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Biomedical subjects

M Mizoguchi

Publications and source records attributed to M Mizoguchi.

At least 19 recordsLinked to original sources

Elevated serum IgA anticardiolipin antibody levels in adult Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis characterized by palpable purpura on the lower extremities and IgA-dominant immune complex deposition within the wall and lumen of dermal vessels in the lesions. This disorder is associated, to varying degrees, with joint, gastrointestinal and renal involvement. Antiphospholipid antibodies, including anticardiolipin antibodies (aCL Abs), are a heterogeneous group of circulating autoantibodies found in patients with autoimmune and infectious diseases. OBJECTIVES: To investigate the possible role of aCL Abs in adult HSP, we measured levels of serum IgA, C-reactive protein (CRP), aCL Abs of the IgG, IgM and IgA isotypes and anti-beta(2)-glycoprotein I (beta(2)GPI)-dependent aCL Abs in adult patients with HSP. We evaluated the correlation between these biological parameters and the clinical manifestations. METHODS: Adult patients with HSP with an initial cutaneous manifestation of palpable purpura on their lower extremities seen between 2001 and 2005 in our department were retrospectively reviewed. Patients with known connective tissue diseases were not included in the study. Histological examination of all patient skin biopsy specimens revealed leucocytoclastic vasculitis in the upper and mid-dermis. Direct immunofluorescence analysis showed prominent deposits of IgA in the capillary walls of all patients. Blood samples were taken at the time that the patient presented. Serum levels of aCL Abs and anti-beta(2)GPI-dependent aCL Abs were measured by enzyme-linked immunosorbent assay. RESULTS: Twenty adult patients with HSP (12 men and eight women), mean age 62.2 years (range 23-81) were enrolled. IgA aCL Abs were found in 15 of the 20 patients (75%). All were negative for IgG aCL Abs, IgM aCL Abs and anti-beta(2)GPI-dependent aCL Abs. The elevation of serum IgA aCL Abs in the 15 patients showed a significant correlation with serum IgA and CRP levels (r(s) = 0.91, P = 0.0007; r(s) = 0.80, P = 0.0026, respectively). Levels of serum IgA aCL Abs were also significantly associated with arthralgia (P = 0.022) and proteinuria according to urinalysis (P = 0.013). CONCLUSIONS: Serum levels of IgA aCL Abs are elevated in the initial active stage of adult HSP, suggesting that serum IgA aCL Abs may play some role in the onset of adult HSP. We believe that serum IgA aCL Abs might be an indicator of adult HSP activity.

Adult↗

Enhanced skin regeneration by nanoegg formulation of all-trans retinoic acid.

All-trans retinoic acid (atRA) which could smooth wrinkles and produce less pigmented skin after a few months of treatment has been studied in research into topical treatments for a potent inhibitor of new melanin production. However, the clinical responses of commercial atRA cream predominantly comprise severe inflammation. We report a novel nanotechnology "nanoegg" system giving improved effects of atRA self-assembly which were coated by CaCO3. Dorsal areas of hairless mouse and porcine skin were employed for administration of nanoegg ointment and commercial products. The mRNA for heparin-binding epidermal growth factor-like growth factor (HB-EGF) from tissues was measured by a real-time PCR method. All tissues were stained for detection of hyaluronate and the thickness of the epidermis. A clinical trial in humans was carried out at St. Marianna University in Japan. As a result, the irritation and inflammation associated with atRA molecules were substantially reduced. The physicochemical instability of atRA was also dramatically improved. Furthermore, nanoegg enhanced marked expression of mRNA for HB-EGF from keratinocytes, which is known as one of the markers of keratinocyte turnover. Also, production of hyaluronate was surprisingly in the intercellular spaces of the basal and spinous cell layers 2 days after treatment. Even at the low concentration of atRA in the nanoegg system, the proliferation and differentiation of keratinocyte was somewhat enhanced. A nanoegg may thus not only prevent adverse effects, but also markedly enhance the main effect.

Administration, Topical↗

Acquired symmetrical dermal melanocytosis (naevus of Hori) developing after aggravated atopic dermatitis.

BACKGROUND: Acquired symmetrical dermal melanocytosis (ASDM) is a pigmentary disorder characterized by blue-brown macules most frequently seen on the face of young and middle-aged Asian women. ASDM developing after other skin diseases has not been previously reported. OBJECTIVES: To characterize the clinical and histopathological features of ASDM associated with atopic dermatitis (AD) and to elucidate the differences between AD-associated ASDM and idiopathic ASDM. METHODS: Sixteen patients with ASDM associated with AD were examined clinically and histopathologically and were compared with 69 patients with idiopathic ASDM. RESULTS: The AD patients associated with ASDM consisted of four men and 12 women with a mean age of 32.8 +/- 13.1 years. Most patients remembered that the pigmented macules appeared in places where refractory eczema had existed for a long time. The marked preponderance in females and the appearance in the early reproductive period were common features of AD-associated ASDM and idiopathic ASDM. AD-associated ASDM was most commonly observed on the forehead (68.8%) and on the backs of the hands (50.0%), whereas 89.9% of idiopathic ASDM was seen on the cheeks. There was no significant difference in the number of dermal melanocytes between AD-associated ASDM and idiopathic ASDM. Electron microscopic studies demonstrated many mature melanocytes and smaller numbers of immature melanocytes in the dermis. Some melanocytes were seen adjacent to mast cells. CONCLUSIONS: AD-associated ASDM does not appear to be rare in Japan. ASDM may be triggered in AD patients by sunlight exposure, some alterations in sex hormones and/or persistent cutaneous inflammation. Histamine and stem cell factor produced by mast cells may play crucial roles in the pathogenesis of AD-associated ASDM.

Adult↗

A successfully treated case of mycetoma due to Nocardia veterana.

We report a successfully treated case of mycetoma from which an unusual Nocardia species was isolated. The isolate was identified as N. veterana by biochemical characterization and 16S ribosomal RNA gene sequencing, and it has not been previously reported as a causative agent of human mycetomas. Treatment with various antibiotics over 6 years and surgical resection failed to cure the disease. However, the combination of intravenous imipenem/cilastatin and amikacin along with oral clarithromycin and minocycline proved very effective in this case. This is the first case report of mycetoma due to N. veterana in a clinical setting.

Adult↗

Excessive expression of Txk, a member of the Tec family of tyrosine kinases, contributes to excessive Th1 cytokine production by T lymphocytes in patients with Behcet's disease.

Excessive Th1 cell function is importantly involved in the pathogenesis of Behcet's disease (BD). We previously found that Txk, a member of the Tec family of tyrosine kinases, acts as a Th1 cell specific transcription factor. To investigate immune aberration in the pathogenesis of BD, we studied the expression of Txk and Th1 cytokines in peripheral blood lymphocytes (PBL) and skin lesions in patients with BD. Cytokine production by the lymphocytes was assessed using ELISA. PBL produced excessive Th1 associated cytokines including IFN-gamma and IL-12 spontaneously and in response to exogenous HSP60-derived peptide stimulation, which was shown to induce proliferation of PBL, in patients with BD. Circulating CD4+ T cells expressed excessive Txk protein. A majority of cells infiltrating into skin lesions expressed IFN-gamma in the BD specimens. IL-12 and IL-18 were also expressed in the mononuclear cell aggregates. Lymphocytes accumulating in the skin lesion expressed higher levels of Txk as compared with atopic dermatitis lesions, a typical Th2 disease. IFN-gamma, IL-18 and Il-12 were detected in the BD skin lesions, which may induce preferential development of Th1 cells in patients with BD. The mononuclear cell aggregates contained Txk expressing cells in such skin lesions. Collectively, Txk expressing Th1 cells and the Th1 associated cytokines may play a critical role in the development of skin lesions in BD.

Adult↗

Combination therapy consisting of week pulses of oral terbinafine plus topical application of terbinafine cream in the treatment of onychomycosis.

BACKGROUND: Terbinafine, based on its pharmacokinetic properties, is a good candidate for pulse therapy. There are, as yet, no current guidelines for a terbinafine 1-week pulse regimine. OBJECTIVE: To determine the optimal 1-week pulse dosing regimen for combination therapy of oral terbinafine with complementary 1% terbinafine cream for the treatment of onychomycosis. DESIGN: A total of 69 onychomycosis patients received 250 mg terbinafine, given orally once daily for 7 days as 1-week pulses, separated by intervals of 2-3 weeks, until the desired improvement was observed. A daily application of 1% terbinafine cream was advised through to the evaluation date at 12 months follow-up. The treatment regimens were compared based on the number of pulses and the duration of treatment. RESULTS: The 45 patients (65.2%) who achieved complete cure received an average of 7.8+/-3.5 pulse treatments over 4.8+/-2.6 months. The optimal terbinafine dosing regimen consisted of alternate 1-week pulses, with most patients on this regimen (19/20 cases; 95%) achieving total cure. CONCLUSION: Favorable treatment outcome was gained from this terbinafine 1-week pulse regimen and also better compliance compared with a standard daily regimen.

Administration, Oral↗

Methotrexate inhibits proliferation and regulation of the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by cultured human umbilical vein endothelial cells.

BACKGROUND: The mechanism by which a low dose of methotrexate (MTX) works to treat psoriasis is not clear. The overexpression of cell adhesion molecules on dermal vessels is important in the pathogenesis of psoriasis and is probably induced by upregulation of tumour necrosis factor (TNF)-alpha. OBJECTIVES: To determine the effects of MTX at concentrations comparable with in vivo levels after the administration of low-dose MTX to human umbilical vein endothelial cells (HUVEC) on the growth and expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). METHODS: Cell proliferation assay, immunostaining, immunoblotting, cell enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were performed to examine the effects of MTX on HUVEC. RESULTS: MTX inhibited the proliferation of HUVEC at 10-7 mol L-1 and 10-6 mol L-1 without showing cytotoxic effects. It also inhibited TNF-alpha-induced ICAM-1 and VCAM-1 expression by HUVEC at 10-6 mol L-1. The inhibitory effect of MTX was more pronounced on ICAM-1 expression than on VCAM-1 expression. RT-PCR analysis revealed that TNF-alpha-induced ICAM-1 gene expression was strongly downregulated by MTX. CONCLUSIONS: Low-dose MTX may act on psoriasis by suppressing the TNF-alpha-induced expression of ICAM-1 and VCAM-1 by vascular endothelial cells. Inhibition of neovascularization may be another mechanism of action of MTX.

Blotting, Western↗

Abbreviated oral itraconazole therapy for tinea corporis and tinea cruris.

The present study was designed to determine the lowest dose of orally administered itraconazole and the shortest duration of therapy necessary for treatment of tinea corporis and tinea cruris. For all patients, the itraconazole dose was 100 mg twice a day immediately after meals. Twenty-eight patients received itraconazole on days 1 and 8, 12 patients received itraconazole on days 1 and 2, and five patients received itraconazole only on day 1. Clinical and mycological evaluations were performed at baseline and on day 14. Based on the clinical and mycological responses, treatment efficacy was classified as excellent, good, fair, or poor. "Excellent" and "good" responses made up 86% of the first group, 100% of the second group, and 20% of the third group. A comparison of efficacy ratings of the three regimens showed that the patients who received a single 200-mg dose had a significantly inferior outcome compared with the other two groups. We conclude that an abbreviated oral regimen of itraconazole for treatment of tinea corporis and tinea cruris requires a total dose of at least 400 mg to induce a favorable outcome.

Administration, Oral↗

Classification of abomasal displacement in cows according to histopathology of the liver and clinical chemistry.

Histopathological features of livers and blood chemical values in cows with abomasal displacement were investigated. Liver biopsy samples were collected during redressment operations in 92 cows with abomasal displacement, and the samples were stained with haematoxylin and eosin or periodic acid Schiff (PAS). Blood was collected for chemical tests. Livers were histopathologically divided into the following four types: normal histology cases (21%), fatty degeneration cases (36%), cloudy swelling cases (19%) and fatty degeneration cases with cloudy swelling (24%). The number of PAS-positive samples was significantly higher in the normal histology group and significantly lower in the severe fatty degeneration group and severe cloudy swelling group. Cows with fatty degeneration had significantly higher levels of serum 3-hydroxybutyric acid, non-esterified fatty acid and aspartate aminotransferase than did those with cloudy swelling or normal histology. The results indicate that the morbid conditions of cows with abomasal displacement can be classified into four types.

3-Hydroxybutyric Acid↗

Mutations of the PKD1 gene among Japanese autosomal dominant polycystic kidney disease patients, including one heterozygous mutation identified in members of the same family.

More than 80 mutations of the PKD1 gene have been reported, mostly in patients from Western Europe. New techniques are being used to detect an increasing number of mutations, even in the homologous region of the PKD1 gene. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) or denaturing high-performance liquid chromatography (DHPLC) analyses were performed in the present study to screen mutations from exon 23 to exon 46 in the PKD1 gene and in the entire PKD2 gene. When an abnormal pattern was found in PCR-SSCP or DHPLC, the PCR products were directly sequenced. Four mutations were identified in the PKD1 gene: a missense mutation (C47413T causing T3509M in exon 35), a splicing mutation (del 20bp in 75 bp of intron 43), and two nonsense mutations (C48566A causing C3693X in exon 38, and C51237T causing Q4124X in exon 45). The nonsense mutation Q4124X existed in only two of three affected sib members in family K68. The pattern of the restriction enzyme digest and the haplotype analysis confirmed the presence of a heterozygous mutation in the family. Fifteen single nucleotide polymorphisms were identified in this study. Two of them (C50439A and C51659T) can be used as intragenic polymorphic markers.

Adult↗

Enhanced expression of the high-affinity receptor for IgE (Fc(epsilon)RI) associated with decreased numbers of Langerhans cells in the lesional epidermis of atopic dermatitis.

Epidermal Langerhans cells (LCs) and the high-affinity receptor for IgE (Fc(epsilon)RI) on their surface are considered important in the pathogenesis of atopic dermatitis (AD). We investigated the numbers of epidermal LCs and their Fc(epsilon)RI expression in patients with AD and healthy controls. Biopsy specimens taken from lesional skin from 17 patients with AD, non-lesional skin from five patients with AD and normal skin from five healthy individuals were immunohistochemically stained with a monoclonal antibody against CD1a or with either of two monoclonal antibodies against two different epitopes of Fc(epsilon)RI alpha chain. Many dendritic cells were positively stained with anti-CD1a antibody in the epidermis of each skin sample, and fewer cells were stained with anti-Fc(epsilon)RI antibodies. The numbers of epidermal LCs positive for Fc(epsilon)RI were significantly increased in both lesional and non-lesional skin from AD patients compared with those in normal skin, suggesting important roles of Fc(epsilon)RI+LCs in the pathogenesis of the disease. In contrast, the numbers of total epidermal LCs (CD1a-positive) were decreased in AD lesional skin compared with those in non-lesional skin from AD patients and in normal skin from healthy subjects. Together with our finding that the numbers of epidermal LCs were negatively correlated with the clinical severity of the AD lesions, we concluded that epidermal LCs may decrease in some conditions of AD, probably in lesions with severe inflammation.

Adult↗

Establishment and characterization of a mouse neural crest derived cell line (NCCmelan5).

Stem cell factor (SCF) and endothelin 3 (EDN3) are both necessary for melanocyte development. We have established an immortal cell population of neural crest cells from C57BL/6 mice, cultivating them with SCF, EDN3 and 15% fetal calf serum without feeder cells, and have designated that line as C57NCC SE. C57NCC SE consists of a population of melanocytes in various stages of differentiation. We used a single-cell cloning method, in which only one cell is transferred to each new culture plate, and succeeded in establishing an immortal cell line named NCCmelan5. All NCCmelan5 cells were positive for KIT (SCF receptor), HMB45 (human melanosomal antigen), tyrosinase-related protein-1 (TYRP1), tyrosinase-related protein-2 (TYRP2), tyrosinase and endothelin receptor B (EDNRB) and all could oxidize 3,4-dihydroxyphenylalanine (DOPA) to form melanin. Measurement of their DNA content revealed that 88.6% of the cells were in the G0-G1 phase, suggesting that they retained normal DNA ploidy. Thus, NCCmelan5 cells have the characteristics of mature melanocytes except that they are immortal; these cells may prove useful to study factors that directly affect melanogenesis and melanocyte development without the influence of feeder cells. It is clear that our attempt to establish immortal cell lines from murine neural crest cells would have never been successful without the addition of SCF and EDN3, since C57NCC SE and NCCmelan5 cells require those factors to proliferate.

Animals↗