bluuebunny/crossref_metadata_2025 huggingface dataset:
Eccrine Hidrocystoma: Two Cases of Robinson and Smith Types
Authors: Kato Naoko , Ueno Hiroo
Published: April 2015

Two cases of eccrine hidrocystoma, one of which is a “classic” Robinson type and the other a Smith type, were reported. The walls of both cysts consisted mainly of two layers of flat or low cuboidal epithelial cells with eosinophilic cytoplasm. Immunostaining for S‐100 protein was negative in the cells of the cyst wall of the Robinson type and only weakly positive in the inner luminal layer of the Smith type. Electron microscopically, the Smith type showed double‐layered cuboidal lining and cell membrane interdigitations as junctions of neighboring cells without any characteristics of the secretory segment of sweat glands, indicating substantial similarity to those of the intradermal portion of the eccrine sweat duct.
Enhancing Effects of Fluorescein on β‐Lactam Rash I: High Incidence of Cefclidin Rashes in an Ophthalmological Volunteer Trial
Authors: Tone Takeshi , Ikezawa Zenro , Nishioka Kiyoshi , Aoki Shigeru , Miyata Mikio
Published: April 2015

Disseminated maculopapular eruptions were frequently observed in a volunteer trial of cefclidin's use in ophthalmological and neurological examinations (8/12; 67%). It appeared at 8–12 days (mean ± SD, 9.6 ±1.1 days) from the initiation of the trial and subsided within 1–2 days (mean ± SD, 1.8 ± 0.4 days). Patch testing with cefclidin produced a ± reaction in 1 of 8 cases, and the drug‐induced lymphocyte stimulation test (DLST) elicited a positive response (SI: 2.8) in 1 of 8 and a weakly positive response (1.8≦SI<2) in 2 of 8. From these findings, it seems likely that the eruptions may be partially mediated by delayed type hypersensitivity (DTH) reactions to cefclidin. No such eruption was observed in the phase II trial of cefclidin where only 2.8% of 1.122 volunteers developed the eruption. The volunteers were given both fluorescein and oxybuprocain in their eyes to measure ocular tension on days –1, 0, 1, 3, 5, 7, 9, 11, 13 and weeks 3, 5, 7 after the initiation of cefclidin. Fluorescein and/or oxybuprocain may affect cefclidin to induce these abnormal reactions in the volunteers.
Actinic Cheilitis Granulomatosa
Authors: Kuno Yoshinori , Sakakibara Shigeru , Mizuno Nobuyuki
Published: April 2015

A granulomatous lesion of the lips caused by UVB‐photosensitivity is described. A 31‐year‐old Japanese man developed depigmented, swollen, erythematous lips with some erosions and bloody crusts which were present for 11 months. Histologic examination revealed a dense dermal infiltration composed mainly of lymphoid‐histiocytic cells. Suprabasal clefts were associated with the invasion of lymphoid cells around them. Results of patch and photopatch testing were negative. The minimal erythema dose 24 h after irradiation was lower than normal, ranging from 295 to 330 nm. The lesion was reproduced by repeated irradiation with monochromatic light of 310 and 320 nm, but not by exposure to 250, 260, 270, 280, 290, 300, or 330 nm. Topical injection of glucocorticoids and application of sunscreen led to improvement We propose the name “actinic cheilitis granulomatosa” for this case.
A Case of Subepidermal Blister Disease Associated with Autoantibody against 450 kD Protein
Authors: Fujiwara Sakuhei , Shinkai Hiroshi , Takayasu Susumu , Owaribe Katsushi , Tsukita Shoichiro , Kageshita Toshiro
Published: April 2015

We report a case of subepidermal blister disease with eruptions distributed on the trunk and extremities. The blisters regressed after administration of corticosteroid and cyclophosphamide. An immunoblot analysis revealed that the patient's serum reacted exclusively with a 450‐kD epidermal polypeptide. It did not react with a 230‐kD or a 180‐kD bullous pemphigoid antigen. The immunofluorescence study showed the patient's serum reacted with the basement membrane zone of human skin.
BCC‐Associated Amyloidosis with a Peculiar Pattern of Deposition
Authors: Nojiri Keiko , Ono Tomomichi , Johno Masayoshi , Kayashima Ken‐ichi , Nogami Reiko , Kikuchi Ichiro
Published: April 2015

An 83‐year‐old Japanese woman with lepromatous leprosy had been treated in a leprosarium. More than 10 years ago, she developed a dome‐like brown tumor on the dorsum of the nose which showed the histology of basal cell carcinoma. The lesion was a well bordered, rounded tumor with tumor cell nests on its periphery extending toward the center as cords of tumor nest and with amyloid depositions between the cords. The tumor nests and amyloid lessened toward the center of the tumor, being replaced by collagen fibers. Amyloidosis showing this peculiar pattern of transition was reported with a review of published cases.
A Rare Association of Localized Gigantism with Tuberous Sclerosis
Authors: Reddy Belum Siva Nagi , Sheriff Mohamed Omar , Garg Bhagat Ram , Ratnakar Chaganti
Published: April 2015

An unusual association of localized gigantism with hypertrophy of the long bones and soft tissues in the left lower limb in an 18‐year‐old male with tuberous sclerosis (TS) is reported. The significance of this association is discussed from the point of view of its common neural crest origin during embryogenesis.
Autoimmune Progesterone Dermatitis
Authors: Lee Chang Woo , Yoon Ki Beom , Yi Jung Uk , Cho Soo Hyun
Published: April 2015

A 35‐year‐old woman had recurrent urticarial erythemas on her trunk and extremities for 3 years. The eruptions appeared regularly 3 to 5 days prior to menstruation and persisted for several days. The patient showed a positive skin test response to progesterone and had circulating antiprogesterone IgG antibodies. A speculative concept of the possible autoimmune damage to the ovary, the major organ producing progesterone, is discussed.
Molecular Bases for Hereditary Cancer‐prone Diseases
Authors: Tatsumi Kouichi , Tachibana Akira , Fujimori Akira
Published: April 2015

Constitutional loss or inactivation of one copy of a tumor‐suppressor gene, as exemplified by hereditary retinoblastoma, increases the propensity for malignancies by reducing the number of events necessary for the complete loss of the negative regulatory function. We developed a selectable mutation assay employing a human lymphoblastoid cell line (LCL) derived from a heterozygous carrier of 2,8‐dihydroxyadenine urolithiasis, adenine phosphoribosyltransferase (APRT) deficiency, for dissecting the second step in loss‐of‐function mutations and for determining the potential of physical and chemical agents for producing such mutations. The mode of mutational events arising in the wild‐type allele of the functionally heterozygous APRT gene resembled that reported for tumor‐suppressor genes in malignancies in that mitotic non‐disjunctions or recombinations as well as deletions prevailed. Ultraviolet light (UV) was much less efficient in inducing these types of mutations than ionizing radiation. A group of autosomal recessive cancer‐prone diseases, including xeroderma pigmentosum (XP), has been characterized as being more susceptible to genomic insults, owing to some defects in DNA processing, such as replication, repair, or recombination. This increased genomic instability may accelerate the gain‐of‐function mutation at a proto‐oncogene and/or the loss‐of‐function mutation at a tumor‐suppressor gene. XP complementation group A (XP‐A) LCLs were extremely sensitive to UV‐mutagenesis at the hypoxanthine phosphoribosyltransferase (HPRT) locus even at equicytotoxic doses. Some unique mechanism may operate in UV‐mutagenesis in XP‐A. We have succeeded for the first time in rendering XP‐A cells tumorigenic in athymic mice by applying multiple exposures to UV and subsequent treatment with TPA. This system can be a good model for clarifying the role of genomic instability in enhancing the malignant transformation of human somatic cells.
Dysplastic Nevus Syndrome: Melanoma‐prone Disease
Authors: Tsukamoto Hidekazu , Hayashibe Kazuhito , Ichihashi Masamitsu
Published: April 2015

Regardless of subsequent clinical courses of patients with dysplastic nevi (DN), substantial evidence supporting DN as one of the melanoma‐prone diseases is not yet available, especially in sporadic DN, due to the lack of genetic information other than retrospective studies in clinical observation. This study aimed at the immunohistological characterization of sporadic DN distinct from common nevi (CN) and at the evaluation of the potentiality of sporadic DN for malignant transformation. We considered our results together with previous immunological and epidemiological reports.

We noted the following three immunohistological characteristics. 1) Proliferating cell nuclear antigen (PCNA), one of the markers for active cell division, could be detected on DN cells in junctional nests of only one among ten DN examined but not on CN cells at all. 2) The altered expression of α‐smooth muscle actin (α‐Sma), often observed in melanoma cells, could not be detected in DN cells. However, anti‐α‐Sma monoclonal antibody (MoAb) clearly demonstrated distinctive hypervascularity in the stroma surrounding DN when compared with CN. 3) ME491 antigen, which is known to be expressed mainly in the radial growth phase of melanoma, was detected with similar intensity on both DN and CN. These data indicate that DN has a somewhat higher potentiality than CN for cell division and secretion of some cytokines which can induce hypervascularity in the surrounding stroma, but that DN has not yet undergone the significant phenotypic changes observed in melanoma cells. Further advancements in understanding molecular events in DN cells will be of great benefit in setting DN in the multiple oncogenic spectrum from pigment cells to melanoma.
Epidermodysplasia Verruciformis
Authors: Kawashima Makoto
Published: April 2015

Epidermodysplasia verruciformis is a rare skin disease characterized by the disseminated, flat, wart‐like lesions caused by human papillomavirus and a high frequency of various skin cancers. The clinical aspects, histological findings, genetic and immunological factors, and human papillomavirus types found in the disease and their roles in skin cancers are reviewed.
Chemoprevention of Skin Cancer in Xeroderma Pigmentosum
Authors: Kraemer Kenneth H. , DiGiovanna John J. , Peck Gary L.
Published: April 2015

Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000‐fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre‐existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13‐cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5‐fold after the drug was discontinued (New Engl J Med 318: 1633–1637, 1988). Toxicity (cutaneous, triglyceride, liver‐function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients.
The Interaction between Langerhans Cells and CD4+ T Cells
Authors: Hauser Conrad
Published: April 2015

The human skin is increasingly exposed to haptens and environmental protein antigens. Because Langerhans cells represent the outermost network of MHC class II+ antigen presenting cells in mammalians, we investigated their interaction with CD4+ T cells. Hapten‐modified Langerhans cells induced proliferation and IL‐2 production in naive resting CD4+ T cells. T cells activated in this manner and subsequently cultured with IL‐2 mediated contact sensitivity in vivo and produced IL‐2 but no IL‐4 upon restimulation in vitro. Thus they corresponded to Th1 cells. Repeated stimulation with Langerhans cells induced a modulation of the lymphokine pattern: IL‐2‐ and IL‐4‐producing Th0‐like cells were identified after 3 to 4 rounds of restimulation; after >5 rounds, Th2‐like cells with an IL‐4+IL‐2− pattern and the capacity for inducing IgE synthesis in B cells was identified. Th2 cells were also recently found to mediate inflammatory tissue lesions containing a cellular infiltrate. This demonstrates that Langerhans cells may activate resting CD4+ T cells, Th1‐, Th0‐ and Th2‐like cells. It further shows that Langerhans cells may promote the differentiation of postthymic CD4+ T cells into subsets with distinct immune functions: Th1 cells which have the potential to mediate inflammatory reactions such as allergic contact sensitivity and Th2 cells which may be responsible for abnormalities associated with atopic dermatis, such as elevated IgE and inflammatory skin lesions containing a cellular infiltrate.
Structure of Desmoplakin and Its Association with Intermediate Filaments
Authors: Green Kathleen J. , Stappenbeck Thaddeus S. , Parry David A.D. , Virata M. Luisa A.
Published: April 2015

Desmoplakins (DPs) I and II are two major related proteins located in the desmosomal plaque where they have been proposed to play a role in attaching intermediate filaments (IF) to the inner cell surface. The predicted amino acid sequence of DP was obtained by analysis of overlapping cDNA clones. Computer‐aided analysis suggests that DPI will form a dumbbell‐shaped homodimer, with a central α‐helical coiled coil rod domain of 132 nm and two globular end domains. The DPII molecule is missing 599 residues from the central domain, resulting in a rod about one third the length of DPI. The carboxyl terminus comprises three subdomains each containing almost 5 repeats of a 38 residue repeating motif with a periodicity in acidic and basic residues similar to that found in the rod domain of IF proteins. This suggests a possible mechanism by which these proteins might interact. The amino terminus contains groups of heptad repeats that are predicted to form at least two major α‐helical rich bundles.

A series of c‐myc‐tagged mammalian expression vectors encoding specific predicted domains of DPI were transiently expressed in COS‐7 cells. Light and electron microscopical observations revealed that DP polypeptides including the 90 kDa carboxyl terminal globular domain of DPI specifically colocalized with and ultimately resulted in the complete disruption of keratin and vimentin IF. This effect was specific for the carboxyl terminus, as the expression of the 95 kDa rod domain of DPI did not visibly alter IF networks. Immunogold localization of COS‐7 cells transfected with constructs including the carboxyl terminus of DP demonstrated an accumulation of mutant protein within which IF subunits were sequestered. These results suggest a role for the DP carboxyl terminus in the attachment of IF to the desmosomal plaque in either a direct or indirect manner.
Control of the Distribution of Hemidesmosome Components in Cultured Keratinocytes: Ca2+ and Phorbol Esters
Authors: Kitajima Yasuo , Owaribe Katsushi , Nishizawa Yuji , Yaoita Hideo
Published: April 2015

DJM‐1 cells (a human squamous cell carcinoma cell line) grown in low Ca2+ medium did not form cell‐cell junctions of desmosome‐keratin intermediate filament (KIF). When they were shifted to normal (high) Ca2+ medium, rapid translocation of desmoplakins from the cytosol to the plasma membrane to form desmosomes and reorganization of 180 kd‐hemidesmosome proteins were induced almost simultaneously. In correlation with these morphological responses, the Ca2+ shift caused a breakdown of inositol phospholipids, a formation of diacylgycerol (DAG) and inositol trisphosphate (IP3), protein kinase C (PKC) activation, and Ca2+ influx. 12‐0‐tetradecanoylphorbol‐13‐acetate (TPA)‐treatment of low Ca2+‐grown DJM‐1 cells also caused desmosome formation in association with PKC activation. These TPA effects were cancelled with PKC inhibitors, 1‐(5‐isoqunolinylsulfomyl)‐2‐methylpiperazine (H7) and staurosporine. Treatment with other PKC‐activating agents, phorbol‐12,13‐butyrate (PDBu) and diaoctanoylglycerol (DOG), also induced desmosome formation. TPA‐treatment of normal Ca2+‐grown cells collapsed the organized distribution of the 180 kd‐hemidesmosome protein and appeared to detach this protein from the cell‐matrix adhering sites. This effect was also inhibited by H7. These results suggest that PKC activation plays important roles in upregulation of cell‐cell junctions and downregulation of cell‐matrix junctions in association with differentiation of keratinocytes.
Regulation of Epidermal Keratin Expression by Retinoic Acid and Thyroid Hormone
Authors: Ohtsuki Mamitaro , Tomic‐Canic Marjana , Freedberg Irwin M. , Blumenberg Miroslav
Published: April 2015

In the epidermis, retinoic acid (RA) is known to regulate the gene expression of keratins, the intermediate filament proteins of epithelial cells. We have cloned the upstream regulatory regions of three human epidermal keratin genes, K5, K10, and K14, and engineered DNA constructs in which these regions drive expression of the CAT reporter gene. By co‐transfecting the constructs into various epithelial cell types along with the vectors expressing the nuclear receptors for RA and thyroid hormone (T3), we have shown that RA and T3 directly regulate expression of these three keratin genes through the action of their nuclear receptors. In this paper, we review our previous results to stress that RA has a dual effect on keratin expression in epidermis: both direct and indirect. We also analyze the DNA sequences upstream from those three RA‐regulated keratin genes and identify the clusters of degenerate consensus half‐site motifs, which may comprise the putative retinoic acid recognition elements (RAREs). Furthermore, our recent results concerning the regulation of K5 and K14 expression by the RA receptor are also shown; these confirm our predictions regarding the location of the RAREs in epidermal keratin genes.
Epidermolysis Bullosa and the Search for the Basis of Hereditary Disorders of the Skin
Authors: Epstein Ervin H.
Published: April 2015

During the past two years the application of newer strategies of molecular genetics has resulted in the identification of genes whose mutations underlie five diseases of the skin. This is likely to be but the start of an unprecedented expansion in our understanding of these disorders and, most likely, of our ability to treat them.
A Model to Study the Fate of Genetically‐marked Keratinocytes in Culture
Authors: Garlick Jonathan A. , Taichman Lome B.
Published: April 2015

In this study we demonstrate a method for analyzing the spatial distribution or fate of progeny keratinocytes derived from single progenitor cells. The method relies upon the use of retroviral vectors to introduce a reporter gene into replicating cells and to effect integration and expression of that new gene. All progeny cells from that initial cell inherit and express the transferred gene. The reporter gene is the E. coli beta‐galactosidase gene (B‐gal), which encodes a histochemically‐detectable product in the cytoplasm. Using this method, we show that foci of genetically marked, B‐gal positive cells can be readily identified in submerged cultures and we term this grouping of cells a “clonal proliferation unit”. Analysis of B‐gal stained whole mounts and paraffin sections allows visualization of the proliferative potential and differentiating capacity of clonogenic cells. This model will allow exploration of how agents known to alter epidermal proliferation and differentiation affect lineage relationships.
5‐S‐Cysteinyldopa in Urine and Tumors
Authors: Hara Hiroyuki , Chino Kazuo , Kawanami Taeko , Sameshima Toshiaki , Morishima Takafumi
Published: April 2015

The urinary 5‐S‐CD contents in malignant melanoma subjects (n=135) and non‐melanoma subjects (n=204) were measured by HPLC. These results suggest that, as a biochemical marker, periodic measurement of urinary 5‐S‐CD is quite useful for evaluating the determinations of stage classification (UICC, 1987), and the detection of metastases, the therapeutic efficacy of operation or immunochemotherapy against malignant melanoma.

Quantitative analyses of 5‐S‐CD values in tissues from primary malignant melanoma lesions (n=24) and pigmentary tumors odier than melanomas (n=136) snowed 80.6–821.4 ng/mg and N.D.‐55.0 ng/mg respectively. In view of the above findings, it was suggested that the pigmentary tumors can be diagnosed as malignant melanoma if the 5‐S‐CD value in the tissues is higher than 100 ng/mg.
Serum 5‐S‐Cysteinyldopa (5‐S‐CD) as a Marker of Melanoma Progression
Authors: Horikoshi Takashi , Ito Shosuke
Published: April 2015

We previously reported that serum 5‐S‐cysteinyldopa (5‐S‐CD) tended to elevate earlier and reflect melanoma progression better than urinary 5‐S‐CD. In patients without metastatic melanomas, serum concentration and urinary excretion of 5‐S‐CD and 6‐hydroxy‐5‐methoxyindole‐2‐carboxylic acid (6H5MI2C) were within the upper limits of normal controls. In this report, we presented more precisely the changes in these melanin‐related markers and clinical courses of four melanoma patients. Serum and 24‐hour urine samples were serially collected and assayed every 1 to 4 months. Three of them developed stage IV malignant melanomas and died of metastatic disease. 6H5MI2C in serum and urine did not reflect the progression of disease. Among the 4 parameters considered, 5‐S‐CD in serum appeared to be the best biochemical marker for melanoma progression. Serum 5‐S‐CD over the upper limit of 10 nmol/L was suggested as a serious sign of the progression of melanoma.
Alteration of Melanoma Melanogenesis by Phenotypic Modifiers
Authors: Takahashi Hiroyuki , Horikoshi Takashi , Wakamatsu Kazumasa , Ito Shosuke , Parsons Peter G.
Published: April 2015

Human melanoma cells (MM96E) were incubated with a phenotypic modifier (L‐ethionine) to compare its effects on phenotypic expression with those induced by sodium butyrate and dimethyl sulfoxide. In contrast to the latter agents, L‐ethionine (8mM) failed to arrest the cell cycle at the G1 phase or to inhibit colony formation ability after 48 hr incubation. Tyrosinase activity changed in parallel with 5‐S‐cysteinyldopa (5‐S‐CD) content during treatment with sodium butyrate or dimethyl sulfoxide. Tyrosinase was inhibited in L‐ethionine‐treated cells, probably because of metabolism of L‐ethionine to sulfhydryl compounds; this remains to be clarified. Gamma‐glutamyl transpeptidase activity changed inversely with tyrosinase activity after sodium butyrate or dimethyl sulfoxide incubation, whereas L‐ethionine did not significantly alter the enzyme activity. In addition, only sodium butyrate induced alkaline phosphatase activity. L‐ethionine was less effective than sodium butyrate or dimethyl sulfoxide in inhibiting expression of the B8G3 melanosomal antigen, as determined by Western blotting. These results suggest that phenotypic modifiers (differentiation inducers) affect melanoma cells in various ways and that melanogenesis therefore reflects only one aspect of differentiation in pigment cells.
Analysis of the Expression of Hanganutziu‐Deicher (HD) Antigen in Human Malignant Melanoma
Authors: Kawachi Shigeo , Saida Toshiaki
Published: April 2015

Hanganutziu‐Deicher (HD) antigen is classified as a heterophile antigen and chemically defined as a ganglioside and/or glycoprotein containing N‐glycolylneuraminic acid (NeuGc). HD antigen is absent from normal tissues in humans and chickens but can be expressed in human malignant neoplasms including melanoma. We analysed HD antigen expression in ganglioside and glycoprotein fractions of human melanoma tissues by means of TLC enzyme‐immunostaining and Western blotting with biotinylated affinity‐purified chicken anti‐NeuGc‐lactosylceramide (anti‐HD3) antibody. No HD‐antigenic gangliosides were detected in 11 specimens of human melanoma. In the glycoprotein fractions, however, a strong HD‐positive band of 58 kD was detected in 3 of 10 specimens and several minor bands (37 kD, 13.5 kD, etc.) were also found in 5 specimens. The positive bands completely disappeared after treatment with neuraminidase. These results suggest that HD antigen is expressed on the carbohydrate chains of glycoproteins but not on those of gangliosides in human melanoma.
Analysis of Expression and Soluble Form of Intercellular Adhesion Molecule‐1 in Malignant Melanoma
Authors: Kageshita Toshiro , Yoshii Akira , Kimura Toru , Ono Tomomichi
Published: April 2015

The effects of interferon (IFN) on the expression of ICAM‐1 in human melanoma cell lines and the shedding of ICAM‐1 into spent media were investigated using an indirect binding assay and a double determinant immunoassay (DDIA). While IFN increased the level of expression of ICAM‐1 on melanoma cell lines, the susceptibility to IFN differed according to cell line. The enhancing effect of IFN‐γ was concentration‐dependent, and it exceeded those of IFN‐α and IFN‐β.

Shedding of ICAM‐1 into spent media was detected effectively, and the results agreed well with the expression of ICAM‐1 on melanoma cells. Immunostaining of the surgically removed melanoma lesions was positively correlated with the thickness of the primary lesion. The expression of ICAM‐1 in primary melanoma lesions was inversely correlated with the disease‐free interval.

The circulating ICAM‐1 with stage 4 melanoma patients significantly exceeded that of stage 1–3 melanoma patients. These observations suggest that ICAM‐1 in its soluble form may play an important role in host immunities and may be useful in evaluating the prognosis of patients with melanoma.
Integrin Expression in Malignant Melanoma and Their Role in Cell Attachment and Migration on Extracellular Matrix Proteins
Authors: Etoh Takafumi , Byers Hugh Randolph , Mihm Martin C.
Published: April 2015

The interaction between melanoma cells and extracellular matrix (ECM) components may be important for invasion and metastasis. The integrins belong to a family of protein heterodimers composed of α and β subunits and the β1‐integrins are especially important as ECM receptors.

We investigated the expression of β1‐integrins on four human melanoma cell lines (two primary, one from the radial growth phase (RGP) and another from the vertical growth phase (VGP), and two metastatic) and examined their attachment and migration on laminin (LN), type IV collagen (CN) and fibronectin (FN). Among LN and/or CN integrin receptors, only α2β1 (VLA2) was expressed at significantly higher levels in the VGP and metastatic cell lines in comparison to the RGP cell line. In addition, enhanced attachment and migration on LN and CN were significantly inhibited by anti‐VLA2 monoclonal antibody (mAb). As to FN receptors, α4β1 and α5β1 expression was heterogeneous among the cell lines, however, it was directly related to enhanced attachment and migration on FN, which also could be inhibited by anti‐VLA4 and anti‐VLA5 mAbs.

Our findings provide evidence for a role in β1‐integrins, in particular α2β1, in melanoma progression and metastasis.
Expression of Neuron‐specific Enolase Immunoreactivity by Cutaneous and Extracutaneous Langerhans‐cell Histiocytoses (“X”)
Authors: Roca‐Miralles Mercedes , Kanitakis Jean , Béjui‐Thivolet Françoise , Schmitt Daniel , Castels‐Rodellas Antonio , Thivolet Jean
Published: April 2015

The immunohistochemical expression of Neuron‐Specific Enolase (NSE) and of S100 protein was studied in 10 cases of cutaneous and 19 cases of extracutaneous Langerhans cell histiocytoses (LCH), including acute/proliferative forms (cutaneous Letterer‐Siwe disease) and chronic/granulomatous forms (eosinophilic granuloma, Hand‐Schüller‐Christian disease). Of the LCH cases, 18 (62%) exhibited detectable NSE‐immunoreactivity as compared to 82.8% for S100. NSE expression was found more frequently and intensely within acute (as compared to chronic) forms of LCH. This result lends further support to the cellular unicity of LCH, but also suggests some degree of heterogeneity among LCH cells. It can be speculated that NSE‐expression is correlated with the proliferation/activation state of (abnormal) Langerhans cells.
Nodular Scleroderma in Systemic Sclerosis under D‐Penicillamine Therapy
Authors: Sasaki Tetsuo , Denpo Kenichi , Ono Hideki , Nakajima Hiroshi
Published: April 2015

A case of systemic sclerosis (SS) which developed keloidal lesions (nodular scleroderma) on the chest during D‐penicillamine (DPC) therapy is reported. The 36‐year‐old woman showed rapidly progressing skin sclerosis with lung and esophageal involvement, and DPC was started at the age of 38. Skin sclerosis as a whole had improved to some extent, when keloidal nodules developed on the upper chest at the age of 44. Since there were no other findings suggestive of adverse reactions caused by DPC, we speculate that activation of the fibroblasts in these lesions occurred despite the suppressive effect of DPC.
An AIDS Patient with Atopic Dermatitis‐like Eruption Responsive to Systemic Anti‐fungal Treatment
Authors: Hoashi Mariko , Imayama Shuhei , Hori Yoshiaki , Kashiwagi Seiichiro
Published: April 2015

Patients with the acquired immunodeficiency syndrome (AIDS) often develop unusual skin complications. We describe a case of a 58‐year‐old man with AIDS who had a history of multiple transfusions with anti‐hemophilic factor A. He developed papulovesicular and lichenified skin lesions on his head, face, neck and the extensor aspects of his extremities accompanied by severe pruritus. Atopic dermatitis was suspected; however, intensive treatment with a potent topical corticosteroid and a systemic antihistamine failed. In addition to the decreased subset of CD4‐positive lymphocytes characteristic of AIDS, this patient showed an elevated level of serum IgE particularly specific for Candida albicans, probably because he had a chronic candidial infection of the digestive tract. Oral administration of anti‐fungal agents Diflucan® and Fungizone® produced almost complete relief from the atopic dermatitis‐like skin disease within 2 weeks.
Expression of Monocyte/Macrophage Markers (CD13, CD14, CD68) on Human Keratinocytes in Healthy and Diseased Skin
Authors: Hunyadi János , Simon Miklós , Kenderessy Anna Sz. , Dobozy Attila
Published: April 2015

The results of several investigations prove that, in special circumstances, human keratinocytes (HKs) synthesize and express cell surface moieties characteristic of effector and/or accessory cells of the immune system, such as CD16, CD36, HLA‐DR, and intercellular adhesion molecule‐1 (CD54), which are all detectable on the surfaces of macrophages. In the present study, skin biopsies from healthy volunteers, from positive tuberculin skin tests, and from patients with acute urticaria (AU), lichen planus (LP), psoriasis vulgaris (PV), mycosis fungoides (MF), and purpura pigmentosa chronica (PPC) were investigated by means of a multistep immunoperoxidase method to examine the reactivity of the HKs with a panel of monoclonal antibodies (MABs) characteristic of monocyte/macrophage cell lines. In biopsies obtained from positive tuberculin tests and from clinically involved skin of patients with LP, PV, MF, or PPC, a multifocal, positive peroxidase reaction was observed on the membranes of HKs of the basal and suprabasal cell layers when the MABs OKM13 (CD13), OKM14 (CD14), and Dako‐Macrophage (CD68) were used. In contrast, specific staining of the HKs was not observed with the same antibodies in the biopsies of healthy volunteers or of patients with AU or in the uninvolved skin specimens obtained from the other patients. The HKs of PV, LP, MF, PPC, and AU patients and those of the healthy subjects all failed to give positive reactions when MABs against CD11b, CD15, or CD33 were used. The published data supplement the known surface characteristics of HKs, reflecting their stage of activation and differentiation.
Atypical Exanthema in a Patient with Infectious Mononucleosis
Authors: Kato Hideyuki , Kitajima Yasuo , Yaoita Hideo , Nishiwaki Munekazu
Published: April 2015

A 19‐year‐old male with a sore throat developed numerous, indistinct, erythematous, maculopapular lesions on the trunk. The eruptions, which mimicked secondary syphilis, continued for seven weeks and faded away without pigmentation or scarring. The laboratory examinations revealed lymphocytosis with atypical lymphocytes, seroconversion of Epstein‐Barr virus titers, and elevation of transaminase in liver function.
A Case of CD8+ T Cell Lymphoma Occurring during Treatment for In situ Malignant Melanoma of the Palate
Authors: Nogami Reiko , Maekawa Yoshihiro
Published: April 2015

A 53‐year‐old Japanese male noticed pigmented lesions on his right upper gingiva and hard palate in February of 1986. Histological examination revealed in situ malignant melanoma. Chemotherapy, β‐interferon, and oral BCG were given. However, tumors subsequently developed in the nasal cavity in March of 1989. The patient died in April of 1990 after developing Garcin's syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Autopsy revealed aggressively infiltrating, whitish tumor masses invading the hard palate, the nasal cavity, the paranasal sinuses, the base of the skull, cranial nerves I‐X, and the pituitary body, as well as severe necrosis of the soft palate. However, there was no evidence of malignant melanoma. Instead, these oval tumor cells had atypical nuclei and scanty cytoplasm. They contained no melanin granules, were negative for S‐100 protein, and were also negative for various melanoma‐associated antigens. They were positive for CD2, CD3, and CD8 by avidin‐biotin‐peroxidase complex immunohistochemistry. It was concluded that the patient had CD8+ non‐Hodgkin's malignant lymphoma (diffuse, large cell type) of the nasopharyngeal region, which was preceded by in situ malignant melanoma of the palate.
Necrotizing Fasciitis Appearing with Petechiae as the First Clinical Sign
Authors: Kato Naoko , Ueno Hiroo
Published: April 2015

A 64‐year‐old Japanese man with necrotizing fasciitis is reported. He developed an Enterobacter agglomerans infection in his left leg without any known causative surgery or trauma, although he had acute myelocytic leukemia as a predisposing condition. Uncommonly, the first clinical sign was petechiae. Surgical debridement could not be performed because of pancytopenia due to his original disease and chemotherapy. The patient died, and an autopsy was performed. Severe intravascular coagulation was observed in the cutaneous infected tissues, while little or no disseminated intravascular coagulation was observed in the major internal organs. The local microorganism factors such as necrotoxins were suspected to cause the intravascular coagulation in the infected tissues.
Clinical Significance of Serum Adenosine Deaminase Activity in Patients with Mycosis Fungoides
Authors: Koizumi Hiroko , Tomizawa Kouki , Tanaka Hideo , Kumakiri Masanobu , Ohkawara Akira
Published: April 2015

Adenosine deaminase is one of the key enzymes in purine nucleotide degradation. This enzyme exists in most of the human tissues and the activity is high in lymphatic tissues, especially in T lymphocytes. Elevated adenosine deaminase activity in T cell leukemia has been reported, and its inhibitor, deoxycoformycin, has been developed as an antitumor agent. In some types of leukemia, serum adenosine deaminase activity increases in accordance with the severity of the disease. Although mycosis fungoides rarely involves peripheral blood, tumor cells do invade the skin. In order to evaluate the clinical significance of adenosine deaminase in mycosis fungoides, adenosine deaminase activity was measured in sera of 15 patients with mycosis fungoides at various stages. The mean enzyme activity was 23.2 IU/l, which was high with statistical significance compared with healthy controls (P<0.001). Nine of twelve patients in the plaque stage (T2N0M0, IB) showed higher adenosine deaminase activity than did the normal population. The mean adenosine deaminase activity in sera in the patients in the plaque stage (T2N0M0, IB) was as high as 19.0 IU/l (range 13.7–21.4) with statistical significance compared with healthy control (P<0.001). Three tumor stage patients without visceral involvement (T3N0M0, IIB) showed higher levels of adenosine deaminase activity (19.7, 21.5, 24.4 IU/l). An erythrodermic patient (T4N0M0, III) also had a high adenosine deaminase activity 28.4 IU/l. Two tumor stage patients with organ involvement (T3N0M1, IVB) exhibited extremely high adenosine deaminase activity (60.9, 32.2 IU/l). The adenosine deaminase activity in sera showed a tendency to become higher with the extension of the stages. From the results obtained in this study, it is suggested that serum adenosine deaminase activity may reflect the tumor progress in mycosis fungoides.
A Case of Superficial Spreading Melanoma In situ 2.5 mm in Diameter
Authors: Ban Masanori , Yoneda Kazufumi , Yanagihara Makoto , Mori Shunji , Seko Toshiyuki
Published: April 2015

A 60‐year‐old woman with superficial spreading melanoma in situ, measuring 2.5 mm in diameter, was examined. She had noticed a very small pigmented lesion 1.2 mm in diameter on her left lower leg in April of 1989. By April of 1990, it had grown to 2.5 mm in diameter. Its edge was irregular, and its color was variegated black to brown. Skin surface markings had disappeared in the center portion. Histopathologically, the lesion was asymmetrical. Atypical large cells nested in the lower epidermis and were scattered singly in the mid and upper epidermis, as seen in Paget's disease. At the periphery of the lesion, single large tumor cells were scattered in the mid epidermis. The tumor cells reacted to monoclonal anti‐melanoma antibody HMB‐45.
A Case of Acquired Lymphangioma of the Vulva
Authors: Akimoto Kayoko , Nogita Toshitatsu , Kawashima Makoto
Published: April 2015

A 46‐year‐old woman developed multiple papules on the right labium majus. A histological examination revealed acanthotic epidermis and dilated vessels in the papillary dermis. The clinical and histological features were compatible with those of lymphangiectasis or acquired lymphangioma of the vulva, which occurs after surgery or irradiation for cervical cancer. This patient, however, had no such past history. Acquired lymphangioma of the vulva arising without obvious causes seems to be unusual.
Cutaneous Eruptions Induced by Granulocyte Colony‐stimulating Factor in Two Cases of Acute Myelogenous Leukemia
Authors: Yamashita Noriko , Natsuaki Masaru , Morita Hideki , Kitano Yukio , Sagami Seiichiro
Published: April 2015

Recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) induced cutaneous eruptions in two cases of acute myelogenous leukemia. In both cases, the eruptions appeared during rhG‐CSF therapy for neutropenia induced by the remission‐induction chemotherapy and disappeared rapidly after the discontinuance of rhG‐CSF therapy. Histopathology of those eruptions revealed dermal cell infiltrations consisting of some neutrophils and atypical cells. It was interesting that, although there were no leukemic cells in the peripheral blood or bone marrow, eruptions containing many leukemic cells appeared. The mechanism of the appearance of these eruptions was unclear, but it was considered that a few leukemic cells might have responded to rhG‐CSF and proliferated in the skin.
A Case of Herpes‐associated Erythema Multiforme in a Japanese Child
Authors: Uemura Tomoko , Nagayama Michiyo , Kawashima Makoto
Published: April 2015

A case of a five‐year‐old Japanese boy with herpes‐associated erythema multiforme (HAEM) was reported. The patient had eleven recurrences of herpes labiaris within one year; four of these recurrences were accompanied by erythema multiforme. A study of the human leukocyte antigens revealed the presence of HLA‐DQW3, which has been reported to be significantly frequent in Caucasian patients with HAEM. Oral administration of acyclovir at the onset of herpes labialis was effective in preventing HAEM. Early administration of oral steroids at the onset of HAEM also prevented its exacerbation.
Current Topics of Immunohistochemistry as Applied to Skin Tumors
Authors: Hashimoto Ken , Fujiwara Keiko , Mehregan Amir
Published: April 2015

Suppressor oncogene p53 is expressed more frequently in the nodular portion than the superficial spreading portion of the same melanoma. PCNA expression follows the same pattern but it is strongly expressed already in the superficial spreading portion. CD34 is found to label dermatofibrosarcoma protuberans. There is the mixture of negative strands but the immunostains are predominantly positive in the three cases studied. Neurogenic tumors are reactive but the intensity of staining is only moderate. Fibrous histiocytoma, dermatofibroma and other fibrohistiocytic tumors are non‐reactive. CD34 is expressed in the outer root sheath of hair follicle below the sebaceous gland level. A case of piloepidermal cyst is CD34 positive. CD34 is expressed in vascular endothelial cells; not only hemangiomas but also lymphangiosarcoma is CD34 positive. A case of indeterminate cell histiocytosis following scabies and superficial variant of clear cell sarcoma are discussed as examples of new entities.
A Case of Lupus Meningitis Treated Successfully with Methylprednisolone Pulse Therapy
Authors: Kanekura Takuro , Mizumoto Junichi , Setoyama Mitsuru
Published: April 2015

A 46‐year‐old female had suffered from systemic lupus erythematosus (SLE) for 8 years. Headache, vomiting and stiff neck appeared in the active phase of SLE. Findings in the cerebrospinal fluid were consistent with those of lupus meningitis. No pathogenic microbes were detected by microbiological or immunological examinations. She was diagnosed as having lupus meningitis.

The method discussed herein which elucidates the cause of fever in SLE using white blood cell count (WBC) and alpha‐2 globulin appeared to be useful for examining this case of meningitis.

Lupus meningitis seems to preferentially occur in SLE patients with positive anti‐ribonucleoprotein (RNP) antibody.

Pulse therapy with methylprednisolone appeared to work well in this lupus meningitis patient who had had a long course of corticosteroid therapy.
Metastatic Behavior and Tumorigenicity of a Human Melanoma Cell Line (MM‐RU) after Injection into Nude Mice
Authors: Stender Ida‐Marie , Etoh Takafumi , Tsuchida Tetsuya , Nakagawa Hidemi , Byers H. Randolph , Imokawa Genji , Ishibashi Yasumasa
Published: April 2015

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 106 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 × 106 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.
Macrophage Markers 25F9 and 27E10 on Human Keratinocytes in Normal and Diseased Skin
Authors: Simon Miklós , Hunyadi János , Gómez Renate Schlegel
Published: April 2015

In the present study, an immunohistochemical analysis was made of the expression pattern of different macrophage markers such as 25F9, 27E10 and RM 3/1 on the surface of human keratinocytes (HK) in biopsies obtained from healthy volunteers and from patients with lichen planus, chronic cutaneous graft‐versus‐host reaction, mycosis fungoides, and purpura pigmentosa chronica. In biopsies from the healthy volunteers and from both clinically involved and uninvolved skin of the patients, the HK of the basal cell layer exhibited a specific peroxidase‐positive reaction when the monoclonal antibody against 25F9 was used. Lesional HK from all patients studied displayed 25F9 and 27E10 in nearly the entire epidermis. The present findings provide further evidence that HK and macrophages share a number of common cell surface moieties.
Pilary Complex Carcinoma: An Adnexal Carcinoma of the Skin with Differentiation towards the Components of the Pilary Complex
Authors: Rahbari Homayoon , Mehregan Amir H.
Published: April 2015

We report twelve cases with a distinctive form of adnexal carcinoma occurring most commonly over the head and neck of relatively old individuals. The growth was single in all cases, deep dermal in location, and consisted of massive proliferation of small basaloid cells with only occasional connection with the surface epidermis. The basaloid tumor masses showed only a few areas of palisading of their outer cell nuclei and occasional retraction space formation. The neoplasm revealed scattered areas of trichilemmal and epidermoid keratinization, foci of sebaceous, and areas of sweat ductal differentiation indicating participation of various components of the pilary complex.
Multiple Agminated Juvenile Melanoma Arising on a Hyperpigmented Macule
Authors: Akasaka Toshihide , Imamura Yuko , Kon Saiichi
Published: April 2015

A case of multiple agminated juvenile melanoma (MAJM) arising on a hyperpigmented macule is reported. The patient, a 1‐year‐old boy, had 9 small nodules on an irregular, hyperpigmented macule on the right shoulder. Histologically, the nodules contained nests of spindle‐shaped cells in their epidermis and at the dermoepidermal junction, and the hyperpigmented macule exhibited increased melanin granules in the basal layer and small nests of epithelioid cells. We concluded that MAJM on a hyperpigmented macule is the subtype of the nevus spilus.
An Evaluation, Using Computerized Image Analysis, of Antimicrobial Efficacy of an Automatic Hand Washing Machine with Ultrasonic Wave Spraying
Authors: Nishijima Setsuko , Namura Shoko , Mitsuya Kaoru , Asada Yasuo
Published: April 2015

We studied the antimicrobial efficacy of hand washing with a quick‐dry hand washing machine [TE‐KIREIKI]® employing ultrasonic wave spraying and its incidental alcohol‐based product [AROKULIN‐E]®. The subjects of this study were 10 males who had been instructed not to use any antimicrobial agent for the previous 2 weeks or any hand soap for the previous 5 hours.

They pressed their palms on agar before and after washing their hands. After 48‐hour incubation at 37°C, the bacterial colonies grown on the agar were counted using the [ASPECT]® image processing system. The colony count was expressed as the post‐stamp versus pre‐stamp percent (%) reduction.

Two patterns of hand washing were examined in this study: [A] a 3‐second hand wash using an alcohol‐based product [AROKULIN‐E]® and [B] a 30‐second hand wash using a non‐medicated detergent soap with running water in addition to hand washing by [A].

The percent (%) reduction after hand washing patterns [A] and [B] were 49.1% and 51.3%. These reduction rates indicated that these patterns did not eradicate bacteria from the hand surface. Therefore, we concluded that this quick‐dry hand washing machine employing an ultrasonic wave spraying method combined with an alcohol‐based product needs improvement.