Search PubMed⌕ Search

Biomedical subjects

Hideoki Ogawa

Publications and source records attributed to Hideoki Ogawa.

At least 73 records · Page 4Linked to original sources
PubMed2005

Transcriptional regulation of ATP2C1 gene by Sp1 and YY1 and reduced function of its promoter in Hailey-Hailey disease keratinocytes.

Hailey-Hailey disease (HHD) is a blistering skin disease caused by malfunction of the Ca2+-dependent ATPase, ATP2C1. In this study, key regulatory regions necessary for the expression of the gene encoding human ATP2C1 were investigated. The transient reporter assay demonstrated that region +21/+57 was necessary for activation of the ATP2C1 promoter, and the electrophoretic mobility shift assay demonstrated that the region was recognized by the transcription factors, Sp1 and YY1. In accordance with this result, when Sp1 or YY1 was overexpressed in keratinocytes, an obvious increase in ATP2C1 promoter activity was observed, which was in contrast with the case where a mutant promoter lacking the binding sites for Sp1 and YY1 was used as the reporter. Ca2+-stimulation signal increased nuclear Sp1 proteins and ATP2C1 mRNA levels in normal keratinocytes. In contrast, both these increases were suppressed in keratinocytes from HHD patients. These results indicate that Sp1 and YY1 transactivate the human ATP2C1 promoter via cis-enhancing elements and that incomplete upregulation of ATP2C1 transcription contributes to the keratinocyte-specific pathogenesis of HHD. This is a report describing the regulation of the expression of ATP2C1.

Base Sequence↗
PubMed2005

Topical application of ketoconazole stimulates hair growth in C3H/HeN mice.

Ketoconazole (KCZ) is an imidazole anti-fungal agent that is also effective in topical applications for treating seborrheic dermatitis and dandruff. Recently, topical use of 2% KCZ shampoo has been reported to have had a clinically therapeutic effect on androgenetic alopecia. The present study was conducted with the purpose of quantitatively examining the stimulatory effect of KCZ on hair growth in a mouse model. Coat hairs on the dorsal skin of seven week-old male C3H/HeN mice were gently clipped, and either 2% KCZ solution in 95% ethanol or a vehicle solution was topically applied once daily for three weeks. The clipped area was photographed, and the ratio of re-grown coat area was then calculated. The results demonstrated that 2% KCZ had a macroscopically significant stimulatory effect compared with the vehicle group (p<0.01, n=10). Repeated experiments showed similar effects, confirming the efficacy of KCZ as a hair growth stimulant. Although the therapeutic mechanism of topical KCZ for hair growth is unclear, our results suggest that topical applications of the substance are useful for treating seborrheic dermatitis accompanied by hair regression or male pattern hair loss.

Administration, Cutaneous↗
PubMed2005

An allogeneic cultured dermal substitute suitable for treating intractable skin ulcers and large skin defects prior to autologous skin grafting: three case reports.

Intractable skin ulcers that arise as secondary lesions from disease and full-thickness skin defects that result from skin tumor excision often need autologous skin grafting to close the wound. We developed an allogeneic cultured dermal substitute (CDS) to shorten the time needed to prepare a wound bed suitable for autologous skin grafting. The CDS was prepared by plating normal human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelo-collagen. The allogeneic CDS was then placed on the rinsed wound surface. This procedure was repeated twice a week for up to five weeks, until the wounds were closed by autologous skin grafting. In all three cases, after CDS treatment for two to five weeks, the wound conditions became suitable for skin grafting; these conditions had not been improved by conventional topical treatments, including topical basic fibroblast growth factor (bFGF). Healthy granulation tissue developed rapidly, concomitant with wound size reduction. The present results indicate that CDS is an excellent biological wound dressing for improving wound conditions so that they are suitable for subsequent autologous skin grafting as well as for shortening the treatment duration for skin ulcers and full-thickness skin defects.

Aged↗
PubMed2005

Localized periorbital edema induced by Ibuprofen.

We documented localized periorbital edema in one patient with ibuprofen sensitivity without underlying chronic urticaria. The reaction developed one hour after ingestion of 200 mg of ibuprofen. No systemic symptoms were observed. No other NSAIDs did not induce symptoms. This patient was able to tolerate doses of ibuprofen after pretreatment with terfenadine. These observations suggest that histamine played a central role in this ibuprofen-induced skin reaction. Treatment with terfenadine enabled the patient to tolerate ibuprofen without experiencing any side effects. To the best of our knowledge, this is the first reported case of periorbital edema induced by ibuprofen.

Adult↗
PubMed2005

Treatment of multiple lesions of Bowen's disease and squamous cell carcinoma with topical imiquimod.

We observed complete clinical and histopathologic remission of papules, plaques and nodules in two patients with multiple lesions of Bowen's disease and squamous cell carcinoma. Our findings indicate that topical imiquimod is a potentially promising therapeutic approach for the local treatment of early forms of cutaneous neoplasia, such as Bowen's disease and squamous cell carcinoma because it is a non-invasive therapy with a good cosmetic outcome. It may therefore be worthy of consideration in a subgroup of patients who cannot have or do not wish to have surgery.

Administration, Topical↗
PubMed2005

Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection.

In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFkappaB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection.

Adenoviridae↗
PubMed2005

Inhibitory effect of polyphenol-enriched apple extracts on mast cell degranulation in vitro targeting the binding between IgE and FcepsilonRI.

Extracts from immature fruit of the apple (Rosaceae, Malus sp.), which contain procyanidins (polymers of catechins) as the major ingredients, are known to inhibit histamine release from mast cells. We analyzed in this study the mechanism for the anti-allergic activity of two polyphenol-enriched apple extracts. These extracts, termed "crude apple polyphenol (CAP)" and "apple condensed tannin (ACT)", reduced the degranulation of mast cells caused by cross-linking of the high-affinity receptor for IgE (FcepsilonRI) with IgE and the antigen in a dose-dependent manner. Furthermore, western blotting revealed that phosphorylation of the intracellular signal-transduction molecules caused by cross-linking of FcepsilonRI was markedly decreased by the addition of CAP or ACT. We then analyzed the effects of CAP and ACT on the binding of the IgE antibody to FcepsilonRI on mast cells, which is the first key step in the allergic reaction mediated by mast cells, and found that this binding was markedly inhibited by both CAP and ACT. These results indicate that the inhibition of binding between FcepsilonRI and IgE by either CAP or ACT was the probable cause of the suppression of mast cell activation. This is the first report demonstrating the molecular mechanism for the anti-allergic effect of procyanidin-enriched extracts from apples.

Anti-Allergic Agents↗
PubMed2005

[An investigation of Trichophyton tonsurans infection in university students participating in sports clubs].

BACKGROUND: The prevalence of the infectious disease Trichophyton tonsurans is rapidly increasing in Japan, particularly in athletes of these sports such as judo. Recognition of the current prevalence of this disease not only in athletes of these sports but also in other athletes is important to prevent its further spread. SUBJECTS AND METHODS: In November, 2002 we used a questionnaire survey and hairbrush culture to identify hair dermatophyte carriers among 31 members of a university judo club. The dermatophyte carriers received antimycotic therapy, and all participants were taught infection prevention. Repeat screenings of the judo club members were performed 9 times over the following 18-month period. In addition, from November, 2003 to February, 2004 we screened 466 students of other university sports clubs for hair dermatophytes using the questionnaire survey and hairbrush culture technique. RESULTS: (1) Initially, we identified 11 (35%) of 31 members of the judo club as dermatophyte-positive by hairbrush culture. These dermatophyte carriers received antimycotic therapy, and implementation of infection prevention measures by all club members was initiated. Members continued to participate in matches and group judo practices under daily instructions for infection prevention. Tests performed on 9 occasions over a 1.5-year period following the initial testing showed all members of the judo club to be dermatophyte-negative and with no signs of tinea corporis. (2) Using a questionnaire and the hairbrush culture technique, we screened 466 members of other sports clubs, including 138 students who had weekly judo lessons and 185 students who were living in a dormitory. All were dermatophyte-negative by hairbrush culture, and no participant acknowledged any history or presence of eruptions suggestive of tinea. CONCLUSIONS: Our investigation suggests that the current spread of T. tonsurans infection in Japan is occurring mainly in athletes of high-contact sports such as judo. The successful control of this disease by the judo club in our university suggests that spread of the infection can be prevented without requiring that training be discontinued in a group fully informed about the disease.

Adult↗
PubMed2004

Deficiency of ATP2C1, a Golgi ion pump, induces secretory pathway defects in endoplasmic reticulum (ER)-associated degradation and sensitivity to ER stress.

Relatively few clues have been uncovered to elucidate the cell biological role(s) of mammalian ATP2C1 encoding an inwardly directed secretory pathway Ca2+/Mn2+ pump that is ubiquitously expressed. Deficiency of ATP2C1 results in a human disease (Hailey-Hailey), which primarily affects keratinocytes. ATP2C1-encoded protein is detected in the Golgi complex in a calcium-dependent manner. A small interfering RNA causes knockdown of ATP2C1 expression, resulting in defects in both post-translational processing of wild-type thyroglobulin (a secretory glycoprotein) as well as endoplasmic reticulum-associated protein degradation of mutant thyroglobulin, whereas degradation of a nonglycosylated misfolded secretory protein substrate appears unaffected. Knockdown of ATP2C1 is not associated with elevated steady state levels of ER chaperone proteins, nor does it block cellular activation of either the PERK, ATF6, or Ire1/XBP1 portions of the ER stress response. However, deficiency of ATP2C1 renders cells hypersensitive to ER stress. These data point to the important contributions of the Golgi-localized ATP2C1 protein in homeostatic maintenance throughout the secretory pathway.

Animals↗
PubMed2004

Differentiation-specific localization of catalase and hydrogen peroxide, and their alterations in rat skin exposed to ultraviolet B rays.

BACKGROUND: It is now well known that to counteract oxidative stress and maintain a redox balance within the cells, the skin is equipped with a network of antioxidant enzymes. Among these enzymes, SOD and CAT are the major antioxidant enzymes protecting the epidermis. OBJECTIVE: In the present study, we have attempted to demonstrate the distribution of endogenous H(2)O(2) and the expression of CAT in the epidermis of newborn rats, in relation to epidermal differentiation, and alterations after UVB irradiation. METHODS: We have localized the antioxidant enzyme catalase (CAT) using immunohistochemical analysis, and hydrogen peroxide (H(2)O(2)) using in situ H(2)O(2) assay. RESULTS: We demonstrated that keratinocytes in the stratum granulosum produced H(2)O(2), and CAT was mainly expressed in the cytoplasm of cells from the stratum granulosum to the lower corneum, and in the cell periphery in the stratum granulosum of newborn rat skin. The results suggested that generation of H(2)O(2) and expression of CAT were coordinated and were indicative of epidermal differentiation as well as of the role of CAT in repairing redox damage by discomposing H(2)O(2). When rat skin was exposed to 50 mJ/cm(2) of ultraviolet B (UVB) rays, the accumulation of H(2)O(2) in the upper epidermis increased twenty-four hours later, while CAT immunoreactivity decreased. CONCLUSION: The results suggested that generation of H(2)O(2) and expression of CAT were coordinated and were indicative of epidermal differentiation as well as of the role of CAT in repairing redox damage by discomposing H(2)O(2). In addition, UVB-induced oxidative stress in the present study seemed to alter the endogenous and differentiation-specific redox balance between H(2)O(2) and CAT.

Animals↗
PubMed2004

Engraftment of umbilical cord epithelial cells in athymic mice: in an attempt to improve reconstructed skin equivalents used as epithelial composite.

BACKGROUND: The umbilical cord (UC) is composed of connective tissue called Wharton Jelly, covered by a simple epithelium believed to derive from amniotic membrane epithelium. In previous studies, we observed that the umbilical cord epithelium (UCE) in situ displayed stratified epithelial structures, in some areas that expressed cytokeratins and differentiation markers as characteristic of keratinocytes under airlifted condition in vitro, UCE cells grown on collagen gel displayed more keratinocytes characteristics. OBJECTIVE: To study the ability of UCE cells to undergo terminal differentiation when grown in the most proper environment. METHODS: UCE cells were seeded onto the surface of a fibroblast-populated collagen gel then grafted onto the back of nude mice and examined using immunohistochemical techniques and by transmission electron microscope (TEM). RESULTS: Post-grafted UCE cells formed a stratified epithelial structure similar to that formed by keratinocytes. Although immunohistochemical staining of UCE cells in skin grafts showed a similar pattern to that seen with the keratinocyte controls, UCE cells maintained many of their own intrinsic characteristics, such as stronger expression of mucous membrane cytokeratins and expression of simple epithelial cytokeratin. Notably, with longer transplant periods, expression of keratinocyte characteristics in UCE cells increased while expression of simple epithelial properties decreased. We observed formation of a complete basement membrane, which had not been achieved using an in vitro model. CONCLUSIONS: Grafted UCE cells in an animal model maintain their own intrinsic characteristics, but display the stratified morphogenesis, terminal differentiation and ultrastructures similar to those seen in keratinocytes.

Animals↗
PubMed2004

Polymorphisms in the Fc epsilon RI beta promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between Fc epsilon RI beta and atopy.

The beta subunit of the high-affinity IgE receptor (FcepsilonRI) plays an important role in IgE-mediated allergic reactions as an amplifier for cell surface expression and signal transduction of FcepsilonRI. FcepsilonRIbeta is presumed to be one of the genes linked with atopic diseases. However, the validity of the associations previously found between single nucleotide polymorphisms (SNPs) in FcepsilonRIbeta and atopic diseases is questionable. In the present study, we found correlation between the SNP of FcepsilonRIbeta at +6960A/G, resulting in a Glu237Gly amino acid substitution, and the cell surface expression level of FcepsilonRI on blood basophils, although it has been shown that the Glu237Gly mutation itself does not affect the surface expression or function of FcepsilonRI. We additionally found four SNPs in the promoter region of FcepsilonRIbeta, among which -426T/C and -654C/T were tightly linked with +6960A/G. Reporter plasmids carrying the -426C and -654T promoter displayed higher transcriptional activity than those carrying the -426T and -654C promoter. We found that transcription factor YY1 preferentially bound and transactivated the -654T promoter. Furthermore, expression of FcepsilonRI beta-chain mRNA in basophils from individuals who have the minor heterozygous genotype was significantly higher than that of the major homozygous genotype. These results suggest that the SNPs in the FcepsilonRIbeta promoter are causally linked with atopy via regulation of FcepsilonRI expression.

5' Flanking Region↗
PubMed2004

MD-2 is required for the full responsiveness of mast cells to LPS but not to PGN.

To address the role played by MD-2 in mast cell recognition of LPS, we examined bone marrow-derived mast cells (BMMCs) from MD-2 gene-targeted mice. BMMCs from MD-2-/- mice showed impaired cytokine production (TNF-alpha, IL-6, IL-13, and IL-1beta) in response to LPS from Escherichia coli, but not to peptidoglycan (PGN) from Staphylococcus aureus. In a mast cell-dependent acute septic model, MD-2 deficiency of mast cell resulted in significantly higher mortality due to defective neutrophil recruitment and the production of cytokines in the peritoneal cavity, which was similar to mice with TLR4-deficient mast cells. The TLR2-dependent activation of skin mast cells by PGN was not altered by the absence of MD-2 in vivo. Collectively, MD-2 is essential for the recognition of LPS by TLR4 but not for that of PGN by TLR2 of mast cells.

Animals↗
PubMed2004

Evidence against requirement of Ser41 and Ser45 for function of PU.1 -- molecular cloning of rat PU.1.

The transcription factor PU.1 plays an important role in the development of the myeloid and lymphoid lineages and regulates the transcription of several genes expressed in these cells. Ser41 is conserved in the acidic region (33-47) of PU.1 from a variety of eukaryocytes and has been reported to be one of the two important Ser residues (S41 and S45) for the function of PU.1. In the present study, however, we found that rat PU.1 has Gly at position 41. To elucidate the role of amino acid residues at 41 and 45 in functions of PU.1, we generated mutants of rat PU.1, G41S, G41A, and S45A, and analyzed their transcription-enhancing activities by using two different systems, transient reporter assay system and retroviral transfection system. The amino acid substitution at 41 of PU.1 causes no effect on both transcription-enhancing activity for M-CSF receptor promoter and the cooperative transcription-enhancing activity with GATA-1 for FcRI alpha-chain promoter. Furthermore, the substitution at 41 also had no effect on the activity to induce monocyte-specific gene expression in the bone marrow-derived hematopoietic cells. From these results, we conclude that Ser41 as well as Ser45 are not essential for the promoter-upregulating function of PU.1.

Amino Acid Sequence↗
PubMed2004

TWEAK/Fn14 interaction stimulates human bronchial epithelial cells to produce IL-8 and GM-CSF.

TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulates cellular proliferation, angiogenesis, inflammation, and apoptosis. In this study, we investigated the effect of TWEAK on human bronchial epithelial cells. A human bronchial epithelial cell line, BEAS2B, expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced IL-8 and GM-CSF upon TWEAK stimulation in a dose-dependent manner, which was abrogated by anti-Fn14 blocking antibody. TWEAK induced phosphorylation of IkappaBalpha and BAY11-7082, a selective inhibitor of IkappaBalpha phosphorylation, inhibited the TWEAK-induced IL-8 and GM-CSF production by BEAS2B cells. Moreover, primary cultured human bronchial epithelial cells also expressed Fn14 and produced IL-8 and GM-CSF upon TWEAK stimulation. Collectively, TWEAK stimulated human bronchial epithelial cells to produce IL-8 and GM-CSF through Fn14. Because IL-8 and GM-CSF are associated with inflammatory conditions, these results suggest that TWEAK/Fn14 interaction may play some roles in airway inflammatory responses.

Apoptosis Regulatory Proteins↗