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H-C Hsu

Publications and source records attributed to H-C Hsu.

At least 19 recordsLinked to original sources
PubMed2007

Differential response to H. pylori eradication therapy of co-existing diffuse large B-cell lymphoma and MALT lymphoma of stomach-significance of tumour cell clonality and BCL10 expression.

We recently reported that low-grade mucosa-associated lymphoid tissue lymphoma (MALToma) and diffuse large B-cell lymphoma (DLBCL) with MALToma (DLBCL[MALT]) of stomach are equally responsive to H. pylori eradication therapy (HPET) and that H. pylori-independent status is closely associated with nuclear translocation of BCL10. However, co-existing MALToma and DLBCL components of gastric DLBCL(MALT) may respond differentially to HPET and the underlying mechanism remains unclear. Tumour tissue samples from 18 patients with microdissectable co-existing MALToma and DLBCL cells were studied. The clonality of lymphoma cells was examined by polymerase chain reaction-based amplification of the CDR3 region of the IgH gene and confirmed by DNA sequence analysis. BCL10 expression was determined by immunohistochemistry. Differential response of co-existing MALToma and DLBCL to HPET was defined as complete eradication of one component while the other component remained. Five (27.8%) of the 18 patients showed different IgH gene rearrangements in the two components and three (60%) of these five patients had differential response of MALToma and DLBCL to HPET. By contrast, 13 patients showed identical IgH gene rearrangements and only one (8%) of them had differential response of the two components to HPET (p = 0.044). Further, all four patients with differential response of MALToma and DLBCL to HPET showed nuclear expression of BCL10 in the H. pylori-independent component and cytoplasmic expression of BCL10 in the H. pylori-dependent component while the expression patterns of BCL10 were identical in both of these components in the 14 patients who had similar tumour response to HPET. We conclude that different clonality is a common reason for the differential response of co-existing MALToma and DLBCL of gastric DLBCL(MALT) to HPET and that immunohistochemical examination of BCL10 expression may help to identify the co-existence of these components.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Cost-effectiveness of postremission intensive therapy in patients with acute leukemia.

BACKGROUND: We assessed the cost-effectiveness of high-dose arabinoside (HiDAC)-based and allogeneic stem-cell transplantation (alloSCT)-based therapy in patients with acute leukemia. PATIENTS AND METHODS: We analyzed the outcome, cost and cost-effectiveness of 106 patients treated from January 1994 to January 2002 [94 acute myelogenous leukemia (AML)/12 acute lymphoblastic leukemia (ALL)]. Forty-two young patients at either intermediate or unknown cytogenetic risk received postremission intensive therapy (24 HiDAC-based/18 alloSCT-based therapy). RESULTS: After a median follow-up of 50 months, the estimated 7-year overall survival for the HiDAC-based group showed a tendency to be higher than the alloSCT-based group (48% versus 28%, P = 0.1452). The HiDAC-based group spent a significantly lower total cost ($US51,857 versus 75,474, P = 0.004) than the alloSCT-based group. Cost-effectiveness analysis showed that the mean cost per year of life saved for the HiDAC-based group is considerably less expensive than the alloSCT-based group ($US11,224 versus 21,564). The reduced total cost for the HiDAC-based group originated from lower cost in room fees, medication, laboratory and procedure, but not in blood transfusion and professional manpower fees. CONCLUSION: For the postremission therapy in young AML patients at either intermediate or unknown cytogenetic risk, cost-effectiveness of HiDAC-based therapy compares favorably with that of alloSCT-based therapy, which deserves further clinical trials.

Adult↗
PubMed2006

Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma.

Stathmin, a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. This study aimed to elucidate its role in the progression, early tumour recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). Stathmin mRNA was overexpressed in 88/156 (56%) resected, unifocal, primary HCCs, while p53 mutation was present in 72 (46%) and osteopontin mRNA overexpression in 79 (51%). Stathmin mRNA expression exhibited high concordance (93%) with protein expression in 107 cases examined by immunohistochemistry. Stathmin overexpression correlated with high alpha-fetoprotein (>200 ng/ml, p = 0.02), larger tumour size (>5 cm, p = 0.012), high tumour grade (p < 0.0002), high tumour stage (stage IIIA-IV) with vascular invasion and various degrees of intrahepatic metastasis (p < 1 x 10(-8)), ETR (p = 0.003), and lower 5-year survival (p = 0.0007). Stathmin protein expression was often more intense in the peripheral regions of tumour trabeculae, tumour borders, and portal vein tumour thrombi. Stathmin overexpression correlated with p53 mutation (p = 0.017) and osteopontin overexpression (p = 1 x 10(-8)), both of which were associated with vascular invasion (both p < 0.0001) and poorer prognosis (p < 0.0004 and p = 0.0004, respectively). Regardless of the status of p53 mutation or osteopontin expression, stathmin overexpression was associated with higher vascular invasion (all p < 0.0001). Approximately 90% of HCCs harbouring stathmin overexpression with concomitant p53 mutation or osteopontin overexpression exhibited vascular invasion, and hence the lowest 5-year survival, p = 0.00018 and p = 0.0009, respectively. However, we did not find that stathmin overexpression exerted prognostic impact independent of tumour stage. In conclusion, stathmin expression correlates with metastatic potential, is an important prognostic factor for HCC, and may serve as a useful marker to predict ETR.

Biomarkers, Tumor↗
PubMed2006

Transvaginal sonography in the morphological and functional assessment of segmental dilation of the distal ureter.

Primary megaureter presents a spectrum of findings ranging from mild, clinically unimportant, stable ureterectasis to severe, progressive obstructive hydroureteronephrosis. We report a patient with a double uterus and ipsilateral renal dystrophy. A previous imaging study had revealed a double uterus and obstructed left hemivagina, into which a single vaginal ectopic ureter inserted. On follow-up intravenous urography 8 years later, the left kidney was non-functioning, and there was segmental dilation of the distal right ureter. Transvaginal sonography with real-time scanning and Doppler were useful in exploring the morphological and functional status of this dilated distal ureter.

Abnormalities, Multiple↗
PubMed2006

Phenotype of genetically regulated thymic involution in young BXD RI strains of mice.

Age-related thymic involution is a multifactorial process related to age-related changes in intrathymic T-cell development and cytokines. In contrast, early thymic involution, because of genetic differences that cause rapid or slow thymic involution at younger age, is less well characterized. Here, we analysed three representative rapid-involuting strains of mice, BXD 8, 18 and 32, compared with three representative slow-involuting strains, BXD 9, 19 and 29, all at 2 months of age. In rapid-involuting strains compared with slow involution strains, thymocyte production, as indicated by CD4+ and CD8+ T-cell receptor recombination excision circle (TREC), were decreased. Rapid-involution strains of mice exhibited a developmental block at the DN1 to DN2 and CD4-CD8- (DN) to CD4+CD8+ (double positive, DP) transition stages. There was also increased susceptibility to H2O2-induced apoptosis, decreased thymic expression of IL-7, decreased expression of an IL-7 downstream anti-apoptosis gene, Bcl-2, and increased expression of a pro-apoptotic gene, Bad. In contrast, IL-7R expression was higher on DN thymocytes of rapid-involution strains. The increased expression of IL-7R was associated with an increased thymocyte proliferation in response to anti-CD3 + IL-7 or anti-CD3 + IL-12 + IL-7. These findings indicate that, even at young age, genetic differences of IL-7/IL-7R regulation pathway in BXD strains of mice can lead to characteristic phenotypic changes that have been previously associated with age-related thymic involution.

Aging↗
PubMed2006

Pulse pressure, aortic regurgitation and carotid atherosclerosis: a comparison between hypertensives and normotensives.

Pulse pressure (PP) has often been associated with cardiovascular morbidity and mortality. Patients with aortic regurgitation (AR) often have increased PP. The aim of this study is to investigate the associations among PP, AR and extracranial carotid artery (ECCA) carotid atherosclerosis (CA) in hypertensives and age- and sex-matched normotensives. Two hundred and sixty-three hypertensive patients and 270 normotensive subjects from the Chin-Shan Community Cardiovascular Cohort participated in this study in 1996. CA, expressed as maximal common carotid artery intima-media thickness (IMT) > or = 75th percentile and ECCA plaque score > 6, was measured using high-resolution B-mode ultrasonography. The presence of AR was assessed by echocardiography, and their relationships with CA were evaluated. Results showed measurements of CA significantly associated with increased PP. Presence of AR associated with CA, but this relationship was attenuated after controlling for age. Multivariate logistic regression analyses revealed that an ECCA score > 6 significantly increase the risk in conjunction with PP, age and smoking in hypertensives. Correspondingly, CA increased with age, smoking and left ventricular hypertrophy on electrocardiography but not PP in normotensives. In conclusion, higher PP is strongly associated with CA in patients with hypertension. In terms of risk stratification, PP is more important in hypertensives than in normotensives which seem to imply that pulsatile haemodynamic component of BP is crucial in association with atherosclerosis.

Aged↗
PubMed2005

Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) generally have an unfavorable clinical course and are under-represented in clinical trials. The aim of this study was to analyze the prognosis and treatment outcome of elderly AML patients. PATIENTS AND METHODS: We studied 205 AML patients aged 65 years or older at our hospital. Prior to study initiation, we designated 13 variables to be analyzed for their impact on complete remission (CR) rate and overall survival (OS). RESULTS: Induction regimen (standard chemotherapy) and good performance status (PS) (Eastern Cooperative Oncology Group PS 0-1) independently influenced the achievement of CR. Multivariate analysis also determined five poor prognostic factors for OS: poor PS (score 2-4), presence of comorbidities, elevated serum lactate dehydrogenase level (> or =2x upper normal limit), extreme leukocytosis (> or =100 x 10(9)/l) and marked thrombocytopenia (< or =20 x 10(9)/l). Age was not an independent contributing factor in terms of either CR attainment or OS duration. Low-risk patients, who possessed one or less non-leukocytosis poor prognostic factor, had significantly longer disease-free survival and OS than their high-risk counterparts. CONCLUSIONS: Elderly AML patients should be risk-stratified at diagnosis. Anthracycline-based induction chemotherapy would be the best therapeutic option for such patients.

Acute Disease↗
PubMed2005

Primary adenovirus-specific cytotoxic T lymphocyte response occurs after viral clearance and liver enzyme elevation.

The virus-specific cytotoxic T lymphocyte (CTL) response is a major obstacle to effective delivery of adenovirus gene therapy. However, its relative role in viral clearance, transgene elimination and hepatotoxicity remains unclear. In this paper, we present an analysis of viral clearance and liver toxicity in relation to the induction of the virus-specific CD8 T-cell response revealed by an MHC class I tetramer. A surprisingly high number of tetramer+ CD8 T cells were found in the liver and lung and reached peak values at days 8 and 10, respectively, post-infection. Nearly 100% of these tetramer+ CD8 T cells expressed high levels of granzyme B and IFNgamma. Remarkably, liver viral load and liver enzyme elevation peaked early, at days 2 and 4, respectively, post-infection, before the specific CTL response was detectable. After generation of CTLs, there was only minimal liver damage or further decrease in virus titer. These results indicated that the primary peak response of tetramer+ CTLs does not correlate with the elimination of adenovirus or liver cytotoxic response.

Adenoviridae↗
PubMed2005

Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of mice.

The BXD2 strain of mice is one of approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult BXD2 mice spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres of rheumatoid factor (RF) and anti-DNA antibody, and a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, and bone and cartilage erosion. The features of lupus and arthritis developed by the BXD2 mice segregate in F2 mice generated by crossing BXD2 mice with the parental B6 and D2 strains. Genetic linkage analysis of the serum levels of anti-DNA and RF by using the BXD RI strains shows that the serum titers of anti-DNA and RF were influenced by a genetic locus on mouse chromosome (Chr) 2 near the marker D2Mit412 (78 cm, 163 Mb) and on Chr 4 near D4Mit146 (53.6 cm, 109 Mb), respectively. Both loci are close to the B-cell hyperactivity, lupus or GN susceptibility loci that have been identified previously. The results of our study suggest that the BXD2 strain of mice is a novel model for complex autoimmune disease that will be useful in identifying the mechanisms critical for the immunopathogenesis and genetic segregation of lupus and erosive arthritis.

Albuminuria↗
PubMed2004

Microvessel density, cyclo-oxygenase 2 expression, K-ras mutation and p53 overexpression in colonic cancer.

BACKGROUND: Tumour angiogenesis, cyclo-oxygenase (COX) 2 expression, K-ras mutation and p53 overexpression are commonly involved in colorectal tumorigenesis, but their interrelationship and clinicopathological effects remain inconclusive. METHODS: Clinicopathological data from 114 consecutive patients with primary stage III colorectal cancer were evaluated prospectively. Microvessel density (MVD) of the tumour was defined by counting the number of microvessels in hotspots, visualized by immunocytochemical staining of endothelial CD34. K-ras mutation was analysed by the restriction enzyme cleavage method. COX-2 expression and p53 overexpression were determined by immunocytochemistry. RESULTS: Increased MVD in hotspots was significantly associated with COX-2 expression (P < 0.001), K-ras mutation (P = 0.007) and p53 overexpression (P = 0.006). COX-2 expression was not associated with either K-ras mutation or p53 overexpression. Clinicopathologically, greater MVD and COX-2 expression were significantly associated with vascular invasion of cancer cells (MVD, P = 0.027 and COX-2 expression, P = 0.006), but p53 overexpression and K-ras mutation were not. Multivariate analysis indicated that greater MVD (P = 0.002) and p53 overexpression (P = 0.016) were significant independent predictors of tumour recurrence, whereas COX-2 expression (P = 0.634) and K-ras mutation (P = 0.356) were not. CONCLUSION: Tumour angiogenesis may be associated with tumour metastasis and is significantly influenced by K-ras mutation, p53 overexpression and COX-2 expression in patients with colonic cancer.

Adult↗
PubMed2004

Identification of multiple genetic loci that regulate adenovirus gene therapy.

A key aspect of the immune response to adenovirus (Ad) gene therapy is the generation of a cytotoxic T-cell (CTL) response. To better understand the genetic network underlying these events, 20 strains of C57BL/6 x DBA/2 (BXD) recombinant inbred (RI) mice were administered with AdLacZ and analyzed at days 7, 21, 30, and 50 for liver beta-galactosidase (LacZ) expression and CTL response. Sera levels of interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were analyzed at different times after AdLacZ. There was a distinct strain-dependent expression of LacZ, which was strongly correlated with the CTL response. Among the five BXD RI strains that exhibited significantly prolonged LacZ expression, four also exhibited a marked defect in the production of Ad-specific CTL. There was a strong correlation between the sera levels of IFN-gamma, TNF-alpha, and IL-6, but cytokine responses were not significantly correlated with LacZ expression or the CTL response. Quantitative trait loci regulating LacZ on day 30 were found on chromosome (Chr) 19 (33 cM) and Chr 15 (42.8 cM). Cytotoxicity mapped to Chr 7 (41.0 and 57.4-65.2 cM), Chr 15 (61.7 cM), and Chr X (27.8 cM). IFN-gamma production mapped to Chr 18 (22, 27, and 32 cM) and Chr 11 (64.0 cM). TNF-alpha and IL-6 production mapped to Chr 6 (91.5 cM) Chr 9 (42.0 cM) and Chr 8 (52 and 73.0 cM). These results indicate that different strains of mice exhibit different pathways for effective clearance of AdLacZ depending on genetic polymorphisms and interactions at multiple genetic loci.

Adenoviridae↗
PubMed2004

Radiation therapy versus chemotherapy as initial treatment for localized nasal natural killer (NK)/T-cell lymphoma: a single institute survey in Taiwan.

BACKGROUND: To clarify the role of intention to treat for patients with localized nasal natural killer (NK)/T-cell lymphoma, and to determine the prognostic factors for these patients. PATIENTS AND METHODS: We conducted a retrospective review of 46 patients with localized nasal NK/T-cell lymphomas treated at a single institute between January 1988 and July 2002. RESULTS: The type of intended treatment was a significant factor for overall survival (OS) (5-year OS: RT versus CT = 83.3% versus 28.6%, P = 0.0269) or failure-free survival (FFS) (5-year FFS: RT versus CT = 83.3% versus 27.1%, P = 0.0247). In the intended chemotherapy group, salvage with radiotherapy was superior to chemotherapy alone for OS (5-year OS: 42.2% versus 20.0%, P = 0.0252) or FFS (5-year FFS: 41.0% versus 20.0%, P = 0.0352). On multivariate analysis, both N stage and serum lactate dehydrogenase level were independent factors for OS and FFS. No radiotherapy was an independent adverse factor for OS; advanced T stage and more than one extranodal involvement were independent adverse factors for FFS. CONCLUSIONS: Patients with localized nasal NK/T-cell lymphomas were better managed with radiotherapy as front-line therapy. The advantage of radiotherapy persisted even as palliative therapy after chemotherapy.

Adult↗
PubMed2004

Post-operative adjuvant thoracic radiotherapy for patients with completely resected non-small cell lung cancer with nodal involvement: outcome and prognostic factors.

The purpose of this study was to analyse the outcome and prognostic factors of non-small cell lung cancer (NSCLC) patients with nodal disease treated by complete tumour resection followed by radiotherapy alone. Between October 1990 and October 1999, 49 NSCLC patients with N1 or N2 stage were treated with complete resection of tumour followed by post-operative radiotherapy in our department. The radiation was delivered with 10 MV X-rays given 5 days per week at 1.8-2 Gy per fraction. Total doses ranged from 40 Gy to 64.8 Gy, with a median dose of 55.8 Gy. All patients had at least 30 months of follow-up. The 5 year overall survival rate (OS), local control rate (LC) and distant metastasis-free rate (DMF) were 34%, 52% and 29%, respectively. In multivariate analysis, stage and margin were found to influence OS. The total number of involved lymph nodes and positive margins were significant factors for LC. Only N stage was found to correlate with DMF. In conclusion, patients with multiple involved lymph nodes, advanced stage or positive surgical margins had a poor outcome even with post-operative radiotherapy. Based on these prognostic factors, new therapeutic regimens and modalities for NSCLC need to be further investigated.

Adult↗
PubMed2003

Diagnostic value of serum transferrin receptor and glycosylated hemoglobin on hemolytic anemia.

Soluble serum transferritin receptor (sTfR) is a new diagnostic tool for iron depletion and erythropoiesis. Glycosylated hemoglobin (GHb) can be used to detect hemolysis. The present study was thus conducted to compare the diagnostic value of sTfR and GHb (measured as Hb A(1)c) in patients with hemolytic anemia. Four groups of subjects entered into our study. Group A included 13 patients with hemolytic anemia with effective erythropoiesis (EE). Group B included 13 patients with hemolytic anemia with ineffective erythropoiesis (IE). Group C included 15 healthy controls and group D summated groups A and B. sTfR, serum ferritin, plasma hemoglobin, complete blood count, reticulocyte, haptoglobin, lactic dehydrogenase (LDH), Hb A(1)c, liver and renal function, direct and indirect bilirubin, and fasting blood sugar were measured. Plasma Hb, hematocrit, mean corpuscular volume (MCV), platelet, haptoglobin, LDH, indirect bilirubin, Hb A(1)c, and sTfR were found to be significantly different between the controls and the hemolytics, either with effective or ineffective erythropoiesis. Reticulocyte count was significantly different only between the two hemolytic groups. Hb A(1)c and sTfR were both good for the diagnosis of hemolysis. Reticulocyte count was a good tool for distinguishing EE from IE.

Anemia, Hemolytic↗
PubMed2003

Age-related thymic involution in C57BL/6J x DBA/2J recombinant-inbred mice maps to mouse chromosomes 9 and 10.

A comprehensive analysis of initial thymus size and involution rate has not been quantitated for different genetic backgrounds of mice, thus genetic linkage analysis of thymic involution has not been possible. Here, we have used a mathematical method to analyze the age-related decline in thymocyte count in C57BL/6 and DBA/2 mice and have observed that thymic involution could be best fit with a negative exponential curve N(t)=beta(0) x exp(-beta(1)t), where t represents the age (day). This regression model was applied to C57BL/6 x DBA/2 (B x D) recombinant inbred strains of mice to identify the genetic loci influencing age-related thymic involution. There was a dramatic genetic effect of B and D alleles on thymocyte count at young age and the age-related thymic involution rate. The strongest quantitative trait loci (QTL) influencing the rate of thymic involution were mapped to mouse chromosome (Chr) 9 (D9Mit20 at 62 cM) and Chr 10 (D10Mit61 at 32 cM). The strongest QTLs influencing the initial thymocyte count were mapped to ChrX (DXMit324 at 26.5 cM) and Chr 3 (D3Mit127 at 70.3 cM). The present study suggests that the initial thymus size and the rate of thymic involution may be influenced by a relatively small number of genetic loci.

Aging↗
PubMed2003

Cellular mechanism of thymic involution.

Involution of the thymus and alterations in the development of thymocytes are the most prominent features of age-related immune senescence. We have carried out a comparative analysis of thymocyte and stroma in rapid thymic involution DBA/2 (D2) strain of mice compared with slow involution C57BL/6 (B6) strain of mice. Analysis of mice at 15 months of age suggested an age-related decrease in the thymocyte cell count, a block in the development of T cells and cortical involution in D2 mice compared with 3-month-old mice. TUNEL (terminal-deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling) staining and fluorescence-activated cell sorter (FACS) analysis showed that there was a significant increase in apoptotic cells in the cortex region of thymus in 15-month-old D2 mice compared with the same aged B6 mice. The thymocyte proliferation rate, as assessed by bromodeoxyuridine (BrdU) staining and [3H]-thymidine incorporation assay, was lower in 3-month-old D2 mice compared with the same age B6 mice. Immunohistochemical staining showed that the arrangement of MTS (mouse thymus stromal)-10+ epithelial cells and MTS-16+ connective tissue staining pattern had become disorganized in 15-month-old D2 mice but remained intact in B6 mice of the same age. These results suggest that, in D2 mice, both the thymocytes and stromal cells exhibit age-related defects, and that the genetic background of mice plays an important role in determining age-related alterations in thymic involution.

Aging↗
PubMed2002

Soluble Fas gene therapy protects against Fas-mediated apoptosis of hepatocytes but not the lethal effects of Fas-induced TNF-alpha production by Kupffer cells.

The elevation of soluble Fas (sFas) in the sera of patients with liver disease suggests a role for sFas in the disease process; whether it is protective or not is controversial. To determine the effects of sFas on Fas-induced liver apoptosis, we manipulated mice to produce sFas by transfecting them in vivo with different amounts of an adenovirus that produces mouse sFas driven by the CMV promoter (AdsFas). Fas-mediated apoptosis was induced by administration of anti-mouse Fas (Jo2; 10 microg/mouse) one week later. The administration of AdsFas (10(3), 10(7), or 10(9) pfu/mouse), which was associated with only minimal side-effects, resulted in a significant reduction in the liver transaminase levels and mortality of the mice on challenge with Jo2, as compared to control mice treated with AdLacZ. However, the protective effect of AdsFas was not complete. The possibility that Jo2-induction of TNF-alpha in the Kupffer cells of the liver contributes to the pathology was therefore tested. Although administration of soluble TNF receptor (sTNFRI) alone did not protect the mice from the lethal effects of Jo2, administration of sTNFRI (200 microg/mouse) after infection with AdsFas (10(9) pfu/mouse) resulted in 100% survival of the mice on challenge with Jo2. To confirm that the production of TNF-alpha by Kupffer cells produce the lethal effects of Jo2 that remained after treatment with AdsFas, these cells were selectively ablated by treatment of the mice with gadolinium chloride prior to challenge with Jo2. This treatment greatly reduced early mortality and hepatocellular damage as well as TNF-alpha production 6 h after injection of Jo2. These results indicate that: (1) AdsFas prevents Jo2-induced apoptosis of hepatocytes; (2) In addition to mediating Fas-mediated apoptosis of hepatocytes, Jo2 can separately induce TNF-alpha production by Kupffer cells resulting in early mortality, and (3) Optimal protection from Jo2-induced mortality can be achieved by protection of liver cells by pretreatment with both AdsFas and sTNFRI.

Animals↗