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Biomedical subjects

M S Wu

Publications and source records attributed to M S Wu.

At least 19 recordsLinked to original sources
PubMed2005

Individual and combined effects of peroxisome proliferator-activated receptor and {gamma} agonists, fenofibrate and rosiglitazone, on biomarkers of lipid and glucose metabolism in healthy nondiabetic volunteers.

This open-label, randomized, placebo-controlled, incomplete-block, 3-period crossover pilot study investigated the effects of peroxisome proliferator-activated receptor alpha- and gamma-agonists on biomarkers of lipid and glucose metabolism in 12 nondiabetic subjects. Plasma samples were collected before and after each 14-day treatment with placebo, fenofibrate (201 mg/d), rosiglitazone (4 mg twice daily), and combined fenofibrate (201 mg/d) plus rosiglitazone (4 mg twice daily). Except for triglycerides (P < .042) and free fatty acids (P < .074), no significant interaction was demonstrated between fenofibrate and rosiglitazone; thus, the effect due to each drug alone was evaluated (presence/absence of drug). Fenofibrate significantly (P < .050) increased lipoprotein lipase activity (35%) and decreased apolipoproteins B (13%) and C-III (20%). Rosiglitazone significantly (P < .050) decreased fasting glucose (7.3%) and increased apolipoprotein C-III (19%) and adiponectin (137%). Fenofibrate and rosiglitazone also produced effects on triglycerides and free fatty acids, but it was not possible to determine if these effects were synergistic in nature.

Adolescent↗
PubMed2004

An integrative genomics approach to the reconstruction of gene networks in segregating populations.

The reconstruction of genetic networks in mammalian systems is one of the primary goals in biological research, especially as such reconstructions relate to elucidating not only common, polygenic human diseases, but living systems more generally. Here we propose a novel gene network reconstruction algorithm, derived from classic Bayesian network methods, that utilizes naturally occurring genetic variations as a source of perturbations to elucidate the network. This algorithm incorporates relative transcript abundance and genotypic data from segregating populations by employing a generalized scoring function of maximum likelihood commonly used in Bayesian network reconstruction problems. The utility of this novel algorithm is demonstrated via application to liver gene expression data from a segregating mouse population. We demonstrate that the network derived from these data using our novel network reconstruction algorithm is able to capture causal associations between genes that result in increased predictive power, compared to more classically reconstructed networks derived from the same data.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

Clinicopathological and molecular biological features of colorectal cancer in patients less than 40 years of age.

BACKGROUND: The aim of the present study was to identify the clinicopathological and molecular biological characteristics of early-onset colorectal cancers. METHODS: The clinicopathological and molecular biological parameters of 138 consecutive patients with colorectal cancer aged less than 40 years were compared with those of 339 patients aged 60 years or more. RESULTS: The younger patients with colorectal cancer had more mucin-producing (14.5 versus 4.7 per cent; P < 0.001) and poorly differentiated (7.2 versus 3.3 per cent; P = 0.015) tumours, a higher incidence of synchronous (5.8 versus 1.2 per cent; P = 0.007) and metachronous (4.0 versus 0.6 per cent; P = 0.023) colorectal cancers, and more advanced tumour stage (P < 0.001) than older patients. The operative mortality rate was lower (0.7 versus 5.0 per cent; P = 0.026), and cancer-specific survival was similar (in stage I, II and III disease; P > 0.05) or better (in stage IV disease; 95 per cent confidence interval 22.50 to 28.41 versus 12.61 to 17.05 months; P < 0.001). There was a higher percentage of normal p53 expression (61.1 versus 46.8 per cent; P = 0.023) and high-frequency microsatellite instability (MSI-H) (29.4 versus 6.3 per cent; P < 0.001), and a similar family history of cancer (17.5 versus 14.2 per cent; P > 0.05), compared with older patients. CONCLUSION: Young patients with colorectal cancer have several distinct clinicopathological and molecular biological features. The mechanisms underlying the inconsistency between the presence of MSI-H and a family history of cancer in these early-onset colorectal cancers deserve further investigation.

Adolescent↗
PubMed2001

Correlation of histologic subtypes and replication error phenotype with comparative genomic hybridization in gastric cancer.

To characterize phenotypic and genotypic changes in gastric cancer (GC), DNA copy number aberrations (CNAs) were assessed in 53 tumors using comparative genomic hybridization (CGH) and correlated with clinicopathologic characteristics and status of TP53 and replication error (RER). The number of CNAs per tumor was 6.8 (gain 5.3, loss 1.5), and the number of changes was significantly higher in tumors with advanced stage, TP53 mutation, and without RER than in those with early stage (7.7 vs. 3.0), no TP53 mutations (12.4 vs. 4.8) or RER phenotype (8.2 vs. 2.6). Frequent abnormalities included gains on chromosomal arms 8q (43%), 6q (26%), 11q (26%), 13q (24%), 7p (23%), 17q (23%), and 20q (23%), and losses on chromosomal arms 16q (26%), 19p (23%), 5q (19%), 3p (15%), 4q(15%), and 1p (15%). Advanced GC demonstrated a higher prevalence of gains of 8q (51% vs. 10%, P < 0.05) and loss of 16q (33% vs. 0%, P < 0.05) than early GC. Gains on 8q (64% vs. 20%, P < 0.05), 17q (39% vs. 4%, P < 0.05) and losses on 3p (25% vs. 4%, P = 0.05) and 5q (32% vs. 4%, P < 0.05) were higher in intestinal GC than in diffuse GC. On the other hand, gains on 13q were more common in the diffuse type (40% vs. 11%, P < 0.05). As compared with noncardia cancer, cardia cancer showed more gains on 7p (58% vs. 12%, P < 0.05) and 20q (58% vs. 12%, P < 0.05) and more losses on 4q (50% vs. 5%, P < 0.05). The finding of histology-related aberrations and the combination of CGH and molecular data thus provide additional evidence suggesting genetic heterogeneity of GC.

Chromosome Aberrations↗
PubMed2001

Renal response during acute unilateral ureteral obstruction in rats.

The early renal response to unilateral ureteral occlusion (UUO) and its mechanism have been extensively studied in dogs but seldom discussed in the most frequently used laboratory animals, rats. The acute phase of the renal response to UUO was studied in female rats weighing 190-236 g. We recorded the ureteral pressure and changes in renal parameters throughout 120 minutes of UUO in control (US, UUO + saline, n = 10), L-arginine-treated (UA, n = 10), and right-nephrectomized rats (UO, UUO in one kidney, n = 9). Ureteral pressure increased in all three groups of rats after complete ureteral obstruction. The extent of the increase was not significantly different between US and UA rats but was significantly higher in the UO rats. In US rats, the cortical microvascular blood flow (CMVBF), measured by a laser Doppler flowmeter, declined significantly, from 321 +/- 10 perfusion units (PU) to 260 +/- 11 PU. The percentage of drop in CMVBF at 120 minutes of UUO was significantly greater in UO (25.7 +/- 3.8 %) than in US (19 +/- 2.1%) and in UA (14 +/- 2%) rats. Acute UUO reduced the glomerular filtration rate (GFR) in US and UO rats, whereas L-arginine attenuated this decrease. The excretion of nitrate/nitrite was increased after UUO. Giving N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 12 mg/kg/h) during UUO did not reduce CMVBF more severely. Western blot analysis of endothelial nitric oxide synthase expression in the renal cortex and medulla protein extracts revealed no differences between US and sham-operated rats. Acute UUO did not lead to renal hyperemia in rats. Reduction of nitric oxide during UUO might contribute to the decrease of renal circulation during UUO.

Acute Disease↗
PubMed2001

Color Doppler sonography for ventral hernias in patients with acute abdomen: preliminary findings.

PURPOSE: We assessed the usefulness of color Doppler sonography (CDUS) in evaluating the vascular status of ventral hernias and distinguishing incarcerated from nonincarcerated ventral hernias. METHODS: In this prospective study, 10 patients who presented with acute abdomen and had ventral hernias underwent CDUS from August 1999 to May 2000. Patient age and sex and the clinical severity, mode of therapy, and outcome in these 10 patients were evaluated in relationship to the CDUS findings. RESULTS: Five patients had readily visible flow in the bowel within the hernial sac on CDUS. Two of these 5 had spontaneous reduction under conservative treatment, and 3 had asymptomatic ventral hernias with acute abdomen caused by spontaneous bacterial peritonitis. Barely visible flow was visualized in the bowel by CDUS in 4 other patients. Three of these underwent emergency surgery because of peritoneal signs; 2 of them were found to have ischemic changes in the bowel. The fourth patient underwent a successful manual reduction. The remaining patient had absent flow in the bowel on CDUS and underwent emergency surgery, which revealed gangrenous changes in the bowel. CONCLUSIONS: The intensity of the Doppler signals on CDUS appears to be a promising predictor of bowel viability in cases of ventral hernia. Thus, CDUS should impact the determination of the treatment plan, including whether to provide conservative treatment or surgery.

Abdomen, Acute↗
PubMed2001

Haematopoietic progenitor cells from the common marmoset as targets of gene transduction by retroviral and adenoviral vectors.

To establish a new non-human primate model for human cytokine and gene therapy, we characterized lymphocytes and haematopoietic progenitor cells of the small New World monkey, the common marmoset. We first assessed the reactions of marmoset bone marrow (BM) and peripheral blood (PB) cells to mouse anti-human monoclonal antibodies (mAbs) for the purpose of isolating marmoset lymphocytes and haematopoietic progenitor cells. Both cell fractions stained with CD4 and CD8 mAbs were identified as lymphocytes by cell proliferation assay and morphological examination. Myeloid-specific mAbs such as CD14 and CD33 did not react with marmoset BM and PB cells. No available CD34 and c-kit mAbs could be used to purify the marmoset haematopoietic progenitor cells. Furthermore, we studied the in vitro transduction of the bacterial beta-galactosidase (LacZ) gene into CFU-GM derived from marmoset BM using retroviral and adenoviral vectors. The transduction efficiency was increased by using a mixed culture system consisting of marmoset BM stromal cells and retroviral producer cells. It was also possible to transduce LacZ gene into marmoset haematopoietic progenitor cells with adenoviral vectors as well as retroviral vectors. The percentage of adenovirally transduced LacZ-positive clusters was 15% at day 4 (multiplicity of infection=200), but only 1-2% at day 14. The differential use of viral vector systems is to be recommended in targeting different diseases. Our results suggested that marmoset BM progenitor cells were available to examine the transduction efficiency of various viral vectors in vitro.

Adenoviridae↗
PubMed2001

Acinar cell carcinoma with hypervascularity.

Acinar cell carcinoma is an uncommon malignancy with a reported incidence of 1% among exocrine tumors of the pancreas. The case of a 60-year-old Taiwanese man who presented with obstructive jaundice, abdominal pain, and body weight loss is described here. A mixed clinical picture of islet cell tumor and ductal carcinoma of the pancreas was shown to be a hypervascular tumor at the pancreatic head region with an irregular stricture at the common channel of the common bile and pancreatic ducts. The patient had normal levels of plasma carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, but an increase in plasma levels of insulin and C-peptide. Immunohistochemical stains and electron microscopic examination of the tumor was consistent with acinar cell carcinoma.

Carcinoma, Acinar Cell↗
PubMed2001

Adjuvant sclerotherapy after ligation for the treatment of esophageal varices: a prospective, randomized long-term study.

BACKGROUND: To assess the efficacy of adjuvant sclerotherapy after banding for the treatment of esophageal varices, a randomized trial was carried out of endoscopic variceal ligation (EVL) alone with sequential sclerotherapy versus sequential ligation-sclerotherapy (SLS) after banding with respect to variceal eradication, associated complications, and recurrence of varices. METHODS: One hundred patients qualified for this study. Fourteen patients were not included for the following reasons: 6 chose not to participate, 4 had fundal varices, and 4 had some form of cancer. Of the remaining 86 patients in the study, 42 underwent EVL alone and the other 44 SLS. Variceal ligation was begun in the region of the gastroesophageal junction, with subsequent ligatures applied cephalad 3 to 5 cm; ligation was repeated every 2 weeks until variceal obliteration. For SLS, ligation was also begun in the region of the gastroesophageal junction and repeated until varices were reduced to F1 size. Subsequently, these patients underwent sclerotherapy with between 6 and 8 mL of sodium tetradecyl sulfate (free hand technique). RESULTS: No significant differences were found between EVL alone and SLS with regard to variceal eradication, development of associated complications, and recurrent bleeding during a follow-up of 2 years. The probability of variceal recurrence requiring further treatment after 1 year was 14% for the SLS group and 26% for EVL group patients. Another year later, the probability of variceal recurrence was 24% and 45%, respectively, for the SLS and EVL groups. CONCLUSIONS: Because a significantly lower rate of variceal recurrence was found for SLS patients, sequential sclerotherapy followed by ligation to eradicate those varices too small to easily band may be a better procedure.

Combined Modality Therapy↗
PubMed2001

Mycophenolate mofetil reduces renal cortical inducible nitric oxide synthase mRNA expression and diminishes glomerulosclerosis in MRL/lpr mice.

Overexpression of inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus glomerulonephritis. Mycophenolate mofetil (MMF), a novel immunosuppressive agent, is currently used in organ transplantation and under evaluation for treatment of autoimmune disorders. Mycophenolic acid, the active metabolite of MMF, has been shown to suppress cytokine-induced nitric oxide production in vitro. The aim of this study was to evaluate the effect of MMF on the expression of renal cortical iNOS mRNA and protection against glomerulonephritis in MRL/lpr mice. Three-month-old MRL/lpr mice (n = 6) displaying clinical symptoms of glomerulonephritis were treated for 3 months with MMF (90 mg/kg/day) dissolved in a vehicle. Controls were age- and sex-matched mice (n = 6) that received the vehicle alone. By reverse-transcription competitive polymerase chain reaction, we found that the renal cortical iNOS/beta-actin mRNA ratio was reduced by 30.8% (P <.05) in MMF-treated mice. Furthermore, MMF significantly reduced urinary nitrite production and degree of glomerulosclerosis. The glomerular volume was reduced by 17.5% (P <.001). Proteinuria was also significantly reduced in the MMF-treated group. However, by electrophoretic mobility shift assay, the nuclear binding of nuclear factor-kappaB (NF-kappaB) was not affected by MMF treatment. We conclude that in addition to its immunosuppressive action, MMF may reduce renal cortical iNOS mRNA expression and diminish glomerulosclerosis in MRL/lpr mice independent of modulation of the NF-kappaB pathway.

Animals↗
PubMed2001

Clinical improvement by increased frequency of on-line hemodialfiltration.

BACKGROUND/AIMS: In spite of the better efficiency of on-line hemodiafiltration (HDF) compared with conventional hemodialysis (HD), it is relatively expensive. The aim of this study was to assess the advantages in the biochemical, hemodynamic and clinical effects in uremic patients treated with on-line HDF and with different frequencies of combination high-flux HD. METHODS: One hundred eleven patients were divided into four groups receiving different frequencies of on-line HDF (thrice, twice, once per week) and high-flux HD. RESULTS: Hemodynamic parameters including maximum drop of systolic blood pressure, episodes of symptomatic hypotension and mean saline infusion volumes during dialysis were reduced when frequencies of on-line HDF were increased. Significant improvements in urea kinetic were observed when frequencies of on-line HDF were increased. On-line HDF significantly reduced the amount of erythropoietin needed and improved intra- and inter-dialysis symptoms, physical well-being, menstruation and skin pigmentation when frequency of HDF is increased to three time per week. CONCLUSION: On-line HDF offers a better cardiovascular stability and clinical improvement. Thrice weekly on-line HDF offers a significant benefit when compared with lower frequencies of HDF per week and high-flux HD.

Female↗
PubMed2001

The effect of an iron supplement on serum aluminum level and desferrioxamine mobilization test in hemodialysis patients.

BACKGROUND: The serum aluminum (Al) measurement with desferrioxamine (DFO) mobilization is a screening test for uremic patients with an Al overload. In these patients, body iron status is one of the factors affecting the serum Al level. This study is designed to elucidate the effects of iron supplements on the serum Al and the DFO mobilization test. METHODS: Our study featured ten hemodialysis patients with iron deficiency anemia. The iron supplement was given intravenously with saccharated ferric oxide, 40 mg three times weekly, at the end of each hemodialysis. The total amount of iron supplement was 1,000 mg. All the patients underwent a DFO test at a dose of 5 mg/kg. The same test was repeated two weeks after completion of the iron supplement. RESULTS: After the iron supplement, patients' iron deficiency anemia improved with a serum ferritin elevation from 312.4 +/- 589.5 to 748.2 +/- 566.2 microg/L (p < 0.01), and iron saturation from 21.6 +/- 20.3 to 41.1 +/- 21.7% (p = 0.06). The basal serum Al level decreased from 34.3 +/- 13.8 to 21.8 +/- 8.5 microg/L (p = 0.01). In the DFO mobilization test, the peak serum Al level decreased from 63.4 +/- 19.3 to 50.7 +/- 20.5 microg/L (p < 0.01). The amount of Al increment (deltaAl) in DFO test was not changed (29.1 +/- 12.0 vs. 28.9 +/- 15.9 microg/L, p = 0.86). The change in basal Al level tended to negatively correlate with the percentage of increment in iron saturation (r = -0.628, p = 0.05). CONCLUSION: Results in this study suggest that iron supplements may significantly reduce the basal serum Al and peak Al in DFO mobilization test, without significant change of the mean deltaAl. The data presented indicate that in the interpretation of serum aluminum levels the iron status should be taken into account.

Adult↗
PubMed2001

Leptospirosis renal disease.

Leptospirosis is a re-emerging infectious disease, affecting both animals and humans worldwide. Multiple organ involvement may be encountered in leptospirosis, and early renal involvement is very common, characterized by tubulo-interstitial nephritis and tubular dysfunction. All 12 patients diagnosed in Chang Gung Memorial Hospital (Taiwan) between 1997 and 1999 had acute renal failure, with five patients requiring dialysis. Leptospira shermani is the main serovar encountered in Taiwan, and penicillin may dramatically rescue patients from multiple organ failure provided it is given early. To understand the mechanism behind tubular injuries by leptospira infection, outer membrane proteins (OMPs) extracted from pathogenic leptospira were given to tubular cells in culture. Our in vitro experiment showed that OMPs of pathogenic leptospira activate nuclear NFkappaB binding and stimulate downstream inducible nitric oxide (iNOS), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) expression. These results indicate that leptospiral infection may induce tubulo-interstitial nephritis through a toxic component in the outer membrane followed by expression of inflammatory genes.

Acute Kidney Injury↗
PubMed2001

Immunohistochemical evaluation of cadherin and catenin expression in early gastric carcinomas: correlation with clinicopathologic characteristics and Helicobacter pylori infection.

Dysfunction of E-cadherin and catenin has been linked to invasiveness and differentiation of tumors. This study aimed to characterize the expression of cadherins and catenins in early gastric carcinoma and their relationship to clinicopathologic characteristics and Helicobacter pylori infection. E-cadherin and alpha-, beta- and gamma-catenins were strongly expressed in normal epithelium but abnormal immunoreactivity of at least one of these four proteins was noted in 48 (90.6%) of 53 early gastric carcinomas. Only 5 cases with intestinal-type tumors had intact expression of E-cadherin and alpha-, beta-, and gamma-catenins. Abnormal immunoreactivity in the tumor tissue was observed in 18 patients (34.0%) for E-cadherin, in 35 (66.0%) for alpha-catenin, in 20 (37.7%) for beta-catenin, and in 37 (69.8%) for gamma-catenin. In diffuse-type tumors, abnormal expression of E-cadherin (60.9 vs. 13.3%, p < 0.0005), alpha-catenin (82.6 vs. 53.3%, p < 0.05) and gamma-catenin (91.3 vs. 53.3%, p < 0.005) was more frequent than in the intestinal type. Ten tumors with lymph node metastasis showed a relatively higher frequency of abnormal expression of E-cadherin (70 vs. 25.6%, p < 0.05) but a lower frequency of abnormal expression of beta-catenin (10 vs. 44.1%, p = 0.07) than those without metastasis. No significant association was found between cadherin/catenin expression and the depth of invasion or the H. pylori status. It was concluded that abnormal expression of E-cadherin and the catenin-mediated cell-cell adhesion system occurs frequently in early gastric carcinogenesis and may play an important role in the genesis of histologic differentiation and in the mode of metastasis of early gastric carcinomas.

Armadillo Domain Proteins↗
PubMed2001

Tumor angiogenesis and its possible role in intravasation of colorectal epithelial cells.

PURPOSE: To determine whether an increase in tumor angiogenesis facilitates intravasation of colorectal epithelial cells, we compared intratumoral microvessel counts with the presence of circulating colorectal epithelial cells in the portal venous blood from patients with colorectal carcinomas. EXPERIMENTAL DESIGN: Circulating colorectal epithelial cells were detected by a reverse transcription-PCR assay to amplify guanylyl cyclase C (GCC) transcripts. The extent of tumor vascularization was quantitatively assessed by immunohistochemical staining with anti-CD31 antibody. RESULTS: Colorectal epithelial cells (as measured by GCC mRNA expression) were detected in the portal venous blood in 30 of 58 patients (52%). The mean (+/- SD) microvessel count in the tumors from patients with expression of GCC mRNA in their portal venous blood was 82.74 +/- 24.97. The corresponding values in the tumors from patients without expression of GCC mRNA in portal venous blood was 65.96 +/- 19. For each 10-microvessel increase per x200 field, the risk of colorectal epithelial cell presence in the portal venous blood increased 1.52-fold (95% confidence interval, 1.19-2.12; P = 0.005). CONCLUSION: High intratumoral vessel count was noted to be a valuable factor for predicting the presence of colorectal epithelial cells in the portal venous blood.

Adenocarcinoma↗