BCG granuloma appearing more than 50 years after vaccination.
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Biomedical subjects
Publications and source records attributed to Mariko Seishima.
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A patient with psoriasis vulgaris developed multiple purpura on the extremities and hemorrhage at the oral mucosa and gingiva with marked thrombocytopenia. This thrombocytopenia was possibly induced by a retinoid agent, etretinate, from the clinical course and data. The total amount of etretinate administered was 2,410 mg over 191 days (41.9 mg/kg body weight, average 15.3 mg/day). A platelet transfusion partially restored the platelet count and the purpura and gingival hemorrhage disappeared approximately 10 days after the cessation of etretinate. However, the platelet count remains at 60-80 x 103/mm3 after two and a half years without etretinate therapy. Although there are only a few case reports of etretinate-induced thrombocytopenia, we should pay more attention to the peripheral platelet count during etretinate therapy.
Psoriasis is recognized as a chronic inflammatory disease characterized by epidermal hyperproliferation. To identify psoriasis-related genes, we compared the mRNA populations of normal and psoriatic skin. We identified one gene, designated as cornifelin, which showed increased expression in psoriatic skin. Human cornifelin contains 112 amino acids and is expressed in the uterus, cervix, and skin. In situ hybridization analysis demonstrated the presence of human cornifelin in the granular cell layer of the epidermis. To investigate the function of cornifelin, we established a transgenic mouse line overexpressing human cornifelin. Using these mice, we have shown that cornifelin is directly or indirectly cross-linked to at least two other cornified envelope proteins, loricrin and involucrin, in vivo. Overexpression of human cornifelin correlated with decreased loricrin expression and increased involucrin expression in the transgenic mouse. However, abnormality of epidermal differentiation was not observed in the transgenic mouse.
Psoriasis is a common skin disease characterized by hyperplastic regenerative epidermal growth and infiltration of immunocytes. The etiology of psoriasis is unknown, although several genetic and cellular factors have been elucidated. To find new psoriasis-related genes, we have cloned cDNAs that are differentially expressed between normal and psoriatic skins. Among these clones, we have identified a new gene that codes for a new member of the type IV cytosolic phospholipase A(2) (cPLA(2)) family. We refer to this gene as cPLA(2)delta. It encodes a polypeptide of 818 amino acids that has significant homology with known cPLA(2) proteins in the C2 and catalytic domains. The cPLA(2)delta gene was mapped to the 15q13-14 chromosomal locus, near to the locus of the cPLA(2)beta gene, from which it is separated by a physical distance of about 220 kb. To identify the phospholipase A(2) activity of cPLA(2)delta, we transfected COS-7 cells with His-tagged cPLA(2)delta. The cell lysate from these cells had calcium-dependent phospholipase A(2) activity. Northern blot analysis revealed that a cPLA(2)delta transcript of about 4 kb is expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. In situ hybridization and immunohistochemistry revealed that cPLA(2)delta is expressed strongly in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin; cPLA(2)alpha is not detected in either normal or psoriatic skin. These results suggest that cPLA(2)delta exhibits a unique distribution pattern compared with that of known cPLA(2) subtypes, and it may play a critical role in inflammation in psoriatic lesions.
BACKGROUND: Most paraneoplastic pemphigus (PNP) cases reported to date have been associated with lymphoproliferative neoplasms. Patients with PNP have autoantibodies against the plakin family (eg, envoplakin and periplakin). Antibodies against desmoglein 3 (Dsg3) and Dsg1, antigens for classic types of pemphigus, have also been reported to play an important role in the initial stage of PNP. OBSERVATIONS: We describe a patient with PNP associated with follicular dendritic cell sarcoma. Antibodies to envoplakin and periplakin were detected. When only mucosal lesions were observed at the early stage, the antibody to Dsg3 but not to Dsg1 was detected by enzyme-linked immunosorbent assay. After skin lesions appeared, antibodies to Dsg1 and Dsg3 were detected. These titers were elevated, with exacerbation of skin lesions. Although the patient received corticosteroid therapy, double-filtration plasmapheresis, and intravenous human immunoglobulin therapy after surgical resection of follicular dendritic cell sarcoma, she died of fungal infective lung embolisms. A direct immunofluorescence study of autopsy samples showed IgG deposition in the epidermis of the skin and oral mucosal membrane, but not in the lungs and kidneys and follicular dendritic cell sarcoma of the para-aortic area. CONCLUSION: In this patient with PNP and follicular dendritic cell sarcoma, there was an association between the clinical phenotype and the anti-Dsg antibody profile, as seen in pemphigus vulgaris.
Psoriasis is a skin disease with epidermal keratinocyte hyperproliferation and altered differentiation. To identify novel psoriasis-related genes, we investigated differentially expressed genes between normal and psoriatic skin. We identified a novel acyl CoA:diacylglycerol acyltransferase 2 (DGAT2) gene, which was decreased in human psoriatic skin. DGAT2 mRNA was expressed in sebaceous glands of normal human skin. DGAT2 protein was detected on endoplasmic reticulum. DGAT2 catalyzes the final step in the production of triglycerides and the accumulation of triglycerides in the tissues is considered to be related to insulin resistance. Therefore, we also investigated the expression of the DGAT2 gene in diabetic mice. DGAT2 mRNA was increased in the adipose, small intestine, and skeletal muscle in diabetic mice.
The autosomal recessive disorder lipoid proteinosis results from mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in several tissues (including skin) and composed of two alternatively spliced isoforms, ECM1a and ECM1b, the latter lacking exon 7 of this 10-exon gene (ECM1). To date, mutations that either affect ECM1a alone or perturb both ECM1 transcripts have been demonstrated in six cases. However, lipoid proteinosis is clinically heterogeneous with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurological abnormalities such as temporal lobe epilepsy. In this study, we sequenced ECM1 in 10 further unrelated patients with lipoid proteinosis to extend genotype-phenotype correlation and to add to the mutation database. We identified seven new homozygous nonsense or frameshift mutations: R53X (exon 3); 243delG (exon 4); 507delT (exon 6); 735delTG (exon 7); 785delA (exon 7); 892delC (exon 7) and 1190insC (exon 8), as well as two new compound heterozygous mutations: W160X/F167I (exon 6) and 542insAA/R243X (exons 6/7), none of which were found in controls. The mutation 507delT occurred in two unrelated subjects on different ECM1 haplotypes and may therefore represent a recurrent mutation in lipoid proteinosis. Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid proteinosis. Clinically, it appears that mutations outside exon 7 are usually associated with a slightly more severe mucocutaneous lipoid proteinosis phenotype, but neurological features do not show any specific genotype-phenotype correlation.
BACKGROUND: Acute human parvovirus B19 (B19) infection induces systemic lupus erythematosus (SLE)-like symptoms. It has been controversial whether B19 infection causes SLE and rheumatoid arthritis (RA). OBJECTIVES: This study prospectively investigated whether symptoms of B19 infection persisted for more than 2 years and whether persistent symptoms contributed to the development of SLE and RA. METHODS: In this prospective study, clinical findings were examined and laboratory examinations were performed in 42 adult patients 1, 2, 6, 12 and 24 months after the first consultation. RESULTS: Most acute symptoms disappeared within 2 weeks. However, arthralgia continued for 2 months in 2 women, 6 months in 1 woman and more than 2 years in 1 woman with positive antinuclear antibody and hypocomplementemia. The clinical findings of the patient with persistent arthralgia did not fulfill the criteria for SLE and RA. CONCLUSION: The symptoms caused by B19 infection were transient in most cases but persisted in 1 case in our series.
BACKGROUND: A patient with allergic contact dermatitis caused by hexavalent chromium plating on a cellular phone has already been reported. OBJECTIVES: This study described the clinical characteristics and results of patch tests in 8 patients with contact dermatitis possibly caused by handling a cellular phone. PATIENTS: The 8 patients were 4 males and 4 females aged from 14 to 54 years. They each noticed skin eruptions after 9-25 days of using a cellular phone. All patients had erythema, and 7 had papules on the hemilateral auricle or in the preauricular region. Three of 8 patients had a history of metal allergy. Chromate, aluminium and acrylnitrile-butadiene-styrene copolymer were used as plating on the cellular phones used by these patients. METHODS: Closed patch tests and photopatch tests were performed using metal standard antigens. RESULTS: The patch test was positive for 0.5, 0.1 and 0.05% potassium dichromate in all 8 patients. The photopatch test showed the same results. One patient was positive for 2% cobalt chloride and one for 5% nickel sulfate. CONCLUSION: It is important to consider the possibility of contact dermatitis due to a cellular phone, possibly caused by chromate, when the patients have erythema and papules on the hemilateral auricle or in the preauricular region.
An antifungal drug, itraconazole (ITZ) is effective for chromomycosis patients, but the distribution of ITZ and its metabolite, hydroxy-intraconazole (OH-ITZ) is unclear in pathological tissues. This study investigated how much ITZ and OH-ITZ accumulated in the lesional tissues of chromomycosis and non-lesional skin after oral treatment with ITZ. We determined the concentrations of ITZ and OH-ITZ in the lesional tissues of chromomycosis by Foncecaea pedrosoi and non-lesional skin after oral treatment with a total dose of 2.3g of ITZ. ITZ concentration was significantly higher in pathological skin than non-pathological skin. The ITZ concentration in the lesional tissues was higher in the central site than in the marginal site. No difference was seen in the OH-ITZ concentrations among three skin parts, the center and the margin in lesional skin, and non-lesional skin adjacent to the lesion. This study showed higher concentrations of ITZ in pathological tissues than in non-pathological tissues.
Microscopic polyangiitis (MPA) is a systemic vasculitis histologically characterized by small-vessel involvement. Antineutrophil cytoplasmic antibodies (especially anti-myeloperoxidase antibodies) (MPO-ANCA) are often positive in serum. Although the skin is affected in 20-70% of patients, the precise description has been limited. This retrospective study analyzed clinical manifestations in patients of MPA with skin eruptions. Ten patients with skin eruptions diagnosed as MPA according to Chapel Hill consensus criteria consisted of 6 men and 4 women aged from 38 to 80 years (62.1 +/- 13.3). Clinical manifestations, laboratory data, and histological findings were examined. Purpura and petechiae in 6 patients, livedo in 2 patients, and erythema in 7 patients, especially erythema on the hands and\or fingers in 4 patients, were observed. Histological findings from the eruptions in 7 patients showed perivascular lymphocyte infiltration in the upper dermis in 4 patients, and infiltration of lymphocytes and a few neutrophils around small arteries in the middle to deep dermis in 2 patients and diffuse infiltration of histiocytes and lymphocytes in the middle dermis in 1 patient. Cutaneous involvements in MPA showed a wide spectrum of clinical and histological findings.