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Biomedical subjects

M Mizoguchi

Publications and source records attributed to M Mizoguchi.

At least 37 records · Page 2Linked to original sources

Serum levels of soluble stem cell factor and soluble KIT are elevated in patients with atopic dermatitis and correlate with the disease severity.

BACKGROUND: Mast cell infiltration in skin lesions of atopic dermatitis (AD) is considered to play an important role in the pathogenesis of the disease. The most common factor that stimulates mast cell growth, migration and differentiation is stem cell factor (SCF), and the interaction of SCF and its receptor, KIT (tyrosine kinase transmembrane receptor), appears to be the key event in the recruitment and proliferation of mast cells. OBJECTIVES: To determine whether any altered metabolism of SCF and/or KIT is present in patients with AD. METHODS: We measured serum levels of soluble SCF (sSCF) and soluble KIT (sKIT) using enzyme-linked immunosorbent assay in 54 patients with AD, five patients with erythrodermic psoriasis vulgaris and 64 healthy individuals. RESULTS: Serum levels of both peptides in AD patients were significantly higher than those in healthy individuals, whereas patients with psoriasis vulgaris did not show any difference from healthy controls. Both sSCF and sKIT levels were positively correlated with the disease severity in AD patients, and decreased after effective treatment with topical corticosteroids. Conclusion Serum levels of sSCF and sKIT may be useful indicators for evaluation of the activity and severity of AD.

Administration, Topical↗

Overexpression of transforming growth factor-beta3 immunohistochemical staining in extramammary Paget's disease, but downregulated expression in Bowen's disease.

BACKGROUND: The role of transforming growth factor-beta (TGF-beta) in carcinogenesis is complex, with some reports indicating a tumor inhibition role and others indicating a tumor promotion role. In particular, TGF-beta3 is thought to play a key role in controlling epithelial homeostasis. Immunopositive p53 has been demonstrated in a variety of human malignant tumors and its role in oncogenesis and tumor progression is thought to be important. Extramammary Paget's disease (EPD) and Bowen's disease are skin cancers of unknown histogenesis. OBJECTIVE: To clarify the role of TGF-beta3 and p53 in EPD and Bowen's disease and to better understand the origin of these disorders. METHODS: Specimens were obtained from 12 patients with EPD and 12 patients with Bowen's disease seen at our clinic between 1993 and 2000. TGF-beta3 and p53 immunohistochemical staining was performed. RESULTS: In three of the 12 EPD patients and five of the 12 Bowen's disease patients, positive p53 staining was detected. In contrast, TGF-beta3 overexpression was detected in all EPD patients, whereas downregulated TGF-beta3 expression was detected in all Bowen's disease patients. CONCLUSIONS: The present data suggest different roles for TGF-beta3 in abnormal epidermal cells in EPD and Bowen's disease. Thus, TGF-beta3 expression may be modulated differently via a p53-dependent or -independent pathway in the pathogenesis of EPD and Bowen's disease. Moreover, high TGF-beta expression appears to be a useful indicator of tumor activity in EPD.

Aged↗

Analysis of p53, p21(Waf1/Cip1) and TGF-beta(3) immunohistochemical staining in Bowen's disease.

BACKGROUND: The p53 gene is one of a family of tumor suppressor genes that have been implicated in the genesis of a wide variety of malignant neoplasms including Bowen's disease. Its role in oncogenesis and tumor progression is thought to be of importance. Transforming growth factor beta (TGF-beta) is the most potent known inhibitor of the progression of normal epithelial cells through the cell cycle. p21(Waf1/Cip1) is thought to mediate p53 signaling induced by DNA-damaging agents to arrest the cell cycle. OBJECTIVE: The present study evaluates the expression of p53, p21(Waf1/Cip1) and TGF-beta(3) protein and speculates on their role in Bowen's disease. METHODS: Sixteen patients seen at our clinic between 1993 and 2000 were examined. We analyzed p21(Waf1/Cip1), p53 and TGF-beta(3) immunohistochemical staining in all specimens. RESULTS: In 7 of the Bowen's disease patients, overexpression of p53-positive cells was present in the middle and basal layers, and intense staining of p21(Waf1/Cip1) was observed in the upper spinous layers. In the other 9 Bowen's disease patients, we found positively stained cells for p21(Waf1/Cip1) but negative p53 immunostaining in the upper epidermal layer. Downregulated TGF-beta(3) expression was detected in all layers except the upper spinous layers. CONCLUSION: These observations suggest different roles for p21(Waf1/Cip1) and p53 within abnormal cells in Bowen's disease. p21(Waf1/Cip1) may induce terminal differentiation to the superficial layer in Bowen's disease via either a p53-independent or -dependent pathway. Moreover, downregualtion of TGF-beta(3) immunostaining provides relevant information concerning the pathogenesis of Bowen's disease.

Aged↗

Safe and effective treatment of refractory facial lesions in atopic dermatitis using topical tacrolimus following corticosteroid discontinuation.

BACKGROUND: Topical corticosteroids are commonly applied in atopic dermatitis (AD) treatment. However, their chronic use may be associated with significant side effects at the application site. Skin atrophy and other undesirable effects are frequently seen after long-term corticosteroid treatment. In addition, when application of corticosteroids is discontinued, a rebound phenomenon in the facial lesions can occur within several days. Topical tacrolimus, an immunosuppressant currently used to prevent rejection after solid-organ transplantation, presents a potential alternative therapeutic agent for AD. OBJECTIVE: The present study is the first trial designed to evaluate the efficacy and safety of topically applied tacrolimus ointment after corticosteroid discontinuation without a washout phase in severe, long-term facial AD. PATIENTS/METHODS: Forty-seven patients with facial refractory AD were recruited, of whom 38 had undergone topical corticosteroid treatment for at least 4 weeks before enrollment (group 1) and the other 9 had not received steroid treatment (group 2). All 47 patients received 0.1% tacrolimus ointment, and the severity index and pruritus score were assessed as an AD clinical activity index every week and compared with baseline data. RESULTS: Both the severity index and pruritus score improved significantly in group 1 after 1 and 2 weeks of application (p < 0.01, respectively). Group 2 showed the greatest improvement at 4 weeks (p < 0.05). In this trial, none of the patients experienced a rebound phenomenon associated with tacrolimus treatment. A transient sensation of burning at the application site was the only adverse event in 31 of the 47 (66%) enrolled patients, but this condition improved after several days. Spectrophotometric assessment of the facial lesion following treatment revealed significant improvement in group 1 (p < 0.05). CONCLUSION: The present results indicate that topical tacrolimus treatment following corticosteroid discontinuation is safe and effective in refractory facial AD.

Administration, Topical↗

Stem cell factor and/or endothelin-3 dependent immortal melanoblast and melanocyte populations derived from mouse neural crest cells.

Stem cell factor (SCF) and endothelin-3 (ET3) are both necessary for melanocyte development. In order to obtain immortal cell populations of melanoblasts that can survive without feeder cells, we first obtained an immortal cell population of neural crest cells (NCCs) from Sl/+ and +/+ mice of strain WB by incubating with a culture medium supplemented with SCF and ET3, and then we designated them as NCC-SE3 cells. NCC-SE3 cells were bipolar, polygonal, or round in shape and possessed melanosomes of stages I-III (mainly stage I). They were positive to dihydroxyphenylalanine (DOPA) reaction and expressed KIT (a receptor tyrosine kinase), tyrosinase, tyrosinase-related protein-1 (TRP1), tyrosinase-related protein-2 (TRP2), and endothelin-B receptor (ETRB) as determined by immunostaining. We next cultured NCC-SE3 cells by changing culture medium from the one supplemented with SCF + ET3 to the one supplemented with SCF or ET3. NCC-SE3 cells cultured with ET3 alone, designated as NCC-E3 cells, were bipolar in shape and had mainly stage II melanosomes and expressed the same proteins as did NCC-SE3 cells. However, NCC-SE3 cells cultured with SCF alone, designated as NCC-S4.1 cells, were polygonal in shape and had mainly stage I melanosomes. They are thought to be more immature because they were positive to KIT, TRP1, and TRP2, but not to ETR(B), tyrosinase, and DOPA reaction. When 12-O-tetradecanoylphorbol 13-acetate and cholera toxin were added to the culture medium, NCC-S4.1 cells changed shape from polygonal to bipolar and became DOPA-positive. This suggests that NCC-S4.1 cells are melanoblasts that have the potential to differentiate into melanocytes. These cell populations will be extremely useful to study factors that affect melanocyte development and melanogenesis.

Animals↗

A case of unilateral dermatomal cavernous haemangiomatosis.

We report a 39-year-old man with unilateral dermatomal cavernous haemangiomatosis (UDCH). Clinically, three haemangiomas were unilaterally distributed in the C6 dermatome. Histologically, these haemangiomas were distinct from routine cavernous haemangioma in that hyperplasia of smooth muscle cells on the vascular wall was observed, and electron microscopy showed that smooth muscle cells contained myofilaments and a crystal-like structure in the endothelial cells. This is distinct from Weibel-Palade bodies, which are rod-shaped cytoplasmic organelles measuring approximately 0.1 microm in diameter with a parallel linear structure. In UDCH, the haemangiomas occur only in the skin. They are clinically and histologically similar to those of blue rubber bleb naevus syndrome (BRBNS), but in BRBNS there are multiple haemangiomas in the digestive tract and other organs. UDCH is distinct from Maffucci syndrome in that enchondromata and malignant tumours are absent. To our knowledge, this is the second case of UDCH reported in the literature.

Adult↗

Neuroendoscopic biopsy of tectal glioma: a case report.

OBJECTIVE AND IMPORTANCE: A type of intrinsic dorsal midbrain glioma known as benign tectal glioma can cause obstructive hydrocephalus. Because of its slow progress and relatively good prognosis, initial treatment should be cerebrospinal fluid diversion and biopsy. CLINICAL PRESENTATION: We report a 24-year-old man with obstructive hydrocephalus from a tectal glioma, who was admitted to the hospital for malfunction of a shunt placed 16 years previously. INTERVENTION: Magnetic resonance imaging demonstrated enlargement of the dorsal midbrain associated with increased signal intensity on T2-weighted images and fluid attenuation inversion recovery (FLAIR) images. No enhancement occurred with contrast administration. We performed a neuroendoscopic third ventriculostomy and biopsy of the tumor. Histologic examination of the specimen obtained disclosed a low-grade astrocytoma. No postoperative neurologic complications occurred. CONCLUSION: FLAIR images were superior to T2-weighted images in demonstrating abnormal intensity in the dorsal midbrain. Neuroendoscopy confirmed a yellowish tumor inferior to the posterior commissure occluding the entrance of the aqueduct, an observation useful in planning biopsy of the lesion. As the tumor apparently had existed for a number of years, the case supports the notion that the prognosis associated with these tumors is good.

Adult↗

Differences among chitin synthase I gene sequences in Trichophyton rubrum and T. violaceum.

Nucleotide sequences of chitin synthase 1 (CHS1) gene were analysed for the phylogenetic relation between Trichophyton violaceum and T. rubrum, including two isolates of T. raubitschekii and one isolate of T. rubrum var. nigricans. About 620-bp genomic DNA fragments of the CHS1 gene were amplified from these dermatophytes by polymerase chain reaction (PCR) and sequenced. The CHS1 nucleotide sequences of these dermatophytes showed more than 95% similarity between the species. The phylogenetic analysis of their sequences revealed that T. rubrum was genetically distinct from T. violaceum. The specific restriction endonuclease site for HinfI was present in the CHS1 gene sequence of T. rubrum but not in that of T. violaceum. A molecular analysis of CHS1 genes will provide useful information for the identification of these Trichophyton species and the understanding of their evolution.

Animals↗

Effect of highly active antiretroviral therapy on the incidence of HIV-related cytomegalovirus retinitis and retinal detachment.

Cytomegalovirus retinitis (CMVR) is the most common intraocular infection encountered in ophthalmic practices. To assess the impact of highly active antiretroviral therapy (HAART) on the incidence of CMVR and subsequent retinal detachments, a retrospective review of the HIV+ patients seen at a single university and community-based practice between 1992-1993 (group 1), before the advent of protease inhibitors, was compared with the data obtained from October 1996 to October 1997 (group 2) and October 1997-1998 (group 3), after the widespread use of HAART. The incidence of CMVR and retinal detachment rates for each group was calculated and compared. Twenty five (2.6%) of 974 HIV+ patients in group 1 developed CMVR. Of these, four patients developed retinal detachment (16%). Group 2 had a total of 1084 HIV+ patients, 18 (1.7%) of whom developed CMVR, which indicates a 35% decline of the incidence of CMV retinitis at our institution (p = 0.052, Odds ratio = 0.533, Confidence interval 0.28-1.01) and three patients (20%) developed retinal detachment. Only 1 patient (0.07%) of 1274 patients in group 3 developed CMVR, which represents a 99% reduction since 1993 (p = 0.0000000456). We conclude that the incidence of CMVR at this institution has decreased significantly with the recent use of HAART therapy. This effect may be related to the aggressive use of HAART and associated immune recovery in this population of AIDS patients. In this small series, however, the rate of retinal detachment appeared unchanged, but was only observed in those individuals who were not on HAART or who had just recently started.

AIDS-Related Opportunistic Infections↗

A comparative study of apoptosis and proliferation in germinoma and glioblastoma.

Intracranial germinoma has a relatively good prognosis when treated with radiotherapy and chemotherapy, whereas glioblastoma has a poor prognosis irrespective of these treatments. Cell proliferation and cell death are opposing processes in tumor growth, with tumor progression reflecting the balance between proliferating and apoptotic cells. We investigated cell proliferation and cell death using MIB-1 staining and nick-end labeling in 13 germinomas in comparison with 11 glioblastomas. Expression of BAX and Bcl-2, which regulate apoptosis, were studied by immunohistochemistry. Although germinomas showed strong MIB-1 immunostaining similar to that seen in glioblastomas, germinomas included significantly more apoptotic cells. The ratio of apoptotic ratio to MIB-1 labeling index for germinomas was 72.9 +/- 36.9 (mean +/- SD), a higher, statistically significant ratio as compared with glioblastomas (14.5 +/- 11.2; P < 0.01). Furthermore, germinomas showed greater expression of BAX than did glioblastomas, while the expression of Bcl-2 was weak in both tumor types. A comparison of these apoptotic-related proteins showed that immunoreactivity for BAX was relatively higher in germinomas than in glioblastomas (P < 0.01), corresponding well to numerous apoptotic cells identified in germinoma tissues. These findings may account for the prognostic difference between germinoma and glioblastoma in the face of a similar proliferation potential according to MIB-1 immunostaining. The balance between cell proliferation and death should be considered when predicting outcomes in patients with intracranial tumors.

Antigens, Nuclear↗

A case of anaphylaxis due to ibuprofen.

A forty-four-year-old Japanese female, who had persistant rhinorrhea, was administered Benza block tablets orally along with two other medicines. Immediately after ingestion, the patient displayed itching of the right upper eyelid, followed by coughing, sneezing, nasal discharge, nasal obstruction, nausea, vomiting, swelling of the face, and dyspnea. She had edema, a wheal extending from the face to the neck, and swelling of the eyelids and lips. Her symptoms subsided after treatment. Her reaction to ibuprofen, which was contained in the Benza Block tablets, was confirmed by a positive reaction to prick testing. From the results of these examinations, our patient was diagnosed as having anaphylaxis due to the ibuprofen in the Benza Block tablets. A review of the literature revealed no previous reports of anaphylaxis due to ibuprofen, although a few cases of ibuprofen urticaria have been reported.

Adult↗

Hair-discoloration of Japanese elite swimmers.

To understand hair-discoloration in relation to swimming, we examined sixty-seven elite swimmers of the Japan National Swimming Team and fifty-four, age-matched subjects as controls. The incidence of hair discoloration (61%) in the swimmers' group was significantly higher than that in controls (0%) (p<0.0001). Interestingly, surface damage of the nail plates coexisted in the swimmers with the scalp-hair discoloration. The hairs picked from the eight swimmers and two age-matched individuals as controls were examined by electron microscope (EM) and EM X-ray microanalyzer. The swimmers' discolored, golden hair revealed complete disappearance of hair cuticle both by scanning EM (SEM) and transmission EM (TEM). The quantity of melanosomes in the cortex decreased, and their diameter was smaller than that of controls. In addition, irregularly shaped melanosomes with variable electron density and less electron-dense melanosomes with white haloes were frequently observed in the swimmers' golden hair. The X-ray elemental spectrograph by SEM revealed that the content of sulfur in all the swimmers' discoloured hair was lower than that in the normal controls and that the content of chlorine in the male swimmers' discoloured hair was higher than that in the female swimmers and the normal controls. The X-ray elemental microanalysis by TEM focused on melanosomes in the cortex of the cross section and detected elemental chlorine in all swimmers' golden hairs. It did not detect any element in the control hairs. The 14C-tyrosine uptake test of hairbulbs found no significant difference between the swimmers and the normal controls. These findings suggest that hair discoloration was mainly due to cuticle damage by friction with water. Hypochlorous acid in the swimming pool water can penetrate to the hair cortex through the cuticle. It can oxidize and degenerate melanosomes there.

Adolescent↗

A case of black dot ringworm with a review of Japanese cases.

Black dot ringworm (BDR), caused by Trichophyton violaceum var. glabrum (T. glabrum), was observed in a 28-year-old Japanese female who had been treated with prednisolone (22.5 mg/day) for systemic lupus erythematosus. It was successfully treated with oral terbinafine (125 mg/day) for 12 weeks. The causative fungus was identified by molecular analysis as well as morphological and biochemical examination. The chitin synthase 1 (CHS1) gene cleavage pattern of the clinical isolate with restricted enzyme HinfI was identical to that of T. violaceum. We reviewed previous reports of BDR to determine the historical trend of this infection in Japan. Since 1974, 93 Japanese cases have been reported. The age distribution was bi-modal: the higher peak consisted of children (aged 0-15 years), and the lower peak was composed of the elderly (aged 60-75 years). In the elderly group, females were predominant (M:F=1:22, p<0.001). T. violaceum, including T. glabrum, was identified as the most common causative fungus of BDR (75.3%). Sixty percent of cases showed slight erythema. In 8 families, 16 cases were found to be intrafamilial infections. A history of previous steroid treatment was described in about 40%.

Adult↗