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Biomedical subjects

P S Wu

Publications and source records attributed to P S Wu.

At least 19 recordsLinked to original sources

Endothelial monocyte activating polypeptide II induces endothelial cell apoptosis and may inhibit tumor angiogenesis.

Endothelial monocyte activating polypeptide II (EMAP-II) is a tumor-derived cytokine with potent effects on endothelial cells in vitro and in vivo including upregulation of tissue factor and the sensitization of human melanoma to systemic TNF treatment via its effects on the tumor vasculature. We investigated the effects of EMAP-II on tumor growth, angiogenesis, vasculogenesis, and apoptosis. EMAP-II inhibited endothelial cell proliferation, vasculogenesis, and neovessel formation. In vivo growth of human melanoma lines expressing high amounts of EMAP-II demonstrated slower growth, smaller tumors, and increased amounts of tumor necrosis than those expressing lower amounts of EMAP-II. EMAP-II induced endothelial-cell-specific apoptosis via a pathway that includes upregulation of the Fas-associated death domain and downregulation of Bcl-2. EMAP-II appears to have important effects on angiogenesis and may play a role in regulating tumor vascular growth.

3T3 Cells↗

Symptomatic and asymptomatic accessory navicular bones: findings of Tc-99m MDP bone scintigraphy.

AIM: The accuracy of bone scintigraphy in diagnosing symptomatic accessory navicular bones has not been well studied. We conducted a retrospective study to explore the results and use of scintigraphy in symptomatic and asymptomatic accessory navicular bones. MATERIALS AND METHODS: Thirteen patients with a total of 13 symptomatic and 10 asymptomatic accessory navicular bones were included in the study. We used a scoring system to grade the scintigraphic abnormalities. The patients' symptoms and scintigraphic findings were recorded. RESULTS: Though focally increased radiopharmaceutical uptake was observed in all symptomatic accessory naviculars, half of the asymptomatic accessory navicular bones had the same manifestations. The scoring system was of no value in differentiating symptomatic from asymptomatic accessory navicular bones. CONCLUSION: Bone scintigraphy is a sensitive but not a specific tool for diagnosing a symptomatic accessory navicular.

Adolescent↗

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Animals↗

Peritoneal scintigraphy for diagnosing periumbilical leakage in a patient on continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) offers several advantages over hemodialysis for patients with end-stage renal disease; however, this technique also includes many documented complications. A case with clinical suspicion of dialysate leakage on CAPD was investigated by peritoneal scintigraphy using technetium-99m macroaggregated human albumin (99mTc-MAA). Peritoneal scintigraphy showed radiotracer accumulation over the periumbilical area at 2 hours 30 minutes after intraperitoneal infusion of 99mTc-MAA. Six hours of imaging revealed more apparent radioactivity at the same site. This study is to illustrate the simple diagnostic helpfulness of peritoneal scintigraphy in a patient with a CAPD-related structural defect.

Adult↗

Alpha 1-adrenergic stimulation inhibits 3,5,3'-triiodothyronine-induced expression of the rat heart sarcoplasmic reticulum Ca2+ adenosine triphosphatase gene.

The interactions between the beta-adrenergic system and thyroid hormone (T3) on cardiac function have been investigated in detail. In addition to beta-adrenoceptors, alpha 1-adrenergic receptors are present in the mammalian heart. The interactions between T3 and the alpha 1-adrenergic system remain, however, poorly understood. T3 stimulates the expression and transcription of the sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) gene, a protein vital in the control of cardiac calcium transients and contractility. We show that in rat cardiac myocytes, the stimulatory effect of T3 on SERCA2 messenger RNA expression and gene transcription is inhibited by an alpha 1-adrenergic agonist. We demonstrate that direct activation of the alpha 1-adrenergic signaling pathway, using a mutant constitutively active G protein (Gq) similarly down-regulated the T3 effect on SERCA2 transcription. The combined effect of thyroid hormone receptor and retinoid X receptors on T3-stimulated SERCA2 gene transcription was also markedly attenuated by alpha 1-adrenergic stimulation. These results suggested that activation of the alpha 1-adrenergic signaling pathway has an inhibitor effect on T3-dependent SERCA2 gene transcription. As this inhibitory effect of alpha 1-adrenergic stimulation occurs when only one thyroid hormone response element (TRE) drives reporter expression, it is most likely mediated by an alteration of the nuclear factors binding to the TRE or by influencing the interaction of the TRE complex with the basal transcriptional machinery.

Animals↗

Frequent loss of heterozygosity on chromosomes 3p and 17p without VHL or p53 mutations suggests involvement of unidentified tumor suppressor genes in follicular thyroid carcinoma.

Follicular thyroid carcinoma (FTC) exhibits frequent loss of heterozygosity (LOH) on chromosomes 10q and 3p, suggesting involvement of tumor suppressor genes. We screened 14 FTC (10 Hurthle cell carcinomas and 4 nonoxyphilic FTC), 14 papillary thyroid carcinomas, and 7 follicular adenomas for LOH on chromosome arms 1p, 3p, 3q, 10p, 10q, 11p, 11q, 13q, 17p, and 17q. LOH was more frequent in FTC than in follicular adenoma or papillary thyroid carcinoma. In FTC, rates of LOH on 3p (86%), 17p (72%), and 10q (57%) were higher than the average rate of LOH (33%; P < 0.05). Most frequently involved were 3p21-25 and 17p13.1-13.3, the sites for the VHL (3p25-26) and p53 (17p13.1) tumor suppressors. We, therefore, characterized these genes by dideoxy fingerprinting and DNA sequencing. Two FTC had mutations in p53, but only 1 of these exhibited LOH at 17p. No VHL gene mutations were found. Thus, neither p53 nor VHL genes play a significant role in the pathogenesis of differentiated thyroid cancer. LOH on 17p, but not on 3p or 10q, was correlated with mortality. Accordingly, 3p and 10q LOH may represent early, and 17p LOH late, events in FTC development. The data suggest the presence of novel tumor suppressor genes on chromosomes 3p and 17p that may be important in the pathogenesis of FTC.

Adenocarcinoma, Follicular↗

Does early growth delay occur in diabetic pregnancy?

OBJECTIVE: To identify the date of ovulation in pregnant women with Type 1 diabetes in order to assess the validity of the concept of early growth delay. DESIGN: Identification of ovulation by measurement of urinary luteinising hormone and assessment of fetal growth using ultrasound scan. SETTING: Diabetic pre-pregnancy and antenatal clinic in a teaching hospital. SUBJECTS: Twenty women with Type 1 diabetes who had attended a pre-pregnancy clinic. MEASURES: Urinary LH, by laboratory and kit methods, during conception cycles. Human chorionic gonadotrophin measured in early pregnancy. Early ultrasound scans by a single observer blind to menstrual and ovulation dates. OUTCOME: Gestation calculated from ovulation date and gestation estimated from menstrual dates, compared with gestation at age indicated by early ultrasound scan. RESULTS: When the date of ovulation was identified in 20 women with Type 1 diabetes there was no evidence of growth delay in any pregnancy. When gestation was estimated from menstrual dates there was apparent early growth delay in six pregnancies. CONCLUSION: This study, together with others discussed, indicates that early growth delay is probably an artefact of incorrectly estimated ovulation date.

Diabetes Mellitus, Type 1↗

Pharmacological and pathological studies on hepatic protective crude drugs from Taiwan (V): The effects of Bombax malabarica and Scutellaria rivularis.

Bombax malabarica DC and Scutellaria rivularis B. were extracted in boiling water and concentrated into 1g/ml solution to investigate their hepatoprotective effect. Carbon tertrachloride (CCL4) was injected into rat subcutaneously with a dose of 3.0 ml/kg to induce experimental acute hepatotoxicity in the animal. The activities of serum glumtamic-oxaloacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) were measured after 72 hours of CCL4 administration. The hepatopathological changes of the liver tissue were observed simultaneously with liver enzyme activities determination. The pharmacological effect of B. malabarica and S. rivularis of Taiwan was compared with that of the Bupleurum chinense from mainland China. B malabarica (p < 0.001), S. rivularis (p < 0.001) and B. chinense (p < 0.05) all demonstrated a significant reduction in the CCL4-induced SGOT and SGPT. Pathological studies of these three drugs extracts demonstrated a marked hepato-protective effects on CCL4-induced liver fatty degeneration and cell necrosis.

Alanine Transaminase↗

The clinical utility of a non-isotopic two-step assay (DELFIA) and an analogue radioimmunoassay (SimulTRAC) for free thyroxine compared.

The analytical and diagnostic performance of a new non-isotopic, two-step immunoassay (DELFIA) for the measurement of free thyroxine (free T4) in plasma or serum has been compared with an established second generation analogue radioimmunoassay (SimulTRAC). Both methods had a good diagnostic specificity in pregnancy, thyroid clinic patients, and patients taking anticonvulsant drugs. In patients presenting to a general medical ward the diagnostic specificity of both methods was poor. Two samples appeared to contain substances which produced assay interference by DELFIA but not by SimulTRAC assays. When free T4 was measured by equilibrium dialysis a clear association between sample dilution and free T4 concentration was demonstrated in sick euthyroid patients. In contrast, using samples obtained from patients with known thyroid disease, free T4 was little influenced by sample dilution. The effects of sample dilution on free T4 measured by DELFIA were similar to those found using equilibrium dialysis. It would appear that free T4 measurements have a relatively poor diagnostic specificity in non-thyroidal illness irrespective of the method used.

Anticonvulsants↗

Inter-relationships between selenium and thyroid hormone metabolism in the rat and man.

Labelling of rat kidney microsomes in vitro with [125I]-bromoacetyl T4 produced two bands on SDS/PAGE with Mr of 55 kDa and 27.5 kDa representing protein disulphide isomerase and type I iodothyronine deiodinase (ID-I) respectively. The amount of the 55 kDa band was unchanged by selenium (Se) deficiency but the 27.5 kDa protein was markedly decreased in kidney microsomal fraction obtained from Se-deficient rats. Concurrent Se and iodine deficiency produced a significant increase in thyroid weight, plasma thyrotrophin (TSH) and a decrease in thyroidal iodine when compared with either single Se or iodine deficiency. These results suggest that ID-I is a selenoprotein and that Se deficiency can exacerbate the hypothyroidism observed in iodine deficiency. In man, blood glutathione peroxidase and blood Se levels were decreased in hyperthyroidism due to Graves' disease whilst normal levels of these analytes were found in patients treated for Graves' disease. These results suggest that thyroid status can affect Se balance rather than Se deficiency predisposes to Graves' disease.

Animals↗

Seroepidemiology of hepatitis B virus, hepatitis D virus, and human immunodeficiency virus infections among parenteral drug abusers in southern Taiwan.

A total of 390 parenteral drug abusers (PDAs) at the Kaohsiung Municipal Narcotics Abstention Institute were examined for markers of hepatitis B virus (HBV), hepatitis D virus (HDV), and human immunodeficiency virus (HIV). All sera were tested for hepatitis B surface antigen (HBsAg), surface antibody (anti-HBs), and core antibody (anti-HBc) by radioimmunoassay (RIA) and for antibody to HIV (anti-HIV) by enzyme-linked immunosorbent assay (ELISA). Hepatitis B e antigen (HBeAg) and antibody to HDV (anti-HDV) were also tested for HBsAg-positive serum samples. Although the HBsAg-positive rate (22.1%) among PDAs was similar to that of the general population in southern Taiwan, the HBV infection rate (99.2%) and the anti-HDV-positive rate (78.5%) among HBsAg-positive subjects were significantly higher than those of the general population in southern Taiwan (P less than 0.0001). None of the PDAs studied were positive for anti-HIV. The levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) among PDAs were significantly higher than those of the general population in southern Taiwan (P less than 0.0001). The more frequent the institutionalisation, the higher the infection rates with HBV and HDV and elevated levels of SGOT and SGPT. Horizontal transmission through parenteral drug abuse may be considered a possible reason for the significantly higher rates of HBV and HDV among parenteral drug abusers.

Acquired Immunodeficiency Syndrome↗

Human monoclonal antibodies to Rh0(D).

B lymphocytes from Rh negative donors with serum anti-D antibodies were isolated and fused with the mouse-human heteromyeloma, SBC-H20, to produce hybridomas secreting IgM or IgG1 human monoclonal antibodies to D antigen. The IgM antibody in hybridoma supernatant agglutinates all normal D positive cells at the immediate spin phase of reactivity. Using concentrated IgM hybridoma supernatant of approximately 50 micrograms/ml, Du cells were also agglutinated. The IgG1 antibody reacts by indirect hemagglutination with all D and Du cells. Against Rh mosaics, different reactivity was noted for each antibody. Furthermore, D positive cells precoated with the IgG1 antibody inhibit the IgM direct hemagglutination, suggesting that the antibodies identify closely associated epitopes. These human monoclonal antibodies will be useful diagnostic reagents and, ultimately, should be useful in the prevention of Rh hemolytic disease of the newborn.

Antibodies, Anti-Idiotypic↗

Stability of carbohydrate-modified vesicles in vivo: comparative effects of ceramide and cholesterol glycoconjugates.

The stability and tissue distribution of lipid vesicles modified at the surface by the incorporation of either a galactosyl ceramide (GalCer) or a galactosyl cholesterol (GalChol) glycoconjugate have been studied in mice by measuring the release of vesicle-entrapped 111In. Although the tissue distributions of both vesicle types were similar, the GalCer-containing vesicles were markedly less stable than those prepared with GalChol, whether administered orally or by intraperitoneal injection. Physical characterization of the vesicles in vitro suggests that the increased disruption rate for GalCer vesicles in vivo is related to structural instabilities induced by the cerebroside, which can then result in either an increased rate of vesicle uptake by tissues or a greater susceptibility to lysis. These studies demonstrate the importance of the nonpolar anchoring groups in determining the fate of surface-modified vesicles in vivo.

Administration, Oral↗

Effect of surface modification on aggregation of phospholipid vesicles.

Phospholipid vesicles have been extensively investigated because of their usefulness as models for biological membranes and their potential application as carriers for drug delivery. However, preparations of small sonicated vesicles tend to aggregate and fuse (on storage at room temperature and at 4 degrees C), resulting in significant changes in turbidity, rate of uptake by macrophage, and proton NMR linewidths. By modification of the surface of phospholipid vesicles with charged groups such as beta-aminogalactose that extend significantly from the vesicle surface, it is possible to obtain preparations that are stable for greater than 7 days.

Animals↗

Phagocytosis of carbohydrate-modified phospholipid vesicles by macrophage.

Modification of the surface of distearoyl phosphatidylcholine vesicles with synthetic glycolipids dramatically affects the rate of uptake of these vesicles by mouse peritoneal macrophage. The high rate of uptake of 6-aminomannose-modified vesicles is effectively inhibited by cytochalasin B and chloroquine but not by colchicine, indicating that the mechanisms of vesicle uptake is phagocytosis. Other modified vesicles appear to have some effect on the rate of uptake of 6-aminomannose-modified vesicles suggesting that the various vesicle types compete for the same initial binding sites. Analysis of 6-aminomannose-modified vesicles by gamma-ray perturbed angular correlation spectroscopy shows that the rotational correlation time of the encapsulated 111In3+ does not change when the vesicles associate with macrophage. This result is consistent with transmission electron microscopy, which indicates that the aminomannose-modified vesicles remain intact after phagocytosis as aggregates of fused and intact vesicles surrounded by a single bilayer membrane structure.

Animals↗