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C S Hsieh

Publications and source records attributed to C S Hsieh.

At least 19 recordsLinked to original sources
PubMed2005

The role of TCR specificity in naturally arising CD25+ CD4+ regulatory T cell biology.

CD25+ CD4+ T cells (TR) are a naturally arising subset of regulatory T cells important for the preservation of self-tolerance and the prevention of autoimmunity. Although there is substantial data that TCR specificity is important for TR development and function, relatively little is known about the antigen specificity of naturally arising TR. Here, we will review the available evidence regarding naturally arising TR TCR specificity in the context of TR development, function, and homeostasis.

Animals↗
PubMed2003

Bacteria ascend to liver from the bilioenteric conduit after choledochojejunostomy in the cholestatic rat.

The high incidence of postoperative cholangitis in children with clinical restoration of bile flow after Roux-Y choledochojejunostomy (RYCJ) assumed the concept of a direct ascending cholangitis caused by pathogens in the intestine, into the intrahepatic bile duct via the porta hepatis. It is also well known that jaundiced animals (patients) are more susceptible to infections of the bile ducts following the procedure of bilioenteric anastomosis. An animal experiment was conducted to compare quantitative bacterial cultures of the choledochojejunostomy area and the liver 24 hours after Escherichia coli (ATCC 25922) or sterile normal saline was injected into the bilioenteric conduit (BEC), following RYCJ in rats with or without the proceeding bile duct ligation. A significant increase of E. coli of the same strain (ATCC 25922), that we injected into the BEC, was proved with pulse-field gel electrophoresis (PFGE) and shown in the liver of the jaundiced rats receiving E. coli (ATCC 25922), compared to that in the nonjaundiced rats with normal saline treatment. It is concluded that bacteria often ascend early to the liver from the BEC following RYCJ. This ascending cholangitis model might be produced for further studies.

Animals↗
PubMed2001

Changes in bacterial concentration in the liver correlate with that in the hepaticojejunostomy after bile duct reconstruction: implication in the pathogenesis of postoperative cholangitis.

Postoperative cholangitis is a frequent and unpredictable complication of unknown etiology following bile duct reconstruction (BDR), particularly for biliary atresia. This study was undertaken to correlate the growth of bacteria in the hepaticojejunostomy with that in the liver after BDR. Quantitative bacterial culture was done on the specimens taken from the liver and from the hepaticojejunostomy at 1 week (group 1, n = 7), 1 month (group 2, n = 7), and 2 months (group 3, n = 7) following BDR with Roux-en-Y hepaticojejunostomy in piglets after 2 weeks of common bile duct ligation. The histological examination of the liver and the hepaticojejunostomy, as well as serial monitoring of hemogram and liver function tests, were performed to correlate the findings with the bacterial concentration of the liver and the hepaticojejunostomy following BDR. The bacterial concentration of the hepaticojejunostomy, expressed as log10 colony-forming units per gram (log10 CFU/g) of the hepaticojejunostomy, showed a progressive decrease from 8.38 +/- 1.36 in group 1, 7.07 +/- 2.54 in group 2, to 3.56 +/- 1.31 in group 3 (p = 0.001). The log10 CFU/g of the liver also showed a progressive decrease from 5.02 +/- 1.59 in group 1, 3.16 +/- 1.56 in group 2, to 2.19 +/- 1.09 in group 3 (p = 0.006). There was a significant positive correlation of the log10 CFU/g of the liver (n = 21) with that of the hepaticojejunostomy (n = 21) following BDR (r = 0.600, p = 0.004). Most of the infectious pathogens isolated from the liver were also isolated from the hepaticojejunostomy. The changes in hemoglobin, bilirubin, albumin, and ammonia significantly correlated with the changes of the bacterial concentration of the liver. The results of the study suggests that hepatic bacterial proliferation after BDR is significantly affected by microbial overgrowth in the bilioenteric anastomosis and is associated with deteriorated liver function and hemogram.

Anastomosis, Surgical↗
PubMed2001

Ascending cholangitis provokes IL-8 and MCP-1 expression and promotes inflammatory cell infiltration in the cholestatic rat liver.

BACKGROUND/PURPOSE: Postoperative cholangitis is one of the most common complications after bile duct reconstruction. The pathogenesis and early consequences of ascending cholangitis still are unidentified. METHODS: Male Sprague-Dawley rats were divided into 5 treatment groups: control (n = 4), blood sampling and liver biopsy only; group I, [BDL/Eschericha coli; n = 6], ligation of common bile duct (BDL) for a week, followed by Roux-en-Y choledochojejunostomy (RYCJ) and injection of E coli (ATCC 25922) into Roux limb after 24 hours; group II, [BDL/NS; n = 5], same procedures as in group I, with injection of normal saline (NS) into Roux limb; group III, [SBDL/E coli; n = 6], primary RYCJ was constructed 1 week after sham ligation of common bile duct (SBDL) followed by the same treatment as group I; Group IV, [SBDL/N.S; n = 6], same procedures as in group III, but injecting NS into Roux limb. All animals were killed after 24 hours of treatment. Blood was sampled for culture and serum cytokine levels. The liver was harvested for quantitative bacterial culture, as well as for MCP-1, interleukin (IL)-8 (CINC in the rat) and transforming growth factor beta1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) and for immunohistochemistry. The choledochojejunostomy was resected for culture. Serum cytokine levels were detected by ELISA kits. RESULTS: A significant increase of E coli ATCC 25922, occurred in the livers of group I rats, compared with group IV (P =.037). MCP-1 expression increased in all groups, compared with control (P =.000). The IL-8 mRNA expression was significantly higher in group I than in control (P =.021). The expression of TGF-beta1 mRNA was similar among the groups (P =.361), consistent with the immunohistochemistry results. The serum MCP-1 and IL-8 levels were higher in the 4 groups than in the control (P =.000) and were significantly higher in group I than in group IV (P =.001). CONCLUSIONS: This study found that a significant colonization of E coli of the same strain was present in the cholestatic rat liver injected into the Roux limb, which was associated with a higher expression of liver MCP-1 and IL-8 mRNA, a significant increase of serum MCP-1 and IL-8, and a more evident inflammatory cell infiltration into the porta hepatis.

Anastomosis, Roux-en-Y↗
PubMed1997

Necrotizing enterocolitis in newborn: nine years' experience.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most significant acquired gastrointestinal (GI) emergency in the neonatal intensive care unit. METHODS: We sought to gain a clinical perspective on NEC by reviewing the records of NEC patients over a 9-year period. The case histories of 22 infants with NEC treated from September 1, 1986 to September 1, 1995 were reviewed. RESULTS: Mean gestational age was 32 weeks and mean birth weight was 1774 grams. Eighteen percent were full term babies and 82% were premature. Average age at the onset of NEC was 11 days. The most common clinical manifestations were abdominal distension (100%), gastric retention (64%), unstable vital signs (59%) and Guaiac-positive vomitus or stool (36%). Sixteen cases (73%) were classified as stage III NEC, which has the highest mortality and/or morbidity. CONCLUSION: Early identification and management are critical to improve the outcome of NEC.

Birth Weight↗
PubMed1996

Genetic susceptibility to Leishmania: IL-12 responsiveness in TH1 cell development.

The genetic background of T lymphocytes influences development of the T helper (TH) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as Leishmania major. With an in vitro model system, a difference in maintenance of responsiveness of T cells to interleukin-12 (IL-12) was detected between BALB/c and B10.D2 mice. Although naive T cells from both strains initially responded to IL-12, BALB/c T cells lost IL-12 responsiveness after stimulation with antigen in vitro, even when cocultured with B10.D2 T cells. Thus, susceptibility of BALB/c mice to infection with L. major may derive from the loss of the ability to generate IL-12-induced TH1 responses rather than from an IL-4-induced TH2 response.

Animals↗
PubMed1996

Endoscopic sympathectomy treatment for craniofacial hyperhidrosis.

OBJECTIVE: To present endoscopic T-2 sympathectomy as a minimally invasive therapy for craniofacial hyperhidrosis (CH). DESIGN: Follow-up study of 30 patients with CH treated by the new method in a 4-year period. The duration of follow-up was from 8 to 44 months (mean, 15 months). SETTING: University hospital. PATIENTS: Thirty consecutive patients with CH (18 men, 12 women) treated by the new method. All patients were essentially in good health except that they suffered from distressing CH to the extent that their daily activities were often disturbed. Their ages ranged from 7 to 63 years (mean age, 42.8 years). INTERVENTION: Endoscopic sympathectomy on both sides was carried out in a 1-stage operation for all patients. MAIN OUTCOME MEASURES: The patients were interviewed 1 week and then 3 months after surgery and then followed up by telephone interview about the alleviation or recurrence of CH and complications. RESULTS: All of the treated patients obtained a satisfactory alleviation of CH. One case was complicated by a mild and transient ptosis of the left eye. No recurrence of CH was noticed during the follow-up period. CONCLUSIONS: This therapeutic procedure is minimally invasive and effective. It causes minimal discomfort and was associated with no major complications in this series. The patients require only an overnight hospital stay and the operation scars are small. Endoscopic sympathectomy has proven to be an effective method in treating patients with distressing CH.

Adolescent↗
PubMed1996

Epidermolysis bullosa letalis with pyloric atresia in an infant.

Epidermolysis bullosa (EB) is a group of inherited diseases, that are characterized by vesiculobullous lesions that arise in response to minimal trauma or friction. The three major groups of EB differ according to the ultrastructural level of cleavage namely: simplex (epidermolytic), junctional and dystrophic (dermolytic). The combination of EB and pyloric atresia in rare and there is a definite association between them. We report a baby boy who died epidermolysis bullosa complications despite successful surgical correction of this pyloric atresia.

Epidermolysis Bullosa, Junctional↗
PubMed1996

Juvenile fibromatosis of the posterior mediastinum with intraspinal extension.

Chest radiography, CT, and MR imaging were performed in a 3-year-old girl who had posterior mediastinal fibromatosis with transforaminal intraspinal and chest wall extension. Chest radiographs and CT scans showed a slow-growing, noncalcified but locally aggressive left paravertebral mass. The mass was slightly hyperintense relative to muscle on both T1-weighted and fast spin-echo T2-weighted MR images.

Child, Preschool↗
PubMed1996

Minimally invasive surgery: video endoscopic thoracic sympathectomy for palmar hyperhidrosis.

Palmar hyperhidrosis (PH) is a common disorder in Taiwan. It often causes social embarrassment and occupational handicaps. So far, there has been no satisfactory treatment for PH. In 1990, we first developed a minimally invasive technique: video endoscopic sympathectomy to treat PH. The procedure has subsequently proven to be a standard treatment for PH. In this study, a survey of 9988 cases of PH patients from 17 hospitals in Taiwan treated by this method during the past 5 years is presented. Although there were some variations in the model of anaesthesia, technique and extent of sympathectomy, the postoperative results were generally satisfactory. Both sides of sympathectomy were mostly accomplished within half an hour in one stage. The operative scars were tiny and concealed in the axillary region. The patients were discharged from the hospital after an overnight stay. Complications such as pneumothorax, haemothorax (0.3%) or Horner's syndrome (0.1%) were rare. There was no surgical mortality in this series. The most common complication was compensatory hyperhidrosis which was usually mild to moderate and tolerable after reassurance. The recurrence rate of PH was approximately 1% in the first year and less than 3% during the 3 years of follow up. Intraoperative monitoring of palmar skin temperature (PST) was advocated to confirm an adequate sympathectomy warranting a definite result. En bloc ablation of T2 segment invariably resulted in a rise of PST to about 2 degrees C and was considered as an adequate extent of sympathectomy for PH. The refined technique was extended to treat young children with PH and patients with craniofacial hyperhidrosis. The therapeutic results were generally excellent with minimal morbidity and rare recurrence. It is concluded that video endoscopic en bloc T2 sympathectomy is a simple, minimally invasive and effective treatment for both adults and children with PH and also for patients with craniofacial hyperhidrosis.

Adolescent↗
PubMed1995

Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells.

Dendritic cells are APCs that are unique in their potency to stimulate proliferation of primary Ag-specific responses in vitro and in vivo. In this study, we demonstrate that dendritic cells can produce IL-12, a dominant cytokine involved in the development of IFN-gamma-producing T cells. This finding resulted from our observations that dendritic cell-induced Th1 development from total CD4+ T cells upon neutralization of endogenous levels of IL-4 was IL-12-dependent. Furthermore, we demonstrate that dendritic cells can induce the development of Th1 cells from Ag-specific naive LECAM-1bright CD4+ T cells obtained from alpha beta-TCR transgenic mice, provided that CD4+ LECAM-1dull T cells, which produce significant levels of IL-4, are not present in the primary cultures. Production of IL-12 by dendritic cells was confirmed by positive immunofluoresence staining with Abs specific for the inducible IL-12 p40 subunit. This suggests that in addition to inducing proliferation and clonal expansion of naive T cells, dendritic cells, by their production of IL-12, play a direct role in the development of IFN-gamma-producing cells that are important for cell-mediated immune responses.

Animals↗
PubMed1995

T cell genetic background determines default T helper phenotype development in vitro.

A host's ability to resist certain pathogens such as Leishmania major can depend upon the phenotype of T helper (Th) subset that develops. Different murine genetic backgrounds are known to significantly alter the direction of Th subset development, although the cellular basis of this influence is poorly understood. To examine the basis of this effect we used an in vitro alpha/beta-T cell receptor (TCR) transgenic system for analysis of Th phenotype development. To control for TCR usage, we derived the DO11.10 alpha/beta-TCR transgene in several genetic backgrounds. Our findings suggest that the effects of genetic background on Th phenotype development reside within the T cell, and not the antigen-presenting cell compartment. Transgenic T cells from both the B10.D2 and BALB/c backgrounds showed development toward either the Th1 or Th2 phenotype under the strong directing influence of interleukin (IL) 12 and IL4, respectively. However, when T cells were activated in vitro under neutral conditions in which exogenous cytokines were not added, B10.D2-derived T cells acquired a significantly stronger Th1 phenotype than T cells from the BALB/c background, correspondent with in vivo Th responses to Leishmania in these strains. Importantly, these cytokine differences resulted in distinct functional properties, because B10.D2- but not BALB/c-derived T cells could induce macrophage production of nitric oxide, an important antimicrobial factor. Thus, the genetically determined default Th phenotype development observed in vitro may correspond to in vivo Th subset responses for pathogens such as Leishmania which do not initiate strong Th phenotype-directing signals.

Animals↗
PubMed1995

Tissue-specific targeting of cytokine unresponsiveness in transgenic mice.

The ubiquitous cellular distribution of certain cytokine receptors has hampered attempts to define the physiologically important cell-specific functions of cytokines in vivo. Herein, we report the generation of transgenic mice that express a dominant-negative IFN gamma receptor alpha chain mutant under the control of either the human lysozyme promoter or the murine lck proximal promoter, which display tissue-specific unresponsiveness in the macrophage or T cell compartments, respectively, to the pleiotropic cytokine, IFN gamma. We utilize these mice to identify previously undefined cellular targets of IFN gamma action in the development of a murine antimicrobial response and the mixed lymphocyte reaction. Moreover, we identify the macrophage as a critical responsive cell in manifesting the effects of IFN gamma in regulating CD4+ T helper subset development. These studies thus represent a novel approach to studying the cell-specific actions of an endogenously produced pleiotropic cytokine in vivo.

Animals↗
PubMed1994

B7 and interleukin 12 cooperate for proliferation and interferon gamma production by mouse T helper clones that are unresponsive to B7 costimulation.

We have previously shown that dendritic cells isolated after overnight culture, which can express B7 and are potent stimulators of naive T cell proliferation, are relatively poor at inducing the proliferation of a panel of murine T helper 1 (Th1) clones. Maximal stimulation of Th1 clones was achieved using unseparated splenic antigen presenting cells (APC). An explanation for these findings is provided in the present study where we show that FcR+ L cells transfected with B7 stimulate minimal proliferation of Th1 clones in response to anti-CD3 antibodies, in contrast to induction of significant proliferation of naive T cells. However, addition of interleukin 12 (IL-12) to cultures of Th1 cells stimulated with anti-CD3 and FcR+ B7 transfectants resulted in a very pronounced increase in proliferation and interferon gamma (IFN-gamma) production. Exogenous IL-12 did not affect the B7-induced proliferation of naive T cells. This showed that whereas costimulatory signals delivered via B7-CD28 interaction are sufficient to induce significant proliferation of naive T cells activated through occupancy of the T cell receptor, Th1 T cell clones require cooperative costimulation by B7 and IL-12. This costimulation was shown to be specific by inhibition of proliferation and IFN-gamma production using chimeric soluble cytolytic T lymphocyte-associated antigen 4-human IgG1Fc (CTLA4-Ig) and anti-IL-12 antibodies. Furthermore, the significant antigen specific proliferation and IFN-gamma production by Th1 clones observed when splenocytes were used as APC was almost completely abrogated using CTLA4-Ig and anti-IL-12 antibodies. Thus two costimulatory signals, B7 and IL-12, account for the ability of splenic APC to induce maximal stimulation of Th1 clones. IL-10 downregulates the expression of IL-12 by IFN-gamma-stimulated macrophages and this may account largely for t the ability of IL-10 to inhibit APC function of splenic and macrophage APC for the induction of Th1 cell proliferation and IFN-gamma production. Indeed we show that IL-12 can overcome the inhibitory effect of IL-10 for the APC-dependent induction of proliferation and IFN-gamma production by Th1 clones. These results suggest that proliferation by terminally differentiated Th1 clones, in contrast to naive T cells, requires stimulation via membrane-bound B7 and a cytokine, IL-12. It is possible that these signals may result in the activation of unresponsive T cells during an inflammatory response. IL-10, by its role in regulating such innate inflammatory responses, may thus help to maintain these T cells in an unresponsive state.

Abatacept↗
PubMed1993

Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages.

Development of the appropriate CD4+ T helper (TH) subset during an immune response is important for disease resolution. With the use of naïve, ovalbumin-specific alpha beta T cell receptor transgenic T cell, it was found that heat-killed Listeria monocytogenes induced TH1 development in vitro through macrophage production of interleukin-12 (IL-12). Moreover, inhibition of macrophage production of IL-12 may explain the ability of IL-10 to suppress TH1 development. Murine immune responses to L. monocytogenes in vivo are of the appropriate TH1 phenotype. Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH phenotype.

Animals↗
PubMed1993

Separation of CD4+ functional responses by peptide dose in Th1 and Th2 subsets expressing the same transgenic antigen receptor.

CD4+ T cells from alpha beta-TCR transgenic mice were used to explore the effect of antigen dose on various functional activities. This transgenic system provides for a source of antigen-specific T cells with the same TCR which can develop into Th1 and Th2 phenotypes under controlled conditions. Of particular interest was to determine if detachment of adherent targets from their substrate could be separated from other functional activities by either antigen dose or functional subset. Using this model, we have found that (a) Th1 and Th2 phenotypes exhibit a similar peptide dose-dependent pattern of detachment and lysis, although Th2 are generally less lytic on both fibroblast and lymphoma targets; (b) detachment and lysis can be dissociated from cytokine production by low peptide doses; (c) detachment and lysis can be physiologically as well as temporally and pharmacologically uncoupled as most targets recovered after detachment by Th2 effectors retain their capacity to proliferate.

Animals↗
PubMed1993

Pathogen-induced Th1 phenotype development in CD4+ alpha beta-TCR transgenic T cells is macrophage dependent.

We used an ovalbumin (OVA)-specific alpha beta-TCR transgenic mouse system to examine the cellular basis of CD4+ T helper (Th) phenotype development in vitro. Heat-killed Listeria monocytogenes (HKLM) strongly promotes the in vitro development of a Th1 phenotype in OVA-specific transgenic T cells. Listeria monocytogenes effects to promote the Th1 phenotype are antigen presenting cell (APC) dependent and occur when splenic APCs, but not the B cell hybridoma TA3, are present during T cell activation. However, addition of FACS-sorted macrophages to TA3 activated cultures restores the ability of Listeria to induce Th1 development. This effect on T cell development does not require MHC-restricted antigen presentation by macrophages, but may act through soluble factors. Although the presence of interferon gamma is necessary for Listeria induction of Th1 development, IFN-gamma alone is insufficient to induce Th1 development. Furthermore, Listeria induction of the Th1 phenotype does not require several known products of activated macrophages, including interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha), IL-6, or nitric oxide. Although transforming growth factor-beta (TGF-beta) may mediate some Listeria effects, it does not fully reconstitute Listeria effects to promote Th1 development. In summary, host interactions with bacterial pathogens can affect the development of specific Th subsets, allowing innate immune cells to direct development of specific immune phenotype. For Listeria monocytogenes, the induction of the Th1 phenotype may involve a novel cytokine distinct from several known factors produced by activated macrophages.

Animals↗