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Biomedical subjects

Shingo Tajima

Publications and source records attributed to Shingo Tajima.

At least 19 recordsLinked to original sources

Abnormal accumulation of inter-alpha-trypsin inhibitor and hyaluronic acid in lichen sclerosus.

Inter-alpha-trypsin inhibitor (ITI) is a recently identified extracellular hyaluronic acid (HA)-binding protein which greatly improves extracellular HA stability. In lichen sclerosus (LS), a broad hyalinized zone of superficial dermis is the most prominent pathological change. To assess the pathogenic role of ITI in accumulation of HA in a broad hyalinized zone in LS, we examined the expression and localization of ITI and HA immunohistochemically. In LS lesional skin sections, ITI staining revealed a strong, diffuse immunoreactivity predominantly in the upper dermis, whereas no staining was detected in normal skin sections. HA staining clearly showed positive reactivity in the superficial dermis, the epidermis, and occasionally the perivascular inflammatory infiltrate in LS skin sections. In normal skin, HA was present only in the epidermis. Double staining for ITI and HA demonstrated that ITI was localized in the areas where HA was abnormally deposited in the superficial dermis of LS. Other HA-binding proteins, CD44 and versican, did not show enhanced staining in the upper dermis of LS compared to normal skin specimens. These findings strongly suggest that ITI is closely implicated in the accumulation of HA in a broad hyalinized zone of the superficial dermis of LS.

Aged↗

Bone morphogenetic protein-mediated type II collagen expression in pilomatricoma and cutaneous mixed tumor.

BACKGROUND: We have previously reported that type II collagen deposition in overlying dermo-epidermal junction (DEJ) of pilomatricoma is mediated by bone morphogenetic protein 2/4 (BMP 2/4) expressed by shadow cells (SCs) of pilomatricoma. OBJECTIVE: This time, we studied the expression of type II collagen and BMP in a large number of cases of pilomatricoma and extended our study to cutaneous mixed tumor (CMT). RESULTS: We found type II collagen deposition in the overlying DEJ (16 of 50 cases) and in the SCs (19/50) of pilomatricoma. The number of case of type II collagen deposition in DEJ (DEJ(+)) and in SCs (SC(+)) of pilomatricoma correlated to the chronological stage of pilomatricoma. We also found type II collagen deposition in overlying DEJ (two of 11) and in the stromal chondroid tissue (four of 11) of CMT. BMP 2 was expressed in most cases of pilomatricoma (37/50) and CMT (seven of 11). CONCLUSIONS: The expression of type II collagen in pilomatricoma is dependent upon the chronological stage of pilomatricoma. Type II collagen expression in the overlying DEJ and chondroid matrix in CMT may be induced by BMP via the same mechanism as in pilomatricoma.

Adolescent↗

Linear hyperpigmentation with extensive epidermal apoptosis: a variant of linear lichen planus pigmentosus?

We report 3 female patients who rapidly developed pigmented patches in a linear arrangement. Histologically there was minimum epidermal basal cell damage and bandlike lymphocyte infiltration in the dermis, but focal massive apoptotic materials positively stained with antikeratin antibody were prominently seen in the papillary and subpapillary dermis. We considered these cases as a variant of linear lichen planus pigmentosus with unique histologic change of severe epidermal apoptosis. These histologic features may represent a severe apoptotic change in the end stage of lichenoid tissue reaction.

Adult↗

Treatment of eosinophilic pustular folliculitis with tacrolimus ointment.

We describe a patient with eosinophilic pustular folliculitis who partially responded to oral indomethacin, but intermittently experienced new eosinophilic pustular folliculitis lesions. Treatment with tacrolimus ointment 0.1% resulted in the rapid improvement of each recurred lesion and allowed withdrawal of indomethacin. To our knowledge, this is the first report of the use of topical tacrolimus in the treatment of eosinophilic pustular folliculitis.

Administration, Oral↗

Multiple elastofibromas.

Elastofibroma is an uncommon fibroelastic tumor or tumorlike process that usually occurs between the scapula and the chest wall of elderly patients. This condition is rarely reported in the dermatologic literature, because it infrequently arises in the skin or within the subcutaneous tissue. We present a 78-year-old man with 15 separate subcutaneous nodules on the buttocks and upper extremities together with bilateral subscapular nodules. All specimens taken from different lesions were histologically confirmed as elastofibromas. As far as we know, this case with 17 distinct elastofibromas demonstrates the largest number ever reported in a single patient. Although the pathomechanism of the occurrence of multiple elastofibromas is unknown, it should be included in the differential diagnosis of multiple subcutaneous nodules.

Aged↗

Immunohistochemical study of chronological and photo-induced aging skins using the antibody raised against D-aspartyl residue-containing peptide.

BACKGROUND: Biologically uncommon D-aspartyl residues have been reported in the elderly tissues such as tooth, eye lens, aorta, and brain. We have previously prepared the antibody against D-aspartyl residue-containing peptide and found that it reacted with elastotic material of actinic elastosis. METHODS: Immunoreactivity of the normal skins obtained from sun-exposed and sun-protected skins of varied ages with this antibody was studied. RESULTS: In the sun-exposed skins, the antibody showed negative reaction with the skin specimens of young donors, whereas it reacted with elastotic materials of actinic elastosis of the elderly. In the sun-protected skins, the antibody recognized elastic fiber-like structures and inner layer of vessels found from the mid to lower dermis of old donors but showed no positive reaction to skin specimens of young donors. CONCLUSIONS: The results suggest that the antibody is a potent marker for chronological and ultraviolet (UV)-induced skin aging. Unusual eosinophilic bodies seen in the superficial dermis in the sun-exposed area of the elderly skins were also immunoreactive with the antibody, suggesting that the eosinophilic bodies resulted from UV-induced skin damage.

Adolescent↗

Type II collagen accumulation in overlying dermo-epidermal junction of pilomatricoma is mediated by bone morphogenetic protein 2 and 4.

Pilomatricoma consists of the cells differentiating towards hair matrix cells. Immunohistochemical study revealed the deposition of type II collagen in the overlying dermo-epidermal junction (DEJ) of this benign tumor. Proalpha(1)(II) mRNA was detected by RT-PCR in the overlying epidermal layer but not in the dermal layer prepared from the lesional skin of pilomatricoma. The neutral salt-soluble proteins extracted from the tumor of pilomatricoma induced proalpha(1)(II) mRNA in the cultured human keratinocytes but not in the cultured dermal fibroblasts. Bone morphogenetic protein 2 or 4 (BMP2 or 4) was immunohistochemically detected in some shadow cells of pilomatricoma. Recombinant BMP2 and BMP4 were found to induce proalpha(1)(II) mRNA concentration dependently in the cultured human keratinocytes but not in the cultured fibroblasts. Proalpha(1)(II) mRNA induced by BMP2 and in cultured keratinocytes contained exon 2, indicating that the mRNA species is non-chondrogenic type IIA form. The results strongly suggest that BMP2 or 4 expressed in pilomatricoma is responsible for the induction of proalpha(1)(II) collagen mRNA in the overlying epidermal cells resulting in the deposition of type II collagen in the DEJ. When human keratinocytes were cultured on type II collagen substratum in vitro, the cell proliferation was accelerated at the early period of culture but was inhibited at the late period of culture, whereas the cell proliferation was persistently accelerated by type I or IV collagen substratum. Type II collagen deposition in the DEJ may potentially exert profound effects on keratinocyte proliferation and differentiation.

Adolescent↗

Expression of 67-kDa elastin receptor in annular elastolytic giant cell granuloma: elastin peptides induce monocyte-derived dendritic cells or macrophages to form granuloma in vitro.

Annular elastolytic giant cell granuloma (AEGCG) is characterized by non-palisading granuloma and elastophagocytic giant cells. Granulomas consist of structured masses of macrophages, dendritic cells, and T lymphocytes which play an essential role in granuloma formation. Two lineage systems of dendritic cells and macrophages originated from peripheral blood monocytes have been established in vitro. To know how elastin fragments are involved in the granuloma formation in AEGCG, we tested in vitro whether elastin fragments potentially induce monocyte-derived macrophages or dendritic cells to form granuloma and multinucleated giant cells. Immunohistochemical studies of the lesional skins of AEGCG (n = 5) revealed that the 67-kDa elastin receptor was specifically expressed in the epithelioid or multinucleated giant cells. Proliferation of factor XIIIa(+) cells and CD68(+) cells was also seen in the lesional skins of AEGCG. Factor XIIIa(+) dendritic cells or CD68(+) macrophages were established by the treatment of granulocyte/macrophage-colony stimulating factor (GM-CSF)/interleukin-4 or M-CSF, respectively. Further treatments of these dendritic cells or macrophages with elastin peptide resulted in the formation of granuloma or multinucleated giant cells which were immunoreactive with anti-67-kDa elastin receptor antibody. These findings suggest that elastic tissue induces factor XIIIa(+) cells and CD68(+) macrophages to form granuloma or multinucleated giant cells and plays an essential role in the formation of granuloma in AEGCG.

Aged↗

Punctate palmoplantar keratoderma with pigmentary lesions on the dorsa of feet and ankles: successful treatment with a combination of low-dose oral etretinate and topical calcipotriol.

We describe a patient with typical keratotic lesions of punctate palmoplantar keratoderma on the hands and feet and unique pigmentary lesions on the dorsa of the feet and ankles. A combination of low-dose oral etretinate (10 mg/day) and calcipotriol ointment 0.005% resulted in a complete regression, whereas pigmentary lesions on the dorsa of the feet and ankles did not change during the treatment.

Administration, Oral↗

Coexistence of spindle cell lipoma and ordinary lipoma.

We report a patient with a spindle cell lipoma on the nape and three ordinary lipomas on the abdomen and extremities. The coexistence of spindle cell lipoma and ordinary lipoma in a single patient is rare. Abundant CD34-positive spindle cells and mast cells were found in the spindle cell lipoma, but in the ordinary lipomas, only a small number of CD34-positive spindle cells were found in the interstitial connective tissue and no mast cells were seen. Because mast cells are known to stimulate mesenchymal cell proliferation and collagen production, mast cell infiltration may be a trigger for the proliferation of CD34-positive spindle cells, leading to the conversion of ordinary lipoma into spindle cell lipoma.

Antigens, CD34↗

Eruptive vellus hair cyst in patients with chronic renal failure.

Two cases of eruptive vellus hair cysts associated with chronic renal failure are reported. Histologically the lesions of both cases showed cystic structures in the dermis lined by squamous epithelium which contained varying amounts of vellus hair shafts. Immunohistochemical studies using monoclonal anti-AGE (advanced glycation end product) antibody demonstrated that keratinous materials within the cystic structures were immunoreactive to the antibody, whereas those of cystic lesions (epidermal cyst, eruptive vellus hair cyst, steatocystoma multiplex, trichofolliculoma and trichilemmal cyst) seen in otherwise healthy individuals were negative. Because it has been reported that plasma and skin levels of AGE are elevated in renal failure patients, AGE-modified keratinous materials may be associated with the formation of cystic structures by stimulating the occlusion of the epithelium.

Epidermal Cyst↗

Immunological detection of D-beta-aspartate-containing protein in lens-derived cell lines.

PURPOSE: Although the presence of biologically uncommon D-beta-aspartate (D-beta-Asp) in lens protein is thought to be related to aging, we recently found this isomer in lens alphaA-crystallin from human newborns. The objective of this study was to examine whether D-beta-Asp occurs in protein from lens-derived cell lines. METHODS: We examined the expression of D-beta-Asp-containing protein in the lens-derived cell lines alphaTN4-1 and N/N1003A, by western blot and immunoprecipitation analysis using a polyclonal antibody against Gly-Leu-D-beta-Asp-Ala-Thr-Gly-Leu-D-beta-Asp-Ala-Thr-Gly-Leu-D-beta-Asp-Ala-Thr (peptide 3R), which corresponds to three repeats of positions 149-153 in human alphaA-crystallin. The anti-peptide 3R antibody, prepared in a previous study, is a useful tool for investigating D-beta-Asp-containing peptides. RESULTS: Western immunoblot and immunoprecipitation analysis showed that a 50 kDa protein in N/N1003A cells was strongly immunoreactive with the anti-peptide 3R antibody. Antibodies against alphaA- and alphaB-crystallin also stained this protein. On the other hand, the alphaTN4-1 cell line only expressed proteins of about 20 kDa, which also reacted to antibodies against alphaA-crystallin and alphaB-crystallin. CONCLUSIONS: The results indicate that the N/N1003A cell line expressed a 50 kDa D-beta-Asp-containing protein, which may share a common amino acid sequence with alphaA- and alphaB-crystallin.

Animals↗

Iontophoresis promotes percutaneous absorption of L-ascorbic acid in rat skin.

BACKGROUND: Percutaneous absorption of ascorbic acid is limited by its impermeability and instability. OBJECTIVE: We attempted to improve the percutaneous absorption of ascorbic acid by use of iontophoresis after topical application of ascorbic acid. METHODS: Radioactivities extracted from epidermal, dermal and blood compartments after topical application of [14C]ascorbic acid was measured in the presence or absence of iontophoresis. Autoradiography was also performed to study the histological distribution of the radioactivity of ascorbic acid. RESULTS: Iontophoresis greatly enhanced percutaneous absorption of [14C]ascorbic acid in the rat skin. Radioactive ascorbic acid in the dermis reached a maximum level at 1 h after application whereas, in the topical application method, the uptake of ascorbic acid in both epidermis and dermis was quite low. Autoradiography of skin specimens indicated that iontophoresis accelerated the absorption of ascorbic acid through both transepidermal and pilo-sebaceous routes. CONCLUSION: Iontophoretic delivery system of ascorbic acid may provide a more efficient tool for its percutaneous absorption than a simple topical application.

Administration, Topical↗

Histological study of the hypertrophic placentas and open eyelids observed in cloned fetuses.

Mice cloned from somatic or ES cells showed signs of phenotypically various abnormalities. These abnormalities are now considered to result from aberrant gene expressions by epigenetic reprogramming errors but it is still unclear when these abnormalities occur and what histological changes occur during the gestation period. To address these issues, we histologically examined the hypertrophic placentas and open eyelids at 12.5, 17.5 and 19.5 days of the gestation period in ES-derived cloned mice that we have previously reported. In the placentas, the histology revealed that the hypertrophy had already occurred at 12.5 dpc and that the main change was the proliferation of trophoblast cells in the labyrinth layer. In the fetuses and placentas at 17.5 and 19.5 dpc, extensive proliferation of spongiotrophoblast and glycogen cells in the spongiotrophoblast layer and enlarged trophoblast giant cells were observed. Open eyelids in cloned mice were observed from 17.5 dpc, whereas the eyelids of the control mice had already been closed. The histology showed the malformation of eyelids where the formation of the stratum corneum and stratum granulosum in the epidermis was insufficient. Based on the histology described here, further comparative studies of the gene expression and histology of abnormalities seen in cloned mice and in gene-targeted and spontaneously mutated mice with similar phenotypic abnormalities could help illuminate these abnormalities and could contribute to the development of somatic cloning technology.

Animals↗

The presence of D-beta-aspartic acid-containing peptides in elastic fibers of sun-damaged skin: a potent marker for ultraviolet-induced skin aging.

Biologically uncommon d-aspartyl residues have been reported in proteins of various elderly tissues. We prepared a polyclonal antibody against d-beta-Asp-containing peptide and examined its immunoreactivity in the skin. The antibody recognized integrated or disintegrated elastic fibers in the sun-exposed skin but not in the sun-protected skin of the elderly donors. Western blot analysis of the proteins isolated from sun-damaged skin demonstrated that the 50 kDa protein was immunoreactive with both antibodies for d-beta-Asp-containing peptide and elastin. Ultraviolet (UV) irradiation on normal skin caused the appearance of d-beta-Asp-containing peptide-immunoreactive fibers in the dermis. These results suggest that UV irradiation is closely related to the formation of d-beta-Asp in the elastic fibers of skin. We propose that the antibody could be a useful indicator for sun damage of the skin.

Aged↗

Expression of 36-kDa microfibril-associated glycoprotein (MAGP-36) in human keratinocytes and its localization in skin.

Microfibril-associated glycoprotein-36 (MAGP-36) is a recently isolated elastin-binding protein and considered to be a member of microfibril-associated glycoproteins (MAGPs). We studied the expression of MAGP-36 in cultured normal human keratinocytes and its localization in the skin. MAGP-36 was found to be expressed in cultured human keratinocytes by Western blot and RT-PCR assays. The levels of MAGP-36 (polypeptide and mRNA) and the number of MAGP-36-producing keratinocytes were greatly increased during Ca(2+)-induced differentiation of keratinocytes. Immunohistochemical studies demonstrated that MAGP-36 colocalized with elastic fibers and formed candelabra like-fibers in the superficial dermis of normal skin. In the elderly skin of sun-exposed region, immunoreactivity of MAGP-36 in the superficial dermis disappeared. In the lesional skin of pseudoxanthoma elasticum which is an elastin-related disorder, immunoreactivity of MAGP-36 was found in the accumulation of disintegrated elastic fibers. The results show that MAGP-36 is a component of elastic fibers in the dermis and co-operates with elastin in normal and diseased conditions.

Aged↗

Immunohistochemical study of membrane type-matrix metalloproteinases (MT-MMPs) and matrix metalloproteinase-2 (MMP-2) in dermatofibroma and malignant fibrous histiocytoma.

Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. Enhanced expression of matrix metalloproteinase-2 (MMP-2) has been demonstrated in dermatofibroma (DF) and malignant fibrous histiocytoma (MFH). MMP-2 has been shown to be activated by membrane-type MMPs (MT-MMPs). To study the role of MT-MMP in the activation of MMP-2, skin specimens of DF (five cases) and MFH (three cases) were immunohistochemically studied using in situ zymography and the antibodies against matrix metalloproteinase-2 (MMP-2) and membrane type 1-3-MMPs (MT1-3-MMPs). Both MMP-2 activity and its expression were significantly activated in the tumor cells in DF and MFH. Anti-MT2-MMP strongly reacted with tumor cells of all cases of DF and MFH, whereas anti-MT1 or 3-MMP antibody showed a weak reaction in some cases of DF and MFH. Double immunofluorescence labeling demonstrated that the immunoreactive cells with anti-MMP-2 antibody in DF and MFH consistently reacted with anti-MT2-MMP antibody. The results suggest that the activation of MMP-2 in the benign and malignant fibrous tumors is related to the activation of MT-MMPs.

Adolescent↗

Type XVI collagen is expressed in factor XIIIa+ monocyte-derived dermal dendrocytes and constitutes a potential substrate for factor XIIIa.

We have previously reported that connective tissue cells in the superficial dermis preferentially express alpha1(XVI) collagen rather than those in the lower dermis. Double immunofluorescence labeling using the antibodies for alpha1(XVI) collagen and factor XIIIa (plasma transglutaminase), which is a marker of dermal dendrocytes, demonstrated that both antibodies reacted with the same cells in the superficial dermis of normal skin as well as the lesional skins of dermal dendrocyte-related disorders, dermatofibroma, and psoriasis. Dermal dendrocytes are considered to be established by a culture of peripheral blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4. Reverse transcription--polymerase chain reaction, metabolic labeling, and immunofluorescence studies demonstrated that treatment of CD14+ peripheral blood monocytes with granulocyte macrophage-colony stimulating factor/interleukin-4 over a period of 8 d resulted in the induction of alpha1(XVI) collagen as well as factor XIIIa. The physiologic significance of colocalization of alpha1(XVI) collagen and factor XIIIa in the tissue and their coordinate induction in CD14+ monocyte-derived dendritic cells in vitro was studied. Considerable incorporation of [3H]putrescine by factor XIIIa into recombinant noncollagenous domain (NC) 11 but not into collagenous domain (COL) 1.NC1 domain of the alpha1(XVI) polypeptide was found. Incubation of recombinant NC11 of alpha1(XVI) polypeptide with factor XIIIa in vitro produced a covalent cross-linking complex on sodium dodecylsulfate-polyacrylamide gel electrophoresis. The results indicate that alpha1(XVI) collagen is constitutively expressed by most dermal dendrocytes in the skin and dendritic cells differentiated from peripheral blood monocytes in vitro. Type XVI collagen is expressed in factor XIIIa+ dermal dendrocytes and may form an intermolecular cross-linking through NC11 domain by the reaction catalyzed by factor XIIIa contributing to the structural integrity of factor XIIIa+ dendritic cell-rich tissues.

Adult↗