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Biomedical subjects

D Chang

Publications and source records attributed to D Chang.

At least 235 records · Page 13Linked to original sources

Effect of vasopressin blockade on blood pressure during water deprivation in intact and baroreceptor-denervated conscious dogs.

Previous studies have provided evidence that vasopressin plays an important role in blood pressure regulation during water deprivation. However, these investigations have been complicated by reflex compensatory increases in cardiac output and renin secretion. The aim of the present study was to investigate the effect of blockade of the vasoconstrictor action of vasopressin in conscious water-deprived dogs in which the low- and/or high-pressure baroreceptors were denervated to minimize reflex responses. Vasopressin blockade in sham-operated dogs (n = 7) did not change arterial pressure. Heart rate rose from 78 +/- 9 to 119 +/- 13 beats/min (P less than 0.01), and plasma renin activity increased from 10.9 +/- 2.1 to 21.6 +/- 4.6 ng.ml-1.3 h-1 (P less than 0.01). In carotid sinus-denervated dogs (n = 6), vasopressin blockade again failed to decrease arterial pressure. Heart rate increased from 105 +/- 10 to 132 +/- 10 beats/min (P less than 0.01), and plasma renin activity rose from 6.8 +/- 1.7 to 15.5 +/- 2.4 ng.ml-1.3 h-1 (P less than 0.01). The antagonist also failed to change blood pressure in cardiac-denervated dogs (n = 5). Heart rate increased from 111 +/- 9 to 119 +/- 1 beats/min (P less than 0.01), but plasma renin activity did not increase significantly. In marked contrast, vasopressin blockade in sinoaortic/cardiac-denervated dogs (n = 7) promptly decreased arterial pressure from 115 +/- 8 to 94 +/- 7 mmHg (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of CRF and ANG II on ACTH and vasopressin release in conscious dogs.

The aim of the present study was to examine the effects of corticotropin-releasing factor (CRF) in conscious dogs and to determine whether the stimulation of adrenocorticotropic hormone (ACTH) release by angiotensin II (ANG II) results from potentiation of the action of CRF. In addition, the possible role of CRF in the stimulation of vasopressin released by ANG II was investigated. The following experiments were performed: 1) intravenous saline infusion; 2) ANG II (10 ng.kg-1.min-1) alone; 3) vasopressin (1 ng.kg-1.min-1) alone; 4) CRF (0.001, 0.01, or 0.1 microgram/kg iv) bolus; 5) vasopressin (1 ng.kg-1.min-1) and CRF (0.1 microgram/kg) together; 6) CRF (0.001, 0.01, or 0.1 microgram/kg) and ANG II (10 ng.kg-1.min-1) together; 7) ANG II (10 ng.kg-1.min-1) followed 15 min later with CRF (0.001, 0.01, or 0.1 microgram/kg). Each dose of CRF was tested on a different day. Infusion of ANG II alone stimulated the release of ACTH, cortisol, and vasopressin. Administration of CRF produced dose-dependent increases in plasma ACTH and cortisol concentrations, and the highest dose of CRF increased plasma vasopressin concentration. CRF given together with ANG II did not potentiate the stimulation of ACTH release by CRF. Vasopressin at the dose tested did not stimulate ACTH release but potentiated the ACTH response to CRF. ANG II stimulated vasopressin release but did not potentiate the AVP response to CRF. These results show that, in conscious dogs, ANG II and CRF each increase plasma ACTH concentration and that the ACTH response to CRF is potentiated by vasopressin but not by ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Women's health and social change: the case of lay midwives.

One reaction to the medicalization of birth has been the comeback of lay midwives in the past 10 years. While many practice alone as did midwives 80 years ago, now midwives are networking and organizing in regional and statewide groups, an important new distinction in the light of increasing regulatory policy formation by many states. Are these groups the beginnings of traditional bureaucratic health professional organizations or are they better described as alternative women's health groups that espouse nonhierarchical philosophies of women's health? In this article, we describe an empirical study of one such group, the Michigan Midwives' Association, and explore the philosophies and practices of individual members as well as the internal organization of the group and its influence on members. Data were collected using individual telephone interviews with 48 of 50 members, group newsletters and documents, and two spokespersons who developed an oral history of the Association since its origin in 1978. Results suggest that the group plays an important role in reinforcing individually held philosophies about women-controlled birth and in providing social support to health workers practicing outside the traditional system.

Adult↗

Pancreatic enzymes in patients with end-stage renal disease maintained on hemodialysis.

We determined serum levels of total amylase, amylase isoenzymes, and lipase in a group of 34 asymptomatic patients with end-stage renal disease (ESRD) before and after hemodialysis. In addition, one ESRD patient was studied during an episode of acute pancreatitis. We also determined amylase activity in the saliva. The results were compared with those obtained in a group of 19 normal individuals. Predialysis serum total amylase activity in the 34 asymptomatic ESRD patients was significantly greater than that found in the control group, and remained unchanged after hemodialysis. Serum lipase activity in the 34 asymptomatic ESRD patients was significantly increased before hemodialysis, and rose further after hemodialysis. The observed rise in serum lipase activity correlated with the cumulative dose of heparin given during dialysis. None of the 34 asymptomatic ESRD patients showed a discernible P3 isoamylase band, despite elevation of serum total amylase level. In contrast, the patient with acute pancreatitis exhibited a marked rise in serum P3 isoamylase (14-17%), along with a marked and transient rise in serum total amylase and lipase above their elevated baseline values. Interestingly, the amylase content of saliva in the ESRD patients was significantly lower than that found in the control group. In conclusion, ESRD patients exhibit a marked elevation of serum amylase and lipase levels in the absence of clinical pancreatitis. The observed hyperamylasemia is not associated with increased P3 isoamylase level unless pancreatitis is present. Furthermore, serum lipase rises with hemodialysis, presumably because of the lipolytic effect of heparin used during this procedure. Accordingly, serum sample for lipase determination should be obtained before dialysis.

Adolescent↗

Vascular endothelial cells and granulopoiesis: interleukin-1 stimulates release of G-CSF and GM-CSF.

Cultured mononuclear phagocytes produce soluble factors that stimulate endothelial cells to release GM-colony-stimulating activity (GM-CSA). One such factor was recently identified as interleukin 1 (IL 1). Studies were designed to determine which types of granulopoietic factors are released by IL 1-stimulated endothelial cells. Supernatants from endothelial cells cultured for 3 days in medium containing IL 1 alpha and beta were tested in both murine and human CFU-GM colony growth assays. The effect of conditioned media on differentiation of WEHI-3B myelomonocytic leukemic cells was also examined. Control media containing IL 1 alone or unstimulated endothelial cell-conditioned media contained no detectable CSA in any bioassay. Medium conditioned by IL 1-stimulated endothelial cells stimulated the clonal growth of both human and murine CFU-GM and induced macrophage differentiation of WEHI-3B cells. Treatment of these conditioned media with a highly specific neutralizing monoclonal G-CSF antibody completely inhibited their activity in the murine CFU-GM assay, but only partially inhibited GM colony growth by human marrow. Treatment of the active conditioned media with a neutralizing rabbit anti-human GM-CSF antibody partially reduced the activity of the media in the human GM-colony growth assay. G-CSF radioimmunoassay of endothelial cell culture supernatants and Northern blot analysis of endothelial cell cytoplasmic RNA for GM-CSF gene transcripts confirmed that IL 1 induced expression of both G-CSF and GM-CSF genes. Because treatment of media with both antibodies abrogated all activity in the human GM colony growth assay, we conclude that IL 1-stimulated endothelial cells release both G and GM-CSF and that these are the only granulopoietic factors detectable in clonogenic assays released by these cells in vitro.

Animals↗

Quantitation of ceftetrame in human plasma and urine by high-performance liquid chromatography.

A method is described for quantifying ceftetrame, the acid metabolite of methylene (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- [(5-methyl-2H-tetrazol-2-yl)-methyl]-8-oxo-5-thia-1-azabicyclo[4.2 .0]oct-2-ene-2-carboxylate pivalate, an orally active cephalosporin. Sodium benzylpenicillin is added to the plasma as the reference standard. The compounds are extracted from plasma or urine using a Bond Elut phenyl column. An aliquot of the methanol eluate is analyzed by high-performance liquid chromatography using a Waters Nova-Pak phenyl column and a UV detector set to 225 nm. The ratios of the peak heights for ceftetrame and sodium benzylpenicillin are calculated and converted to concentrations of analyte with calibration curves that are generated from the analysis of analyte-free plasma or urine fortified with various amounts of ceftetrame and a fixed amount of sodium benzylpenicillin. For plasma, the limit of quantitation for the assay is 0.48 microgram/ml and the inter-assay precision (relative standard deviation) is 9.3%. For urine, the limit of quantitation for the assay is 19.1 micrograms/ml, and the inter-assay precision is 4.9%.

Adult↗

Therapeutic actions of alpha-human atrial natriuretic polypeptide in 16 clinical cases.

Alpha-human atrial natriuretic polypeptide (alpha-hANP) was applied to 16 clinical patients, 6 patients with essential hypertension, 7 patients with congestive heart failure and 3 patients with cirrhosis. Following intravenous bolus injection of 400 micrograms of synthetic alpha-hANP, a hypotensive effect of very rapid onset was found, which was more potent in the hypertensive patients than in the normotensive cases. Cardiac functions were improved significantly with a similar time course as the depressor response in the cases of heart failure or hypertension. Hemodynamic observations showed a marked increase in cardiac output, cardiac index, stroke volume, ejection fraction and ejection rate, and a concomitant decrease of the pressure in the right side of the heart and pulmonary circulation in these subjects. In addition, the renal response to alpha-hANP induced obvious increases in urine volume, electrolytes and creatinine excretions in all the subjects. Finally, plasma levels of aldosterone, Arg-vasopressin and noradrenaline were also altered by alpha-hANP. No significant side effects were registered. The above result confirms the therapeutic actions of alpha-hANP in human subjects and opens the possibility to research alpha-hANP as a powerful pharmacological tool as well as potential new medicine for human disorders.

Adult↗

Structure and evolution of human apolipoprotein genes: identification of regulatory elements of the human apolipoprotein E gene.

The structures of the major human apolipoprotein genes have been determined. The genes for apoE, apoC-I, apoC-II, apoC-III, apoA-I, apoA-II and apoA-IV have similar structures, consisting of four exons and three introns, which suggests that they evolved from a common ancestral gene. The third and fourth exons of the ancestral gene appear to have evolved from the duplication of a 66-nucleotide repeat unit that encodes a 22-residue alpha-helical peptide element of amphipathic character. The apoA-I, apoC-III and apoA-IV genes are linked closely within a 20-kilobase (kb) span of chromosome 11. The apoE and apoC-I genes, together with an apoC-I' pseudogene, are linked closely within a 25-kb span of chromosome 19. To characterize potential functional relationships among the apolipoprotein genes, initial studies have been done to identify the molecular elements involved in the regulation of the human apoE gene. Fragments of the 5'-flanking portion of this gene were inserted into appropriate plasmid vectors, which contained the bacterial chloramphenicol acetyl transferase gene, and were examined for promoter activity and potential enhancer activity after transfection into cultured mammalian cells. Deletion mapping of the promoter region has identified multiple functional elements, including an enhancer, two G-C boxes (Sp 1 transcription factor binding sites) and an upstream control element. In addition, there is an enhancer located in the first intron. Interactions among these various control elements are likely to determine the ways in which the expression of the apoE gene is regulated.

Apolipoproteins E↗

Pancreastatin and islet hormone release.

The effect of pancreastatin on the release of insulin, glucagon, and somatostatin was studied in the isolated perfused rat pancreas. After an initial equilibration period (-20 to 0 min) with a basal glucose concentration (3.3 mM), the pancreata were perfused with either 16.7 mM glucose (0-40 min) or with 20 mM arginine (0-20 min). Pancreastatin was introduced 10 min prior to and throughout the administration of the high glucose and arginine and continued during their perfusion. As expected, the glucose and the arginine augmented insulin and somatostatin release. Pancreastatin (1 and 10 nM) markedly suppressed the first phase of insulin release with both insulinogogues used, while the early somatostatin secretion was not significantly decreased. However, the peak incremental somatostatin response to arginine was reduced by 50% (P less than 0.05). Conversely, the peptide (10 nM) tended to augment arginine-induced glucagon release. Pancreastatin (100 nM) also suppressed glucose-stimulated insulin release from isolated rat islets. These pancreastatin-mediated alterations in islet hormone release are reminiscent of those known to characterize non-insulin-dependent diabetes. Therefore, the significance of pancreastatin in islet physiology and pathophysiology deserves special consideration.

Animals↗

Deposition and cross-linking of newly synthesized type IV procollagen in lung matrix.

Type IV procollagen (PC) is a major structural component of alveolar basement membranes; however, the mechanisms of type IV deposition in lung matrix have not been defined. We have examined the deposition and cross-linking of newly synthesized type IV in slices of adult rat lung. Type IV was rapidly deposited and selectively and covalently cross-linked in lung matrix. After a 4-h labeling with radioactive L-proline, greater than 40% of the newly synthesized type IV was insoluble in neutral salt buffers or 2 M guanidine-HCl (GuHCl). Re-extraction of the GuHCl residue in the presence of 10 mM dithiothreitol (DTT) recovered greater than 80% of the remaining type IV. By contrast, less than 20% of the total type IV PC was solubilized with 1 M NaCl containing as much as 50 mM DTT. The GuHCl plus DTT extracts contained pro alpha chains and aggregates of pro alpha chains stabilized by nondisulfide cross-links involving the pepsin-sensitive carboxy-terminal domain of the pro alpha 1 (IV) chain. There was a time-dependent increase in the recovery of type IV participating in intermolecular disulfide and nondisulfide bonds, and in the recovery of cross-linked amino-terminal domains (i.e., "7S-collagen"). Our results further support the hypothesis that the intact secreted form of type IV PC is a major structural subunit of pulmonary basement membranes, and demonstrate that the rapid insolubilization of type IV in lung matrix involves the formation of strong noncovalent interactions that are stabilized by intermolecular disulfide and nondisulfide bonds involving the terminal domains of type IV procollagen.

Animals↗

Antiserum developed for the E peptide region of insulin-like growth factor IA prohormone recognizes a serum protein by both immunoblot and radioimmunoassay.

Nucleotide sequencing of the two known cDNAs encoding human insulin-like growth factor I (IGF-I) predicts two different prohormone forms of IGF-I. The predicted prohormone amino acid sequences (E peptide regions) extend the carboxy-terminus of IGF-I by either an additional 35 (IGF-IA) or 77 (IGF-IB) amino acids. We developed an antiserum directed against a synthetic peptide which is unique to the E peptide region of IGF-IA prohormone. In a RIA using this antiserum, synthetic E peptide immunoreactivity was found in the serum of patients with chronic renal failure. The protein recognized by this antiserum has a mol wt of about 13,000 by neutral gel filtration and about 19,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. These data suggest that the E peptide region of the IGF-IA prohormone is expressed and circulates as part of the prohormone.

Blood Proteins↗

Atriopeptin and spontaneous hypertension in rats.

The involvement of atriopeptin in hypertension was investigated in spontaneously hypertensive rats (SHR). It was found that intravenous injection of atriopeptin III (20-80 nmol/kg) markedly decreased the mean arterial pressure in anesthetized SHR in a dose dependent manner. The heart rate was not significantly affected. The contents of atriopeptin immunoreactive material in the rat atrium and plasma were measured with radioimmunoassay. Both the atrium and plasma contents of atriopeptin immunoreactive material were found to be significantly higher in SHR than in the normotensive control Wistar Kyoto (WKY), indicating an increase in the biosynthesis and release of atriopeptin in SHR. Whether this change was a compensatory response induced by hypertension remains to be investigated.

Animals↗