M. Akiyama
Keio University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by M. Akiyama.
American Journal of Dermatopathology | 1993
Arata Kikuchi; M. Akiyama; Hiroshi Hanyaku; Hiroshi Shimizu; Naka W; Takeji Nishikawa
We describe two cases of malignant schwannoma in the skin that did not originate from a nerve trunk and was not associated with neurofibromatosis. Light microscopy showed that both tumors were composed predominantly of atypical spindle-shaped cells. Immunohistochemical analysis was performed with various monoclonal antibodies against mesenchymal determinants. In both patients, tumor cells were positive for S-100 alpha and S-100 beta, neuron-specific enolase, vimentin, neurofilament protein, and myelin basic protein, and negative for HMB-45, glial fibrillary acidic protein, epithelial membrane antigen, and desmin. Electron microscopy revealed that the tumor cells possessed indented nuclei with an electron-lucent cytoplasm. Immunoelectron microscopy showed diffuse fine granular staining for S-100 alpha, not detectable in normal Schwann cells, in the cytoplasm of the tumor cells.
Gene Therapy | 2005
Daisuke Sawamura; Mizuki Goto; Akihiko Shibaki; M. Akiyama; James R. McMillan; Yoshihiro Abiko; Hiroshi Shimizu
Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the epidermis and observed HBD3 in the intercellular spaces and lamellar bodies of the upper epidermal layers. This result showed HBD3 expressed and assembled in the outer layers of the epidermis was suspected to counter the invading microorganisms. Next, we established a keratinocyte cell line that stably expressed HBD3 and found that the culture medium showed antibacterial activity. Furthermore, we prepared an epidermal sheet of these cells with the HBD3 gene and grafted this onto a dermal wound on a nude rat. The HBD3 engineered epidermis demonstrated significant antimicrobial activity. Skin ulcers without epidermis are constantly exposed to invading microorganisms. Biopsy samples of re-epithelizing epidermis from patients with skin ulcers were collected, and HBD3 mRNA level measured in the epidermis. The epidermal samples from the ulcer skin expressed 2.5 times higher levels of HBD3 transcript than those in the control skin. These results, taken together, indicate that the therapeutic introduction of the HBD3 gene into somatic cells may provide a new gene therapy strategy for intractable infectious diseases.
Prenatal Diagnosis | 1998
M. Akiyama; Beverly A. Dale; Lynne T. Smith; Hiroshi Shimizu; Karen A. Holbrook
Harlequin ichthyosis (HI) is a severe congenital ichthyosis in which newborn infants are covered with a thick plate of stratum corneum. We examined skin specimens from a variety of regions of the body including the scalp, face, tongue, trunk, upper and lower extremities, digits, palms, and soles of three fetuses affected with HI that were diagnosed prenatally. In all the skin regions, characteristic morphological abnormalities (absent or abnormal lamellar granules and intercellular lamellae, lipid inclusions in the cornified cells) were expressed in the late second trimester of the fetal period. The cornified cells in hair canals showed morphological abnormalities of HI more strongly than the interfollicular epidermis. Immunoblot study of epidermal extracts revealed that profilaggrin was much more prominent than filaggrin in all the hairy skin regions where the hair canals were extensively keratinized, but filaggrin was prominent in the palm. These observations support the idea that, in the hairy skin, HI phenotype expression is associated with keratinization and abnormal filaggrin metabolism in hair. In addition, the prenatal diagnosis or prenatal exclusion of HI is thought to be possible from whichever site of the fetal body the skin biopsy is taken in the late second trimester of the fetal period.
Journal of Cutaneous Pathology | 2006
M. Akiyama; K. Yoneda; Soo-Youl Kim; Hirofumi Koyama; Hiroshi Shimizu
Long‐term survivors of harlequin ichthyosis (HI) have raised a controversy over the differences between HI and lamellar ichthyosis (LI). Abnormal lamellar granules and the failure of conversion from profilaggrin to filaggrin have been reported in HI. On the other hand, malformation of the cornified cell envelope as a result of mutation of keratinocyte transglutaminase has been found in LI. In the present study, we analyzed the distribution of keratins, filaggrin/profilaggrin and cornified cell envelope proteins in the epidermis in HI. We studied a newborn Japanese male with typical clinical features of HI. Electron microscopic observation of a skin biopsy specimen taken from the trunk revealed the presence of lipid inclusions within the cornified cells, the absence of lamellar granules in the granular layer keratinocytes, and a lack of extracellular lamellar structures between the first cornified cell and the granular cell. Immunohistochemical labeling showed a normal distribution of keratins (keratins 1,5, 10, and 14), filaggrin/profilaggrin and cornified cell envelope proteins (involucrin, small proline‐rich proteins, and loricrin) in the epidermis of lesional skin. The present observations of the patients skin verified that keratins and cornified cell envelope proteins are normally expressed in HI, thus demonstrating a different pathogenesis between HI and LI.
British Journal of Dermatology | 1992
Arata Kikuchi; K. Sakuraoka; S. Kurihara; M. Akiyama; Hiroshi Shimizu; Takeji Nishikawa
Two cases are reported of cutaneous anaplastic large‐cell lymphoma with the suppressor/cytotoxic (CD8) phenotype. In both cases there was a solitary skin tumour in which there was a dense infiltrate with large irregularly shaped cells which on immunophenotyping expressed CD8. DNA hybridization analysis showed rearrangements of the T‐cell‐receptor gene in both cases.
Journal of Cutaneous Pathology | 1989
M. Akiyama; Wataru Naka; Takashi Harada; Takeji Nishikawa
We report a case of angiosarcoma and dermal melanocytosis occurring simultaneously in the same lesion. We examined the primary and 2 metastatic lesions. Histopathologically, the anaplastic angiosarcoma cells had a tendency to form irregularly shaped small cavities. Immunohistochemically, they were strongly reactive with Ulex europaeus agglutinin (UEAI) stain. The mid and deep dermis of the same lesion had spindle or elongated slender melanocytes containing melanin granules. The melanocytes were positive with S‐100 protein stain. Ultrastructurally, pinocytotic vesicles, fine filaments, and Weibel‐Palade body‐like dense granules were observed in the cytoplasm of angiosarcoma cells. Dermal melanocytes had external lamina and melanosomes in various stages. The melanocytes showed no similarity to the neoplastic tumor cells and there was no apparent intermediate form between the 2 kinds of cells. The etiological implications of dermal melanocytosis with a tumor of vascular origin are discussed.
Journal of Cutaneous Pathology | 1990
M. Akiyama; K. Hayakawa; Yonosuke Watanabe; Takeji Nishikawa
Lectin‐binding sites in clear cell acanthoma (CCA) were studied using an avidin‐biotin complex (ABC) with 9 lectins. Formaldehyde‐fixed, paraffin‐embedded sections of 7 CCA lesions were employed. Positive stainings, similar to those seen in normal epidermis, were observed on the cell surface in CCA with Ricinus communis agglutinin I (RCA‐I), Ricinus communis agglutinin II (RCA‐II), and wheat germ agglutinin (WGA). Reduced reactivities were observed with Concanavalin A (ConA) and peanut agglutinin (PNA) in CCA. In some areas of CCA lesions, faint stainings were seen with Ulex europaeus agglutinin I (UEA‐I). Capability of staining with soybean agglutinin (SBA) was completely lost in the lesions. With Bandeiraea simplicifolia agglutinin II (BSA‐II), cytoplasmic stain was seen in a part of upper and spinous layers in CCA lesions. Dolichos biflorus agglutinin (DBA) did not bind to either CCA or normal epidermis. These results indicate that the lectin‐binding sites of proliferating cells of CCA resemble those of epidermal keratinocytes and suggest that CCA is a tumor of epidermal origin.
Pathology International | 1991
M. Akiyama; Yonosuke Watanabe; Takeji Nishikawa
To clarify the origin and function of human cutaneous mast cells (CMCs), immunohistochemical characterization was done in 19 cases of urticaria pigmentosa (cutaneous mastocytosis) using 9 antibodies (anti leukocyte common antigen, MX‐PanB, anti lysozyme, anti α1, antitrypsin, anti α1‐antichymotrypsin, anti vimentin, anti‐neuron specific enolase, anti factor VIII related antigen, and anti‐ACTH). CMCs showed positive reactions with anti α1 anti‐chymotrypsin and anti vimentin in almost all of the specimens. In more than half of the specimens, CMCs were stained positively with anti ‐α1‐antitrypsin, MX‐PanB, and anti factor VIII related antigen. Anti‐leukocyte common antigen and anti ACTH also showed positive reactions in some specimens. These results confirm the existence of vimentin filaments in CMCs and suggest a functional role of CMCs in hemostasis via factor VIII. Furthermore, immunohistochemical similarity between CMCs and granulocyte/macrophage group cells is also suggested.
Journal of Dermatology | 1990
M. Akiyama
In 21 cases of urticaria pigmentosa (UP), clinical and histological observations and evaluation of mast cell (MC) volume density in the lesions using a morphometric point counting method were performed. The mutual correlations between clinical and histological findings were statistically assessed by a method of multiple regression analysis. Clinical items employed in the analyses were as follows: sex, the age of onset, the age of biopsy, the duration of lesions, the type of skin lesions, sites involved, the presence or absence of Dariers sign and symptoms, and serum histamine level. Histological items included the localization and infiltration pattern of MC, the level of basal melanosis, the presence or absence of inflammatory cell infiltration, and the MC volume density in the lesions. Statistical significance of the partial regression coefficients was obtained for 6 pairs of the criteria (p=0.05), including the age of onset and the age of biopsy, the age of onset and the level of basal melanosis, the duration of lesions and the level of basal melanosis, and the type of skin lesions and the level of basal melanosis. No significant correlations were observed between the MC volume density in the lesions and any of the other items. These results suggest that the basal melanosis in a UP lesion may not be a direct reaction to the transitory massive infiltration of MC, but rather be due to a relatively long‐term effect of MC infiltration. Furthermore, the MC volume density in the lesion is not likely to be an important factor in determining the clinical manifestations of a UP lesion.
Dermatology | 2010
Nao Saito; Teruki Yanagi; M. Akiyama; H.‐Y. Lin; S. Kasai; Yasuyuki Fujita; N. Yamane; Daisuke Inokuma; Satoru Kase; K. Ono; H. Minakawa; Hiroshi Shimizu
Pyoderma gangrenosum (PG) of the eyelid is extremely rare, and its proper management is essential for the preservation of visual function. Here, we report 2 cases of PG of the eyelid with intraorbital involvement. In both cases, the skin and intraorbital lesions improved after systemic immunosuppressive therapies; however, corneal perforation occurred in 1 case. In order to assess the clinical features of PG of the eyelid and to obtain clues for optimal treatment, we reviewed 15 well-documented cases in the literature, including the present cases. Corneal perforation occurred in 4 cases and defective ocular motility in 1 case. Three patients eventually underwent enucleation of the affected eye. Our cases and the literature review clearly indicate that MRI is a powerful tool for evaluating the extent of extracutaneous PG lesions around the eye and that early diagnosis and immediate immunosuppressive therapy are crucial for the preservation of visual acuity.