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Biomedical subjects

Y Mizukawa

Publications and source records attributed to Y Mizukawa.

At least 19 recordsLinked to original sources
PubMed2001

Immunohistochemical detection of skin-homing T cells expressing fucosyltransferase VII (Fuc-TVII) in vitro and in situ.

Although expression of cutaneous lymphocyte-associated antigen (CLA) is thought to be a specific marker of skin "homing" T cells, it has become clear that CLA is a good marker for high levels of fucosyltransferase VII (Fuc-TVII) activity but does not necessarily represent the epitope required for binding to E-selectin (Wagers et al, 1996, 1997). Therefore, expression of Fuc-TVII is an attractive candidate for identifying skin "homing" T cells. However, analyses of Fuc-TVII expression in human T cells have been performed only at the mRNA level (Nakayama et al, 2000) because of the lack of mAB: In this study Fuc-TVII was for the first time visualized in individual cells by using a novel mAb that we developed. Double immunofluorescence and immunohistochemistry demonstrated the coexpression of Fuc-TVII and CLA in cell lines in which Fuc-TVII mRNA was shown to be expressed at high levels: whereas CLA expression was seen in the cell membrane, Fuc-TVII was identified in a supra- or perinuclear location. Cytoplasmic Fuc-TVII expression was also detectable in both CD4(+) and CD8(+) T cells purified from peripheral blood. Fuc-TVII was also expressed at high levels in many CLA(+) T cells infiltrating the skin. In these peripheral T cells, unlike in cell lines, cytoplasmic expression of Fuc-TVII was not always associated with surface CLA expression. This mAb would serve as a valuable tool for selectively identifying a novel subset of skin "homing" T cells that are not detected by the conventional method because of the lack of CLA expression.

Antibodies, Monoclonal↗
PubMed2001

The cytokine profile in a transient variant of angioedema with eosinophilia.

Episodic angioedema with eosinophilia is characterized by recurrent angioedema, fever and weight gain with a remarkable eosinophilia. A transient type, predominantly reported in Japan, in which the disease is limited to a single attack, is usually less severe than the episodic type described in the U.S.A. and Europe, and provides an ideal disease model in which to study the mechanisms for resolution of eosinophilic inflammation. The aim of this study was to evaluate the relationship between cytokine responses and clinical course in three patients with the transient type. Serum levels of interleukin (IL) -5 were only marginally elevated even during an attack, unlike those in reported cases of the episodic type. Significant elevations in granulocyte-macrophage colony-stimulating factor levels were also noted during an attack in two cases in which it was measured. A dramatic increase in tumor necrosis factor (TNF) -alpha levels was subsequently observed in relation to resolution of clinical symptoms. No major changes in the serum levels of soluble Fas and soluble Fas ligand were found throughout the course. These results suggest that relatively lower levels of IL-5 and a subsequent increase in TNF-alpha levels are characteristic features of the transient type. The differences in clinical symptoms and course observed between the two types may be partly explained by the differences in the cytokine profiles.

Adult↗
PubMed2001

Development and characterization of a monoclonal antibody specific for fucosyltransferase VII (Fuc-TVII): discordant expression of CLA and Fuc-TVII in peripheral CD4+ and CD8+ T cells.

Although cutaneous lymphocyte-associated antigen (CLA) is thought to be specifically expressed on skin "homing" T cells, it has become clear that CLA is not directly involved in binding to E-selectin but represents an excellent marker for high levels of fucosyltransferase VII (Fuc-TVII): Fuc-TVII can regulate the ability of T cells to migrate into the skin by generating a binding site for E-selectin. In this study, by using a novel monoclonal antibody for Fuc-TVII, we investigated whether expression of Fuc-TVII could be selectively detected in various CLA+ cell lines and peripheral blood T cells. Fuc-TVII was readily detected in the cytoplasm, but not in the membrane, of CLA+ cell lines. Cytoplasmic Fuc-TVII expression was also detectable in both CD4+ and CD8+ T cells purified from peripheral blood mononuclear cells. Nevertheless, there were significant numbers of CLA-expressing CD4+ or CD8+ T cells that did not coexpress Fuc-TVII, and vice versa: either the CD4+ or the CD8+ T cell population consisted of a variable ratio of CLA+ Fuc-TVII+, CLA+ Fuc-TVII-, and CLA- Fuc-TVII+ cells; and CLA+ Fuc-TVII- cells were the most abundantly identifiable phenotype in peripheral blood CD4+ and CD8+ T cells. Thus, according to their expression pattern, skin "homing" T cells can be subdivided into at least three populations, CLA+ Fuc-TVII+, CLA+ Fuc-TVII-, and CLA- Fuc-TVII+ cells. Our study provides convincing evidence that skin "homing" T cells are phenotypically heterogenous and that Fuc-TVII expression, in combination with CLA expression, is a useful phenotypic marker for identifying skin "homing" T cells in mixed cell populations.

Antibodies, Monoclonal↗
PubMed2000

Virus-induced immune dysregulation as a triggering factor for the development of drug rashes and autoimmune diseases: with emphasis on EB virus, human herpesvirus 6 and hepatitis C virus.

There are a considerable amount of empirical and theoretic medical literature regarding the possible role of viruses in the development of drug rashes and autoimmune diseases: under these conditions, interactions of viruses with the immune system would serve as an accelerating factor of disease pathogenesis. Recent reports have provided evidence to indicate that immune responses against infections with Epstein Barr (EB) virus and human herpesvirus 6 (HHV-6), which are lymphotropic members of the herpes virus group, not only aid the direct elimination of the virus but also contribute to a favorable milieu for the initiation or acceleration of drug rashes. Viruses that can persist for the lifetime of the host despite strong immune responses against them, such as EB virus and hepatitis C virus (HCV), would be also relevant to the pathogenesis of autoimmune diseases. HCV has been reportedly associated with a wide variety of dermatoses that, in common, show histologically the lichenoid tissue reaction. Although porokeratosis that manifests lichenoid histopathological features had long been regarded as being associated with immunosuppression, we found that HCV could act as trigger for the development of porokeratosis during states of immunosuppression. Thus, the main purpose of this review is to describe recent work on the etiology of drug rashes and autoimmune disease with special reference to viral infections.

Autoimmune Diseases↗
PubMed2000

Expression of cutaneous lymphocyte-associated antigen regulated by a set of glycosyltransferases in human T cells: involvement of alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I.

Cutaneous lymphocyte-associated antigen (CLA), which plays a key part in skin homing of human CD4+ memory T cells via CLA/E-selectin binding, is upregulated by IL-12 and downregulated by IL-4. Although alpha1,3-fucosyltransferase VII is essential for synthesis of the CLA carbohydrate epitope, little is known about how the CLA expression is regulated by a number of glycosyltransferases. A 6 wk long-term culture for the in vitro differentiation of naïve Th cells to memory Th1 cells was employed. By repeated activation in the presence of IL-12, naïve T cells differentiated into memory Th1 cells, resulting in the upregulation of CLA expression. The switching of cytokine from IL-12 to IL-4 at three cycles resulted in a marked downregulation of CLA. The transcript levels of 16 glycosyltransferases and P-selectin glycoprotein ligand-1, all considered to be potentially involved in CLA synthesis, were determined after each cycle. The level of CLA expression was well correlated with the amounts of alpha1,3-fucosyltransferase VII and beta1,4-galactosyltransferase I. Both were upregulated by IL-12 and downregulated by IL-4. In particular, alpha1,3-fucosyltransferase VII levels decreased markedly in the presence of IL-4. P-selectin glycoprotein ligand-1 and Core 2 beta1, 6-N-acetylglucosaminyltransferase were progressively up-regulated by repeated IL-12 stimulation, but they were not downregulated by IL-4. The transcript levels of some genes examined were constitutive without any correlation to CLA expression. These results suggest that the level of CLA expression is determined by alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I, the other enzymes merely participating in the synthesis of CLA. In peripheral blood mononuclear cells, IL-12 and IL-4 profoundly upregulated and downregulated the alpha1,3-fucosyltransferase VII transcripts, respectively, but not the beta1,4-galactosyltransferase I ones, within only 2 h of in vitro culture. This suggested that alpha1,3-fucosyltransferase VII is transcriptionally regulated directly by IL-12 and IL-4.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2000

Pemphigus foliaceus induced by exposure to sunlight. Report of a case and analysis of photochallenge-induced lesions.

BACKGROUND: Although there are many reports on photo-induced pemphigus, careful analysis in the development of acantholytic blister have rarely been performed in the lesions induced by photochallenge. OBJECTIVE: The study was intended to elucidate the mechanisms by which ultraviolet light (UV) radiation causes the skin lesions of pemphigus foliaceus. METHODS: Photochallenge-induced lesions were examined histologically and immunohistochemically over the time course with three biopsy specimens. Neutrophil adhesion assay was performed using the specimens prepared from the photochallenged lesions as substrates. RESULTS: A small number of neutrophils were seen at 5 h after photochallenge in the dermis and epidermis, and slight acantholysis was detected at 72 h. In neutrophil adhesion assay, greater numbers of neutrophils adhered to the upper epidermis of the skin obtained at 5 h after challenge. CONCLUSIONS: Our results suggest that both enhanced binding of autoantibodies to the epidermis after UV radiation and preferential adhesion of neutrophils to the UV-irradiated epidermis contribute to the development of acantholysis in photo- induced pemphigus foliaceus. Intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes is not primarily responsible for the epidermal migration of neutrophils.

Cell Adhesion↗
PubMed1999

An immunohistochemical study of beta1,4-galactosyltransferase in human skin tissue.

An immunohistochemical investigation of beta1,4-galactosyltransferase (beta1,4-GalT) on human skin tissue was performed on formalin-fixed paraffin-embedded sections using a monoclonal antibody, MAb8628, which specifically recognizes a protein moiety of human beta1,4-GalT. Distribution of the galactose beta1,4-N-acetylglucosamine (Gal beta1,4GlcNAc)-R epitope was also detected by staining with Ricinus communis agglutinin (RCA) 120. The beta1,4-GalT was observed to be localized at the perinuclear region of epidermal keratinocytes. The fine localization was also observed at the supranuclear region in the cells of apocrine glands, eccrine ducts and glands. The positive staining with RCA 120 was well colocalized with the cells expressing the beta1,4-GalT. An electron microscopic study revealed that positive signals of beta1,4-GalT definitely reside in the Golgi apparatus. No immunoreactivity was observed in any other intracellular structure or on the cell surface. These findings strongly indicated that the beta1,4-GalT is the major enzyme responsible for the Gal beta1,4GlcNAc-R epitope synthesis in human skin tissue.

Epidermal Cells↗
PubMed1998

Fixed drug eruption presenting as erythema dyschromicum perstans: a flare without taking any medications.

Fixed drug eruption (FDE) can present as multiple pigmented macules that flare at fixed sites even when the patient has taken no medications. Although this presentation is not characteristic of FDE, it must be borne in mind in order to make a correct diagnosis. We describe such a patient whose condition was initially diagnosed as erythema dyschromicum perstans (EDP). Immunohistochemically intraepidermal T cells were distributed between basal and suprabasal keratinocytes in the lesional skin, a finding suggestive of FDE. A flare occurred not only with exposure to theophylline but also without exposure. A flare has never recurred and pigmented macules faded gradually after avoiding theophylline. On the basis of these findings, we recommend that patients with an EDP-like presentation be examined completely for causes such as drugs before labeling the cutaneous lesions.

Child↗
PubMed1994

Lectin binding pattern in normal human labial mucosa.

The pattern of lectin binding in normal human labial mucosa was examined by light and electron microscopy using eight different lectins (ConA, LCA, WGA, UEA-1, RCA-1, SBA, DBA and PNA) and compared with the patterns in normal human skin and oesophageal mucosa. As seen by light microscopy, ConA, LCA, and WGA stained cell membranes in all layers of the mucosae. RCA-1 stained the plasma membrane of cells in the basal and middle layers, whereas cells in the superficial layers showed little positive staining. UEA-1, SBA, and PNA stained the cells in the middle layers weakly in some cases. No positive staining for DBA was seen. By electron microscopy, reaction product indicating ConA-binding sites was observed in the plasma membrane, cisternae of the endoplasmic reticulum, nuclear envelope and the Golgi apparatus. Binding of LCA, WGA, and RCA-1 was observed in the plasma membrane. These results show that the binding pattern of PNA, SBA, and RCA-1 in labial mucosa is different from that in the normal skin or oesophageal mucosa, although the labial mucosal epithelium, epidermis, and oesophageal epithelium are all stratified squamous epithelia. These differences in the cell-surface sugar residues are likely to be related to the possible functional differences in these tissues.

Adult↗
PubMed1985

Microbial phosphorylation of compactin (ML-236B) and related compounds.

Several fungal strains were found to convert compactin (ML-236B) to 5'-phosphocompactic acid. The product was isolated by solvent extraction and column chromatography, and identified by IR, UV, 1H NMR, 13C NMR and 31P NMR spectroscopy. Related structures (monacolin K, L and X) were also transformed to their corresponding phosphorylated analogues. The products were re-converted back to respective parental compounds by treatment with alkaline phosphatase of calf intestine.

Alkaline Phosphatase↗