Shih-Tzu Tsai

Cerebrospinal Fluid lnterleukin-6, Prostaglandin E2 and Autoantibodies in Patients with Neuropsychiatric Systemic Lupus Erythematosus and Central Nervous System Infections

Cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) disorders was assayed for cytokines, prostaglandins, and autoantibodies. CSF interleukin-6 (IL-6) in patients with CNS infection (374.24 ± 92.61 pg/mL) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (71.40 ± 5.89 pg/mL) were significantly higher than in patients with CNS inflammation (33.92 ± 29.36 pg/mL) or controls (non-inflammatory CNS diseases) (4.35 ± 3.00 pg/mL). Interleukin-1β, interferon α, and tumor necrosis factor α were undetectable in these samples: CSF prostaglandin E2 (PGE2) also exhibited similar patterns as IL-6. CSF immunoglobulin G (IgG) in patients with NP-SLE (8.84 ± 1.80 mg/dL) was much higher than in patients with CNS infection (4.65 ± 3.09 mg/dL), CNS inflammation (2.54 ± 1.24 mg/dL), or controls (2.11 ± 1.03 mg/dL). CSF autoantibodies against calf thymus antigens were present in patients with NP-SLE but not in patients with CNS infection as demonstrated by immunoblot. These results su...

Hepatitis C virus infection-related Type 1 diabetes mellitus

Background  Hepatitis C virus (HCV) has been associated with Type 2 diabetes mellitus, and many other viral infections have been associated with Type 1 diabetes mellitus (Type 1 DM). An association between HCV and Type 1 DM, however, has never been reported. We report the case of a 66‐year‐old man who developed Type 1 DM 1 year after a blood transfusion‐related HCV infection. Testing of serum specimens obtained in the weeks following blood transfusion demonstrated evidence of both acute HCV infection and development of Type 1 DM‐related autoantibodies.

The effect of human polyclonal anti-dsDNA autoantibodies on apoptotic gene expression in cultured rat glomerular mesangial cells

In our previous studies, we found that polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) purified from sera of patients with active systemic lupus erythematosus (SLE) were cytotoxic to cultured rat glomerular mesangial cells (RMC) through an apoptotic mechanism. In order to determine whether these nephritogenic antibodies affect the expression of apoptosis-related genes in the tissues, the expression of Fas, p53, c-myc, and bcl-2 genes in the kidneys and livers of 12-week-old normal BALB/c and autoimmune MRL-lpr/lpr mice was detected by a reverse transcription-assisted polymerase chain reaction (RT-PCR). We found the mRNA of the four genes were expressed in the tissues of the normal mice. In contrast, decreased expression of the four genes in the kidney and absent expression of bcl-2 in the liver of the lpr mice were noted. Interestingly, RMC only expressed p53 and c-myc, but not Fas or bcl-2, in culture. The purified polyclonal anti-dsDNA dose-responsively (50-200 IU/ml) suppressed the 3H-thymidine incorporation of RMC after incubation for 48 h. However, the incubation of 100 IU/ml of anti-dsDNA with RMC for 4 h did not affect the expression of these apoptotic genes. The results suggest that anti-dsDNA induce RMC apoptosis via an unidentified mechanism different from Fas, c-myc or p53 pathway.

Hepatitis B infection and changes in interferon‐α and ‐γ production in patients with systemic lupus erythematosus in Taiwan

According to previous reports, the prevalence of hepatitis B virus (HBV) infection in patients with systemic lupus erythematosus (SLE) is varied. There has been no report on Taiwan, a hyperendemic area for HBV infection. Furthermore, impaired production of interferon (IFN) in peripheral blood mononuclear cells (PBMC) has been reported to be potentially pathogenic to both chronic HBV infection and SLE. However, the production of IFN in patients with both diseases coexisting is unknown. The aims of this study were to evaluate the prevalence of HBV infection in lupus patients in Taiwan and to measure the production of IFN in patients with both diseases coexisting. One hundred and seventy‐three consecutive lupus patients and a control group of 692 ageand sex‐matched healthy subjects were included for evaluation of the prevalence of HBsAg. Four groups of subjects (patients with SLE and HbsAg, SLE, chronic hepatitis B and normal controls) were selected for evaluation of the in vitro production of IFN‐α and ‐γ. Six (3.5%) of the 173 SLE patients were positive for HBsAg, which was significantly lower than that of controls (14.7%; P< 0.0001). Patients with coexistent SLE and chronic HBV infection had less lupus activity, including less proteinuria (P= 0.02) and a lower serum titre of anti‐double stranded DNA antibodies (anti‐dsDNA; P= 0.04), than HBsAg‐negative lupus patients. The in vitro production of IFN‐α in patients with chronic hepatitis B was significantly lower than in those patients with SLE or in the normal control group (P<0.01). The yields of IFN‐α and ‐γ in patients with coexistent SLE and chronic HBV infection were significantly different from those patients with SLE alone (P<0.05), but close to those of patients with chronic HBV infection. In conclusion, the prevalence of HBsAg carriers is significantly lower in lupus patients in Taiwan. Patients with coexistent SLE and chronic HBV infection had less lupus activity. Interferon‐α and ‐γ may play a role in the above phenomenon.

Interleukin 8 modulates interleukin-1β, interleukin-6 and tumor necrosis factor-α release from normal human mononuclear cells

Abstract Recombinant human interleukin 8 (IL-8) enhanced the release of inflammatory cytokines including interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) from normal human mononuclear cells in a dose-related manner (from 1 ng/ml to 10 ng/ml with a maximal effect at 5 ng/ml( when the cells incubated with IL-8 for 24 h. This cytokine-releasing activity of IL-8 is temperature-dependent and required protein synthesis since low temperature (4°C) and cycloheximide (100 μg/ml) minimized the cytokine release from MNC. However, when IL-8 concentration was greater than 20 ng/ml, the cytokine release was supressed. For further investigating the subcellular mechanism of the adverse effect of high dose IL-8 (20 ng/ml) in cytokine synthesis, human mononuclear cells (1 × 106/ml) were stimulated with PHA (1 μg/ml) in the presence of 20 ng/ml IL-8 for 3 days. We found not only [3H]thymidine incorporation of MNC was tremendously inhibited but DNA fragmentation appeared. Subsequently, the cell cycle of PHA-stimulated MNC retarded in the phase of G0/G1. These results suggest that in low concentration (5–10 ng/ml) IL-8 not only activated neutrophil phagocytosis but facilitated the release of inflammatory cytokines from mononuclear cells. Higher dose of IL-8 (more than 20 ng/ml) conversely suppressed these cytokine release from damaged cells by its cytotoxic effect. This newly found cytokine-releasing activity of IL-8 may play a role in the modulation of inflammation.

Bilateral carpal tunnel syndrome secondary to tophaceous compression of the median nerves.

A 65-year-old man with long-term gouty arthritis developed bilateral carpal tunnel syndrome. At surgery a chalky substance, which showed negative birefringence on polarized microscopy, was found infiltrating around the intensely inflamed transverse carpal ligaments. In differential diagnosis of carpal tunnel syndrome, tophaceous compression over the median nerve should be taken into consideration.

Tamm-Horsfall glycoprotein (THG) is a binder for surface membrane proteins on blood cells and glomerular mesangial cells

A macromolecule with a molecular weight of 90-100 kDa was purified from normal human pregnancy urine. The molecule was proved to be the Tamm-Horsfall glycoprotein (THG) by Western blot analysis. The macromolecule contains carbohydrate as detected by an enzyme immunoassay. Functionally, the glycoprotein can adhere to and stimulate the thymidine incorporation of human mononuclear cells (MNC) in modest degree via its membranotropic property. In addition to MNC, the protein can also bind to the surface of human polymorphonuclear neutrophils (PMN), red blood cells (RBC) and rat glomerular mesangial cells (RMC). Western blot analysis of various cell lysates with/without proteinase K pretreatment before cell lysis revealed that a 60 kDa and a molecule larger that 94 kDa on the surface of PMN, a 60 kDa protein on MNC and a 32 kDa protein on RBC are the binding molecules for THG. In contrast, many proteins on the surface of RMC could be bound by THG. Immunoprecipitation of membranous iodinated MNC lysates also confirmed that the 60 kDa molecule on MNC is the binding protein for THG. A number of monosaccharide including N-acetylneuraminic acid, N-acetyl-galactosamine, N-acetyl-glucosamine and alpha-methyl-D-mannoside could not inhibit the mitogenic effect of THG on human mononuclear cells. These results suggest that THG is capable of reacting with surface membrane proteins on different cells, but not through the specific carbohydrate-containing lectin-like receptors on the cell surface.

Improvement of Active Rheumatoid Arthritis After Etanercept Injection: A Single-center Experience

Background: To study the clinical effectiveness and adverse reactions of etanercept in patients with active rheumatoid arthritis (RA), in whom combination therapies with disease‐modifying antirheumatic drugs (DMARDs) had failed. Methods: One hundred and thirty‐three patients with active RA who had been treated without satisfactory effect with DMARDs were entitled, by the Taiwan Bureau of National Health Insurance, to undergo etanercept injection (25 mg subcutaneously, twice weekly) along with oral methotrexate (15 mg weekly) in Taipei Veterans General Hospital. The disease activity score in 28 swollen and 28 tender joints (DAS28), erythrocyte sedimentation rate (ESR), serum C‐reactive protein (CRP), rheumatoid factors (RFs), tender joint count (TJC), and swollen joint count (SJC) were recorded at the beginning, 3, 6, 9, and 12 months after treatment. Any adverse event, relevant or irrelevant to the therapy, was recorded throughout the whole course of treatment. Results: Ninety‐four patients completed the 1‐year therapeutic program. There were significant improvements in all parameters (DAS28, ESR, CRP, TJC and SJC), which approached satisfactory values at the end of the first 3 months and which were sustained thereafter in most patients. Patients also tolerated the treatment protocol well, with adverse events occurring sporadically. Significant clinical response occurred as early as 3 months after the start and might last beyond 1 year in some patients. Adverse effects such as injection site reaction or infections rarely occurred. Conclusion: Combination therapy with etanercept and DMARDs seemed to be effective at improving the aching symptoms associated with rheumatoid activity and was well tolerated in this cohort study. It was generally safe, though a small number of non‐fatal infections were observed.

Pure red cell aplasia in a man with RA.

A 65 year-old man with long-standing rheumatoid arthritis (RA) developed pure red cell aplasia (PRCA), which was apparently not caused by drugs or viral infections. The condition responded favorably to danazol in combination with sulfasalazine. This was probably the 2nd case of RA with PRCA in a male patient.

Osteochondroma in a Patient with Juvenile Ankylosing Spondylitis Associated with Idiopathic Thrombocytopenic Purpura and a Thalassemia

An unusual combination of osteochondroma, ankylosing spondylitis, thalassemia alpha, and thrombocytopenia was found in a young man who had once been an amphetamine addict. The association of these settings might have been coincidental but it cannot be excluded that the preexisting inflammatory processes or tissue destruction in the latter 3 diseases might have rendered the patient prone to the development of osteochondroma.