Assessment of a Difference in ALDH2 Heterozygotes and Alcoholic Liver Injury

We have speculated that the degree of liver dysfunction in alcoholic liver disease with ALDH2*1/2*2 may be less pronounced than that with ALDH2*1/2*1 . In the present study, outpatients with alcoholic liver injury were examined for ALDH2 genotype and biochemical data. The number of patients was 29 cases of nonspecific changes, 16 cases of fatty liver, 5 cases of liver fibrosis, and 44 cases of liver cirrhosis. Biochemical data were evaluated with ALDH2 heterozygotes data obtained by PCR-SSCP. The ALDH2*1/2*1 and ALDH2*1/2*2 genotypes accounted for 90% and 10%, respectively. As for ALDH2*1/2*2 , there were three patients with nonspecific changes, three with fatty liver, one with liver fibrosis, and two with liver cirrhosis. In alcoholic liver disease patients, when the ALDH2*1/2*2 genotype was compared with the ALDH2*1/2*1 genotype with biochemical data, the γ-GTP value in patients with ALDH2*1/2*2 was significantly higher than with ALDH2*1/2*1 ( p < 0.005). When the frequency of ALDH2 genotype was determined in patients with alcoholic liver injury, ALDH2 heterozygotes accounted for 15% for the non-cirrhosis group, and 5% for the cirrhotic group. When a relationship between the amount of ethanol intake and biochemical data were determined in patients with alcoholic liver injury who have ALDH2 heterozygotes, the glutamic oxaloacetic transaminase (GOT) and γ-GTP values were significantly higher at an ethanol intake amount of ethanol more than 100 g per day than intake less than 100 g per day ( p < 0.05). The alcoholic patients with ALDH2*1/2*2 drink a slight amount of ethanol, the liver injury is found to be stronger than those with ALDH2*1/2*1 when they drink more than 100 g ethanol per day.     

Pathogenic importance of fibronectin in the superficial region of articular cartilage as a local factor for the induction of pannus extension on rheumatoid articular cartilage.

To identify the local factors in cartilage that are responsible for the induction of pannus invasion, a 14 day organ culture study in which rheumatoid synovium was grown in contact with cartilage pieces was carried out. Rheumatoid synovium preferentially extended over hyaluronidase treated cartilage pieces, but detached from untreated pieces. Rheumatoid synovium extended over hyaluronidase treated cartilage surfaces containing fibronectin more extensively than over surfaces treated with hyaluronidase only. Extension over hyaluronidase treated cartilage surfaces containing immune complexes was small. The adherence of synovial cells to hyaluronidase treated cartilage slices in vitro was specifically inhibited by the synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, which is the adhesive portion of the fibronectin molecule. Furthermore, synovial fibroblast-like cellular extension, morphologically similar to rheumatoid pannus, was observed in the organ culture experiments in which rheumatoid synovium grew over hyaluronidase treated cartilage surfaces containing fibronectin. Synovial tissue extension over fibronectin coated surfaces was inhibited when hyaluronic acid and chondroitin-4-sulphate, major components of cartilage proteoglycans, were present on the cartilage surface. These findings suggest that fibronectin present in the superficial region of cartilage potentiates rheumatoid synovial extension and proteoglycans and immune complexes inhibit rheumatoid synovial extension. It is likely that fibronectin deposited on the eroded surface of articular cartilage induces pannus formation in rheumatoid arthritis.     

Alpha-interferon treatment for adult T cell leukemia: low levels of circulating alpha-interferon and it's clinical effectiveness

Summary We describe a patient with adult T cell Leukemia to whom alpha-interferon therapy was highly effective. Although a combination chemotherapy (ACVP) first introduced was effective in reducing total leukocyte counts, the percentage of leukemic cells relative to total leukocyte counts was decreased first after the institution of alpha-interferon therapy. The patient is now under complete remission for four years. It was noted in this patient that circulating alpha-interferon, measured by a sensitive radioimmunoassay, was consistently low as compared with the value found in the age-, sexmatched healthy control (p<0.001). Since adult T cell leukemia is pathogenetically related to the retrovirus infection, low levels of circulating alpha-interferon of the patient may be important from both pathogenetic and therapeutic standpoints. Alpha-interferon therapy may be an useful additive for the chemotherapy of adult T cell leukemia.     

Easy and accurate diagnosis of rheumatoid arthritis using anti-cyclic citrullinated peptide 2 antibody, swollen joint count, and C-reactive protein/rheumatoid factor

OBJECTIVE: To determine an easy-to-use diagnostic criterion for early rheumatoid arthritis (RA) that may be useful for general physicians, using anti-cyclic citrullinated peptide (CCP) antibody. METHODS: We prospectively studied 435 patients who first visited the hospital with arthritic symptoms within 24 months, including 264 visitors within 6 months. The diagnosis was made on their first visit by examination and laboratory tests including anti-CCP antibodies, rheumatoid factor (RF) and C-reactive protein (CRP), and radiograph. RESULTS: The diagnostic specificity and positive predictive value (PPV) of anti-CCP2 assay were 94.9% and 87.8%, respectively, and those of anti-CCP2 plus RF were 96.9% and 90.9% for the patients who first visited having morning stiffness, arthralgia, and/or joint swelling within 3 months from onset (n = 165). For the patients who first visited later, but within 24 months from onset (n = 260), the diagnostic specificity and PPV were extremely high, 98.7% and 95.5%, when anti-CCP2 assay was coevaluated with RF, CRP, and more than 3 swollen joints. Respective combinations of anti-CCP2 assay plus either 2 of 3 measures were also highly specific. CONCLUSION: A diagnostic criterion including anti-CCP2 assay in combination with RF, CRP, and/or swollen joints is less sensitive but highly specific, and accurately predicts future development of RA among those with arthritic symptoms who first consulted doctors within 2 years after onset. It should be highly useful for the general physician without special techniques or devices.