Emel Erkek

A Mouse Skin Multistage Carcinogenesis Model Reflects the Aberrant DNA Methylation Patterns of Human Tumors

Whereas accepted models of tumorigenesis exist for genetic lesions, the timing of epigenetic alterations in cancer is not clearly understood. We have analyzed the profile of aberrations in DNA methylation occurring in cells lines and primary tumors of one of the best-characterized mouse carcinogenesis systems, the multistage skin cancer progression model. Initial analysis using high-performance capillary electrophoresis and immunolocalization revealed a loss of genomic 5-methylcytosine associated with the degree of tumor aggressiveness. Paradoxically, this occurs in the context of a growing number of hypermethylated CpG islands of tumor suppressor genes at the most malignant stages of carcinogenesis. We have observed this last phenomenon using two approaches, a candidate gene approach, studying genes with well-known methylation-associated silencing in human tumors, and a mouse cDNA microarray expression analysis after treatment with DNA demethylating drugs. The transition from epithelial to spindle cell morphology is particularly associated with major epigenetic alterations, such as E-cadherin methylation, demethylation of the Snail promoter, and a decrease of the global DNA methylation. Analysis of data obtained from the cDNA microarray strategy led to the identification of new genes that undergo methylation-associated silencing and have growth-inhibitory effects, such as the insulin-like growth factor binding protein-3. Most importantly, all of the above genes were also hypermethylated in human cancer cell lines and primary tumors, underlining the value of the mouse skin carcinogenesis model for the study of aberrant DNA methylation events in cancer cells.

Latex allergy: diagnosis and management

ABSTRACT:  Latex allergy is an IgE‐mediated immediate hypersensitivity response to natural rubber latex (NRL) protein with a variety of clinical signs ranging from contact urticaria, angioedema, asthma, and anaphylaxis. Major allergens include dipped latex products such as gloves and balloons. In highest risk for NRL allergy are patients with spina bifida, but health care workers and others who wear latex gloves are also at risk. NRL allergic patients may also react to fruits/foods, especially banana, kiwi, and avocado. Diagnosis is made by a positive latex RAST and/or skin prick test or challenge test to NRL. Allergen avoidance and substitution and the use of latex‐safe devices including synthetic gloves (vinyl, synthetic polyisoprene, neoprene, nitrile, block polymers, or polyurethane) are essential for the affected patient. Accommodation in the workplace may include the use of powder‐free, low‐allergen NRL gloves or synthetic gloves. These preventive measures have significantly reduced the prevalence of reported reactions to NRL. Hyposensitization is not yet feasible.

Increased tumor necrosis factor alpha (TNF‐α) and interleukin 1 alpha (IL1‐α) levels in the lesional skin of patients with nonsegmental vitiligo

Increased tumor necrosis factor alpha (TNF-α) and interleukin 1 alpha (IL1-α) levels in the lesional skin of patients with nonsegmental vitiligo Dear Sir, Depigmentation in vitiligo is caused by melanocyte destruction. There are different hypotheses including neural, selfdestruction, and immune hypotheses to explain the pathogenesis of vitiligo There is growing evidence that cytokines are important in the depigmentation process of vitiligo. Granulocytemacrophage colony-stimulating factor (GM-CSF), endothelins, b-FGF are the mitogens for melanocytes whereas TNFα, IL1α, IL-6, TGFβ are the potent inhibitors of melanocyte growth. IL1α is remembered as one of the cytokines of inflammation, and is also known as a B-cell activating factor. It produces similar biological effects with TNF α and is produced in most inflammatory and immunological diseases. b-FGF, produced by fibroblasts and epidermal keratinocytes, is a polypeptide and is capable of promoting angiogenesis and mitogenesis through autocrine and paracrine mechanisms. The role of peripheral blood and lesional cytokine expression in patients with vitiligo has not been clarified yet. Herein we wanted to investigate the levels of cytokines in the skin and serum of vitiligo patients and to compare them with the levels in healthy controls. Six female and 18 male vitiligo patients aged (32 years ± 17 SD) were enrolled in the study after giving informed consent. Thirteen (54.2%) had symmetrical generalized, seven (29.2%) had acrofacial, and four (16.7%) had focal vitiligo. Six (25%) had progressive and 18 (75%) had stabile vitiligo (no new depigmentation had been observed for more than 3 months). Fourteen ageand sex-matched healthy volunteers consisted the control group. Samples of peripheral blood from patients and healthy volunteers were collected by venipuncture. Serum was separated and stored at −70 °C before use. Four-millimeter punch biopsies were taken in all patients from lesional skin and nonlesional skin (at least 3 cm far from lesional biopsy) and from healthy volunteers. The biopsies were frozen in liquid nitrogen (−196 °C) and preserved at −70 °C. Levels of IL1α, TNFα, and b-FGF were measured with specific ELISA kits (Biosource International, Camarillo, California, USA) according to the manufacturer’s instructions. Skin cytokines were measured as described by Lowry et al. Level of the cytokines were expressed as μmol/mg protein. Statistical analysis was carried out using spss 10.0. Differences in values of cytokine amount between lesional vs. healthy volunteers, nonlesional vs. healthy controls, serum of patients vs. serum of healthy volunteers were carried out using Mann– Whitney U-test. The parameters of lesional vs. nonlesional skin were analyzed by the Wilcoxon-signed rank test. P-value of less than 0.05 was considered to be statistically significant. The mean (± SD) values of IL1α, TNFα, b-FGF in lesional, nonlesional, healthy skin, and the serum from healthy controls and the study group are given in Table 1. The expression of IL1α and TNFα was significantly higher in lesional skin than in nonlesional skin in patients with vitiligo (P = 0.007 and P = 0.002), respectively. The exact mechanism how cytokines effect pigmentation is not fully understood. The different hypotheses are: (a) TNFα induces IL1α promoting B-cell differentiation and immunoglobulin production. (b) Cytokines such as IFNγ, TNFα, TNFβ, IL1α, and IL-6 can induce cell surface ICAM-1 on melanocytes which is necessary for leukocyte–melanocyte attachment. ICAM-1 may also induce B-cell activation, increasing autoantibody production and may cause melanocyte damage in vitiligo. (c) TNFα and IL1α also have the capacity to induce apoptosis in many cell types. (d) Melanogenesis is also inhibited by TNFα through an inhibitory effect on tyrosinase and tyrosinase related protein. Moretti et al. found increased levels of IL-6 and TNFα in the epidermis of lesional skin compared with the healthy controls. Swope et al. investigated the role of epidermal cytokines in pigmentation and found that IL1α, TNFα, and IL-6 elicited a dose-dependent decrease in the activity of the enzyme tyrosinase of cultured normal human melanocytes and also inhibited melanocyte proliferation. Ozdemir et al. demonstrated increased skin blister fluid b-FGF levels and serum levels in vitiligo patients compared with healthy controls and proposed that b-FGF plays a role in the pathogenesis of vitiligo. However,

Hepatitis C virus infection prevalence in lichen planus: examination of lesional and normal skin of hepatitis C virus-infected patients with lichen planus for the presence of hepatitis C virus RNA

Hepatitis C virus (HCV) is the main cause of parenterally transmitted non‐A, non‐B viral hepatitis. In recent years, a significant association between lichen planus and chronic HCV infection has been reported. Anti‐HCV antibody status was evaluated by ELISA in 54 patients with lichen planus and 54 patients with minor dermatological disorders. PCR was used to examine HCV RNA from serum and lesional and nonlesional cutaneous biopsy samples of HCV‐infected patients. Seven patients with lichen planus (12.9%) and two patients in the control group (3.7%) were anti‐HCV antibody positive. Five out of seven patients with anti‐HCV antibodies had demonstrable HCV RNA in lesional skin biopsies. The viral RNA was absent in three out of four patients with lichen planus whose serum samples were positive for HCV RNA and agreed to biopsy of nonlesional skin. The prevalence of HCV infection is not increased in Turkish patients with lichen planus. However our findings suggest that the virus may play a potential pathogenic role by replicating in cutaneous tissue and triggering lichen planus in genetically susceptible HCV‐infected patients.

Examination of Bcl-2, Bcl-X and bax protein expression in psoriasis

Background  Psoriasis is an inflammatory skin disease characterized by epidermal hyperplasia and greatly accelerated epidermal turnover. The blockage of normal apoptotic process in the epidermis is one of the factors implicated in the pathogenesis of psoriasis.

Giant condyloma acuminata of Buschke–Löwenstein: successful treatment with a combination of surgical excision, oral acitretin and topical imiquimod

Human papillomavirus (HPV) is the most common sexually transmitted disorder in young, sexually active populations in the USA and Europe. Giant condyloma acuminatum (GCA) is a unique variant of condyloma acuminata, characterized by local aggressive behaviour despite benign histology. It carries a substantial risk of squamous cell carcinoma. Various treatments have been used, but response is often poor and recurrence rates high. We present a case of GCA successfully treated with a combination of surgical excision, oral acitretin and topical imiquimod. The diagnosis was based on histological examination, immunohistochemical analysis and in situ hybridization for HPV 6 and 11. We recommend a trial of oral retinoid and topical imiquimod in selected cases of GCA.

Peripheral Neuropathy in Behçet's Disease

Behçets disease (BD) is a multisystem disorder. Since its first description, the involvement of many organ‐systems has been studied. However, the involvement of the peripheric nervous system has not been well documented yet. Twenty‐six patients involved in the study were without prominent complaints of neuropathic symptoms. They were surveyed through the outpatient clinic of the department of dermatology. Each patient filled out a total neuropathy score (TNS) questionaire after their neurologic exam. A neurology specialist conducted the electrophysiological study. Our results were noteworthy because this complication was present without significant complaint. We hypothesized that the nerve dysfunction or peripheral neuropathy of BD is an axonal type of distal polyneuropathy and predominantly involves the lower extremities. We did not find a predominant motor or sensory nerve involvement. This complication is mentioned and reported rarely in BD.

A case of porokeratotic eccrine ostial and dermal duct naevus of late onset

We describe the case of a 21‐year‐old man with an 8‐year history of porokeratotic eccrine ostial and dermal duct naevus (PEODDN) of late onset. The patient had pruritic, keratotic papules on the dorsal surface of his left hand, bilaterally on his palms and multiple yellowish lesions on the plantar surface of his feet. On histopathological examination cornoid lamella‐like parakeratotic columns above eccrine sweat ducts were observed. The acrosyringium was also dilated. The lesions were refractory to treatment with salicylic acid in petrolatum and acitretin for 2 months. This entity should be taken into consideration in the differential diagnosis of linear keratotic cutaneous eruptions.

Response to vaccination against hepatitis B in patients with Behcet's disease

Background and Aim:  Hepatitis B virus infection is an important public health problem in Turkey. Although hepatitis B vaccination is regarded as safe and effective for the general population, recommendations for hepatitis B immunization in patients with Behcets disease are not clear. The aim of the present study was to elucidate the response of patients with Behcets disease to hepatitis B vaccination and to determine whether hepatitis B vaccination has any adverse effects on the course of the disease.

Focal acral hyperkeratosis: A rare cutaneous disorder within the spectrum of costa acrokeratoelastoidosis

Abstract:  Acrokeratoelastoidosis and focal acral hyperkeratosis share similar clinical features and identical histologic epidermal alterations. These disorders are distinguished solely on the basis of the absence of elastorrhexis in the latter. We present a case of focal acral hyperkeratosis in a 9‐year‐old girl. The lesions consisted of translucent polygonal papules clustered on the thenar regions of the palms and over the metacarpophalangeal and interphalangeal joints. Histopathologic examination revealed orthohyperkeratosis within focal clavus‐like depressions of the epidermis and prominent hypergranulosis. There was no evidence of alterations in elastic tissue. The clinicopathologic distinction between focal acral hyperkeratosis and acrokeratoelastoidosis is blurred. There is enough evidence to consider the former as a histologic variant of Costa acrokeratoelastoidosis syndrome, and a better nomenclature for this disorder would be “acrokeratoelastoidosis without elastorrhexis.”