Clinical utility of an interferon-gamma-based assay for mycobacterial detection in papulonecrotic tuberculid.
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Adult↗
Biomedical subjects
W Fujimoto
Publications and source records attributed to W Fujimoto.
A failure of mucocutaneous lymphangiogenesis may underlie the clinical features of lipoid proteinosis.
Lipoid proteinosis (LiP) (OMIM 247100) is a rare autosomal recessive disease caused by loss of function mutations in the extracellular matrix protein 1 gene, ECM1, on chromosome 1q21. LiP is characterized clinically by hoarseness in early infancy, followed by waxy papules and plaques on the face and body along with pox-like and acneiform scars. We studied a 20-year-old Japanese woman with LiP. She was born of consanguineous parents. Biopsy specimens obtained from a nodule on the elbow were used for histopathology, immunohistology and electron microscopy. Exons 6 and 7 of ECM1 were amplified by polymerase chain reaction (PCR) from genomic DNA from the proband, her parents, her brother and an unrelated person. PCR products were sequenced to detect the mutation. Histopathological examination revealed an irregular mass of calcium beneath deposits of a hyaline material in the dermis. Immunofluorescence double staining showed that the CD31-positive microvascular density was increased but that staining for the lymphatic-specific hyaluronan receptor LYVE-1 was drastically diminished in lesional compared with nonlesional skin of the patient and with normal skin. Electron microscopy revealed marked concentric reduplication of basal laminae not only around blood vessels but also around solitary dermal cells positive for Weibel-Palade bodies scattered in the hyaline material. Sequencing of the PCR products revealed a homozygous frameshift mutation, 507delT, in exon 6. This led to a premature stop codon 23 bp downstream. The results of immunopathological and ultrastructural characterization suggest that a failure of mucocutaneous lymphangiogenesis may underlie the clinical features of LiP. Identification of mutation 507delT in a Japanese patient with LiP further supports the thesis that this mutation represents a recurrent mutation in ECM1 in patients with LiP. To our knowledge, this case represents the first report of calcinosis cutis occurring in LiP.
Adult↗
Lichen planus pemphigoides and multiple keratoacanthomas associated with colon adenocarcinoma.
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Adenocarcinoma↗
Confocal laser scanning microscopic observation of glycocalyx production by Staphylococcus aureus in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus.
BACKGROUND: Glycocalyx collapses during dehydration to produce electron-dense accretions. Confocal laser scanning microscopy (CLSM) may be used to visualize fully hydrated microbial biofilms. OBJECTIVES: Using CLSM, to analyse glycocalyx production by Staphylococcus aureus cells in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus. A second objective was to compare numbers of S. aureus cells in tissue sections prepared by different methods for routine light microscopy. METHODS: S. aureus cells in skin lesions of impetigo, atopic dermatitis and pemphigus were stained with safranin, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. RESULTS: All S. aureus cells tested in skin lesions of impetigo, atopic dermatitis and pemphigus were covered with glycocalyx and formed microcolonies. The numbers of S. aureus cells in a routine light microscopy section were significantly lower than those in a frozen section that had not been dehydrated with ethanol. CONCLUSIONS: S. aureus cells generally produce glycocalyx in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus, which accounts for the difficulty of removing S. aureus cells from these skin lesions. The glycocalyx may collapse during dehydration and most of the S. aureus cells may be carried away during preparation of routine light microscope sections.
Acetic Acid↗
Amicrobial pustular dermatosis in two patients with immunological abnormalities.
We report two patients with severe amicrobial pustular dermatosis with immunological abnormalities: a 63-year-old woman with a 30-year-history of discoid lupus erythematosus and sicca syndrome, and a 35-year-old woman with high levels of gamma-globulinemia and positive antinuclear antibodies. Both patients presented with crusty and eroded erythematous plaques studded with aseptic pustules on the back, face, and scalp. Histological examination showed acanthosis, neutrophilic exocytosis to the epidermis, and neutrophilic and lymphocytic infiltration with nuclear dust in the dermis. These patients were diagnosed as having "amicrobial pustulosis associated with autoimmune diseases". The eruptions improved with combination treatment of oral prednisolone with cyclosporin A or diaminodiphenylsulphone. Although the pathogenesis remains unclear, amicrobial pustular dermatosis might be one of the cutaneous complications in autoimmune diseases.
Administration, Oral↗
Thyroid gland tumour, pemphigus foliaceus and myasthenia gravis in the daughter of a woman with myasthenia gravis.
We describe a rare case of pemphigus foliaceus associated with familial myasthenia gravis (MG). A 35-year-old woman developed MG during oral corticosteroid treatment for pemphigus foliaceus. She had been operated on for a thyroid gland tumour that was confirmed histopathologically to be papillary carcinoma without metastasis. At the time of treatment, her mother had had MG for 30 years and undergone thymectomy 22 years ago. A specific ELISA technique showed that antidesmoglein 1 antibody was present in the daughter. There are many reports of multiple diseases such as pemphigus, thymoma, malignancy, and other autoimmune diseases associated with MG. However, familial MG following pemphigus foliaceus has not been reported previously.
Adult↗
Expression pattern of the bcl-2 homologous protein bad in normal skin, psoriasis vulgaris and keratinocytic tumors.
Previous investigations focused on the mechanisms and regulation of apoptotic process have found that bcl-2 and its homologous proteins are central regulators of the mitochondrial phase of apoptosis. Expression of several members of the bcl-2 family has been studied in various tissues including skin under normal as well as disease conditions. In this report, we investigated the expression of bad, the pro-apoptotic member of the BH3 subfamily, in normal and psoriatic epidermis, keratoacanthoma, and basal and squamous cell carcinomas. Normal and psoriatic epidermis showed accentuation of the staining in the lower suprabasal compartment. A weak, predominantly diffuse staining pattern was observed in the upper epidermis of psoriatic plaques. Keratoacanthoma showed strong but diffuse immunostaining for pro-apoptotic bad, however we found only weak bad expression in squamous cell carcinoma. Seven out of 15 basal cell carcinomas failed to express bad protein. There was no correlation between bad positivity and depth of tumour infiltration. Our observation suggests that the pro-apoptotic bad may function as one of regulators involved in the maintenance of epidermal homeostasis and this function could be altered depending on the disease state.
Carrier Proteins↗
Linear IgA disease with IgA antibodies directed against 200- and 280-kDa epidermal antigens.
We report an 80-year-old man with the lamina lucida type of linear IgA disease, with IgA autoantibodies reactive with 200-kDa and 280-kDa epidermal proteins. The patient presented with widespread bullous lesions on his trunk and extremities without mucosal involvement. Histopathology of lesional skin showed a subepidermal blister with papillary microabscesses of neutrophils and a few eosinophils. Direct immunofluorescence microscopy of perilesional skin showed linear deposits of IgA and C3 at the basement membrane zone. The patient's serum contained IgA autoantibodies that bound exclusively to the epidermal side of 1 mol L-1 NaCl split skin as determined by indirect immunofluorescence microscopy. Circulating IgA autoantibodies to 200- and 280-kDa antigens were detected in the patient's serum by immunoblot analysis using extracts from normal human epidermis and human epidermal keratinocytes. These two antibodies, eluted from individual nitrocellulose membranes, reacted with the epidermal side of 1 mol L-1 NaCl split skin on indirect immunofluorescence microscopy, and bound to hemidesmosomes as determined by immunoperoxidase electron microscopy. This observation suggests the presence of hitherto uncharacterized 200- and 280-kDa hemidesmosomal proteins distinct from BPAG1, BPAG2 and beta4 integrin as target antigens in linear IgA disease.
Aged↗
Anti-epiligrin cicatricial pemphigoid with IgG autoantibodies to the beta and gamma subunits of laminin 5.
Anti-epiligrin cicatricial pemphigoid is an autoimmune subepithelial blistering disorder of mucous membranes and skin. By immunoblot analyses, sera of most patients with antiepiligrin cicatricial pemphigoid have been shown to react specifically with the alpha3 chain of laminin 5. We describe the first patient with anti-epiligrin cicatricial pemphigoid in whom circulating IgG autoantibodies directed against the beta3 and gamma2-chains of laminin 5 were detected. Treatment with oral prednisolone was beneficial in controlling the disease.
Aged↗
Pachyonychia congenita type 2: keratin 17 mutation in a Japanese case.
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Adult↗
A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.
The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that has a pivotal role in adipocyte differentiation and expression of adipocyte-specific genes. The PPARgamma1 and gamma2 isoforms result from alternative splicing and have ligand-dependent and -independent activation domains. PPARgamma2 has an additional 28 amino acids at its amino terminus that renders its ligand-independent activation domain 5-10-fold more effective than that of PPARgamma1. Insulin stimulates the ligand-independent activation of PPARgamma1 and gamma2 (ref. 5), however, obesity and nutritional factors only influence the expression of PPARgamma2 in human adipocytes. Here, we report that a relatively common Pro12Ala substitution in PPARgamma2 is associated with lower body mass index (BMI; P=0.027; 0.015) and improved insulin sensitivity among middle-aged and elderly Finns. A significant odds ratio (4.35, P=0.028) for the association of the Pro/Pro genotype with type 2 diabetes was observed among Japanese Americans. The PPARgamma2 Ala allele showed decreased binding affinity to the cognate promoter element and reduced ability to transactivate responsive promoters. These findings suggest that the PPARgamma2 Pro12Ala variant may contribute to the observed variability in BMI and insulin sensitivity in the general population.
Adult↗
Detection of anti-type VII collagen antibody in Sjögren's syndrome/lupus erythematosus overlap syndrome with transient bullous systemic lupus erythematosus.
Bullous systemic lupus erythematosus (SLE) is a chronic, widespread, non-scarring, subepidermal blistering eruption associated with autoimmunity to type VII collagen. We describe a patient with Sj ogren's syndrome/lupus erythematosus overlap syndrome who showed transient blistering eruptions over limited skin surface and in oral mucosa. At the time of aggravation, the patient's serum contained IgG autoantibodies that bound to the dermal side of 1 mol/L NaCl-split normal skin, as determined by an indirect immunofluorescence test, and that reacted to type VII collagen, as determined by immunoblotting on dermal extract. Our observations suggest that a chronic, widespread, blistering eruption is not a prerequisite for the diagnosis of bullous SLE, and a mild, transient, blistering eruption could be a manifestation of type I bullous SLE.
Adult↗
Anti-epiligrin cicatricial pemphigoid: a case associated with gastric carcinoma and features resembling epidermolysis bullosa acquisita.
A 48-year-old woman with anti-epiligrin cicatricial pemphigoid (CP) who showed clinical features resembling epidermolysis bullosa acquisita was found to have adenocarcinoma of the stomach. Histological examination of lesional skin demonstrated a subepidermal blister. Direct immunofluorescence microscopy of perilesional skin revealed linear deposits of IgG and C3 at the basement membrane zone. The patient's serum contained IgG autoantibodies that bound to the dermal side of 1 mol/L NaCl-split normal human skin as determined by indirect immunofluorescence microscopy, and the lamina lucida as determined by indirect immunoelectron microscopy. The patient's serum immunoprecipitated laminin-5 from extracts and media of biosynthetically radiolabelled human keratinocytes. Immunoblot studies showed that the patient's autoantibodies specifically bound the alpha3 subunit of this laminin isoform. Fragility of the skin and bullous lesions disappeared after total gastrectomy, but soon reappeared possibly in association with metastatic disease in a lymph node. The possibility that anti-epiligrin CP may develop paraneoplastically in some patients is discussed.
Anti-Inflammatory Agents↗
Expression of the bcl-2 homologue bax in normal human skin, psoriasis vulgaris and non-melanoma skin cancers.
Bax (bcl-2-associated X protein) is a recently identified member of the bcl-2 family and one of the principal inducers of apoptosis. We examined the distribution of bax protein in normal human skin and several skin diseases by immunohistochemistry. Bax immunoreactivity was present in normal epidermis and its appendages, with the suprabasal compartment being stained more strongly than basal keratinocytes. Bax immunostaining was also detected in the epidermis of psoriasis vulgaris and 5 keratoacanthomas examined. We could observe only weak bax immunoreactivity in 15 squamous cell carcinomas examined, with the exception of well-differentiated tumour islands in two tumours, which expressed immunostaining for bax comparable to that of normal suprabasal epidermis. Immunostaining for bax was negative in 12 out of 17 basal cell carcinomas and the remaining five tumours showed weak bax reactivity in tumour cells scattered within tumour masses and in palisading layers of some tumour formations. Western blot analysis confirmed the expression of bax protein in normal skin, psoriasis vulgaris and squamous cell carcinoma as well as the absence of bax in basal cell carcinoma. Our findings suggest that the loss of pro-apoptotic bax protein in basal cell carcinoma and its reduced expression in squamous cell carcinoma might be an important step in the development of these two skin cancers.
Apoptosis↗
Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B.
Both insulin and insulin-like growth factor 1 (IGF-1) are known to reduce glucose-dependent insulin secretion from the beta cells of pancreatic islets. In this paper we show that the mechanism by which IGF-1 mediates this effect is in large part through activation of a specific cyclic nucleotide phosphodiesterase, phosphodiesterase 3B (PDE3B). More specifically, in both isolated pancreatic islets and insulin-secreting HIT-T15 cells, IGF-1 inhibits insulin secretion that has been increased by glucose and glucagonlike peptide 1 (GLP-1). Moreover, IGF-1 decreases cAMP levels in parallel to the reduction of insulin secretion. Insulin secretion stimulated by cAMP analogs that activate protein kinase A and also are substrates for PDE3B is also inhibited by IGF-1. However, IGF-1 does not inhibit insulin secretion stimulated by nonhydrolyzable cAMP analogs. In addition, selective inhibitors of PDE3B completely block the ability of IGF-1 to inhibit insulin secretion. Finally, PDE3B activity measured in vitro after immunoprecipitation from cells treated with IGF-1 is higher than the activity from control cells. Taken together with the fact that pancreatic beta cells express little or no insulin receptor but large amounts of IGF-1 receptor, these data strongly suggest a new regulatory feedback loop model for the control of insulin secretion. In this model, increased insulin secretion in vivo will stimulate IGF-1 synthesis by the liver, and the secreted IGF-1 in turn feedback inhibits insulin secretion from the beta cells through an IGF-1 receptor-mediated pathway. This pathway is likely to be particularly important when levels of both glucose and secretagogues such as GLP-1 are elevated.
Animals↗
IRF-1 expression in normal human epidermal keratinocytes.
Interferon gamma (IFN-gamma) is a potent inducer of cell growth arrest in human epidermal keratinocytes. Interferon regulatory factor-1 (IRF-1), an interferon-inducible gene, is a mediator of interferon action. It has also been suggested that IRF-1 may have a functional role as a tumor suppressor gene and may be associated with the antiproliferative effect of IFN-gamma. We examined the expression of IRF-1 mRNA in normal human epidermal keratinocytes (NHEK). Northern blot analysis demonstrated an increased expression of IRF-1 mRNA by IFN-gamma in NHEKs. This increased expression of IRF-1 mRNA by IFN-gamma was not blocked by treatment with cycloheximide, but was abolished by treatment with actinomycin D. In addition, neither pretreatment with TPA, a protein kinase C (PKC) activator, nor treatment with H7, a PKC inhibitor, affected the induction of IRF-1 mRNA by IFN-gamma. These results indicate that IFN-gamma-induced IRF-1 mRNA in NHEKs is transcriptional and PKC-independent.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts.
We compared the patterns of keratin 10 (K10) and keratin 17 (K17) expression in epidermoid cysts, trichilemmal cysts, eruptive vellus hair cysts, and steatocystoma multiplex. Epidermoid cysts expressed K10 and eruptive vellus hair cysts expressed K17, whereas trichilemmal cysts and steatocystoma multiplex showed expression of both K10 and K17. Our findings support the opinion that eruptive vellus hair cysts, which stained negative for K10, and steatocystoma multiplex are distinct entities and not variants of one disorder.
Cysts↗
Differential expression of human cornifin alpha and beta in squamous differentiating epithelial tissues and several skin lesions.
Cornifins/small proline-rich proteins (SPRRs) belong to a family of proline-rich proteins that function as cornified envelope precursors. We report here an immunohistochemical analysis of human cornifin-alpha and -beta expression in several stratified squamous epithelia. In normal human skin, cornifin-alpha was expressed in the granular layer of the epidermis of palmoplantar skin, in the inner lining cells of the follicular infundibulum, and in the inner root sheath of the hair follicle. It was also expressed in the upper squamous layers of the oral, esophageal, and vaginal epithelia. Cornifin-beta was detected in oral, esophageal, and vaginal epithelia, but not in normal skin. Immunoblot analysis revealed quantitative differences in cornifin-alpha expression in skin from different regions. Studies of specimens from various skin diseases showed that (i) cornifin-alpha was upregulated in inflammatory skin diseases, hyperplastic lesions, and in well-differentiated squamous cell carcinomas (SCCs), (ii) the expression of cornifin-beta was absent in inflammatory skin but was detected in highly differentiated keratinocytes in well-differentiated SCCs of the skin and some other hyperproliferative skin lesions, and in SCCs of the oral mucosa and esophagus. Northern blot analysis revealed that cornifin-alpha mRNA was present in all the squamous epithelial tissues studied, whereas cornifin-beta mRNA was expressed in oral mucosal epithelia and verrucous carcinoma of the skin but neither in normal nor in psoriatic skin. These results indicate that (i) the amount of cornifin alpha/SPRR1 expression in normal human skin depends on the body region, (ii) cornifin-alpha/SPRR1, but not cornifin-beta, contributes to the integrity of the hair follicle, and (iii) the expression of cornifin-beta is induced in some hyperplastic skin diseases only when the keratinocytes undergo extensive squamous differentiation.
Blotting, Northern↗