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Biomedical subjects

S L Wu

Publications and source records attributed to S L Wu.

At least 73 records · Page 4Linked to original sources

Role of endotoxaemia in hyperdynamic circulation in rats with extrahepatic or intrahepatic portal hypertension.

This study investigated the role of endotoxaemia in the development of hyperdynamic circulation observed in rats with extrahepatic (high collateralization) or intrahepatic (low collateralization) portal hypertension. Compared with sham-operated rats, decreased mean arterial pressure and systemic vascular resistance were detected on days 1, 4, and 14 following partial portal vein ligation. By day 1, the cardiac index of portal vein-ligated rats was similar to that of sham-operated rats and progressively increased, thereafter, reaching statistically higher values days 4 and 14. No differences in plasma endotoxin levels were found between portal vein-ligated and sham-operated rats throughout the observation period. Both carbon tetrachloride-induced cirrhotic rats with and without ascites had a higher cardiac index and lower systemic vascular resistance. Plasma endotoxin levels were higher in cirrhotic rats with ascites (8.6 +/- 2.0 pg/mL; P < 0.01) than those of control rats (2.2 +/- 0.3 pg/mL) and cirrhotic rats without ascites (2.4 +/- 0.6 pg/mL). These results suggest that factors other than endotoxaemia play a role in the development of hyperdynamic circulation observed in rats with extrahepatic portal hypertension and cirrhotic rats without ascites, but that endotoxaemia may contribute to the maintenance of hyperdynamic circulation found in cirrhotic rats with ascites. The severity of liver disease may be a more important factor than the presence of portosystemic shunting for the development of endotoxaemia in portal hypertensive states.

Animals↗

Effect of verapamil on renal haemodynamics in a portal hypertensive rat model.

In order to investigate the effects of verapamil on renal haemodynamics in rats with portal hypertension, verapamil was given at either a low (0.2 mg/kg) or high (2 mg/kg) dose to rats after portal vein ligation. An approximate 12% decrease in mean arterial pressure followed administration of low dose verapamil, with a significant decrease in cardiac output and renal blood flow, as well as reduced portal pressure, observed; these signs were all indicative of a rise in renal vascular resistance. In contrast, the marked fall in both mean arterial pressure and cardiac output with high dose verapamil, accompanied by a significant decrease in portal pressure and no change in renal blood flow, suggests a reduction in renal vascular resistance. This study shows that the acute effects of verapamil on renal haemodynamics may vary with the dose used. Also, acute verapamil administration tends to decrease renal blood flow to alter the autoregulation of the kidney; thus, caution should be taken in the clinical use of verapamil in the treatment of cirrhosis with portal hypertension.

Animals↗

Clinical significance of complements in ascitic diseases: elevated complement levels disapproving the liver disease origin.

In a two-year period, ascitic fluid concentrations of complement 3c and complement 4 were measured in 110 patients with sterile cirrhotic ascites, 31 patients with spontaneous bacterial peritonitis, 65 patients with hepatocellular carcinoma, 36 patients with peritoneal carcinomatosis and 12 patients with miscellaneous diseases (nephrotic syndrome 4, systemic lupus erythematosus 3, secondary peritonitis 2, cardiac ascites 1, eosinophilic peritonitis 1 and tuberculosis peritonitis 1) to assess the clinical utility of ascitic fluid complements. The ascitic fluid level of complements 3c or C4 was significantly higher in patients with peritoneal carcinomatosis (32.8 +/- 10.2, 13.4 +/- 7.4 mg/dL) than in patients with sterile cirrhotic ascites (9.2 +/- 5.2, 4.5 +/- 3.9 mg/dL, p < 0.001), spontaneous bacterial peritonitis (8.2 +/- 4.1, 3.8 +/- 2.4 mg/dL, p < 0.001) or hepatocellular carcinoma (12.8 +/- 8.3, 5.6 +/- 4.4 mg/dL, p < 0.001). However, it was not significantly different from the miscellaneous disease group. To verify that ascites formation is not related to liver disease origin, diagnostic sensitivity, specificity and accuracy were 83.3%, 92.7% and 90.9%, respectively, by the ascitic fluid level of complement 3c higher than the cut-off value (20 mg/dl); or 60.4%, 89.8% and 84.3%, respectively, by the ascitic fluid level of complement 4 higher than the cut-off value (10 mg/dL). A direct correlation was found between the ascitic fluid protein level and the ascitic fluid complement 3c (r = 0.70) or complement 4 (r = 0.57) level. Based on results in this study, we can conclude that measuring ascitic fluid complements is clinically useful in disapproving the liver disease origin of ascites formation. However, it is of little value in diagnosing spontaneous bacterial peritonitis or hepatocellular carcinoma.

Ascites↗

Sequential hemodynamic changes for large volume paracentesis in post-hepatitic cirrhotic patients with massive ascites.

Large volume paracentesis (4.8 to 15.5 liters) was performed in 42 patients with post-hepatitic cirrhosis and massive ascites, not only to derive parameters capable of predicting the development of severe clinical hypotension after large volume paracentesis, but also to determine the optimal time to introduce preventive volume expanders. Systemic hemodynamics were sequentially measured for 72 hours in thirty-two patients. Severe clinical hypotension occurred in 13 (31.0%) patients 4-62 hours from the start of paracentesis. Univariate analysis, with the Mantel-Cox test used to compare Kaplan-Meier curves, and the subsequent multivariate analysis by stepwise Cox regression procedure were utilized to identify two variables, withdrawn ascitic fluid greater than 7.5 liters (p = 0.0121) and the absence of peripheral edema (p = 0.0148), reaching statistical significance to predict the occurrence of severe clinical hypotension. Compared to the baseline value, the cardiac output of patients not developing severe clinical hypotension increased (6.26 +/- 0.66 vs. 6.65 +/- 0.69 liter/min, p < 0.01) one hour from the start of paracentesis and right atrial pressure decreased (11.2 +/- 2.4 vs. 8.7 +/- 2.3 mmHg, p < 0.05). The cardiac output returned to the baseline value at the 9th hour. Based on the results presented herein, we can conclude that severe clinical hypotension occurs in a high percentage of patients with post-hepatitic cirrhosis and massive ascites within 72 hours from the start of large volume paracentesis. At potential risk of this occurring are those patients without peripheral edema and withdrawn ascitic fluid greater than 7.5 liters. Volume expanders should be introduced before 4th hour from the start of large volume paracentesis.

Adult↗

Characterization of recombinant polioviruses expressing regions of rotavirus VP4, hepatitis B surface antigen, and herpes simplex virus type 2 glycoprotein D.

Recombinant polioviruses expressing antigens from rotavirus, herpes simplex virus type 2, and hepatitis B virus were generated. Fusion of the heterologous polypeptides to the amino terminus of the poliovirus polyprotein did not prevent myristylation of VP0, suggesting a novel mechanism of myristylation for these recombinant viruses. The effects of the parental genetic background, different foreign sequences, and different insert sizes on growth characteristics were compared. Both the size and the nature of the heterologous sequence appeared to be factors influencing the growth and stability of recombinant polioviruses. All of the recombinants showed a temperature-sensitive phenotype, regardless of the genetic background (attenuated or wild type) from which they were derived. Preliminary studies with transgenic mice carrying the poliovirus receptor gene are discussed.

Animals↗

A model of experimental acute necrotizing pancreatitis.

BACKGROUND: A model of moderate acute necrotizing pancreatitis is essential for the study of the pathophysiology of the disease and novel therapies. We tried to establish a model of bile salt-induced acute necrotizing pancreatitis in rats. METHODS: Acute pancreatitis was induced by retrograde infusion of bile salt into the cannulated pancreatobiliary duct. Twenty-six rats wee divided into 3 groups. Group I (n = 8) received 0.2 ml of glycodeoxycholic acid (GDOC) 10 mmol/l; group II (n = 10) 0.2 ml of 2.5% sodium taurodeoxycholate (NaTDC); group III (n = 8) the mixture of 0.2 ml GDOC 10 mmol/l and 10 U enterokinase. Serum levels of amylase and lipase, hematocrit, mean arterial pressure and heart rate were determined at baseline and 5 hours later. Then the pancreas was removed for histopathology and grading (0-3; absent-severe) with regard to leukocyte infiltration, edema, necrosis, hemorrhage and acinar cell vacuolization. RESULTS: Serum levels of amylase and lipase increased significantly in 5 hours in all the groups. Serum amylase levels were significantly lower in group III than in group II. No significant difference of serum lipase was found among the groups. Group II had the highest scores of necrosis and acinar cell vacuolization, whereas group III had the highest scores of leukocyte infiltration and edema. The degree of necrosis was significantly more severe in group II than in group I. The hematocrit increased significantly in 5 hours in groups I and II. The mean arterial pressure in 5 hours decreased significantly in group I. There was no significant difference of the changes of heart rate in 5 hours among 3 groups. CONCLUSIONS: Intraductal infusion of NaTDC was a good method to induce moderate acute necrotizing pancreatitis in rats. GDOC caused mild pancreatitis, and pancreatic injury was aggravated when enterokinase was added. The severity of pancreatic histopathology was not correlated with the changes of serum levels of pancreatic enzymes, hematocrit or mean arterial pressure at the early stage of pancreatitis.

Acute Disease↗

TSH and TSH receptor antibody-binding sites in fibroblasts of pretibial myxedema are related to the extracellular domain of entire TSH receptor.

The role of TSH receptor antibodies in the pathogenesis of pretibial myxedema is still unclear. This study was designed to determine whether patients with pretibial myxedema had higher serum titers of TSH receptor antibodies, and whether there were TSH and TSH receptor antibody-binding sites on plasma membranes of fibroblasts derived from the skin of pretibial myxedema. If there were, were the binding sites similar to the TSH receptor? The TSH receptor antibodies were determined with radioreceptor assay in 20 normal subjects, 18 hyperthyroid Graves' disease patients without ophthalmopathy, 26 hyperthyroid Graves' disease patients with ophthalmopathy, and 11 patients with pretibial myxedema associated with Graves' ophthalmopathy. TSH and TSH receptor antibody-binding sites were studied on plasma membranes of fibroblasts cultured from the skin of pretibial myxedema with radioreceptor assay. RNA was also extracted from the fibroblasts of pretibial myxedema and reverse transcribed using random primers as the primers for cDNA synthesis. The resulting cDNAs were subjected to amplification by polymerase chain reaction with the use of a set of primers spanning the 5' region (+256/+275 and +616/+635) and the 3' region (+1819/+1838 and +2405/+2424) of the TSH receptor cDNA (+1 transcription start codon). They were further identified by Southern blot hybridization, with the probe spanning the 5' region (+272/+612) and the 3' region (+1908/+2268) of the TSH receptor cDNA (+ 1 transcription start codon), and sequencing. The results showed that patients with pretibial myxedema had higher titers of TSH receptor antibodies in the serum. TSH and TSH receptor antibody-binding sites were present on plasma membranes of fibroblasts derived from the skin of pretibial myxedema patients and related to the extracellular domain of the TSH receptor. These data suggest a common antigenic site in the skin and in the thyroid as a putative target for TSH receptor antibodies or lymphocytes of Graves' disease.

Adult↗

Serum pancreas-specific protein in acute pancreatitis. Its clinical utility in comparison with serum amylase.

To compare the clinical utility of serum pancreas-specific protein and serum amylase in the diagnosis of acute pancreatitis, the study was conducted in 134 normal subjects and 70 patients (36 with acute pancreatitis and 34 with other acute abdominal diseases as control group). The serum level of pancreas-specific protein in 134 healthy adults was 29.6 +/- 1.6 micrograms/l, with 95% within 7.3-67.2 micrograms/l. The upper reference limit was set at 70 micrograms/l. Serum levels of pancreas-specific protein and amylase within 12 h of arrival were significantly higher in patients with acute pancreatitis than in the control group (647.3 +/- 79.3 versus 33.8 +/- 4.8 micrograms/l (p < 0.0001) and 2536 +/- 344 versus 175 +/- 35 IU/l (p < 0.0001)). No significant difference in the levels of pancreas-specific protein was noted between biliary and alcoholic pancreatitis or between severe and mild attacks. The sensitivity, specificity, and accuracy of diagnosing acute pancreatitis were 100%, 94.1%, and 97.1% with serum pancreas-specific protein > 70 micrograms/l and 97.2%, 91.2%, and 94.3% with serum amylase > 360 IU/l. The result demonstrated that pancreas-specific protein may be a good serum marker in the diagnosis of acute pancreatitis.

Acute Disease↗

[A clinicopathological study of 8 cases of Castleman's disease].

Castleman's disease (CD) is a chronic lymphoproliferative disorder characterized by presence of giant lymphoid masses. The clinical features and histopathologic findings of 8 cases of CD diagnosed according to the criteria described by Frizzera were reported. 2 were male and 6 female; their age ranged from 26-66 years. Four patients with localized CD (three with hyaline vascular type and one with mixed type) had no systemic symptoms and had survived for a long time after surgery. Four patients with multicentric CD developed anemia, fever, elevated ESR, polyclonal immunoglobulinemia and manifestations of multisystem involvement. Steroids, chemotherapy, and radiotherapy had only resulted in partial remission in multicentric CD. The clinicopathologic differential diagnosis of CD from reactive lymph node hyperplasia in chronic infections, malignant lymphoma, connective tissue disease and angio-immunoblastic lymphadenopathy and the pathogenesis of CD were discussed.

Adult↗

The role of EDRF in the modulation of blood pressure and vascular reactivity in estrogen-treated rats.

The role of EDRF in the modulation of blood pressure and vascular reactivity in estrogen-treated rats was investigated both in vivo and in vitro studies. In vivo, long-term subcutaneous injection of ethinyl estradiol (EE2, 0.2 micrograms/day, s.c.) for 6 weeks significantly induced an elevation of systolic blood pressure from 117.1 +/- 2.7 to 129.9 +/- 3.6 mmHg. In vitro, the endothelium-dependent relaxation of ACh (10(-8)-10(-5) M) in intact aortic rings from EE2-treated rats was significantly blunted compared with normal control rats. Meanwhile, the contractile responses to PE (10(-8)-10(-5) M) was no difference between intact and denuded aortic rings from EE2-treated rats. The results indicate that the reduction of vasodilator response to ACh and the loss of enhanced contractile responses to PE in denuded rings may be due to altered endothelial function after long-term treatment with EE2. Furthermore, the high potassium (12.5-62.5 mM) induced-contraction and nitroglycerin (3 x 10(-8)-3 x 10(-6) M) induced-relaxation were not different between EE2 and control groups. These results indicate that the function of vascular smooth muscle did not alter after long-term treatment with EE2. In conclusion, the alteration of function of endothelium may play an important role in the modulation of estrogen-induced mild hypertension.

Acetylcholine↗

Diagnostic parameters for spontaneous bacterial peritonitis in hepatitis B-related cirrhosis: comparison of ascitic fluid polymorphonuclear cell count, lactate and pH values.

BACKGROUND: The clinical value of ascitic fluid pH or lactate in the diagnosis of spontaneous bacterial peritonitis was debated in alcoholic cirrhosis. It was rarely discussed in hepatitis B-related cirrhosis. We investigated the best rapid diagnostic method in spontaneous bacterial peritonitis of patients with hepatitis B-related cirrhosis. METHODS: Ascitic fluid polymorphonuclear cell count, ascitic fluid pH, arterial-ascitic fluid pH gradient, ascitic fluid lactate, and arterial-ascitic fluid lactate gradient were analyzed in 79 patients with sterile portal hypertension-related ascites, 31 patients with spontaneous bacterial peritonitis, 16 patients with hepatocellular carcinoma, 15 patients with malignancy-related ascites and 9 patients with other miscellaneous diseases. RESULTS: The sensitivity, specificity and accuracy of the diagnosis of spontaneous bacterial peritonitis were 100, 94 and 95% with the cut-off value of an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3, and were 86, 98 and 96% with that value > or = 500 cells/mm3, respectively. The sensitivity, specificity and accuracy were 29, 92, 80% using ascitic fluid pH < or = 7.35 as a cut-off value; 38, 91, 82% using arterial-ascitic fluid pH gradient > or = 0.1 as a cut-off value; 52, 92, 85% using ascitic fluid lactate > or = 32 mg/dL as a cut-off value, and 38, 96, 85% using arterial-ascitic fluid lactate gradient > or = 20 mg/dL as a cut-off value. CONCLUSIONS: The sensitivity of ascitic fluid pH or lactate was too low to aid in a diagnosis of spontaneous bacterial peritonitis in hepatitis B-related cirrhosis in spite of the acceptable specificity. An ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3 or > or = 500 cells/mm3 was the major and appropriate aids in the rapid diagnosis of spontaneous bacterial peritonitis.

Adult↗

Baculovirus-expressed herpes simplex virus type 2 glycoprotein D is immunogenic and protective against lethal HSV challenge.

Herpes simplex virus type 2 glycoprotein D (gD2) was cloned and expressed in the baculovirus-Spodoptera frugiperda system. Milligram quantities of glycoprotein were recovered from suspension culture and subjected to purification by ion-exchange and immunoaffinity chromatography. The resultant purified gD existed as a homogeneous 57,500 MW monomeric species demonstrating reactivity with anti-gD monoclonal antibodies including those directed at a non-sequential neutralizing epitope of gD. Immunization of Balb/c mice with doses of 0.1-10.0 micrograms of AlPO4-absorbed gD resulted in elicitation of humoral and cellular responses to both HSV1 and HSV2 as well as to purified gD1 and gD2. Immunized mice receiving an infectious dose of 1 x 10(6) p.f.u. of HSV2 via the footpad route were significantly protected against infection at all doses tested when compared with unimmunized AlPO4 and uninoculated control animals.

Animals↗

Determination of peptide 520 in human plasma using post-column photolysis with electrochemical detection in liquid chromatography.

A simple LC method for the determination of peptide 520 in human plasma was developed. Based on micellar chromatography, sodium octyl sulphate (SOS) was added into the mobile phase in order to separate the peptide from human plasma components. The procedure was fast and sensitive for the determination of the peptide in untreated human plasma. The electrochemical (EC) detection limit for peptide 520 in human plasma was 0.5 microgram ml-1. Linearity of the calibration plot for peptide 520 in human plasma was 0.999. This approach represents a direct injection technique for the potential detection and analysis of numerous peptides in biofluids, besides just plasma, with absolute quantification.

Chromatography, Liquid↗

The role of cyclic AMP and phosphodiesterase activity in the mechanism of action of tetramethylpyrazine on human and dog cardiac and dog coronary arterial tissues.

The aim of the present experiments was to explore the underlying cellular mechanisms responsible for the actions of tetramethylpyrazine (TMP) on atrial, ventricular and coronary arterial tissues. Transmembrane potentials of cardiac tissues were detected by means of the glass microelectrode technique and contractile tension by a force transducer. Tissue cyclic (c) AMP level was determined by protein binding assay. Results show that in human atrial and dog Purkinje fibres, high concentration of TMP (3 mM) induced a persistent positive inotropic effect only in the presence of adrenaline. Also, 3 mM TMP increased the cAMP level of the atrial muscle fibres, especially in the presence of adrenaline. Determination of the activity of cAMP-phosphodiesterase revealed that 0.3 and 3 mM TMP inhibited the phosphodiesterase activity of dog coronary artery and human atrial tissues in a concentration-dependent manner. When compared at the lower concentration (0.3 mM), the inhibitory effect of TMP was about 60% that of theophylline. The above findings indicate that the cardiovascular effects of TMP are related to the inhibition of phosphodiesterase activity and the subsequent elevation of the cAMP concentration.

3',5'-Cyclic-AMP Phosphodiesterases↗

Conformational effects in the reversed-phase chromatographic behavior of recombinant human growth hormone (rhGH) and N-methionyl recombinant human growth hormone (Met-hGH).

This paper examines the retention behavior of recombinant DNA-derived human growth hormone (rhGH) in reversed-phase chromatography and its separation from the closely related N-methionyl variant (Met-hGH). It is first shown that retention for rhGH decreases with increasing column temperature when 1-propanol (1-PrOH) is used as organic modifier. On the other hand, retention increases with temperature when acetonitrile (CH3CN) is employed. The differences in behavior for the two organic modifiers could be related to conformational changes in the protein as determined by solution and adsorption intrinsic fluorescence spectroscopy. Specifically, desorption and elution of rhGH using 1-PrOH could be correlated with a solvent-induced conformational change, with retention decreasing with increasing temperature due to the increasing ease of structural alteration. On the other hand for CH3CN the increase in retention correlated with temperature rise was related to a partial structural change yielding a more hydrophobic species. In this case, a surface-driven process is suggested. The work then turned to the separation of rhGH and Met-hGH where it was found for both organic modifiers optimum separation occurred at 45 degrees C and pH 6.5. Separate studies revealed that during the conformational change Met-hGH appeared more hydrophobic than rhGH since protein-protein aggregation was observed at a lower 1-PrOH concentration. It is suggested that this hydrophobic difference, which was optimized under the conditions cited above, resulted in the separation. The study demonstrates the importance of conformational changes in retention behavior and separation of protein samples.

Chromatography, Liquid↗

Three DNA sequencing methods using capillary gel electrophoresis and laser-induced fluorescence.

Capillary gel electrophoresis is demonstrated for the four-spectral-channel sequencing technique of Smith, the two-spectral-channel sequencing technique of Prober, and the one-spectral-channel sequencing technique of Richardson and Tabor. Sequencing rates up to 1000 bases/h are obtained at electric field strengths of 465 V/cm. At lower electric field strengths, capillary electrophoresis produces useful data for fragments greater than 550 nucleotides in length with 2 times better resolution than slab gel electrophoresis. An on-column detector produces detection limits of 200 zmol (1 zmol = 10(-21) mol = 600 molecules) for the four-spectral-channel technique. A postcolumn detector, based on the sheath flow cuvette, produces detection limits of 20 and 2 zmol for the two- and one-spectral-channel techniques, respectively.

Base Sequence↗