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Biomedical subjects

Saburo Kishimoto

Publications and source records attributed to Saburo Kishimoto.

At least 19 recordsLinked to original sources
PubMed2006

Relationship of serum brain-derived neurotrophic factor level with other markers of disease severity in patients with atopic dermatitis.

Elevated serum levels of neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been reported in allergic and autoimmune diseases. The aim of this study was to assess serum levels of BDNF in patients with atopic dermatitis (AD) and to investigate the relationship of the BDNF level with other markers of disease severity. Serum BDNF concentration was significantly higher in patients with AD (n=62) compared to control subjects (n=20) (P<0.01). Stepwise multiple regression analysis showed a significant influence of the peripheral blood eosinophil counts (F=6.90) and the percentage of CD4(+)IL-4(+) (Th2) cells (F=6.61). Moreover, after remission of AD patients with conventionally treated AD patients (n=14), serum levels of BDNF, eosinophil counts and percentage of Th2 cells were decreased significantly. These results suggest that serum BDNF may be a useful marker of disease activity in AD and that both eosinophils and Th2 cells are major cellular sources of serum BDNF.

Adolescent↗
PubMed2006

Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling.

BACKGROUND: Sonic hedgehog (Shh) is a prototypical morphogen known to regulate epithelial-mesenchymal interaction during embryonic development. Recent observations indicate that exogenous administration of Shh can induce angiogenesis and may accelerate repair of ischemic myocardium and skeletal muscle. Because angiogenesis plays a pivotal role in wound repair, we hypothesized that activation of the hedgehog pathway may promote a favorable effect on microvascular remodeling during cutaneous wound healing and thereby accelerate wound closure. Because diabetes is associated with impaired wound healing, we tested this hypothesis in a diabetic model of cutaneous wound repair. METHODS AND RESULTS: In Ptc1-LacZ mice, cutaneous injury resulted in LacZ expression, indicating that expression of the Shh receptor Patched was induced and therefore that the Shh signaling pathway was intact postnatally and upregulated in the process of wound repair. In diabetic mice, topical gene therapy with the use of naked DNA encoding for Shh resulted in significant local gene expression and acceleration of wound recovery. The acceleration in wound healing was notable for increased wound vascularity. In bone marrow transplantation models, the enhanced vascularity of the wound was shown to be mediated, at least in part, by enhanced recruitment of bone marrow-derived endothelial progenitor cells. In vitro, Shh promoted production of angiogenic cytokines from fibroblasts as well as proliferation of dermal fibroblasts. Furthermore, Shh directly promoted endothelial progenitor cell proliferation, migration, adhesion, and tube formation. CONCLUSIONS: These findings suggest that a simple strategy of topically applied Shh gene therapy may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as occurs in diabetes.

Angiogenic Proteins↗
PubMed2006

Cutaneous tissue angiotensin-converting enzyme may participate in pathologic scar formation in human skin.

BACKGROUND: Many studies have shown that up-regulation of angiotensin-converting enzyme (ACE) participates in adverse fibrous remodeling. Although this has become an accepted fact in the cardiovascular field, the relationship between ACE and cutaneous fibrous remodeling, such as keloid or hypertrophic scars, remains unknown. OBJECTIVE: We sought to investigate ACE in normal skin, wounded skin, and pathologic scars. METHODS: Ten samples undergoing a normal wound-healing process, 14 samples of pathologic scar tissue, and 15 samples of normal skin were used in this study. Cutaneous tissue ACE activities were measured with high-pressure liquid chromatography. Localization of ACE was assessed by immunohistochemistry. RESULTS: The ACE activity in pathologic scar tissue was significantly higher than in normal and wounded skin. Immunohistochemical studies demonstrated that myofibroblasts were stained with anti-ACE antibody. LIMITATIONS: The study is small. CONCLUSIONS: These results suggest that up-regulated ACE may participate in cutaneous pathologic scar formation the same as the cardiovascular system.

Adolescent↗
PubMed2006

Dibutyryl cAMP influences endothelial progenitor cell recruitment during wound neovascularization.

Delayed wound healing is one of the major complications of diabetes, and is caused by delayed cellular infiltration, reduced angiogenesis, and decreased formation and organization of collagen fibers. Recently, endothelial progenitor cells (EPC) isolated from peripheral blood were shown to accumulate at sites of neovascularization during wound healing. The present study tested the hypothesis that sodium N-6,2'-O-dibutyryl adenosine-3',5'-cyclic phosphate (DBcAMP), which has been shown to accelerate wound healing, promotes recruitment of EPC into wounds and contributes to the stimulation of neovascularization in genetically diabetic mice. Topical application of DBcAMP resulted in significant acceleration of wound healing and wound vascularization partly via enhanced recruitment of EPC. EPC in DBcAMP-treated wounds were mainly localized to cell clusters at the border of the granulation tissue, a site where blood supply is most insufficient. DBcAMP treatment increased the mRNA expression of angiogenic cytokines vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1alpha (SDF-1alpha) in vivo in wound tissue and in cultured fibroblasts and macrophages, in vitro. Culture supernatants of DBcAMP-treated cells enhanced EPC migration. Taken together, these results indicate that DBcAMP promotes neovascularization in wound healing, at least partly by increasing the accumulation of EPC at wound sites.

Animals↗
PubMed2006

Prolonged topical application of tacrolimus inhibits immediate hypersensitivity reactions by reducing degranulation of mast cells.

We studied the effects of prolonged topical application of tacrolimus on immediate hypersensitivity reactions. Tacrolimus, betamethasone or petrolatum was applied to the footpad of mice for up to 28 days after immunization, and the foot-swelling response to allergen was estimated. The reactions in tacrolimus-treated mice decreased significantly from day 14, while those in betamethasone-treated mice decreased significantly from day 7. Although the number of mast cells in the foot skin of each group did not differ significantly, the percentage of degranulated mast cells decreased in the tacrolimus-treated group on days 7 and 14. The TUNEL method indicated that there were no apoptotic mast cells in the foot skin of tacrolimus-treated mice. Continuous application of topical tacrolimus ointment may suppress immediate hypersensitivity reactions by reducing the degranulation of mast cells, rather than by decreasing their number.

Administration, Topical↗
PubMed2006

Successful treatment of diabetic gangrene with topical application of a mixture of peripheral blood mononuclear cells and basic fibroblast growth factor.

Diabetic gangrene is a non-healing skin ulcer that is often resistant to most common treatments. It is caused by microvascular disorders and an immunocompromised state which are induced by diabetes mellitus. We report a 65-year-old man with an aggressive, refractory diabetic gangrene on his left foot. Treatment of his diabetic gangrene with topical application of a mixture of peripheral blood mononuclear cells (PBMC) and basic fibroblast growth factor (bFGF) resulted in a dramatic improvement in a short time. The ulcer was completely closed and, in the past 6 months, no new ulceration has been observed. The patient is able to stand and walk by himself. Topical application of a mixture of PBMC and bFGF appears to be a useful, non-invasive and convenient method for the treatment of diabetic gangrene.

Administration, Cutaneous↗
PubMed2006

Vaccination of Japanese patients with advanced melanoma with peptide, tumor lysate or both peptide and tumor lysate-pulsed mature, monocyte-derived dendritic cells.

We performed a clinical trial to assess the feasibility and efficacy of immunotherapy with peptides, tumor lysate or both peptides and tumor lysate-pulsed mature, monocyte-derived dendritic cells (DC) for advanced malignant melanoma patients that are resistant to conventional therapies. Sixteen patients were enrolled in this trial. All patients received DC vaccines i.d. in the proximal thigh, close to the inguinal lymph nodes, one treatment per week or 2 weeks. Several factors such as clinical findings, computed tomography (CT) images, delayed type hypersensitivity (DTH) response, enzyme-linked immunosorbent spot (ELISPOT) assay, and immunohistochemistry in primary, metastatic lesions and the DTH site were evaluated. Clinical results through DC vaccination were as follows: in 11 evaluable cases, three stable disease, six progression of disease and two disease-free from the time of study entry to the completion of one vaccination course. One patient showed reduction of the tumors in the metastases on chest CT during the first and second course of DC vaccination. Ten out of 14 evaluable cases showed positive DTH responses to more than one treatment with melanoma peptides or tumor lysate. Eight out of 13 evaluable cases showed positive immunological responses to more than one treatment with melanoma peptides or tumor lysate in an ELISPOT assay. As for the experiences with toxicity and adverse reactions, autosensitization dermatitis-like eruptions appeared in five cases during DC vaccination. No severe adverse effects were seen in any of the patients. In our study, the clinical efficacy in prolongation of the patients' survival was confirmed. At the same time, cancer immunoediting of the tumor was also found. It will be necessary to improve the tumor-specificity of this therapeutic approach and to analyze the mechanism(s) of tumor escape from immunosurveillance in melanoma.

Adult↗
PubMed2006

Features and prognoses of infantile patients with atopic dermatitis hospitalized for severe complications.

Although atopic dermatitis (AD) itself is regarded as a non-life threatening disease, childhood AD may be rarely accompanied by some serious complications. Six infantile AD patients who were hospitalized because of severe systemic complications, in addition to severe dermatitis on almost the entire body surface, are described. They were complicated by hypoproteinemia, hypovolemia, thrombocytosis, reduced serum immunoglobulin G, elevated serum liver enzymes and growth retardation. They had not been treated with topical corticosteroid before hospitalization. They were treated with topical corticosteroid and their eruption remarkably improved within 20 days (median) of hospitalization. Most of the abnormal clinical data including platelet numbers, serum levels of total protein, and liver enzymes had become normal at the day of discharge. After 30 +/- 4 months of follow up, their skin condition was fair with daily application of moisturizer and occasional use of topical corticosteroid, without any systemic problems. Although severe infantile AD may be accompanied by potentially life-threatening systemic complications, their prognoses concerning AD are favorable if they are treated adequately from the beginning of their infancy.

Administration, Cutaneous↗
PubMed2006

[A case of drug eruption induced by hydroxyzine pamoate].

A 62-year-old woman with rheumatoid arthritis, Basedow's disease and arrhythmia has been treated with antirheumatic, antiarrhythmic drugs and so on. She developed pruritic diffuse erythema with papules on the trunk and extremities 2 days after taking hydroxyzine pamoate for asteatotic eczema. Laboratory data showed increased levels of eosinophils. Histopathological examination revealed a infiltrate of inflammatory cells in the upper dermis. Patch tests with hydroxyzine pamoate and hydroxyzine hydrochloride were positive. From these findings, we diagnosed this case as drug eruption due to hydroxyzine. Her eruption subsided after she discontinued hydroxyzine pamoate and other drugs which were started within 5 days before the onset of the eruption and was treated with systemic steroid, systemic antiallergic drug and topical steroid.

Drug Eruptions↗
PubMed2005

Histamine induces the generation of monocyte-derived dendritic cells that express CD14 but not CD1a.

The local cytokine environment and the presence of stimulatory signals determine whether monocytes acquire dendritic cell or macrophage characteristics and functions. In this study, we examined the effect of histamine, a prototypic mediator of allergic inflammation, on the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation of monocytes into monocyte-derived dendritic cells (MoDC), which typically showed CD1a+CD14- phenotype. Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of histamine, and the phenotypes and function of these cells were analyzed. Histamine induced the generation of CD1a-CD14+ cells, which exhibited cytological and phenotypical characteristics of dendritic cells (DC), showed enhanced phagocytic activity and cytokine-producing capacity, but demonstrated weak allo-stimulatory capacity compared with CD1a+CD14- MoDC. The inhibitory effects of histamine on CD1a+CD14- MoDC differentiation were antagonized by cimetidine, an H2 receptor antagonist, but not by H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. Culture supernatant of histamine-treated monocytes also inhibited CD1a+CD14- MoDC differentiation, which was restored by the removal of IL-10. These results suggest that histamine-driven CD1a-CD14+ DC amplify their antigen-independent inflammatory reaction and may contribute to the exacerbation of allergic diseases.

Antigens, CD1↗
PubMed2005

Erythema nodosum induced by the synergism of acupuncture therapy and flu-like infection.

A 32-year-old female patient developed erythema nodosum-like lesions at needle prick sites after acupuncture therapy. Over the next few days, she developed similar new lesions over the extremities, trunk and face along with flu-like symptoms. There were neither genital ulcerations nor eye lesions. A skin biopsy specimen from an extremity lesion showed the characteristic findings of erythema nodosum. Treatment with oral potassium iodide at a dose of 750 mg/day was effective, and there has not been any recurrence to date. We diagnosed this case as erythema nodosum induced by a synergism between acupuncture therapy and a flu-like infection.

Acupuncture Therapy↗
PubMed2005

Atypical fibroxanthoma on a bald scalp.

We present the clinical, histopathological and immunohistochemical findings of an atypical fibroxanthoma (AFX) on the bald scalp of an 81-year-old French man who had worked at a private high school in Japan as a janitor for over 40 years. The patient had a history of basal cell carcinoma on the nape, and chronic solar radiation seemed to be a predisposing factor in the pathogenesis of this association. This case showed the typical clinical and histopathological characteristics of AFX, and the immunohistochemical results suggested differentiation of histiocytes and myofibroblasts. The AFX was completely resected, and the patient has not had tumor recurrence or metastasis for over four postoperative years. This case therefore provides further support to the theory that AFX displays a clinically benign course, even though it is essentially a malignant tumor histologically located in the dermis. Therefore, we must excise AFX completely with great care and perform regular physical examinations for several years after operation.

Aged, 80 and over↗
PubMed2005

Scrotal Ulcers Arising during Treatment with All-trans Retinoic Acid for Acute Promyelocytic Leukemia.

All-trans retinoic acid (ATRA) is effective in approximately 90% of the cases of acute promyelocytic leukemia (APL) with a low incidence of adverse effects. We report a patient with APL who developed skin ulcers of the scrotum concomitant with high fever during treatment that included ATRA. Severe fever was promptly alleviated with discontinuation of ATRA, while the ulcers improved gradually over 3 months. As the clinical features are similar to those of Sweet's syndrome, we should be aware of the possibility that this rare adverse effect may occur in the treatment with ATRA.

Adult↗