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Akimichi Morita

Publications and source records attributed to Akimichi Morita.

At least 19 recordsLinked to original sources
PubMed2026

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans↗
PubMed2006

Antigen-specific peripheral tolerance induced by topical application of NF-kappaB decoy oligodeoxynucleotide.

Activation and maturation of dendritic cells (DC) are crucial for the establishment of delayed-type hypersensitivity (DTH). However, antigen presentation by immature DC (iDC) might lead to antigen-specific peripheral tolerance. NF-kappaB plays significant roles in upregulation of co-stimulatory molecules and cytokines in DC and therefore we investigated whether NF-kappaB decoy oligodeoxynucleotide (ODN) might induce tolerance to DTH. NF-kappaB decoy ODN suppressed ovalbumin (OVA)-induced DTH responses not only in naïve but also in presensitized mice. The suppressive effect was found to be antigen-specific. NF-kappaB decoy ODN-induced tolerance involved CD4(+)CD25(+) regulatory T cells (Treg), because in vivo depletion of CD25(+) T cells abrogated the tolerance, whereas adoptive transfer of such T cell population from tolerant mice induced tolerance. Furthermore, the induction of Treg was related to insufficient migration and/or maturation of DC, because a sizable DC population still remained in peripheral tissue even after exposure to exogenous antigen in NF-kappaB decoy ODN-treated mice. Even if they migrated into lymph nodes, they showed insufficient upregulation of co-stimulatory molecules and impaired antigen-specific activation of T cells. Topical application of NF-kappaB decoy ODN might thus be a new approach to induce antigen-specific peripheral tolerance.

Animals↗
PubMed2006

Successful treatment with topical tacrolimus in four cases of discoid lupus erythematosus.

Discoid lupus erythematosus (DLE), a cutaneous form of lupus erythematosus, is characterized as atrophic and scaly erythema and the lesions are often refractory to a wide range of topical or systemic therapies. Herein, we present four cases of DLE that were successfully treated with topical tacrolimus. Tacrolimus ointment (0.1%) was applied to DLE lesions twice daily and the erythematous plaques readily diminished after 4-8 weeks. Adverse effects, such as burning sensation or irritations, were not observed. These results indicate that topical tacrolimus might be an effective and alternative treatment to control DLE.

Administration, Cutaneous↗
PubMed2006

Regulation of NF-kappaB signaling by decoy oligodeoxynucleotides.

The nuclear factor-kappa B (NF-kappaB) plays a critical role in regulating expression of genes responsible for a wide range of cellular processes, including innate and adoptive immune responses, and pathways related to cell survival and proliferation. Based on its property as a transcription factor, NF-kappaB has been considered as a good target for the treatment of inflammatory immune diseases. To regulate gene expression, "decoy" oligodeoxynucleotides (ODNs) are ideal tools to interfere with binding of transcription factors to promoter regions in genes. Herein we review the application of NF-kappaB decoy ODNs to control inflammatory disorders and transplantation tolerance. In addition, we provide information about induction of antigen-specific peripheral tolerance by their topical application. Regulation of NF-kappaB signaling by NF-kappaB decoy ODNs might be an effective tool to control a variety of disorders caused by inflammatory immune responses.

Animals↗
PubMed2006

Comparison of the efficacy of calcipotriol and maxacalcitol in combination with narrow-band ultraviolet B therapy for the treatment of psoriasis vulgaris.

BACKGROUND: Combination treatment with topical vitamin D(3) and narrow-band ultraviolet B (UVB) radiation is effective against psoriasis vulgaris. We compared the efficacy of the topical vitamin D(3) derivatives calcipotriol and maxacalcitol in combination therapy. MATERIALS AND METHODS: In this retrospective observational study, 21 patients admitted to Nagoya City University Hospital between April 2001 and September 2004 were enrolled. RESULTS: Combination treatment with calcipotriol or maxacalcitol and narrow-band UVB was effective against psoriasis vulgaris. Calcipotriol induced a more rapid improvement and required lower levels of narrow-band UVB irradiation to be effective. Serum calcium levels were slightly increased after 4 weeks of treatment, but there was no significant difference between the two groups. No other adverse effects were observed in either of the two groups. CONCLUSION: The findings of this retrospective observational study indicated that combination treatment with topical vitamin D(3) derivatives and narrow-band UVB is effective against psoriasis without any obvious side-effects. These findings provide further evidence that calcipotriol has advantages over maxacalcitol regarding the narrow-band UVB-accumulated treatment dose and improvement rate of psoriasis area and severity index (PASI) scores.

Administration, Cutaneous↗
PubMed2005

Dermal mast cells play a central role in the incidence of scratching behavior in mice induced by multiple application of the hapten, 2,4,6-trinitrochlorobenzene.

Repeated application of 1% 2,4,6-trinitrochlorobenzene (TNCB) in acetone solution causes chronic skin inflammation in BALB/c mice. Associated scratching behavior gradually appeared, and chronic scratching behavior was established over 40 days after the initial application of TNCB. In order to explore the possible involvement of T cells and mast cells in the appearance of pruritus, we examined the response of athymic nude mice and genetically mast-cell-deficient mice. We could not detect either severe skin inflammation or immunoglobulin (Ig)E production in T-cell-deficient BALB/c nu/nu mice even after 80 days of TNCB treatment, whereas typical severe skin inflammation and IgE production were observed in mast-cell-deficient WBB6F1-W/Wv and WBB6F1-Sl/Sld mice. Furthermore, we observed persistent scratching behavior in WBB6F1-W/Wv mice, but not in BALB/c nu/nu and WBB6F1-Sl/Sld mice. Histological examination of TNCB-treated animals revealed the development of dermal mast cells in W/Wv mice but not in Sl/Sld mice. Degranulation of dermal mast cells was observed in the WBB6F1-W/Wv genotype, but most mast cells remained intact in TNCB-treated BALB/c nu/nu mice. These results suggest that mast cells play a pivotal role in the incidence of scratching behavior in this chronic pruritus model.

Acetone↗
PubMed2005

Pyoderma gangrenosum associated with nasal septal perforation, oropharyngeal ulcers and IgA paraproteinemia.

We report a case of pyoderma gangrenosum (PG) associated with nasal septal perforation, pharyngeal ulcers and IgA paraproteinemia. A 28-year-old woman first developed painful undermined ulcers on her perianal, inguinal and axillary areas when she was 22 years old. Histological findings from the cutaneous ulcers showed dermal and epidermal infiltrate of neutrophils, which was compatible with PG. Laboratory examinations did not detect any associations of systemic diseases other than polyclonal IgA paraproteinemia. Nasal fiberscopy revealed septal perforation and multiple ulcers on her pharynx. The biopsy specimen from the pharyngeal ulcers showed a polymorphous cellular infiltrate without necrotizing vasculitis or granuloma. However, there were no atypical lymphocytes that are typically seen in nasal NK/T lymphoma. By immunohistochemical analysis, the infiltrated lymphocytes were proved to be T cells and Epstein-Barr virus encoded RNA (EBER) was not detected. No pulmonary or renal lesions resembling Wegener's granulomatosis were found. Taken together, the nasal septal perforation was considered as nasal involvement of PG.

Adult↗
PubMed2005

Topical tacrolimus therapy for pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a type of neutrophilic disorder with a chronic clinical course. Immunosuppressive agents have been used for its management. Among them, corticosteroid is known as the most effective. However, other immunosuppressants including cyclosporine A have been selected for patients with PG who were refractory to systemic steroids. Herein we report a case of PG resistant to systemic steroids, who was successfully treated with topical tacrolimus. A fifty-four year-old male had a 14-year history of PG. In 2002, necrotic ulcers appeared on his right leg that were refractory to oral prednisolone (30 mg/day). The application of topical tacrolimus to the border of the ulcers hastened epithelization of the ulcers and allowed for reduction of the oral prednisolone. Topical tacrolimus therapy may be an effective alternative for PG when the lesion is poorly controlled by corticosteroid.

Administration, Topical↗
PubMed2005

Recombinant cholera toxin B subunit activates dendritic cells and enhances antitumor immunity.

Activation of dendritic cells (DC) is crucial for priming of cytotoxic T lymphocytes (CTL), which have a critical role in tumor immunity, and it is considered that adjuvants are necessary for activation of DC and for enhancement of cellular immunity. In this study, we examined an adjuvant capacity of recombinant cholera toxin B subunit (rCTB), which is non-toxic subunit of cholera toxin, on maturation of murine splenic DC. After the in vitro incubation of DC with rCTB, the expression of MHC class II and B7-2 on DC was upregulated and the secretion of IL-12 from DC was enhanced. In addition, larger DC with longer dendrites were observed. These data suggest that rCTB induced DC maturation. Subsequently, we examined the induction of tumor immunity by rCTB-treated DC by employing Meth A tumor cells in mice. Pretreatment with subcutaneous injection of rCTB-treated DC pulsed with Meth A tumor lysate inhibited the growth of the tumor cells depending on the number of DC. Moreover, intratumoral injection of rCTB-treated DC pulsed with tumor lysate had therapeutic effect against established Meth A tumor. Immunization with DC activated by rCTB and the tumor lysate increased number of CTL precursor recognizing Meth A tumor. The antitumor immune response was significantly inhibited in CD8+ T cell-depleted mice, although substantial antitumor effect was observed in CD4+ T cell-depleted mice. These results indicated that rCTB acts as an adjuvant to enhance antitumor immunity through DC maturation and that CD8+ T cells play a dominant role in the tumor immunity. Being considered to be safe, rCTB may be useful as an effective adjuvant to raise immunity for a tumor in clinical application.

Adjuvants, Immunologic↗
PubMed2004

New strategy for efficient selection of dendritic cell-tumor hybrids and clonal heterogeneity of resulting hybrids.

Heterotypic hybrids created between dendritic cells (DC) and tumor cells represent an efficient approach for loading DC with tumor-associated antigens (TAA) and DC-tumor hybrid vaccines have shown promising outcomes in various preclinical and clinical studies. Conventional DC-tumor hybrid preparations, however, are unavoidably contaminated by DC-tumor aggregates and DC loaded with tumor cell debris. Here we describe a new strategy for selecting genuine DC-tumor hybrids. A HAT-sensitive/zeocin-resistant DC clone (XS106-7 Zeo) was fused with a GFP-transduced fibrosarcoma clone (S1509a-GFP) by polyethylene glycol and heterotypic hybrid clones were established by limiting dilution in the presence of HAT and zeocin. CD45 (DC origin) and GFP (tumor origin) were both expressed in 91% (51/56 clones) of the resulting clones, indicating high efficiency of our strategy. Marked heterogeneity was observed among the hybrid clones and only one clone exhibited characteristic features of DC (CD86 and I-A expression, dendritic morphology, T cell-stimulatory capacity and IL-1beta, IL-6 and TNFalpha production), suggesting that only small fractions of DC-tumor hybrids acquire and maintain the properties of parental DC. Finally, vaccination with this hybrid clone protected mice from subsequent growth of S1509a tumor cells, documenting the in vivo activity of DC-tumor hybrids in the complete absence of exogenous TAA.

Animals↗
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

A case of bullous Sézary syndrome.

Sézary syndrome is an aggressive variant of cutaneous T cell lymphoma with poor prognosis and clinically characterized by erythroderma and Sézary cells in the blood. Here we report a case of bullous Sézary syndrome. A seventy-year-old male presented with erythroderma and inguinal lymph node swelling. Histopathological examination showed dermal and epidermal infiltration of atypical lymphocytes and Sézary cells could be detected in peripheral blood samples. He was therefore diagnosed as Sézary syndrome. Four months after the onset, he developed bullae on axillary and inguinal areas, featuring subepidermal blistering with basal cell degeneration and dense infiltration of atypical lymphocytes. Autoimmune bullous diseases were excluded by negative immunofluorescence. Bullous forms of Sézary syndrome are extremely rare although several cases of a bullous variant of mycosis fungoides have been reported.

Aged↗
PubMed2003

Altered decorin expression of systemic sclerosis by UVA1 (340-400 nm) phototherapy: immunohistochemical analysis of 3 cases.

BACKGROUND: Ultraviolet A1 (340-400 nm, UVA1) phototherapy is highly effective in sclerotic lesions of systemic sclerosis (SSc). Histological evaluation of skin specimens obtained before and after UVA1 phototherapy revealed loosening of collagen bundles and the appearance of small collagen fibers. We have previously shown that UVA1 irradiation induced collagenase in vitro study by using SSc fibroblasts. The increased levels of mRNA and protein of decorin in SSc fibroblasts were reported. In this study, we focus on the lesional expression of small dermatan sulfate proteoglycan, decorin that has a role of binding to collagen and fibrillogenesis. CASE PRESENTATION: We employed immunohistochemical analysis of decorin before and after UVA1 phototherapy. The skin specimens from three patients who were effectively treated with UVA1 phototherapy were analysed. Monoclonal antibody 6B6 as the specific reactivity to decorin was used. The increased decorin was focally accumulated in the newly synthesized collagen fibers in the sclerotic lesion of SSc. After UVA1 phototherapy, decorin was decreased in upper to middle dermis, although decorin was slightly increased in papillary dermis. CONCLUSIONS: These results suggest that decreased and normalized levels of accumulated decorin may relate to the efficacy of sclerotic lesions in UVA1 phototherapy.

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↗