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Biomedical subjects

T Tojo

Publications and source records attributed to T Tojo.

At least 73 records · Page 4Linked to original sources

Desulfation of tyrosine-O-sulfated peptides by some eukaryotic sulfatases.

Three mammalian and eight non-mammalian arylsulfatases were investigated for their activities toward tyrosine-O-sulfate (TyrS) in peptides. None of the mammalian arylsulfatases exhibited detectable activities toward TyrS-containing peptides. Of the non-mammalian arylsulfatases tested, Types VII, VIII, and H-1, 2, and 5 displayed strong activity on endo-TyrS residues. The prokaryotic sulfatase, Type VI, was active only on free TyrS and N-terminal TyrS of Leu-enkephalin. All the sulfatases were active on p-nitrophenyl sulfate and p-nitrocatechol sulfate.

Peptides↗

Reevaluation of enzyme-linked immunosorbent assay with ultraviolet-treated polystyrene microtiter plates for measurement of antibodies to dsDNA.

We reevaluated the efficacy of enzyme-linked immunosorbent assay (ELISA) with ultraviolet (UV)-treated polystyrene microtiter plates (UV-ELISA) for the detection of human serum anti-dsDNA antibodies. The subjects consisted of 38 patients with systemic lupus erythematosus (SLE). The titers of IgG serum anti-dsDNA antibodies by UV-ELISA were significantly (p < 0.01) higher in sera from 26 active SLE patients than in those from 12 inactive SLE patients. ELISA with poly-L-lysine coated microtiter plates (PLL-ELISA) revealed the similar results. However, the background ratio was only 1.0 +/- 0.9% by UV-ELISA, which was significantly (p < 0.01) lower than that by PLL-ELISA (16.8 +/- 10.8%). These results demonstrated the efficacy of ELISA with UV-treated polystyrene microtiter plates for the measurement of human serum anti-dsDNA antibodies in patients with SLE.

Antibodies, Antinuclear↗

[A case of mucoepidermoid carcinoma of the thymus].

A 19-year-old man was admitted to our hospital with anterior mediastinal cystic tumor. Subtotal thymectomy with the tumor was performed. The tumor was localized inside the thymus without outer infiltration. It weighed 145 g and measured 9 x 8 x 5 cm. The cut surface was cystic and spongy, partially with a solid focus. Pathological findings of the solid area was compatible with mucoepidermoid carcinoma of the thymus. The histogenesis of mucoepidermoid carcinoma of the thymus was discussed.

Adult↗

Clinical features of patients with juvenile onset mixed connective tissue disease: analysis of data collected in a nationwide collaborative study in Japan.

OBJECTIVE: To analyze the clinical features and outcome of juvenile-onset mixed connective tissue disease (MCTD). METHODS: Clinical and laboratory findings were compared in 2 groups of MCTD patients divided according to age at onset: juvenile onset: under 16 yrs: adult onset: 16 yrs or older). RESULTS: Systemic lupus erythematosus-like symptoms, such as facial erythema, photosensitivity. LE cells, lymphadenopathy, and cellular casts, were more frequent in juvenile onset MCTD than in the adult form of the disease. On the other hand, scleroderma-like symptoms, such as esophageal hypomotility, scleroderma-like lesions evident on skin biopsy, pulmonary involvement, proximal scleroderma, and pitting scars, were less frequent in juvenile onset MCTD than in the adult form. Patients with juvenile onset MCTD more frequently met the classification criteria for systemic lupus erythematosus (SLE) and less frequently met those for progressive systemic sclerosis (SSc), compared to patients with adult onset MCTD. At disease onset, hand edema and stiffness were observed less frequently in juvenile onset MCTD than in the adult form. Furthermore, the mortality rate was lower in the former than in the latter (2.8% vs 8.4%). CONCLUSION: Although previous studies have reported severe symptoms and adverse outcome for juvenile onset MCTD, we conclude from this nationwide study in Japan that patients with juvenile onset MCTD exhibit more SLE-like and fewer SSc-like features and have a relatively favorable outcome.

Adolescent↗

Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis.

OBJECTIVE: To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. METHODS: Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-prostaglandin F1 alpha, 2,3-dinor-6-keto-PGF1 alpha, and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. RESULTS: Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE)(p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF1 alpha decreased and there were no significant changes in the urinary TXB2/6-keto-PGF1 alpha ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. CONCLUSION: The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904.

Adult↗

CD40 signaling-mediated induction of Bcl-XL, Cdk4, and Cdk6. Implication of their cooperation in selective B cell growth.

Signals sent through CD40 play crucial roles in B cell differentiation, including blocking apoptosis of germinal center B cells. In this study, using a murine B cell WEHI-231 line that undergoes apoptosis by the cross-linking of surface Ag receptors (sIgM), we have demonstrated that CD40 signalings are linked to induction of the Bcl-xL, Cdk4, and Cdk6 proteins whose expression was significantly suppressed by the apoptotic signal through sIgM. Mutational analyses of CD40 revealed that the domain of human CD40 required for blocking apoptosis of WEHI-231 cells coincides with that required for Bcl-xL induction. Signals through sIgM arrest cells in the G1 phase of the cell cycle, which is followed by apoptosis. However, while constitutive expression of Bcl-XL leads to the inhibition of apoptosis. Nevertheless, Bcl-xL fails to induce S phase entry. By CD40 signalings, both Cdk4 and Cdk6 resume their normal expression levels, which are sufficient for passing the restriction point in G1 even in the presence of the apoptotic signals mediated by sIgM. These results suggest that cooperation of Bcl-xL, Cdk4, and Cdk6 induced by CD40 signaling plays a key role in CD40-mediated selective growth of B cells.

Amino Acid Sequence↗

Flow cytometric analysis of the DNA content of thymomas.

In this study, the prognostic value of determining the nuclear DNA content of thymomas by flow cytometry was evaluated. Of a total 31 resected thymomas, 10 (32%) showed DNA aneuploidy, the presence of which was significantly correlated with an advanced clinical stage of disease. The patients with an aneuploid tumor had a poorer prognosis than those with a diploid tumor, demonstrating a survival rate of 50% at 7 postoperative years, which was considerably less favorable than that of the patients with a diploid tumor, being 100% in the same period (p < 0.05). Moreover, patients with a high DNA index (DI), i.e., a DI >or= 1.5, tended to have a poorer prognosis than those with a low DI. These findings indicated that the DNA content can be an important prognostic index in patients with thymomas.

Adult↗

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 Sjögren's 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 Sjögren's 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.

Aged↗

[A case of adult onset Still's disease complicated with adult respiratory distress syndrome and disseminated intravascular coagulation].

A 71 year-old man with adult onset Still's disease was admitted to our hospital because of fever, sore throat, myalgia and macular nonpruritic salmon pink eruption. He was treated with prednisolone, 40 mg daily and these symptoms disappeared. When the dose of prednisolone was reduced to 30 mg daily, he began to notice fever. 5 days later he developed adult respiratory distress syndrome (ARDS). The dose of prednisolone was increased to 50 mg daily and oxygen administration was started. All symptoms began to improve immediately and the dose of prednisolone was decreased to 40 mg daily. 10 days later he noticed fever and skin rash. Laboratory investigation showed platelet counts of 69,000/mm3, a ferritin of 37,000 ng/ml, and increased fibrinogen degradation product, indicating increased activity of adult onset Still's disease associated with disseminated intravascular coagulation (DIC). The dose of prednisolone was again increased to 60 mg daily, and 100 mg of nafamostat mesilate was administrated intravenously. All above symptoms associated with adult onset Still's disease and DIC disappeared. The dose of prednisolone was gradually decreased and the clinical course was uneventful with daily administration of 10 mg of prednisolone. Although there are a couple of case report which described the association of adult onset Still's disease with either ARDS or DIC, the association of adult onset Still's disease with both ARDS and DIC have not been reported yet.

Aged↗

[Efficacy of beraprost sodium on Raynaud's phenomenon in patients with systemic sclerosis].

Raynaud's phenomenon is an important clinical manifestation in patients with systemic sclerosis (SSc). No effective therapy, however, has been established for this phenomenon. Beraprost sodium, a stable prostacycline (PGI2) analogue, has been reported to improve hemorrheological impairment in patients with rheumatic diseases. In this study, we, therefore, examined the efficacy of beraprost sodium on Raynaud's phenomenon in 30 patients with SSc. Sixty micrograms per day of beraprost sodium was found to be effective in 14 patients (47%) in the period of 15.0 +/- 12.5 weeks. Raynaud's phenomenon in patients who responded to beraprost sodium was characterized by infrequent nail fold thrombosis and narrower hand areas affected by Raynaud's phenomenon, with mild secondary symptoms such as pain. These results indicate that beraprost sodium is effective for mild forms of Raynaud's phenomenon in patients with SSc.

Adult↗

[Morphological examination of the lung tissue ablated with Nd;YAG laser in the treatment of bullous pulmonary disease].

We conducted a morphologic examination of ablated pleurae and bullae to assess the efficacy of Nd;YAG laser irradiation to the lung tissue for the treatment of bullous pulmonary disease. Pleurae and bullae from surgically resected lung tissue to treat pulmonary carcinoma were ablated using a Nd;YAG laser at a power of 10 watts and 1.5 seconds within a 1-centimeter-diameter circle (about 0.2 joule/cm2). Samples were analyzed by light microscopy and scanning electron microscopy. Nd;YAG laser irradiation caused elastic fiber-contraction and gel from collagen both in pleurae irradiated once and in bullae irradiated three times. We conclude that Nd;YAG laser irradiation can be applied to ablate pleurae and bullae into a tight and continuous structure which is important in preventing air leak from the pulmonary parenchyma.

Emphysema↗

[Current status and problems in the treatment of patients with Sjögren's syndrome].

Current status of treatment of patients with Sjögren's syndrome in Japan was reviewed. Although the number of patients with the syndrome has been increasing due to the recent progress in diagnosing and understanding of the disease, treatment of patients still remains unsatisfactory. However a wide variety of methods have become available in the management of patients who have significant dryness of eye and mouth. This includes artificial tear, artificial saliva, moisture shields of glasses, and many other medical and nonmedical preparations. All patients with sicca complaints should receive therapy of tear replacement and intensive oral hygiene. New potential therapeutic approaches for treatment of Sjögren's Syndrome was also reviewed.

Anti-Inflammatory Agents↗

IL-6-anti-IL-6 autoantibody complexes with IL-6 activity in sera from some patients with systemic sclerosis.

Anti-IL-6 IgG autoantibodies, often found in sera from patients with systemic sclerosis, may increase to the level sufficient to bind significant amounts of IL-6 in serum. In our study of the role of anti-IL-6 autoantibodies in serum, we found that some sera with the autoantibodies possessed considerably higher IL-6 levels (more than 100 pg/ml) compared with most of sera without the autoantibodies. Size-exclusion HPLC of the sera with these autoantibodies demonstrated that a significant part of the serum IL-6 activity was attributable to circulating IL-6-anti-IL-6 autoantibody complexes. Gel filtration of IL-6-anti-IL-6 IgG complexes made in vitro by incubation of rIL-6 and IgG purified from the autoantibody-positive sera demonstrated that the complexes at 200 to 250 kDa were dominant ones and that IL-6 bound to the autoantibodies retained more than 60% of the original IL-6 activity. Moreover, IL-6-anti-IL-6 autoantibody complexes were shown to bind to recombinant soluble IL-6 receptors. Estimated affinity of anti-IL-6 IgG autoantibodies from two patients was fairly high (4.2 x 10(9) to 3.3 x 10(10) L/M). Therefore, the retention of IL-6 activity by IL-6-anti-IL-6 autoantibody complexes may be explained by intact receptor-binding sites on the autoantibody-bound IL-6 molecules. Taken together, these results suggest that the properties of anti-IL-6 autoantibodies are consistent with a potential role as specific carriers for IL-6 in the circulation.

Antigen-Antibody Complex↗

Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis.

OBJECTIVE: To clarify the clinical features and prognosis of systemic sclerosis (SSc) based on serum antinuclear antibodies (ANA). METHODS: We studied 275 consecutive Japanese patients newly diagnosed as having SSc, who were first evaluated during the period 1971-1990. Eight SSc-related ANA were identified using indirect immunofluorescence, double immunodiffusion, or immunoprecipitation assays. Clinical and prognostic features were retrospectively analyzed in patient groups, categorized by their serum ANA. RESULTS: Cumulative survival rates at 10 years after diagnosis of SSc were 93% in patients with anticentromere antibodies (ACA), 72% in those with anti-U1 RNP, 66% in those with anti-DNA topoisomerase I (anti-topo I), and 30% in those with anti-RNA polymerases I, II, and III (anti-RNAP). Major organ involvement linked to cause of death included biliary cirrhosis in patients with ACA, isolated pulmonary arterial hypertension and cerebral hemorrhage in those with anti-U1 RNP, pulmonary interstitial fibrosis in those with anti-topo I, and cardiac and renal involvement in those with anti-RNAP. CONCLUSION: Determinations of serum ANA in SSc patients are useful in predicting organ involvement and long-term outcome.

Adolescent↗

Clinical significance of antibodies to native or denatured 60-kd or 52-kd Ro/SS-A proteins in Sjögren's syndrome.

OBJECTIVE: To evaluate the clinical significance of antibodies to native or denatured (anti-n or anti-d) 60- or 52-kd Ro/SS-A proteins (60K or 52K) in Sjögren's syndrome (SS). METHODS: The presence of antibodies to denatured and native Ro/SS-A proteins was determined by immunoblotting and immunoprecipitation, respectively. Salivary gland dysfunction was evaluated by salivary function scintigraphy. RESULTS: The incidence of anti-d-60K without anti-d-52K was lower among patients with systemic lupus erythematosus with SS (SLE/SS) and among those with primary SS, compared with patients who had SLE without SS, whereas anti-d-52K without anti-d-60K was more common in SLE/SS patients and primary SS patients than in SLE patients without SS. All of the patients with anti-Ro/SS-A had anti-n-60K. Serologic abnormalities and salivary gland dysfunction were associated with anti-n-60K in SS, whereas Hashimoto's thyroiditis in SS was related to anti-d-60K. Anti-d-52K was not associated with any extraglandular or glandular symptoms in SS. CONCLUSION: The data indicate that anti-n-60K, which appears to recognize conformational epitopes, is associated with clinical features of SS characterized by glandular dysfunction.

Autoantibodies↗

Racial differences in the distribution of systemic sclerosis-related serum antinuclear antibodies.

OBJECTIVE: To determine racial differences in the frequencies of systemic sclerosis (SSc)-related serum antinuclear antibodies (ANA). METHODS: We tested serum samples from 275 Japanese, 416 North American Caucasian, and 24 North American black SSc patients for 8 SSc-related serum ANA, using indirect immunofluorescence, double immunodiffusion, and radioimmunoprecipitation assays. RESULTS: In comparing the 3 racial groups, we found that anti-U1 RNP, anti-RNA polymerase I, II, and III, and anti-U3 RNP antibodies were the most frequently detected antibodies in Japanese, Caucasian, and black patients, respectively. Anti-PM-Scl antibody was found exclusively in Caucasians. CONCLUSION: The production of SSc-related serum ANA is related to immunogenetic background.

Antibodies, Antinuclear↗