PubMed Health⌕ Search

Biomedical subjects

Yau-Lin Tseng

Publications and source records attributed to Yau-Lin Tseng.

17 recordsLinked to original sources
PubMed2006

Allosensitization does not increase the risk of xenoreactivity to alpha1,3-galactosyltransferase gene-knockout miniature swine in patients on transplantation waiting lists.

BACKGROUND: The recent availability of alpha1,3-galactosyltransferase knockout (GalT-KO) miniature swine has eliminated anti-Gal antibodies as the major barrier to xenotransplantation, potentially bringing this modality closer to clinical application. Highly-allosensitized patients, who have poor prospects of receiving a suitable cross-match negative human organ, might be the first patients to benefit from xenotransplantation of porcine organs. However, concerns exist regarding cross-reactivity of alloreactive anti-human leukocyte antigen (HLA) antibodies against xenogeneic swine leukocyte antigen (SLA) antigens. We have investigated this question using sera from such patients on GalT-KO target cells. METHODS: Using flow cytometry and complement-dependent cytotoxicity (CDC) assays, we have tested a panel of 88 human serum samples from patients awaiting cadaveric renal allotransplantation for reactivity against: 1) human; 2) standard miniature swine; and 3) GalT-KO peripheral blood lymphocytes (PBL) and cultured endothelial cells. RESULTS: Anti-swine IgM and IgG antibody binding, as well as CDC, were significantly attenuated on GalT-KO versus standard swine. No correlation was found between the degree of anti-human panel reactive antibodies (PRA) and xenoreactivity against either standard or GalT-KO miniature swine. Treatment of sera with dithiothreitol (DTT) showed that the majority of remaining lymphocytotoxicity against GalT-KO swine was mediated by preformed IgM antibodies. Patients with high alloreactivity but low anti-GalT-KO xenoreactivity were readily identified. CONCLUSIONS: Highly allosensitized patients awaiting renal transplants appear to be at no increased risk of xenosensitization over their non-sensitized cohorts, and could therefore be candidates for xenotransplantation using GalT-KO swine donors.

Animals↗
PubMed2006

Elicited antibodies in baboons exposed to tissues from alpha1,3-galactosyltransferase gene-knockout pigs.

BACKGROUND: This study investigates anti-nonGal antibodies (Abs) in baboons after alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pig heart transplantation (Tx). METHODS: Four baboons underwent pig heart Tx under chronic immunosuppression, which was discontinued after graftectomy. During follow-up, one baboon also received a pig splenocyte infusion. Hearts and splenocytes were from GalT-KO pigs (n = 3) or pigs with low Gal expression (Gal-low, n = 2), all of swine leukocyte antigen (SLA) dd haplotype. Several weeks after graftectomy, sera were tested by flow cytometry and cytotoxicity assay on porcine peripheral blood mononuclear cells (PBMC) for elicited anti-nonGal Abs. Sera were adsorbed on a Gal immunoaffinity matrix, and tested for SLA haplotype specificity using PBMC from SLA aa, cc, and dd haplotypes. RESULTS: Before heart Tx, no baboon had anti-nonGal Abs demonstrable by binding or cytotoxicity to GalT-KO PBMC. All four baboons developed anti-nonGal Abs after Tx, demonstrable by flow cytometry, and three sera from baboons showed cytotoxicity to GalT-KO PBMC of SLA(dd) haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLA(dd), SLA(aa), SLA(cc)). CONCLUSIONS: Anti-nonGal Abs developed after GalT-KO pig heart Tx into baboons. The most potent of these antibodies appeared to detect antigens shared by the three pig haplotypes tested. It remains unclear whether these antibodies are directed towards shared SLA determinants or other pig antigens, and whether antibodies with specificity for allelic SLA determinants are also present, but at lower titer.

Alleles↗
PubMed2005

Immunological unresponsiveness in chimeric miniature swine following MHC-mismatched spleen transplantation.

BACKGROUND: In rodents, spleen allotransplantation (SpTx) induces tolerance. We investigated the induction of chimerism and donor-specific unresponsiveness following pig SpTx. METHODS: Thirteen pigs underwent splenectomy (day 0); all received a blood transfusion. In 11/13 pigs, SpTx was performed across a MHC class I (n=1) or full (n=10) barrier; two control pigs received no SpTx. All pigs were monitored for chimerism, and anti-donor immune responses, including suppressor assays. Four pigs (two asplenic controls and two with SpTx) underwent delayed donor-matched kidney transplantation without immunosuppression. RESULTS: Six of the 11 spleen grafts were lost from rejection (n=5) or splenic vein thrombosis (n=1), and five remained viable. All 11 SpTx recipients developed multilineage chimerism, but chimerism was rapidly lost if the graft failed. Two control pigs showed <6% blood chimerism for 4 and 11 days only. Pigs with functioning spleen grafts had multilineage chimerism in blood, thymus and bone marrow for at least 2-6 months, without graft-versus-host disease. These pigs developed in vitro donor-specific hyporesponsiveness and suppression. In 2 pigs tolerant to the spleen graft, donor MHC-matched kidney grafts survived for >4 and >7 months in the absence of exogenous immunosuppression; in two asplenic pigs, kidney grafts were rejected on days 4 and 15. CONCLUSIONS: Successful SpTx can result in hematopoietic cell engraftment and in vitro donor-specific unresponsiveness, enabling prolonged survival of subsequent donor-matched kidney grafts without immunosuppression.

Animals↗
PubMed2005

alpha1,3-Galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months.

BACKGROUND: The recent generation of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs has allowed investigation of the survival of GalT-KO pig organs in nonhuman primates. METHODS: Heterotopic heart transplantation from GalT-KO pigs was carried out in baboons (n=8) using a human antihuman CD154 monoclonal antibody-based immunosuppressive regimen. RESULTS: In six of the eight cases, graft survival extended to between approximately 2 and 6 months. All grafts developed thrombotic microangiopathy (TM). In particular, the clinical course of one baboon in which the graft functioned for 179 days is summarized. This baboon received aspirin (40 mg on alternate days) from day 4 in addition to heparin, which may have been a factor in the delay of onset and progression of TM and in prolonged graft survival. Maintenance therapy with anti-CD154 mAb, mycophenolate mofetil, and methylprednisolone was associated with persistently low numbers of CD3CD4 and CD3CD8 cells. Despite persisting depletion of these cells, no infectious complications occurred. CONCLUSIONS: It remains to be established whether TM is related to a very low level of natural preformed or T-cell-induced antibody deposition on the graft, inducing endothelial activation and injury, or to molecular incompatibilities in the coagulation mechanisms between pig and baboon, or to both. However, function of a pig organ in a baboon for a period approaching six months, which has not been reported previously, lends encouragement that the barriers to xenotransplantation will eventually be overcome.

Animals↗
PubMed2005

Porcine hematopoietic progenitor cell transplantation in nonhuman primates: a review of progress.

The critical shortage of human donor organs for transplantation would be overcome if a suitable animal, e.g., the pig, could be used as an organ source. There are, however, several immune barriers that have to date resulted in limited function of pig organs transplanted into nonhuman primates. It would be beneficial, and indeed may be essential, to induce a state of tolerance in the primate recipient to the pig organ. In allotransplantation, the successful transplantation of hematopoietic progenitor cells with the development of mixed chimerism is associated with the induction of tolerance toward a donor-specific organ. For some years, this approach has been explored in the pig-to-nonhuman primate model. This experience is briefly reviewed. The problems of natural and elicited anti-pig antibodies, recipient platelet adhesion to pig hematopietic progenitor cells, and the rapid removal of these cells by the host macrophage-phagocytic system are highlighted. Recent experience with the use of hematopoietic cells from pigs homozygous for alpha1,3-galactosyltransferase gene-knockout is reported.

Animals↗
PubMed2004

Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience.

Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody-based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2-6 months (median, 78 d); the predominant lesion associated with graft failure was a thrombotic microangiopathy, with resulting ischemic injury. There were no infectious complications directly related to the immunosuppressive regimen. The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies.

Animals↗
PubMed2004

Posttransplant lymphoproliferative disease after allogeneic transplantation of the spleen in miniature swine.

Spleen transplantation (SpTx) was performed in miniature swine across full major histocompatibility complex barriers to study the tolerogenic effect of the spleen. This study describes the development of posttransplant lymphoproliferative disease (PTLD) after allogeneic SpTx. Recipient pigs underwent whole body irradiation (100 cGy), thymic irradiation (700 cGy), and native splenectomy (day 0), and received a 45-day course of intravenous cyclosporine (trough level 400-800 ng/ml). After SpTx, two of seven pigs developed PTLD (1 donor-type, 1 host-type). These two pigs had greater T cell depletion and higher trough levels of cyclosporine. Early changes that occurred prior to the development of clinical features of PTLD were increased porcine lymphotropic herpesvirus-1 viral loads in blood and tissues, and increased numbers of leukocytes, B cells, and total serum IgM. PTLD can occur after allogeneic SpTx in swine. This model may be useful in studies of the pathogenesis of PTLD.

Animals↗
PubMed2004

alpha1,3-Galactosyltransferase gene-knockout miniature swine produce natural cytotoxic anti-Gal antibodies.

BACKGROUND: The expression of galactose alpha 1,3 galactose (Gal) in pigs has proved a barrier to xenotransplantation. Miniature swine lacking Gal (Gal pigs) have been produced by nuclear transfer/embryo transfer. METHODS: The tissues of five Gal pigs of SLA dd haplotype (SLA) were tested for the presence of Gal epitopes by staining with the Griffonia simplicifolia IB4 lectin. Their sera were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from wild-type (Gal) SLA-matched pigs; serum cytotoxicity was also assessed. The cellular responses of PBMC from Gal swine toward Gal SLA-matched PBMC were tested by mixed leukocyte reaction and cell-mediated lympholysis assays. RESULTS: None of the tissues tested showed Gal expression. Sera from all five Gal pigs manifested IgM binding to Gal pig PBMC, and sera from three showed IgG binding. In all five cases, cytotoxicity to Gal cells could be demonstrated, which was lost after treatment of the sera with dithiothreitol, indicating IgM antibody-mediated cytotoxicity. PBMC from Gal swine had no proliferative or cytolytic T-cell response toward Gal SLA-matched PBMC. CONCLUSIONS: Gal pigs do not express Gal epitopes and develop anti-Gal antibodies that are cytotoxic to Gal pig cells. The absence of an in vitro cellular immune response between Gal and Gal pigs is related to their identical SLA haplotype and indicates the absence of immunogenicity of Gal in T-cell responses. The model of Gal organ transplantation into a Gal SLA-matched recipient would be a valuable large animal model in the study of accommodation or B-cell tolerance.

Animals↗
PubMed2004

Computed tomographic assessment of the surgical risks associated with fibrocavernous pulmonary tuberculosis.

PURPOSE: We evaluated the surgical risks associated with fibrocavernous pulmonary tuberculosis by retrospectively examining chest computed tomography (CT) scans. METHODS: We reviewed the records of 40 patients who underwent pulmonary resection for fibrocavernous pulmonary tuberculosis, for whom preoperative CT scans were available. The disease was categorized as class I, defined as a cavity within one lobe without remarkable pleural thickness, in 21 patients; class II, defined as a cavity extending beyond one lobe or within one lobe with remarkable pleural thickness, in 10 patients; and class III, defined as bilateral cavities, in 9 patients. Four of the nine patients with bilateral cavities underwent bilateral pulmonary resection and five underwent unilateral pulmonary resection. The study parameters were intraoperative blood loss, operative time, hospital stay, major operative morbidity, and hospital death. RESULTS: Intraoperative blood loss and operative time were significantly greater and hospital stay was significantly longer in patients with advanced disease (P = 0.046, P = 0.000, and P = 0.143, respectively). Major surgical morbidity mainly occurred in association with advanced disease (P = 0.028) at the following incidences: class I, 5%; class II, 30%; class III, 44.4%. Two hospital deaths occurred, both following bilateral pulmonary resection for class III disease, accounting for an overall 5% mortality rate. CONCLUSION: The surgical risks associated with fibrocavernous pulmonary tuberculosis were well correlated with anatomic involvement, according to the extent of cavitation and the severity of pleural thickness, as depicted by CT. Staged pulmonary resection or the combination of one-sided resection with other modalities is recommended for the treatment of bilateral cavities.

Blood Loss, Surgical↗
PubMed2004

Suppression of natural and elicited antibodies in pig-to-baboon heart transplantation using a human anti-human CD154 mAb-based regimen.

Natural and elicited antipig antibodies (Abs) lead to acute humoral xenograft rejection (AHXR). Ten baboons underwent heterotopic heart transplantation (Tx) from human decay-accelerating factor (hDAF) pigs. Depletion of anti-Galalpha1, 3Gal (Gal) Abs was achieved by the infusion of a Gal glycoconjugate from day-1. Immunosuppression included induction of antithymocyte globulin, thymic irradiation, and cobra venom factor, and maintenance with a human antihuman CD154 mAb, mycophenolate mofetil, and methylprednisolone; heparin and prophylactic ganciclovir were also administered. Pig heart survival ranged from 4 to 139 (mean 37, median 27) days, with three functioning for >50 days. Graft failure (n = 8) was from classical AHXR [4], thrombotic microangiopathy [3], or intragraft thrombosis [1], with death (n = 2) from pneumonia [1], or possible drug toxicity (with features of thrombotic microangiopathy) [1]. Anti-Gal Abs (in microg/mL) were depleted by Gal glycoconjugate before graft implantation from means of 41.3 to 6.3 (IgM) and 12.4-4.6 (IgG), respectively, and at graft excision were 6.3 and 1.7 microg/mL, respectively. No elicited Abs developed, and no cellular infiltration was seen. The treatment regimen was effective in maintaining low anti-Gal Ab levels and in delaying or preventing AHXR. The combination of costimulatory blockade and heparin with Tx of a Gal-negative pig organ may prolong graft survival further.

Animals↗
PubMed2003

Massive upper gastrointestinal bleeding after acid-corrosive injury.

Our purpose was to delineate the characteristics and outcome of massive upper gastrointestinal bleeding (UGI) caused by acid-corrosive injury and to determine its management protocol. From June 1988 to June 2000, all patients with the history of acid-corrosive injury at our institution were reviewed. Patients with massive UGI bleeding (hematocrit level <25% or transfusion of three or more units of whole blood required to restore normal vital sign) were enrolled into this study. Altogether, 12 (3.2%) of 378 patients with acid-corrosive injury developed massive bleeding: 8 gastric bleeding, 2 duodenal bleeding, and 2 first gastric and then duodenal bleeding. Gastric bleedings started an average of 12.1 days after the initial injury (range 9-21 days). Duodenal bleeding usually occurred later, at 10.1 days (range 6-18 days) after a gastric or esophagogastric operation. Nine of the ten patients with gastric bleeding underwent surgery during the subacute stage: three esophagogastrectomy, three gastric mucosectomy with gastrostomy and jejunostomy, and three total or subtotal gastrectomy. Operative findings were hemorrhagic gastritis with diffuse mucosal bleeding. Two of four patients with duodenal bleeding underwent duodenotomy with suture-ligation of bleeding vessels, and the other two had conservative treatment. Nine patients (75%) had postoperative complications. One patient (8%) died from complications of surgery performed to stop duodenal bleeding. Massive UGI bleeding rarely occurs after acid-corrosive injury; but when it does, it occurs during the subacute stage. Aggressive surgical treatment is mandatory for gastric bleeding. How duodenal bleeding can be better managed requires further study.

Adult↗
PubMed2003

Thymic carcinoma: involvement of great vessels indicates poor prognosis.

BACKGROUND: Thymic carcinoma is a rare, indolent, and invasive cancer. This study investigated the treatment results of thymic carcinoma and clinical prognostic factors. METHODS: From June 1988 to January 2002, 38 patients were enrolled in this study with the diagnosis of thymic carcinoma in the Cheng-Kung University Hospital based on Rosai's and Muller-Hermelink's classification. Clinical and pathologic data were retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier, log rank, and Wilcoxon tests. Statistical significance was defined as p < 0.05. RESULTS: Pathology revealed 14 poorly differentiated, 6 moderately differentiated, and 8 well-differentiated squamous cell carcinomas; 8 lymphoepithelioma-like carcinomas; and 2 other carcinomas. Pathologic staging using the Masaoka system included 6 stage II, 23 stage III, and 9 stage IV patients. Six biopsies, five debulkings, and 27 complete resections were performed. All patients were followed from 15 months to 10 years 9 months, with an average of 53.8 months. Median survival time was 81 months, and median recurrence time was 52 months. Eighteen patients are still alive, and 7 are alive with disease. Well-differentiated squamous cell carcinoma had better prognosis than other carcinomas (p = 0.022). Complete resection significantly increased survival rate (p < 0.001). Tumor invasion of the superior vena cava, pulmonary vessels, or aorta were significant predictors for poor prognosis (p = 0.016, 0.002, and 0.002, respectively). CONCLUSIONS: Only patients with thymic carcinoma who underwent complete resection had long-term survival. Prognosis of thymic carcinoma seemed mainly dependent on tumor invasion of the great vessels.

Adult↗
PubMed2002

Outcome of acid ingestion related aspiration pneumonia.

BACKGROUND: The objective of this study is to assess the incidence and long-term results of a rarely discussed medical problem -- aspiration pneumonia resulting from the intentional ingestion of acid. MATERIALS AND METHODS: The medical records of 370 patients treated at one tertiary care institution for corrosive acid injury during a 12-year period were reviewed retrospectively. The study subjects included any patients who were found to have acid ingestion related aspiration pneumonia confirmed by chest film within 24h of injury. All available data of these patients with or without aspiration pneumonia were analyzed. RESULTS: Of the 370 patients with corrosive acid injury, 15 (4.2%) had acid-aspiration pneumonia which was related to their intentional ingestion of a strong acid, hydrochloric acid (pH<1). The data for 14 patients with aspiration pneumonia and 268 without aspiration pneumonia was complete and available for analysis. Patients with aspiration pneumonia were found to be significantly older (52.2+/-6.2 to 41.7+/-0.9 years old, P=0.017), had a higher incidence of nasogastric tube irrigation (35.7-6.0%, P=0.000), had more conscious disturbance (50.0-17.5%, P=0.016), and required more endotracheal tube intubation (50.0-3.0%, P=0.000). Aspiration pneumonia was found to significantly increase the mortality rate in acid injured patients who required emergency abdominal surgery (87.5-32.0%, P=0.000) and in those who did not (28.5-5.1%, P=0.05). Two of the six survivors of aspiration pneumonia later developed laryngeal sequelae. CONCLUSIONS: Aspiration pneumonia rarely occurs as a consequence of acid ingestion. When it does occur, it greatly increases the mortality rate of those involved. For those who survive, physicians can expect some laryngotracheal sequel in long-term follow-up.

Adolescent↗
PubMed2002

Early surgical correction for isolated gastric stricture following acid corrosion injury.

OBJECTIVE: To evaluate the feasibility and long-term results of early gastric surgery for patients with isolated gastric stricture following acid corrosion injury. MATERIALS AND METHODS: Upper gastrointestinal (UGI) series was routinely performed around the 4th week after acid corrosion injury. Patients with gastric stricture and no risk of delayed esophageal stricture underwent early solitary gastric surgery, which was defined when performance of the procedure took place within 2 months of the injury. RESULTS: From June 1988 to June 2000, 35 of 378 patients with acid corrosion injury developed isolated gastric stricture. Twenty-four (68.6%) lesions were located in the antrum, and 11 (31.4%) in the gastric body. Postprandial vomiting presented earlier for the antral stricture group (17.6 +/- 1.1 versus 25.4 +/- 3.4 days after injury; p = 0.005). The UGI series was performed from 16 to 41 days after injury (average 25 days). Of the 35 acid corrosion injury patients in this study, 4 were excluded because of late referrals to our institution or the patient's hesitation which resulted in delayed surgery. The remaining 31 patients underwent gastric surgery 35.7 +/- 3.2 days after ingestion (34.6 +/- 3.6 and 38.1 +/- 3.4 days for cases of antral and gastric body stricture, respectively). Surgical procedures consisted of hemigastrectomy (n = 16), antrectomy (n = 2), gastroenterostomy (n = 2), subtotal gastrectomy (n = 6), and total gastrectomy (n = 5). There were 4 cases of postoperative complications (12.9%) including adhesion ileus (n = 2), wound infection (n = 1), and massive, postoperative UGI bleeding (n = 1). Surgical mortality was zero. All patients tolerated oral intake well after surgery. During the minimum follow-up period of 1 year, 1 patient developed esophagojejunostomy stenosis, which was resolved by dilation, and there was 1 case of dumping syndrome, which was treated by diet control. CONCLUSION: Early surgery correction is feasible and safe if patients with isolated gastric stricture following acid corrosion injury are carefully selected. All patients in our study recovered early, with a low morbidity rate.

Adolescent↗