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Biomedical subjects

C J Wu

Publications and source records attributed to C J Wu.

At least 19 recordsLinked to original sources
PubMed2006

Ten-year experience with living related donated splenic transplantation for the treatment of hemophilia A.

AIM: Six cases of hemophilia A treated with living related donated splenic transplantation (LRDST) were performed over 10 years. METHODS: We reviewed the six consecutive cases of LRDST from 1992 to 2002. Three patients received whole spleen allografts and the other three, partial spleen allografts. All allografts were transplanted to the extraperitoneal space in the right iliac fossa by an end-to-end anastomosis between the splenic artery and the internal iliac artery and an end-to-side anastomosis between the splenic vein and the external (or common) iliac vein. After the operation, a combined regimen with cyclosporine, azathioprine, anti-lymphocyte globulin, OKT3, was administered to suppress the immune reaction. RESULTS: The functional period of the allografts varied between 30 days to 4 years. Patient factor-VIII (F-VIII) levels rose from less than 5% before operation to 15% to 56% postoperatively. One patient died from central nervous system complications. Another lost his graft because exogenous F-VIII was not supplemented in timely fashion at the onset of rejection. And the third could no longer afford the expensive immunosuppressive drugs at 2 years after the operation and eventually lost the spleen. The remaining three patients presently have regained self-support, among whom one has survived for 4 years. CONCLUSION: Though the sample pool is relatively small, our clinical observations tend to confirm LRDST as a feasible, effective treatment for hemophilia A.

Drug Therapy, Combination↗
PubMed2006

Aim, design and methods of the 'reasons for not intensifying antihypertensive treatment' (RIAT): an international registry in essential hypertension.

Failure of physicians to adhere to hypertension guidelines may partly account for the failure to achieve blood pressure (BP) goals in clinical practice. The aim of this trial is a comprehensive description of the approach of physicians in the management of high BP among primary care patients. It will primarily assess what are the Reasons for not Intensifying an Antihypertensive Treatment (RIAT), when predefined individual BP goals are not achieved. Open intervention survey was conducted in 17 countries in Latin America, Eastern Europe, Africa and Asia in family practices, government and private clinics. The registry is based on a three-step epidemiological design. Step one shall identify guidelines and recommendations taken as reference in each country for the management of hypertension. Step two will assess the variance between individual targets defined by physicians in their practice compared to guidelines and recommendations. Step three is a prospective registry where physicians collect patient data at baseline; determine individual target BP values. Several follow-up visits are proposed to monitor achievement of these targets. Step three of RIAT aims at providing responses to several key objectives. Recruitment is under way aiming at enrolling 33,000 patients. To identify, what is the BP targeted according to the risk factor profile and what are the reasons for not modifying an antihypertensive treatment when BP goals are not reached, and to analyse the type of antihypertensive drugs prescribed according to compelling indications and to assess the percentage of patients reaching target figures.

Antihypertensive Agents↗
PubMed2006

Randomized comparison of two rescue therapies for Helicobacter pylori infection.

BACKGROUND: Bismuth salts are not available worldwide. It remains unknown whether clarithromycin can replace bismuth salts as an adjuvant agent in the rescue regimens for Helicobacter pylori infection. We therefore designed the prospective study to compare the efficacies of two rescue therapies for H. pylori infection after standard triple therapies. PATIENTS AND METHODS: Ninety-three patients who failed H. pylori eradication using proton pump inhibitor plus clarithromycin and amoxicillin were randomly assigned to undergo rescue therapy with esomeprazole, clarithromycin, tetracycline and metronidazole (ECTM group, n = 46) or esomeprazole, bismuth subcitrate, tetracycline and metronidazole (EBTM group, n = 47). Follow-up endoscopy was performed at 8 weeks after the end of treatment to assess the treatment response. RESULTS: Intention-to-treat analysis demonstrated both groups had similar eradication rates (ECTM 74% vs. EBTM 77%; P = 0.76) and drug compliance (ECTM 94% vs. EBTM 96%; P = 0.68). However, the frequency of adverse events in the ECTM group was higher than that in EBTM group (ECTM 57% vs. EBTM 36%, P = 0.05). In the EBTM group, eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (67%[8/12] vs. 100%[9/9], P = 0.05). However, eradication rates were similar between metronidazole-susceptible and metronidazole-resistant strains in ECTM group (69%[9/13] vs. 70%[7/10], P = 1.00). CONCLUSIONS: The new ECTM second-line therapy can achieve similar eradication rate as standard EBTM therapy. It may be very useful in countries where bismuth salts are not available.

Adult↗
PubMed2005

Redox regulation of matrix metalloproteinase gene family in small cell lung cancer cells.

It has been implicated that reactive oxygen species (ROS) play important roles in modulating tumor progression. However, the mechanisms by which redox-regulated tumor progression are largely unknown. We previously demonstrated that reduced intracellular redox conditions could be achieved in stably transfected small cell lung cancer cells with gamma-glutamylcysteine synthetase (gamma-GCSh) cDNA which encodes a rate-limiting enzyme in the biosynthesis of glutathione (GSH), a major physiological redox regulator. In the present study, using DNA microarray analyses, we compared the expression profiles between the gamma-GCSh-transfected cells and their nontransfected counterpart. We observed downregulation of several matrix metalloproteinases (MMPs), i.e., MMPI and MMP3, and MMP10 in the transfected cells. Dot blot and Northern blot hybridizations confirmed that, among the 18 MMP gene family members and four tissue inhibitors of matrix metalloprotein family (TIMP) analyzed, the expression levels of these three MMPs were consistently reduced. Transiently increased gamma-GCSh expression using tetracycline-inducible gamma-GCSh adenoviral expression system also showed down-regulation of MMP3 and MMP10, but not MMP1. Our results demonstrated that redox regulation of MMP1, MMP3 and MMP10 expression depend upon different modes of redox manipulation. These results bear implication that antioxidant modulation of antitumor progression may be contributed at least in part by the downregulation of a subset of metrix metalloproteins.

Blotting, Northern↗
PubMed2003

Anti-leukemic immunity against U937 cells in uremic patients.

To examine anti-tumor immunity in uremic patients undergoing regular hemodialysis, we designed this study using in vitro mononuclear cell (MNC) cultures, with human leukemic U937 cells as the target. MNC were collected and cultured from uremic subjects and age- and gender-matched healthy controls. Conditioned media from the cultures (MNC-CM) were collected after stimulation with various concentrations of phytohemagglutinin (PHA). The proliferation-inhibiting and differentiation-inducing activities of the PHA-MNC-CM on U937 cells were evaluated. The growth inhibition activity of uremic patients' PHA-MNC-CM was lower than that of controls. The differentiation-inducing effects were evaluated by morphological scoring, superoxide production, and monocyte-associated antigen expression (CD14 and CD68). All three parameters demonstrated that the differentiation-inducing effect of MNC-CM increased with increasing doses of PHA. These effects, however, were significantly less in uremic patients compared to controls at higher doses of PHA. The levels of TNF-alpha and IFN-gamma in PHA-MNC-CM increased in a PHA dose-dependent manner and were much higher in the controls. We conclude that the capacity of MNC from uremic hemodialysis patients to produce anti-leukemic immunity is significantly lower than that of healthy controls.

Aged↗
PubMed2002

Association between serum inflammatory cytokines and disease activity in juvenile idiopathic arthritis.

Circulating interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha), osteocalcin, and conventional parameters of inflammation were examined serially in 14 children with juvenile idiopathic arthritis (JIA) to determine any correlation with the disease activity. Serum IL-1beta was undetectable in all JIA patients. Serum IL-6, white blood cell counts, platelet counts, erythrocyte sedimentation rate and C-reactive protein levels were significantly elevated in the active phase of JIA, whereas hemoglobin levels were significantly lower. Osteocalcin levels were decreased and TNF-alpha increased in active JIA status, but these differences showed no statistical significance. We concluded that inflammatory cytokines play an important role in JIA. Monitoring IL-6 in children with JIA is useful in determining disease activity and response to therapy. These findings confirm earlier reports.

Adolescent↗
PubMed2001

Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?

PURPOSE: To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes. METHODS AND MATERIALS: At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-alpha, mIL-1 alpha, mIL-1 beta, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-gamma) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay. RESULTS: Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg) suppresses both basal cytokine mRNA levels and this early response when given immediately after irradiation. However, by 24 h, in mice treated with DEX alone or DEX plus radiation, there was a strong rebound effect that lasted up to 3 days. Modification of the early radiation-induced response by DEX did not change the second wave of cytokine gene expression in the lung that occurs at 1 to 2 weeks, suggesting that early cytokine gene induction might not determine subsequent molecular events. A single dose of DEX attenuated, but did not completely suppress, increases in cytokine mRNA levels induced by lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no significant rebound effect was seen. Five days of dexamethasone treatment in the pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and, again, there was a rebound effect after withdrawal of the drug. CONCLUSIONS: Our findings suggest that short-term use of dexamethasone can temporarily suppress radiation-induced pro-inflammatory cytokine gene expression, but there may be a rebound after drug withdrawal and the drug does little to change the essence and course of the pneumonitic process.

Animals↗
PubMed2001

The tyrosine phosphatase SHP-2 is required for mediating phosphatidylinositol 3-kinase/Akt activation by growth factors.

SHP-2 is a ubiquitously expressed non-transmembrane tyrosine phosphatase with two SH2 domains. Multiple reverse-genetic studies have indicated that SHP-2 is a required component for organ and animal development. SHP-2 wild-type and homozygous mutant mouse fibroblast cells in which the N-terminal SH2 domain was target-deleted were used to examine the function of SHP-2 in regulating Phosphatidylinositol 3-Kinase (PI3K) activation by growth factors. In addition, SHP-2 and various mutants were introduced into human glioblastoma cells as well as SHP-2(-/-) mouse fibroblasts. We found that EGF stimulation and EGFR oncoprotein (DeltaEGFR) expression independently induced the co-immunoprecipitation of the p85 subunit of PI3K with SHP-2. Targeted deletion of the N-terminal SH2 domain of SHP-2 severely impaired PDGF- and IGF-induced Akt phosphorylation. Ectopic expression of SHP-2 in U87MG gliobastoma cells elevated EGF-induced Akt phosphorylation, and the effect was abolished by mutation of its N-terminal SH2 domain. Likewise, the reconstitution of SHP-2 expression in the SHP-2(-/-) cells enhanced Akt phosphorylation induced by EGF while rescuing that induced by PDGF and IGF. Further lipid kinase activity assays confirmed that SHP-2 modulation of Akt phosphorylation correlated with its regulation of PI3K activation. Based on these results, we conclude that SHP-2 is required for mediating PI3K/Akt activation, and the N-terminal SH2 domain is critically important for a "positive" role of SHP-2 in regulating PI3K pathway activation.

Animals↗
PubMed2001

Quantitation of T-cell neogenesis in vivo after allogeneic bone marrow transplantation in adults.

Following myeloablative therapy, it is unknown to what extent age-dependent thymic involution limits the generation of new T cells with a diverse repertoire. Normal T-cell receptor gene rearrangement in T-cell progenitors results in the generation of T-cell receptor rearrangement excision circles (TRECs). In this study, a quantitative assay for TRECs was used to measure T-cell neogenesis in adult patients with leukemia who received myeloablative therapy followed by transplantation of allogeneic hematopoietic stem cells. Although phenotypically mature T cells had recovered by 1 to 2 months after bone marrow transplantation (BMT), TREC levels remained low for 3 months after BMT. T-cell neogenesis became evident by 6 months, and normal levels of adult thymic function were restored at 6 to 12 months after BMT. Subsequent leukemia relapse in some patients was associated with reduced TREC levels, but infusion of mature donor CD4(+) T cells resulted in rapid restoration of thymic function. These studies demonstrate that T-cell neogenesis contributes to immune reconstitution in adult patients and suggest that thymic function can be manipulated in vivo. (Blood. 2001;98:1116-1121)

Adult↗
PubMed2001

CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia.

This report describes a tumor-associated antigen, termed CML66, initially cloned from a chronic myelogenous leukemia (CML) cDNA expression library. CML66 encodes a 583-aa protein with a molecular mass of 66 kDa and no significant homology to other known genes. CML66 gene is localized to human chromosome 8q23, but the function of this gene is unknown. CML66 is expressed in leukemias and a variety of solid tumor cell lines. When examined by Northern blot, expression in normal tissues was restricted to testis and heart, and no expression was found in hematopoietic tissues. When examined by quantitative reverse transcription-PCR, expression in CML cells was 1.5-fold higher than in normal peripheral blood mononuclear cells. The presence of CML66-specific antibody in patient serum was confirmed by Western blot and the development of high titer IgG antibody specific for CML66 correlated with immune induced remission of CML in a patient who received infusion of normal donor lymphocytes for treatment of relapse. CML66 antibody also was found in sera from 18-38% of patients with lung cancer, melanoma, and prostate cancer. These findings suggest that CML66 may be immunogenic in a wide variety of malignancies and may be a target for antigen-specific immunotherapy.

Amino Acid Substitution↗
PubMed2001

A CD4+ T cell clone selected from a CML patient after donor lymphocyte infusion recognizes BCR-ABL breakpoint peptides but not tumor cells.

BACKGROUND: In patients with chronic myelocytic leukemia (CML), the breakpoint cluster region and fusion between the BCR and the c-ABL genes (BCR-ABL) oncogen product is a potential tumor-specific antigen. Previous studies have shown that T cells specific for the junctional region peptides of the BCR-ABL oncoprotein can be detected in healthy individuals as well as in patients with CML in chronic phase. We assessed whether BCR-ABL- specific T cells could be found in a patient achieving a complete cytogenetic remission after CD4+ donor lymphocyte infusion. METHODS: Using dendritic cells pulsed with BCR-ABL breakpoint peptides as antigen-presenting cells, we stimulated patient peripheral blood lymphocytes to isolate peptide-specific T cell clones present at the time of the cytogenetic response. T cell clones were isolated and the cellular specificity of these cells was examined. RESULTS: A CD3+ CD4+ T cell clone (1F7) that recognizes overlapping p210 junctional peptides presented by HLA-DR molecules was identified and expanded in vitro. Clone 1F7 failed to recognize autologous tumor cells as well as dendritic cells derived from patient CML cells. Clone 1F7 did not inhibit the growth and differentiation of CML precursor cells in a standard colony formation assay. Finally, using a clone-specific probe, 1F7 cells could not be detected in patient peripheral blood at the time of the donor lymphocyte infusion response. CONCLUSIONS: These results suggest that clone 1F7 was selected in vitro using highly potent peptide pulsed dendritic cells but was not representative of the anti-leukemia immune response in vivo. Based on these findings, CD4+ T cells with BCR-ABL specificity do not appear to be mediators of the anti-leukemia response in vivo after donor lymphocyte infusion.

Adult↗
PubMed2001

Inhibition of neointimal formation in porcine coronary artery by a Ras mutant.

BACKGROUND: Therapeutic approaches to reduce the neointimal formation caused by balloon injury have been focused mainly on experimental models of restenosis in the rat carotid artery. However, restenosis in rat carotid artery may not replicate the coronary arterial responses to injury in larger animals and humans. METHODS: In this study, we used pig coronary arteries as an animal model to evaluate the preventive effects of a virus-mediated dominant negative mutant RasN17 on balloon injury-induced restenosis. The viral particles were delivered to the balloon-injured coronary arteries via a dispatch catheter to keep the virus in a confined arterial segment for 10 min to reach optimal transfection. Six weeks after balloon injury, the pigs were sacrificed and the left anterior descending arteries were isolated for histological analysis. RESULTS: Neointima formation was prominent in the group receiving balloon injury as compared with the uninjured controls. A remodeling process with migration of collagen was also found in the injured coronary arteries. The application of AdRasN17 led to a 56% decrease in neointima formation and a 75% increase in lumen size, as compared with the balloon-injured vessels treated with AdLacZ control. CONCLUSIONS: These results suggest that AdRasN17 is an effective therapeutic gene in preventing balloon injury-induced neointimal formation in pig coronary arteries.

Animals↗
PubMed2001

The presence of three isoflavonoid compounds in Psoralea corylifolia.

The optimization of a high-performance liquid chromatographic method to determine three isoflavonoids (daidzein, genistein, and biochanin A) in the fruit of Psoralea corylifolia is developed and validated. Dried psoralea fruit powder is extracted with aqueous methanol followed by the hydrolysis of the analytes' conjugated glycosides with hydrochloric acid. The HPLC assay is performed on a reverse-phase C18 column with gradient elution using acetonitrile and 10% acetic acid as the mobile phase at a flow rate of 0.8 mL/min. Flavone is used as the internal standard and the substances are detected at 260 nm. Calibrations are linear (correlation coefficient > or = 0.995) for all three analytes. The limits of detection are 0.01 microg/mL for daidzein and genistein and 0.1 microg/mL for biochanin A. The overall intra- and interassay precision range from 2.5% to 4.9% and from 0.5% to 4.7%, respectively. The method proved to be sensitive, specific, accurate, and precise for the determination of daidzein, genistein, and biochanin A in Psoralea corylifolia.

Calibration↗
PubMed2001

Unusual complication of retrograde dissection to the coronary sinus of valsalva during percutaneous revascularization: a single-center experience and literature review.

BACKGROUND: While coronary dissection, which is one of the most frequently occurring complications during interventional procedures, has various forms, extensive coronary dissection retrograde to the coronary sinus of Valsalva (CSV) is very rarely observed. METHODS AND RESULTS: Within the last 5 years, we retrospectively reviewed our experience with 4,700 consecutive patients who underwent angioplasty procedures, 7 of whom (0.15%) developed extensive coronary dissection retrograde to the CSV. Six of the seven patients developed retrograde dissection of the right CSV during angioplasty to the right coronary artery. One of the seven patents developed retrograde dissection of the left CSV during angioplasty to the left anterior descending artery. Retrograde dissection, which extended to the ascending aorta in two patients, was observed by transthoracic echocardiography and surgical findings, respectively. Five patients were successfully treated by coronary stenting. However, this complication caused four patients to have acute myocardial infarctions, resulting in emergency surgery for one patient and in-hospital death for another. CONCLUSIONS: Our experience increased our understanding of this very rare complication. However, this complication may be life threatening, and patients in this clinical setting may have a potential risk for acute myocardial infarction, emergency surgery, or even sudden cardiac death. Therefore, it is important to learn how to promptly diagnose and manage this complication.

Aortic Dissection↗
PubMed2001

Effect of primary angioplasty on total or subtotal left main occlusion: analysis of incidence, clinical features, outcomes, and prognostic determinants.

BACKGROUND: Although acute left main coronary artery (LMCA) occlusion is a rare clinical entity, it carries a very high mortality rate. The purposes of this study were to evaluate the effect of primary angioplasty for a severely obstructed or totally occluded LMCA, and to determine the incidence, clinical features, outcome, and prognostic determinants in this clinical setting. MATERIALS AND METHODS: Between May 1993 and July 2000, a total of 740 patients with acute myocardial infarction underwent primary angioplasty in our hospital. Eighteen of 740 patients (2.4%) with a severely obstructed or totally occluded LMCA constituted the population of this study. RESULTS: Seventeen of 18 patients (94.4%) experienced pulmonary edema (including 14 patients in cardiogenic shock). Six patients (33.3%) sustained sudden death due to malignant ventricular tachyarrhythmias. Coronary angiography showed that there were variable grade flow of intercoronary collaterals in 12 patients (66.7%), a totally occluded LMCA in 8 patients (44.4%), an incompletely occluded LMCA in 10 patients (55.6%), and a dominant right coronary artery (RCA) in 16 patients (88.9%). Primary angioplasty of the LMCA was performed with a 72.2% procedural success rate. Four patients (22.2%) received coronary artery bypass surgery after angioplasty. Six patients (33.3%) died in the hospital. Two patients died after discharge. Ten of 18 patients (55.6%) survived in long-term follow-up (mean +/- SD, 44 +/- 14 months). Those patients who survived to be discharged had significantly higher combined coexisting incidence of intercoronary collaterals, dominant RCA, and incompletely occluded LMCA (100% vs 0.0%, p = 0.0006) than those patients who died in the hospital. CONCLUSIONS: Acute obstructive LMCA disease generally presented as pulmonary edema, cardiogenic shock, or sudden death. Only those who had combined coexistence of intercoronary collaterals, a dominant RCA, and an incompletely occluded LMCA could survive to be discharged. Our experience suggests that primary LMCA angioplasty is a feasible and effective procedure, and it may save lives in this clinical setting.

Adult↗
PubMed2001

Successful metallic stent placement for recurrent stenosis after balloon angioplasty of membranous obstruction of inferior vena cava.

A 23 year-old Taiwanese male presented with complete membranous obstruction of the inferior vena cava at its suprahepatic portion. After 3 angioplasty procedures using Inoue-balloon catheters, a Wall stent was deployed for restenosis 4 years after the first procedure. Venography at 6 months showed no significant restenosis. At 20 months transfemoral venography confirmed patency of the vena cava.

Adult↗