Takeshi Tojo

Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis.

We have identified a novel autoantibody reactive with all three classes of RNA polymerases, well-characterized nuclear enzymes, in sera from patients with systemic sclerosis (SSc). After incubation with [35S]methionine-labeled HeLa cell extracts, 14 of 275 SSc sera immunoprecipitated 12 or 14 proteins with similar molecular weights as those of several subunit proteins of eukaryotic RNA polymerases I, II, and III. Purified IgG from these two types of sera inhibited RNA transcription catalyzed by RNA polymerases I, II, and III in vitro. Immunoblot analysis using RNA polymerase-enriched fraction showed that the majority of these sera reacted with 42- or 25-kD protein. Anti-RNA polymerase antibody was highly specific to SSc, especially to diffuse cutaneous SSc. Clinical features associated with this antibody included a high frequency of heart and kidney involvement and a poor survival rate at 5 yr after first visit. These findings indicate that the autoantibody to three classes of RNA polymerases is a new marker for a unique subset of diffuse cutaneous SSc.

Relationship between Autoantibodies and Clinical Parameters in Sjögren's Syndrome

Glandular function as estimated by salivary function scintigraphy and extraglandular manifestations were compared among 174 Sjögrens syndrome (SS) patients according to their anti-Ro/SSA, anti-La/SSB, and anti-U1RNP autoantibody status, to clarify the relationship between these autoantibodies and clinical parameters in SS. These antibodies were detected by RNA-immunoprecipitation. Anti-La/SSB or only anti-Ro/SSA antibody was common in 84 primary SS (P-SS) patients, whereas the frequency of only anti-U1RNP was high in 90 secondary SS (S-SS) patients, especially in those with systemic lupus erythematosus (SLE). Antibody-negativity was common in SS with rheumatoid arthritis and was also found in 33% of P-SS. In P-SS, salivary gland dysfunction and parotid swelling were severe in patients who had serological abnormalities with anti-Ro/SSA and with or without anti-La/SSB. They were mild in antibody-negative patients who had mild extraglandular symptoms and in patients with only anti-U1RNP antibody who had Raynauds phenomenon, pulmonary fibrosis, and later disease onset. P-SS patients positive for both anti-Ro/SSA and anti-U1RNP had SLE-like features. SS could be classified clinically according to these autoantibodies.

Development of anti-Sm and anti-DNA antibodies followed by clinical manifestation of systemic lupus erythematosus in an elderly woman with long-standing Sjögren's syndrome

A 69-year-old Japanese women who had been followed up for 10 years as a primary Sjögrens syndrome, is reported. She suddenly developed serological and clinical characteristics of systemic lupus erythematosus (SLE): anti-Sm and anti-dsDNA antibodies followed by nephrotic syndrome and pancytopenia. This case suggests that the diagnosis of primary Sjögrens syndrome should be considered as tentative in certain cases and that the development of serological characteristics precede and are associated with the development of clinical symptoms of SLE.

Nodular regenerative hyperplasia of the liver in a patient with systemic sclerosis

SummaryWe report on a 33-year-old female patient with systemic sclerosis and nodular regenerative hyperplasia of the liver (NRHL). A needle biopsy of the patients liver did not reveal the histology of NRHL or liver cirrhosis at her first visit to our hospital, when portal hypertension was demonstrated by percutaneous transhepatic portography. After 11 years, the patient died of hepatic and renal failure. At the time of autopsy, multiple nodules were found in the liver, and a microscopic examination showed a histology compatible with NRHL. It is suggested that the immunological disturbance was related to the patients portal hypertension and NRHL.

Pulmonary Pseudolymphoma Presented with a Mass Lesion in a Patient with Primary Sjögren's Syndrome: Beneficial Effect of Intermittent Intravenous Cyclophosphamide

A 61-year-old woman with primary Sjögrens syndrome (SS) presented with fever, dry cough, dyspnea on exertion, and a mass lesion with reticular shadowing at both bases on her chest X-ray. Pulmonary pseudolymphoma was diagnosed by transbronchial lung biopsy which revealed infiltration of T cell-like slightly atypical lymphoid cells. After three infusions of cyclophosphamide (750 mg every 4 weeks) combined with prednisolone, the pulmonary mass lesion was diminished and her symptoms improved. Evaluation of the 12 reported cases of pulmonary pseudolymphoma with SS that presented with mass lesions showed an increase in IgM level, frequent pulmonary fibrosis, precedence of SS, and better prognosis with immunosuppressants in those patients.

Inhibition of topoisomerase I by antibodies in sera from scleroderma patients

Purified type I topoisomerase from calf thymus as well as nuclear and cytoplasmic extracts from EGF‐stimulated human and mouse fibroblasts in cell culture efficiently convert supercoiled plasmid DNA to the relaxed form. The purified IgG fraction from the sera of Japanese patients with the rheumatic disease scleroderma were shown to inhibit this relaxation activity. Thus, these patients likely produce autoantibodies to topoisomerase I. In addition, the human, bovine and murine enzymes share antigenic determinants recognized by the antisera.

Pyloric stenosis in a patient with progressive systemic sclerosis

SummaryA 64-year-old Japanese woman with progressive systemic sclerosis (PSS) who developed severe pyloric stenosis is described. The conservative treatments brought only the temporary symptomatic relief, and pyloroplasty became necessary. No ulcerative lesions or tumors were found in the resected stomach or duodenum specimens implicated for stenosis. The histological examinations revealed edema and replacement fibrosis in the pyloric ring. The possible mechanisms of pyloric stenosis are discussed.

Investigations on the therapeutic regimen of a novel non-steroidal anti-inflammatory drug, the UHAC62 capsule.

A double-blind comparative study among 9 medical centers was conducted in order to investigate the optimal daily administration schedule of UHAC62 (Generic name: Meloxicam), a kind of non-steroidal anti-inflammatory oxycam agent. The daily 10 mg of UHAC62, which had been considered as an optimal dose, was administered either once daily, immediately after supper (Group O), or given twice a day divided into 5 mg immediately after breakfast and supper (Group T), both for weeks to patients with rheumatoid arthritis.Out of the total 52 patients, 1 patient was excluded from the analyses; and 41 patients (Group O: 23 cases, Group T: 18 cases), 51 patients (Group O: 27 cases, Group T: 24 cases) and 44 patients (Group O: 24 cases, Group T: 20 cases) were subjected to the ratings of Final Global Improvement, Overall Safety, and Usefulness, respectively. The results showed the following:(1) The ratio of the patients who showed a better than “Moderate Improvement” in the Final Global Improvement Rating was 30.4 % and 27.8 % in the Group O and Group T, respectively.(2) The ratio of the patients on whom the test drug was shown to be “Completely Safe” in the Overall Safety Rating was 88.9% and 91.7% in the Group O and Group T, respectively. All of the adverse drug reactions which were seen in the patients of Group O and the 2 patients of the Group T were assessed as “mild”.(3) The ratio of the patients on whom the test drug was rated as better than “Useful” was 29.2% and 25.0 % in the Group O and Group T, respectively.There was no significant difference in the overall evaluations and the improvement rating of the symptoms between the groups.According to these results, it was considered that the once daily administration of UHAC62 might be more promising for materializing a higher compliance in the patients who need long-term administration, although both regimens, the once and the twice daily administrations are applicable.