PubMed Health⌕ Search

Biomedical subjects

D Chow

Publications and source records attributed to D Chow.

50 records · Page 3Linked to original sources
PubMed1981

The 21-hydroxylase activity in the glomerulosa and fasciculata of the adrenal cortex in congenital adrenal hyperplasia.

In the two clinical syndromes of congenital adrenal hyperplasia due to a 21-hydroxylation defect of adrenal steroidogenesis, the simple virilizing and the salt-wasting forms, the 21-hydroxylase activity was studied considering the zona fasciculata and the zona glomerulosa of the adrenal cortex as two separate glands under different regulation. To test this hypothesis, we stimulated adrenal steroidogenesis by ACTH infusion or dietary sodium restriction in eight patients with congenital adrenal hyperplasia (four patients with the simple virilizing form and four with the salt-wasting form of congenital adrenal hyperplasia) and in six normal children. Both the 17-hydroxy and 17-deoxy pathways of adrenocortical steroid biosynthesis were examined by measuring serum concentrations of 17-hydroxyprogesterone, cortisol, progesterone, deoxycorticosterone, corticosterone, and aldosterone and the excretion of free deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, cortisol, and aldosterone. We considered the steroids 18-hydroxycorticosterone and aldosterone to be primarily of zona glomerulosa origin. These studies indicated that the zona fasciculata of both the salt-wasting and the simple virilizing forms is defective in 21-hydroxylation of 17-hydroxy and 17-deoxy steroids. The zona glomerulosa demonstrated deficient 21-hydroxylation only in the salt-wasting form, whereas in the simple virilizing form, the glomerulosa was spared this defect.

Adrenal Cortex↗
PubMed1981

Adrenal glomerulosa function in patients with dexamethasone-suppressible hyperaldosteronism.

The response of the adrenal glomerulosa to renin stimulation was determined in 10 patients with dexamethasone-suppressible hyperaldosteronism. The patients were treated continuously with 2 mg/day dexamethasone (DEX) and were studied on a regular sodium diet (87 meq/m2 . day) and on a 10 meq/day sodium diet. With DEX treatment all patients showed a prompt suppression of adrenal fasciculata function as evidenced by suppression of serum cortisol, corticosterone, desoxycorticosterone, and urinary 18-OH-desoxycorticosterone. The complete suppression of urinary pH 1 aldosterone (aldo) by DEX, unique to this disorder, was paralleled by a prompt suppression of urinary 18-OH-corticosterone. With continued DEX administration, plasma renin activity rose to the normal or supranormal range. Dietary sodium restriction resulted in a further rise in plasma renin activity and a rise in urinary pH 1 aldo and 18-OH-corticosterone. We conclude that in DEX-suppressible hyperpaldosteronism, although ACTH appears to be the primary stimulus for aldo secretion in the untreated state, when ACTH is suppressed, the adrenal glomerulosa responds normally to the stimulation of renin-angiotensin II.

18-Hydroxycorticosterone↗
PubMed1980

Aldosterone response to prolonged ACTH infusion in juvenile hypertension.

The effects of a continuous 5-day ACTH infusion (40 units/24 hr) on plasma aldosterone (aldo) concentration and urinary excretion of aldosterone pH 1 conjugate, tetrahydroaldosterone and free aldo were investigated in 6 normotensive children, and 7 children with hypertension of unknown origin. In both groups, an initial rise of plasma aldo and all urinary aldo metabolites and a subsequent fall were observed during the ACTH test. The decline in plasma aldo correlated significantly with a decrease in plasma renin activity and serum K+. There was, however, evidence for another regulatory factor of aldo secretion during ACTH infusion because on a low salt diet. ACTH produced a similar aldo pattern which could not be attributed to the changes in plasma renin activity or serum K+. Urinary excretion of both free aldo and tetrahydroaldosterone, a metabolite formed in the liver, showed a slower decrease during ACTH infusion than aldosterone pH 1 conjugate, which is of renal origin. The change in pattern of urinary aldo metabolites may be caused by a relative increase of the free, nonprotein bound plasma fraction of aldo and an enhanced metabolism of aldo in the liver during ACTH infusion. Neither in the baseline state nor during the ACTH test was there a difference between the normotensive and the hypertensive group in any of the aldo parameters.

Adolescent↗
PubMed1980

New studies of the 11 beta-hydroxylase and 18-hydroxylase enzymes in the hypertensive form of congenital adrenal hyperplasia.

Studies in four children with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency provide evidence for two separate 11 beta-hydroxylating systems in the adrenal zona fasciculata and zona glomerulosa. In addition, these studies support the proposal that the adrenal 11 beta- and 18-hydroxylating activities are related and may involve the same enzyme protein and catalytic site. In the untreated or poorly treated state, despite elevation of deoxycorticosterone (DOC) and tetrahydrodeoxycorticosterone, urinary free 18-hydroxy-DOC was in the low normal range and did not increase normally with ACTH. PRA and urinary free 18-hydroxycorticosterone (18-OHB), tetrahydroaldosterone (TH Aldo), and pH 1 aldosterone were suppressed in the untreated and ACTH periods. Glucocorticoid administration suppressed plasma ACTH, and urinary tetrahydro-DOC and free DOC excretion decreased to the normal range. Concomitantly, there was a rise in PRA accompanied by parallel increase in urinary 18-OHB, urinary TH Aldo, and pH 1 aldosterone. While on dexamethasone, a low sodium diet (10 meq/day) resulted in prompt sodium retention, with a further rise in PRA and urinary 18-OHB, TH Aldo, and pH 1 aldosterone. These studies indicate the presence of both an 11 beta- and an 18-hydroxylase deficiency in the zona fasciculata and normal 11 beta- and 18-hydroxylase function in the zona glomerulosa, suggesting that these two enzymatic functions are related and that separate enzyme systems are present in the two zones.

Adolescent↗
PubMed1979

Adrenocortical function, electrolyte metabolism, and blood pressure during prolonged adrenocorticotropin infusion in juvenile hypertension.

The effect of a continuous 5-day ACTH infusion (40 U/24 h) on adrenocorticoid function, electrolyte metabolism, and blood pressure was investigated in eight normotensive children and eight patients with hypertension of unknown origin. There was a continuous rise of plasma cortisol and deoxycorticosterone in all patients. Plasma aldosterone rose transiently in the normotensive and the hypertensive group. A transient kaliuresis and a continuous fall in serum K+ were observed in all patients. ACTH induced sodium retention and weight gain. The observed increase in systolic blood pressure correlated significantly with the cumulative sodium retention in the normotensive and the hypertensive groups. No correlation between sodium retention and diastolic pressure was found. ACTH on a low salt diet (10 meq/24 h) produced a blood pressure rise which was smaller than that on regular salt. The blood pressure rise did not correlate with any of the hormones measured. This study provides evidence for an unidentified ACTH-stimulable adrenal factor capable of raising blood pressure in normotensive children and patients with juvenile hypertension. The ACTH-induced blood pressure rise is only partly salt dependent and the mechanism of the rise remains unclear.

Adolescent↗
PubMed1974

Modification of zymosan-induced release of lysosomal enzymes from human polymorphonuclear leukocytes by cytochalasin B.

During the process of phagocytosis, polymorphonuclear leukocytes (PMN) release lysosomal enzymes into the extracellular medium. When the antibiotic cytochalasin B (CB) is present in the incubation medium along with phagocytable particles, enhanced recovery of enzyme activities from the incubation medium has been observed. These findings have led to the interpretation that CB enhances lysosomal enzyme release. Our results contradict this interpretation. The lysosomal enzymes acid phosphatase and beta-galactosidase are unstable after they are released from cells. During the first 5-15 min of phagocytosis, significant amounts of both acid phosphatase and beta-galactosidase can be recovered from the extracellular medium. After this, the recovery of enzyme from the medium declines, presumably because the rate of loss of lysosomal enzyme activity exceeds the rate of release at later time periods. In the presence of CB, the appearance of lysosomal enzymes in the extracellular medium of cells exposed to zymosan is retarded for 5-10 min, after which it begins and then continues for approximately 20 min. At the end of a 30-min incubation period, therefore, in the absence of CB, extracellular levels of lysosomal enzymes (especially those which are unstable) are declining toward low levels while, in the presence of CB, extracellular enzyme levels are continuing to rise. We also measured the lysosomal enzyme remaining within cells after exposure to zymosan. CB retarded the disappearance of enzyme from cells and resulted in significantly less total cell enzyme loss. Thus, in the presence of CB, a greater proportion of the lysosomal enzyme lost from cells is recovered in the extracellular medium. In contrast to the previous conclusions that CB enhances lysosomal enzyme release, our results indicate that CB delays and decreases the zymosan-stimulated release of lysosomal enzymes from PMN. Since CB inhibits phagocytosis by PMN, our results indicate that the antibiotic modifies the mechanism of release of lysosomal enzymes, resulting in zymosan stimulation of their release independently of phagocytosis.

Acid Phosphatase↗
PubMedDate not supplied

Adsorption of polymorphonuclear leukocyte lysosomal enzymes to monosodium urate crystals.

Monosodium urate (MSU) crystals induced prompt release of lysozyme, and slower release of beta-glucuronidase, alpha-mannosidase, and lactic dehydrogenase (LDH) from polymorphonuclear leukocytes. At increasing crystal concentrations, an increasing delay in the apparent onset of beta-glucuronidase release was detected which appears to be due to selective absorption of enzyme activities to the MSU crystals: beta-glucuronidase greater than LDH greater than alpha-mannosidase greater than lysozyme. Lysosomal enzyme adsorption by MSU crystals may then contribute to experimental error or may modulate gouty inflammation.

Adsorption↗
PubMedDate not supplied

Poly(ethylene glycol)-conjugated anti-EGF receptor antibody C225 with radiometal chelator attached to the termini of polymer chains.

Several biological barriers, including significant liver uptake, limit the clinical application of radiolabeled antibodies in radioimmunoscintigraphy. Here, a general approach is described for radiolabeling of monoclonal antibodies conjugated with poly(ethylene glycol) (PEG). This strategy is demonstrated with C225, a monoclonal antibody directed against epidermal growth factor (EGF) receptor. We synthesized a heterofunctional PEG with one end attached to a radiometal chelator, diethylenetriaminepentaacetic acid (DTPA), and the other end to a protected thiol group, S-acetylthioacetate. After a deprotection step, the resulting DTPA-PEG-SH was conjugated to maleimide-activated C225 to yield DTPA-PEG-C225 conjugate. Characterization of DTPA-PEG-C225 with immunoprecipitation and Western blot analysis revealed that the conjugate was biologically active in binding to the EGF receptor in A431 cells. Competitive EGF receptor binding assay in MDA-MB-468 cells showed that DTPA-PEG-C225, with up to 60% of the amino groups in C225 substituted, retained 66% of C225's binding affinity. Moreover, DTPA-PEG-C225 with increasing degrees of NH(2) substitution from 20% to 70% retained the activity of C225 to induce apoptosis in DiFi cells. More importantly, DTPA-PEG-C225 demonstrated less nonspecific interaction than DTPA-C225. Pharmacokinetic analysis using (111)In-labeled compounds revealed narrower steady-state distribution of (111)In-DTPA-PEG-C225 than (111)In-DTPA-C225, probably due to reduced nonspecific binding of PEG-modified antibody to tissues. The terminal half-life (t(1/2,)(gamma)) of (111)In-DTPA-PEG-C225, 21.1 h, was shorter than that of (111)In-DTPA-C225, 52.9 h. These data suggest that (111)In-DTPA-PEG-C225 may provide better imaging characteristics than (111)In-DTPA-C225, and that using PEG as a linker between the monoclonal antibody and DTPA may be a promising strategy in optimizing the imaging characteristics of immunoscintigraphic agents.

Antibodies, Monoclonal↗
PubMedDate not supplied

Drug and poison information resources on the Internet, Part 2: Identification and evaluation.

The Internet is a potential source of information for practitioners and researchers of pharmaceutical sciences. Despite its explosive growth and popularity, pharmacists and other health care providers have been slow to use the Internet as a source of clinical information. We have identified and evaluated several sites available on the Internet that are devoted to providing information related to professional practice, pharmacotherapy, and toxicology. We have concerns, however, regarding the quality of the available information and advise users to be cautious in using the data they obtain.

Computer Communication Networks↗