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The explant culture of small skin specimens is a good model of in vivo epidermal growth. In this model epidermal cells are not dislodged and remain in vitro under the influences of the original mesenchyme, at least during early growth. Recently we attempted to grow epidermal cells from the skin lesions of some acantholytic dermatoses (Darier's disease [DD], Hailey-Hailey's disease [HHD], and pemphigus vulgaris [PV]) in explant culture, and we observed the behavior of outgrown epidermal cells for a relatively short time after explantation. The cell outgrowth from the skin of a patient with PV, which seemed to be apparently normal but showed positive Nikolsky's sign, formed a well organized flat sheet 48 to 96 hours after explantation, as seen in cultures of normal human adult skin. In contrast, the outgrown cells from the skin lesions of three patients with DD, as well as those from three patients with HHD, showed a characteristic disorganized outgrowth. They did not form the well-organized flat sheet, but showed a marked cell dissociation and conspicuously increased locomotive ability. These findings seems to clearly exhibit the processes of "acantholysis" in vitro and strongly suggest that the cells from these 2 latter dermatoses have a genetically determined insufficiency or defect in cell adhesion. From these results the authors conclude that the mechanism of cell dissociation in DD and HHD is fundamentally different from that in PV.

SummaryThe effects of cell dissociation in HHD and DD on normal outgrown epidermal cells in explant culture were investigated, and the results were obtained as follows:1) The outgrown epidermal cells from skin fragments of patients with HHD or OD reveal characteristic dissociative behavior in explant culture. This phenomenon is considered to be “acantholysis” at the level of tissue culture.2) The outgrown epidermal cells from the normal skin fragments can dissociate when they are cultured together with those from patients with HHD or DD. The latter exhibits distinct dissociative behavior.3) These cell dissociations can be stopped by changing the medium to a new one.4) These dissociations reappear by decreasing the amount of the medium to a certain low level.5) The dissociation of outgrown epidermal cells from normal skin fragments occurs on transference of the medium in which the cell dissociations were observed.

SummaryIt has been reported that pig skin epidermis contains at least four independent adenylate cyclase systems, i.e. 1) beta-adrenergic-, 2) histamine H2-, 3) adenosine and, 4) prostaglandin E-adenylate cyclase systems, resulting in the accumulation of cyclic AMP. Using human skin epidermis, we investigated the responses of adenylate cyclase to epinephrine, histamine, and adenosine. In normal human skin, all three agents increased cyclic AMP levels of the skin. The epinephrine effect was inhibited by a beta-adrenergic blocking agent, propranolol. The histamine effect was inhibited by a histamine H2 inhibitor, cimetidine. The adenosine effect was inhibited by theophylline. The effects of epinephrine and histamine were augmented by the addition of the cyclic AMP phosphodiesterase inhibitor, theophylline. Another phosphodiesterase inhibitor, papaverine, augmented the effects of all three agents. In contrast to pig skin epidermis, where histamine and adenosineinduced cyclic AMP accumulations were marked, in human skin, epinephrine-induced cyclic AMP accumulation was more marked than those induced by histamine and adenosine.Using the epidermis of Darier’s disease, we also investigated the effects of epinephrine, histamine and adenosine on the cyclic AMP levels of the skin. The involved skin of Darier’s disease was shown to be characterized by a defective beta-adrenergic responsiveness.These findings show that normal human skin possesses at least three independent adenylate cyclase systems (beta-adrenergic, histamine H2-, and adenosine-adenylate cyclase), as in pig skin epidermis, with a different responsiveness pattern to these stimulators.Our data also show that the responsiveness to each receptor-adenylate cyclase system may be modified in a pathological condition of epidermis such as in Darier’s disease. The significance of decreased beta-adrenergic responsiveness in the involved skin in Darier’s disease was discussed in relation to our previous finding of the same type of defect in the psoriatic-involved epidermis.

A 31-year-old Japanese man presented to our hospital in December 1990 with swelling of the lower lip and cheek which he had noticed 8 months earlier. Before his first visit to us, systemic corticosteroids had been administered for a week. This treatment resulted in remarkable improvement of the swelling of both sites; however, after discontinuation of these corticosteroids, recurrent episodes of the swelling occurred. Our examination revealed an enlarged, soft, nontender lower lip and a swollen cheek (Fig. 1). Bilateral hilar lymphadenopathy was not found by a chest radiograph. Computed tomography of the abdomen was normal. Laboratory investigations disclosed that lactic dehydrogenase was 195 U/L and that angiotensin converting enzyme (ACE) was 29.4 IU/L. The antibody against HTLV-I was negative and a biopsy of the lower lip revealed a relatively dense infiltration of the inflammatory cells composed mainly of lymphocytes and histiocytes. Atypia of lymphocytes was not prominent and some muscle fibers showed degenerative changes (Fig. 2). A skin biopsy of the cheek disclosed a dense lymphohistiocytic infiltrate in the dermis. Based on the clinical findings, we tentatively diagnosed this case as cheilitis granulomatosa and reinstituted systemic corticosteroid therapy. In December 1991 the patient was admitted for evaluation of muscle weakness of the forearms. Electric myography revealed a myogenic pattern. He showed neither a heliotrope eruption nor Gottron's papules. Laboratory investigation showed that the white cell count was 14 600/mm3 (lymphocytes 27%), creatinine phosphokinase (CPK) was 679 U/L, and ACE was 28.0 IU/L. A biopsy of the deltoid muscle disclosed muscle atrophy and a dense atypical lymphocytic infiltrate around the muscle fibers (Fig. 3). Immunohistochemical findings revealed that most of the Infiltrating cells were CD3(+) and CD4(+). Although molecular biologic investigation did not disclose the monoclonality of the gamma T-cell receptor gene, this time we diagnosed the case from the histologic findings as T-cell lymphoma. Needle biopsy of the bone marrow suggested the infiltration of lymphoma cells. In January 1992, chemotherapy of MACOP-BV (MTX, doxorubicin hydrochloride, CPA, VCR, prednisolone, BLM, and etoposide) was started, but we were unable to prevent the progression of muscle weakness, and in April 1992 the patient died of pneumonia. No autopsy was performed.

A case of so-called mixed tumor of the skin arising on the wrist was reported. Immunohistochemical staining of keratins of several molecular weights (AE1/AE3, RCK102, NCL-5D3 and 35 beta H11), carcinoembryonic antigen (CEA), S-100 protein, and desmin was performed. AE1/AE3 and RCK102 were positive in all the tumor cells; CEA, NCL-5D3 and 35 beta H11 were positive mainly in luminal cells of the tubuloalveolar structures. S-100 protein was positive in peripheral cells of the tubular lumina and in scattered cells in the mucous stroma. Desmin was negative in all the tumor cells. Immunohistochemical findings lent further support to the hypothesis that so-called mixed tumor of the skin differentiates into the secretory and ductal portions of the sweat gland.

Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for fibroblastic cells. In the early stage of wound healing. PDGF is released from aggregated platelets and it is believed that its chemotactic activity may play a key role in the influx of connective tissue cells into wound sites. Using the Boyden chamber assay, we investigated factors that alter the migratory response of human skin fibroblasts to PDGF. The response was related to the growth state of cells; that is, growing cells at low cell density exhibited a greater migratory response to PDGF than density-arrested quiescent cells. The level of random migration was also elevated in growing cells, compared to quiescent cells. The chemotactic response after 3-h exposure to serum was markedly decreased (50%). Three-hour preincubation of the cells with transforming growth factor-beta (TGF-beta) or with epidermal growth factor reduced the migratory response to approximately half that in the nonstimulated control. In contrast, cells treated with TGF-beta or basic fibroblast growth factor for 24 h exhibited a two- to threefold greater chemotactic response to PDGF than control cells. This stimulatory effect of TGF-beta on the fibroblast migration induced by PDGF suggests that TGF-beta acts synergistically with PDGF on the influx of connective tissue cells into human wound sites and may explain the potent wound healing activity of TGF-beta in vivo.

We describe a 56-year-old woman with Stewart-Treves syndrome who had severe dyspnea from a pleural effusion caused by metastatic angiosarcoma in the right lung. Tumor infiltrating lymphocytes (TIL) in the pleural effusion were cultured and expanded in vitro in the continuous presence of recombinant interleukin 2 with periodic stimulation by CD3 antibody. The expanded TIL were administered intrapleurally seven times at I- to 4-week intervals in combination with intravenous infusion of recombinant interleukin 2. A panel of T-cell clones was also obtained from TIL. Immunotherapy dramatically improved the patient's dyspnea and pleural effusion. A CD4 + T-cell clone and a CD8 + T-cell clone established from TIL had specific cytotoxicity to the tumor cells.

Background. Extramammary Paget disease appears in anogenital, axillary, or other areas. In this study, the authors addressed the question of whether the histogenesis of 35 cases of Paget disease arising at different sites was the same. Methods. Specimens of 35 cases of extramammary Paget disease (16 genital; 9 invasive carcinomas of genital; 6 axillary; 1 periumbilical; and 3 perianal), 4 cases of mammary Paget disease, 4 cases of breast carcinomas, and 6 cases of anal carcinomas of perianal spread from primary rectal adenocarcinomas were retrieved and stained by the avidin-biotin-complex method, using various kinds of monoclonal antikeratin antibodies. Results. There was no significant difference in cytokeratin expression among these cases of extramammary Paget disease. Simple epithelial keratins were expressed in Paget cells in extramammary Paget disease, but no expression of differentiation-specific or noncornifying stratified squamous epithelial keratins was observed, regardless of the degree of invasion. Paget cells in extramammary Paget disease revealed a similar cytokeratin expression to that in secretory cells of normal apocrine or eccrine glands. In addition, there was no significant difference in cytokeratin expression in tumor cells among extramammary and mammary Paget disease, breast carcinomas, and anal carcinomas. Conclusions. Cases of Paget disease arising at different locations could not be distinguished from each other based on cytokeratin expression. In addition, antikeratin antibodies against simple epithelial keratins were demonstrated to be more useful for the identification of Paget cells in the paraffin sections than were conventional antibodies, such as an antibody against carcinoembryonic antigen (CEA).

Sparfloxacin is a recently developed fluoroquinolone. The drug has shown potent antimicrobial activity against a wide range of Gram-positive and Gram-negative bacteria, glucose non-fermenters, anaerobes, Legionella spp., Mycoplasma spp., Chlamydia spp. and Mycobacterium spp. Methicillin-resistant Staphylococcus aureus is also susceptible to sparfloxacin. Plasma sparfloxacin concentrations reach a peak (Cmax) of approximately 0.7 mg/L at 3 to 5 hours after a 200mg oral dose. This is followed by a monophasic slow decrease, with an elimination half-life (t1/2) of 15 to 20 hours. The Cmax and area under the plasma concentration-time curve show dose-related increases. Food intake does not affect the absorption and pharmacokinetics of sparfloxacin. Sparfloxacin binds weakly to plasma protein (37%), and exhibits excellent tissue distribution and effective penetration into extracellular fluids. Concentrations of the drug in most tissues are similar to, or higher than, concomitant plasma concentrations. Sparfloxacin distributes slightly into cerebrospinal fluid. The drug is metabolised to a glucuronide. The urinary excretion of the unchanged drug accounts for 10 to 14% of the given dose. The ratio of Cmax values after multiple and single oral doses is 1.3 to 1.4, but other pharmacokinetic parameters of sparfloxacin are not influenced by multiple doses. Even in patients with severe renal failure, no significant prolongation of the half-life is observed after oral administration. Sparfloxacin appears unlikely to affect the pharmacokinetics of theophylline. Antacids containing aluminium hydroxide reduce the oral bioavailability of sparfloxacin by 25 to 35%. Probenecid does not affect sparfloxacin pharmacokinetics. The pharmacokinetic properties of sparfloxacin allow once-daily administration in the treatment of various infections.

A case of 77-year-old man with extramammary Paget's disease of the bilateral axillae was reported. 9 years ago, he was affected by urinary bladder carcinoma (transitional cell carcinoma, grade 1) and was treated by TUR.At first, he noticed erythema of the bilateral axillae, and subsequent some nodules on the right. As the nodules increased in number, swelling of the right arm appeared. The course had been quite rapid, and his death was caused by bacterial pneumonia after a year and a half since the first clinical appearance. In autopsy, metastasis were observed in lungs, liver, vertebral bodies, spleen, several lymph nodes and so on. It will be the first report in Japan which was died of extramammary Paget's disease of the axillae.

Although tuberous sclerosis is supposed to be a phacomatosis inherited as an autosomal dominant trait, many cases develop without any affected parents or grandparents. In recent years, many vigorous investigations have been concentrated on finding the mutant gene, and possible candidate genes have been mapped on 9q34 and other chromosomes. In order to find a way of diagnosing asymptomatic carriers or patients, we tried to detect restriction fragment length polymorphisms (RFLPs) using the technique of polymerase chain reaction (PCR). We used a probe, MCOA12, which is located on 9q34 and has been known to show RFLPs in Caucasian tuberous sclerosis patients. However, we could not find a correlation between the phenotype and RFLP pattern in seven of eight families.

A late phase II study of CPT-11 was conducted to evaluate for antitumor activity and safety in patient with squamous cell carcinoma of skin (SCC) and malignant melanoma (MM) by 22 multi-institutional study group in Japan. Forty-two patients in SCC and 38 in MM were enrolled from June 1990 to November 1992. Patients were administered at a dose of 100 mg/m2 weekly by intravenous infusion.The characteristics of 41 eligible patients with SCC were median age: 67 yr. (43-86), male/female: 31/10, P.S. 0-1/2-3: 35/6, no prior therapy: 27. Thirteen patients including 2 complete responses (CRs) responded to CPT-11. The response rate was 39.4% (13/33) . Two CRs were confirmed histologically. Out of 11 partial responses (PRs) 7 was able to resect completely tumor site after the treatment. Antitumor activity was observed not only in primary site but also in distant metastases such as lungs and lymph nodes.The characteristics of 35 eligible patients with MM were median age: 55yr. (29-81), male/female: 20/15, P.S. 0-1/2-3: 32/3, prior therapy: 30 (chemotherapy 26) . Three patients were achieved PR for a response rate of 9.4% (3/32) . Out of them 2 were recurrence patients with lung metastases, having received prior chemotherapy, DAV.Major adverse reactions were nausea/vomiting, diarrhea, anorexia, leukopenia and anemia for the incidence (≥ grade 2) of 47.4% (36/76), 36.8% (28/76) and 52.6% (40/76), 56.6% (43/76) and 26.3% (20/76), respectively. These adverse reactions were well tolerable and reversible. It was thought that CPT-11 should be given carefully after confirming laboratory data and patients conditions.Inconclusion, CPT-11 is very effective against SCC, but less effective against MM in this study. Further clinical studies of CPT-11 combined with other agents are warranted.

We have established a new diagnostic method using a points system to evaluate patients with early scleroderma and those with scleroderma spectrum disorders (SSD). To examine the clinical usefulness of this method, it was applied to a total of 215 cases including 97 patients with scleroderma, 32 with SSD, 28 with presumed primary Raynaud's phenomenon (RP) and 58 with other connective tissue disorders (CTD). A total score was obtained for each patient as the sum of the following five factors: (1) extent of skin sclerosis (maximum, 10 points); (2) pulmonary changes (maximum, 4 points); (3) antinuclear antibodies (maximum, 5 points); (4) pattern of Raynaud's phenomenon (maximum, 3 points); and (5) nailfold bleeding (maximum, 2 points). Of the 97 scleroderma patients, 86 (89%) had 9 or more points, and of the 32 SSD patients, 28 (88%) had 5 to 8 points. In contrast, all patients with presumed primary RP and 54 of 58 (93%) patients with other CTD had 0 to 4 points. These data suggest that this diagnostic method is very useful not only for clinical evaluation of SSD, but also for the differentiation of scleroderma and SSD from other CTD and primary RP.

The cytokeratin expression of seborrheic keratosis was studied by means of immunohistochemistry and compared with that of normal human skin. The following findings were obtained in seborrheic keratosis: (1) a partial lack of high molecular weight cytokeratin (#1/68 kD, #10/56.6 kD) in all ten cases examined; (2) the detection of cytokeratin typical for simple epithelia (#8/52.5 kD, #18/45 kD, #19/40 kD) in eight of ten cases; and (3) the detection of cytokeratin #5/58 kD in suprabasal cells in 5 of 10 cases. An immunoelectron-microscopic investigation, using an anti-keratin antibody against cytokeratin #19/40 kD, revealed a whirl-like arrangement of keratin filaments within immunoreactive cells, in contrast to a linear, parallel arrangement in non-immunoreactive cells. Cells known to express cytokeratin typical for simple epithelia, such as sweat gland cells or Merkel cells, were not observed. The altered cytokeratin gene-expression in seborrheic keratosis may be attributable to de-differentiation of tumor cells or potential re-differentiation towards embryonic keratinocytes.

Background: CD1 antigens are classified serologically into at least three groups, CD1a, CD1b, and CD1c, and many kinds of monoclonal antibodies are available for each subgroup of CD1 antigens. CD1a, CD1b, and CD1c antigens have been shown to be selectively and differentially expressed on epidermal Langerhans cells and dermal dendritic cells in normal human skin. Objective: The objective was to further delineate the localization of epitopes of CD1 antigens in human skin. Methods: We examined the immunoreactivity of 14 different CD1 antibodies (seven CD1a, five CD1b, and two CD1c antibodies) with the immunoperoxidase technique. We also studied the reactivity of NU-T2 (CD1b) antibody by immunogold electron microscopy. Results: The epitopes for CD1a, CD1b, and CD1c antigens were differentially mapped on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in human skin. Conclusion: These CD1 antibodies may be useful to analyze the phenotypic alteration of immune and nonimmune cells in various skin diseases.

A 15-year-old Japanese girl had widespread annular serpiginous erythematous plaques, bilateral granulomatous uveitis, bloody diarrhea, and seronegative arthralgia. She also had anemia and leukopenia. The histopathologic findings were compatible with those of annular elastolytic giant cell granuloma. Elastolytic granulomas were also found in the cervical lymph nodes, terminal ileum, parietal peritoneum, and mesentery. Bilateral hilar lymphadenopathy, hypercalcemia, and an increased level of angiotensin converting enzyme were not observed throughout the clinical course. To the best of our knowledge, systemic elastolytic granulomatosis has not been previously described in annular elastolytic giant cell granuloma or sarcoidosis. This case may represent a type of granulomatosis in the broad spectrum of annular elastolytic giant cell granuloma and sarcoidosis.

Summary The effect of platelet-poor plasma from patients with von Recklinghausen's disease (neurofibromatosis, NF) on the cell growth of cultured neurofibroma-derived fibroblast-like cells (NF fibroblast-like cells grown from plant cultures of cutaneous neurofibromas) was examined. Platelet-poor plasma and sera from nine NF patients and nine control individuals were examined. When comparing platelet-poor plasma from patients with NF with control individuals, the former stimulated the proliferation of fibroblast-like cells derived from neurofibromas, not that of normal fibroblasts.

DAPI-DNA顕微蛍光測光を用いて細胞核DNA量の観点から, 悪性黒色腫における radial and vertical growth phaseで悪性度の異なる細胞群が存在すること, 高発癌性疾患である汗孔角化症の皮疹部表皮の腫瘍性クローンが増殖, 発達し悪性化する過程を明らかにした。いずれも皮膚悪性腫瘍の多段階発展過程の一端を示すものと考えた。

顔面肩甲上腕型筋ジストロフィー, ジルベルト症候群, 出血傾向を伴った眼皮膚白皮症患者に合併した無色素性黒色腫の一例を報告した。症例: 58歳, 男性。左上磐部に急速に増大した, 局所熱感, 軽度の発赤を伴う8×7×3cm大の有痛性の皮下腫瘤。表面平滑で弾性硬, 境界不明瞭。組織学的に, 腫瘍細胞はS-100蛋白陽性の異型性の強い明澄細胞。悪性黒色腫の転移を疑い検索したところ, 右前腕に原発巣が認められた。

There is an increase in the number of CD23+ cells in peripheral blood mononuclear cells (PBMC) in atopic dermatitis (AD). We analysed the subpopulation of CD23+ PBMC in 11 patients with AD and in 10 healthy controls and found that B cells (CD20+) and non-T, non-B cells (CD3- CD20-) (mainly monocytes) were responsible for the elevation of CD23+ cells. CD23+ T cells (CD3+) comprised only 4.6% of total CD23+ cells in AD. The percentage of CD23+ cells did not correlate with the serum log IgE level nor with clinical severity of AD. Interleukin 4 (IL-4) induced the expression of CD23 antigen in PBMC both in AD and in healthy controls in a dose-dependent manner in vitro. This enhancing effect of IL-4 was completely abrogated by the addition of anti-IL-4 monoclonal antibody. Other cytokines such as IL-1, IL-2, IL-3, IFN-alpha, IFN-gamma and TNF-alpha had no significant effects on CD23 expression.

Summary A patient with neurofibromatosis developed neurofibrosarcoma (NFS). The tumour was composed of spindle-shaped cells with atypical nuclei arranged in a fascicular or sheet-like fashion. The tumour cells had discontinous basement membrane-like structures and were positively stained with the monoclonal antibody against S100 protein α chain. Both the primary tumour and its cultured cells contained GM3 and GD3 as major gangliosides. The ganglioside pattern of the primary tumour corresponds to that of NFS in our previous study. In the cultured NFS cells, the relative amount ratio of GM3 to GD3 is almost reversed compared to that of the primary tumour. This reversion may reflect some environmental influence on the ganglioside metabolism of NFS.

Cultured epidermal keratinocytes and dermal fibroblasts derived from porokeratosis (PK) patients' skin lesions or normal-appearing skin had numerical and sometimes structural chromosomal abnormalities. Such abnormal cells were seen in 4.08% and 0.375% of all the studied epidermal keratinocytes derived from affected skin and normal-appearing skin, respectively. Similar abnormalities were present in 1.70% and 3.67% of the dermal fibroblasts from the patients' affected skin and normal-appearing skin, respectively. Chromosomal abnormalities were more frequent in keratinocytes and fibroblasts from the patients' skin than in keratinocytes (0.429%) or in fibroblasts (1.22%) derived from normal control donors. Clonal proliferation of such abnormal cells was frequently seen in keratinocytes from the patients' affected skin. The frequent appearance of chromosomal abnormalities and clonal proliferation in epidermal keratinocytes may explain skin lesion formation and skin cancer development in PK patients.

T cell growth factors such as interleukin-2 (IL-2) and interleukin-4 (IL-4) act as potent comitogenic factors for purified human T cells in the presence of phorbol myristate acetate (PMA). We investigated the effects of gangliosides on the IL-4-driven or IL-2-driven proliferation of human T cells, using these comitogenic assays. Bovine brain gangliosides inhibited the proliferation of human T cells activated by PMA + IL-4 or PMA + IL-2. These inhibitory effects were dose and time-dependent and were significant at concentrations higher than 50 microM. PMA + IL-2 stimulation was more sensitive to the inhibitory effects of gangliosides (I50 = 77.2 microM) than PMA + IL-4 stimulation (I50 = 105.9 microM). Differential inhibitory effects were also examined among the panel of various gangliosides. GD1b and GT1b showed the most potent inhibitory actions in each assay; the inhibitory effect of GD1a was somewhat less potent than GD1b or GT1b. GM2 and GD3 were only weakly inhibitory, and the inhibitory effect of GM3 was almost negligible. These findings suggest that gangliosides may play an immunomodulatory role by interfering with IL-4 or IL-2-driven proliferation of human T cells.

Although the pathogenesis of atopic dermatitis (AD) is unknown, many immunologic abnormalities such as high levels of serum IgE and increase of IgE Fc receptor-positive lymphocytes have been demonstrated. Recently, interleukin 4 (IL-4) has been shown to induce enormously the production of IgE and to enhance the expression of IgE Fc receptor by B cells, suggesting the possible involvement of IL-4 in the pathogenesis of AD. We examined IL-4 responsiveness or interleukin 2 (IL-2) responsiveness of peripheral blood mono- nuclear cells of 31 patients with AD, 19 healthy individuals, and seven patients with other skin diseases. We found that IL-4 responsiveness of AD was higher than that of non-AD control, although IL-2 responsiveness of AD showed no significant change. However, the value of the IL-4 responsiveness did not significantly correlate with the clinical severity, personal history of respiratory allergy, serum IgE level, or clinical course of patients with AD. The hyperresponsiveness to IL-4 detected in AD was not likely to be due to the effects of steroids or anti-mast cell drugs because the value of IL-4 responsiveness was significantly low, compared to AD, in patients with other skin diseases who were treated similarly. Because the T-cell – enriched population, but not the B-cell – enriched population, showed significant proliferation in response to exogeneous IL-4 or IL-2, T cells were the main population that reacted in our proliferation assay. These results indicate that IL-4 – driven proliferative response may be efficiently operative in T cells in patients with AD.

29歳男子。10歳頃より日光裸露部に小色素斑が多発。11歳時, 右鼻翼に基底細胞上皮腫, 25歳時, 左角膜に扁平上皮癌を生じた。基底細胞上皮腫は局所再発傾向が強く, 難治であつた。神経症状は認めなかつた。患者由来培養皮膚線維芽細胞は10J/m2の紫外線誘発不定期DNA合成(unscheduled DNA synthesis, 以下UDS)が正常人の45%と低下しており, 相補性テストでC群色素性乾皮症(xeroderma pigmentosum, 以下XP)と診断した。同培養細胞は紫外線の致死効果に対し, 高い感受性を示したが, 他のC群患者由来の細胞と比較すると, やや感受性が低かつた。

The effects of sera and of platelet-poor plasma from patients with scleroderma on endothelial cell survival in vitro were studied. The survival ratio of rat heart endothelial cells was studied both in 10% test serum and in 10% platelet-poor plasma. Sera from patients with scleroderma decreased the survival ratio significantly when compared with sera from normal controls. In contrast, there was no significant difference between platelet-poor plasma from patients with scleroderma and that from normal controls. Our data indicate that platelets in the patients with scleroderma may cause vascular damage by affecting endothelial cell survival.

Multicentric Bowen's disease developed in a 73-year-old man in areas involved with disseminated porokeratosis. The porokeratotic lesions were brownish; some were small and solitary, and others were coalesced and of variable size. Some lesions were erythematous. The histologic findings of the small, solitary or brownish, coalesced lesions were those of porokeratosis without apparent dysplasia; however, the erythematous coalesced lesions revealed epidermal dysplasia. Study revealed DNA ploidy abnormalities in the epidermal cells of these porokeratotic skin lesions. The skin lesions progressed in their degree of DNA ploidy abnormality from small solitary lesions to brownish coalesced ones and further to erythematous, coalesced ones. These observations suggest the direct and sequential growth of potentially malignant neoplastic clones in the patient's porokeratotic skin lesions and explain the multicentric development of Bowen's disease.

Immunohistochemical and ultrastructural studies were conducted to elucidate the nature and origin of osteosar-comatous changes in malignant melanoma in a 43-year-old Japanese man. Immunohistochemical studies with the use of antisera against human S-100 protein and neuron-specific enolase demonstrated positive reactions in the tumor cells within the osteosarcomatous area. UI-trastructurally, the neoplastic cells showed marked similarities to those from osteosarcomas. Additionally, occasional neoplastic cells contained round or ellipsoidal os-miophilic organelles, presumably melanosomes. These findings indicate that osteosarcomatous changes in malignant melanoma are produced by the dedifferentiated melanoma cells.

In order to elucidate the origin and fate of Merkel cell granules (MCGs), electron microscopic studies were carried out in fetal rat skin at day 20 of gestation. In addition to the ordinary processing of the tissue, we incubated a part of the tissue with a solution containing ionophore A23187 in order to capture the rarely observable exocytotic event. Based on our findings, a hypothetical model for the life cycle of Merkel cell granules is proposed as follows: I) Granule morphogenesis takes place in the rough endoplasmic reticulum and the GERL, from where immature granules are budding off, thereby exhibiting a bristle-like coat. II) Maturation and storage of MCGs takes place in the cytoplasm. III) Following stimulation, MCGs are released. IV) After the exocytotic granule release, MCG membranes are retrieved in the form of coated pits.

An 18-year-old Japanese male presented with a normal-skin-colored, dome-shaped, slightly tender tumor on his left palm. Histopathologically, the tumor consisted of distinct lobules, which were separated by fibrous connective tissue. Each lobule was composed of spindle or round cells within a myxoid matrix pathognomonic of nerve sheath myxoma. The mucinous material was positively stained by Alcian blue (pH 2.5) and toluidine blue (pH 4.0). Immunohistochemically, the majority of spindle cells were positive for S-100 protein (β-subunit) and neuron-specific enolase. Our findings lend further support to the hypothesis that nerve sheath myxoma is derived from Schwann cells.

Background: Palmoplantar pustulosis (PPP) is often associated with osteoarthritis. The relation between osteoarthritis in PPP and other types of seronegative arthritis remains unclear. Objective: The purpose of this study was to investigate the distribution and the frequency of osteoarthritis in patients with PPP and to compare HLA antigen frequencies in osteoarthritis in PPP, psoriatic arthritis, and ankylosing spondylitis. Methods: Clinical findings were identified and HLA-A, -B, -C, and -DR were determined in 84 Japanese patients with PPP. Bone scintigraphic studies were conducted for forty-one patients. Results: In addition to the anterior aspect of the chest wall, the knee, spine, and ankle were frequently involved. HLA-DR9 frequency was the highest in patients with PPP who had osteoarthritis. Conclusion: Involvement of the knees, spine, ankles, and the anterior aspect of the chest wall was noted in patients with osteoarthritis and PPP. Osteoarthritis in PPP seems to be a distinct entity from a genetic point of view.

Ichthyosis bullosa of Siemens (IBS) is an autosomal dominant skin disorder that resembles epidermolytic hyperkeratosis (EHK). We have indentified mutations in two families originally diagnosed with EHK and in four families diagnosed with IBS at the same codon in the highly conserved carboxy terminal of the rod domain of keratin 2e, thus revealing a mutational hot spot. Our results allow a differential diagnosis to be made between IBS and EHK at the genetic level and we suggest that patients diagnosed with EHK, but lacking keratin K1 or K10 mutations, should be re-examined for mutations in their K2e genes.

The cutaneous basement membrane zone (BMZ) is composed of a large number of molecular components. We have recently reported that one of the CD1b monoclonal antibodies (MoAb), NU-T2, reacts to the BMZ of the normal human skin, esophagus and stomach. In order to further elucidate the biological properties of the NU-T2-BMZ antigen, we investigated the expression of NU-T2-BMZ antigen and type VII collagen (well identified component of anchoring fibrils) in various skin tumors such as basal cell epithelioma (BCE), squamous cell carcinoma, Bowen's disease, actinic keratosis and seborrheic keratosis. NU-T2 MoAb failed to react to the BMZ in all BCE. Anti-type VII collagen MoAb showed reduced staining of the BMZ in some nests of BCE. Both antigens, however, were preserved in the BMZ of other skin tumors as in the normal adjacent skin. Furthermore, anti-type VII collagen MoAb demonstrated the clear intratumoral staining in all BCE examined. The abnormal expression of NU-T2-BMZ antigen and type VII collagen may partly explain the space formation between the BCE nests and the surrounding stroma frequently observed in histology.

Porokeratosis (PK) is a rare genetic skin disorder inherited as an autosomal dominant trait and regarded as a disease predisposing to cancer. To evaluate chromosomal radiosensitivity of PK cells, we examined chromosome aberration frequency after X-irradiation of cultured skin fibroblasts derived from PK patients and controls. Without X-ray exposure, frequencies of chromosome-type aberrations (exchanges or deletions) were not different between the patients and controls. Following X-ray irradiation, frequencies of deletions in the patient group were significantly increased, whereas those of exchanges were not elevated. No differences in chromatid-type aberration frequency were found between the patients and controls with or without exposure to X-ray. The observed radiosensitivity, though not as high as in ataxia telangiectasia (AT) cells, agrees well with the previously reported higher radiosensitivity of PK fibroblasts in survival analysis.

The serum level of procollagen type I carboxyterminal propeptide (P1CP), which has been used as an index of collagen synthesis in patients with various fibrotic diseases during the active stage, was measured using enzyme-linked immunosorbent assay in 61 patients with systemic sclerosis (SSc) and in 21 control subjects. The mean P1CP level in the SSc patients was significantly higher than in the normal controls (mean +/- SD, 326 +/- 319 vs 128 +/- 87 ng/ml; p0.005). In 36% of the SSc patients, the serum P1CP level was significantly elevated more than two standard deviations above the mean control value. The mean serum P1CP level in patients with diffuse SSc was significantly higher than in those with limited SSc (411 +/- 373 vs 255 +/- 199 ng/ml; p0.05). In addition, the SSc patients with elevated serum P1CP levels showed a significantly greater incidence of lung fibrosis and joint involvement than those with normal P1CP levels (p0.005 and p0.05, respectively). These results suggest that the serum P1CP level is a useful indicator of the severity of disease in SSc patients.

Genetic polymorphisms in HLA-A, -B, -C and -DR antigens were investigated in 78 unrelated Japanese patients with palmoplantar pustulosis (PPP) and compared with a total of 472 normal persons. Only HLA-DR9 showed a significantly increased frequency among all HLA antigens investigated (chi 2 = 11.57, p < 0.001). It is suggested that major histocompatibility complex class II antigens including HLA-DR antigen may determine the susceptibility to PPP and PPP may be a distinct disease entity from psoriasis.

The ability of the human amelanotic melanoma cell line MM-RU to produce experimental metastases and to grow tumors at subcutaneous inoculation sites in 4-week-old nude mice was examined. After i.v. inoculation of 10(6) cells, all injected mice (n = 21) developed consistent numbers of metastatic pulmonary colonies within 32 days. The coefficients of variation for the number of colonies were between 17%-23% in three independent experiments. Survival time after i.v. inoculation was 63 +/- 7 days (mean +/- SD) (n = 20). Within 20 days, subcutaneous inoculation of 5 x 10(6) cells resulted in tumor growths of 13 +/- 3 mm (mean +/- SD) at the inoculation sites in all nude mice (n = 12). The MM-RU cell line seems to be a simple, fast vehicle for testing the effect of melanoma growth modulators on experimental pulmonary metastases as well as on subcutaneously growing melanoma.

Objective. To study the prevalence and antigen specificity of antihistone antibodies (AHA) in localized scleroderma. Methods. Forty-nine serum samples from patients with localized scleroderma were examined by an enzyme-linked immunosorbent assay (ELISA) and by immunoblottin. Results. By ELISA, AHA were demonstrated in 47% (23 of 49) of patients with localized scleroderma and in 87% (13 of 15) of patients with generalized morphea. Immunoblotting revealed that the predominant antigens were histones H1 and H3. The presence of AHA correlated with that of anti–single-stranded DNA antibody. Conclusion. Some of the major antigens for antinuclear antibodies in patients with localized scleroderma are histones.

Melanomas are rare in patients who have albinism, compared with the frequent occurrence of squamous cell carcinomas and basal cell carcinomas. This report describes amelanotic metastatic melanoma in a 58-year-old Japanese man who had tyrosinase-positive oculocutaneous albinism. A prolonged bleeding time, facioscapulohumeral muscular dystrophy, and Gilbert syndrome were also present. Superficial spreading melanoma with evidence of spontaneous regression on his right forearm was suspected as a possible primary site. Twenty-two cases of melanomas in persons who have albinism have been reported.

Background: The early detection of scleroderma spectrum disorders (SSD) is important. Objective: Our purpose was to determine the prevalence of nailfold bleeding in SSD. Methods: We examined patients for nailfold bleeding in the following three groups: (1) 8 patients with SSD including 50 patients with scleroderma, 10 with mixed connective tissue disease, and 21 with Raynaud's phenomenon having specific antinuclear antibody (ANA) (2) 99 patients with other connective tissue diseases or primary Raynaud's phenomenon; and (3) 200 patients with common skin diseases. Results: The frequency of nailfold bleeding was significantly higher in SSD (75.3%) than it other connective tissue diseases (12.1%) and in controls (3.0%). The presence of nailfold bleeding in two or more fingers showed a 98.3% specificity for SSD. Among the patients with SSD, the incidence of nailfold bleeding in scleroderma, mixed connective tissue disease, and Raynaud's phenomenon with specific ANA was similar. Nailfold bleeding strongly correlated with the presence of anticentromere antibody. Conclusion: The presence of nailfold bleeding is useful for the early detection of SSD.