bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractDesmoplakins (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

AbstractDJM‐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

AbstractIn 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

AbstractDuring 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

AbstractIn 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

Abstract

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

AbstractWe 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

AbstractHuman 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 Expression and Soluble Form of Intercellular Adhesion Molecule‐1 in Malignant Melanoma
Authors: Kageshita Toshiro , Yoshii Akira , Kimura Toru , Ono Tomomichi 
Published: April 2015

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractA 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

AbstractPatients 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

AbstractThe 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

AbstractA 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

AbstractA 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

AbstractA 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

AbstractAdenosine 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

AbstractA 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.