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Biomedical subjects

Takuro Kanekura

Publications and source records attributed to Takuro Kanekura.

At least 19 recordsLinked to original sources
PubMed2006

A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma.

CD147 plays a critical role in the invasive and metastatic activity of malignant melanoma cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases and vascular endothelial growth factor. We developed a system that blocks CD147 in the human malignant melanoma cell line, A375, using RNA interference. By transfecting melanoma cells with the small interfering RNA (siRNA) that targets human CD147, we were able to establish two stable clones in which CD147 expression was significantly down-regulated. This resulted in the decreased proliferation and invasion of A375 cells in vitro. CD147 siRNA also down-regulated the expression of vascular endothelial growth factor in these cells and reduced the migration of vascular endothelial cells. The reduction in the CD147 level suppressed the size of s.c. tumors and the microvessel density in an A375 s.c. nude mouse xenograft model. In addition, the in vivo metastatic potential of A375 cells transfected with CD147 siRNA was suppressed in a nude mouse model of pulmonary metastasis.

Animals↗
PubMed2006

Cytochemical analysis of storage materials in cultured skin fibroblasts from patients with I-cell disease.

BACKGROUND: In cultured fibroblasts from I-cell disease patients the transport of many lysosomal enzymes is defective, and affected cells contain inclusion bodies filled with undegraded substrates. However, the contents of these inclusion bodies have not been well characterized yet. We attempted to identify accumulated substances in cultured I-cell disease fibroblasts cytochemically. METHODS: Cultured fibroblasts from I-cell disease patients were double-stained with a monoclonal antibody to lysosome-associated membrane protein-1 (LAMP-1) and that to GM2 ganglioside, or a series of lectins that specifically bind to sugar moieties. RESULTS: The patients' cells were granularly stained with the antibody to GM2 ganglioside and the lectins including Maakia amurensis, Datura stramonium, and concanavalin A. Their localization was coincident with that of LAMP-1. CONCLUSIONS: GM2 ganglioside and various kinds of glycoconjugates having sialic acidalpha2-3galactose, galactosebeta1-4N-acetylglucosamine and mannose residues accumulate in enlarged lysosomes in I-cell disease fibroblasts.

Cells, Cultured↗
PubMed2006

Syringoma-like eccrine sweat duct proliferation induced by radiation.

We report a 45-year-old woman with breast cancer who had undergone surgery and radiation and anti-estrogen therapy and presented with many reddish papules in the irradiated breast area. Skin biopsy of the affected area disclosed proliferation of eccrine sweat ducts and cystic structures; the clinical and histopathological features were consistent with syringoma-like eccrine sweat duct proliferation. The lesions spread rapidly on her chest during radiation therapy and regressed spontaneously 3 weeks after its completion. We postulate that the lesions were induced by radiation, and promoted by anti-estrogen therapy.

Breast Neoplasms↗
PubMed2006

Granulomas induced by subcutaneous injection of leuprorelin acetate.

Leuprorelin acetate, a chemotherapeutic agent used to treat prostate cancer, is a synthetic luteinizing hormone-releasing hormone (LHRH) agonist. We report a 75-year-old man who presented with several large subcutaneous nodules at the site of leuprorelin acetate injections for his prostatic cancer. A biopsy of the nodules disclosed epithelioid granulomatous inflammation and resulted in a diagnosis of drug-induced granulomatous reaction to leuprorelin acetate.

Abdomen↗
PubMed2006

Contact dermatitis due to orchids (Cymbidium and Oncidium).

A 64-year-old male who cultivated orchids as a hobby, had noticed itchy erythematous lesions on both hands since 6 months earlier. His eruptions had gradually worsened and scales and fissures had appeared. Although he was treated with topical corticosteroids by a doctor, his erythema showed no improvement. Patch tests with the orchids he cultivated, fertilizers, antiseptics and insecticides showed positive reactions to the stems of Cymbidium and Oncidium orchids. A diagnosis of contact dermatitis attributable to the cultivated orchids was made.

Dermatitis, Allergic Contact↗
PubMed2006

Crusted scabies in an adult T-cell leukemia/lymphoma patient successfully treated with oral ivermectin.

We report an adult T-cell leukemia/lymphoma (ATL) patient whose crusted scabies was successfully treated with oral ivermectin. This 63-year-old man had previously been treated with oral prednisolone, sobuzoxane and etoposide for approximately 1 year. When he developed crusted scabies, he received two doses of oral ivermectin (200 microg/kg) 10 days apart and the concomitant topical application of crotamiton containing 30% benzyl benzoate. This produced remarkable results, suggesting that oral ivermectin should be considered for the treatment of crusted scabies even in immunocompromised patients. While ivermectin may be useful for treating intractable scabies, attention must be paid to the possible appearance of ivermectin-resistant mites.

Administration, Oral↗
PubMed2006

Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria.

A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from seven non-consanguineous families and found two distinct genomic DNA abnormalities. In six patients from five families, there was a G-to-A point-mutation at the first position of the intron 9 donor site; it resulted in aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found an A-to-G point-mutation 4 bases from the 3" terminus of intron 4 that led to the in-frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single nucleotide polymorphisms were detected in another patient. We analyzed intron polymorphism at IVS3-48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. All patients were C/C homozygous for IVS3-48. The allelic frequency of IVS3-48C polymorphism in the healthy Japanese volunteers was 67.8% (103/152).

Adolescent↗
PubMed2006

Bidens pilosa suppresses interleukin-1beta-induced cyclooxygenase-2 expression through the inhibition of mitogen activated protein kinases phosphorylation in normal human dermal fibroblasts.

Bidens pilosa (BP) Linn. var. radiata is a plant used in traditional folk medicine. It is clinically effective in various diseases; the pathogenesis of most of these involves cyclooxygenase (COX)-2. To investigate the mechanism on which the clinical effectiveness of BP is based, we examined its effects on COX-2 expression and its major product, prostaglandin (PG)E(2), under conditions of inflammation. We induced inflammation in normal human dermal fibroblasts with interleukin (IL)-1beta and examined the effects of BP on COX-2 expression and PGE(2) production using Western blotting and competitive enzyme immunoassay, respectively. The functional involvements of mitogen activated protein kinases (MAPK) ERK1/2, p38, and JNK in COX-2 expression were also examined by Western blotting. IL-1beta-induced COX-2 expression was regulated by MAPK pathways, especially by p38. BP inhibited the phosphorylation of MAPKs, COX-2 expression, and subsequent PGE(2) production. The physiological activities and clinical effectiveness of BP observed under diverse conditions may be partly attributable to its ability to inhibit MAPK, mainly p38, activity, COX-2 expression, and subsequent PGE(2) production.

Bidens↗
PubMed2006

Eruptive pruritic papular porokeratosis: a pruritic variant of porokeratosis.

Porokeratosis is a chronic skin disorder characterized clinically by the presence of crater-like patches with an elevated thick keratotic border and central atrophy. Histology reveals cornoid lamellae. While porokeratosis is practically asymptomatic, a pruritic variant has been reported. We recently encountered an 82-year-old man with pruritic porokeratosis. He presented with erythematous papules and intensively itchy patches on his lower limbs that had been present for 6 months. Histopathological examination revealed the characteristic cornoid lamellae. We describe this case in detail and provide a review of the published work.

Aged↗
PubMed2006

Primary squamous cell carcinoma of the frontal sinus.

We report a 74-year-old Japanese man with squamous cell carcinoma (SCC) originating in the frontal sinus. It presented as a cutaneous nodule on his right forehead. Magnetic resonance imaging (MRI) revealed invasion of the anterior wall of the ethmoid sinus, the frontal bone, and possibly the meninx by a frontal sinus carcinoma. Despite right fronto craniotomy with en bloc resection followed by two courses of radiation therapy and chemotherapy with 5-fluorouracil and nedaplatin or TS-1 he died of disease-related causes 20 months later. Herein, we present a detailed description of this patient and a review of the published work.

Aged↗
PubMed2006

Granulocyte and monocyte adsorption apheresis for cutaneous allergic vasculitis.

Cutaneous allergic vasculitis (CAV) is characterized clinically by purpuric patches with secondary ulcerations, and histologically by leukocytoclastic vasculitis with neutrophil infiltrates. Granulocyte and monocyte adsorption apheresis (GCAP) is an extracorporeal apheresis instrument using a column containing cellulose acetate beads designed to remove pathogenic granulocytes. Here we report our assessment of the efficacy of GCAP for recurrent leg ulcers in a 49-year-old woman with CAV. She underwent five GCAP treatments at one-week intervals. In each treatment session, 1800 mL of blood was processed. Her leg ulcers responded well and her white blood cell and neutrophil counts and the expression level of CD11b/CD18, a marker for activated neutrophils, on her peripheral neutrophils were reduced from 7500/microL to 6500/microL, 4350/microL to 3315/microL, and 64.9 MFI (mean fluorescence intensity) to 27.0 MFI (normal controls: 10.5 +/- 1.2 MFI) by GCAP, respectively. These results suggest that GCAP is useful for skin disorders with leucocytoclastic vasculitis.

Blood Component Removal↗
PubMed2006

Granulocyte and monocyte adsorption apheresis (GCAP) for refractory skin diseases caused by activated neutrophils and psoriatic arthritis: evidence that GCAP removes Mac-1-expressing neutrophils.

In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.

Adsorption↗
PubMed2005

Blood group A glycosphingolipid accumulation in the hair of patients with alpha-N-acetylgalactosaminidase deficiency.

In the hair of individuals with blood group AB, the level of blood group A glycosphingolipids is much lower than that of blood group B. We hypothesized that in hair, blood group A determinants are converted by alpha-N-acetylgalactosaminidase (alpha-NAGA, E.C.3.2.1.49) to H determinants. To address our hypothesis, the relative amount of ABH glycosphingolipids in hairs and nails of normal subjects, patients with Kanzaki disease, and heterozygous carriers of alpha-NAGA deficiency were analyzed by dot-blotting and enzyme-linked immunosorbent assay. In hair from normal subjects with blood group B, ABH glycosphingolipids consisted of 88% blood group B- and 12% blood group H glycosphingolipids. In blood group A subjects, 14% were group A- and 86% were group H glycosphingolipids. In Kanzaki patients, 81% were blood group A- and 19% were blood group H glycosphingolipids. In 2 alpha-NAGA deficiency carriers, the ABH glycosphingolipids consisted of 67% blood group A- and 33% blood group H glycosphingolipids. These results indicate that blood group A glycosphingolipids are catabolized to H glycosphingolipids by alpha-NAGA, resulting in lower levels of blood group A glycosphingolipids in the hair of normal subjects, and alpha-NAGA deficiency causes accumulation of blood group A glycosphingolipids in the hair of Kanzaki patients. This finding is of clinical relevance because it suggests that hair may be used to diagnose and assess the alpha-NAGA status of individuals.

ABO Blood-Group System↗
PubMed2005

Extramammary Paget's disease/carcinoma successfully treated with a combination chemotherapy: report of two cases.

We have treated two patients with extramammary Paget's disease/carcinoma (EMPD/C), a 62-year-old woman and a 78-year-old man. In both patients, lymph nodes in the areas of the bilateral inguinal, external iliac arteries, and abdominal aorta were affected. After surgery, they underwent 5 courses of systemic combination chemotherapy at 4-week intervals to residual or recurrent lymph node metastasis. Each course consisted of 3.5 mg mitomycin C and 50 mg epirubicin (day 1), 0.6 mg vincristine (days 1 and 7), 30 mg cisplatin (days 1, 2, and 3), and 350 mg 5-fluorouracil (days 3, 4, 5, 6, and 7). The affected lymph nodes in both patients subsided in response to the chemotherapy. Positron emission tomography (PET) scans confirmed the complete remission of lymph node metastasis in Case 1. In Case 2, they were reduced by more than 90% on computed tomography (CT) scans. Adverse effects included leukocytopenia, vomiting, hypesthesia, and constipation, all of which disappeared after the completion of chemotherapy. While surgery with wide local excision is the treatment of choice in patients with EMPD/C, there is currently no standardized treatment for advanced cases with metastasis. We describe two patients with EMPD/C whose metastatic lesions responded well to this combination of chemotherapy.

Aged↗
PubMed2005

Beneficial effects of tissue inhibitor of metalloproteinases-2 (TIMP-2) on chronic dermatitis.

Chronic dermatitis, such as contact dermatitis (CD) or atopic dermatitis (AD), is a longstanding inflammatory skin disease with cutaneous damage such as erosion, ulceration, and lichenification due to itch-induced scratching. The resultant lesion can be considered to be a kind of wound. The tissue inhibitor metalloproteases-2 (TIMP-2) accelerates wound healing by enhancing the proliferation and migration of epidermal keratinocytes and dermal fibroblasts; it is also a physiologic inhibitor of matrix metalloproteinases. The aim of this study was to test the effect of TIMP-2 on chronic dermatitis. NC/Kuj mice were sensitized with Dermatophagoides farinae (Df) extract. Eczema was induced by repeated applications of this mite allergen to the skin of 20 sensitized mice that were maintained under specific pathogen-free conditions. One group of 10 mice was then treated with topical TIMP-2 solution (0.1 ml, 0.5%) for 28 days, and the other with vehicle alone and the effects of TIMP-2 were evaluated macro- and microscopically. The effect on skin barrier function was estimated by measuring transepidermal water loss (TEWL). Scoring of gross skin findings showed that TIMP-2 significantly reduced the severity of eczema (P<0.05) on days 12-28. Histological examination revealed that TIMP-2 treated mice manifested lower degrees of hyperkeratosis, acanthosis, and spongiosis in the epidermis and fewer inflammatory cells in the dermis than vehicle-treated mice. There were significant reductions in the epidermal thickness and dermal inflammatory cells in the TIMP-2 treated animals (P<0.01); their TEWL was significantly decreased on day 28 (P<0.05). Our results suggest that NC/Kuj mice with Df extract-induced chronic eczema may be a useful model for investigating chronic dermatitis, and that TIMP-2 may be a good agent for treating chronic dermatitis as well as chronic ulcers.

Administration, Topical↗