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Biomedical subjects

P A Sullivan

Publications and source records attributed to P A Sullivan.

At least 19 recordsLinked to original sources

Enalapril versus combined enalapril and nadolol treatment: effects on blood pressure, heart rate, humoral variables, and plasma potassium at rest and during exercise in hypertensive patients.

The effect of enalapril alone and in combination with nadolol on resting and exercising blood pressure, heart rate, plasma renin activity, aldosterone, noradrenaline, and potassium levels was studied in 10 hypertensive patients (diastolic blood pressure between 95 and 114 mmHg). Patients received placebo for 4 weeks, enalapril (mean daily dose 24.5 mg) for 8 weeks, and nadolol, 40 mg once daily, was added for the remaining 8 weeks of the study. Exercise testing (modified Bruce, treadmill) was conducted at the end of the placebo run-in phase and at the end of each treatment period. Enalapril reduced resting and exercising blood pressure independent of any change in heart rate: This effect was increased with combination treatment. Plasma renin activity at rest and during exercise was increased by enalapril. Combination treatment attenuated this response and significantly reduced plasma aldosterone. Neither treatment had any effect on plasma noradrenaline levels. Resting plasma potassium levels were increased with combination treatment, whereas both treatment regimens increased plasma potassium levels during exercise. There were no clinically relevant episodes of hyperkalemia. Further investigation is required to qualify the nature of the blood pressure and plasma potassium response with combination treatment.

Adult

Short-term strenuous exercise training: effects on blood pressure and hormonal levels in mild hypertension.

The effect of a six-week strenuous exercise training programme (modified Bruce protocol, treadmill, three times per week) on resting and exercising blood pressure, heart rate, plasma catecholamines, chromogranin A, renin activity and aldosterone levels was investigated in 15 patients with mild hypertension. An identical exercise test was conducted at baseline and study close (six weeks). At follow-up, seven to ten days after study close, patients completed an exercise test of equivalent intensity to that at baseline, achieving comparable heart rate levels at maximal exercise. On each occasion, blood pressure, heart rate and hormonal variables were measured at rest (supine), maximal exercise and ten minutes after stopping exercise. Resting and exercising blood pressure and heart rate were reduced by the six-week exercise regimen. There was a trend, although not statistically significant, for resting plasma noradrenaline levels to be lower at study close. The reduction in blood pressure and heart rate at maximal exercise was associated with a significant attenuation of the plasma renin response to exercise. Plasma catecholamines also appeared to be lower after exercise training, although this effect was not statistically significant. Plasma levels of chromogranin A and aldosterone measured at rest and maximal exercise were not influenced by the exercise regimen. Further controlled studies are required to corroborate the results of this preliminary study.

Adult

A second gene for a secreted aspartate proteinase in Candida albicans.

The gene (PRA11) encoding a secreted aspartate proteinase of Candida albicans has been cloned and sequenced. The nucleotide and deduced amino acid sequences of PRA11 are 77 and 73% identical, respectively, with the reported sequences of PRA10 also cloned from C. albicans. Southern analyses indicated that the genome of each strain examined (ATCC 10231 and ATCC 10261) contains PRA10 and PRA11. Northern (RNA) analyses showed that PRA11 was expressed at a much higher level than was PRA10 when secretion of the proteinase by strain ATCC 10261 was induced with albumin.

Amino Acid Sequence

A secreted beta-glucan-branching enzyme from Candida albicans.

A Mr 34,000 wall protein was isolated as a by-product of the purification of an endo-(1-3)-beta-glucanase from the culture filtrate of Candida albicans. The purified fraction contained no exo- or endo-beta-glucanase activity, and analysis by SDS poly-acrylamide gel electrophoresis (SDS-PAGE) showed one protein band at Mr 34,000. Analysis by gel filtration high performance liquid chromatography (HPLC) of reaction products from incubations of the protein fraction with laminarioligosaccharides of five glucosyl units or greater revealed a unique glucanosyl transferase activity. The enzyme specifically cleaved laminaribiaose (G2) from the reducing-end of a linear beta-(1-3)-glucan and transferred the remainder to another laminarioligosaccharide. The reaction with laminaripentaose (G5) produced G2 and a product eluting at the position of G8. Analysis of the latter transferase product by 13C- and 1H-nuclear magnetic resonance (NMR) spectroscopy shows it to be a branched molecule containing a beta-(1-3)-beta-(1-6)-branchpoint. It is suggested that the Mr 34,000 wall protein is a glucan branching enzyme, perhaps the key enzyme responsible for the transformation of the initial linear beta-(1-3)-glucan into the branched beta-(1-3)-beta-1-6)-glucan as found in the cell wall of C. albicans.

1,4-alpha-Glucan Branching Enzyme

Subcritical flutter in collapsible tube flow: a model of expiratory flow in the trachea.

Using an axisymmetric geometry that retains certain qualitative features of the trachea, we extend one-dimensional modeling of flow in collapsible tubes to include both curved shell effects and, for untethered tubes, wall inertia. A systematic scaling of the finite deformation membrane equations leads to an approximate set which is consistent with the one-dimensional fluid model; axial and normal wall variables are coupled elastically, but only axial inertia is retained. Transverse curvature causes elastic coupling that can give rise to axial wall motion and a flutter instability. The source of instability is the product of a nonzero reference axial curvature with axial tension variation due to axial stretching. The numerical results suggest that this mechanism may be significant even in processes which cannot be assumed one-dimensional.

Biomechanical Phenomena

Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies.

Chromogranin-A (CgA) is an acidic soluble protein with a virtually ubiquitous occurrence in normal human neuroendocrine tissues. Of the many potential tissue sources of CgA immunoreactivity, which contribute to basal (unstimulated) circulating CgA? To explore this question we studied the effects of selective and nonselective suppression of secretion at several sites within the neuroendocrine system. Selective disruption of sympathetic outflow by trimethaphan decreased basal CgA by 25%, suggesting that sympathetic neurons contribute to circulating CgA. Plasma CgA in patients with unilateral and bilateral adrenalectomy fell within the range observed in normal subjects, weighing against the adrenal medulla as a major source of basal circulating CgA. Selective suppression of a variety of anterior and posterior pituitary cell types decreased plasma levels of the usual resident peptide hormones, but left plasma CgA unperturbed. After propranolol treatment, plasma CgA remained unaltered. Secretin suppressed plasma PTH and calcitonin, but did not alter plasma CgA levels. On the other hand, widespread nonselective suppression of a variety of neuroendocrine secretory cells by somatostatin decreased plasma CgA by 48%. Plasma catecholamines were unaltered by somatostatin infusion, suggesting that somatostatin inhibited CgA release from nonsympathoadrenal sources. During the infusion of somatostatin, the plasma epinephrine increment in response to insulin-induced hypoglycemia was maintained, and plasma CgA did not fall, nor did it rise after somatostatin cessation. Taken together, these findings suggest that somatostatin did not inhibit transport of stimulation-released CgA from the adrenal medulla to the circulation. In conclusion, although the adrenal medulla is the major tissue source of CgA immunoreactivity in man, other neuroendocrine sites, including sympathetic axons and multiple endocrine glands, appear to influence the basal circulating concentration of CgA.

Adrenal Glands

Changes in cell envelope glycoproteins during germ-tube formation of Candida albicans.

Germ-tube formation by Candida albicans induced by N-acetylglucosamine resulted in the appearance of a 43 kD protein in a cell envelope fraction. The protein increased quantitatively in the cell envelope during the emergence of the germ-tube and the amount in the envelope fraction reflected the efficiency of the morphogenesis. The 43 kD protein was labelled by the lactoperoxidase catalysed iodination procedure confirming a surface location for the antigen. Concanavalin A binding to the 43 kD protein demonstrated that this protein contained carbohydrate. Tunicamycin inhibited both germ-tube formation in C. albicans and the appearance of the 43 kD protein in the cell envelope fraction. Instead the presence of tunicamycin resulted in the appearance of a new protein of 39 kD molecular weight in the cell envelope which did not bind concanavalin A. Endoglycosidase H digestion of the 43 kD protein produced a 39 kD protein. Peptide mapping of the 43 kD protein from germ-tube cells and the 39 kD protein from tunicamycin-treated cells indicated that these proteins are homologous.

Autoradiography

Common-sense ethics in administrative decision making. Part I, Preparatory steps.

This is Part 1 of two articles demonstrating the relevance of business ethics to nurse administrators as they confront value-laden issues such as the advantages and disadvantages of 10-12-hour scheduling patterns, understaffing, emerging registered nurse partnerships, and other administrative problems. Common-sense ethics can serve as the basis of just administrative decisions. The authors present a model of preparatory attitudes and behaviors. The steps that they propose do not guarantee success, but if implemented, they may facilitate the nurse administrator's management of diverse ethical issues.

Commerce

Common-sense ethics in administrative decision making. Part II, Proactive steps.

This article is the second in a two-part study on common-sense ethics. In Part 1 (October 1991 JONA), the authors presented preparatory steps for the nurse administrator to consider in the management of diverse ethical issues. In Part 2, the authors delineate proactive steps to facilitate the resolution of administrative problems with economic, social, and ethical dimensions. They apply the model to the problem of the nursing shortage. Although no guarantees are assured in following the steps, decision making may be facilitated during the ethical conflict.

Decision Making, Organizational

Evidence for a role for secreted aspartate proteinase of Candida albicans in vulvovaginal candidiasis.

The presence of the secretory aspartate (acid) proteinase in the vaginal fluid of candidal vaginitis patients and controls was studied by ELISA and immunoblot (Western blot). In addition, a proteinase-deficient mutant strain of Candida albicans (IR24) was compared with the wild-type parent strain (10261) for ability to infect the vagina of pseudoestrus rats under estradiol treatment. Among the 67 women examined, proteinase was detected only in 22 harboring C. albicans (range, 42-233 ng/ml of vaginal fluid), at concentrations significantly higher in the 14 vaginitis patients than in the 8 asymptomatic fungal carriers. Western blots confirmed the presence of only one protein band of approximately 43 kDa, corresponding to that of the purified proteinase, in the ELISA-positive vaginal fluids. Experimental vaginal infection was significantly more extensive and persistent in rats infected with the proteinase-producer strain than in those challenged with the proteinase-deficient mutant, and the enzyme was detected in the vaginas of the former but not of the latter animals. Both strains 10261 and IR24 developed hyphal forms to a roughly similar extent during infection, and both showed a comparable adherence in vitro to vaginal and buccal epithelial cells. The clinical and experimental evidence support a role for secretory proteinase as a virulence factor in the pathogenesis of candidal vaginitis.

Adult

The secreted aspartate proteinase of Candida albicans: physiology of secretion and virulence of a proteinase-deficient mutant.

It was established that Candida albicans grew rapidly in a simple medium containing yeast extract (0.2%, w/v) plus glucose (2%, w/v). These cultures were in or near to a state of nitrogen limitation and the concentration of secreted aspartate proteinase increased rapidly (within 3-4 h) on addition of BSA. Synthesis and secretion were apparently controlled both positively (induction by albumin or, more probably, the peptides produced from it) and negatively (repression by NH4Cl). A small intracellular pool of the enzyme was detected during production of the enzyme and this pool decreased with the cessation of synthesis and secretion. A stable mutant, IR24, was isolated which secreted less than 0.3% of the amount of the proteinase exported by the parent strain ATCC 10261. The LD50 values for mutant IR24 and the parent strain administered intravenously to mice were greater than 1.0 x 10(9) and 1.6 x 10(6) c.f.u. kg-1 respectively.

Animals

Purification and properties of two lactose hydrolases from Trichosporon cutaneum.

Two enzymes that hydrolysed lactose were purified essentially to homogeneity from cell extracts of the oleaginous yeast Trichosporon cutaneum. One enzyme of Mr 120,000 had properties typical of a beta-galactosidase (EC 3.2.1.23). It hydrolysed lactose, lactulose and nitrophenyl-beta-D-galactosides. The enzyme required K+ or Rb+ for activity, and other monovalent cations tested were not effective. Enzyme activity was abolished by EDTA and stimulated by Mg2+, Mn2+ and Ca2+. The beta-galactosidase was induced by lactose, galactose, lactulose and lactobionic acid. The other enzyme, a beta-glycosidase (EC 3.2.1.21) of Mr 52,000 showed no ionic requirements and it hydrolysed lactose, nitrophenyl-beta-D-galactosides, 4-nitrophenyl-beta-D-glucoside, cellobiose, laminaribiose, laminaritriose and sophorose, but not gentiobiose, 4-nitrophenyl-beta-D-mannoside or sucrose. This enzyme was induced by lactose, galactose and lactulose, and also by cellobiose.

Cations

Is physiologic sympathoadrenal catecholamine release exocytotic in humans?

In cultured cells and isolated perfused organs, catecholamines are coreleased with chromogranin A (CgA) from adrenal chromaffin cells and sympathetic neurons. The corelease suggests that exocytosis is the mechanism of catecholamine secretion. To investigate whether physiologic catecholamine secretion is exocytotic in humans, we measured plasma norepinephrine, epinephrine, and CgA responses to differentiated stimuli of sympathoadrenal discharge. The CgA radioimmunoassay antibody recognized authentic CgA in normal human adrenal chromaffin vesicles. Insulin-induced hypoglycemia and caffeine ingestion, in decreasing order of potency, selectively stimulated epinephrine release from the adrenal medulla. During hypoglycemia, plasma levels of epinephrine and CgA rose, and peak plasma levels of epinephrine and CgA correlated, suggesting that gradations in epinephrine release represented gradations in exocytosis. However, significant increments in plasma CgA were not observed after caffeine ingestion. Furthermore, the rise of CgA levels during hypoglycemia lagged 60 minutes behind those of epinephrine. A less-pronounced temporal dissociation between CgA and epinephrine release was also shown in isolated chromaffin cells in vitro. Selective adrenal vein catheterization suggested a barrier to CgA transport across the adrenal capillary wall. Short-term, high-intensity dynamic exercise, assumption of the upright posture, prolonged low-intensity dynamic exercise, and smoking, in decreasing order of potency, stimulated norepinephrine release from sympathetic nerve endings. Only the first sympathetic neuronal stimulus resulted in significant increments in plasma CgA, increments considerably less than those attained during adrenal medullary activation by insulin hypoglycemia. During high-intensity exercise, peak plasma norepinephrine and CgA levels correlated, suggesting that gradations in norepinephrine release represented gradations in exocytosis. The human adrenal medulla was a far more prominent tissue source of CgA than human sympathetic nerves--adrenal medullary homogenates contained 97-fold more CgA (micrograms/g) than sympathetic nerve homogenates. In conclusion, catecholamine secretion during selective stimulation of either sympathetic nerves or the adrenal medulla is, at least in part, exocytotic. Furthermore, stimulation of the former results in comparatively modest changes in plasma CgA compared with changes attained during stimulation of the latter. CgA appears to be transported by a route different from that of catecholamines from adrenal medullary chromaffin cells to the circulation in vivo.

Adrenal Glands

Policy considerations related to AIDS.

The nurse administrator faces many legal obligations as well as administrative responsibilities in the care of patients and staff with AIDS infection or at risk of infection. The authors discuss several resources nurse administrators can use to develop and implement policy for patients and staff at risk for or with AIDS infection.

Acquired Immunodeficiency Syndrome

Fosenopril, an angiotensin-converting enzyme inhibitor, and propranolol: comparative effects at rest and exercise on blood pressure, hormonal variables, and plasma potassium in essential hypertension.

Fosenopril sodium, a prodrug, is converted to its active diacid during and after intestinal absorption. Its excretion is equally divided between hepatic and renal routes. This placebo-controlled, randomized, double-blind, parallel group study evaluated the efficacy and safety of fosenopril compared to propranolol, at rest and during exercise, on blood pressure, plasma potassium, plasma renin activity, and plasma aldosterone. Exercise testing utilized bicycle ergometry, and individual subjects underwent an identical exercise protocol on placebo and on active treatment. The fosenopril group comprised nine subjects who were matched to nine subjects on propranolol. Blood pressure fell significantly and equally at rest (fosenopril--157/103 to 141/95 mmHg, p less than 0.005; propranolol--159/100 to 149/90 mmHg p less than 0.005) and during exercise in both groups. Plasma potassium fell significantly at rest (4.25 to 3.98 mmol/l, p less than 0.05) and during exercise (5.18 to 4.87 mmol/l, p less than 0.05) on fosenopril, but rose in subjects on propranolol during exercise (4.99 to 5.44 mmol/l, p less than 0.01). Plasma renin activity rose on fosenopril and fell on propranolol. Plasma aldosterone was uninfluenced by either drug. Fosenopril was well tolerated and its antihypertensive profile is similar to that of beta blockers and other ACE inhibitors.

Aldosterone

Strenuous short-term dynamic exercise: effects on heart rate, blood pressure, potassium homeostasis, and packed cell volume in mild hypertension.

This study examined the effect of strenuous short-term dynamic exercise on the heart rate, blood pressure, plasma potassium and packed cell volume in mildly hypertensive subjects. At baseline a symptom-limited Bruce Exercise Protocol was carried out with blood pressure, heart rate, plasma potassium and packed cell volume measurements at fixed time points at rest and during and after the exercise. After 6 weeks of taking exercise sessions (Bruce protocol) to fatigue three times a week, the subjects were restudied. Blood pressure and the heart rate fell significantly at rest and during and after exercise. The packed cell volume was higher at all study points and plasma potassium was higher in the postexercise period after the exercise conditioning. Strenuous short-term exercise has a beneficial antihypertensive effect, raises packed cell volume and has a favourable effect on plasma potassium homeostasis.

Adult

Identification of envelope proteins of Candida albicans by vectorial iodination.

Intact Candida albicans yeast cells were radiolabelled with 125I, and cell wall, mixed membrane and soluble fractions prepared. The majority (67%) of the 125I was detected in the protein of the cell wall fraction at a specific activity 70-fold higher than that in the membrane or soluble fractions. SDS treatment of the cell wall fraction released 52% of the total protein but only 3% of the wall-bound 125I, and the extract was shown to be severely contaminated with cytosolic and membrane proteins. Zymolyase digestion of SDS treated walls liberated material which contained 93% of the 125I and on electrophoresis migrated as a single diffuse zone (average Mr 260 kD) typical of heterogenous mannoproteins. Protein (1.5%), GlcN (0.08%) and hexose (98.4%) content was measured and amino acid analysis showed enrichment in Ser (15.9%) and Thr (20.2%). These results indicate that the major iodinated protein(s) in the cell envelope is a 260 kD mannoprotein fraction containing both O-linked and Asn-linked oligosaccharides.

Amino Acids