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B C Williams

Publications and source records attributed to B C Williams.

At least 145 records · Page 8Linked to original sources
PubMed1985

The adrenal secretion of progesterone stimulates testicular steroidogenesis in the rat in vitro.

We have used a multicolumn isolated cell superfusion system to investigate the interaction between isolated rat adrenal and testicular cells in the secretion of sex steroids. The steroid responses of a mixed population of adrenal and testicular cells to the administration of ACTH 100 pg/ml was compared with the responses of the separate cell types. Steroid responses from 5 separate experiments were analysed. We have demonstrated increased secretion of 17 alpha-hydroxyprogesterone (P less than 0.0005), androstenedione (P less than 0.05) and testosterone (P less than 0.0005) by a mixture of cells when compared with the responses of either cell type alone. In contrast, the secretion of progesterone (P less than 0.0005) and corticosterone (P less than 0.005) was reduced in the mixed cell population, suggesting that progesterone is preferentially converted by testicular cells to 17 alpha-hydroxyprogesterone, androstenedione and testosterone. This is confirmed by increased secretion of 17 alpha-hydroxyprogesterone, androstenedione and testosterone but not corticosterone by a mixed population following the administration of progesterone 10 ng/ml. These results suggest that the adrenal secretion of progesterone can stimulate testicular steroidogenesis in the male rat in vitro.

Adrenal Glands↗
PubMed1985

Functional characterization of luteinizing hormone responsiveness and desensitization in perifused interstitial cells.

The characteristics of the steroidogenic response of isolated rat testis interstitial cells to repeated 10 min pulses of ovine LH at 2 h intervals were examined in a Bio-gel perifusion system. Maximal responsiveness of the perifused interstitial cells could be maintained for 6-8 h. Thereafter, both basal and LH-stimulated testosterone production declined gradually despite supplementation of the perifusion medium with 1% and 5% foetal calf serum or 0.5 microgram/ml insulin. In contrast to the time-related steroidogenic decline, a dose-dependent refractoriness of the interstitial cells could be induced by repeated exposure to LH pulses from 0.01 to 10 ng/ml during the first 6 h of perifusion. The higher the stimulating dose of LH, the greater was the rate and magnitude of the resultant desensitization. With lower doses (0.01 and 0.1 ng/ml) of LH, an initial sensitization or priming effect was also observed. These changes in steroidogenic response occurred in the absence of any significant alterations in LH/hCG receptor binding of the perifused interstitial cells, nor could the refractory state be overcome by stimulation with analogues of cAMP. The perifused interstitial cells, when desensitized with low doses of LH (0.1 ng/ml), were capable of increasing or maintaining testosterone production in response to further stimulation with higher doses of LH (1 and 10 ng/ml). The mechanism(s) underlying the in vitro desensitization of perifused interstitial cells by LH may best be explained on the basis of the interaction between the negative effects of substrate depletion and the positive influence of mobilization of substrate(s) into the metabolically active pool for cholesterol side-chain cleavage. It was concluded that the dose of LH used in the pulsatile stimulation of perifused interstitial cells is critically important not only in determining the total amount of testosterone produced, but also in the pattern of response in terms of the degree of sensitization and desensitization induced.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

The role of lumbar puncture in the evaluation of dementia: the Durham Veterans Administration/Duke University Study.

The use of lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis in the routine, initial evaluation of patients with dementia continues to be questioned. This is especially true in the investigation of infectious causes of dementia. To explore this question further, the authors performed a retrospective analysis of 672 hospitalized patients specifically evaluated for dementia. LP and CSF analysis were performed on 402 patients (60 per cent); routine bacteriologic, acid-fast, and fungal cultures were also obtained for 333 of these patients. Most patients were white (64 per cent) and male (63 per cent), their mean age being 66 +/- 11 years. Four patients were diagnosed as having meningitis--two with Cryptococcus neoformans, one with apparent Mycobacterium tuberculosis, and one with coagulase-positive Staphylococcus aureus. These patients were characterized by a subacute change in mental status, fever or meningismus, and CSF pleocytosis with abnormal CSF chemistries. None of the patients were found to have newly diagnosed neurosyphilis. The authors conclude that LP and CSF analysis should not be part of the routine evaluation of patients with dementia and should be performed only in the presence of such indications as a subacute duration of dementia, fever, and signs of meningeal irritation.

Aged↗
PubMed1985

Plasma free captopril concentrations during short and long term treatment with oral captopril for heart failure.

Plasma free captopril concentrations and haemodynamic response to captopril were studied in 20 patients with severe chronic heart failure. A 25 mg oral dose of captopril produced a 36% reduction in systemic vascular resistance, with individual responses varying from 13% to 64%. Mean systemic pressure fell by 20% and cardiac output rose 28%. The absorption of captopril was rapid. Peak plasma free captopril concentration occurred at 45 minutes after the dose and was followed by a smaller second peak. Peak plasma free captopril concentrations varied more than 20-fold but did not correlate with the maximal reduction in systemic vascular resistance. Elimination half life was seven hours. Fourteen patients were restudied after 1-2 months of captopril treatment and 12 showed symptomatic benefit. There was a sustained improvement in haemodynamic state and in non-invasive indices of myocardial function. During long term treatment the predose plasma free captopril concentration correlated well with dosage, but steady state captopril concentrations did not show a significant relation with haemodynamic response. On a dosage regimen of 25-50 mg three times daily the morning predose plasma free captopril concentration and plasma renin activity were relatively low and suggested that maximal inhibition of the renin-angiotensin system was not maintained throughout the dosage interval.

Aged↗
PubMed1985

The effect of sodium intake on the renin response to dopamine in superfused rat renal cortical cells.

In addition to its natriuretic effect in the kidney, dopamine can also stimulate renin release. This study employs an in vitro system to examine the relationship between sodium intake and dopamine-induced renin release. Enzymically dispersed renal cortical cells obtained from rats on low, normal and high sodium diets were superfused at 37 degrees C with Krebs buffer [0.2% glucose, 0.2% bovine serum albumin (BSA)]. Dopamine was given as 10-min infusions and renin activity was measured in the superfusate as angiotensin I generated following incubation of samples with excess nephrectomized sheep renin substrate. Rats on a low sodium diet showed a higher basal cellular renin release and an enhanced renin response to dopamine (10(-7), 10(-6) mol/l) compared with the normal sodium diet group. Rats on a high sodium diet, in contrast, showed a lower cellular renin release and a decreased sensitivity to dopamine (10(-7), 10(-6) mol/l) compared with the normal sodium diet group. These results demonstrate that the renin response to dopamine is dependent upon sodium intake.

Angiotensin I↗
PubMed1985

Inhibition of the renin-angiotensin-aldosterone axis by low dose intravenous captopril as a treatment for accelerated phase hypertension.

A parenteral preparation of captopril has been used to produce a smooth reduction of blood pressure in patients presenting with accelerated phase hypertension. In five out of six patients studied, an intravenous infusion of captopril at dose rates ranging from 250-2000 micrograms/h lowered blood pressure from 199 +/- 13/115 +/- 5 to 143 +/- 14/86 +/- 5 mmHg over several hours without adverse effects. Partial inhibition of the angiotensin converting enzyme was demonstrated by a rise in plasma renin activity (PRA) and a fall (although not to normal) in elevated levels of angiotensin II and aldosterone. The plasma level of free captopril at the point of blood pressure control was 15 +/- 4 ng/ml and its short effective half-life was demonstrated by a rise in blood pressure within 15 minutes of stopping the infusion. These data demonstrate that very small amounts of captopril can produce a dose-dependent inhibition of angiotensin converting enzyme without abrupt changes in blood pressure.

Adult↗
PubMed1984

The specificity of ketanserin in the inhibition of serotonin-induced steroidogenesis in the rat adrenal zona glomerulosa.

Although the biological effects of ketanserin were originally attributed to its specific interaction with serotonin type 2 (5HT2) receptors, at high doses (greater than 10(-8)M) it also appears to act as an alpha 1-antagonist in some tissues. This in vitro study examines the possibility that Ketanserin may inhibit serotonin-induced steroidogenesis by blockade of alpha 1-receptors. Rat zona glomerulosa cells prepared by collagenase digestion of adrenal capsular tissue were incubated at 37 degrees C in Krebs-Ringer bicarbonate buffer (0.2% glucose, 0.2% bovine serum albumin) for 30 min with increasing doses of serotonin (10(-9)-10(-6)M) alone or in the presence of ketanserin (10(-6)M), methysergide (a 5HT-receptor antagonist) 10(-6)M) or prazosin (an alpha 1-antagonist)(10(-6)M). Cyclic AMP, Corticosterone and aldosterone outputs were measured by radioimmunoassay. Serotonin produced correlative sigmoidal dose responses for cyclic AMP, corticosterone and aldosterone which were inhibited by ketanserin and methysergide but not by prazosin. These results suggest that ketanserin does not act by alpha 1-blockade in the adrenal zona glomerulosa but rather as a specific 5HT-receptor antagonist.

Adrenal Cortex↗
PubMed1983

Development and optimisation of a radioimmunoassay for plasma captopril.

A specific and sensitive radioimmunoassay has been developed to monitor plasma levels of captopril, the first orally active angiotensin-converting enzyme inhibitor. Because of the reactive nature of the captopril thiol group, captopril was measured as the captopril-N-ethylmaleimide complex (captopril-NEM). Accuracy studies, using samples with known added concentrations of captopril, were satisfactory (r = 0.95, p less than 0.001, y = 0.97x - 2.02), and the radioimmunoassay results compared well with those determined by a gas chromatography/mass spectrometric method (r = 0.98, p less than 0.0005, y = 1.2x - 19). The minimum detection limit of the assay was 2 micrograms captopril/litre plasma.

Antibody Specificity↗
PubMed1982

Human gamma-melanotropin precursor potentiates corticotropin-induced adrenal steroidogenesis by stimulating mRNA synthesis.

Circulating human gamma-melanotropin precursor (76 amino acids) [N-POC(1-76) enhances the corticosterone and aldosterone response to corticotropin by isolated perfused rat adrenal cells [Al-Dujaili, Hope, Estivariz, Lowry & Edwards (1981) Nature (London) 291, 156-159]. Actinomycin D (4 x 10(-6) mol/litre) did not significantly affect corticotropin-induced corticosterone or aldosterone outputs, but completely inhibited the potentiating action of gamma-melanotropin precursor on rat adrenal cells. This suggests that the precursor enhances corticotropin-induced steroidogenesis via an increase in available mRNA produced from DNA transcription.

Adrenal Glands↗
PubMed1981

The development and application of a direct radioimmunoassay for corticosterone.

A direct, simple and highly specific radioimmunoassay for corticosterone has been developed. The assay does not require preliminary solvent extraction of the sample or any chromatographic step. The assay utilises a highly specific antibody raised in rabbits against corticosterone-3-(0-carboxymethyl)-oxime-BSA immunogen and gamma-labeled corticosterone of high specific activity. An excellent correlation was obtained between results of the direct assay and those measured after paper chromatography (r = 0.99, P less than 0.001). The coefficients of variation for intra-assay and inter-assay determinations of samples from normal and high plasma pools were 4.6-6.2% and 6.4-8.2% respectively. The minimum limit of detection was 5 pg/assay tube (0.1 ng/ml). The assay has been applied to assess plasma corticosterone levels in various physiopathological and pathophysiological studies. It is extremely practical to the extent that a single technician can assay up to 1000 samples in a working week. Finally, the direct assay has been validated and employed for in vitro adrenal superfusion studies using either rat or human adrenal cells. The large numbers of samples produced by these studies would have exceeded the capacity of earlier radioimmunoassays requiring initial extraction and chromatography.

Adrenal Glands↗
PubMed1980

Further studies on the stimulation of rat adrenal capsular cells: four types of response.

Preparations of capsular rat adrenal cells consisting mainly of zona glomerulosa with less than 5% zona fasciculata contamination are described. The responses of the aldosterone and corticosterone outputs of these preparations to various stimuli were of four types. (1) Variations in K+ concentration gave a maximum aldosterone response at 5.9-8.4 mM-K+, about sixfold greater than the control output at 3.6 mmol/l. At higher K+ concentrations such as 13 mmol/l, the response decreased. (2) Serotonin (at a concentration of about 10(-4) mol/l) gave only a slightly lower maximal aldosterone response than did K+ but this did not decrease significantly at higher concentrations. Serotonin gave significant steroidogenic response at 10(-8) mol/l. (3) [Asp1,Val5]-Angiotensin II (10(-10) mol/l) with 3.6 mM-K+ gave a significant response and a constant maximal response at 2.5 x 10(-8) mol/l. This maximum response was about half that found for both aldosterone and corticosterone when stimulated maximally by K+ or serotonin: [des-Asp1,Ile5]- and [des-Asp1,Val5]-angiotensin II (angiotensin III) gave similar response characteristics but had a lower potency in this cell preparation. The initial maximum response could be further increased at a higher concentration (from 2.5 x 10(-5) mol/l) of a preparation of [Asn1,Val5]-amide angiotensin II (Hypertensin-Ciba) and might eventually be greater than with K+. This additional response was, to a major extent, due to stimulation of the contaminating zona fasciculata cells and was not seen with high concentrations of the free acid, angiotensin II. It was also not seen in two experiments with pure [Asn1]-amide angiotensin II and therefore it could have been due to some impurity in Hypertensin-Ciba. (4) Adrenocorticotrophin (Synacthen) at 3 x 10(-11) mol/l gave a significant steroidogenic response. Higher concentrations (3 x 10(-10) to 7.5 x 10(-9) mol/l) gave no constant maximum but the response could be much greater than for other stimuli such as K+, serotonin and [Asp1]-angiotensin II. This additional response was again due to steroid precursors, e.g. deoxycorticosterone and corticosterone from contaminating zona fasciculata cells. Similar results were obtained with ACTH (ACTHAR) in three experiments. Threshold sensitivity (a significant increase in steroidogenesis) for ACTH (Synacthen) was, in two experiments, greater for zona fasciculata-reticularis cells (3 x 10(-12) mol/l) than for zona glomerulosa cells (3 x 10(-11) mol/l). The data show that aldosterone output was approximately a function of the square of the corresponding corticosterone value. Specific effects on this pathway can be shown by values of aldosterone/corticosterone2 greater than one. Of all stimuli used, only K+ concentrations of 5.3, 5.9 and 13 mmol/l gave such effects. However, because of several considerations, only positive results with other stimuli may be meaningful. Calculation of this parameter might be useful as a screening test in bioassays for substances with aldosterone-stimulating activity.

Adrenal Cortex↗
PubMed1978

Effect of mast cell degranulation on gastric mucosal damage produced by sodium taurocholate in the rat.

The source of the histamine released during damage to the gastric mucosa has been investigated in rats using perfused total gastric pouches. Two groups of rats were treated with either intraperitoneal normal saline or compound 48/80, and agent that produces mast cell degranulation, over a 5-day period. On the 5th day, total gastric pouches were prepared and connected to a perfusion circuit that enabled a 20-ml volume to be circulated through the pouches. The experiments consisted of three 30-min periods during which transmucosal potential difference was monitored and ionic (hydrogen and sodium) flux measured; standard acid solution was used in the first two periods and a taurocholate solution in the third. Sodium taurocholate produced a significant increase in ionic flux and fall in the potential difference, the magnitude of the changes being similar in the 48/80- and saline-treated groups. Histamine was released from the mucosa in significantly greater amounts during the taurocholate period, and the increase was similar in both groups of rats. Histological examination of the stomachs confirmed mast cell degranulation in the 48/80-treated groups. We conclude that the histamine released during mucosal damage is probably derived from the "nonmast cell pool" and that this histamine may play a role in mediating the mucosal damage.

Animals↗
PubMedDate not supplied

A patient-based system for describing ambulatory medicine practices using diagnosis clusters.

OBJECTIVE: To develop a patient-based classification system to describe the clinical content of ambulatory medicine practices. DESIGN: A system of 100 diagnosis clusters was developed based on retrospective review of computerized problem lists of patients from a university practice, and then applied to the problem lists of patients in a community practice. Chart review of a 5% random sample (n = 184) of university practice patients who had problem lists was carried out to assess the accuracy of the computerized problem lists. SETTING: A university ambulatory medicine practice and a community ambulatory medicine practice. PATIENTS/PARTICIPANTS: For the same one-year period, all 4,490 patients seen in the university practice and all 1,294 patients seen two or more times in the community practice. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 27,634 problems listed for university patients and the 5,648 problems listed for community patients, 22,629 (82%) and 4,924 (87%), respectively, were assigned to diagnosis clusters. For the university and community practices, the mean numbers of problems per patient were 6.1 (SD 5.4) and 4.4 (SD 3.7), and the mean numbers of diagnosis clusters per patient were 4.5 (SD 3.7) and 3.6 (SD 3.0), respectively. Among the ten most common diagnosis clusters in both practices were HYPERTENSION, SYMPTOM OR SIGN, OBESITY, and DIABETES. Only 18% (SD 3%) of patient problem lists in the university practice omitted one or more chronic, important medical problems (e.g., hypertension, dementia, COPD). CONCLUSIONS: This system of diagnosis clusters effectively and efficiently described the clinical content of two types of internal medicine practices, and has important applications in medical education, epidemiology, clinical and health services research, and public policy.

Ambulatory Care↗