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Der-Yuan Chen

Publications and source records attributed to Der-Yuan Chen.

12 recordsLinked to original sources
PubMed2024

Platelet-derived mitochondria regulate lipid metabolism in nonalcoholic steatohepatitis through extracellular vesicles.

BACKGROUND AND AIMS: Immune system activation, along with lipotoxicity due to excessive lipid droplet (LD) accumulation in the liver, are key drivers of NASH. Extracellular vesicles (EVs) released by cells that carry biological signals contribute to intercellular communication. However, the roles of immune cell-derived EVs in the pathogenesis of NASH are unclear. APPROACH AND RESULTS: Platelets are abundant in blood. We explored the role of platelet-derived EVs (pEVs) in LD accumulation from 30 patients with nonalcoholic fatty liver disease of different severity as well as 20 healthy subjects, a rat model, and an in vitro cell-based assay. There was increased platelet activation, accompanied by pEVs release, in NASH patients/rat model, and palmitate-treated cells. The mitochondria in the platelets and pEVs from NASH patients/rats were increased but dysfunctional, including a reduction in fatty acid β-oxidation, inactivated acetyl-CoA carboxylase 2, and suppressed oxidative phosphorylation system complex II/III/IV activity. These damaged mitochondria could be transferred to hepatocytes through pEVs to increase the number of lipid droplet-bound mitochondria. An increase in dysfunctional lipid droplet-bound mitochondria in hepatocytes affects lipid metabolism, resulting in excessive LD accumulation, elevated mitochondrial reactive oxygen species production, and apoptosis. CONCLUSIONS: We offer a novel molecular mechanism that connects platelets, pEVs, and excessive LD accumulation to the development of NASH. Our results suggest that NASH progression may be alleviated by specifically inhibiting the production and release of pEVs, or by targeting pEV components and inhibiting their uptake. Additional experiments are required to confirm this potentiality.

Non-alcoholic Fatty Liver Disease↗
PubMed2006

Elevated levels of soluble Fas (APO-1, CD95), soluble Fas ligand, and matrix metalloproteinase-3 in sera from patients with active untreated adult onset Still's disease.

To investigate serum levels of soluble Fas (sFas), soluble Fas ligand (sFas-L), and matrix metalloproteinase-3 (MMP-3) in patients with active untreated adult onset Still's disease (AOSD). Serum levels of sFas, sFas-L, and MMP-3 were determined by enzyme-linked immunosorbent assays in 20 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. Linear regression was used to evaluate the correlation between clinical activity scores and serum levels of sFas, sFas-L, and MMP-3 in AOSD patients. Significantly higher levels of sFas, sFas-L, and MMP-3 in sera were found in active untreated AOSD patients compared to healthy controls. Serum levels of sFas, sFas-L, and MMP-3 correlated well with clinical activity scores of AOSD patients (r=0.467, 0.694, and 0.798, respectively). There was a significant correlation between CRP values and serum levels of sFas-L as well as MMP-3 (r=0.583 and r=0.582, respectively, both p<0.01), and a positive correlation between serum sFas-L levels and serum MMP-3 levels (r=0.726, p<0.001) in AOSD patients. Significantly higher levels of serum sFas-L were found in AOSD patients than in RA patients. Serum levels of sFas, sFas-L, and MMP-3 fluctuated and were found to be parallel to disease activity of AOSD. sFas, sFas-L, and MMP-3, which were significantly elevated in sera of active untreated AOSD patients and paralleled disease activity, may be involved in the pathogenesis of this disease. Further studies are needed to determine the pathophysiologic role of sFas, sFas-L, and MMP-3 in AOSD.

Adult↗
PubMed2006

Subcutaneous panniculitis-like T-cell lymphoma presenting with hemophagocytic lymphohistiocytosis and skin lesions with characteristic high-resolution ultrasonographic findings.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an unusual type of skin lymphoma, characterized by subcutaneous soft tissue infiltration with pleomorphic T-cells and benign macrophages that mimic panniculitis. Hemophagocytic lymphohistiocytosis is a rare but potentially fatal disorder which is thought to result from uncontrolled activation and proliferation of T-cells and excessive activation of macrophages. Hemophagocytic lymphohistiocytosis have been reported as the presenting feature in 37% of SPTCL patients. High-resolution ultrasonographic appearance of SPTCL with a characteristic finding has been described in only one patient. We report a 28-year-old woman with hemophagocytic lymphohistiocytosis presented with nonremitting fever, thrombocytopenia, hypofibrinogenemia, hyperferritinemia, increased serum levels of soluble interleukin (IL)-2 receptors and hemophagocytosis in bone marrow examination. Markedly elevated level of serum IL-18 was also demonstrated in our patient. The fever subsided and the ferritin level declined to normal after treatment with oral steroid and etoposide. No evidence of hemophagocytosis was revealed in a follow-up bone marrow examination. However, nonremitting high fever and panniculitis-like skin lesions over her back, arm, lower abdominal wall, and bilateral pretibial regions developed 1 month later. A high-resolution ultrasonography revealed thickening of the subcutaneous fat layer with homogeneous hyperechogenicity pattern and poor-defined margin over the skin lesions. An ultrasound-guided excision biopsy of the nodular lesion over left upper arm was performed and the histopathology showed neoplastic cells with hyperchromatic nucleoli, which extended from deep dermis to subcutaneous fat. The immunochemical stain showed a T-cell lineage of tumor cells. SPTCL was diagnosed and the skin lesions subsided gradually after treatment with anthracycline-based combination chemotherapy.

Adult↗
PubMed2006

Late-onset and rare far-advanced pulmonary involvement in patients with sarcoidosis in Taiwan.

BACKGROUND: Sarcoidosis is still considered a rare multisystem disorder in Taiwan, and data on the disease course and outcome are limited. We analyzed the clinical manifestations, disease course and complications in Taiwanese patients with sarcoidosis. METHODS: A retrospective cohort design was used. Fifty-six patients with sarcoidosis diagnosed between 1985 and 2004 were included. Their clinical features, laboratory findings at initial presentation, disease course, and complications were analyzed. RESULTS: Forty-three patients (76.8%) were female. The mean age at symptom onset was 47 years. The most common clinical symptoms were pulmonary (82.1%), cutaneous (23.2%), ophthalmic (19.6%), and articular (17.8%). Only two patients presented with Löfgren's syndrome. There was a seasonal variation in disease onset, with higher incidence in winter and early spring. No advanced pulmonary involvement was noted. Elevated levels of serum angiotensin converting enzyme (sACE) were found in 72.5% (29/40) of patients with active sarcoidosis, and significantly higher levels of sACE were found in patients with lung involvement (27.98+/-1.71 IU/L vs. 18.2+/-2.76 IU/L; p<0.01). In 50% (20/40) of patients, sACE levels declined significantly in parallel with clinical remission (24.75+/-1.53 IU/L vs. 16.33+/-1.21 IU/L; p<0.05). Spontaneous complete remission was found in 20.7% of patients, whereas 39.6% of patients with multiple extrapulmonary involvement responded poorly to intensive corticosteroids plus various immunosuppressants. CONCLUSION: In this series, the mean age of disease onset was in middle age (mean, 47 years old), there was a low incidence of Löfgren's syndrome (3.6%), and no patients had advanced pulmonary syndrome. The results of this study also suggest that sACE might be a marker of pulmonary involvement that is also useful in monitoring disease activity.

Adolescent↗
PubMed2005

Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still's disease.

OBJECTIVE: To investigate the association of intercellular adhesion molecule 1 (ICAM-1) with clinical manifestations and interleukin-18 (IL-18) levels in patients with active untreated adult-onset Still's disease (AOSD). METHODS: We determined serum soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay in 50 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. The levels of ICAM-1 messenger RNA expression in IL-18-stimulated peripheral blood mononuclear cells (PBMCs) and in biopsy specimens obtained from AOSD patients with Still's rash or synovitis were investigated using real-time quantitative polymerase chain reaction. RESULTS: Significantly higher serum levels of sICAM-1 were observed in patients with active untreated AOSD compared with those with active RA and healthy controls. Serum sICAM-1 levels were significantly correlated with the clinical activity score (r = 0.565, P < 0.001), ferritin values (r = 0.462, P < 0.005), and IL-18 levels (r = 0.462, P < 0.005) in patients with AOSD. The serum sICAM-1 level was identified as a predictor of hepatic dysfunction (odds ratio [OR] 1.016, P = 0.011) and disseminated intravascular coagulation (DIC) (OR 1.013, P = 0.023). Up-regulation of ICAM-1 gene expression was demonstrated in IL-18-stimulated PBMCs from patients with AOSD. Increased levels of ICAM-1 transcripts were observed in the biopsy specimens obtained from AOSD patients with Still's rash or synovitis compared with healthy skin and patients with osteoarthritis. CONCLUSION: The serum sICAM-1 level may be used as a clinical marker to assess disease activity and may predict the occurrence of hepatic dysfunction and DIC in AOSD. IL-18-up-regulated gene expression of ICAM-1 may contribute to the inflammatory response in AOSD.

Adult↗
PubMed2004

A comparative study of etanercept plus methotrexate and methotrexate alone in Taiwanese patients with active rheumatoid arthritis: a 12-week, double-blind, randomized, placebo-controlled study.

BACKGROUND AND PURPOSE: Etanercept (Enbrel), a recombinant tumor necrosis factor receptor fusion protein, has been shown to be effective in the treatment of patients with rheumatoid arthritis (RA). The purpose of this study was to compare the efficacy and safety of etanercept in combination with methotrexate (MTX) and MTX alone in Taiwanese patients with active RA. METHODS: In this double-blind study, 58 patients with active RA who were maintained on MTX therapy at a stable dose of 12.5 to 20 mg per week for 4 weeks were randomized to receive either etanercept 25 mg (n = 29) or placebo (n = 29) by subcutaneous injection twice weekly over a period of 12 weeks. The primary endpoint was the reduction of tender and swollen joint counts by 20% (ACR 20), 50% (ACR 50), and 70% (ACR 70) as determined by the American College of Rheumatology criteria at the 12th week. RESULTS: The addition of etanercept to MTX resulted in a greater reduction in the number of tender (7.00 vs 2.45, p = 0.012) and swollen joints (8.55 vs 3.86, p = 0.017), and in serum levels of C-reactive protein (1.26 mg/dL vs 0.45 mg/dL, p = 0.014) compared to MTX alone after 12 weeks of therapy. In addition, the global assessment of disease activity by both physicians and patients, duration of morning stiffness, pain visual analog scale score, and Health Assessment Questionnaire were all improved by etanercept plus MTX therapy. Results for the overall improvement in disease activity assessed by ACR 20 (90% vs 34%), ACR 50 (66% vs 10%) and ACR 70 (24% vs 0%) all favored the etanercept plus MTX group. However, the adverse events were comparable between the 2 treatment groups. CONCLUSION: Etanercept in combination with MTX was well tolerated and provided significantly more clinical benefit than MTX alone in Taiwanese patients with active RA.

Antirheumatic Agents↗
PubMed2004

A mucolipidosis III patient presenting characteristic sonographic and magnetic resonance imaging findings of claw hand deformity.

Mucolipidosis III (ML-III), or pseudo-Hurler polydystrophy, is an autosomal recessive Hurler-like disorder without mucopolysacchariduria. The diagnosis is challenging for rheumatologists since the musculoskeletal presentation is similar to some rheumatic diseases. We report a case of ML-III in a 16-year-old Taiwanese boy. The characteristic findings of sonography and magnetic resonance imaging (MRI) of claw hand deformity are described. A 16-year-old boy was referred to our rheumatologic clinic because of progressive claw hand deformity, multiple joint stiffness and tightness of the skin over the fingers at the age of 6 years. Sonography and MRI examination disclosed tendon sheath thickening over extensor tendons of both wrists and fingers without features of active inflammation over tendons or joints nor thickening of skin. Urinary glycosaminoglycans were normal. The diagnosis of ML-III was confirmed by the presence of elevated activities of beta-glucuronidase (2141.99 nmol/mg protein/hour), arylsulfatase A (1237.7 nmol/mg protein/hour) and alpha-fucosidase (52.95 nmol/mg protein/hour) in his plasma and decreased activity of these lysosomal enzymes in cultured skin fibroblasts. Sonography and MRI screening for claw hand deformity may offer important clues enabling early diagnosis of ML-III.

Adolescent↗
PubMed2004

Proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult onset Still's disease.

OBJECTIVE: To investigate concentrations of proinflammatory cytokines in the sera and their mRNA expression in biopsy specimens of evanescent rash and synovitis from patients with active untreated adult onset Still's disease (AOSD). METHODS: We measured serum levels of interleukin 6 (IL-6), IL-8, and tumor necrosis factor (TNF-alpha) by immunochemiluminescence method and serum IL-18 levels by ELISA in 50 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. Multivariate analysis was used to evaluate the correlation between serum cytokine levels and disease activity and clinical features of AOSD. We also evaluated the expression of cytokine transcripts by real-time quantitative polymerase chain reaction in biopsy specimens of evanescent rash and synovitis from 12 patients with active untreated AOSD. RESULTS: Significantly higher levels of IL-6, IL-8, IL-18, and TNF-alpha in sera were found in patients with active untreated AOSD compared to healthy controls. Serum levels of IL-6 and IL-18 correlated well with clinical activity score of AOSD patients. Multiple logistic regression analysis showed that serum IL-6 level was a possible predictor for the occurrence of evanescent rash (p = 0.0593), serum IL-8 level was a significant predictor of persistent arthritis, and serum IL-18 level predicted occurrence of liver dysfunction. The levels of mRNA expression of IL-6, IL-18, and IL-8 were significantly higher in the biopsy tissue of Still's rash from AOSD patients compared with those in controls. Levels of mRNA expression of IL-18, IL-8, and TNF-alpha were significantly higher in the synovial membranes of AOSD patients compared with those in osteoarthritis controls. Significantly lower levels of TNF-alpha and IL-8 were found in the sera and in the synovial membranes of AOSD patients compared with those in RA patients. AOSD patients who had a chronic articular course had significantly higher levels of serum IL-8 compared with those who had a monocyclic systemic course. CONCLUSION: Significantly higher levels of IL-6, IL-8, IL-18, and TNF-alpha were seen in both sera and pathological tissues of patients with active AOSD. The associations between levels of cytokine profile and distinct clinical manifestations and various patterns of disease course suggest the heterogeneity of pathogenesis in AOSD.

Adult↗
PubMed2004

Clinical manifestations, disease course, and complications of adult-onset Still's disease in Taiwan.

BACKGROUND AND PURPOSE: Data on the disease course and ultimate outcome of adult-onset Still's disease (AOSD) are limited. We analyzed the clinical manifestations, disease course, and complications of patients with AOSD in Taiwan. METHODS: A retrospective cohort design with prospective follow-up was used. Eighty two patients with AOSD diagnosed between 1983 and 2003 were evaluated. Their clinical features and laboratory findings at presentation, disease course, and complications were analyzed. RESULTS: Fifty nine patients (72%) were female and 55 (67.1%) were aged between 16-35 years at onset. The most common clinical manifestations were fever (100%), articular symptoms (100%), evanescent rash (87%), and sore throat (84%). Dermatographism was noted in 59% of patients. Elevation of erythrocyte sedimentation rate and C-reactive protein, which were significantly correlated with disease activity score (both p < 0.01) occurred in more than 90% of AOSD patients. Elevation of serum ferritin, which was significantly correlated with disease activity score and hepatic enzyme levels, was present in 91% of patients. Polycyclic systemic course was the most common (45%), followed by monocyclic systemic course (34%); only 20% of patients progressed to chronic arthropathy. CONCLUSIONS: The multisystemic involvement and various patterns of disease course in this series illustrate the heterogenic nature of AOSD. Serum ferritin levels can be used as a marker for monitoring disease activity in AOSD.

Adolescent↗
PubMed2002

Association between molecular variants of the angiotensinogen gene and hypertension in Amis tribes of eastern Taiwan.

BACKGROUND AND PURPOSE: Molecular variants (M235T and T174M) in the angiotensinogen (AGT) gene and a mutation in the promoter region that involves the presence of an adenine (A) instead of a guanine (G) 6 bp upstream from the transcription initiation site (G-6A) have been reported to have a positive correlation with hypertension. This study evaluated the association of the M235T, T174M, and G-6A mutations of the AGT gene with hypertension in Taiwanese aboriginals. METHODS: This case-control study recruited 107 subjects with hypertension and 96 normotensive subjects from the Amis tribes of eastern Taiwan. Genomic DNA was amplified using the polymerase chain reaction (PCR) and the PCR product was analyzed using automated sequencing. RESULTS: The frequencies of MM, MT, and TT genotypes at amino acid 235 were different between hypertensive (1%, 13%, 86%) and normotensive subjects (0%, 30%, 70%; p = 0.008), whereas the 174 variants of the AGT gene were not different between these two groups (1%, 14%, 85% in hypertensives, 1%, 17%, 82% in normotensives; p = 0.868). The distribution of GG, GA, and AA genotypes differed between the two groups (1%, 15%, 84% in hypertensives vs 1%, 31%, 68% in normotensives; p = 0.021). The frequency of the 235T allele was higher among hypertensives than normotensives (93 vs 85%; p = 0.015) and the odds ratio for association with the 235T allele (vs 235M) in hypertensives was 2.20. The frequency of the 174M allele was not different between the two groups (1 vs 1%). The frequency of the -6A allele was higher among hypertensives (83 vs 68%; p = 0.011) and the odds ratio association of hypertension with the -6A allele (vs -6G) was 2.18. Haplotype analysis showed that the -6A-235T allelic frequencies significantly differed between the two groups (chi 2 = 1.39, P = 0.001). CONCLUSIONS: The prevalences of the 235T and -6A variants of the AGT gene in the Amis tribes of eastern Taiwan are high and are significantly associated with hypertension, whereas the 174M variant is not. The haplotype combining the 235T and -6A variants is also associated with hypertension. The prevalences of the 235T allele and -6A allele in this study and other studies in ethnic Chinese subjects are higher than those in Japanese.

Aged↗
PubMedDate not supplied

Solid-phase radionuclide esophageal transit in progressive systemic sclerosis.

BACKGROUND/AIMS: In most patients with progressive systemic sclerosis the esophagus is affected. Reflux symptoms are most frequent whilst dysphagia also occurs. The radionuclide esophageal transit study is a sensitive screening test for esophageal dysfunction. In this study, we evaluated the esophageal motility of patients with progressive systemic sclerosis using a solid-phase radionuclide esophageal study. METHODOLOGY: Thirty-two patients with progressive systemic sclerosis and 30 normal volunteers were studied with solid-phase radionuclide esophageal study. Each subject was placed in a supine position above a gamma camera linked to a computer and was given a 4-mL bolus of solid gelatin containing 1 mCi of Tc-99m phytate. Data were acquired in the list mode. RESULTS: Twenty-nine of the 32 patients (91%) had abnormal findings from the study. CONCLUSIONS: The radionuclide esophageal transit study can be regarded as a useful tool for evaluating the esophageal function in patients with progressive systemic sclerosis and in the follow-up of treatment.

Administration, Oral↗