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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Transient renal glycosuria in a patient with acute pyelonephritis.

Glycosuria was detected in a 37-year-old Chinese woman by a urinary examination in a local clinic with clinical evidence of acute pyelonephritis (APN). Transient glycosuria is an unusual complication of acute pyelonephritis in non-diabetic patients. As there is growing prevalence of type 2 diabetes in the population worldwide, it must be recognized that mistaken diagnosis of diabetes mellitus by glycosuria may predispose patients to an unfavorable hypoglycemic episode. Thus definite diagnosis of diabetes mellitus should be made only after recovery of APN by means of urinalysis or by simultaneous blood glucose concentration analysis.

Acute Disease↗

Retrograde transcatheter occlusion of patent ductus arteriosus: preliminary experience in Gianturco coil technique without heparinization.

BACKGROUND: The aim of this study was to report the initial experience of using the Gianturco coil (Cook Cardiology, Bloomington, Indiana) without heparinization to close patent ductus arteriosus (PDA). PATIENTS AND METHODS: Forty consecutive patients (30 females, 10 males) underwent transcatheter closure of a PDA via the right femoral artery approach without heparinization. Patients ages ranged from 7 months to 55 years (median, 6.8 years); weights ranged from 7.8 65 kg (median, 18.3 kg). Twenty-one patients had cardiomegaly (n = 21), congestive heart failure (n = 10), or both (n = 10). The PDAs measured 0.8 4.5 mm (median, 2.6 mm) at the narrowest diameter; the mean Qp/Qs ranged from 1.0 2.6 (1.4 +/- 0.4). The helical diameter of the coil that we chose was 1.7 times the narrowest PDA diameter. The length of the coil was sufficient to produce 4 or 5 loops. RESULTS: Successful coil placement was accomplished in all 40 patients. Thirty-five patients (87.5%) underwent single coil implantation, 2 patients (5%) had 2 coils, and 3 patients (7.5%) had 3 coils. Complete ductus occlusion was achieved in 80% of cases at the end of the procedure, while 8 patients had minimal shunt detected by aortography or echocardiography. The occlusion rate increased to 87.5% by the next day, 90% by 1 month, 92.5% by 3 months, 95% by 6 months, and 97.5% by 9 and 12 months. Only one asymptomatic patient had minimal residual shunt detected by color Doppler at 12 months follow-up. At a median follow-up of 17 months (range, 5 25 months), no patient had thromboembolism, endocarditis, coil migration, diminished femoral pulse or hemolysis. CONCLUSION: Our preliminary results suggest that retrograde transcatheter closure of PDA with the Gianturco coil without heparinization is feasible, safe and efficacious. A single coil allowed complete occlusion of PDA 3 mm in diameter.

Adolescent↗

Growth pattern of renal angiomyolipoma on computed tomography: report of two cases.

The incidence of renal angiomyolipoma is increased in patients with tuberous sclerosis. Renal angiomyolipomas frequently exhibit both intratumoral and subcapsular or perirenal hemorrhage when they grow into the extrarenal space. Evidence of serial morphologic change is crucial to decision-making for surgical exploration in patients with growing renal angiomyolipomas. We report two cases of angiomyolipoma of the kidney with expansion of an angiomyolipoma into the subcapsular region. Neither patient had tuberous sclerosis and both developed bleeding when the mushroom-shaped tumor reached the extrarenal space. These cases suggest that expansion of the tumor into the subcapsular region is indicative of impending rupture of a renal angiomyolipoma.

Adult↗

Primary angioplasty in acute inferior myocardial infarction with anomalous-origin right coronary arteries as infarct-related arteries: focus on anatomic and clinical features, outcomes, selection of guiding catheters and management.

BACKGROUND: Inferior wall myocardial infarction caused by obstruction of an anomalous-origin right coronary artery (RCA) is a rare angiographic finding; primary angioplasty to an anomalous-origin RCA has never been reported. METHODS: In 185 patients with acute inferior wall myocardial infarction resulting from RCA occlusion who underwent primary angioplasty, eight patients (4.3%) had anomalous-origin RCAs. RESULTS: Coronary angiography showed that all 8 patients had a dominant RCA. Six patients (75%) had an anomalous-origin RCA arising from the anterior aspect of the ascending aorta above the sinotubular line and the other 2 patients (25%) had an anomalous-origin RCA arising from the left sinus of Valsalva with a separate ostium from the left main coronary artery. The standard Judkins right guiding catheter did not offer adequate support in these patients. In the group of 6 patients, an Amplatz guiding catheter offered good support, while a standard Judkins left guiding catheter was adequate in the other 2 patients. Obstruction of the proximal RCA occurred in 6 patients (75%). Successful reperfusion was achieved in 6 patients (75%), resulting in an uneventful clinical course and long-term survival (mean follow-up, 24.9 +/- 16.5 months). Two patients (25%) had unsuccessful reperfusion and died from cardiogenic shock. CONCLUSIONS: In this small series, anomalous-origin RCAs were the dominant artery and predisposed to atherosclerosis at the proximal portions. We suggest that appropriate guide catheter selection and careful manipulation are essential for the success of revascularization. Complete reperfusion results in an excellent clinical and long-term outcome in patients with anomalous-origin RCAs.

Angioplasty, Balloon, Coronary↗

Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subjects with juvenile rheumatoid arthritis.

BACKGROUND: To evaluate T helper 1 (Th1)/Th2 cells and cytokines in patients with three different subtypes of juvenile rheumatoid arthritis (JRA). METHODS: Peripheral blood was obtained from 25 children with JRA suffering from active arthritis (8 systemic, 9 pauciarticular and 8 polyarticular). Eight healthy children were recruited as controls. T helper cells from peripheral blood mononuclear cells (PBMC) were evaluated by using intracellular staining analysis of cytokine production with 3-colored flow cytometry. A Th1 cell was defined as an interferon-gamma (IFN-gamma) producing CD4+ cell, and a Th2 cell as an interleukin-4 (IL-4) producing CD4+ cell. The production of IL-2, IL-4, IL-5 and IFN-gamma from PBMC was measured by ELISA. RESULTS: In comparison with normal controls, the patients with JRA had significantly fewer Th2 cells among their PBMC (0.78 +/- 0.56% vs. 5.44 +/- 2.33%, p < 0.001). The percentage of Th1 cells among PBMC was not different between patients and normal controls (4.32 +/- 3.24% vs. 4.52 +/- 2.56%, p > 0.5). The ratio of Th1/Th2 cells in the patient group was significantly higher than the control group (8.38 +/- 8.63 vs. 0.95 +/- 0.66, p < 0.001). After 24-hour culture, the PBMC from JRA patients produced less IL-4 than that of controls (3.61 +/- 0.56 pg/mL vs. 4.29 +/- 0.68 pg/mL, p = 0.002). The production of IL-2, IL-5, and IFN-gamma did not show significant differences between JRA patients and normal controls. CONCLUSION: Decreased IL-4 producing T-helper cells were identified in all three subtypes of JRA. This implicates that an imbalance of Th sub-populations might be a predominant factor in JRA pathogenesis.

Adolescent↗