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Biomedical subjects

Y J Chiang

Publications and source records attributed to Y J Chiang.

At least 19 recordsLinked to original sources
PubMed2001

Effective treatment of small murine hepatocellular carcinoma by dendritic cells.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. This investigation examined whether dendritic cell-based immunotherapy can treat murine HCC effectively. Bone marrow-derived dendritic cells were propagated from C57BL/10J mice in GM-CSF (4 ng/mL) and interleukin (IL)-4 (1,000 micro/mL). The dendritic cells were pulsed with a Hepa1-6 lysate overnight and employed to treat murine HCC. For in vivo study, HCC was created by inoculation of hepa1-6, 5 x 10(5) cells, in the flank of C57BL/10J mice. HCC were categorized into small (3 x 3-mm) and large (5 x 5-mm) tumors. These HCC were treated by dendritic cells intravenously, twice at weekly intervals. The results revealed that lymphocytes could be gathered around small HCC after administration of Hepa1-6 lysate-pulsed dendritic cells. Seven of 12 (58.3%) small HCC could be eradicated completely by dendritic cell-based immunotherapy, and 33.3% of the small tumors responded to immunotherapy partially which were held in a stable condition for 34.0 +/- 7.4 days before the tumors regrew. For large HCC, lymphocytes did not gather around the tumors, and the tumors cannot be eradicated effectively by dendritic cells. However, dendritic cell-based immunotherapy could slow down the growth rate of large tumors (116.2 +/- 91.4 mm(3) vs. 234.0 +/- 149.1 mm(3) of the control on day 7, P =.043; and 280.3 +/- 224.7 mm(3) vs. 870.0 +/- 418.9 mm(3) of the control on day 17, P <.001). Conclusively, dendritic cells pulsed with a Hepa1-6 lysate can be employed to treat small HCC in vivo effectively. However, the efficacy of dendritic cell-based immunotherapy decreases while tumors grow.

Animals↗
PubMed2001

CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the interleukin-3 survival signal.

The Ces-2/E2A-HLF binding element (CBE) is recognized by Caenorhabditis elegans death specification gene product Ces-2 and human acute lymphocytic leukemia oncoprotein E2A-HLF. In an attempt to identify a cellular CBE-binding protein(s) that may be involved in apoptosis regulation in mammals, multiple nuclear binding complexes of CBE were identified in various mammalian cell lines and tissues by electrophoretic mobility shift assay. Cyclic AMP (cAMP)-responsive element (CRE)-binding protein (CREB) was present in one major CBE complex of Ba/F3 and TF-1 cells, and both in vitro-translated and Escherichia coli-synthesized CREB bound to CBE. Activation of CREB by cAMP-elevating chemicals or the catalytic subunit of protein kinase A (PKAc) resulted in induction of the CBE-driven reporter gene. Stimulation of Ba/F3 cells with interleukin-3 (IL-3) promptly induced phosphorylation of CREB at serine(133) partially via a PKA-dependent pathway. Consistently, Ba/F3 cell survival in the absence of IL-3 was prolonged by activation of PKA. Conversely, treatment of cells with a PKA inhibitor or expression of the dominant negative forms of the regulatory subunit type I of PKA and CREB overrode the survival activity of IL-3. Last, the bcl-2 gene was demonstrated to be one candidate cellular target of the CREB-containing CBE complex, as mutations in the CRE and CBE sites significantly reduced the IL-3 inducibility of the bcl-2 promoter. Together, our results suggest that CREB is one cellular counterpart of Ces-2/E2A-HLF and is part of IL-3 dependent apoptosis regulation in hematopoietic cells.

Animals↗
PubMed2001

Liver-derived dendritic cells induce donor-specific hyporesponsiveness: use of sponge implant as a cell transplant model.

Spontaneously accepted mouse liver allografts are capable of protecting subsequently transplanted donor organs from rejection; however, the underlying mechanisms are unclear. Dendritic cells (DC) residing in liver grafts are likely important in tolerance induction. DC propagated from mouse liver with GM-CSF are phenotypically and functionally immature. They are poor allostimulators in MLR and prolong survival of pancreatic islet allografts. It has been problematic to perform mechanistic studies in an islet transplant model because of difficulties in obtaining sufficient graft infiltrating cells. In this study, we used a sponge allograft model [i.e.. a subcutaneously implanted sponge matrix loaded with B10 (H2b) spleen cells]. To investigate the influence of administration of donor (B10) liver-derived DC on alloimmune reactivity of C3H (H2k) hosts, sponge graft infiltrating cells (SGIC) and recipient spleen cells were isolated, and their immunophenotype and donor-specific cytotoxic T lymphocyte (CTL) activity were examined. The results illustrate that donor-specific CTL activity of T cells are lower in recipients that had received systemic treatment with liver-derived immature DC, associated with a decrease in CD8+ cell population and an increase in Gr-1+ cells in SGIC, compared with recipients treated with mature bone marrow (BM)-derived DC. Interestingly, administration of liver DC directly into the sponge did not inhibit T cell responses. These data suggest that systemic administration of donor liver DC induces donor-specific hyporesponsiveness, probably not by direct inhibition of graft infiltrating T cells. The increased Gr-1+ cells may play immune regulatory roles in induction of host donor-specific hyporesponsiveness.

Animals↗
PubMed2000

Cbl-b regulates the CD28 dependence of T-cell activation.

Whereas co-stimulation of the T-cell antigen receptor (TCR) and CD28 triggers T-cell activation, stimulation of the TCR alone may result in an anergic state or T-cell deletion, both possible mechanisms of tolerance induction. Here we show that T cells that are deficient in the adaptor molecule Cbl-b (ref. 3) do not require CD28 engagement for interleukin-2 production, and that the Cbl-b-null mutation (Cbl-b(-/-)) fully restores T-cell-dependent antibody responses in CD28-/- mice. The main TCR signalling pathways, such as tyrosine kinases Zap-70 and Lck, Ras/mitogen-activated kinases, phospholipase Cgamma-1 and Ca2+ mobilization, were not affected in Cbl-b(-/-) T cells. In contrast, the activation of Vav, a guanine nucleotide exchange factor for Rac1/Rho/CDC42, was significantly enhanced. Our findings indicate that Cbl-b may influence the CD28 dependence of T-cell activation by selectively suppressing TCR-mediated Vav activation. Mice deficient in Cbl-b are highly susceptible to experimental autoimmune encephalomyelitis, suggesting that the dysregulation of signalling pathways modulated by Cbl-b may also contribute to human autoimmune diseases such as multiple sclerosis.

Adaptor Proteins, Signal Transducing↗
PubMed2000

The role of free to total prostate-specific antigen ratio for prostate cancer in screening patients with total serum levels between 4 and 20 ng/ml.

BACKGROUND: We retrospectively tried to determine if the free to total prostate-specific antigen (f/t PSA) ratio could improve the specificity of PSA in prostate cancer screening of patients with total serum levels between 4 and 20 ng/ml. METHODS: Two hundred ninety-five patients with serum PSA levels from 4 to 20 ng/ml had undergone sextant prostate needle biopsy. Each patient had no prior history of prostate cancer, acute urine retention, or prostatitis. Prebiopsy free PSA values were measured in 155 patients. Total PSA levels were determined with the AxSYM enzyme-linked immunosorbent assay. Free PSA levels were measured with the AxSYM microparticle enzyme immunoassay. RESULTS: Mean f/t PSA ratios were 0.114+/-0.004 in men of the cancer group and 0.161+/-0.008 in men of the benign group (p<0.002). Based on the analysis of sensitivity and specificity in relation to f/t PSA ratios, use of the 18% cutoff point could detect 89% of cancer cases, and at the same time could avoid 35% of unnecessary prostate biopsies. The areas under the receiver-of-characteristic curve for f/t PSA ratio and total PSA were 0.649 and 0.545, respectively. CONCLUSION: Serum f/t PSA ratios were significantly lower in patients with prostate cancer than in patients with benign disease. The determination of an appropriate f/t PSA ratio should be based on the generated data such as that demonstrated in this study in order to improve diagnostic accuracy and specificity for patients with equivocal PSA values and to avoid conducting unnecessary prostate biopsies.

Aged↗
PubMed1999

Enterovesical fistula: experiences with 41 cases in 12 years.

BACKGROUND: A retrospective analysis of enterovesical fistula treated at Chang Gung Memorial Hospital was conducted to determine the optimal diagnosis and management of this disease. METHODS: The records of 41 patients who presented from 1984 to 1996 and had a final diagnosis of enterovesical fistula were retrospectively reviewed. The etiology, symptoms on presentation, diagnostic tools, and modality of treatment were analyzed. RESULTS: The majority of these cases were associated with malignancy (38, 92.7%), and the others with diverticulitis (2, 4.9%) and iatrogenic causes (1, 2.4%). In those with malignancy, 15 patients (39.5%) were found to have tumor recurrence. The most frequent symptom in enterovesical fistula was fecaluria (58.5%), followed by abdominal pain (22%) and dysuria (14.6%). Diagnostic tools included the barium enema, cystography, and cystoscopy; these methods could identify the fistula in 63.2%, 60%, and 53.8% of the patients, respectively. Methods of management included diversion only (39%), one-stage fistula repair (36.6%), and watchful surveillance (24.4%). CONCLUSION: Enterovesical fistula should be considered if fecaluria, pneumaturia, or persistent non-specific urinary tract infection present as the initial complaint. A thorough surgery for a possible underlying malignancy is mandatory when confronted with enterovesical fistula, since the incidence of inflammatory bowel disease is low in this area. An abdominal computer tomography (CT) scan, barium enema, and cystogram can be useful diagnostic tools. Treatment of this entity should be individualized according to each patients clinical status.

Adult↗
PubMed1997

Application of cryoablation in the management of prostate cancer.

BACKGROUND: Radical prostatectomy is the most common and effective therapy for localized prostate cancer. But in addition to its surgical complications, even highly selected series carry a positive margin rate of 35 to 50%. Radiotherapy is another alternative for prostate cancer, but following radiotherapy there have been high positive biopsies reported. Cryosurgery, defined as in situ freezing and hence, devitalization of neoplastic tissues, has currently raised the interest of urologists in the management of localized prostate cancer or failed radiotherapy. MATERIAL: Five patients underwent transperineal cryosurgery of prostate in Chang Gung Memorial Hospital. Among them, three cases were stage D, one stage B and another failed radiotherapy of stage C prostate cancer. All patients received hormone therapy too. RESULTS: PSA declined in 3 patients and biopsies showed intraductal neoplasia. All 5 patients suffered from urine incontinence and one persisted. No mortality has been reported. CONCLUSION: Cryoablation of the prostate is an alternative for treatment of prostate cancer.

Aged↗
PubMed1995

[Analysis of 117 cases of hypospadias--its location, operation and complication].

Hypospadias is a common congenital anomaly in male newborns. The incidence is about one in 300 live male births. In the U.S., about 6000 boys with hypospadias are born each year. For this study, we collected 117 recent (with the last 5 years) cases (88 fresh and 29 referred) who received an operation in our department. We calculated the hypospadias location and the complication rate with the desire of finding out the relationships between them. Our overall complication rate is 51.3% which is much higher than other recent studies and may be related to a different distribution of the hypospadias locations.

Adolescent↗
PubMed1989

The clinical manifestations of the tuberculous pleural effusion in adult patients.

The clinical data of 52 patients with tuberculous pleural effusion were analyzed. Their average age was 48 years old. Thirty two (62%) of them were sick for less than one week. Fever, chest pain and cough were the predominant pictures. Six of the 52 patients had coexisting disease. Intermediate strength protein purified derivative (PPD) test was found to be positive in 14 out of 31 (45%) patients. Their pleural effusions were usually unilateral, right-sided, and nearly half of them occupied more than half of the hemithorax. One third of these patients and concomitant pulmonary tuberculosis and pleural effusion. None of the patients had grossly bloody effusion. All of the effusions were exudative, and the glucose levels in the pleural fluid were invariably above 60 mg/dl. Presence of mesothelial cells in the pleural fluid was found in 28% of them, but none of the patients presented with significant eosinophils in the pleural fluid. Pleural fluid and sputum cultures for Mycobacterium tuberculosis usually reveal a negative study unless a concomitant pulmonary lesion was present. Combined antituberculosis and prednisolone treatment decreased the duration of constitutional symptoms and hastened the resolution of pleural effusion. In conclusion, tuberculous pleural effusion should be considered in elderly patients presenting with massive exudative pleural effusion even with a negative PPD study. Cultures of sputum and pleural fluid are less helpful in patients without parenchymal disease. Prednisolone is recommended in extremely ill patients.

Adolescent↗