Search PubMed⌕ Search

Biomedical subjects

W F Young

Publications and source records attributed to W F Young.

At least 109 records · Page 6Linked to original sources
PubMed1990

Human liver tyrosylsulfotransferase.

The sulfation of tyrosine is a common posttranslational modification of peptides and may regulate the biological activity of a peptide. The biological activity of cholecystokinin is dependent on sulfation at the tyrosyl residue. Study of the enzyme(s) responsible for this activation step should provide the basis for future studies of the posttranslational control of peptide biological activity. The experiments reported here were designed to determine the subcellular distribution and biochemical properties of tyrosyl-sulfotransferase activity in normal human liver tissue. tert-Butoxycarbonylcholecystokinin octapeptide (desulfated) served as the sulfate-acceptor substrate. Subcellular distribution studies showed that tyrosyl-sulfotransferase activity was localized to the membrane-bound fraction. Tyrosylsulfotransferase was characterized by a pH optimum of 5.8, and activity was increased in the presence of sodium chloride and manganese chloride. The addition of detergents inhibited this enzyme activity. Using the optimized assay conditions, tyrosylsulfotransferase was measured in 20 individual human liver samples. Twenty-fold interindividual variation was found--variation that may be related to individual differences in the degree of posttranslational sulfation of proteins. The level of tyrosylsulfotransferase activity did not correlate with the levels of activity of two soluble sulfotransferases, thermostable and thermolabile phenol sulfotransferase. These results provide the basis for future studies to determine the role of sulfation of peptides in humans and whether individual variations in tyrosylsulfotransferase activities correlate with individual differences in the degree of sulfate conjugation of peptides.

Chromatography, High Pressure Liquid↗
PubMed1990

The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases.

A histologic and immunocytochemical study of 69 autopsy-obtained pituitaries from women who died during pregnancy, after abortion, or in the postpartum period revealed an accumulation of large chromophobic to slightly acidophilic and periodic acid-Schiff-negative pregnancy cells that were immunoreactive for prolactin but not for other pituitary hormones. This increase in the number of prolactin cells was confirmed by cell counts. Thus, pregnancy cells are capable of prolactin production. The finding of mitotic figures in such cells supports the view that they arise by multiplication from preexisting prolactin cells. With use of "mirror section" techniques, no mammosomatotrophs (cells immunoreactive for growth hormone and prolactin) were identified. Hyperplasia of prolactin cells was evident at 1 month of pregnancy and gradually disappeared within several months after delivery or abortion; the process of involution seemed to be retarded in the one lactating patient investigated. In some pituitaries, the accumulation of prolactin cells was so extensive that the hyperplastic foci resembled microadenomas. Another striking change in the pituitaries of pregnant women was appreciable reduction of immunostaining of gonadotropic cells, a process that was reversible as soon as 1 month after delivery. Among the 69 pituitaries studied, 8 noninvasive microadenomas (12%) were encountered (7 contained prolactin only and 1 was plurihormonal). Prolactin-producing adenomas were no more numerous or larger than were similar tumors encountered in nonpregnant women or normal men; thus, pregnancy neither initiates formation of pituitary adenomas nor accelerates their growth. In the pituitaries that harbored prolactin-producing adenomas, massive pregnancy cell hyperplasia was evident outside the tumor; thus, prolactin production by adenoma cells did not seem to suppress the proliferation of prolactin-containing pregnancy cells.

Adenoma↗
PubMed1990

Primary aldosteronism: diagnosis and treatment.

The syndrome of primary aldosteronism produces few signs or symptoms. The diagnosis should be suspected when either spontaneous hypokalemia or easily provoked hypokalemia is found in a patient with hypertension. Hypokalemia in association with inappropriate kaliuresis, low plasma renin activity, and a high plasma aldosterone concentration/plasma renin activity ratio are the findings on initial screening tests that should suggest primary aldosteronism. The diagnosis must be confirmed by demonstrating nonsuppressible aldosterone excretion in conjunction with normal cortisol excretion. The choice of therapy is based on distinguishing unilateral from bilateral adrenal disease. With a unilateral adrenal adenoma, surgical removal reverses the hypokalemia and frequently cures the hypertension. In most patients with bilateral adrenal hyperplasia who are treated surgically, however, hypertension persists; thus, the initial treatment in these patients should be pharmacologic.

Adenoma↗
PubMed1990

Diagnosis of corticotropin-producing bronchial carcinoid tumors causing Cushing's syndrome.

Cushing's syndrome due to ectopic production of adrenocorticotropic hormone (corticotropin) has been recognized for many years. Traditionally, clinicians have thought that most cases were due to lung carcinomas and that the clinical manifestations differed from those for pituitary-dependent Cushing's syndrome. We report two cases of corticotropin-producing bronchial carcinoid tumors that were clinically and biochemically indistinguishable from pituitary-dependent Cushing's syndrome. Review of the literature revealed that bronchial carcinoid tumors are the most common cause of Cushing's syndrome due to ectopic secretion of corticotropin. On biochemical and anatomic studies, they are frequently indistinguishable from pituitary-dependent Cushing's syndrome and thus may be difficult to diagnose. Inferior petrosal sinus sampling for corticotropin and computerized imaging of the chest may be the best aids in making the diagnosis.

ACTH Syndrome, Ectopic↗
PubMed1990

Ovine corticotropin releasing hormone stimulation test: normal value study.

We determined the pituitary-adrenal response to 1 microgram/kg of ovine corticotropin releasing hormone (oCRH) administered as an intravenous bolus injection in 50 normal subjects. Brief facial flushing was noted in 44% of the subjects; no other side effects were reported. Plasma corticotropin levels increased from a median of 30.2 pg/ml at baseline to a median peak level of 77.8 pg/ml after administration of oCRH; the peak response occurred at the 30- to 45-minute or the 45- to 60-minute time point. Plasma cortisol levels increased from a median of 10.8 micrograms/dl at baseline to a median peak level of 22.0 micrograms/dl after administration of oCRH; the peak response occurred at the 45- to 60-minute time point. Plasma beta-endorphin levels increased from a median of 9.5 pg/ml at baseline to a median peak level of 23.0 pg/ml after administration of oCRH; the peak response occurred at the 15- to 30-minute or the 30- to 45-minute time point. The responsiveness to oCRH was unaffected by age, sex, or body mass index of the subjects.

Adrenocorticotropic Hormone↗
PubMed1989

Flow cytometric analysis of deoxyribonucleic acid ploidy in benign and malignant aldosterone-producing neoplasms of the adrenal gland.

Studies of nuclear deoxyribonucleic acid (DNA) ploidy were performed to determine if ploidy was a marker of a malignant disease or a predictor of prognosis. Paraffin-embedded specimens from 20 benign and six malignant aldosterone-producing neoplasms were examined by flow cytometry. For 17 of the benign aldosteronomas, the DNA histograms were similar to those for samples of normal adrenal cortical parenchyma of adult humans. The three DNA histograms from benign (histologically and clinically) aldosteronomas and all six malignant aldosterone-producing neoplasms were abnormal. Tissue from the adrenal gland from three of the patients with malignant aldosterone-producing tumors exhibited a DNA tetraploid and polyploid pattern; adrenal tissue from three other patients with malignant tumors were classified as having DNA aneuploid histogram patterns. Only patients with DNA aneuploid histogram patterns subsequently died of the disease. Flow cytometry may have an important role prognostically, rather than diagnostically, in the evaluation of aldosterone-producing malignant neoplasms, because the DNA histograms from three benign adenomas were abnormal.

Adenoma↗
PubMed1988

Cushing's syndrome due to primary multinodular corticotrope hyperplasia.

In this report, a case of Cushing's syndrome due to primary multinodular corticotrope hyperplasia is described. The patient had typical features of Cushing's syndrome and dynamic pituitary-adrenal testing, which suggested an ectopic adrenocorticotropic hormone (ACTH) syndrome. Results of petrosal sinus catheterization indicated that the pituitary gland was the source of excess ACTH. Total hypophysectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed multinodular corticotrope hyperplasia. Plasma corticotropin releasing hormone (CRH) was undetectable, and computed tomography of the chest and abdomen disclosed no neoplastic source of CRH. We speculate that either an abnormality in hypothalamic CRH secretion or corticotrope hypersensitivity to CRH might have been responsible for Cushing's syndrome in this patient.

Adrenocorticotropic Hormone↗
PubMed1988

Triiodothyronine: a substrate for the thermostable and thermolabile forms of human phenol sulfotransferase.

The enzyme(s) responsible for the sulfate conjugation of L-T3 in man has not been characterized. T3 sulfotransferase (T3-ST) activity was characterized in normal human liver tissue obtained during clinically indicated surgical resection. Subcellular distribution studies showed that the T3-ST activity was localized to the cytoplasmic fraction. This finding raised the possibility that T3-ST activity might be similar to the 2 previously identified forms of cytoplasmic phenol sulfotransferase (PST) found in human tissue. A thermostable (TS) form of PST catalyzes the sulfate conjugation of micromolar concentrations of p-nitrophenol, and a thermolabile (TL) form catalyzes the sulfate conjugation of dopamine and other monoamines. Thermal stability and enzyme inhibitor experiments showed that T3-ST activity in pooled liver homogenates was very similar to the TS form of PST. The apparent similarity of T3-ST to TS PST was studied further by measuring T3-ST, TS PST, and TL PST activities in 20 individual liver samples. T3-ST activities correlated significantly with TS PST activities (r = 0.939; P less than 0.001) measured with p-nitrophenol, but not with TL PST activities (r = -0.118; P greater than 0.6) measured with dopamine. However, sulfation of T3 by the TL form of the enzyme might have been masked by the 18-fold higher specific activity of TS than TL PST in human liver homogenates. When the two forms of PST were separated by ion exchange chromatography, T3 was found to be a substrate for both the TS and TL forms of PST. "True" Km values for T3 were similar for TS and TL PST (81 and 127 microM, respectively).

Adult↗
PubMed1988

Primary aldosteronism. Diagnostic evaluation.

The regulation of mineralocorticoid secretion and the pathophysiology of primary aldosteronism are reviewed. For conceptual and practical purposes, the diagnostic evaluation of primary aldosteronism is discussed as two series of studies. The first series involves the studies necessary to confirm the diagnosis. The second series of studies guides the therapeutic approach by distinguishing unilateral from bilateral adrenal disease.

Humans↗
PubMed1987

Adrenocortical carcinoma: nuclear deoxyribonucleic acid ploidy studied by flow cytometry.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with use of paraffin-embedded specimens were performed by flow cytometry on 52 adrenocortical carcinomas. Specimens were prepared by the combined techniques of Hedley and Vindeløv. Clinical course was obtained by chart review and follow-up examination. Nine (17%) tumors had a normal (diploid) DNA pattern, 13 (25%) were DNA tetraploid, and 30 (58%) were DNA aneuploid. The DNA aneuploid group was subdivided: 18 tumors with one stemline and 12 tumors with two stemlines of abnormal DNA cells. For tumors that were resected for cure, the 5-year Kaplan-Meier disease-free survival rates of the five patients with DNA diploid tumors and of the six patients with DNA tetraploid tumors were 80% and 33%, respectively. For 21 patients of whom 12 had one-stemline and nine had two-stemline DNA aneuploid tumors, the survival was 67% and 0%, respectively. Following palliative resection, the 4-year survival rates of the four patients with DNA diploid, seven with DNA tetraploid, five (omitting one with short follow-up) with one-stemline DNA aneuploid, and three with two-stemline DNA aneuploid tumors were 0%, 0%, 0%, and 33%, respectively. Although adrenocortical carcinoma is in general markedly aggressive, the addition of nuclear DNA ploidy studies may help to identify certain groups of patients who have a relatively favorable prognosis.

Adrenal Gland Neoplasms↗
PubMed1986

Human monoamine oxidase. Lack of brain and platelet correlation.

Monoamine oxidase (MAO) exists in two forms, MAO A and MAO B. Both are present in human brain, but the human platelet contains only MAO B. We studied whether individual variations in the activity of human platelet MAO B reflect individual variations in cerebral cortical MAO activities. Optimal conditions were determined for the measurement of MAO activities in both the platelet and cerebral cortex, obtained from 14 patients with epilepsy during clinically indicated neurosurgery. There was no significant correlation between the activities of MAO B in the cerebral cortex and platelets of these patients. Platelet MAO B activities also failed to correlate significantly with cerebral cortical MAO A activities. However, there was a significant positive correlation between cerebral cortical MAO A and MAO B activities. Individual variations in platelet MAO B activities do not reflect individual variations in either cerebral cortical MAO B or MAO A activities in patients with epilepsy who undergo neurosurgery.

Adolescent↗
PubMed1985

Human phenol sulfotransferase: correlation of brain and platelet activities.

Phenol sulfotransferase (PST; EC 2.8.2.1) catalyzes the sulfate conjugation of phenolic and catechol neurotransmitters and drugs. The human blood platelet has been the most thoroughly studied source of PST because of the possibility that the regulation of the enzyme in this easily accessible tissue might reflect the regulation of PST in the CNS. The human brain and platelet contain at least two forms of PST, forms designated as thermostable (TS) and thermolabile (TL) PST. TS PST catalyzes the sulfate conjugation of micromolar concentrations of phenol and p-nitrophenol and TL PST catalyzes the sulfate conjugation of dopamine and other monoamines. This study was performed to determine whether individual variations in the activities of human platelet TS and TL PST reflect individual variations in cerebral cortical PST activities. PST activities were measured in platelets and in cerebral cortical tissue obtained from 15 patients with epilepsy during clinically indicated neurosurgery. There was a highly significant correlation between the activities of the TS form of PST in cerebral cortex and platelets of these patients (r = 0.940, p less than 0.001), but there was not a significant correlation between activities of the TL form of PST in the two tissues (r = 0.396, p greater than 0.14). In addition to variations in the level of enzyme activity, there are also wide individual variations in the thermal stability of platelet TS PST.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

L-thyroxine contamination of pharmaceutical D-thyroxine: probable cause of therapeutic effect.

Studies have shown that pharmaceutic preparations of the stereo isomers of thyroxine differ with respect to thyromimetic potency and lipid level-lowering effects. We applied a stereospecific assay for dextrothyroxine (DT4) and levothyroxine (LT4) to determine whether the biologic effects observed after the administration of DT4 (Choloxin; Flint Laboratories) resulted from inherent biologic activity of DT4, conversion of DT4 to LT4 in vivo, or LT4 contamination of Choloxin tablets. Choloxin was administered in a dose of 8 mg/day for 5 mo to nine athyreotic subjects who were then treated with pharmaceutic LT4 (Synthroid), 0.2 mg/day for an additional 5 mo. Analysis showed that LT4 contamination of Choloxin tablets ranged from 0.50% to 2.30%. This degree of contamination resulted in physiologically significant doses of LT4 in the 8 mg/day doses of Choloxin. During the treatment with two different lots of Choloxin, serum LT4 accounted for 33% to 53% of the measurable serum total thyroxine. The degree of LT4 contamination in Choloxin tablets was sufficient to account for the observed serum LT4 levels and casts doubt on the conclusions derived from previous studies in which Choloxin was used as the source of "DT4."

Adolescent↗
PubMed1984

Human brain phenol sulfotransferase: biochemical properties and regional localization.

Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of catecholamines and phenol and catechol drugs. The human blood platelet contains a thermolabile (TL) form of PST that catalyzes the sulfate conjugation of dopamine and other monoamines and a thermostable (TS) form that catalyzes the sulfate conjugation of micromolar concentrations of phenol and p-nitrophenol. Experiments were performed to determine whether the brain contains forms of PST analogous to the TL and TS forms found in the human platelet, and to determine whether there are regional variations in human brain PST activity. We found that the human brain contains at least two forms of PST, forms that are similar to the platelet TS and TL forms of the enzyme with respect to substrate specificity, apparent Km constants, thermal stability, and sensitivity to inhibitors. Optimal conditions were determined for the measurement of these two activities in brain homogenates. The stability of PST activities in the human brain after death was determined in five samples of cerebral cortex that were obtained during clinically indicated neurosurgical procedures. An average of 76 +/- 8% and 80 +/- 9% (mean +/- SEM) of the basal TL and TS PST activities, respectively, remained in these five samples of cerebral cortex after 8 h of storage under simulated post-mortem conditions. Six human brains were then obtained less that 8 h after death from patients who had no neurological disease prior to death. The mean activities of the TL and TS forms of PST were measured in 17 different regions of the six brains. If the pituitary was excluded from consideration, TL and TS PST activities both varied approximately fivefold among these regions, and both activities were highest in cerebral cortex. However, the average TS activity in the anterior pituitary, a tissue of non-neural origin embryologically, was 6.5-fold greater than the highest average TS PST activity found in cerebral cortex.

Arylsulfotransferase↗
PubMed1984

Erythrocyte catechol-O-methyltransferase, platelet monoamine oxidase, and platelet phenol sulfotransferase activities in patients with prolactin-secreting pituitary adenomas.

Dopamine is metabolized by oxidative deamination catalyzed by monoamine oxidase, O-methylation catalyzed by catechol-O-methyltransferase, and sulfate conjugation catalyzed by phenol sulfotransferase. This study was performed to determine whether platelet monoamine oxidase, red blood cell catechol-O-methyltransferase and platelet phenol sulfotransferase enzymatic activities in patients with prolactinomas were quantitatively different from the same enzyme activities in blood samples from normal subjects. The mean enzyme activities in blood samples from 22 women with histologically proven prolactinomas were compared to the mean enzyme activities in blood samples from 32 normal women. The blood levels of these 3 enzymatic activities were not significantly different between the two groups (P greater than 0.4). If the regulation of these catecholamine-metabolizing enzyme activities in blood elements reflects the regulation of the enzymes in the hypothalamic-hypophyseal region, these results suggest that a defect in the regulation of dopamine-metabolizing enzymes is not associated with the pathogenesis of prolactinomas.

Adenoma↗