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W Hsueh

Publications and source records attributed to W Hsueh.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effect of fasting on hyperoxic lung injury in mice. The role of glutathione.

Fasted mice exposed to 100% oxygen have more lung damage and die sooner than do fed mice. The mechanism responsible for this phenomenon has not been identified. We performed the following experiments to test the hypothesis that reduced glutathione content in lung tissue of fasted mice contributes to the increased susceptibility to hyperoxic lung damage. First, air-exposed mice were fasted for as long as 3 days. They had little change in lung levels of superoxide dismutase (SOD) or catalase, but they had a 41% decrease in glutathione by Day 3 (p less than 0.001). Second, fed mice and fasted mice were exposed to 100% oxygen for as long as 4 days. Both groups had nearly identical values of lung SOD and catalase, but the fasted mice had lower levels of glutathione (p less than 0.001). Third, fed mice received the glutathione synthesis inhibitor buthionine sulfoximine (BSO; 20 mM) in their drinking water for 2 wk and were then exposed to either air or 100% oxygen. Air-exposed mice receiving BSO for 14 days had no change in lung SOD content, a 43% increase in catalase (p less than 0.001), and a 41% decrease in glutathione (p less than 0.01). Oxygen-exposed, BSO-treated mice had no change in SOD and an increase in catalase, but lower glutathione levels, more deaths, and increased lung damage on Day 3 (BAL protein: 1.72 +/- 0.21 versus 0.94 +/- 0.08 mg/ml; p less than 0.01) than did diluent-treated mice. Fourth, fasted mice were given liposomes containing glutathione intratracheally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn.

Platelet activating factor (PAF) is an endogenous phospholipid mediator that causes pulmonary hypertension and thrombocytopenia in experimental animal models. To investigate circulating PAF in persistent pulmonary hypertension of the newborn (PPHN), we studied PAF and its degradative enzyme, acetylhydrolase. Thirteen neonates with PPHN, diagnosed by routine clinical methods including echocardiography, were compared to six age-matched control patients with respiratory distress. Overall, plasma PAF levels were elevated in patients with PPHN compared to control patients (20.1 +/- 3.9 versus 1.6 +/- 0.7 ng/ml, p less than 0.01). In addition, plasma PAF concentrations in patients with PPHN correlated with the severity of disease as defined by the delta AaPO2 (r = 0.65, p = 0.015). In three patients with elevated PAF levels, as the clinical status improved, the plasma PAF values decreased. Acetylhydrolase activity was similar in both groups (3.96 +/- 0.90 versus 3.78 +/- 1.44 nmol/ml/min, p = NS). We conclude that PAF production is increased in PPHN and that abnormal production of PAF may be associated with pulmonary hypertension.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

Effects of in vivo 'priming' on endotoxin-induced hypotension and tissue injury. The role of PAF and tumor necrosis factor.

Exogenously administered tumor necrosis factor-alpha (TNF) and bacterial endotoxin (LPS) induce shock and tissue injury. Here, the authors studied the effect of endogenous TNF on LPS-induced hypotension and tissue injury and investigated the role of PAF in these responses. Rats were primed with intraperitoneal injection of zymosan 24 hours before, or Bacillus Calmette-Guérin (BCG) 12 to 15 days before intravenous injection of low dose (0.5 mg/kg) LPS. It was found that nonprimed animals showed mild hypotension and moderate leukopenia in response to LPS. In contrast, zymosanprimed rats developed shock and marked leukopenia, and more severe bowel injury than nonprimed rats. The authors then showed that, following LPS injection, zymosan-primed animals had higher TNF and platelet-activating factor (PAF) levels than nonprimed rats. Pretreatment of the animal with PAF antagonist, SRI 63-441, markedly ameliorated the hypotension and tissue injury. Interestingly, BCG-primed rats did not show aggravation of LPS-induced hypotension. Only TNF (but not PAF) level in these animals was increased. Thus, it appears that TNF release alone, without a sufficient increase in PAF, is incapable of causing severe hypotension. However, most of the BCG-primed animals showed tissue injury, which could be prevented by pretreatment with PAF antagonist. The authors discuss the possible mechanisms of this discrepancy between systemic and local responses in BCG-primed animals.

Animals↗
PubMed1990

The role of the complement system in shock and tissue injury induced by tumour necrosis factor and endotoxin.

It has previously been shown that tumour necrosis factor-alpha (TNF), together with bacterial lipopolysaccharide (LPS), induces shock and bowel necrosis in the rat. Since the complement system plays an important role in inflammation and tissue injury, its role has been studied in a similar model in mice. In most of the present experiments, a low dose (0.2 micrograms/g) of TNF was used for priming, followed 30 min later by LPS (3 micrograms/g), and the experiment was terminated in 150 min. It is shown that: (i) TNF exerts no systemic effects by itself; LPS elicits only mild hypotension but causes no lethality; (ii) TNF-primed mice show exaggerated effects of shock, hypothermia, haemoconcentration and bowel injury after LPS; the majority of these mice died within 150 min; (iii) administration of LPS alone mildly activates the complement system in vivo, while TNF alone has no effect; (iv) the effects of TNF and LPS on complement activation are synergistic; (v) the acute development of shock and bowel injury in response to TNF-LPS is dependent on an intact complement system, more specifically C5, since C5-deficient mice were protected from TNF-LPS-induced shock and tissue injury; C5-deficient mice also showed less hypotension, hypothermia, haemoconcentration and better intestinal perfusion compared with C5-sufficient animals; (vi) however, when the priming dose of TNF was raised to 0.5 micrograms/g, most of the C5-deficient mice developed marked hypothermia, hypotension, haemoconcentration, bowel injury and died. Thus, it is concluded that TNF and LPS act synergistically in activating the complement system, which plays an important role in mediating the tissue injury and lethality induced by these agents.

Animals↗
PubMed1989

Surgery for duplex kidneys with ectopic ureters: ipsilateral ureteroureterostomy versus polar nephrectomy.

Conventional surgery for the ectopic ureter stresses polar nephrectomy, while preserving a functioning upper pole by ipsilateral ureteroureterostomy is performed less commonly. During the last 15 years we operated on 35 children for ectopic ureter. High ipsilateral ureteroureterostomy (15 patients) was performed when the upper pole cortex appeared to be smooth and pink, and the anastomosis was surgically feasible. Upper pole nephrectomy and upper ureterectomy (21 patients) were performed when the involved segment appeared grossly to be pale, cystic or otherwise abnormal. One low ipsilateral ureteroureterostomy was performed concomitant with contralateral ureteral reimplantation. Complications after ipsilateral ureteroureterostomy and partial nephrectomy were similar. Histological evidence of dysplasia of the polar nephrectomy specimens was focal in 7 patients (33 per cent), marked in 2 (10 per cent) and not detected in 12 (57 per cent). Ipsilateral ureteroureterostomy is an appropriate means to manage the ectopic ureter in selected cases because dysplasia in these upper pole renal units seldom is significant, and because ipsilateral ureteroureterostomy and polar nephrectomy have similar postoperative morbidity rates.

Child↗
PubMed1989

Pharmacological manipulation of inflammation in rabbit hydronephrosis: effects of a combined cyclooxygenase/lipoxygenase inhibitor ethoxyquin, a thromboxane synthase inhibitor RS-5186 and a PAF antagonist L-659,989.

The rabbit hydronephrotic kidney (HNK) is a model of renal inflammation characterized by a marked increase in arachidonic acid metabolism that is temporally associated with an inflammatory cell influx into the injured tissue. The HNK exhibits an exaggerated elaboration of eicosanoids ex vivo in response to either bradykinin or the inflammatory cell agonist n-formyl-methionyl-leucyl-phenylalanine (fMLP) compared with the unobstructed contralateral kidney. To pharmacologically manipulate inflammatory cell influx into the HNK we administered ethoxyquin (200 mg/kg p.o.), a combined cyclooxygenase/lipoxygenase inhibitor, RS-5186 (10 mg/kg p.o.), a thromboxane synthase inhibitor or L-659,989 (5 mg/kg p.o.), a platelet activating factor antagonist, before and at various times during the development of hydronephrosis. Only ethoxyquin reduced inflammatory cell influx into the HNK and thereby prevented the enhancement of microsomal cyclooxygenase activity and attenuated the elaboration of eicosanoids ex vivo. Collectively, these results suggest a primary role of an eicosanoid, possibly leukotriene B4, but not thromboxane A2 or the chemotactic phospholipid, platelet activating factor, as a mediator of inflammatory cell influx resulting from ureter obstruction.

Animals↗
PubMed1988

Bilateral adrenal ganglioneuroblastoma with neuromelanin. Clinical and pathologic observations.

A case of bilateral adrenal ganglioneuroblastoma in an adolescent boy is described. The clinical evolution was remarkable for its quiescent course, despite unfavorable prognostic indicators that included: intraabdominal primary site, large tumors on both sides of the midline, and "unfavorable" pathologic subtype. There was no family history of neuroblastomas. Production of neuromelanin was manifested by this unusual tumor. A review of published cases of multifocal neuroblastomas suggests that these tumors follow an uncommon natural history, at variance with the expected behavior of the usual unicentric and sporadic type of neuroblastoma.

Adolescent↗
PubMed1988

Sequential release of leukotrienes and norepinephrine in rat bowel after platelet-activating factor. A mechanistic study of platelet-activating factor-induced bowel necrosis.

We have developed a model of ischemic bowel necrosis in the rat by injecting synthetic platelet-activating factor into the mesenteric vascular bed. Our previous studies have shown that the development of ischemic necrosis was not due to thrombus formation, but to release of vasoconstricting mediators from the intestinal tissue, such as leukotriene C4. However the release of leukotriene C4 was transient and could not account for the prolonged intestinal vasoconstriction. In the present study, we show that (a) the release of norepinephrine from intestinal tissue was increased after injection of platelet-activating factor, and was responsible, at least in part, for the prolonged vasoconstriction; (b) in vivo treatment with reserpine abolished both the prolonged vasoconstriction and the release of norepinephrine from the perfused small intestine; (c) the release of norepinephrine was largely secondary to leukotriene C4 production and direct injection of leukotriene C4 caused catecholamine release; and (d) there was a concomitant release of epinephrine (of a lesser magnitude) after injection of platelet-activating factor.

Animals↗
PubMed1988

Role of oxygen derived free radicals in platelet activating factor induced bowel necrosis.

The mechanism of tissue and cell injury in ischaemic bowel necrosis is unclear. The present study investigated the role of oxygen derived free radicals in the development of bowel necrosis using injections of platelet activating factor (PAF) into the mesenteric vasculature. Animals were pretreated with allopurinol or superoxide dismutase together with catalase, before administration of PAF. Superoxide dismutase/catalase markedly improved the PAF-induced lesions, indicating that most of the intestinal damage after PAF injection is because of the release of oxygen radicals. The major source of oxygen radicals is xanthine oxidase, as allopurinol ameliorated small bowel lesions. Pretreatment with allopurinol produced a significant (p less than 0.01) preventive effect on PAF induced hypotension. In contrast, superoxide dismutase/catalase did not alter PAF induced hypotension. Superoxide dismutase/catalase pretreatment improved PAF induced haemoconcentration and leucopenia, while allopurinol showed no effect.

Allopurinol↗
PubMed1988

Hyperoxic lung damage in mice: appearance and bioconversion of peptide leukotrienes.

High concentrations of oxygen damage the lung and increase bronchoalveolar lavage (BAL) fluid levels of leukotrienes. We sought to identify the specific leukotrienes produced and their relationship to the severity of the lung damage and the inflammatory cell populations by exposing mice to 100% oxygen for up to 4 days. Leukotrienes were not detected in BAL fluid from air-exposed mice. Leukotriene D4 (LTD4) was found after 2 days of exposure to 100% oxygen, increased with longer periods of exposure, and then decreased while LTE4 appeared when the lung damage became severe. LTB4 and LTC4 were not found at any time. Neutropenic mice had identical results, indicating that neutrophils were not the source of the leukotrienes. To determine why LTC4 was not found and why LTD4 decreased and LTE4 increased on day 4, we measured the metabolic capacity of BAL supernatant for leukotrienes. Incubation of LTD4 in BAL supernatant from air-exposed mice resulted in the conversion of LTD4 to LTE4, which was blocked by L-cysteine, a dipeptidase inhibitor. Faster conversion occurred after exposure to 100% oxygen for 3 and 4 days. The rate of bioconversion correlated with the BAL protein concentration (r = 0.756, P less than 0.001), and it was similar in neutropenic and nonneutropenic mice. Little LTC4 and no LTE4 were converted in BAL supernatant from air- or oxygen-exposed mice. The early and progressive increase in LTD4 suggests that sulfidopeptide leukotrienes may play a role in the pathogenesis of hyperoxic lung damage. The increased dipeptidase activity during hyperoxic exposure may serve a protective role by converting the more potent LTD4 to the less potent LTE4.

Animals↗
PubMed1988

Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor.

We have developed a rat model of ischemic bowel necrosis associated with shock by injection of platelet-activating factor (PAF) or a combination of PAF and endotoxin. Recent investigations have shown that tumor necrosis factor (TNF) also induces shock and necrosis of the gastrointestinal tract. The morphological changes of TNF-induced bowel lesions are indistinguishable from those caused by PAF. The mechanism of TNF-induced bowel necrosis is unclear. In the present study, we have shown that (a) TNF caused PAF production in bowel tissue; (b) the effects of TNF and LPS on PAF production in the intestine are additive; (c) TNF and LPS are synergistic in inducing bowel necrosis; and (d) TNF-induced bowel necrosis is due to PAF release and can be prevented by pretreatment with PAF antagonists.

Animals↗
PubMed1988

Role of the lipoxygenase pathway in angiotensin II-mediated aldosterone biosynthesis in human adrenal glomerulosa cells.

We studied the role of the lipoxygenase pathway of arachidonic acid metabolism in angiotensin II (AII)-stimulated aldosterone secretion in normal and adenomatous human adrenal glomerulosa tissue. In freshly isolated normal adrenal glomerulosa cells, the AII-mediated stimulation of aldosterone secretion was not altered by cyclooxygenase blockade with ibuprofen. In contrast, BW755c (10(-5) mol/L), a nonselective lipoxygenase inhibitor, and baicalein (10(-6) mol/L), a more selective 12-lipoxygenase blocker, inhibited AII-mediated aldosterone secretion, but did not alter basal aldosterone secretion. The glomerulosa cells produced the lipoxygenase products 12- and 15-hydroxyeicosatetraenoic acid (HETE) in the basal state, as measured by high pressure liquid chromatography and RIA. However, AII selectively stimulated only 12-HETE production [basal, 1329 +/- 207 (+/- SE) pg (3.99 +/- 0.62 pmol)/10(5) cells.h; AII, 2365 +/- 333 (7.09 +/- 1.0); n = 9; P less than 0.02], suggesting that 12-lipoxygenase activation may be involved in AII-mediated aldosterone secretion by normal cells. In addition, the lipoxygenase inhibitors that blocked AII-mediated aldosterone secretion also prevented AII-mediated 12-HETE formation. In contrast, neither ACTH nor K+ stimulated 12-HETE formation, suggesting that 12-lipoxygenase activation is primarily involved in AII action in normal glomerulosa cells. BW755c caused a marked dose-dependent inhibition of basal aldosterone secretion in freshly isolated cells from aldosterone-producing adenomas [APA; basal, 66 +/- 3 ng (182 +/- 8 pmol)/10(6) cells.h; 10(-5) mol/L BW755c, 49 +/- 2 (136 +/- 6); 10(-4) mol/L BW755c, 30 +/- 2 (83 +/- 6)]. In contrast, the cyclooxygenase inhibitor indomethacin and the selective 5-lipoxygenase inhibitor U60257 did not alter basal aldosterone secretion by these cells. The APA cells produced 12- and 15-HETE, and BW755c at the same dose that inhibited aldosterone secretion also inhibited the production of both 12- and 15-HETE. In the cultured APA cells, AII-stimulated aldosterone secretion was inhibited by BW755c [basal, 26 +/- 8 pg/mL (72.0 +/- 22.1 pmol/L); AII, 336 +/- 79 (930 +/- 218); AII plus BW755c, 92 +/- 38 (255 +/- 105) n = 13; P less than 0.01]. The lipoxygenase products 12- and 15-HETE restored the stimulatory effect of AII during inhibition by BW755c, indicating a role for these lipoxygenase pathways in AII-mediated aldosterone secretion in APA cells. These results suggest that the stimulatory effects of AII on aldosterone secretion are mediated by stimulation of the lipoxygenase pathway in human zona glomerulosa cells.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

Central and renal hemodynamic effects and hormonal response to diltiazem in severe congestive heart failure.

The central and renal hemodynamic effects and the hormonal response to single doses of 60 mg and 90 mg of diltiazem were evaluated in 10 patients with severe chronic left ventricular (LV) systolic dysfunction (ejection fraction 0.22 +/- 0.08). Diltiazem administration resulted in only mild and mostly statistically insignificant changes. After 60 mg, only heart rate (from 86 +/- 10 beats/min at baseline to 79 +/- 14 beats/min at 4 hours) and pulmonary vascular resistance (from 231 +/- 108 to 165 +/- 74 dynes s cm-5 at 4 hours) changed significantly. Administration of 90 mg of diltiazem resulted in no significant change in any of the measured or calculated central hemodynamic variables. Individual data, however, revealed an increase stroke volume index in 3 patients but a decrease in 1 patient and a persistent increase in mean pulmonary artery wedge pressure in another patient. These hemodynamic changes were not associated with symptomatic deterioration in any of the patients. Both renal blood flow and glomerular filtration rate were impaired at baseline on both days and did not show a significant change 1, 2 and 4 hours after diltiazem administration. Similarly, no significant change was noted after either diltiazem dose in plasma catecholamine levels and renin concentration. In conclusion, administration of 60 to 90 mg of diltiazem in patients with severe chronic LV systolic dysfunction results in only mild and mostly insignificant acute effects on central and renal hemodynamics, plasma hormonal levels and patient clinical status.

Diltiazem↗
PubMed1987

Platelet-activating factor: an endogenous mediator for bowel necrosis in endotoxemia.

We have developed a model of isochemic bowel necrosis in the rat by injecting platelet-activating factor (PAF) or PAF in combination with bacterial endotoxin. PAF causes profound hypotension, and it has been suggested that it is released during endotoxin shock. Because ischemic bowel necrosis is often associated with shock or infection, it is possible that PAF is the endogenous mediator that causes shock and bowel necrosis during sepsis. In this study, we have demonstrated that: 1) normal intestine contained a small amount of PAF; 2) necrotic lesions of the intestine could be induced by endotoxin injection; 3) PAF production in the bowel is markedly increased in animals treated with endotoxin; 4) pretreatment of the animal with PAF antagonists prevent endotoxin-induced necrosis; 5) isolated, buffer-perfused small intestine produced a small quantity of PAF in response to endotoxin injection. Therefore, we conclude that PAF is a likely endogenous mediator in endotoxemia, which causes bowel necrosis and shock.

Animals↗
PubMed1987

Large-cell lymphoma. Diagnostic difficulties and case study.

The present report describes the difficulties attending the establishment of a correct diagnosis in an adolescent patient with a large retroperitoneal tumor. It is known that clinical and pathologic findings may sometimes be insufficient to effect a distinction between germ-cell and lymphomatous origin of a large-celled neoplasm. Our purpose is to demonstrate that these difficulties may persist even when current methods of morphologic study, including electron microscopy, are complemented with the application of many antibodies that are commonly available for immunohistologic use. In the young, the differential diagnosis of large-celled neoplasm must include "rhabdoid" tumor, and the poorly characterized nature of this neoplasm compounds the unusually difficult diagnostic dilemma. Our problem case expressed none of many lymphoid tissue markers used, was positive for epithelial membrane antigen (EMA), and was comprised of so-called "anemone" cells visible by electron microscopy, which appearance may correspond to that of carcinomas or lymphomas. Study of gene rearrangement provided additional evidence that the neoplasm was of lymphomatous origin, by showing rearrangement of genes for immunoglobulins. This valuable technique has an important place in diagnostic surgical pathology.

Adolescent↗
PubMed1987

Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure.

Sustained therapy with nitroglycerin (NTG) has been reported to provoke the development of early tolerance. Because continuous intravenous NTG infusion is commonly used in patients with coronary artery disease and heart failure, we evaluated the incidence of early tolerance developed within the first 24 hr of therapy in 31 responders to NTG. After documentation of response to NTG, defined as a 10 mm Hg or greater or a 30% or greater reduction in mean pulmonary arterial wedge pressure (PAWP), 16 patients were blindly, randomly assigned to receive placebo and 15 patients were continued on same-dose NTG. Both groups showed an identical fall in PAWP at peak NTG titration (11 +/- 4 mm Hg). Discontinuation of NTG in the placebo group resulted in a rapid increase in PAWP to levels not significantly different from baseline (19 +/- 5 mm Hg at 2 hr vs 23 +/- 6 mm Hg at baseline; p = NS). In the NTG group, PAWP fell from 27 +/- 9 to 14 +/- 7 mm Hg, was 16 +/- 9 mm Hg at 2 hr (p less than .05 vs baseline), and continued to be significantly lower than baseline for 8 hr; however, due to attenuation of effect, PAWP values at 12, 20, and 24 hr were not significantly different from placebo or baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗