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Biomedical subjects

M L Watson

Publications and source records attributed to M L Watson.

At least 91 records · Page 5Linked to original sources
PubMed1987

A study of genetic linkage heterogeneity in adult polycystic kidney disease.

The mutation for adult polycystic kidney disease (APKD) has previously been localised to chromosome 16 by the demonstration of genetic linkage with the loci for the alpha-chain of haemoglobin and phosphoglycolate phosphatase. These studies were carried out, however, on only nine families so that the possibility remained that mutations at other genetic loci might produce the disease. Such genetic heterogeneity of linkage would invalidate the general use of chromosome 16 markers for the purposes of detection of the disease, and complicate the characterisation of APKD at the molecular level. Therefore further families were studied to address this question. A total of 28 northern European pedigrees were analysed, all apparently unrelated, and with origins in England, Scotland, Holland and eastern Finland. No evidence was found to suggest heterogeneity of genetic linkage between alpha-globin and the APKD locus in this population.

Adult↗
PubMed1987

Abnormal diurnal urinary sodium and water excretion in diabetic autonomic neuropathy.

1. Diurnal patterns of urine output and sodium and potassium excretion were studied in 10 diabetic patients with and 10 without autonomic neuropathy, and in 10 normal subjects. 2. The diurnal patterns of excretion in the diabetic patients with autonomic neuropathy differed significantly from the two other groups, as a smaller proportion of the 24 h output of urine, sodium and potassium was excreted during the day and a larger proportion was excreted at night. 3. Similar changes were noted in the diurnal patterns of urinary kallikrein excretion in diabetic patients with autonomic neuropathy, and urinary kallikrein output correlated significantly with urine volume but not with urinary sodium excretion. 4. The diurnal patterns of excretion of urinary prostaglandin E2 and 6-keto-PGF1 alpha were not significantly different in diabetic patients with autonomic neuropathy. 5. Nocturia was a common complaint in this group, and the number of nocturnal voidings correlated with night urine volume. There was no evidence of premature bladder emptying. 6. The changes observed in the day/night urine output and sodium excretion could not be explained by glycosuria, insulin regimens, impaired renal function or abnormal diurnal prostaglandin excretion; their possible relevance to the diurnal changes of urinary kallikrein excretion is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Studies of genetic linkage between adult polycystic kidney disease and three markers on chromosome 16.

Adult polycystic kidney disease (APKD) is a common genetic disorder that is inherited as an autosomal dominant trait. Recent reports show that, in some families, the APKD gene shows close genetic linkage to two chromosome 16 specific genetic markers. We have been conducting a genetic linkage study using 29 polymorphic isoenzyme and antigenic markers in 184 members of 12 APKD families. We present here the results of linkage analysis using three of these markers which have also been reported to be located on chromosome 16: phosphoglycolate phosphatase (PGP), glutamate pyruvate transaminase (GPT), and haptoglobin (HP). The results show that APKD is closely linked to the PGP locus on the short arm of chromosome 16 (16p13----p12), which is consistent with the previously reported linkage both to PGP and to the alpha globin locus. The genetic distance between PGP and APKD shows a maximum likelihood value of the recombination fraction at zero with a lod score of 5 X 5. There is no evidence of linkage between APKD and either GPT or HP. The PGP polymorphism potentially provides a useful predictive test to complement the use of alpha globin probes in genetic counselling. These tests should provide an efficient means of primary screening of family members at risk, as well as introducing the possibility of prenatal diagnosis.

Alanine Transaminase↗
PubMed1986

Systemic synthesis of prostaglandin I2 following sustained infusion of angiotensin II in conscious dogs.

Acute infusion of pharmacological doses of angiotensin II stimulates the release of prostaglandin I2 (PGI2), which may modulate the vasoconstrictor response. It is uncertain whether sustained small increases in the plasma concentration of angiotensin II has the same effect. To investigate this further, low doses of angiotensin II were infused into conscious sodium replete dogs for 3 h. PGI2 synthesis was assessed by measurement of a major metabolite of PGI2, 2,3-dinor-6-keto PGF1 alpha, in urine and plasma, using gas chromatography mass spectrometry. Angiotensin II infusion (15 ng/min per kg body weight) resulted in a 3-fold increase in plasma angiotensin II (50.8 +/- 5.4 to 149 +/- 11.2 pg/ml, P less than 0.01). Mean blood pressure increased (84.8 +/- 4.3 to 108 +/- 4.7 mm Hg, P less than 0.02) and renal blood flow decreased (201 +/- 46 to 127 +/- 13 ml/min, P less than 0.01) throughout the infusion. However there was no change in either the plasma concentration (11.3 +/- 2.5 to 9.1 +/- 1.0 pg/ml) or rate of urinary excretion of dinor-6-keto PGF1 alpha (1.75 +/- 0.28 to 1.85 +/- 0.41 ng/30 min) during the angiotensin II infusion. The results suggest that small sustained elevations of the plasma concentration of angiotensin II such as are likely to occur in conscious animals, do not persistently stimulate release of PGI2 in the systemic circulation.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Chronic effects of oral sulindac on renal haemodynamics and hormones in subjects with chronic renal disease.

The effects of oral sulindac, 600 mg daily, on renal function and plasma hormones were studied in eight subjects with chronic renal failure. Renal function and plasma hormones were measured before drug administration and then after taking sulindac for 28 days. Effective renal plasma flow was reduced in all subjects after 28 days but the glomerular filtration rate did not change. Plasma renin activity, potassium and aldosterone concentrations and urinary sodium excretion did not change but urinary prostaglandin E2 excretion fell significantly. Sulindac may be a relatively renal-sparing drug in its effects on the hormonal control of glomerular function.

Adult↗
PubMed1986

Vascular sensitivity to prostaglandin I2 and urinary excretion of 6-keto-prostaglandin F1 alpha in conscious dogs.

A method is described for measuring the urinary excretion of 6-keto-prostaglandin F1 alpha, the stable hydrolysis product of prostaglandin I2, by stable isotope dilution gas chromatography-mass spectrometry. Three different doses of prostaglandin I2 were infused intravenously into conscious dogs and the effects on systemic and renal haemodynamics and urinary sodium excretion were observed. The two highest infusion rates of prostaglandin I2 (15 and 30 ng min-1 kg-1 body weight) induced significant decreases in systematic blood pressure and dose-related increases in sodium excretion, but no change in renal haemodynamics. There was a linear relationship between urinary excretion of 6-keto-prostaglandin F1 alpha and the rate of infusion of prostaglandin I2. The calculated basal rate of entry of prostaglandin I2 into the systematic circulation in conscious dogs is 4 ng min-1 kg-1 body weight, which is substantially higher than that previously reported in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The contribution of PGI2 to the effects of captopril in conscious dogs in differing states of sodium balance.

There is some evidence that increased prostaglandin synthesis may mediate some of the effects of the angiotensin converting enzyme inhibitor captopril. The potential role of prostaglandin (PG)I2 in this process was assessed by measurement of changes in urinary 6-keto-PGF1 alpha excretion after captopril in eight sodium replete and depleted conscious dogs. In sodium replete animals captopril induced a small decrease in blood pressure, transient increases in effective renal plasma flow and urinary 6-keto-PGF1 alpha excretion, and progressive increases in plasma renin activity (PRA) and urinary sodium excretion. By contrast, during sodium depletion captopril induced a large decrease in blood pressure, a transient increase in effective renal plasma flow and urinary 6-keto-PGF1 alpha excretion, an early large but transient increase in PRA and small progressive increase in sodium excretion. The time course of changes after captopril suggested that increased PGI2 synthesis may contribute to the transient decrease in renal vascular resistance. The increase in PRA during sodium depletion was not associated with any change in urinary 6-keto-PGF1 alpha excretion.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

A study of genetic linkage heterogeneity in adult polycystic kidney disease.

The mutation for APKD has previously been localized to chromosome 16 by the demonstration of genetic linkage with both the alpha-chain of hemoglobin and phosphoglycolate phosphatase. These studies were carried out, however, on a limited number of families, and the possibility remained that mutations at other genetic loci might produce the disease. Such genetic heterogeneity of linkage would invalidate the general use of chromosome 16 markers for the purpose of detection of the disease and complicate the characterization of the APKD mutation at the molecular level. Therefore, further families were studied to resolve this issue. A total of 27 Northern European pedigrees were analyzed, all apparently unrelated and with origins in England, Scotland, Holland, and Eastern Finland. No evidence was found to suggest heterogeneity of genetic linkage between alpha-globin and the disease locus in this population.

Adult↗
PubMed1985

Haemodynamic and endocrine responses of the kidney to frusemide in mild essential hypertension.

Prostaglandin-dependent, frusemide-induced changes in renal plasma flow, glomerular filtration rate and plasma renin activity were measured in 14 patients with mild essential hypertension. The renal haemodynamic responses to frusemide were the same as in 10 normal subjects. Frusemide-induced changes in urinary PGE and kallikrein excretion were also the same as in normal subjects. Impaired renal release of vasodilator prostaglandins in essential hypertension is likely to be secondary to the hypertension rather than an underlying factor in its development.

Adult↗
PubMed1985

Urinary kallikrein and systemic prostacyclin synthesis during sodium chloride infusion in normal man.

An intravenous infusion of 3 litres of sodium chloride solution (saline: 150 mmol/l) was given over 1 h to normal subjects. During and immediately after the infusion, renal plasma flow increased in the majority of subjects, but the rise was not statistically significant. Significant increases in urine flow, sodium excretion, urinary kallikrein excretion and urinary excretion of dinor-6-keto prostaglandin (PG) F1 alpha, a measure of systemic PGI2 synthesis, were noted. Plasma renin activity and plasma protein concentration were significantly lowered by the infusion. At 2 h after the end of the infusion, although urine flow fell significantly, sodium excretion had not decreased. The reduction in plasma renin activity and plasma proteins persisted, and excretion of kallikrein and the PGI2 metabolite returned to control values. Overall, urinary kallikrein excretion correlated significantly with urine flow and with sodium excretion. Peak kallikrein excretion occurred in the second 30 min of the infusion, and preceded maximal urine flow and sodium excretion. The results suggest that increased systemic synthesis of PGI2 occurs in response to an acute infusion of sodium chloride, and may be an adaptive response of the vasculature to volume expansion. They support a role for the renal kallikrein-kinin system in the early diuretic and natriuretic response to saline infusion; the reduction in plasma renin activity and plasma protein concentration may be involved in both the early response and the persistent natriuresis 2 h after the infusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Insertion and internalization of acetylcholine receptors at clustered and diffuse domains on cultured myotubes.

Two populations of acetylcholine receptors (AChRs) are present in cultured myotubes. One forms large aggregates or clusters and the other has a much lower density of AChRs, which are diffusely distributed. Both clustered and diffuse AChRs are inserted and removed (internalized) from the sarcolemma. To determine the insertion and removal rates of AChRs in these two plasma membrane domains, we used a double label technique to distinguish and quantitate newly inserted and "old" AChRs. Application of our method revealed that the rate of AChR internalization is the same at the clustered and diffuse regions of the plasma membrane, whereas the rate of insertion is threefold greater at the clusters than elsewhere in the plasma membrane. Thus, the increase in AChR number at the clusters is not due to an increase in their half-life, but to an increase in their rate of insertion.

Animals↗
PubMed1985

Intrinsic sympathomimetic activity of cardioselective beta-adrenoceptor blockers and effects on renal function.

The effects of a 21 infusion of isotonic sodium chloride on renal haemodynamics and sodium excretion were measured in nine normotensive volunteers. Changes in these responses to volume expansion induced by cardioselective beta-adrenoceptor blockade by drugs with (epanolol) and without intrinsic sympathomimetic activity (atenolol) were examined. Renal plasma flow was significantly lower before, during and after sodium chloride infusion whilst on treatment with atenolol compared with epanolol. Urinary sodium excretion was lower on atenolol than epanolol. Glomerular filtration rate was unchanged by either drug. Basal urinary kallikrein excretion was diminished by atenolol and both epanolol and atenolol inhibited the rise in urinary kallikrein excretion after sodium chloride infusion. Although some of these findings may be due to a more potent hypotensive effect of atenolol, intrinsic sympathomimetic activity may contribute to the apparent protective effects of epanolol on renal function.

Adrenergic beta-Antagonists↗
PubMed1985

The opposition to fluoride programs: report of a survey.

State dental directors were surveyed in spring 1984 regarding fluoridation and fluoride programs. Forty-four states reported existing fluoride mouth-rinse programs in schools; 22, fluoride tablets in schools. About 90 percent of directors felt that support for fluoride programs by state departments of health and constituent dental societies either had remained the same or increased over the previous five years. Approximately half felt the antifluoridation movement to be as strong as five years earlier. About one-third indicated a shift in focus by water fluoridation opponents to include other fluoride systems. Most felt this shift occurred during 1981-82. Information was reported on 255 individual challenges to fluoride programs. Results of this survey indicate that expenditure of considerable resources and effort continues to be necessary to ensure the longevity of public fluoride systems.

Fluoridation↗
PubMed1984

Angiotensin sensitivity and prostaglandins in dogs with renal hypertension.

During established two-kidney one clip hypertension in dogs blood pressure is elevated despite only slightly raised plasma renin activity. Dose dependent effects of exogenous angiotensin II on systemic and renal haemodynamics were examined before and after induction of this type of hypertension in conscious dogs. There was no difference in the response of blood pressure to angiotensin II in each group, suggesting that altered pressor sensitivity to angiotensin II is not the cause of the persisting hypertension. However sodium excretion, effective renal plasma flow and glomerular filtration rate were all decreased by angiotensin II in the normotensive group, but were unchanged or increased in the hypertensive group. Renal prostaglandin E excretion was also increased in the hypertensive animals, and further increased during infusion with angiotensin II. The altered renal response to angiotensin II in the hypertensive group may reflect changes in occupancy of angiotensin II receptors and/or enhanced renal release of vasodilator prostaglandins.

Angiotensin II↗
PubMed1984

Left ventricular function and the distribution of pulmonary and total blood volume in hypertensive and normotensive man.

Using radionuclide methods the relationship between total and central blood volume and left ventricular function was studied in 12 patients with untreated essential hypertension and contrasted with the findings in eight normotensive subjects. The principal findings were of an increased stroke volume and end-diastolic volume with an increase in the ratio of pulmonary to total blood volume in the hypertensive patients. Left ventricular ejection fraction was similar in both groups but end-systolic volume was increased presumably in response to the increased afterload of the ventricle. The increased pulmonary blood volume may be secondary to altered left ventricular mechanics and not a primary determinant of cardiac function.

Adult↗