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Mutations of p53 and PTCH gene, two candidate tumor suppressor genes for basal cell carcinoma (BCC), were screened in 15 cases of sporadic BCCs that developed in sun-exposed skin region in a Korean population. p53 and PTCH mutations were detected at a frequency of 33 and 40%, respectively, and the mutations were predominantly UV-signature transition, C-->T transitions at dipyrimidine sites and CC-->TT tandem mutations. In both genes, the most common mutations were missense mutations resulting in amino acid substitution, which is different than the results from Caucasian BCCs where mutations are frequently predicted to make truncated or absent proteins. All mutations, except for one, occurred on the nontranscribed strand where is little efficient removal of UV-induced pyrimidine dimers relative to the transcribed strand. Loss of heterozygocity (LOH) of 9q22 for PTCH loci was found in eight of 15 informative cases of BCCs (53%), but none of the cases were informative for LOH of 17p13 for p53 loci. Not only do our data indicate the key role played by p53 and PTCH in the development of BCCs, these findings also suggest that UVB may significantly contribute to BCC tumorigenesis. Moreover, molecular epidemiology composed of incidence of p53 and PTCH mutations, difference in the type of mutation and repair bias of UV-induced DNA lesions might affect the distinct features of BCCs between different racial population.

The increased susceptibility of neonates to infections has been ascribed to the immaturity of their immune system. More particularly, T cell-dependent responses were shown to be biased towards a Th2 phenotype. Our studies on the in vitro maturation of umbilical cord blood T cells suggest that the Th2 bias of neonatal response cannot be simply ascribed to intrinsic properties of neonatal T cells. Phenotypically, neonatal CD4 + T cells are more immature than their adult CD45RO − /RA + naive counterparts and they contain a subset (10–20%) of CD45RO − /RA + CD31 − cells which is very low in adults and displays some unique functional features. The activation and maturation of neonatal CD4 + T cells is particularly dependent upon the strength of CD28-mediated cosignal which dictates not only the cytokine profile released upon primary activation but also the response to IL-12. Activation of adult as well as neonatal CD4+ T cells in the context of low CD28 costimulation yields to the production of low levels of only one cytokine, i.e. IL-2. In contrast, strong CD28 costimulation supports the production of high levels of type 1 (IL-2, IFNγ and TNFβ) and low levels of type 2 (IL-4 and IL-13) cytokines by neonatal T cells. The low levels of naive T cell-derived IL-4 are sufficient to support their development into high IL-4/IL-5 producers by an autocrine pathway. The ability of IL-12 to prime neonatal CD4 + T cells for increased production of IL-4 (in addition to IFNγ) is observed only when CD28 cosignal is minimal. Under optimal activation conditions (i.e. with anti-CD3/B7.1 or allogenic dendritic cells) the response and the maturation of neonatal and adult naive T cells are similar. Thus the Th2 bias of neonatal immune response cannot be simply ascribed to obvious intrinsic T cell defect but rather to particular conditions of Ag presentation at priming. Unlike CD4 + T cells, neonatal CD8 + T cells strictly require exogenous IL-4 to develop into IL-4/IL-5 producers. Most importantly, anti-CD3/B7-activated neonatal CD8 T cells coexpress CD4 as well as CCR5 and CXCR4 and are susceptible to HIV-1 infection in vitro.

We previously reported that human naive CD4 T cells differentiate into effector cells producing type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-5, IL-10) cytokines after priming with anti-CD3 mAb presented on irradiated CD32-transfected mouse L fibroblasts, in the absence of exogenous cytokine. Here we first show that the CD32 L fibroblasts act not only by cross-linking anti-CD3 mAb but also by providing a B7-mediated co-stimulation signal which is required for the activation of naive T cells. Using a selected anti-CD3 mAb (64.1) we next demonstrate that colligation of CD3 and CD28 with soluble mAb is sufficient to activate highly purified naive CD4 T cells for proliferation, IL-4 mRNA expression, IL-4 secretion, and maturation into IL-4- and IL-5-producing cells. Finally, we show that the intensity of B7 co-stimulation at priming markedly affects the lymphokine-producing phenotype of primed cells. Indeed, cells primed on CD32-B7 double L transfectants produce much more IL-4 and IL-5 and slightly less IFN-gamma than those primed on CD32 L cells. The enhanced IL-4/IL-5-producing capacity of cells primed on CD32-B7 L fibroblasts may be related to increased IL-4 production during priming. It is suggested that the maturation of naive T cells along the Th2 or Th1 pathway may be regulated by the level of B7 expressed on APC.

Background. Syringomas usually develop in women as multiple skin-colored papules primarily seen on the periocular regions and cheeks. They can cause cosmetic problems and lead to poor self-esteem. Though several treatment modalities have been established, such as excision, electro/cryosurgery, chemical peeling, and CO2 laser surgery, none of them are satisfactory due to their limitations and side effects, for example, pain, prolonged healing time, postoperative erythema/pigmentary changes, and scarring. Objective. The objective of this study was to develop a new treatment method for syringoma and to minimize the side effects through selective destruction of the tumor. Methods. Six patients with multiple periorbital syringomas were enrolled in this study. The surface epithelium of the syringomas was vaporized by CO2 laser, and black ink was introduced in order to allow penetration to the dermis using iontophoresis. Subsequently the artificial tattoos were removed by Q-switched alexandrite laser. The results were evaluated clinically by both physicians and patients at 1, 2, 4, and 8 weeks after treatment. Results. The majority of syringoma in the six patients disappeared by the first follow-up 1 week after treatment. There were no cases of prolonged erythema persisting beyond 2 weeks. Additional treatment was repeated in the same manner in order to remove the remaining syringomas in one patient. There were no recurrences during the 8-week follow-up period. Conclusion. Our new treatment was safer, less painful, nonscarring, and there was a quicker recovery period and less of a burden to repeat treatment when necessary.

A 41-year-old man noted the presence of a punched-out ulcer on the anterior midline of the neck. There was no previous history of trauma or radiation to the head and neck region. Physical examination showed a draining sinus surrounded by a cribriform scar on the anterior midline of the neck ( Fig. 1). There was no adenopathy in the neck. The head and neck were otherwise normal, as were T3 and T4, routine blood and urine tests, and chest X-rays. Thyroid scan was performed which demonstrated normal uptake and normal location of the thyroid gland. Computed tomographic scan showed a 2.5×1.0×1.0-cm-sized ovoid, hypodense cystic mass extending to the cricoid cartilage. Because there was doubt as to the extent of the fistulous tract and its ramifications, a roentgen study of the tract after injection of a contrast medium was performed. The fistulogram showed that the injected contrast medium was observed at the base of the tongue through a faintly opacified thread-like fistulous tract from the skin. Figure 1. Punched-out ulcer surrounded by cribriform scar on the anterior midline of the neck At surgical exploration, a thyroglossal duct tract was identified and a Sistrunk procedure was performed. This involved the removal of the thyroglossal duct cyst and the central portion of the hyoid bone, and the tracing of the thyroglossal duct tract to the foramen cecum at the base of the tongue. The pathology of the thyroglossal mass showed a thyroglossal duct cyst lined by columnar epithelium and small acini, with solid groups of large polyhedrial or round cells with pleomorphic hyperchromatic nuclei and eosinophilic granular cytoplasm, consistent with Hurthle cell adenoma ( Figs 2 and 3). No evidence of capsular invasion or penetration was observed. The patient was discharged in a good condition 1 week later, and was well at follow-up 6 months later. Figure 2. Hurthle cell adenoma (right) and thyroglossal duct cyst lined by columnar epithelium (left) are seen on the photomicrograph of the resected specimen (hematoxylin and eosin stain;×50) Figure 3. High-power photomicrograph of the Hurthle cell adenoma showing polyhedrial or round cells with abundant eosinophilic granular cytoplasm and pleomorphic hyperchromatic eccentric nuclei (hematoxylin and eosin stain;×400)

Clinical manifestations of atopic hand-foot (H-F) dermatitis have not been well studied. This study examined 108 atopic dermatitis (AD) patients with H-F dermatitis between May 1997 and July 1999 at our AD clinic to determine the clinical characteristics of atopic H-F dermatitis and to assess its etiologic associations. It usually began in childhood with an early onset of AD. Pruritus was the most frequent symptom, and erythema, scales, lichenification, hyperkeratosis, fissures, and keratolysis exfoliativa were also common signs. Both the hands and feet were involved in 47 (44.0%) patients, and either hand or foot involvement was observed in 15 (13.9%) and 46 (42.6%) patients, respectively. Palmar or plantar surfaces were more frequently involved than the dorsal aspects. The great toe was affected more often than the other toes. Two-thirds of patients presented with manifestations of the ichthyosis triad and sandpaper-like skin lesions on the elbow, knee, and lateral malleolus. Palmar or plantar hyperhidrosis was reported in 15% and 20%, respectively. The ichthyosis triad-associated group showed a significantly higher incidence of sandpaper-like (thickened, roughened) skin lesions, and these patients had lesions on the dorsal hands or heels and lateral malleolus more frequently than ichthyosis triad-absent patients. The hyperhidrosis-associated group showed an association with glassy lesions, localized to palmar or plantar areas. Atopic H-F dermatitis is associated with the nonallergic etiologies of AD and clinical subgroups can be identified on the basis of nonallergic backgrounds.

Background Recent studies have demonstrated that two T cell-derived lymphokines, interferon-gamma (IFN-γ) and interleukin-4 (IL-4), play a crucial role in the pathogenesis of atopic dermatitis (AD). It is known that neuropeptides, such as substance P (SP) and vasoactive intestinal peptide (VIP), have various immunomodulatory effects. Elevated levels of these neuropeptides and increased staining of SP positive nerve fibers have been reported in AD patients. Objective The study was designed to examine the effects of SP and VIP on the production of IFN-γ and IL-4. The aim of the study was to establish whether these neuropeptides acted to affect cytokine release in the peripheral blood mononuclear cells (PBMCs) of AD patients. Methods The effects of SP and VIP on the production of IFN-γ and IL-4 in phytohemagglutinin stimulated PBMC cultures over a 48-hour period were analyzed by enzyme-linked immunosorbent assay in 15 AD patients. Non-atopic individuals were used as a control group. Results Base cytokine profiles of AD patients showed significantly decreased IFN-γ and increased IL-4 when weighed against non-atopic controls. Compared with controls, SP had a significant percentage enhancing effect on both IFN-γ and IL-4 production at concentrations of 10 −8 M and 10 −6 M, however, this IFN-γ up-regulatory effect of SP was reversed by spantide, a SP antagonist. The ratios of IFN-γ:IL-4 production were significantly elevated in the SP treated AD group. Although VIP had no specific noticeable effects on the IFN-γ and IL-4 production. Conclusions Our data may suggest that SP has an influence on the immunomodulation of AD patient by regulating IFN-γ production, either directly or indirectly. Vasoactive intestinal peptide, on the other hand, has no modulatory effects on the cytokine production of AD patients.

Background Minor cutaneous features are important in atopic dermatitis (AD) because they are related to the ethnic or genetic background and to the etiopathogenesis of the disease other than atopic allergy. In addition, they can be used as auxiliary diagnostic criteria in patients with uncertain major features. It is our experience that our AD patients have characteristic features that have not been described previously in the literature. Methods AD patients (n = 130) and control subjects (n = 198) were examined for the 32 conventional and seven additional minor features (sandpaper-like skin lesions on elbow/knee/lateral malleolus, hangnail, ventral wrist dermatitis, itchy hyperkeratotic papules on the dorsum of the hands, oily skin, fissured heel, and palmar erythema). The frequency of each feature was compared between AD patients and controls. The diagnostic significance of these minor features was analyzed separately in the childhood and adolescent–adult AD groups, and the age-related changes were documented. Results The seven additional features were significant for the diagnosis of AD in South Korean patients. Many of the other conventional minor features were also significant. Nine features were of diagnostic importance only in the adolescent–adult AD group, and three features were characteristic only in the childhood AD group. Conclusions Our data suggest that ethnic backgrounds influence the phenotype of AD and that an additional seven features need to be examined to confirm the ethnic effect. As the general clinical presentation of AD is dependent upon age, the frequency of minor features varied in the different age groups.

The maturation of naive CD4 T cells into interleukin (IL)-4-producing effectors was shown to require the presence of IL-4 at priming, the cellular origin of which remains unclear. We demonstrate here that naive T cells themselves release IL-4 at very low levels that are nevertheless sufficient to promote their development into Th2-like cells. This conclusion is based on three observations: (1) highly purified human naive CD4 T cells, of neonatal or adult origin, develop into Th2 effectors upon repetitive cycles of stimulation with anti-CD3 monoclonal antibody (mAb) cross-linked to CD32-B7 transfected L fibroblasts followed by IL-2 expansion; (2) IL-4 protein is readily detectable in the concentrated supernatant fluids of priming cultures performed in the presence of anti-IL-4 receptor mAb; and (3) addition of anti-IL-4 or anti-IL-4 receptor mAb at priming markedly inhibits the acquisition of IL-4- and IL-5-producing capacity while enhancing that of interferon-gamma.

Trichilemmal horn (trichilemmal keratosis) is a rare keratinizing tumor that resembles a cutaneous horn. Histologically,it is characterized by an abrupt maturation of keratinocytes into lamellar keratin without the formation of a granular layer. We describe a case of a trichilemmal horn on the right cheek of a 78-year-old woman. (Ann Dermatol 13(2) 110~112, 2001).

A 38-year-old man presented with a black pigmented patch overlying his upper lip, a part of the gingiva and the hard palate. An intradermal tumor mass was palpated at the central portion of the pigmented patch of the upper lip. Diphenylcyclopropenone (DPCP) is a potent contact sensitizer that could stimulate non-specific immunity. We report a case of desmoplastic malignant melanoma (DMM) in which an atypical lentiginous pigmentation disappeared with topical DPCP immunotherapy and the dermal tumor mass was removed by a surgical wedge-shaped excision. Though an atypical lentiginous pigmentation of DMM sometimes undergoes extensive spontaneous regression, in our case it could be attributed to the therapeutic effect of topical DPCP immunotherapy rather than a spontaneous regression. (Ann Dermatol 13(1) 44~47,2001).