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Biomedical subjects

Takuo Tsuji

Publications and source records attributed to Takuo Tsuji.

8 recordsLinked to original sources
PubMed2004

Different susceptibility of malignant versus nonmalignant human T cells toward ultraviolet A-1 radiation-induced apoptosis.

Ultraviolet (UV) A-1 (340-400 nm) radiation is highly effective in inducing apoptosis in skin-infiltrating T cells and thereby exerts beneficial effects in patients with T cell-mediated skin diseases. In this in vitro study, we report that malignant and normal T cells differ in their susceptibility toward UVA-1 radiation-induced apoptosis. Dose-response studies revealed that malignant CD4+ T cells isolated from a patient with adult T cell leukemia and Sezary's syndrome as well as malignant T cell lines exhibited a significantly higher susceptibility toward UVA-1 radiation-induced apoptosis 4 h (early apoptosis) and 24 h (late apoptosis) after exposure than normal, CD4+ T cells. This difference was specific for UVA-1 irradiation because it was not detected when apoptosis was induced in these cells through exposure to UVB radiation or stimulation with cell-permeable ceramides. It has been shown that UVA-1 radiation-induced T cell apoptosis is initiated through the generation of singlet oxygen. This is in agreement with the present observation that stimulation of unirradiated cells with a singlet oxygen-generating system induced apoptosis in malignant cells to a greater extent than in normal cells. Moreover, downregulation of FAS surface expression in malignant T cells was associated with the inhibition of UVA-1 radiation/singlet oxygen-induced apoptosis in these cells. It was thus of great interest to learn that addition of the caspase inhibitor Z-VADfmk decreased and interferon-gamma stimulation, which is known to upregulate caspase levels including caspase-3, increased the sensitivity of T cells toward UVA-1 radiation-induced apoptosis. Furthermore, malignant T cells had significantly higher procaspase-3 levels when compared with normal cells. These studies indicate that the susceptibility of human T cells toward UVA-1 radiation-induced apoptosis is related to the availability of caspases such as caspase-3 and that strategies directed at upregulating caspase levels will increase the efficacy of UVA-1 phototherapy.

Apoptosis↗
PubMed2004

Trial of low-dose 5-fluorouracil/cisplatin therapy for advanced extramammary Paget's disease.

BACKGROUND: An effective chemotherapy for advanced extramammary Paget's disease has not yet been established. Recently, a low dose 5-fluorouracil/cisplatin (FP) regimen has been reported to be effective for adenocarcinoma, including gastric and colon carcinoma. However, this chemotherapeutic option has not been evaluated as to its effectiveness for extramammary Paget's disease. OBJECTIVE: We evaluated chemotherapy in a patient with advanced extramammary Paget's disease of the male genitalia unassociated with an underlying malignancy. METHODS: In order to treat a patient with extramammary Paget's disease who had multiple metastases, 500 mg/day of 5-fluorouracil (7 days per week) and 5 mg/day of cisplatin (5 days per week) were administrated intravenously for 24 hours and 1 hour, respectively. This protocol was continued for 6 weeks. RESULTS: A partial response was observed in both primary disease and metastatic disease. The primary tumor resolved almost entirely, leaving only a scar. Computed tomography scan revealed liver metastases that appeared to change into necrotic tissue; the metastases in lymph nodes and adrenal glands were markedly decreased and hardly detectable. In addition, the carcinoembryonic antigen level, a useful tumor marker for extramammary Paget's disease, decreased remarkably. It is suggested that this patient's survival period could have been prolonged. Serious side effects were not observed during this treatment. CONCLUSION: In one patient with extramammary Paget's disease and multiple metastases, low-dose FP therapy appeared to be beneficial. This regimen may be effective for extramammary Paget's disease with systemic nodular metastasis as an adjuvant therapy combined with surgery.

Aged↗
PubMed2003

Tobacco smoke extract induces age-related changes due to modulation of TGF-beta.

We have recently shown that tobacco smoking, like ultraviolet A radiation, is an important factor contributing to premature skin aging. We found that tobacco smoke extract decreased type I and III procollagen, increased tropoelastin mRNA, and induced abnormal accumulation of proteoglycans and matrix metalloproteinase (MMP)-1 and MMP-3 in cultured skin fibroblasts. This indicated that common molecular features might underlie the premature aging of the skin induced by tobacco smoke extract, including abnormal regulation of extracellular matrix deposition through elevated MMPs, reduced collagen production, abnormal tropoelastin accumulation, and altered proteoglycans. With the exception that reactive oxygen species were mediated in the aging process, transforming growth factor (TGF)-beta1 was found to play a crucial role in the age-related alterations induced by tobacco smoke extract. Here we report that tobacco smoke extract blocks cellular responsiveness to TGF-beta1 through the induction of a non-functional latent form of TGF-beta1, and downregulation of the TGF-beta1 receptor. This paper shows the evidence for the role of tobacco smoking in skin aging and describes how modulation of TGF-beta1 levels might retard premature skin aging.

Aging↗
PubMed2003

The expression of matrix metalloproteinase-1 mRNA induced by ultraviolet A1 (340-400 nm) is phototherapy relevant to the glutathione (GSH) content in skin fibroblasts of systemic sclerosis.

The excessive deposition of collagen in systemic sclerosis (SSc) is thought to be due to an abnormal function of fibroblasts, which may be the result of an immune dysregulation in skin. Ultraviolet A1 (UVA1) irradiation has been shown to be an effective therapy. This is thought to be due to its capacity to induce matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. In the present in vitro study, the effect of UVA1 irradiation on MMP-1 was studied using skin fibroblasts from healthy controls (n=5) and patients with systemic sclerosis (n=5). In vitro irradiation studies showed that gene expression for MMP-1 after UVA1 irradiation (p<0.05) was induced in all the fibroblasts studied, but that the induction rate was greater in SSc fibroblasts than in normal ones (p<0.05). The glutathione (GSH) level was lower in SSc fibroblasts than in controls before UVA1 irradiation. However, after UVA1 irradiation, GSH levels were increased and equivalent between normal and SSc fibroblasts. These findings indicated that the relatively stronger increase in MMP-1 expression in SSc fibroblasts was due to the lower antioxidant capacity. These data support the concept that clinical responses to UVA1 radiation are influenced by the antioxidative state of the patients' skin.

Base Sequence↗
PubMed2002

Characterization of an anti-decorin monoclonal antibody, and its utility.

6B6 is a monoclonal antibody raised against a purified small dermatan sulfate proteoglycan from human ovarian fibroma capsule, has Although it been widely used as an anti-decorin monoclonal antibody, its epitope has not yet been characterized at the molecular level. Here, we show that 6B6 is specific to decorin. The antibody recognized human, mouse, and bovine decorin core protein, but not biglycan. Using recombinant decorin domains, we determined that the epitope lies within the region of amino acid residues 50-65, termed the cysteine cluster region. Cross-reactivity among species further narrowed it down to a primary sequence of residues 57-65. We also established the conditions for immunostaining. 6B6 stained both frozen and fixed sections. Whereas the glycosaminoglycan chain of decorin inhibited access of the antibody in immunoblotting, pretreatment of tissue sections with chondrotinase ABC did not affect the intensity of staining, suggesting that the glycosaminoglycan chain is integrated and the Cys cluster region oriented outside of the collagen fibrils in the tissue. When 6B6 was applied to enzyme-linked immunosorbent assay, a concentration as low as 0.5 microg/ml of decorin was detectable by either direct or sandwich ELISA. 6B6 is thus a sensitive and reliable antibody to study functions of decorin from various aspects.

Animals↗
PubMed2002

Localized linear scleroderma with cutaneous calcinosis.

A 38-year-old woman developed sclerotic and atrophic changes of the left femur in the winter of 1976. In 1980, she was referred to our dermatology clinic and was diagnosed with localized linear scleroderma from the results of the physical examinations and the histological findings. Although several local and systemic treatments were employed over the following 10 years, the sclerotic lesion did not show any remarkable improvement. In 1991, several hard and white papules appeared in the lesion, and a biopsy specimen of these white papules revealed calcinosis.

Adult↗