PubMed Health⌕ Search

Biomedical subjects

W Fujimoto

Publications and source records attributed to W Fujimoto.

At least 37 records · Page 2Linked to original sources
PubMed1997

Expression of bcl-2 antagonist bak in inflammatory and neoplastic skin diseases.

Bak (bcl-2 homologous antagonist/killer) is a proapoptotic member of the ever-expanding bcl-2 gene family, a recently described category of oncogenes that is critical for the regulation of programmed cell death. We investigated the expression of bak in several inflammatory and neoplastic skin diseases in comparison with normal skin. Immunohistochemical analysis revealed positive bak staining in epidermal keratinocytes of normal skin, with the granular layer being stained slightly more strongly than the basal and spinous layers, and in psoriasis vulgaris, lichen planus, actinic keratosis, keratoacanthoma and squamous cell carcinoma. We demonstrated the expression of bak in the follicular infundibulum in contrast to the outer root sheath of the lower follicle, which showed only negative to weak bak expression. Seventeen of 20 basal cell carcinomas examined showed negative immunostaining for bak, and the remaining three basal cell carcinomas showed only partial weak positivity, mainly in the palisading layers of some tumour formations. Immunoblot analysis using cultured normal human epidermal keratinocytes revealed the presence of bak protein in both undifferentiated and differentiated keratinocytes. The results of our study suggest that the loss of bak expression, in conjunction with the previously reported overexpression of bcl-2, might contribute to the pathogenesis of basal cell carcinoma.

Blotting, Western↗
PubMed1996

Regulation of cornifin alpha expression in the vaginal and uterine epithelium by estrogen and retinoic acid.

In this study, we analyze the regulation of the squamous-specific gene, cornifin alpha, by estrogen and retinoic acid in vaginal and uterine epithelial cells. In ovariectomized animals, the vaginal epithelium consists of a stratified, nonkeratinizing epithelium which changes into a highly-stratified, keratinizing epithelium upon treatment with estradiol. This transition is accompanied by a dramatic induction of the crosslinked envelope precursor, cornifin alpha. An increase in cornifin mRNA can be detected as early as 3 h after treatment. A similar effect is observed for the synthetic estrogenic agent diethylstilbestrol while other steroid hormones, including testosterone, progesterone or dexamethasone have little effect on cornifin expression. In contrast to the vagina, estradiol induces neither squamous differentiation nor expression of cornifin alpha in the uterine epithelium. Similar to the action of estradiol, vitamin A-deficiency greatly enhances squamous differentiation and keratinization in the vaginal epithelium. But unlike estradiol, it induces squamous metaplasia in the normally columnar, uterine epithelium, which eventually is replaced by a keratinizing epithelium in severe deficiency. This transition is associated with an induction of cornifin alpha expression. Immunohistochemical and in situ hybridization analysis localizes cornifin protein and mRNA in the suprabasal layers of the squamous epithelium. Our results demonstrate that estrogen and retinoids play key roles in the regulation of differentiation and cornifin alpha expression in the uterine and vaginal epithelium.

Animals↗
PubMed1996

Cloning and regulation of cornifin beta, a new member of the cornifin/spr family. Suppression by retinoic acid receptor-selective retinoids.

In this study, we describe the isolation and characterization of a cDNA clone C12 that encodes a new member of the cornifin/small proline-rich protein (spr) family, which we have named cornifin beta. C12 encodes a 1.1-kilobase pair mRNA and a 24.3-kDa cytosolic protein with a high proline content (19%). Its total amino acid sequence exhibits a 37-66% identity while the first 30 amino acids at the amino terminus are 87% identical to that of members of the cornifin family. At its carboxyl terminus, cornifin beta contains 21 tandem repeats of an octapeptide. Cornifin beta expression is restricted to several squamous epithelia. It is highly expressed in esophagus, tongue, and oral mucosa but, in contrast to cornifin alpha, is not detectable in the epidermis. Both retinoic acid and a retinoid selective for the nuclear retinoic acid receptors were very potent suppressors of cornifin beta expression while an analog selective for the nuclear retinoid X receptors was much less effective, suggesting that a specific retinoid signaling pathway is involved in this suppression. Cornifin beta can function through some of its Gln residues as an amine acceptor in transglutaminase-catalyzed cross-linking reactions. These results indicate that cornifin beta functions as a cross-linked envelope precursor.

Amino Acid Sequence↗
PubMed1996

Impaired glucose tolerance, diabetes, and cardiovascular disease risk factor profiles in the elderly. The Honolulu Heart Program.

OBJECTIVE: The relationship between glucose tolerance status and other cardiovascular disease (CVD) risk factors was evaluated in a cohort of Japanese-American men (n = 3,741) ages 71-93 years who participated in the fourth examination of the Honolulu Heart Program in 1991-1993. RESEARCH DESIGN AND METHODS: In this cross-sectional study, subjects were classified by reported diabetes and glucose tolerance status using questionnaires and the World Health Organization (WHO) criteria, respectively. RESULTS: The prevalence of reported diabetes was 17%. Among the men who completed an oral glucose tolerance test and had no history of diabetes (n = 1,900), 23% were diagnosed as diabetic and 39% had impaired glucose tolerance (IGT) by WHO criteria. The CVD risk factor profiles of men with IGT and diabetes were significantly more adverse compared with men with normal glucose tolerance after adjustment for age. The rates of hypertension, mean levels of BMI, waist-to-hip ratio, triglycerides, and fasting insulin were higher in men with IGT and diabetes compared with normal subjects. Opposite trends were observed for HDL cholesterol. Two-hour insulin was significantly higher among men with IGT and previously undiagnosed diabetes. Men with known diabetes had a lower physical activity index and higher fibrinogen levels than normal subjects. No significant differences were observed for current smoking and alcohol intake. Differences in risk factor levels by glucose tolerance status remained after adjustment for age, physical activity, BMI, and waist-to-hip ratio. CONCLUSIONS: These findings show that among elderly men of Japanese ancestry, impaired glucose tolerance and undiagnosed and known diabetes are highly prevalent, and these conditions are associated with adverse CVD factor profiles.

Age Factors↗
PubMed1996

The GENNID Study. A resource for mapping the genes that cause NIDDM.

OBJECTIVE: To develop a resource, consisting of comprehensive data and lymphoblastoid cell lines, of well-characterized NIDDM families that will be available to the scientific community for genetic studies of NIDDM. RESEARCH DESIGN AND METHODS: Non-Hispanic white, Hispanic, African-American, and Japanese-American multiplex NIDDM families, with a minimum of one affected sib-pair, are being collected by the eight Harold Rifkin Family Acquisition Centers. Detailed family and medical histories are obtained from all participants. Family members with diabetes have fasting blood samples drawn, while nondiabetic family members have an oral glucose tolerance test and, when possible, insulin sensitivity and insulin secretion measurements by frequently sampled intravenous glucose tolerance testing or euglycemic insulin clamp. Lymphoblastoid cell lines are established for all participants. RESULTS: Over 1,400 individuals from approximately 220 families have been studied since the start of the GENNID (Genetics of NIDDM) program in July 1993. The goal is that by July 1997, data from 300 non-Hispanic white families, > 100 Hispanic families, > 100 African-American families, and 15 Japanese-American families will have been collected. CONCLUSIONS: The identification of the genes responsible for NIDDM may now be achievable, but only if sound phenotypic data are linked to genetic material from a large number of well-described multiplex families. The GENNID project of the American Diabetes Association is creating a comprehensive resource that will expedite the identification of the genetic basis of NIDDM.

Black or African American↗
PubMed1996

Hypertension in Japanese Americans: the Seattle Japanese-American Community Diabetes Study.

AMONG SEATTLE'S JAPANESE AMERICANS, hypertension is associated with older age, male gender (in the younger age groups), glucose intolerance (impaired glucose tolerance and diabetes), and visceral obesity (measured by computed tomography). The gender difference in prevalence of hypertension is absent in those ages 65 to 74 and in those with diabetes. In the absence of diabetes, hypertension is not associated with fasting plasma insulin levels in the older second generation, but it is in the younger third generation. The association of hypertension with plasma insulin in the third generation may be due to the association between diabetes and plasma insulin and the presence of many prediabetic individuals in this generation. About three-fourths of Japanese Americans are aware of their hypertension, slightly more than half of hypertensive Japanese Americans are being treated with anti-hypertensive medication, and of those receiving anti-hypertensive medication, less than half have their hypertension controlled. Women tend to be less aware of hypertension, to receive anti-hypertensive medication less often, and to have their hypertension less well-controlled than men.

Adult↗
PubMed1995

Identification and characterization of a novel squamous cell-associated gene related to PMP22.

In this study, we identify and characterize a novel gene, CL-20, that encodes a 17.8-kDa protein with sequence and structural similarity to the growth arrest-specific gene gas3/peripheral myelin protein gene PMP22. The CL-20 protein exhibits a 43% identity with PMP22. The positions of the four lipophilic domains and the N-glycosylation site of PMP22 are conserved in CL-20, suggesting that it also is an integral membrane glycoprotein. The CL-20 gene is located on human chromosome 12 rather than 17 and encodes a 2.8-kilobase mRNA instead of 1.7-kilobase mRNA. These observations indicate that the CL-20 gene is related to but distinct from PMP22. In contrast to PMP22, CL-20 mRNA and protein are induced during squamous differentiation of rabbit tracheal epithelial cells in vitro, and Northern blot analysis and in situ hybridization demonstrated that CL-20 mRNA is most abundant in squamous epithelia. These results indicate that the high expression of CL-20 is closely correlated with squamous differentiation. The differences in tissue-specific expression and regulation between CL-20 and PMP22 suggest different roles for these two proteins. Retinoids, which inhibit squamous differentiation, repress the induction of CL-20. The retinoic acid receptor-selective retinoid SRI-6751-84 is the most effective in suppressing CL-20, suggesting that the activation of the retinoic acid receptor signaling pathway is important in this suppression.

Amino Acid Sequence↗
PubMed1995

Allergic granulomatosis (Churg-Strauss) associated with cutaneous manifestations: report of two cases.

Allergic granulomatosis (Churg-Strauss) is sometimes associated with cutaneous manifestations. Biopsies of these manifestations are characteristic enough to allow for the diagnosis of this disease through histological examination. Case 1 involved a 34-year-old man who developed a low-grade fever, blood eosinophilia, paralysis of the right oculomotor nerve, and a polymorphic eruption. In addition, he suffered from preceding asthma and paresthesia of the legs and eventually developed heart failure. The histological examination of a biopsy taken from a hemorrhagic bulla showed a dense perivascular infiltration of eosinophils in the upper dermis and basophilic degeneration of collagen fibers. Case 2 involved a 41-year-old man who was afflicted with urticarial erythemas, livedoid erythemas, preceding asthma, and blood eosinophilia. During the course of his illness, he also developed bilateral peroneal nerve paralysis and two small erythemato-bullous lesions. The histological examination of a urticarial lesion revealed an abundant eosinophil perivascular infiltration; examination of a nodule revealed basophilic degeneration with a granulomatous reaction. Clinical and laboratory studies strongly suggested the diagnosis of allergic granulomatosis in both of these cases. The diagnosis was also supported by a histological examination of the skin lesions.

Adult↗
PubMed1994

TAK1: molecular cloning and characterization of a new member of the nuclear receptor superfamily.

Using polymerase chain reaction and two degenerate primers whose designs were based on the two best conserved regions of the DNA-binding domain of the nuclear receptor superfamily, we identified and cloned a novel orphan receptor, named TAK1. The open reading frame of TAK1 encodes a protein of 596 amino acid residues. Based on the modular structure and the presence of a DNA-binding domain containing two zinc fingers TAK1 belongs to the steroid/thyroid hormone receptor superfamily. The amino acid sequence of TAK1 is most closely related to the orphan receptor TR2-11. Their overall sequence homology is 64%, with the highest similarity (82%) being observed in the DNA-binding domain. Northern blot analysis using RNA from multiple human tissues showed that a 9.4 kilobase TAK1 transcript was expressed ubiquitously and that the presence of a 2.8 kilobase mRNA was largely restricted to the testis. In situ hybridization using sections of rat and mouse testes and Northern blot analysis using RNA from testes of rats at various ages revealed that TAK1 is most abundantly expressed in spermatocytes whereas little expression was observed in other germ cells or somatic cells. In situ hybridization using other mouse and rat tissues revealed cell type-specific expression of TAK1 in several tissues. Our observations suggest a role for this putative transcription factor in the regulation of gene expression in specific cell types. In the testis, TAK1 appears to control gene expression during spermatogenesis, particularly during the meiotic phase.

Amino Acid Sequence↗
PubMed1993

Expression of cornifin in squamous differentiating epithelial tissues, including psoriatic and retinoic acid-treated skin.

The expression of cornifin, a putative cross-linked envelope precursor, was investigated in several squamous differentiating tissues by in situ hybridization and immunohistochemical analysis. Cornifin mRNA and protein, which are absent in the normal mucociliary tracheal epithelium, are induced in the suprabasal layers of the squamous metaplastic tracheal epithelium of vitamin A-deficient hamsters. Similar to the induction of squamous metaplasia in vivo, culture of rabbit tracheal cells in the absence of retinoids results in squamous differentiation and expression of cornifin. This induction of cornifin expression is suppressed by retinoic acid and several of its analogs. Cornifin mRNA and protein are also detected in the suprabasal layers of the squamous epithelium of rabbit esophagus and tongue. The distribution of cornifin in human epidermis was compared with that of two other crosslinked envelope precursor proteins, involucrin and loricrin. The localization of cornifin and involucrin is very similar. Both are induced in the spinous layer and appear at an earlier stage during epidermal differentiation than loricrin. The expression of cornifin is greatly increased in psoriatic skin. Cornifin mRNA is barely detectable in normal epidermis, whereas it is present at relatively high levels in the suprabasal layers of psoriatic epidermis. Topical treatment with RA results in thickening of the skin and increases the level of cornifin mRNA and protein in the upper spinous layers of mouse skin. Cornifin expression correlates generally with squamous differentiation in a variety of tissues and is abnormally regulated in psoriatic skin and in skin treated topically with retinoic acid.

Administration, Topical↗
PubMed1993

Prominent telangiectasia associated with marked bleeding in CREST syndrome.

A 64-year-old woman with CREST syndrome developed prominent telangiectases mimicking hereditary hemorrhagic telangiectasia (HHT) of Osler-Rendu-Weber. We have been following her since she first came to us with discrete telangiectatic mats and Raynaud's phenomenon 11 years ago. Telangiectatic lesions have been seen on her larynx and esophagus in addition to commonly affected sites. She has experienced spontaneous epistaxis and marked bleeding from the lesions on her lips, oral mucous membrane, and soles. This case illuminates new aspects of telangiectasia in CREST syndrome.

Calcinosis↗
PubMed1993

Regulation of glutamic acid decarboxylase diabetes autoantigen expression in highly purified isolated islets from Macaca nemestrina.

Macaca nemestrina, which may have larger and more numerous pancreatic islets than other species, was used for large scale islet isolation by ductal collagenase perfusion and Ficoll gradient centrifugation. The average yield was 51,000 islet equivalents per pancreas, or 8,750 islets equivalents per g. The average purity was 91%, often exceeding 95%. These are the highest reported size, purity, and yield per g of any nonautomated primate islet series. Perifusion with glucose, arginine, and isobutylmethylxanthine showed appropriate biphasic insulin secretion. Unlike that in the rat, human islet glutamic acid decarboxylase (GAD) isoform expression is restricted. However, glycemic regulation of GAD expression has been shown only in rats. We, therefore, tested hypotheses that M. nemestrina islets also have restricted GAD expression, that GAD expression in primates is stimulated by glucose, and that this stimulation remains restricted to the 64,000 mol wt (GAD65) isoform. Immunoprecipitation of labeled islet extracts showed that GAD65 expression increased 16.7 +/- 0.6-fold during high glucose in vitro culture. After controlling for observed increases in protein synthesis, specific glucose stimulation was still 4.2 +/- 0.2-fold. Specific antisera revealed no GAD67 expression under basal conditions, and isoform restriction was maintained during stimulation. Increased GAD65 synthesis thus accounts for glucose stimulation of 64K expression. These time- and concentration-dependent effects of glucose suggest that hyperglycemia increases autoantigenicity and may accelerate beta-cell destruction in primates, supporting a role for beta-cell rest in insulin-dependent diabetes mellitus prevention.

Animals↗
PubMed1992

Cornifin, a cross-linked envelope precursor in keratinocytes that is down-regulated by retinoids.

In this study, we have characterized the cDNA clone SQ37 that was isolated previously from a rabbit squamous cell library. The gene encodes a 14-kDa protein that appears to function as a component of the cross-linked envelope in squamous differentiating cells. The protein, which has been named cornifin, has a high content of proline (31%), glutamine (20%), and cysteine (11%) and contains 13 repeats of an octapeptide (consensus sequence, EPCQPKVP) at its C terminus. SQ37 mRNA and protein are induced during squamous differentiation of rabbit tracheal (RbTE) cells and human epidermal keratinocytes. This induction is repressed by retinoids. Immunohistochemical studies reveal SQ37 immunoreactivity in fragmented cross-linked envelopes from squamous-differentiated RbTE cells and in the suprabasal layers of the epidermis. In situ hybridization analysis showed that the presence of SQ37 mRNA is restricted to the suprabasal layers. Treatment of RbTE cells with a Ca2+ ionophore induces cross-linking of the SQ37 protein into higher molecular weight complexes. This cross-linking reaction appears to be mediated by transglutaminase type I. Our observations suggest that the protein encoded by SQ37 participates in the assembly of the cross-linked envelope.

Amino Acid Sequence↗
PubMed1992

Retinoic acid receptors as regulators of human epidermal keratinocyte differentiation.

To examine the role of nuclear retinoic acid (RA) receptors (RARs) in the regulation of squamous differentiation in normal human epidermal keratinocytes (NHEK), we analyzed binding activity, mRNA expression, and transcriptional activity of the endogenously expressed RARs. Specific RA-binding activity eluted from size-exclusion HPLC with an apparent mol wt of 50 kilodaltons and was predominantly (greater than 95%) associated with the NHEK nuclear cell fraction. This RAR-binding activity represented in part the expression of RAR alpha and RAR gamma genes, whose transcripts were expressed in similar abundance in undifferentiated NHEK. Differentiation resulted in lower mRNA expression of RAR alpha relative to the mRNA expression of RAR gamma. Treatment of NHEK cells with 10(-6) M RA did not induce expression of RAR beta mRNA. Similarly, three squamous cell carcinoma cell lines derived from human skin and oral cavity expressed RAR alpha and RAR gamma transcripts, but not RAR beta transcripts. Transfection of NHEK with chloramphenicol acetyltransferase (CAT) reporter plasmids indicated that the endogenously expressed RARs could activate transcription through the RAR beta response element in a concentration-dependent manner with doses of 10(-9) M RA and higher. CAT expression was not activated through TRE, a palindromic thyroid hormone response element with purported RA responsiveness. The competitive binding of benzoic acid derivatives of RA to RAR correlated with the ability of each analog to suppress mRNA expression of the squamous cell markers, involucrin, type I transglutaminase, and SQ37, and to activate transcription of the RAR beta response element-CAT reporter. These results demonstrate that the control of NHEK differentiation by RA is consistent with the interaction of the retinoid with RAR and the regulation of transcription by that ligand-receptor complex.

Base Sequence↗
PubMed1990

[Expression pattern of retinoic acid receptor genes in normal human skin].

Expression pattern of the retinoic acid receptor (RAR) genes in normal human skin was investigated by in situ hybridization method. Using the riboprobes from cDNAs for three subtypes of RAR, we found that the RAR-alpha and the RAR-gamma genes were expressed in the epidermis. Significant expression of the RAR-beta gene was detected neither in the epidermis nor in the dermis. Expression of the RAR-alpha and -gamma genes was detected both in te basal cell layer and in the squamous cell layers. Moreover, the RAR-alpha and -gamma genes were expressed in the eccrine sweat glands as well. These results indicate that the target cells for retinoic acid (RA) in human skin are keratinocytes and the epithelial cells of epidermal appendages. These findings thus demonstrate that, among three subtypes of RAR, both RAR-alpha and RAR-gamma are essential for control of epidermal and epithelial cell differentiation in human skin.

Carrier Proteins↗
PubMed1990

[Cutaneous infection by Mycobacterium fortuitum biovariant "third group"--a case report and bacteriological examination of the isolate].

A 22-year-old woman with ten-year history of atopic dermatitis first noticed an erythematous ++, indurated, and fluctuant lesion on her back six month prior to visiting our hospital in February 1989. The dusky red skin lesion gradually spread to the right side of her trunk and drained small amount of purulent or serosanguineous fluid. A skin biopsy specimen showed mixed pattern of nonspecific inflammatory infiltrate and granulomatous infiltrate in the dermis. A culture of the biopsy specimen showed a rapidly growing atypical acid-fast bacteria, which was identified as Mycobacterium fortuitum and classified as biovariant "third group" by positive growth on mannitol and inositol. Minimum inhibitory concentrations (MICs) of different antimicrobial agent using broth medium showed that the isolate was susceptible to the new quinolones such as ofloxacin and ciprofloxacin. The patient responded to treatment with doxycycline followed by with ofloxacin. Subspecies classification and antibiotic susceptibilities were discussed with special reference to treatment of rapidly growing mycobacteria.

Adult↗
PubMed1989

Expression of retinoic acid receptor genes in keratinizing front of skin.

We found, by an in situ hybridization method with riboprobes synthesized from human cDNA of the retinoic acid receptor (RAR), that the RAR genes (predominantly gamma-subtype) are intensively expressed in the epidermis of normal and psoriasic human skins, and also in keratinizing fronts of 4-day-old mouse skins, nail matrices and hair follicles. Thus, target cells of retinoic acid in the skins are concluded to be keratinocytes, which is quite consistent with the fact that retinoic acid regulates keratinization of epidermis in vivo and also modulates expression of the keratin gene in vitro.

Animals↗