Hachiro Tagami

Dermatofibrosarcoma protuberans is a unique fibrohistiocytic tumour expressing CD34

Summary Dermatofibrosarcoma protuberans (DFSP) is a slow growing, locally invasive tumour whose differentiation from other fibrohistiocytic tumours sometimes poses serious diagnostic problems. We investigated CD34 expression immunohistologically in various fibrohistiocytic tumours including dermatofibroma, DFSP, malignant fibrous histiocytoma (MFH), infantile myofibromatosis, fibrosarcoma, hypertrophic scar and keloid. Among these, DFSP was unique in that tumour cells themselves expressed CD34, whereas in other tumours, CD34 expression was observed only on vascular endothelial cells amongst the tumour cells. Until now, there have been no reports of useful immunohistological markers for DFSP. CD34 expression by the tumour cells can be an extremely useful marker in establishing a definitive diagnosis of DFSP.

High Commitment of Embryonic Keratinocytes to Terminal Differentiation through a Notch1-caspase 3 Regulatory Mechanism

Embryonic cells are expected to possess high growth/differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-delta, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation.

Human oculocutaneous albinism caused by single base insertion in the tyrosinase gene

Tyrosinase-negative oculocutaneous albinism (OCA) is an inborn error of metabolism, characterized by a complete lack of melanin pigments in the eyes and skin. We have isolated and characterized the tyrosinase gene of one affected child (S.S.) with tyrosinase-negative OCA. Sequence analysis reveals a single-base insertion in the exon 2 that shifts the reading frame and introduces a premature termination signal (TGA codon) after the amino acid residue 298. Functional analysis of the mutated gene indicates that such a truncated tyrosinase lacking one potential copper-binding region is catalytically inactive. We therefore conclude that the albino phenotype of the patient S.S. is a consequence of the inactive tyrosinase caused by the nonsense mutation in the tyrosinase gene.

A toxicologic and dermatologic assessment of cyclic and non-cyclic terpene alcohols when used as fragrance ingredients ☆

University of Missouri (Kansas City), c/o American Dermatology Associates, LLC, 6333 Long Avenue, Third Floor, Shawnee, KS 66216, USA Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Avenue, New York, NY 10032, USA Malmo University Hospital, Department of Occupational and Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Institute for Miliovurdering, Environmental Assessment Institute, Linnesgade 18, 1st Floor, Copenhagen 1361K, Denmark e Technical University of Munich, Institute for Toxicology and Environmental Hygiene, Hohenbachernstrasse 15-17, Freising-Weihenstephan D-85354, Germany Oregon Health Sciences University, Department of Dermatology L468, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA Boston University School of Medicine, Department of Pathology and Laboratory Medicine, 715 Albany Street, L-804, Boston, MA 02118-2526, USA Hospital Cantonal Universitaire, Clinique et Policlinique de Dermatologie, 24, Rue Micheli-du-Crest, Geneve 14 1211, Switzerland Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA 3-27-1 Kaigamori, Aoba-ku, Sendai 981-0942, Japan

The association of latent Epstein-Barr virus infection with hydroa vacciniforme.

Patients with hydroa vacciniforme (HV)‐like eruptions and malignant potential have been reported from Asia and Mexico, and those patients frequently had an associated latent Epstein–Barr virus (EBV) infection. In order to elucidate the association of latent EBV infection with HV, we studied six children with typical manifestations of HV by detection of EBV genes and EBV‐related RNAs in biopsy specimens from cutaneous lesions. Cutaneous lesions of all six children with typical HV contained EBV‐encoded small nuclear RNA (EBER)+ cells in 3–10% of the dermal infiltrates, whereas no Bam HI‐H, l‐fragment (BHLF) mRNA, or transcripts encoding EA‐D antigen, were detected. No EBER + cells were detected in other inflammatory or benign lymphoproliferative skin disorders tested. Polymerase chain reaction amplification confirmed the presence of EBV DNA sequences in five of six biopsy specimens from the patients. Latent EBV infection is associated with the development of cutaneous lesions of HV.

Contact Sensitivity to Pityrosporum ovale in Patients With Atopic Dermatitis

Contact sensitivity and immediate hypersensitivity to extracts from Pityrosporum ovale were studied in patients with atopic dermatitis (AD). In a chamber-scarification patch test, 75 (64%) of 118 patients with AD responded positively, compared with 1 (3%) of 35 healthy volunteers. However, no significant statistical correlations were found between contact sensitivity to P ovale in patients with AD and any of the following factors: age, sex, distribution of skin lesions, presence of pruriginous papules, history of infantile seborrheic dermatitis, or concomitance of other atopic diseases. Lymphocyte transformation test with P ovale antigen confirmed that those with positive patch test reactions showed significantly high stimulation indexes. The antigenic substances divided by gel filtration high-performance liquid chromatography were found in a fraction of components with molecular weights above 60 kd. In addition, 25 (71%) of 35 patients with AD showed a positive immediate response to P ovale extract in a prick test, whereas none of 11 healthy volunteers showed any response. Although the incidence of the positive immediate responses was similar to that in contact sensitivity, there was no clear correlation between the delayed and immediate hypersensitivity reactions. Based on these results, we think that P ovale plays a role as an allergen derived from the host environment in the exacerbation of the skin lesions of AD.

Inverse correlation between CD34 expression and proline-4-hydroxyase immunoreactivity on spindle cells noted in hypertrophic scars and keloids

The CD34 positive (CD34+) spindle cells constitute a special population of spindle cells which show a unique distribution in the skin. So far, however, the functional role of CD34+ spindle cells and the regulation of CD34 expression on dermal spindle cells are totally unknown. We examined immunohistologically the pattern of the expression of CD34 and proline‐4‐hydroxylase, a marker for the fibroblasts that participate in active collagen synthesis, on dermal spindle cells at various stages of scar and keloidal tissues.

Simple chemicals can induce maturation and apoptosis of dendritic cells

As is well known in the case of Langerhans cells, dendritic cells (DCs) play a crucial role in the initiation of immunity to simple chemicals such as noted in the contact hypersensitivity. Because DCs are scattered in non‐lymphoid organs as immature cells, they must be activated to initiate primary antigen‐specific immune reactions. Therefore, we hypothesized that some simple chemicals must affect the function of DCs. In this paper, we first demonstrated that human monocyte‐derived DCs responded to such simple chemicals as 2,4‐dinitrochlorobenzene (DNCB), 2,4,6‐trinitrochlorobenzene (TNCB), 2,4‐dinitrofluorobenzene (DNFB), NiCl2, MnCl2, CoCl2, SnCl2, and CdSO4 by augmenting their expression of CD86 or human leucocyte antigen‐DR (HLA‐DR), down‐regulating c‐Fms expression or increasing their production of tumour necrosis factor‐α (TNF‐α). In addition, the DCs stimulated with the chemicals demonstrated increased allogeneic T‐cell stimulatory function. Next, we found that, among these chemicals, only NiCl2 and CoCl2 induced apoptosis in them. Finally, we examined the effects of these chemicals on CD86 expression by three different macrophage subsets and DCs induced from the cultures of human peripheral blood monocytes in the presence of macrophage colony‐stimulating factor (M‐CSF), M‐CSF + interleukin‐4 (IL‐4), granulocyte–macrophage colony‐stimulating factor (GM‐CSF), and GM‐CSF + IL‐4, respectively. Among them, only DCs dramatically augmented their expression of CD86. These observations have revealed unique characteristics of DCs, which convert chemical stimuli to augmentation of their antigen presenting function, although their responses to different chemicals were not necessarily uniform in the phenotypic changes, cytokine production or in the induction of apoptosis.

Functional characteristics of the stratum corneum in photoaged skin in comparison with those found in intrinsic aging.

Among various functions of the skin, the most vital one is carried out by the stratum corneum (SC), because the SC effectively protects our body from desiccation even in a dry environment as well as from external invasion of injurious agents. Despite the general decline of various bodily functions in advanced age, the barrier function of the SC does not deteriorate but rather improves with aging, reflecting the reduced epidermal proliferation associated with slower desquamation of the SC. Although the intercellular lipid production that is crucial for the SC barrier is reduced in aged epidermis, it is compensated by the thicker SC, consisting of larger corneocytes covering the aged skin surface due to the retardation of the desquamating process. However, such SC is deficient in water-binding capacity, another important function of the SC that keeps the skin surface soft and smooth, due to decreased amounts of water-binding substances in the SC. Thus, large portions of the covered skin begin to develop xerotic changes in a dry environment of winter, being frequently accompanied by pruritus. In contrast, most elderly individuals display the unique features of photoaging on their exposed skin such as the face and hands due to chronic exposure to the ultraviolet light (UV) of sunlight. However, functional derangements of the SC are rather mild in the photoaged skin. Our functional analyses of the SC of the chronically sun-exposed skin found in the symmetrical located areas, i.e., the dorsa of the hands in middle-aged Japanese golf players who always wore a glove only on the one of the hands demonstrated significant impairment in SC water-binding capacity in the sun-exposed side, while its barrier function was well retained. Despite the decreased water content of the SC, elderly people can live without any inconvenience even when they expose the facial skin to the dry environment of winter, because there take place sebum excretion and non-apparent sweating by comparison with the skin of the sun-protected areas such as the trunk and limbs that easily develop xerotic changes in cold seasons.

In vitro treatment of human transforming growth factor‐β1‐treated monocyte‐derived dendritic cells with haptens can induce the phenotypic and functional changes similar to epidermal Langerhans cells in the initiation phase of allergic contact sensitivity reaction

Human monocyte‐derived dendritic cells (MoDCs) obtained from peripheral blood monocytes (PBMC) cultured with granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐4 (IL‐4) can be activated in vitro by a variety of simple chemicals such as haptens and several metals. Recently, it has been demonstrated that transforming growth factor‐β1 (TGF‐β1) can induce further differentiation of MoDCs to the cells that share some characteristics with epidermal Langerhans cells, i.e. they contain Birbeck granules and express E‐cadherin. In this study, using such TGF‐β1‐treated dendritic cells (TGF‐β1+ DCs), we examined the in vitro effects of representative haptens, i.e. NiCl2 and dinitrochlorobenzene (DNCB), on their phenotypic and functional characteristics, comparing with those reported in vivo in epidermal Langerhans cells during the sensitization phase of a contact sensitivity reaction. Treatment of TGF‐β1+ DCs with NiCl2 increased their expression of the molecules related to antigen presentation such as CD86, major histocompatibility complex class I and class II, and CD83, although weakly, in addition to that of those essential for their migration to the regional lymph nodes, such as CD49e, CD44 and its variant 6, while it down‐regulated the expression of the molecules required for homing to the skin and staying in the epidermis, such as cutaneous leucocyte antigen (CLA) and E‐cadherin. It also increased the production of tumour necrosis factor‐α, but not that of IL‐1β or IL‐12. DNCB also increased their CD86 expression and down‐regulated E‐cadherin and CLA, but did not affect other phenotypic changes that were observed in TGF‐β1+ DCs treated with NiCl2. TGF‐β1+ DCs treated with either NiCl2 or DNCB increased their allogeneic T‐cell stimulatory function. In addition, reverse transcribed polymerase chain reaction revealed augmented expression of chemokine receptor 7 mRNA by TGF‐β1+ DCs when treated with either NiCl2 or DNCB. Moreover, consistent with this data, TGF‐β1+ DCs treated with these chemicals chemotactically responded to macrophage inflammatory protein‐3β. These data suggest the possibility that TGF‐β1+ DCs present a good in vitro model to study the biology of epidermal Langerhans cells.