Elevation of serum KL-6 in patients with psoriasis treated with anti-tumour necrosis factor-α therapy.

We report three patients with psoriasis whose serum level of Krebs Von Den Lungen (KL)-6 increased during therapy with anti-tumour necrosis factor (TNF)-α. A diagnosis of early-phase or subclinical interstitial pneumonia was made in two patients, and their KL-6 level decreased after anti-TNF-α discontinuation. The rise in KL-6 in the other patient was attributed to methotrexate. We propose that serum KL-6 should be monitored routinely in patients treated with anti-TNF agents.

The etiologic role of human papillomavirus in penile cancers: a study in Vietnam.

BACKGROUND: We investigated the aetiologic role of human papillomavirus (HPV) in 120 penile squamous cell carcinomas (PSCCs) from Vietnam. METHODS: Human papillomavirus DNA was detected by PCR using SPF10 primers and a primer set targeting HPV-16 E6. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus-16 viral load and physical status were determined by real-time PCR. P16(INK4A) protein expression was investigated by immunohistochemistry. RESULTS: Human papillomavirus DNA was detected in 27 of 120 (23%) PSCCs. The most frequently detected genotype was HPV-16 (24 of 27 cases, 89%). In 16 of 18 (89%) HPV-16-positive cases, the HPV DNA was considered to be integrated into the host genome. The geometric mean of the HPV-16 viral load was 0.4 copies per cell. P16(INK4A) overexpression was significantly related to PSCCs infected with high-risk HPV (P=0.018) and HPV-16 copy numbers (P<0.001). CONCLUSION: Human papillomavirus-16 DNA integration and p16(INK4A) overexpression in high-risk HPV detected PSCCs suggested an aetiologic role of high-risk HPV in the development of PSCCs.

Extensive multiple piloleiomyoma in the submental region treated successfully by surgery and reconstruction with a submental perforator flap.

Piloleiomyoma is a benign tumour originating in the smooth muscles of the arrector pili muscle in the skin. The lesions are often sensitive to touch, cold and emotional disturbance. We present a patient with multiple piloleiomyoma (MPL) of the submentum who underwent reconstructive surgery using a submental perforator flap. The result was excellent and there were no postoperative complications. MPL of the submental region is relatively rare; to our knowledge, ours is the first report of MPL treated successfully with a submental perforator flap.

Multiple intravascular papillary endothelial hyperplasia affecting skin and bone.

We report a 75-year-old man with multiple recurrent black papules involving his entire body. In the course of 3 years, 20 lesions were resected, which were histologically confirmed as intravascular papillary endothelial hyperplasia (IPEH). A similar vascular lesion was found on his tibia. The occurrence of multiple IPEH affecting skin and bone is extremely rare. The patient's medical history included hepatitis C, hepatoma and associated coagulopathy. We suggest that this patient's multiple lesions were induced by microthrombus formation due to liver dysfunction.

Multifocal haemangioma with extracutaneous involvement associated with hypergalactosaemia.

Neonatal haemangiomatosis, characterized by multiple haemangiomas, is a rare disease that develops during the neonatal period with or without visceral involvement. We report a 1-month-old Japanese boy with multifocal haemangiomas with extracutaneous involvement. A haemangioma on his left lower eyelid, present at birth, increased in size during the first postnatal month and more lesions developed during the same period. Neonatal mass screening showed hypergalactosaemia. Laboratory investigations found raised total bile acid and ammonia. Computed tomography and abdominal ultrasonography studies showed multiple hepatic haemangiomas and intrahepatic portovenous shunts. The child's cutaneous and hepatic haemangiomas disappeared spontaneously with normalization of laboratory data, and galactose accumulation improved with the feeding of lactose-free milk. There were no complications and the child has had no recurrence of the symptoms. Our case implies a possible association of multiple haemangioma and hypergalactosaemia, suggesting the necessity for visceral investigation.

Graft-versus-adult T-cell leukemia/lymphoma effect following allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven effective in adult T-cell leukemia/lymphoma (ATL) patients. To study the graft-versus-ATL (Gv-ATL) effects after allo-HSCT, we analyzed 21 ATL patients who had been treated at our hospital. Of these, 18 had acute-, 2 had lymphoma- and 1 had chronic-type ATL; at allo-HSCT, seven patients were in CR, one was in PR, five had stable disease (SD) and eight had progressive disease (PD). Disease state after allo-HSCT was CR in 14, PR in 3, SD in 1 and PD in 3 patients. Among 15 patients who survived longer than 100 days, ATL relapsed in 10 patients, skin relapsed in 9 patients and 5 had relapsed on the skin alone. After we discontinued immunosuppressant therapy in these 10 patients, 8 manifested GVHD; ATL was ameliorated to CR in 6 patients. Donor lymphocytes were infused into two patients who did not show GVHD; one obtained CR. In five patients with skin relapse alone, four patients achieved CR following the discontinuation of the immunosuppressants. Our results demonstrate that relapse of ATL after allo-HSCT tends to develop on skin, and Gv-ATL effects played a critical role in the outcome of allo-HSCT for ATL.

Transcripts of the human herpesvirus 8 genome in skin lesions and peripheral blood mononuclear cells of a patient with classic Kaposi's sarcoma.

We report a 75-year-old Japanese woman with classic Kaposi's sarcoma. PCR amplified human herpesvirus 8 (HHV-8) DNA sequences from her skin lesions and peripheral blood mononuclear cells (PBMC), but not her plasma, saliva or urine. An antibody test against HHV-8 lytic antigens was positive. Immunohistochemical staining detected latent antigen. There was no evidence of HHV-8 infection in her husband, sister or daughter. Genes coding for HHV-8-encoded viral interleukin-6, viral macrophage inflammatory protein I, viral G protein-coupled receptor, viral cyclin D and viral Bcl-2 were expressed to the same degree in both her skin lesion and PBMC. Latency-associated T0.7 mRNA and HHV-8-encoded viral tegument protein genes were expressed in her PBMC at levels lower than in the skin lesions. Based on the gene expression profile, we concluded that lytic HHV-8 infection was present in her skin lesions and PBMC.

Immunoelectron-microscopic detection of globotriaosylceramide accumulated in the skin of patients with Fabry disease.

BACKGROUND: Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of alpha-galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL-3). To date, no direct detection of GL-3 by immunoelectron microscopy has been reported. OBJECTIVES: To examine whether GL-3 is accumulated exclusively in lysosomes of cutaneous cells using an anti-GL-3 monoclonal antibody (mAb) and immunoelectron microscopy. METHODS: Skin specimens from seven patients with Fabry disease were examined immunohistochemically by light and electron microscopy using an anti-GL-3 mAb. RESULTS: By light microscopy, the cytoplasm of vascular endothelial cells, eccrine gland cells, and perineurium was stained with mouse anti-GL-3 antibody. Electron microscopically, positive signals for GL-3 were limited to dilated lysosomes in the cytoplasm of endothelial cells, pericytes, eccrine gland cells, dermal fibroblasts and perineurium. CONCLUSIONS: Our results demonstrate that the cytoplasmic deposit in Fabry disease was GL-3 and the accumulated GL-3 was localized essentially to lysosomes.

Selenium deficiency: report of a case.

We report an 18-month-old Japanese boy with selenium deficiency. He had dry skin with irregularly shaped, erythematous changes on the cheeks, groin, hip, and extremities, erosions on the external urethral and anal orifices, and sparse, short, thin, light-coloured hair. He had received parenteral nutrition for 5 months because of juvenile polyposis. At presentation, his serum selenium level was less than 2.0 microg/dL (normal range, 10.6-17.4 microg/dL). His skin lesions responded well to supplementary treatment with sodium selenite. His skin symptoms were similar to those attributable to a deficiency of zinc which, like selenium, is an essential trace element. According to the literature, selenium deficiency is responsible for cardiomyopathy, which was diagnosed in our patient. The clinical similarity to zinc deficiency and the literature yielded important clues for a diagnosis of selenium deficiency in this patient.

Ultrastructural localization of basigin in normal human epidermis.

Basigin is a glycosylated transmembrane protein belonging to the immunoglobulin superfamily. It is thought to play roles in intercellular recognition involved in cell differentiation. We previously demonstrated at the light microscope level a correlation between basigin expression and epidermal differentiation. In the present study, the ultrastructural localization of basigin in normal human epidermal keratinocytes was investigated by immunoelectron microscopy. The basigin labeling was strongest on membranes of basal cells, weaker on prickle cells, and absent in granular and horny cells. On the membrane of basal cells, labeling was observed on the apical and lateral sides but not on the dermal side. Gold particles were mostly observed on the surface of microvilli, especially on their tips. There were fewer on the intermicrovillous membrane and they were absent on the desmosome. These results are consistent with our previous report that basigin expression is correlated with differentiation of epidermal keratinocytes. Microvilli on basal and suprabasal keratinocytes might play roles in the differentiation of keratinocytes through basigin on the tips of microvilli.

Cyclooxygenase-2 expression and prostaglandin E2 biosynthesis are enhanced in scleroderma fibroblasts and inhibited by UVA irradiation.

OBJECTIVE: We and others reported on the beneficial effects of combined therapy using 8-methoxypsoralen and long wave ultraviolet light (PUVA therapy) in the treatment of scleroderma. We now investigate the mechanism by which PUVA therapy is effective by comparing interleukin 1beta (IL-1beta) mediated signal transduction in scleroderma fibroblasts and those from normal skin. METHODS: Prostaglandin E2 (PGE2) production and expression of cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, and COX-2 (enzymes that regulate PGE2 production) were examined in untreated and IL-1beta treated fibroblasts from scleroderma involved and normal skin. The effect of UVA irradiation on enzyme expression and PGE2 production was examined. PGE2 was measured by a competitive radioimmunoassay and enzyme expression was analyzed by Western immunoblotting and Northern blotting. RESULTS: Constitutive PGE2 production was significantly upregulated and IL-1beta induced PGE2 production was increased by the enhancing expression of both COX-2 mRNA and protein in fibroblasts from scleroderma involved skin; PGE2 production and COX-2 expression were inhibited by UVA irradiation. CONCLUSION: Enhanced PGE2 production regulated by COX-2 expression in scleroderma fibroblasts may contribute to the development of this disorder. PUVA therapy might exhibit its beneficial effect, at least in part, by inhibiting COX-2 expression transcriptionally and translationally, with subsequent inhibition of PGE2 production.

Expression of Basigin in human fetal, infantile and adult skin and in basal cell carcinoma.

BACKGROUND: Basigin is a glycosylated transmembrane protein belonging to the immunoglobulin superfamily and is thought to be associated with cell development and differentiation. We investigated the relation between Basigin expression and epidermal development in this study. METHODS: Basigin expression was immunohistochemically investigated during organogenesis of human skin and in human basal cell carcinoma (BCC). RESULTS: Human fetal skin showed negative staining at 10 weeks of gestation. At 20 weeks, the cytoplasm and membranes of adnexal germ and hair follicular cells were strongly positive, while epidermal basal cells showed weakly positive staining. After birth, basal cells, suprabasal cells, anagen hair follicular cells and eccrine glandular cells showed positive staining. Membranes of basal cells expressed more Basigin compared to other cell components. Basigin was not detectable in granular cells and telogen hair follicular cells. Sixteen of 30 BCCs were entirely negative for Basigin. However, cells at budding areas of tumor masses were positive in 14 of the 30 BCCs. CONCLUSIONS: These findings suggest that 1) Basigin is associated with epidermal proliferation and differentiation, 2) most parts of BCCs might be derived from early fetal epidermal basal cells, and 3) that a part, only the budding area of BCCs, has the characteristics of epithelial germ cells.

[Expression of matrix metalloproteinases in metastatic lesions of cutaneous squamous cell carcinoma].

OBJECTIVE: To investigate the expression of matrix metalloproteinases (MMPs) and its correlation with basigin/CD147 expression in metastatic lesions of cutaneous Sequamous cell carcinoma (SCC). METHODS: Expressions of MMPs and basigin/CD147 were examined by DAB and ALP immunohistochemical staining in 14 metastatic SSCs, and immunoblot analysis was used to observe the basigin/CD147 expression in metastatic samples. RESULTS: Normal skin and lymph nodes were basically negative for MMPs, but expressions of MMP-1, MMP-2, MMP-3 and MTl-MMP were increased in both tumor cells and stromal cells in metastatic SCC. Strongly positive or positive staining was observed in 4 or 8 of metastatic SCCs for basigin/CD147 in tumor cells respectively. Significant correlations were found between basigin/CD147 expression in tumor cells and MMP-1, MMP-2, MMP-3, MTl-MMP expression in surrounding stromal cells (p-values: 0.012, 0.024, 0.047 and 0.026, respectively). Immunoblot analysis revealed that basigin/CD147 expression increased in metastatic SCC. CONCLUSION: These results suggest that MMPs produced by both tumor cells and stromal cells play a role in metastasis of cutaneous SCC, and increased MMPs in stromal cells might be induced by basigin/CD147 expressed in tumor cells.