/- 84 nmol/liter (mean +/- SD; n = 12 cell suspensions) after the addition of ATP (10(-4) M). Bovine inner zone cells also demonstrated a dose-dependent increase in intracellular cAMP measured after 1 min of stimulation with ATP. It was not possible to account for the cAMP response on the basis of conversion of ATP to adenosine, which then acted at an A2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1994

Determinants of Drosophila zw10 protein localization and function.

We have examined several issues concerning how the Drosophila l(1)zw10 gene product functions to ensure proper chromosome segregation. (a) We have found that in zw10 mutant embryos and larval neuroblasts, absence of the zw10 protein has no obvious effect on either the congression of chromosomes to the metaphase plate or the morphology of the metaphase spindle, although many aberrations are observed subsequently in anaphase. This suggests that activity of the zw10 protein becomes essential at anaphase onset, a time at which the zw10 protein is redistributed to the kinetochore region of the chromosomes. (b) The zw10 protein appears to bind to kinetochores in mitotically arrested cells, eventually accumulating to high levels within the chromosome mass. Our results imply that zw10 may act as part of a novel feedback pathway that normally renders sister chromatid separation dependent upon spindle integrity. (c) The localization of zw10 protein is altered by two mitotic mutations, rough deal and abnormal anaphase resolution, that specifically disrupt anaphase. These findings indicate that the zw10 protein functions as part of a multicomponent mechanism ensuring proper chromosome segregation at the beginning of anaphase.

Anaphase↗
PubMed1994

ADL dependent people may also be sick: neglect of the "home health" population in the home care debate.

Fear of large new public outlays have muted debate over recent proposals to expand subsidized supportive (non-medical) home care services for the elderly. Data from the billing portion of the 1984 National Long Term Care Survey demonstrate that of the approximately one million community-dwelling elderly persons whose chronic functional impairments would make them eligible for many proposed home care programs, nearly one third (31%) received services from a home health agency over a 12-month period. Since home health agencies provide substantial amounts of supportive services to enrollees, it is estimated that between three and six million non-medical visits are provided annually to chronically functionally impaired persons through home health agencies. These existent services should be taken into account in predicting the incremental public service burden and costs of proposed supportive home care programs.

Activities of Daily Living↗
PubMed1994

Regulation of 11 beta-hydroxysteroid dehydrogenase activity by the hypothalamic-pituitary-adrenal axis in the rat.

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) inactivates glucocorticoids and thereby modulates their access to both mineralocorticoid and glucocorticoid receptors. Since 11 beta-OHSD activity influences the biological responses of the hypothalamic-pituitary-adrenal axis, it might be regulated by components of this axis. We examined 11 beta-OHSD activity in adrenalectomized rats treated for 9 days with dexamethasone and with or without ACTH. Adrenalectomy and low-dose (2 micrograms/day) dexamethasone had no effect on 11 beta-OHSD activity in renal cortex, hippocampus or heart, and reduced enzyme activity in aorta. High-dose dexamethasone (50 micrograms/day) had no effect in renal cortex but increased enzyme activity by at least 50% in all other sites. This effect of dexamethasone was unaffected by the co-administration of ACTH. We also examined the metabolism of dexamethasone by 11 beta-OHSD in homogenized rat tissues. Only in kidney, in the presence of NAD rather than NADP, was dexamethasone converted to a more polar metabolite previously identified as 11-dehydrodexamethasone. We conclude that: dexamethasone induction of 11 beta-OHSD is tissue-specific, and includes vascular tissues and hippocampus but not kidney; this tissue-specificity may be explained by contrasting metabolism of dexamethasone by the isoforms of 11 beta-OHSD; fluctuations of glucocorticoid levels within the physiological range may not have a biologically significant effect on 11 beta-OHSD activity; and the inhibitory effect of ACTH, observed previously in humans, is likely to depend on the presence of intact adrenal glands.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Activities of daily living and costs in nursing homes.

Functionality, as measured by activities of daily living (ADL), is the most important predictor of the cost of nursing home care. Data from a field-test version of the federally mandated Minimum Data Set (MDS) were examined using analysis of variance (ANOVA) and recursive partitioning methods to determine the relationships between ADL limitations and nursing cost (wage-weighted nursing time) among nursing home residents (n = 6,663). From this analysis, an index based on limitations in four ADLs was created. The developed ADL index is a readily determined measure of functional status useful in allocating nursing staff within nursing homes and in comparing the functional status of groups of residents, explaining 30 percent of variance in nursing costs among nursing home residents.

Activities of Daily Living↗
PubMed1994

Social approaches to lowering infant mortality: lessons from the European experience.

Western European countries achieve more favorable infant mortality than the United States. Most of the excess U.S. mortality occurs in the first week of life, largely associated with very low birthweight. European countries provide extensive social and financial support for pregnant women and families with young children. Prenatal and obstetric care in Europe is more social in orientation and less interventional than in the U.S. Attention to the social and economic needs of women may more effectively reduce U.S. infant mortality than additional medical care.

Europe↗
PubMed1994

Direct and indirect effects of carbenoxolone on responses to glucocorticoids and noradrenaline in rat aorta.

BACKGROUND: In the kidney carbenoxolone impairs inactivation of glucocorticoids and facilitates their access to mineralocorticoid receptors by inhibiting 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). 11 beta-OHSD is also expressed in vascular smooth muscle, and, in humans, carbenoxolone potentiates vasoconstrictor sensitivity to cortisol and noradrenaline. OBJECTIVE: To establish in vitro whether the vascular effects of carbenoxolone are mediated by inhibition of 11 beta-OHSD. METHODS: Noradrenaline-induced vasoconstriction was measured in helical de-endothelialized rat aortic strips following 2-5 h exposure to one or more of: carbenoxolone, corticosterone, a mineralocorticoid-receptor antagonist (spironolactone) and a glucocorticoid- and progesterone-receptor antagonist (RU 38486). RESULTS: Carbenoxolone potentiated noradrenaline-induced vasoconstriction in aortae from adrenalectomized rats, an effect which was prevented by spironolactone but not by RU 38486. By contrast, when corticosterone was added or when aortae from non-adrenalectomized rats were studied, carbenoxolone attenuated noradrenaline-induced vasoconstriction. CONCLUSIONS: Carbenoxolone has a direct effect, independent of 11 beta-OHSD, which potentiates noradrenaline-induced vasoconstriction and might be mediated by activation of mineralocorticoid receptors. Carbenoxolone also has an indirect effect, attenuating noradrenaline-induced vasoconstriction dependent on corticosterone and, therefore, mediated by inhibition of 11 beta-OHSD. Although experiments with carbenoxolone must be interpreted with caution because of its direct effect, the present data confirm that 11 beta-OHSD modulates vascular sensitivity to glucocorticoids and noradrenaline. Therefore, 11 beta-OHSD activity might influence blood pressure by effects in both the kidney and the vasculature.

Adrenalectomy↗
PubMed1993

Modulators of calcium and potassium channels: their effects on endothelin-1 binding to cardiac membranes.

Endothelin-1 (ET-1) causes long-lasting vasoconstriction associated with a prolonged elevation of intracellular free Ca2+. Because this may be mediated through an effect on membrane ion channels, we investigated the effects of the dihydropyridine calcium channel antagonist nifedipine; two structurally distinct K+ channel openers, pinacidil and levcromakalim; and the inactive stereoisomer of levcromakalim (D-cromakalim), as well as ET-1 and ET-3, on binding of 125I-labeled endothelin-1 to rat cardiac membranes. Specific binding of 125I-ET-1 was inhibited in a concentration-dependent manner by unlabeled ET-1 (IC50 = 1.56 +/- 0.78 nM; slope = -0.49 +/- 0.10) and ET-3 (IC50 = 314 +/- 54 nM; slope = -0.34 +/- 0.11). Nifedipine, in concentrations < or = 10(-5) M, did not affect 125I-ET-1 binding. However, levcromakalim significantly inhibited 125I-ET-1 binding (maximum binding 49 4/- 9%; p = 0.04), whereas the inactive isomer, D-cromakalim, had no effect. Pinacidil also inhibited 125I-ET-1 binding, although to a lesser extent than levcromakalim (maximum binding 63 +/- 7%). These findings provide evidence for a stereospecific interaction between K(+)-channel openers and ET-1 binding in rat cardiac membranes. Because the slope of the logistic fit was substantially less than unity, and the effects of pinacidil and levcromakalim were incomplete, there may be two or more receptors for ET-1 in rat heart, only one of which is sensitive to K(+)-channel openers.

Animals↗
PubMed1993

Endothelin-1 and aggregation of human platelets in vitro.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by endothelial cells. We investigated whether ET-1, like other potent endothelium-derived vasoactive agents, interacts directly with human platelets in vitro. Platelet-rich plasma was obtained from healthy male volunteers and incubated with ET-1 (1 microM) or vehicle (sodium chloride 154 mM) for 10 min at 37 degrees C. Platelet aggregation was measured by the Born method, using light transmittance through the plasma sample as an index of activation. Although a significant increase in light transmittance was observed when plasma was incubated with ET-1 compared with vehicle, (3.8 +/- 0.4% versus 2.7 +/- 0.2%; n = 24; p = 0.038), this effect was small and is unlikely to be of biologic significance. To investigate the possibility that ET-1-stimulated platelet nitric oxide (NO) synthesis might be masking a direct aggregatory effect of ET-1, in a second study in six subjects NG-monomethyl-L-arginine (L-NMMA, 10 and 100 microM), an inhibitor of NO synthase, was preincubated with the plasma before the addition of ET-1 (1 nM and 1 microM). No significant difference was observed whether samples were incubated with L-NMMA alone or with L-NMMA and ET-1. The results of this study suggest that ET-1 does not have a major direct effect as a platelet aggregating agent.

Adult↗
PubMed1993

How different are VA nursing home residents?

OBJECTIVE: To identify similarities and differences between VA nursing home residents and other nursing home residents. DESIGN: Comparison of cross-sectional data from three sources. PARTICIPANTS: Residents of VA nursing homes nationwide in early October 1986 (n = 10,117); participants in the 1985 National Nursing Home Survey (NNHS) (n = 5,243); residents assessed in New York State nursing homes in 1988 (n = 94,840). MEASURES: Age-stratified comparisons were made between the VA and the NNHS for gender, marital status, race, ethnicity, length of stay, activities of daily living (ADL) status, and selected diagnoses and conditions. Additionally, case-mix data were compared between the VA and the New York State populations. MAIN RESULTS: The population of VA nursing homes is overwhelmingly men (96.1% versus 28.4% in the NNHS), and 31.2% of the VA population is under 65 years of age compared with 11.6% in the NNHS. Young ( < 65) VA residents are considerably more impaired in ADL than young residents in the NNHS; differences are less pronounced in those over 65 years old. VA case mix is slightly higher than the overall New York State population though the distribution of residents into categories in the Resource Utilization Groups, Version II system is somewhat different. CONCLUSIONS: VA nursing homes contain a substantial distinctive population of seriously impaired residents under 65 years of age. Though differences exist, older VA residents have many similarities to residents of non-VA nursing homes and constitute a functionally impaired population that can provide insights into the status of nursing home residents generally.

Activities of Daily Living↗
PubMed1993

Length of stay in VA nursing homes. Comparative characteristics of brief-, medium-, and long-stay residents.

To examine the patterns and determinants of length of stay among residents of nursing homes of the Department of Veterans Affairs (VA), the authors conducted a retrospective follow-up study of all persons (n = 4,918) admitted to VA nursing homes between October 1986, and April 1987, using computerized records of the VA. Brief-stay (< 1 month; n = 1,139) residents had most often had previous admissions to VA nursing homes and were usually discharged alive from the nursing home. Medium-stay (1-6 months; n = 1,947) residents were the least functionally impaired and most likely to receive rehabilitative services. Long-stay residents (> 6 months; n = 1,832) were older and more functionally impaired than other residents. Medium- and long-stay residents of VA nursing homes most resembled "short-" and "long-stay" residents among non-VA nursing home residents, respectively. Brief-stay residents may be persons admitted for "respite" services or may be serial users of both VA and non-VA health services. Further study of this population may identify opportunities to decrease "revolving-door" use of nursing home services.

Activities of Daily Living↗
PubMed1993

Angiotensin II stimulates growth and steroidogenesis in zona fasciculata/reticularis cells from bovine adrenal cortex via the AT1 receptor subtype.

Primary cultures of bovine adrenocortical zona fasciculata/reticularis (zfr) cells responded to angiotensin II (AII) with a dose-dependent increase in [3H]thymidine incorporation into DNA. The effect was maximal at 100 nmol/liter AII, and was dose dependently inhibited by (sar1, ala8)-AII (saralasin) and DuP753, but not by PD123177. Both AII-stimulated cortisol secretion and phosphoinositidase C activity were also inhibited by saralasin and DuP753, but not by PD123177. Pharmacological analysis of the antagonism of AII-stimulated cortisol secretion by saralasin and DuP753 produced pA2 values of 8.79 and 7.02, respectively. Whereas the pA2 for saralasin agreed closely with previous measurements in other systems, DuP753 was at least one order of magnitude less potent in inhibiting the action of AII in bovine zfr cells compared to previous measurements in rabbit vascular smooth muscle. We conclude that the steroidogenic and mitogenic effects of AII in bovine zfr cells are mediated by the AT1 receptor.

Angiotensin II↗
PubMed1993

Nitric oxide stimulates cyclic GMP in human thyrocytes.

Sodium nitroprusside spontaneously breaks down in solution to produce the vasodilator nitric oxide. In many cell types, this stimulates the cytosolic form of the enzyme guanylate cyclase, resulting in the elevation of cyclic GMP (cGMP). We have investigated the effect of sodium nitroprusside on the generation of cGMP in primary human thyrocytes and the SV40-transfected human thyroid cell line SGHTL-189. A dose-dependent increase in cGMP was obtained and the maximum response was observed with concentrations above 10 microM sodium nitroprusside in both cell types. Methylene blue (50 microM) had no significant effect on basal cGMP production but inhibited the effect of sodium nitroprusside at all concentrations tested, thus demonstrating that the effect was due to nitric oxide. Sodium nitroprusside had no effect on cyclic AMP (cAMP) production in these cells. TSH at 100 and 1000 microU/ml significantly stimulated the production of cAMP, but not that of cGMP, in primary human thyrocytes. Sodium nitroprusside had no significant effect on basal or TSH-stimulated triiodothyronine secretion in primary human thyrocytes. Forskolin (10 microM) significantly stimulated cAMP production in both primary thyrocytes and SGHTL-189 cells. Although forskolin had no significant effect on basal cGMP production, sodium nitroprusside-stimulated cGMP production was significantly reduced by forskolin. However, this inhibitory effect was not related to the production of cAMP.

Cells, Cultured↗
PubMed1992

Studies of hormone-sensitive and -insensitive pools of phosphoinositides in cultured bovine zona fasciculata/reticularis cells. Evidence that acetylcholine and angiotensin II stimulate the breakdown of a common pool of phosphoinositides.

The effects of acetylcholine (ACh) and manganese pre-incubation on angiotensin II (AII)-stimulated incorporation of [3H]inositol into phosphoinositide, phosphoinositol and free inositol fractions of adrenocortical cells isolated from the bovine zona fasciculata/reticularis (zfr) were investigated. In cells pre-labelled for 6 hr with [3H]inositol, ACh and AII stimulated the incorporation of cytosolic [3H]inositol into a common hormone-sensitive pool of phosphoinositides, which was distinct from the non-hormone-sensitive pool labelled in the presence of manganese. Regression analysis of the cortisol versus [3H]inositol headgroup responses for both AII (10(-11)-10(-7) M) and ACh (10(-9)-10(-3) M) showed that the gradients of these responses were not significantly different. These data provide strong evidence that in cultured bovine zfr cells, ACh and AII stimulate the breakdown and resynthesis of a common pool of phosphoinositides.

Acetylcholine↗
PubMed1992

The potassium channel opener BRL 38227 inhibits binding of [125I]-labelled endothelin-1 to rat cardiac membranes.

Binding of [125I]-labelled endothelin-1 (ET-1) to rat cardiac membranes and the effects of endothelin-1 (ET-1), endothelin-3 (ET-3), the calcium channel antagonist nifedipine, and both enantiomers of the potassium channel opener cromakalim (BRL 34915) on binding have been examined. Specific binding of [125I]-ET-1 was inhibited in a concentration dependent manner by both unlabelled ET-1 (10(-12)-10(-7) M) and ET-3 (10(-12)-10(-6) M). Nifedipine (10(-11)-10(-5) M) did not affect [125I]-ET-1 binding. However, BRL 38227 (10(-11)-10(-5) M), the biologically active isomer of cromakalim, significantly inhibited [125I]-ET-1 binding. The inactive isomer, BRL 38226 (10(-11)-10(-5) M) had no effect. These findings provide the first evidence for a stereospecific interaction between BRL 38227 and an ET-1 binding site in rat cardiac membranes.

Animals↗