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Biomedical subjects

J R Gill

Publications and source records attributed to J R Gill.

At least 19 recordsLinked to original sources
PubMed1996

Early presentation of metastatic medullary carcinoma in multiple endocrine neoplasia, type IIA: implications for therapy.

A girl 5 years 11 months of age, belonging to an extensive kindred with multiple endocrine neoplasia, type IIA (MEN IIA), was found to have multifocal medullary thyroid carcinoma with metastasis in one paraglandular lymph node after positive findings on a calcium-pentagastrin stimulation test. Her sister, 3 years 8 months of age, also had an elevated calcitonin level, and thyroidectomy revealed C-cell hyperplasia and a focus of medullary thyroid carcinoma. These two cases underscore the need for prophylactic thyroidectomies in MEN IIA patients as young as 5 years of age and strict yearly provocative screening beginning at age 1 year.

Carcinoma, Medullary↗
PubMed1994

Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.

Liddle's syndrome (pseudoaldosteronism) is an autosomal dominant form of human hypertension characterized by a constellation of findings suggesting constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel. We demonstrate complete linkage of the gene encoding the beta subunit of the epithelial sodium channel to Liddle's syndrome in Liddle's original kindred. Analysis of this gene reveals a premature stop codon that truncates the cytoplasmic carboxyl terminus of the encoded protein in affected subjects. Analysis of subjects with Liddle's syndrome from four additional kindreds demonstrates either premature termination or frameshift mutations in this same carboxy-terminal domain in all four. These findings demonstrate that Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel and have implications for the regulation of this epithelial ion channel as well as blood pressure homeostasis.

Amino Acid Sequence↗
PubMed1994

Urinary excretion rate of endothelin-1 in patients with essential hypertension and salt sensitivity.

To assess the possible role of ET-1 in the pathogenesis of hypertension and salt sensitivity levels of immunoreactive endothelin-1 (irET-1) were measured in plasma and urine of 17 patients with essential hypertension and in 19 normotensive control subjects. Effects of alterations in dietary sodium content on urinary irET-1 levels also were assessed. Plasma levels of irET-1 did not differ between the hypertensives and normotensive groups (1.1 +/- 0.3 and 1.3 +/- 0.1 pg/ml). Urine samples of both groups contained high concentrations of irET-1. However, the mean daily urinary excretion of irET-1 in the hypertensives was less than one-third that in controls (29 +/- 3 vs. 109 +/- 21 ng/day, respectively, P < 0.01). Changing dietary sodium content in the hypertensives had no effect on mean irET-1 excretion. However, on either low, intermediate, or high salt diet, "salt sensitive" hypertensives had lower levels of the peptide than "salt resistant" patients (23 +/- 3 vs. 36 +/- 5 ng/day, respectively, P < 0.05). The data demonstrate a marked reduction in irET-1 excretion in patients with essential hypertension, despite normal plasma levels of the peptide. Since ET-1 has diuretic and natriuretic properties, the decreased renal excretion of ET-1 may be of relevance to the pathophysiology of hypertension and salt sensitivity.

Adult↗
PubMed1994

Erythrocyte and mononuclear blood cell magnesium concentrations are normal in hypomagnesemic patients with chronic renal magnesium wasting.

OBJECTIVE: The purpose of this study was to determine the plasma, erythrocyte, and mononuclear blood cell (MBC) magnesium concentrations in patients with chronic, severe hypomagnesemia due to a chronic magnesium-wasting tubulopathy. METHODOLOGY: Six patients with Bartter's syndrome and five patients with magnesium-wasting tubulopathy were compared with normal subjects. We determined magnesium in plasma, erythrocytes, and MBCs. RESULTS: Patients with chronic magnesium-wasting tubulopathy had a significantly lower plasma magnesium concentration than controls, but erythrocyte magnesium concentration and MBC magnesium concentration and content did not differ significantly between patients and controls. CONCLUSION: Two disorders with chronic magnesium-wasting tubulopathies are associated with a low plasma magnesium concentration but normal erythrocyte and MBC magnesium.

Bartter Syndrome↗
PubMed1993

Role of muscarinic receptors in renal response to acetylcholine.

Renal arterial infusion of acetylcholine (ACh) (40 micrograms/min) in control dogs produced an ipsilateral increase in renal plasma flow (RPF) and in sodium excretion (UNaV) without a change in glomerular filtration rate (GFR). The increase in RPF and UNaV was maintained during the infusion of ACh. In indomethacin (Indo)-treated dogs (5 mg/kg) ACh produced a transient rise in RPF and UNaV, followed by a progressive decline in RPF and UNaV. The profound renal vasoconstriction was accompanied by a decline in GFR. To determine the role of the muscarinic receptor in the renal vasodilation and in vasoconstriction produced by ACh in Indo-treated dogs, atropine at 6, 60, and 600 micrograms/min was infused into the renal artery before and during the infusion of ACh. In Indo-treated dogs, all dosages of atropine prevented renal vasoconstriction by ACh. Renal arterial infusion of atropine at 600 micrograms/min completely inhibited the renal vasodilation produced by ACh. Atropine infused at 60 micrograms/min partially inhibited, whereas 6 micrograms/min atropine failed to inhibit, the renal vasodilation produced by ACh. Our data suggest that the renal vasodilator and vasoconstrictor effects of ACh in Indo-treated dogs are mediated by two separate types of muscarinic receptors.

Acetylcholine↗
PubMed1992

Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase.

Patients with glucocorticoid-remediable aldosteronism (GRA) from 12 kindreds possess chimaeric gene duplications arising from unequal crossing-over, fusing regulatory sequences of steroid 11 beta-hydroxylase to coding sequences of aldosterone synthase. These chimaeric genes are specific for GRA and explain the biochemistry, physiology and genetics of this form of hypertension. Sites of crossing over range from intron 2 to intron 4. Most mutations have arisen independently from either sister or non-sister chromatid exchange between these genes, which are only 45 kilobases apart. The possibility of a susceptibility allele for GRA of Irish origin is suggested. These findings indicate the utility of a direct genetic test for this disorder.

Alleles↗
PubMed1992

Distinction between hyperaldosteronism due to bilateral hyperplasia and unilateral aldosteronoma: reliability of CT.

Hyperaldosteronism due to a unilateral adenoma must be distinguished from hyperaldosteronism due to bilateral hyperplasia to enable the proper choice between surgical treatment (for adenoma) or medical treatment (for hyperplasia). To compare the efficacy of computed tomography (CT) and adrenal venous sampling, both examinations were performed in 24 patients with primary aldosteronism. All patients with a diagnosis of adenoma based on findings at venous sampling underwent adrenalectomy. The CT-based diagnosis was unilateral aldosteronoma in 17 patients and hyperplasia in seven patients. On the basis of venous sampling, unilateral adenoma was diagnosed in 22 patients; this diagnosis was confirmed by means of unilateral adrenalectomy in 21 patients. The most common error was diagnosis of hyperplasia based on the presence of bilateral nodules on CT scans: In six of seven patients with such a diagnosis, venous sampling and subsequent surgery revealed a unilateral adenoma. In hyperaldosteronism with multiple bilateral nodules, CT cannot reliably permit distinction between hyperplasia and adenoma.

Adenoma↗
PubMed1991

Effects of prostaglandins, cAMP, and changes in cytosolic calcium on platelet aggregation induced by a thromboxane A2 mimic (U46619).

The effects of U46619, a thromboxane mimic, on cytosolic Ca2+ concentration and platelet aggregation were determined in human platelets. Cytosolic Ca2+ concentration was determined by Quin-2 fluorescence and platelet aggregation quantitated with an aggregometer. Addition of U46619 (1 x 10(-7) M) to the platelet suspension produced a rapid increase in cytosolic Ca2+ and platelet aggregation. Pretreatment of platelets with EGTA (3 x 10(-3) M), verapamil (5 x 10(-4) M), a calcium entry blocker, or 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (1 x 10(-3) M), an inhibitor of intracellular Ca2+ release, either blunted or markedly delayed the rate, but not the magnitude, of increase in cytosolic Ca2+ and prevented platelet aggregation by U46619. Pretreatment of platelets with prostaglandin I2 (PGI2) (5 x 10(-8) M), PGD2 (5 x 10(-8) M), PGE1 (5 x 10(-8) M), PGF2 alpha (1 x 10(-5) M), dibutyryl cAMP (5 x 10(-3) M), or forskolin (1 x 10(-6) M) prevented both the increase in cytosolic Ca2+ and the associated platelet aggregation induced by U46619. These data suggest that U46619 may induce platelet aggregation through an increase in cytosolic Ca2+, and that both Ca2+ entry and its release from intracellular storage sites probably contribute to the increase in cytosolic Ca2+. Furthermore, the rate of the increase in cytosolic Ca2+ concentration, as well as the magnitude of the increase, appear to be critical for platelet aggregation induced by U46619. Our data are consistent with the hypothesis that PGs inhibit U46619-induced platelet aggregation by preventing the increase in cytosolic Ca2+, and that these effects may be mediated via an increase in cAMP, since they were induced by PGs and cAMP.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension.

Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for 7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p less than 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Defective fasciculata zone function as the mechanism of glucocorticoid-remediable aldosteronism.

Glucocorticoid-remediable aldosteronism is characterized by unusual sensitivity of aldosterone secretion to ACTH. Suppressibility by glucocorticoid and continued stimulability by exogenous ACTH has provided the basis for diagnosis and treatment of the disorder. A qualitative biochemical abnormality consisting of marked overproduction of the products of the cortisol C-18 oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, has been examined in 10 patients with the disorder and compared to the normal C-18 oxidation products of corticosterone, aldosterone, and 18-hydroxycorticosterone. The technique, based on stable isotope dilution mass fragmentography, measured the tetrahydro urinary metabolites of aldosterone, 18-hydroxycorticosterone, and 18-oxocortisol and unmetabolized 18-hydroxycortisol. All 4 C-18 oxygenated corticosteroids were markedly elevated in the untreated state and showed rapid parallel suppression with low doses of glucocorticoid. The proportional changes in C-18 oxygenated cortisols together with aldosterone and 18-hydroxycorticosterone suggested the mechanism of a common catalytic site of a cytochrome P450 methyl oxidase serving both cortisol and corticosterone substrates. The ACTH-dependent secretion of the C-18 oxidation products of both corticosterone and cortisol in the disorder is attributed to the acquisition of methyl oxidase activity by the fasciculata zone, where there are abundant pools of these precursors.

Adolescent↗
PubMed1989

Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans.

1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown. 2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week. 3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation. 4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.

Adult↗
PubMed1988

Plasma and urinary catecholamines in salt-sensitive idiopathic hypertension.

Nineteen patients with normal renin idiopathic hypertension were arbitrarily classified as salt-sensitive or salt-resistant depending on whether their mean arterial pressure did or did not increase by 8% or more when sodium intake was increased. The responses of the two subsets and of five normal subjects to sodium intakes of 9, 109, and 249 mEq/day given for 7 days were as follows: The salt-sensitive subjects retained more sodium than normal and plasma or urinary norepinephrine did not decrease when they were given a high sodium intake; urinary dopamine was normal but did not increase normally when sodium intake was increased. The salt-resistant subjects excreted sodium normally and plasma and urinary norepinephrine was decreased by 30 and 37%, respectively, when they were given a high sodium intake; urinary dopamine was supernormal and did not increase further when sodium intake was increased. Cumulative sodium retention during the high sodium intake was directly related to the percentage of change in plasma norepinephrine in the hypertensive subjects, suggesting that renal adrenergic activity was a factor in the impaired sodium excretion in the salt-sensitive patients. Cumulative sodium retention and the percentage of change in plasma norepinephrine were inversely related to urinary dopamine in the hypertensive subjects, suggesting that increased formation of dopamine in renal and neural tissue in the salt-resistant subjects may have been responsible for the differences between the subsets in renal and adrenergic responses to a high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗