bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure, Function and Possible Clinical Application of Transforming Growth Factor‐β
Authors: Miyazono Kohei , Heldin Carl‐Henrik
Published: April 2015

Transforming growth factor‐β (TGF‐β) is a family of multifunctional 25 kDa proteins. TGF‐β was originally identified because of its ability to induce the growth of normal rodent fibroblasts in soft agar, but is now known as a potent growth inhibitor for many different cell types. In addition, TGF‐β is known to regulate the differentiation of cells, induce chemotaxis of cells, and to induce the accumulation of extracellular matrix proteins. In vivo, TGF‐β stimulates the repair of soft as well as hard tissues. It also acts as a potent immunosuppressant.

TGF‐β is produced as latent high molecular weight complexes; since it is produced by many different cell types, and most cells have receptors for TGF‐β, the activation of latent TGF‐β is likely to be an important step in the regulation of its action. TGF‐β exerts its effects by binding to specific cell surface receptors. The type I and type II TGF‐β receptors are suggested to be the most important for signal transduction; a recent report has disclosed that the type II receptor has a serine/threonine kinase domain.

Since TGF‐β is a potent growth regulator with multifunctional activity, it may be useful in the treatment of certain clinical disorders. Local application of TGF‐β is shown to accelerate wound healing. Since an increase in TGF‐β activity is often observed in various fibrotic disorders, antagonists for TGF‐β might be valuable in the treatment of such diseases.
Stimulation of Keratinocyte Migration by Growth Factors
Authors: Tsuboi Ryoji , Sato Chiyo , Shi Chong‐Ming , Ogawa Hideoki
Published: April 2015

Migration of keratinocytes from the wound edge is thought to be one of the critical features of reepithelialization. A quantitative migration assay was carried out using normal human keratinocytes. Keratinocytes, seeded on 12 well plates, were grown in serum free, keratinocyte growth medium (KGM, Curabo Co) with 0.08mM Ca++. The medium was switched from KGM to keratinocyte basal medium (KBM) 6 h prior to the wounding. Half of the plate's confluent monolayer of keratinocytes was removed with a razor blade, and the remaining keratinocytes were incubated in KBM for 16 hrs in the presence of indicated growth factors. After incubation, the cells were fixed and counted at 100 magnification. Migration was quantitated by counting the number of cells in ten successive 125‐μm zones.

Transforming growth factor α (TGF‐α), acidic and basic fibroblast growth factor (aFGF, bFGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and insulin‐like growth factor‐I (IGF‐I) stimulated the migration of keratinocytes, while TGF‐β suppressed it.
The Effects of Basic Fibroblast Growth Factor and Doxorubicin on Cultured Human Skin Fibroblasts: Relevance to Wound Healing
Authors: Sasaki Tetsuo
Published: April 2015

The effects of basic fibroblast growth factor (bFGF) and doxorubicin on cultured human skin fibroblasts were examined in order to determine their relevance to wound healing. bFGF is shown to stimulate fibroblast collagenase production per cell, and this effect in vitro seems to be one explanation for its efficacy in wound healing. Doxorubicin inhibited not only fibroblast proliferation but also collagen production by inactivating prolyl hydroxylase. This result may explain the reduced wound healing in patients undergoing treatment with doxorubicin. These studies indicate the importance of assessing the effects of growth factors on matrix metabolism in order to understand their roles in wound healing.
A Wound Healing Model Using Healing‐impaired Diabetic Mice
Authors: Tsuboi Ryoji , Shi Chong‐Ming , Rifkin Daniel B. , Ogawa Hideoki
Published: April 2015

A quantitative histological approach was employed to evaluate the effects of basic fibroblast growth factor (bFGF) in healing‐impaired diabetic mice. The dorsal areas of female mutant diabetic mice, C57BL KsJ db/db (Jackson Lab.), were given two 6 mm‐size full thickness wounds with a punch biopsy instrument. After application of bFGF, the wounds were left open. 8 days after wounding, the mice were sacrificed, and histological sections were evaluated using several histological parameters, such as the degree of wound closure, granulation tissue thickness, matrix density, and capillary numbers.

Application of 5 μg of bFGF for 5 days induced significant responses by all of these dermal parameters when compared to those of non‐treated db/db mice (p<0.001). A minimum of 0.5 μg bFGF per day was required for a significant effect. Time‐course experiments indicated that the granulation response in bFGF‐treated mice peaked between 8 and 12 days and decreased after 12 days, while matrix density continued to increase until the 18th day.
Alterations of Mitogenic Responses of Mononuclear Cells by Arsenic in Arsenical Skin Cancers
Authors: Yu Hsin‐Su , Chang Kee‐Lung , Wang Ching‐Ming , Yu Chia‐Li
Published: April 2015

We have studied the endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan. The effects of arsenic on the mitogenic responses of mononuclear cells (MNC) derived from patients with arsenical skin cancers in that area were evaluated. The subjects enrolled in this study included patients with 1) Bowen's disease, 2) arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 3) non‐arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 4) nasopharyngeal cancer and 5) healthy controls from endemic and non‐endemic areas. Phytohemagglutinin (PHA) stimulated [3H]thymidine incorporation in MNC in all groups except the arsenical skin cancer group. However, when a low concentration of As2O3 (2.5 × 10−7 M) was added to PHA‐stimulated MNC, a tremendous amplification of the uptake of [3H]thymidine was noticed in patients with arsenical skin cancer. In this study, this phenomenon did not occur in cancers not related to arsenic. This result shows that arsenical carcinomas are hyperreactive to its specific etiology—arsenic. Arsenic seems to play a role as a co‐stimulant of PHA similar to interleukin‐1.
Skin‐infiltrating Lymphocytes in Normal and Disordered Skin: Activation Signals and Functional Roles in Psoriasis and Mycosis Fungoides‐type Cutaneous T Cell Lymphoma
Authors: Cooper Kevin D.
Published: April 2015

T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non‐specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell‐related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage‐related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume “psoriatic” phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA‐DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.

In conclusion, certain APC subsets dominate epidermal and dermal compartments in normal and diseased skin, and may influence the level of activation and type of differentiation of freshly recruited SIL's. Established SIL's demonstrate functions that serve to propagate the self sustaining pathophysiology of chronic disease.
In vitro Keratin Expression of Hair Cells
Authors: Kitano Yukio , Saito Katsuyuki , Okamoto Eriko , Okano Yuri , Tanigaki‐Obana Noriko , Ito Kaoru , Tazawa Toshio , Ito Masaaki
Published: April 2015

Human hair follicles were isolated from the scalp by dispase and collagenase treatment and dispersed into a cell suspension by trypsin. These cells proliferated well and could be subcultured 7 to 8 times. The medium used was MCDB 153 HAA medium further supplemented with some amino acids, hydrocortisone, insulin, EGF, and bovine brain extract. The concentration of Ca++ was adjusted to 0.1 mM. Immunohistochemically, these cells were proved to possess keratins specific to hair forming cells.
Gangliosides of Melanoma
Authors: Tsuchida Tetsuya , Ishibashi Yasumasa
Published: April 2015

The relationships between the ganglioside composition of melanomas and their biologic behavior were investigated. (1) The amount of GM2 and/or GD2 in melanoma cells injected into nude mice correlated with the tumor growth rate. (2) GD2 content of melanoma cell lines correlated with sensitivity to radiation and vincristine. (3) GM2 expression of melanoma cells correlated with sensitivity to lymphokine‐activated killer cells. (4) Gangliosides inhibited the proliferation of human T cells stimulated with interleukin‐4 or interleukin‐2.

Based on these results, we proposed a hypothesis for the role of melanoma‐associated gangliosides in the biologic behavior of melanomas and suggested a prospective melanoma treatment related to the gangliosides.
Melanoma‐associated Antigen Synthesized In vitro for Active Specific Immunotherapy
Authors: Hayashibe Kazuhito
Published: April 2015

The immunogenicity of the antigen molecule is a prerequisite for active specific immunotherapy for melanoma. Since most of the melanoma‐associated antigens recognized by the murine immune system are known to be not immunogenic in man, a detection and analysis system for melanoma‐associated antigens is required to reflect in vivo immune responses in patients with melanoma. One of the promising approaches, an attempt to develop human monoclonal antibodies from B lymphocytes of patients with melanoma, has met with limited success due to the difficulties of producing large amounts of antibodies and using them in immunochemical assays, because most of them belong to the IgM class and have low affinity.

Our approach is to utilize the screening of a cDNA expression library constructed from mRNA extracted from cultured melanoma cells with antibodies from patients with melanoma. The cloned cDNA, designated as D‐1, had 1029 bp and showed no significant homology with viral and mammalian sequences stored in GENETYX. cDNA D‐1 hybridized to a 2.0 kb mRNA species from 3 different cell lines of human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cells, but not from a renal carcinoma cell line, normal peripheral lymphocytes, or normal fibroblasts.

The in vivo expression and distribution of mRNA related to cDNA D‐1 has been examined in tissue specimens by in situ hybridization and shown to be rather restricted on melanoma cells. The polypeptide antigen encoded by cDNA D‐1 may be a valuable immunogen for implementing active specific immunotherapy in patients with melanoma.
The Neuropathology of Tuberous Sclerosis
Authors: Scheithauer Bernd W.
Published: April 2015

Tuberous sclerosis, an autosomal dominant disorder associated with hamartomas in multiple organs, prominently affects the central nervous system; principle lesions include subependymal nodules and giant cell astrocytomas, white matter heterotopias, and cortical tubers. Histologic, immunocytochemical, and ultrastructural features of these processes suggest they have their basis in abnormal cell migration and differentiation. Aberrant expression of cystoskeletal proteins appears to be common to the multisystem hamartomas of this disorder and may, in part, underlie their pathogenesis.
Mechanisms of Local, Low‐dose UVB‐induced Immunosuppression in Contact Hypersensitivity
Authors: Tokura Yoshiki
Published: April 2015

Preirradiation of contact sensitizing sites to low‐dose ultraviolet B (UVB) renders animals unresponsive to challenge reaction. This unresponsiveness is known as local, low‐dose UVB‐induced immunosuppression. Although researchers in this area have developed theories, the exact mechanisms of UVB‐induced immunosuppression are still a matter of controversy. This article reviewed various scientific data on UVB‐induced immunosuppression, categorizing them into individual sequential steps in the whole cascade.
Keratin: A Journey of Three Decades
Authors: Freedberg Irwin M.
Published: April 2015

During the past three decades, major progress has been made in our understanding of the processes which lead to the formation of a keratinized epidermis in normal and pathologic situations. Stimulated by clinical studies of exfoliative dermatitis and related diseases, a series of investigations have been performed which proved initially that the pathways and controls of epidermal protein synthesis were equivalent to protein synthetic pathways in all other tissues of the body. Keratin was identified as not only an insoluble protein which makes up the vast majority of the intracellular protein in the stratum corneum, but as a member of the intermediate filament family of cytoskeletal proteins. Of all such proteins, the keratins are most complex, occurring in two families separable on the basis of size, structure and isoelectric point. The keratin intermediate filaments are heteropolymers of two paired components, one from each family.

The pairs of keratins which form the intermediate filaments in basal and differentiated layers of epidermis and other epithelia have been defined and antibodies to specific keratins are now being used for diagnostic purposes. Sophisticated biochemical, physicochemical, and molecular biologic studies have led to complete definitions of almost all the epithelial keratin molecules and to cloning of their genes. These genes are currently being used in analyses of control of keratin expression and definition of the specific abnormalities associated with “keratinopathies” including epidermolysis bullosa simplex and epidermolytic hyperkeratosis.
Trichilemmal Carcinoma Occurring in a Lesion of Solar Keratosis
Authors: Misago Noriyuki , Tanaka Tatsurou , Kohda Hiromu
Published: April 2015

A case of trichilemmal carcinoma occurring in a lesion of solar keratosis was reported. A 92‐year‐old woman had an erythematous plaque on her face that contained a reddish nodule. Histological examination of the nodule revealed typical features of trichilemmal carcinoma accompanied by those of solar keratosis in the marginal zone. The histological features of the erythematous plaque corresponded with those of solar keratosis. However, in situ the carcinoma developed in the epithelium of a hair follicle as well as in the interfollicular epidermis in the lesion of solar keratosis. We considered it likely that bowenoid malignant transformation occurred in both interadnexal and adnexal epithelium because of actinic damage, and a trichilemmal carcinoma arose. The paper also discussed the histogenesis of trichilemmal carcinoma.
Warty Dyskeratoma with Multiple Lesions
Authors: Azuma Yuko , Matsukawa Ataru
Published: April 2015

A 63‐year‐old man with multiple nodules and pathological findings of acantholysis is reported as a case of warty dyskeratoma presenting with multiple lesions. The number of nodules is the highest in the records as far as we know. We conclude that warty dyskeratoma originates from the hair follicle.
Analysis of 70 KD Heat Shock Protein (HSP70) Expression in the Lesional Skin of Lupus Erythematosus (LE) and LE Related Diseases
Authors: Ghoreishi Mehran , Katayama Ichiro , Yokozeki Hiroo , Nishioka Kiyoshi
Published: April 2015

Biopsied specimens from skin lesions of SLE were studied for expression of 70 KD heat shock protein (HSP70). The pattern of HSP70 expression in SLE was diffuse in whole epidermis, hair follicles, and sweat gland cells and rather more intense than that in other control groups or normal skin. No significant differences in HSP70 expression were observed between sun‐exposed and protected areas of SLE skin lesions. Unlike SLE, reduced or no expression of HSP70 was observed in skin lesions of DLE. In tissue culture, UVB radiation in vitro induced relatively intense expression of HSP70 in the nuclear area of keratinocytes. A few γδT cell receptor positive cells which might respond to HSP70 expressing cells were detected in the basal layer of skin lesions of diseases.

These studies suggest that abberant expression of HSP70 in skin lesions of SLE might contribute to both skin lesions and antibody formation in SLE.
Cactus Granuloma of the Skin
Authors: Suzuki Hiroyuki , Baba Shunichi
Published: April 2015

A case of cactus granuloma due to the thorns of Opuntia bieglovii Engelman is reported. A 24‐year‐old Japanese man contacted the thorns of this cactus in Palm Springs, California, U.S.A., and, three months later, numerous, slightly elevated papules 2 to 4 mm in diameter appeared on the dorsum of his right hand and fingers. Histopathological examination revealed many small granulomas surrounding the bristle fragments throughout the dermis. The granulomas consisted of epithelioid cells, Langhans type and foreign body type giant cells. The fragments of the barbed bristles gave strongly positive reactions with PAS. Two hypothetical mechanisms, one allergic and the other non‐allergic, are offered to explain this granuloma formation and are discussed with reference to the literature.
Clinical Efficacy and Side Effects of Acitretin on the Disorders of Keratinization: A One‐year Study
Authors: Kullavanijaya Preya , Kulthanan Kanokvalai
Published: April 2015

Acitretin, Ro 10‐1670, the principal and free acid metabolite of etretinate, was used to treat twenty patients with disorders of keratinization. An open, prospective study of clinical efficacy, tolerability, and the effects of acitretin on lipid metabolism, hepatic function, and the osteoarticular system was performed over a one year period. Each patient was initially treated with 30 mg/day of acitretin or approximately 0.6 mg/kg/day. Doses were adjusted according to the clinical efficacy and maintained for one year. There were no statistically significant changes in liver function tests or lipid profile. Twelve of eighteen evaluated patients developed asymptomatic skeletal changes; the most common change was disc space narrowing, especially at thoracic‐spine level (7 of 18 patients). The earliest bone change was detected 9 months after treatment. Acitretin is effective in improving the disorders of keratinization with mild mucocutaneous side effects and asymptomatic osteoarticular changes.
A Case of Cystic Dermal Duct Tumor Corresponding to Poroid Hidradenoma
Authors: Ichioka Shigeru , Yamada Atsushi
Published: April 2015

A case of dermal duct tumor on the back of a 61‐year‐old male, representing a cystic lesion, is reported. Such cystic dermal duct tumors seem to be considered poroid hidradenomas according to the recently suggested classification of poromas. Poroid hidradenoma is rarely mentioned in the literature, and no description of its clinical features has yet been published. Carcinoembryonic antigen (CEA) immunostaining was positive in the tumor cells adjacent to the cystic space. We suppose that these CEA‐positive cells were associated with cyst formation in our case.
Calcinosis Cutis in Juvenile Dermatomyositis Responsive to Aluminum Hydroxide Treatment
Authors: Nakagawa Toshifumi , Takaiwa Takashi
Published: April 2015

Calcinosis cutis is a frequent complication of juvenile dermatomyositis; however, its treatment remains unsatisfactory. We report a case of calcinosis cutis in juvenile dermatomyositis which was successfully treated with oral aluminum hydroxide. Almost complete clearing of calcinosis was observed after 8 months of therapy. There were no adverse effects from therapy. Aluminum hydroxide is worth trying in treating calcinosis cutis.
Intravascular Papillary Endothelial Hyperplasia on the Penis: Report of a Case
Authors: Dekio Satoshi , Tsujino Yoshio , Jidoi Joji
Published: April 2015

An 82‐year‐old Japanese man with intravascular papillary endothelial hyperplasia on the penis is described. To the best of our knowledge, this is the first report of a patient who developed this tumor on his penis.
Acral Ichthyosiform Mucinosis in Association with Sjögren's Syndrome: A Peculiar Form of Pretibial Myxedema?
Authors: Yamazaki Sayuri , Katayama Ichiro , Satoh Takahiro , Yokozeki Hiroo , Nishioka Kiyoshi
Published: April 2015

Two Japanese women developed well‐dermarcated ichthyosiform plaques on the lateral aspect of their lower legs. Deposition of mucin was demonstrated throughout the papillary dermis, unlike the site of mucin deposition seen in pretibial myxedema. Their thyroid function was normal. The condition of both women was complicated by Sjögren's syndrome. One of them who presented with positive anti‐microsomal and anti‐thyroglobulin antibodies had goiter, suggesting that her malady was also complicated by Hashimoto's thyroiditis.

Their skin manifestations differed from those described in cutaneous mucinosis including pretibial myxedema, specifically with regard to the well‐demarcated ichthyosiform appearance, the mucin deposition in the papillary dermis, and the association with Sjögren's syndrome. To the best of our knowledge, our cases may thus be considered to be a previously undescribed form of cutaneous mucinosis associated with Sjögren's syndrome.
Organ Culture of Mouse Vibrissal Hair Follicles in Serum‐free Medium
Authors: Jindo Toshimasa , Imai Ryusuke , Takamori Kenji , Ogawa Hideoki
Published: April 2015

We developed a method for organ culture of mouse vibrissal hair follicles in a serum‐free medium. Cultures conducted at 31°C in 95% O2‐5% CO2 were found to be suitable for the follicles, with several findings of considerable interest pertaining to hair growth. During the 96 h culture period, the length of the isolated follicles significantly increased; the hair bulb cells maintained their normal morphology; and DNA and protein synthesis within the bulb increased time‐dependently. Furthermore, autoradiography showed that 3H‐thymidine‐labeling was localized in the matrix cells below Auber's critical line in the hair bulb; 3H‐leucine‐labeling was found in the epithelial region; and 35S‐cysteine‐labeling was detected in the cortex of hair, particularly in the keratogenous zone. These results indicate that the culture system using mouse vibrissal hair would be potentially useful as an effective model for examination of hair growth.
Dolichonychia in a Patient with the Marfan Syndrome
Authors: Cohen Philip R. , Milewicz Dianna M.
Published: April 2015

Dolichonychia is a descriptive term for elongated, slender nails. Although published observations of this finding are uncommon, dolichonychia has previously been seen in patients with connective tissue disorders, with hypohidrotic ectoderma dysplasia, or with abnormal hormonal states. Dolichonychia is a clinical feature which may be observed in patients with the Marfan syndrome. A woman with the Marfan syndrome and dolichonychia is described. Measurements of the patient's arm span, height, lower segment, hand length, and middle finger length were performed. In addition, the length‐to‐width ratio of each of her finger nails was determined. The mean of finger nail length‐to‐width quotients in the patient with the Marfan syndrome was 1.54. In conclusion, the detection of dolichonychia should prompt the physician to rule out associated systemic conditions: after eunuchoidism, hypohidrotic ectodermal dysplasia, and hypopituitarism have been excluded, an evaluation for Ehlers‐Danlos syndrome and the Marfan syndrome should be considered.
Cutaneous Reactions Induced by Calcium Channel Blocker: High Frequency of Psoriasiform Eruptions
Authors: Kitamura Kazuko , Kanasashi Mugiko , Suga Chizuka , Saito Sumi , Yoshida Sadao , Ikezawa Zenro
Published: April 2015

Fifteen cases with cutaneous reactions to calcium channel blockers (Ca‐antagonist), dihydropiridine (including nicardipine, nifedipine, nisoldipine), verapamil, and diltiazem are reported. The patients from Yokohama City University Hospital and affiliated hospitals included 4 males and 11 females with cardiovascular diseases. Their average age was 64.7 (54 to 82) years. They had been taking Ca‐antagonists for an average of 95 days (7 days to 10 years) before they developed dermatitis. The frequency of reactions to Ca‐antagonists was high with diltiazem (5/16: 31.25%) and dihydropyridine (7/16: 43.75%), including nifedipine (4/7), nisoldipine (1/7), and nicardipine (2/7). Stevens‐Johnson syndrome (MCOS) was associated only with verapamil.

A notable type of eruption was the psoriasiform type, including exacerbation of psoriasis, which was resolved or easily controlled after discontinuation of the drug. Provocation tests verified the Ca‐antagonist as the cause in 7 cases of psoriasiform eruption.

The frequency of positive patch tests to Ca‐antagonists was low except for diltiazem. Patch tests with diltiazem showed positive reactions in 54% (7 of 13 patients), based on our experience and papers published in Japan.

Ca‐antagonists are occasional causes of a wide spectrum of cutaneous reactions and should also be considered as causative factors in patients who develop psoriasiform eruptions or in patients whose psoriasis is exacerbated while using these drugs.
Familial Cases of Psoriasis Vulgaris and Pustulosis Palmaris et Plantaris
Authors: Matsuoka Yukari , Okada Natsuko , Yoshikawa Kunihiko
Published: April 2015

Two familial cases of psoriasis vulgaris and pustulosis palmaris et plantaris and their HLA types were examined. Our cases suggest a close genetic relationship between these two diseases.
Quantitative Analysis of Stratum Corneum Lipids in Xerosis and Asteatotic Eczema
Authors: Akimoto Kayoko , Yoshikawa Nobuko , Higaki Yuko , Kawashima Makoto , Imokawa Genji
Published: April 2015

Sphingolipids, a major constituent of intercellular lipids, are an important determinant for both water‐holding and permeability barrier function in the stratum corneum. To assess the pathogenic role of sphingolipids in the stratum corneum of dry skin disorders such as xerosis and asteatotic eczema in leg skin, ceramides were quantified by thin layer chromatography after n‐hexane/ethanol extraction of resin‐stripped stratum corneum and evaluated as μg/mg stratum corneum. In healthy leg skin (n=49), there was age‐related decline in the total ceramide, whereas xerosis (n=25) and asteatotic eczema (n=16) suffering significantly reduced water‐holding properties, exhibited no definite decrease, rather slight increase in ceramide quantity with the same composition of each individual ceramide as compared to healthy age‐matched controls. These data indicate that the seemingly elevated level of ceramide is an artificial effect due to inflammatory processes which result from susceptibility to dryness. Analysis of sebum‐derived lipids present in the stratum corneum revealed that there was a significant decline in free fatty acids in xerosis and asteatotic eczema as compared to age‐matched healthy controls, and a similar decline in triglycerides in the above three groups when compared to younger controls. Although the observed decrease in the stratum corneum lipids may well explain the high incidence of winter dry skin in older people, the progression toward asteatotic eczema can not be accompanied solely by a decrease in ceramide quantity, suggesting that the evolution of xerotic skin is associated with other moisturizing factors and/or environmental stimuli.
A Case of Progressive Systemic Sclerosis Associated with Sarcoidosis and Esophageal Adenocarcinoma
Authors: Maekawa Yoshihiro , Nogami Reiko
Published: April 2015

A 50‐year‐old Japanese female with progressive systemic sclerosis (PSS, CREST syndrome) is reported. During treatment for PSS, she was diagnosed by clinical and laboratory findings as having sarcoidosis, which was confirmed by histological examination of the skin and lymph nodes in July of 1991. She complained of back pain in August of 1991. Reflux esophagitis and Barrett's esophagus, found by endoscopy, progressed into a well‐differentiated tubular adenocarcinoma. This is a very rare case of PSS associated with sarcoidosis and esophageal adenocarcinoma developing from Barrett's esophagus.
Erythroderma, Hair Loss, and Sinus Histiocytosis with Massive Lymphadenopathy in a XYY‐Male
Authors: Tsukahara Tetsuya , Horiuchi Yasuhiro , Ohkawa Tsukasa , Masuzawa Mikio , Nishiyama Shigeo , Ohida Makiko
Published: April 2015

This paper presents a case of sinus histiocytosis with massive lymphadenopathy (SHML) presenting as erythroderma in an XYY‐male aged 27. The patient had little or no scalp, axillary, or pubic hair. Histologically, lymph nodes indicated dilatation of the sinuses with proliferation of benign‐appearing histiocytes possessing abundant clear cytoplasm, admixed with giant cells and pericapsular fibrosis. Infiltrating histiocytes in the lymph nodes were OKM‐1 (CD11b) positive, which is characteristic of monocyte‐granulocyte lineages. In the present case, the abnormal presence of erythroderma, hair loss, SHML, and a chromosomal abnormality, XYY, were thought to be incidental features.
Immunotherapy of Melanoma: Current Status and Prospects for the Future
Authors: Irie Reiko F. , DeNunzio F. David
Published: April 2015

As one of the most immunogenic human malignancies, melanoma has served as a prototype for the development of immunotherapy against human cancer in a number of treatment modalities over the past two decades. These studies have included augmentation of host immunity with lymphokines and other biological response modifiers, lymphokine‐activated killer cells, and cytotoxic T‐cells; active immunotherapy using purified antigens, tumor cell vaccines, and anti‐id antibodies; and passive immunotherapy with monoclonal antibodies. The results of these investigations are discussed as well as the prospect for future treatments of melanoma incorporating immunotherapeutic techniques. A report on a recent trial of gene therapy of human melanoma performed by Dr. Steven Rosenberg is also presented.
Effects of Ultraviolet‐B and PUVA on Ornithine Decarboxylase Activity, DNA Synthesis, and Protein Kinase C Activity in Mouse Skin
Authors: Mizuno Nobuyuki , Kono Takeshi , Taniguchi Shoji , Fukuda Michio , Maekawa Naoki , Hisa Tomoyuki , Otani Shuzo , Hamada Toshio
Published: April 2015

Ultraviolet‐B and PUVA share several biological events with phorbol ester tumor promoters. The effects of ultraviolet‐B irradiation and topical PUVA treatment on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity, which are known to be induced or activated by phorbol ester tumor promoter, were investigated in hairless mouse skin. Ornithine decarboxylase activity was remarkably enhanced by ultraviolet‐B and PUVA. Although PUVA did not affect DNA synthesis significantly, ultraviolet‐B stimulated epidermal DNA synthesis approximately 5‐fold over control values at 48 h. However, unexpectedly, neither cytosolic nor membrane‐bound protein kinase C activity showed any change during the 2 h after either treatment. These results suggest that the protein kinase C system is not involved in the initial signal transduction system of ultraviolet‐B or PUVA, unlike the case with phorbol ester tumor promoter.
Generalized Eruptive Histiocytoma: Report of a Pediatric Case
Authors: Izaki Seiichi , Kitamura Keijiro , Arai Eiichi
Published: April 2015

A one‐year‐old boy was seen with brownish, flat papules on his face, neck, and upper arms. The lesions were symmetric, discrete, slightly raised, firm to the touch, and asymptomatic papular eruptions. Histological and immunohistochemical investigation revealed monomorphous infiltration of S‐100 negative, lysozyme negative, and α1‐antitrypsin negative, but α1‐antichymotrypsin positive and vimentin positive histiocytic cells with small numbers of lymphocytic cells. The histiocytic cells did not show any foamy changes in the cytoplasm. No giant cells were found. The lesions increased in number during the first few years and then spontaneously regressed by the sixth year of age, leaving partial brownish pigmentation.
Keratoacanthoma with Glandular Proliferation
Authors: Akiyama Masashi , Hata Yasuki , Nishikawa Takeji
Published: April 2015

A case of keratoacanthoma (KA) with glandular proliferation was reported. The tumor was a firm, dome‐shaped, elevated nodule on the cheek of an 82‐year‐old Japanese male. Generally, the tumor showed the typical histopathological features of KA; slight nuclear atypia and mitotic figures were present in a cup‐shaped proliferation of keratinocytes and, in the center of the lesion, a keratin‐filled crater with nests of dyskeratotic and acantholytic cells was seen. In the bottom of the lesion, a glandular structure forming branching, thin lumina was observed. The epithelium of the lumina was made up of two or more layers of columnar or cuboidal cells without keratinization. Tall columnar cells with oval nuclei were located in the luminal row and small cuboidal cells with round nuclei and scanty cytoplasm were in the outer layer. Immunohistochemical staining revealed that only the glandular structure was carcinoembryonic antigen positive. Lectin binding patterns observed in the glandular proliferation were similar to those reported for the apocrine gland. KA sometimes exhibits an adenoid structure in its lesion because of acantholytic changes. However, KA associated with true glandular proliferation has not been reported as far as we know, and our case is the first reported one. KA is thought to be a tumor of follicular origin, and the glandular proliferation observed in the present case seemed to have certain characteristics that suggest its apocrine origin.
Dystrophic Calcinosis of the Penis
Authors: Katoh Norito , Okabayashi Keiko , Wakabayashi Shunji , Kishimoto Saburo , Yasuno Hirokazu
Published: April 2015

A 22‐year‐old man had had a dome‐shaped tumor on his penis for one year. Neither his particular past history nor family history was available. The excised specimen contained numerous von Kossa‐positive deposits. Four types of histologic pattern were identified: 1) a cystic structure filled with amorphous material lined by a few layers of epithelial cells, 2) a cyst containing calcified deposits in the keratinous material, 3) a large calcified nodule lined by attenuated epithelial cyst walls, 4) numerous calcium collections without an epithelial wall. The cystic structure showed the histologic features of syringoma or sweat duct milia. The luminal cells of the cyst showed positive immunoreactivity for both keratin and carcinoembryonic antigen. These findings suggested that the keratinous contents of syringoma had gradually calcified, the cyst wall had been attenuated, and, finally, numerous calcium collections without an epithelial wall were formed. Our case further supported the hypothesis that penile calcinosis as well as scrotal calcinosis might derive from syringoma.
Medullasin Levels in Neutrophils of Patients with Pustulosis Palmaris et Plantaris
Authors: Nakamura Takehiko , Ono Tomomichi , Aoki Yohsuke
Published: April 2015

Medullasin is one of the serine proteases found in human bone marrow cells. The protease in granulocytes is assumed to play an important role in the induction of chronic inflammation.

We measured the medullasin levels as a parameter of neutrophil function in granulocytes from patients with pustulosis palmaris et plantaris. All 17 patients studied underwent tonsillectomies, and the changes in the amount of medullasin were followed after surgery. Seven of the 17 patients were cured during the follow‐up period (average: 21 months). In all the patients in whom PPP improved, the medullasin levels decreased significantly from the period of active disease when pustules were present to the inactive period. The amount of medullasin did not fall significantly in patients whose PPP did not improve. It is concluded that medullasin levels may reflect the activity of PPP and may serve as a criterion for performing a tonsillectomy.
Pharmacokinetics of Meropenem in Experimentally Burned Rats
Authors: Yoshida Tetsunori , Homma Ken‐ichi , Azami Kenji , Sugihara Tsuneki , Ohura Takehiko
Published: April 2015

The pharmacokinetics of meropenem were investigated to examine its penetration into the skin of third degree burned rats. The rats were divided into two groups. One group acted as the control, and the other group had third degree burns induced by immersing their backs into 80°C water for 20 seconds. The rats in each group were given 20 mg/kg of body weight of meropenem intravenously by one bolus injection seven days after burn inducement or depilation. In the non‐burned control group, the maximum concentrations of meropenem in the serum and skin of 6.03 µg/ml and 0.12 µg/g were respectively obtained 15 minutes after the injection and decreased very rapidly thereafter. In the burned rats, the maximum concentrations of meropenem in the serum, skin (eschar), and exudate fluid of 7.07 µg/ml, 1.44 µg/g and 5.99 µg/ml were respectively obtained 15 minutes after the injection and decreased very slowly. The penetration of meropenem into the burned skin was higher than that into the normal skin. These results suggest that meropenem is a very useful antibiotic in the treatment of burn infection.
Two Sisters with Leprosy
Authors: Ishii Norihisa , Sugita Yasuyuki , Nakajima Hiroshi
Published: April 2015

Leprosy is a rare entity in Japan, but remains quite common in developing countries. We report two sisters with leprosy from Brazil but currently working in Japan who presented to our clinic. The younger sister was infected with the BB type with HLA‐A2, A24, B51, Bw52, DR2, DRw8, DRw52, DQwl, and DQw3. The elder sister had the TT type with HLA‐A2, A31, B51, Cw3, DRw6, DRw8, DRw52, DQwl, and DQw3.

Immunohistochemical findings revealed that CD4+, 4B4+ helper/inducer T‐cells were dominant in the granulomas of both cases. Bacilli were not detectable in the biopsy specimens. However, Mycobacterium leprae‐specific DNA fragments were found in their peripheral blood and biopsy specimens by polymerase chain reaction.
Chédiak‐Higashi Syndrome: Report of a Case and Review of the Japanese Literature
Authors: Fukai Kazuyoshi , Ishii Masamitsu , Kadoya Atsuko , Chanoki Miyako , Hamada Toshio
Published: April 2015

We report the case of a Japanese female infant with Chédiak‐Higashi syndrome born to consanguineous parents. At birth she had fair skin but, when she was three months old, marked hyperpigmentation of the sun‐exposed skin areas developed. Microscopic examination of blood and electron microscopic examination confirmed the diagnosis. She enjoyed good health until she was two years old when she had pneumonia with marked hepatosplenomegaly. It is important for dermatologists and pediatricians to be aware of the skin manifestations of this disease because hyperpigmentation after sun exposure may be a characteristic, initial feature of this condition.
Chronic Graft‐versus‐Host Disease with Follicular Involvement
Authors: Miyazaki Katsuko , Higaki Shuichi , Maruyama Tomohiro , Takahashi Shozo , Morohashi Masaaki , Ito Kaoru
Published: April 2015

The clinical and histopathological findings in a 25‐year‐old Japanese male patient who suffered from chronic graft‐versus‐host‐disease (GVHD) with follicular involvement are described. The patient had been diagnosed as aplastic anemia and underwent an allogeneic bone marrow transplant (BMT). In the eighth month thereafter, pruritic follicular red papules developed over his trunk and extremities. A biopsy specimen revealed histological exocytosis of lymphocytes into the hair follicles and basal‐cell vacuolization of the follicular epithelium. Analysis of T‐lymphocyte subpopulations in the dermis revealed a predominance of CD4 positive cells. To our knowledge, several cases of acute follicular GVHD have been reported (1, 2); however, the occurrence of chronic GVHD with follicular involvement (chronic follicular GVHD) has not been clearly documented.
Angiokeratoma Corporis Circumscriptum Naeviforme with Transepidermal Elimination
Authors: Miwa Norimasa , Kobayashi Taisuke , Kanzaki Tamotsu , Tsuji Takuo
Published: April 2015

A 5‐year‐old Japanese boy visited our clinic for treatment of a dark bluish papulonodular lesion on his right thigh. The histopathology of the lesion indicated angiokeratoma corporis circumscriptum naeviforme. Topical antibiotics were prescribed for occasional bleeding from the site. Frequent bleeding started in April of 1992, when erythema and itching were observed around the angiokeratoma. Histopathology of the lesion showed heavy lymphoid cell infiltration around dilated capillaries and irregular acanthosis engulfing dilated capillaries. Interestingly, there were confined masses of red blood cells in the epidermal layer as well as both in and on the horny layer. This is a feature of transepidermal elimination. This transepidermal elimination appeared to be triggered or enhanced by the concomitant contact dermatitis due to topical antibiotics. To the best of our knowledge, this is the first report of angiokeratoma in which the angiokeratoma itself reduced in size through transepidermal elimination, possibly caused by contact dermatitis.
An Immunohistochemical Study of BCA‐225 in Various Skin Cancers
Authors: Ansai Shinichi , Hozumi Yutaka , Kondo Shigeo
Published: April 2015

We performed an immunohistochemical study of BCA‐225, which is a glycoprotein secreted by the T47D breast carcinoma cell line and recognized by monoclonal antibody BRST‐1 (clone name: CU‐18), in normal skin and various skin cancers. In normal skin, BCA‐225 was positive only in the secretory portion of both eccrine and apocrine glands and in mature cells of the sebaceous gland. We observed 10 cases of squamous cell carcinoma of the skin, 10 cases of basal cell carcinoma without sebaceous differentiation, 3 cases of basal cell carcinoma with sebaceous differentiation, 6 cases of malignant trichilemmoma, 8 cases of eccrine porocarcinoma, 3 cases of ductal carcinoma, 1 case of malignant clear cell hidradenoma, 1 case of apocrine adenocarcinoma, 6 cases of extra‐ocular sebaceous carcinoma, 5 cases of extramammary Paget's disease with underlying adenocarcinoma, and 11 cases of extramammary Paget's disease without underlying adenocarcinoma. Most of the cases of sweat gland carcinoma, basal cell carcinoma with sebaceous differentiation, sebaceous carcinoma, and extramammary Paget's disease were positive for BCA‐225, while none of the cases of squamous cell carcinoma, basal cell carcinoma without sebaceous differentiation, or malignant trichilemoma were positive. Based on these findings, we believe that BCA‐225 is useful in distinguishing tumors with sweat gland and sebaceous differentiation and extramammary Paget's disease from tumors without such differentiation.
Sebaceous Epithelioma
Authors: Watanabe Rikio , Kawai Kazuhiro , Ito Masaaki , Ito Kaoru , Ikeda Kazuto
Published: April 2015

An 83‐year‐old woman had developed an asymptomatic, yellowish, dome‐shaped skin tumor on her scalp which had enlarged for a period of 60 years to 10 times 10 times 10 mm in size. Histopathologically, the tumor consisted of undifferentiated basaloid cells, differentiated sebaceous cells and transitional cells. Although the basaloid cells resembled those of basal cell epithelioma (BCE), the tumor was distinct from BCE in the following points; existence of cystic spaces, no peripheral palisading, no proliferation of connective tissue stroma, and no tendency toward local invasion. Immunohistochemical studies using antikeratin monoclonal antibodies revealed that the tumor contained both the keratin types of BCE and of sebaceous glands. Electron microscopically, the tumor cells contained lipid droplets and keratohyaline granules in their cytoplasm. It is suggested that “sebaceous epithelioma” is a benign skin tumor which may be distinguished cytologically from BCE.
Febrile Ulceronecrotic Mucha‐Habermann's Disease
Authors: Maekawa Yoshihiro , Nakamura Takehiko , Nogami Reiko
Published: April 2015

Febrile ulceronecrotic Mucha‐Habermann's disease (FUMH) was first described by Degos in 1966. In the literature, nine cases of FUMH have been reported in both children and adults. We report a 16‐year‐old boy with the febrile ulceronecrotic type. A review of the nine cases in the literature showed acute necrotic lesions, as well as rare complications such as fever, superinfected lesions and viral infection which are not as common in pityriasis lichenoides et varioliformis acuta. There is no definitive treatment, but systemic corticosteroid, methotrexate, antibiotics (tetracycline, erythromycin), aciclovir, and 4,4‐diaminodiphenyl sulfone (DDS) have been frequently used. The most common histologic feature is mononuclear perivascular infiltrates consisting of T lymphocytes. The etiology is not known, but a hypersensitivity reaction, possibly to an infectious agent, is suggested.
Generalized Argyria after Habitual Use of AgNO3
Authors: Lee Seung Min , Lee Seung Hun
Published: April 2015

Generalized argyria, the systemic dissemination and tissue deposition of silver‐containing particles, is characterized by slate gray discoloration of skin, most pronounced in sun exposed areas.

A 33‐year‐old woman visited our dermatologic clinic complaining of frequent oral ulceration for 10 years and generalized discoloration of her skin for 5 years. She had had her tongue painted with silver nitrate repeatedly 6 years ago for the treatment of oral ulcers. Physical examination showed slate gray discoloration of her skin, most pronounced on the face and neck. The oral mucosa, tongue, sclera, and conjunctiva also had a slightly blue‐gray discoloration. Biopsy specimens from the oral mucosa and forearm revealed small brown‐black granules scattered in the dermis and basal lamina of eccrine sweat glands, blood vessels, and hair follicles under the light microscope. Tiny black granules were most numerous in the basal laminae of vessels in electron microscopic observation. Energy dispersive X‐ray microanalysis (EDXA) confirmed that many of the granules contained silver.
Microfluorocytometric Detection of Nuclear DNA Damage to Cancer Cells in Squamous Cell Carcinoma after Hyperthermia
Authors: Ishiguro Kazumori , Hatcho Masahiro , Miyoshi Norio , Fukuda Masaru , Ueda Keiichi
Published: April 2015

An 84‐year‐old woman had a squamous cell carcinoma on her left thigh. Before operation, half of the tumor mass was irradiated with a microwave at 43°C for an hour. After the hyperthermia, the tumor mass was removed, and the DNA instability was investigated by microfluorocytometric measurement of the cells stained with pararosaniline‐Feulgen after hydrolysis with 2N HCl at 30°C. The kinetic parameters k1, which is the rate constant for the generation of an apurinic acid, k2, which is the rate constant for the depolymerization of the apurinic acid and which reflects the degree of DNA instability for acid hydrolysis, and y0, which is the theoretical value of the single‐stranded DNA present initially and reflects the degree of DNA damage, were determined by a computer fitting of the Bateman function to the hydrolysis curve plotting of the fluorescence intensity of the pararosaniline‐Feulgen staining the apurinic acid against the different hydrolysis times. The parameter values y0 and k2 of the cells treated by hyperthermia were much higher than those of the cells treated without hyperthermia. It is our conclusion that this microfluorometric detection would be valuable as an evaluation method for a cancer therapy, although more data from other cancers and treatments will be needed.