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Biomedical subjects

S Itami

Publications and source records attributed to S Itami.

At least 19 recordsLinked to original sources
PubMed2005

Prevention of amputation caused by rheumatic diseases following a novel therapy of exposing bone marrow, occlusive dressing and subsequent epidermal grafting.

BACKGROUND: Wounds with exposed bones caused by rheumatic diseases commonly result in amputation despite progress in our understanding of wound-healing mechanisms. OBJECTIVES: To determine whether an experimental therapy of bone marrow exposure, an occlusive dressing and subsequent grafting of epidermal sheets accelerates healing and reduces the need for amputation in patients with rheumatic diseases. METHODS: Fifteen patients, including those with rheumatoid arthritis or systemic sclerosis, who had wounds with exposed bones were treated either with the standard procedure, consisting of local wound care, debridement with a scalpel, bed rest and parenteral antibiotics (n = 8), or with a newly developed experimental procedure (n = 7). In that new procedure, the affected bone was initially exposed by debridement with a scalpel, followed by partial excision with a bone scraper until bleeding was observed from the exposed bone. The lesions were immediately covered with an occlusive dressing, and were eventually treated with epidermal grafts obtained from suction blisters. RESULTS: A comparison with standard therapy demonstrated that the time needed for wound healing was similar, but that the newly developed combination therapy reduced the risk of amputation (P = 0.020). No skin ulcers or erosions were observed for at least 1 year in five of seven patients (72%) due to the adoption of stable palmoplantar-type characteristics in grafts derived from the trunk epidermis. CONCLUSIONS: Our study indicates that exposure of bone marrow cells plus an occlusive dressing accelerates the healing of skin ulcers at least partly through the preparation of a healthy well-granulated wound bed and that subsequent epidermal grafting achieves site-specific differentiation through epithelial-mesenchymal interactions.

Adult↗
PubMed2005

Bone marrow cells differentiate into wound myofibroblasts and accelerate the healing of wounds with exposed bones when combined with an occlusive dressing.

BACKGROUND: The usefulness of bone marrow cells in accelerating wound healing has not been evaluated despite increasing evidence that bone marrow contains mesenchymal stem cells that have multipotentiality to differentiate into various types of cells after they enter the microenvironment of a specific tissue (niche). OBJECTIVES: To determine the effects of bone marrow cells and occlusive dressings in promoting wound healing in rats. METHODS: We investigated by grafting, biopsy and immunohistochemistry whether various types of cells derived from green fluorescent protein (GFP)-transgenic rats would differentiate into wound component cells when administered topically on the wounds of rats. We also investigated whether topical application of bone marrow cells with an occlusive dressing would accelerate the healing of wounds with exposed bones, as measured by planimetry. RESULTS: GFP-labelled bone marrow cells contained multipotent stem cells that sufficiently differentiated into wound myofibroblasts presenting with alpha-smooth muscle actin in granulation tissue. Other types of cells, including myocytes, adipocytes, peripheral blood cells from buffy coat and dermal fibroblasts, did not express myofibroblast characteristics morphologically or immunohistochemically. Application of bone marrow cells and an occlusive dressing accelerated the repair of wounds with exposed bones, compared with an occlusive dressing only or with the topical administration of bone marrow cells plus a semidry to dry dressing. CONCLUSIONS: Our study indicates that bone marrow cells accelerate the healing of wounds at least in part through their differentiation into wound myofibroblasts. Thus, treatment of wounds with bone marrow cells and a supportive occlusive dressing is effective in promoting the formation of healthy granulation tissue and also for the preparation of an ideal wound bed.

Animals↗
PubMed2004

Rapid healing of intractable diabetic foot ulcers with exposed bones following a novel therapy of exposing bone marrow cells and then grafting epidermal sheets.

BACKGROUND: Diabetic foot ulcers with exposed bones commonly result in amputation. OBJECTIVES: To determine whether exposure of bone marrow cells and subsequent grafting of epidermal sheets accelerates healing and reduces the need for amputation. METHODS: Thirty-eight patients with chronic wounds caused by diabetes mellitus were enrolled in this study. Epidermal sheets obtained from suction blisters of each patient were grafted on to diabetic foot ulcers without exposed bones (n = 10) and were compared with the standard treatment of local wound care, debridement with a scalpel when indicated, bed rest and parenteral antibiotics (n = 8). In another group of patients, diabetic wounds with exposed bones were treated either with the standard procedure (n = 9) or with a newly developed experimental procedure (n = 11). In that new procedure, the affected bone was initially exposed by debridement with a scalpel, followed by partial excision with a bone scraper until fresh bleeding was observed from the exposed bone. The lesions were then immediately covered with an occlusive dressing, and finally the wound was covered with an epidermal graft of skin harvested from suction blisters. Patients in each group were matched with their counterparts by age, sex, wound size, wound infection and wound duration, to compare the time needed for total skin repair and rates of amputation. RESULTS: Epidermal grafting significantly accelerated the healing of diabetic foot ulcers (P = 0.042) without exposed bones, with site-specific differentiation. The newly developed combination therapy resulted in the healing of all diabetic ulcers with exposed bones without the occurrence of osteomyelitis or the necessity for amputation (P < 0.0001). CONCLUSIONS: Our study indicates that early aggressive debridement of diabetic foot ulcers with exposed bones down to a bleeding vascularized base and then grafting epidermal sheets significantly improves healing and reduces the rate of amputation.

Adult↗
PubMed2002

Construction of engineered CHO strains for high-level production of recombinant proteins.

We constructed engineered CHO strains that can be used for high-level production of foreign proteins by gene-targeting. After transfecting dihydroforate reductase (DHFR)-deficient CHO cells with a plasmid carrying a loxP-green fluorescent protein (GFP) fusion gene and a DHFR gene, we screened colonies by fluorescent intensity. We selected 16 clones that expressed high levels of GFP and carried one copy of the plasmid in their chromosomes and treated them with methotrexate (MTX) to examine their ability for DHFR-mediated gene amplification. Two clones, MK1 and MK2, showed increased GFP expression upon gene amplification. In those clones, the loxP-GFP gene was integrated at a transcription-active, DHFR-mediated, gene-amplifiable locus in the chromosomes. A gene-targeting vector, carrying a loxP-fused hygromycin-resistance gene, was constructed to target desired genes in chromosomal loxP by Cre recombinase-mediated site-specific recombination. Using this cell-vector system, we could reproducibly obtain high producers of recombinant proteins by gene-targeting and gene amplification. In human monoclonal antibody production, after gene-targeting of loxP in MK2 and gene amplification with MTX, the MTX-resistant colonies showed high levels of antibody production. The most productive clone was able to produce 160 mg/l in 7 days in a low-protein medium in a spinner-flask.

Animals↗
PubMed2002

Giant basal cell carcinoma affecting the lower abdominal, genital and bilateral inguinal regions.

We describe a giant basal cell carcinoma, measuring 40 cm x 20 cm, of the lower abdominal, genital and bilateral inguinal regions. The rectus abdominis muscle and the adductor magnus muscle were exposed centrally, and the penis and scrotum were completely destroyed. Reconstruction was performed with a fillet thigh flap, and an excellent result was obtained 1 year after surgery.

Abdominal Wall↗
PubMed2001

A new IFN-like cytokine, limitin, modulates the immune response without influencing thymocyte development.

A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN-alphabeta receptor, although it lacked growth suppression on myeloid and erythroid progenitors. Here we have studied diverse effects of limitin on T lymphocytes and compared limitin with previously known IFNs. Like IFN-alpha and -beta, limitin modified immunity in the following responses. It suppressed mitogen- and Ag-induced T cell proliferation through inhibiting the responsiveness to exogenous IL-2 rather than suppressing the production of IL-2. In contrast, limitin enhanced cytotoxic T lymphocyte activity associated with the perforin-granzyme pathway. To evaluate the effect of limitin in vivo, a lethal graft-versus-host disease assay was established. Limitin-treatment of host mice resulted in the enhancement of graft-versus-host disease. Limitin did not influence thymocyte development either in fetal thymus organ cultures or in newborn mice injected with limitin-Ig, suggesting that limitin is distinguishable from IFN-alpha and -beta. From these findings, it can be speculated that the human homolog of limitin may be applicable for clinical usage because of its IFN-like activities with low adverse effects on, for example, T lymphopoiesis, erythropoiesis, and myelopoiesis.

Adjuvants, Immunologic↗
PubMed2001

Potential anti-androgenic activity of roxithromycin in skin.

Since acne formation is a multistep process accelerated by androgens, we examined whether a new anti-acne antibiotic roxithromycin (RXM) may act as anti-androgen using transient transfection assays in human skin fibroblasts. The result showed no significant effect of 0.5, 1 and 5 microg/ml RXM on 10(-9) M R1881-induced androgen receptor (AR) transcriptional activity. While the cotransfection of exogenous ARA55, a novel AR coactivator, increased AR transactivation up to 2.59-fold, this increase was attenuated by 5 microg/ml RXM to 64.7%. Semiquantitative RT-PCR results showed that 0.1 mM H(2)O(2) treatment increased ARA55 mRNA expression level, indicating that reactive oxygen species increase the expression of ARA55 in skin. These results suggest that RXM may serve as anti-androgen only in the hypersensitive state to androgen, but not in the physiological state, through modulating end-organ hypersensitive condition to androgen possibly involving the pathway from reactive oxygen species to ARA55.

Androgen Antagonists↗
PubMed2001

Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival.

This study describes abnormalities of the thymus in mice in which the Stat3 gene has been specifically disrupted behind the keratin 5 promoter. In these mice, virtually all of the thymic epithelial cells (TEC) were deficient for Stat3 activation. Adult mutant mice developed severe thymic hypoplasia, which included alterations in the cortical TEC architecture that coincided with the loss of thymocytes. Even during the asymptomatic period of preadolescence, these mice exhibited a higher susceptibility of the thymus to suboptimal doses of dexamethasone or gamma-irradiation, while their thymocytes per se were no more sensitive than controls. These results indicate that Stat3 in TEC plays an essential role in maintaining thymic architecture and thymocyte survival.

Animals↗
PubMed2001

Tissue regeneration: hair follicle as a model.

The Cre-loxP strategy has allowed us to generate the mice whose keratinocytes are devoid of Stat3, which play a pivotal role in the signal transduction following the stimulation with various growth factors/cytokines, such as EGF, HGF, or IL-6. Although keratinocyte-specific Stat3-disrupted mice were born normal with intact skin and the first hair cycle, they exhibited retardation of wound healing and absence of the second hair cycle onward, leading to development of spontaneous skin ulcers and alopecia as they aged. Thus, analyses of these mice reveal that Stat3 in keratinocytes contributes to the regeneration of epidermis and hair cycle process.

Animals↗
PubMed2001

Impaired responses of peripheral blood mononuclear cells to T-cell stimulants in alopecia areata patients with a poor response to topical immunotherapy.

BACKGROUND: Topical immunotherapy with a contact allergen is effective in alopecia areata (AA). However, the mechanism of the effect is still unknown, and pretreatment prediction of the outcome of therapy in each patient remains difficult. OBJECTIVES: To predict the clinical effect of this therapy in AA patients, we investigated the relationship between clinical responses to topical immunotherapy and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to T-cell stimulants. METHODS: PBMC were taken from 67 AA patients before or during diphenylcyclopropenone immunotherapy and from 14 healthy controls, and proliferative responses to phytohaemagglutinin and staphylococcal enterotoxin B were evaluated by measuring [3H]-thymidine incorporation. RESULTS: PBMC from the AA patients with a good clinical response to immunotherapy showed a normal level of proliferation, whereas PBMC from the poor responders showed a markedly suppressed proliferative response and interleukin (IL)-2 production, but increased IL-4 production compared with the controls. CONCLUSIONS: The proliferative response of PBMC to T-cell stimulants may be one of the indicators of the clinical effect of topical immunotherapy for AA.

Adolescent↗
PubMed2001

A case of lichenoid purpura possibly caused by diltiazem hydrochloride.

A 65-year-old Japanese man presented with itchy purpuric lichenoid papules of six months' duration on his legs and buttock. A topical glucocorticoid ointment was not effective. The biopsy specimen histologically showed a dense lichenoid infiltration of lymphocytes and histiocytes into the dermoepidermal junction; red blood cells were seen in the infiltration. Based on the clinical and pathological findings, we diagnosed this case as lichenoid purpura of Gougerot-Blum. The lesions disappeared when the diltiazem hydrochloride that he had been taking was discontinued.

Aged↗
PubMed2001

Churg-Strauss syndrome involving medium-sized arteries.

A 69-year-old Japanese man suffered from bronchial asthma, atrial fibrillation, general fatigue, high fever, and weight loss of about 5 kg within a month. He also had intermittent claudication, a tingling feeling in his fingers and toes, and an ulcer on his toe. His laboratory data revealed leukocytosis with absolute eosinophilia. The patient was treated with predonisolone 30 mg daily. Although the ulcers healed once, the lesions recurred with tapering predonisolone. The patient visited us because of the ulcer on his toe. Physical examination showed a 2 cm ulcer surrounded by slight erythema on his right fourth toe. Magnetic resonance angiography detected tapering stenosis of the medium-sized arteries in both legs. A biopsy from his myocardium showed the infiltration of eosinophils into the myocardium. The neuron conduction rate of his lower leg was slower than that of the normal control, demonstrating mononeuritis. From these findings, we diagnosed this patient as Churg-Strauss syndrome.

Aged↗