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Biomedical subjects

R D Watson

Publications and source records attributed to R D Watson.

At least 73 records · Page 4Linked to original sources

Competency of Manduca sexta prothoracic glands to synthesize ecdysone during development.

Prothoracicotropic hormone (PTTH) is the primary regulator of ecdysone biosynthesis by insect prothoracic glands. In Manduca sexta, a stimulatory protein from larval hemolymph appears to be an important secondary regulator of gland activity. A third level of regulation may involve the competency of the glands to respond to these effectors. To investigate this possibility, glands were removed from larvae on each day of the fifth instar and incubated in vitro, either alone or in the presence of PTTH, the hemolymph protein, or both. Glands were refractory to stimulation by either effector alone, or to a combination of both for the first 2 days of the instar. Subsequent to this, the glands were responsive to either factor alone, but the patterns of responsivity to PTTH and the stimulatory protein were different. After day 2, glands stimulated by a combination of both effectors exhibited a uniform maximal response. The prothoracic glands are, therefore, regulated not only by neuroendocrine and humoral effectors, but also by the competency of the glands to respond to those effectors.

Aging↗

Properties of serum high-density lipoproteins in the crab, Cancer antennarius Stimpson.

Two classes of high-density lipoprotein (HDL) comprise virtually all the lipoprotein mass in female hemolymph. These lipoproteins have hydrated densities of 1.187 g/ml (HDL3) and 1.112 g/ml (HDL2). A third species (HDL1, density 1.080 g/ml) appeared in ovigerous crabs. The mean annual HDL protein concentration was 109 mg/dl of which 67% was HDL3. HDL proteins of both HDL2 and HDL3 were mostly insoluble in tetramethylurea. Three major components with apparent mol. wts of 185,000, 100,000 and 84,000 daltons were identified by gel electrophoresis in SDS. Amino acid compositions are reported. Electron microscopy indicated that the HDL are polymorphic and discoidal. Similarities in shape and differences in size of HDL3 and HDL2 particles were consistent with their lipid and protein composition. Phospholipids, mostly phosphatidylcholine, were the dominant lipid class (74%); no cholesteryl esters were detected. Palmitic and oleic acids were the major fatty acid components of esterified lipids.

Animals↗

Sick sinus syndrome aggravated by carbamazepine therapy for epilepsy.

A case of sick sinus syndrome aggravated by carbamazepine prescribed for epilepsy is described. A 70 year old woman with previously stable psychomotor epilepsy experienced syncope of increased frequency after her anticonvulsant was changed to carbamazepine. ECG monitoring confirmed a severe sick sinus syndrome which improved on carbamazepine withdrawal. Failure to distinguish carbamazepine-induced cardiac syncope from epileptic attacks may lead to an increase in dosage and aggravation of syncope.

Aged↗

The pressor and metabolic effects of alcohol in normotensive subjects.

Changes in blood pressure, pulse rate, and plasma catecholamines, renin activity, cortisol, and calcium were studied in 16 normotensive subjects (eight with a family history of hypertension) for 5 hours following ingestion of alcohol-free and alcohol-loaded beer. Both systolic and diastolic blood pressure rose after alcohol consumption; maximum responses occurred at peak blood alcohol concentrations and were significantly higher than those seen after placebo. Pulse rate was also significantly higher after alcohol ingestion and continued to rise throughout the study. There was no difference in the pressor response to alcohol between the groups with and without a family history of hypertension. No difference was found in plasma norepinephrine or epinephrine levels between alcohol and placebo phases. However, subjects with no family history of hypertension had significantly higher plasma norepinephrine levels (p less than 0.01) than did those with a family history during both the alcohol and placebo phases, although baseline blood pressures were not significantly different. Plasma epinephrine level was similar in both groups. Plasma renin activity was unchanged throughout, but plasma cortisol fell during both phases. Plasma calcium showed a small but significant fall with alcohol consumption in both groups (p less than 0.001). These results indicate that in normotensive subjects alcohol ingestion causes a rise in systolic and diastolic blood pressure that is not influenced by a family history of hypertension. This effect does not appear to be sympathetically mediated but may be due to a direct vasoconstrictor effect of alcohol, possibly with an alcohol-induced shift in intracellular calcium.

Adult↗

Effects of eyestalk removal on cholesterol uptake and ecdysone secretion by crab (Cancer antennarius) Y-organs in vitro.

Y-Organs and control tissues from intact (intermolt) and 48-hr de-eyestalked Cancer antennarius donors were cultured for 12 and 24 hr in crustacean saline supplemented 10% with crab serum and containing [14C]cholesterol. Under these conditions, Y-organs took up significantly more [14C]cholesterol than ovary or muscle, and Y-organs from 48-hr de-eyestalked crabs took up threefold more than Y-organs from intact crabs. The labeled cholesterol of the culture medium was observed to bind rapidly to the lipoproteins of the serum supplement; subcellular fractionation of the activated Y-organs after incubation showed 59% of the label localized in the cytosolic fraction. The increase in cholesterol uptake did not result from a change in extracellular volume, and was not accompanied by a change in Y-organ total cholesterol. It was, however, accompanied by a greater than threefold increase in ecdysone secretion.

Animals↗

Biosynthesis of ecdysteroids from cholesterol by crab Y-organs, and eyestalk suppression of cholesterol uptake and secretory activity, in vitro.

Precursor incorporation studies were conducted in vitro with activated Y-organs from 48-hr de-eyestalked Cancer antennarius donors. When the glands were prelabeled in vivo by systemic injection of [3H]cholesterol 12 hr prior to removal, and subsequently incubated 24 hr in label-free medium, the glands secreted 3H-labeled ecdysone. The glands also secreted an unidentified ecdysteroid with comigrating 3H-label with characteristic retention time on normal-phase HPLC of 4 min (4-min unknown). The compound is less polar, and is secreted in a quantity and apparent specific activity approximately fivefold greater, than ecdysone. Compared with chromatographic retention times and competitive binding curves of authentic standards, the 4-min unknown was determined not to be ponasterone A, inokosterone, makisterone, or several other possible products or intermediates. In contrast with Y-organs from intact donors, those from de-eyestalked crabs exhibit greatly increased cholesterol uptake and secretion of both ecdysone and 4-min unknown in vitro. All three responses were suppressed in dose-dependent manner by eyestalk extract in the dose range, 1-4 eyestalk equivalents/Y-organ. Secretion of 4-min unknown was the response most sensitive to eyestalk extract (requiring the least dose for 50% inhibition).

Animals↗

Inhibition of the baroreceptor heart rate reflex by angiotensin II in normal man.

Eight normotensive male subjects were infused with angiotensin II or phenylephrine in a single blind fashion. Measurements were made of blood pressure and pulse interval every 3 min, and blood drawn for plasma catecholamines at the beginning and end of the infusion. Phenylephrine produced a rise in blood pressure which was associated with a bradycardia in all subjects. A statistically significant relationship between blood pressure and pulse interval was observed in all subjects. In contrast, angiotensin II infusion produced an equal pressor response, but the change in pulse interval was statistically significantly less than that seen following phenylephrine infusion. In seven of eight subjects no significant relationship was observed between blood pressure and pulse interval. Plasma noradrenaline levels were similar before each pressor infusion and were unchanged during each infusion. These observations are consistent with central inhibition of the baroreceptor heart rate reflex by angiotensin II in man.

Adult↗

Calcium channel blockers--are they diuretics?

Seven untreated patients with essential hypertension but without target organ damage were admitted to hospital. Urine was collected the following day from 08.00 to 13.00 h, 13.00 to 18.00 h, and 18.00 to 08.00 h. The protocol was repeated the next day following 30 mg oral nicardipine. Intra-arterial blood pressure (IABP), plasma volume, and plasma renin activity (PRA) also were measured daily. Following the single-dose study, the patients were treated as outpatients and received oral nicardipine 20, 30, or 40 mg four times daily. They were readmitted 2 months later for further study, at which time the protocol was repeated. Urine output between 08.00 and 13.00 h significantly increased after the single- and multiple-dose studies. Following the single-dose study, this diuresis was associated with a natriuresis. Urine output increased over the 24 h following multiple-dose treatment, but this increase was not statistically significant. During the multiple-dose 24 h study, there was an increase in urinary potassium (P less than 0.05). Mean IABP was reduced significantly after the single- and multiple-dose studies (P less than 0.02 and less than 0.05, respectively). During the study, there were no significant changes in plasma volume, weight, or plasma renin activity.

Adult↗

[Effect of nifedipine on arterial pressure and control of the cardiac reflex].

Nine patients with untreated essential hypertension (random blood pressure 173/109 +/- 14/7 mmHg) were studied before and after 16 weeks' treatment with oral nifedipine 10 mg three times a day. Direct continuous measurement of the systolic and diastolic blood pressures showed that both values were significantly reduced during the 24 hour period. Nifedipine did not change the variability of the blood pressure. There was no significant change in the heart rate after treatment with nifedipine. Long-term nifedipine induced an increase in blood flow in the forearm and decreased the vascular resistances which confirmed the vasodilator effects of the drug. The absolute responses of the blood pressure during postural changes, the hand grip test and cold pressor test were reduced but the treatment did not change the percentage increase in blood pressure during these tests. Long-term nifedipine therapy did not affect the plasma renin activity. The sensitivity and characteristics of the baroreflex response to intravenous phenylephrine were measured. After long-term nifedipine therapy we observed a normalisation of the sino-aortic baroreflex and an increase in its sensitivity. Normalisation of the blood pressure by nifedipine induced a significant reduction in the index of left ventricular mass.

Adult↗

Acute and chronic effects of the loop diuretic, piretanide, on baroreflex set point and sensitivity in hypertensive man.

Intra-arterial blood pressure (IABP), baroreflex sensitivity and set point were measured in nine patients with essential hypertension during a control period and then after acute (4 h after a 12 mg oral dose) and chronic (after 3 months) treatment with the loop diuretic piretanide, mean dose 10 mg. Acutely, there was a fall in mean systolic IABP (P less than 0.05) associated with a reduction in pulse interval (P less than 0.01). Chronically, mean systolic IABP remained significantly reduced (P less than 0.01) but pulse interval returned to control values. There were no significant changes in baroreflex sensitivity, either acutely or chronically. These results demonstrate acute deactivation of the vagal efferent limb of the baroreflex followed by a chronic resetting of the baroreflex-heart rate mechanism. We conclude that changes in baroreflex sensitivity are not responsible for the hypotensive effects of this drug and that resetting of the reflex arc is likely to be due to physiological adaptation rather than to any direct drug effect.

Adult↗

The Birmingham Trial of permanent pacing in patients with intraventricular conduction disorders after acute myocardial infarction.

Patients surviving 2 weeks after myocardial infarction who had persistent conduction disorder (right bundle branch block alone or associated with left anterior or posterior hemiblock [LPH] or LPH alone) were allocated at random to permanent pacing or control groups. Throughout follow-up, up to 5 years, there was no significant difference in survival: at 2 years 14 of 23 (61%) of paced patients had died compared with 11 of 27 (41%) control patients. Progression of conduction disorder was not observed and measurement of infranodal conduction time (HV interval) did not predict outcome. Ventricular tachyarrhythmias were an important cause of death in these patients and pacing appears to offer no benefit.

Bundle-Branch Block↗

Baroreflex setting and sensitivity after acute and chronic nicardipine therapy.

Intra-arterial pressure, baroreflex sensitivity and the baroreflex set point were measured in eight patients with essential hypertension during a control period and then after acute treatment (2 h after a 30 mg oral dose) and after chronic treatment (at least 2 months) with nicardipine hydrochloride, a calcium channel antagonist. Mean intra-arterial blood pressure fell after the acute treatment from 130 +/- 14 (SD) control to 118 +/- 11 mmHg, P less than 0.05, and after chronic treatment to 112 +/- 19 mmHg, P less than 0.05. Heart rate increased from 72 +/- 11 control to 81 +/- 16 beats/min, P less than 0.05, during acute treatment indicating activation of the baroreflex control mechanism, but returned to control values with chronic treatment (72 +/- 11 control vs 69 +/- 9 beats/min chronic), indicating a significant shift to the left of the baroreflex set point. There was no change in baroreflex sensitivity after either acute or chronic treatment (control 4.7, acute 4.3, chronic 5.1 ms/mmHg, P not significant for all values). Nicardipine significantly reduces mean intra-arterial pressure both acutely and chronically; the latter is associated with a return of the heart rate to control values due to resetting of the baroreflex control mechanism.

Adult↗

Feed associated haemorrhagic disorder in pigs accompanied by pancreatic lesions.

The introduction of a new batch of feed to 400 pigs aged five to eight weeks resulted in 38 deaths and further morbidity associated with multiple haemorrhages. Signs abated within two days of withdrawal of the feed. Widespread haemorrhages were present in many tissues including the pancreas. Additional pancreatic lesions comprised focal necrosis, atrophy and fibrosis of exocrine tissue. The condition was reproduced experimentally in pigs and vitamin K protected mice against the injurious effects of the feed. The cause was not determined but it is speculated that more than one toxic factor and an imbalance of nutritional factors may have been present in the diet.

Animal Feed↗

Effect of environment on blood pressure: home versus hospital.

The effect of environment on blood pressure was studied by recording intra-arterial pressure continuously in nine patients with essential hypertension during controlled periods of activity and rest at home and in hospital. Mean systolic pressure was higher at home (152 +/- 16 mm Hg) than in hospital (138 +/- 11 mm Hg, p less than 0.01), the difference being greatest during the period of activity (165 +/- 21 v 142 +/- 13 mm Hg, p less than 0.001); heart rates and diastolic pressures did not differ significantly at these times. Systolic pressure recorded by conventional sphygmomanometry was also higher at home (173 +/- 23 v 159 +/- 23 mm Hg, p less than 0.01), as was diastolic pressure (98 +/- 10 v 89 +/- 11 mm Hg, p less than 0.02). Systolic pressure was consistently higher at home, and this effect was independent of the pressure of an observer. This must be taken into consideration when assessing blood pressure and efficacy of treatment in hospital.

Adult↗

The effect of nifedipine on arterial pressure and reflex cardiac control.

Nine patients with untreated essential hypertension (mean casual blood pressure 173/109 +/- 14/7 mm Hg) (+/- SD) were studied in the control state and after 16 weeks of treatment with nifedipine, 10 mg orally every 8 hours. Direct arterial blood pressure monitored continuously over 24 hours showed that nifedipine significantly reduced systolic and diastolic blood pressure throughout the day and the night. The variability of blood pressure was not altered by nifedipine therapy. There was no significant change in heart rate after nifedipine therapy. Chronic nifedipine therapy increased forearm blood flow and decreased forearm vascular resistance, consistent with its action as a vasodilator. The absolute blood pressure responses to tilt, handgrip and cold were reduced, but the percent increase in pressure was not altered by therapy. Plasma renin activity was not altered by chronic nifedipine therapy. At each study, the sensitivity and setting of the baroreflex response to i.v. phenylephrine was measured. After chronic nifedipine therapy there was resetting of the sinoaortic baroreflex and an increase in its sensitivity. Successful control of blood pressure with nifedipine led to a significant reduction in the left ventricular mass index.

Adult↗