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Biomedical subjects

S Hirohata

Publications and source records attributed to S Hirohata.

133 records · Page 8Linked to original sources
PubMedDate not supplied

Cerebral hemiatrophy in systemic lupus erythematosus: report of a case.

An 18-year-old woman with systemic lupus erythematosus developed neuropsychiatric disorders, including aseptic meningoencephalitis, organic brain syndrome and seizure. A series of computed axial tomography scans revealed the progression of marked atrophy of the right cerebral hemisphere for a period of 3 years without occlusion or stenosis of large vessels on cerebral angiography. I-123 IMP single photon emission computed tomography disclosed a markedly decreased uptake of I-123 IMP in the right cerebral hemisphere, and also in the left cerebellar hemisphere (crossed cerebellar diaschisis), which disappeared within 2 years.

Adolescent↗
PubMedDate not supplied

FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo.

Gene transfer vectors will dramatically increase the safety and effectiveness of cancer gene therapy, if they could restrict expression of the therapeutic products to the target tumors. To realize such a tumor-targeting system, telomerase is one of the most promising candidates. It is because telomerase activity is detected in the vast majority of tumors, but not in most normal cells. Activation of telomerase is tightly regulated at the transcriptional level of the telomerase catalytic subunit (hTERT). Therefore, the use of the hTERT promoter-driven vector system could restrict the expression of therapeutic products to telomerase-positive tumors. In this study, we constructed the expression vector of FADD gene with death domain afforded by the hTERT promoter (hTERT/FADD) and investigated its effect on tumors in vitro and in vivo. Transient transfection with the hTERT/FADD construct induced apoptosis in telomerase-positive tumor cells of wide range. In contrast, normal fibroblast cells without telomerase did not undergo apoptosis following the hTERT/FADD transfer. Furthermore, the growth of subcutaneous tumors in nude mice was significantly suppressed by the intratumoral injection of the hTERT/FADD construct (every day for one week) compared to the control (P<0.0005). The findings described here indicate the high potentiality of a novel telomerase-specific gene therapy of tumors with telomerase.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Regulation of in vitro anti-DNA antibody production by a novel disease modifying anti-rheumatic drug, Lobenzarit.

Lobenzarit (CCA) is a novel disease modifying anti-rheumatic drug. Although CCA has been shown to prevent the development of the autoimmune disorders in NZB/W F1 mice and in MRL/l mice, the precise mechanism of its action has not yet been clarified. The current study examined the effect of CCA on the in vitro production of anti-DNA antibody, a hallmark of the autoimmune disorders. In vitro anti-DNA antibody production was induced from highly purified B cells of normal human individuals by stimulation with Staphylococcus aureus and CD4+ T cells or with immobilized anti-CD3 activated CD4+ T cells. CCA suppressed the production of anti-DNA antibody as well as IgM at pharmacologically obtainable concentrations (10-50 micrograms/ml). CCA did not inhibit the initial stages of B cell activation in either culture system, but rather suppressed the maturation of previously activated B cells. Although CCA suppressed IL2 production by immobilized anti-CD3 activated CD4+ T cells, its suppressive effects on B cells were not overcome by the addition of IL2 or factors generated from mitogen activated T cells (TF). CCA did not suppress IL6 production by immobilized anti-CD3 activated CD4+ T cells nor that by B cells activated with SA+ IL2. These results indicate that CCA suppresses the production of anti-DNA antibody by directly inhibiting activated B cells. The data therefore suggest the possible efficacy of CCA in suppressing the function of activated B cells in human SLE patients.

Adult↗
PubMedDate not supplied

Correlation between rheumatoid factor and IL-6 activity in synovial fluids from patients with rheumatoid arthritis.

Synovial fluids (SF) and sera (S) from patients with rheumatoid arthritis (RA) were examined for IgM, IgM-rheumatoid factor (IgM-RF), albumin and interleukin-6 (IL-6) activity. The quotient of SF/S IgM-RF was elevated compared with that of SF/S albumin in 7 patients with seropositive RA, although the quotient of SF/S IgM was lower than that of SF/S albumin. SF IL-6 activity was much higher than serum IL-6 activity in all the 7 RA patients. In synovial fluids from 22 seropositive RA patients, SF IL-6 activity was significantly correlated with the SF IgM-RF, IgG-RF and IgA- less than RF, but not with SF IgM, IgG or IgA. Moreover, SF IgM-RF as well as SF IL-6 activity was significantly correlated with the Westergren erythrocyte sedimentation rate (ESR) or the Lansbury articular index. These results indicate that IL-6 and RF might be produced within the rheumatoid joints as a result of abnormal immune system activation, which is associated with the disease activity of RA. Three of the 4 seronegative RA patients, however, showed high SF IL-6 without detectable levels of SF IgM-RF, indicating that IL-6 alone is not sufficient for IgM-RF production.

Adult↗
PubMedDate not supplied

Treatment of systemic lupus erythematosus with lobenzarit: an open clinical trial.

An open clinical trial was designed to examine the efficacy and safety of lobenzarit (CCA), a newly developed disease modifying anti-rheumatic drug, in combination with conventional treatment with prednisolone for patients with systemic lupus erythematosus (SLE). Fifteen patients with SLE were given CCA 40 mg b.i.d. for the first 2 weeks, 80 mg b.i.d. for the next 4 weeks, and 80 mg t.i.d. or b.i.d. until the end of the 12-month trial, in addition to prednisolone, whose doses were kept unchanged throughout the trial. The patients' clinical responses to CCA, including alterations in various laboratory parameters and the development of complications, were evaluated at the end of 12 months. Fourteen of the 15 patients completed the 12-month trial. Significant increases in the white blood cell count and CD4/CD8 ratio, as well as decreases in serum anti-DNA antibody, were noted after the trial. Five patients presented with adverse effects, including mild liver dysfunction, gastrointestinal symptoms and dizziness. Only one patient who developed dizziness withdrew at 9 months. Eleven patients could be reevaluated after discontinuation of CCA, and only 2 of them have experienced recurrence of active disease 6 months after discontinuation. In one additional patient who had not responded to prednisolone 35 mg daily, administration of CCA resulted in improvement of the disease activity. These results indicate that CCA in combination with corticosteroids is a useful adjunct in the treatment of SLE. A placebo-controlled study will be necessary to confirm these results.

Adolescent↗
PubMedDate not supplied

Pleurisy in primary Sjögren's syndrome: T cell receptor beta-chain variable region gene bias and local autoantibody production in the pleural effusion.

Pleurisy with or without effusion has not been considered to be associated with primary Sjögren's syndrome (SS), but rather to represent a manifestation of the underlying disorder, usually rheumatoid arthritis in secondary SS. We describe a patient with primary SS who presented with pleural effusions (PE) as an initial manifestation. Serological studies of paired serum and PE specimens demonstrated the occurrence of local immune reactions in the pleura, including the production of rheumatoid factor and anti-SS-A antibody, the formation of immune complexes, and activation of complement. In addition, the analysis of T cell receptor beta-chain variable (V beta) regions in the PE revealed the overexpression of a number of V beta gene products, including V beta 2 and V beta 13 that have previously been shown to be over-represented in the salivary glands of patients with SS. Thus, our report not only calls for an awareness of pleurisy as an extraglandular manifestation of primary SS, but suggests that a common biased T cell response might play a critical role in the pathogenesis of the glandular as well as extraglandular manifestations.

Aged↗