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Biomedical subjects

Gürkan Kaya

Publications and source records attributed to Gürkan Kaya.

At least 19 recordsLinked to original sources
PubMed2006

Severe eczematous skin reaction after high-dose intravenous immunoglobulin infusion: report of 4 cases and review of the literature.

BACKGROUND: High-dose intravenous immunoglobulins (IVIGs) are increasingly used to treat inflammatory and/or autoimmune disorders. In dermatology, they provide therapeutic benefit in Kawasaki disease and certain cases of dermatomyositis. While most adverse effects following IVIG treatment are not severe, occasionally more severe adverse effects occur, including anaphylactic reactions and acute, usually transient, renal failure. OBSERVATIONS: We report 4 cases of a characteristic severe extensive eczematous reaction that occurred approximately 10 days after IVIG infusion for polyradiculoneuritis. In all cases, onset was characterized by dyshidrotic lesions on the palms, rapidly followed by pruriginous maculopapular lesions involving the whole body. All patients were treated with topical and/or systemic steroids, and complete resolution of skin lesions was observed within 1 month. To date, 33 cases of cutaneous rash following IVIG infusion have been reported in the literature, mostly in neurology journals, and the features are identical to those reported herein. CONCLUSIONS: Severe eczematous skin reaction with a characteristic initial localization to the palms and/or soles that then extends to the rest of the body is a rare but characteristic adverse effect of high-dose IVIG therapy. Although the precise mechanism of this cutaneous eruption remains to be elucidated, its occurrence within days of IVIG infusion, its characteristic distribution at onset, and its clinical course should be recognized by dermatologists.

Biopsy↗
PubMed2006

Fatal GvHD as a complication of liver transplantation for undetermined fulminant hepatic failure and associated aplastic anemia.

Fulminant hepatic failure of unknown origin is the most common cause of fulminant hepatitis with high incidence of aplastic anaemia. Furthermore, the association of liver failure and aplastic anaemia has an increased mortality rate. In this report we describe a 16-month-old boy who presented with aplastic anaemia preceding a non-A, non-B, non-C fulminant liver failure. He developed severe graft versus host disease (GvHD) after liver transplantation, proven by the presence of donor cells in the peripheral blood and in the skin biopsy. He received conventional therapy (steroids, mycophenolate, anti-IL-2 monoclonal antibodies, anti-thymocyte globulin) without success. In an attempt to obtain T cell depletion and reduce the GvHD, he was treated with Alemtuzumab, a first time use for this indication. Aplastic anaemia was extensively investigated, especially exploring the possibility of primary immunodeficiency and reticular dysgenesis which were excluded based on clinical history. However, another form of primary immunodeficiency could be the cause of the uncontrollable proliferation of the donor lymphocytes derived from the liver transplant. Despite aggressive treatment GvHD progressed and the patient died of multiorgan failure. The majority of authors mention aplastic anaemia as a secondary event post liver transplant, whereas in our view this might be a haematopoietic stem cell disorder preceding fulminant hepatic failure. These patients also need to be evaluated extensively in order to exclude a primary immunodeficiency. The underlying disease will determine the choice of immunosuppressive treatment, especially in case of development of GvHD caused by the transplanted lymphocytes inhabiting the donor liver.

Anemia, Aplastic↗
PubMed2006

CD44 and hyaluronate expression in follicular mucinosis.

BACKGROUND: CD44 is a membrane glycoprotein and the major cell-surface receptor of hyaluronate (HA). Lack of CD44 expression in mouse epidermis leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism. Decrease of epidermal CD44 expression in patients of lichen sclerosus et atrophicus is potentially responsible for dermal deposition of HA in this disease. Stromal HA accumulation is associated with decreased or lost expression of CD44 in perifollicular solitary cutaneous myxoma, myxoid dermatofibroma, and dermatofibrosarcoma protuberans. METHODS: We examined the expression of CD44 and HA in the skin biopsy specimens of 10 patients with follicular mucinosis by using CD44-specific antibodies and biotinylated HA-binding protein (HABP), respectively. RESULTS: No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin-accumulated areas compared to the interfollicular keratinocytes. CONCLUSION: Our results suggest an active secretion of HA by follicular cells in follicular mucinosis.

Adult↗
PubMed2006

Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism.

BACKGROUND: Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present. METHODS AND FINDINGS: Atrophic skin displays a decreased hyaluronate (HA) content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF) on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da) but not with small-size HAF (HAFs; <50,000 Da) or large-size HAF (HAFl; >400,000 Da) induced wild-type (wt) but not CD44-deficient (CD44-/-) keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF) and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3), and by tissue inhibitor of metalloproteinase-3 (TIMP-3). CONCLUSIONS: Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.

Adult↗
PubMed2005

Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging.

Skin aging (intrinsic aging) and photoaging (extrinsic aging) involve a similar process that leads to the typical creased appearance of the skin, with the progressive loss of its physical and biologic properties. Photoaging is a premature skin aging caused by long-term exposure to the ultraviolet B radiations of the sun, and is more frequently associated to skin cancer than intrinsic aging. Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and penetrate the epidermis easily. Their biologically active forms can modulate gene expression by binding to nuclear receptors and then to specific DNA sequences. Because of their ability to modulate genes involved in cellular differentiation and proliferation, they appear as good candidates to treat and prevent photoaging. Hyaluronate and collagen, two major constituents of the dermis, are progressively decreased and altered during aging. Various retinoids were shown to increase their synthesis and concentration in the skin and reduce their rate of degradation. Furthermore, retinoids share a common chemical structure containing several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, thereby protecting cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. Therefore, retinoids may be beneficial in treating skin aging and photoaging because of their biologic, chemical, and physical properties, which act at several levels.

Journal Article↗
PubMed2005

Topical calcineurin inhibitors decrease the production of UVB-induced thymine dimers from hairless mouse epidermis.

BACKGROUND: An increased incidence of ultraviolet-light-related skin tumours is a well-known problem in patients undergoing posttransplantation immunosuppression with systemic calcineurin inhibitors such as cyclosporine A or tacrolimus. UV-related carcinogenesis as a consequence of long-term treatment of sun-exposed sites with topical calcineurin inhibitors is therefore of theoretical concern. RESULTS: In this study, we show that tacrolimus acts as a UVB filter when incorporated into liposome membranes. In hairless mice pretreated with 1% pimecrolimus cream, 0.1% tacrolimus ointment or vehicle, the amount of epidermal thymine dimers, measured 1 h after 1 J/cm2 of UVB irradiation, was decreased by 89, 84 and 47%, respectively, as compared to untreated mice. Forty-eight hours after UVB irradiation, 97, 89 and 93% of epidermal thymine dimer levels were removed in pimecrolimus-, tacrolimus- or vehicle-treated mice, respectively. In contrast, 69% of thymine dimers, originally present in much higher amounts than in treated mice, were removed from untreated controls. UVB-induced apoptosis was less pronounced in treated mice. CONCLUSION: Taken together, these results suggest that topical calcineurin inhibitors prevent DNA photodamage due to a filter effect of both vehicle and active components, whereas they do not affect the clearance of DNA photoproducts.

Administration, Cutaneous↗
PubMed2004

Myc-transformed epithelial cells down-regulate clusterin, which inhibits their growth in vitro and carcinogenesis in vivo.

Effective treatment of malignant carcinomas requires identification of proteins regulating epithelial cell proliferation. To this end, we compared gene expression profiles in murine colonocytes and their c-Myc-transformed counterparts, which possess enhanced proliferative potential. A surprisingly short list of deregulated genes included the cDNA for clusterin, an extracellular glycoprotein without a firmly established function. We had previously demonstrated that in organs such as skin, clusterin expression is restricted to differentiating but not proliferating cell layers, suggesting a possible negative role in cell division. Indeed, its transient overexpression in Myc-transduced colonocytes decreased cell accumulation. Furthermore, clusterin was down-regulated in rapidly dividing human keratinocytes infected with a Myc-encoding adenovirus. Its knockdown via antisense RNA in neoplastic epidermoid cells enhanced proliferation. Finally, recombinant human clusterin suppressed, in a dose-dependent manner, DNA replication in keratinocytes and other cells of epithelial origin. Thus, clusterin appears to be an inhibitor of epithelial cell proliferation in vitro. To determine whether it also affects neoplastic growth in vivo, we compared wild-type and clusterin-null mice with respect to their sensitivity to 7, 12-dimethylbenz(a)anthracene /12-Otetradecanoylphorbol-13-acetate (DMBA/TPA)-induced skin carcinogenesis. We observed that the mean number of papillomas/mouse was higher in clusterin-null animals. Moreover, these papillomas did not regress as readily as in wild-type mice and persisted beyond week 35. The rate of progression toward squamous cell carcinoma was not altered, although those developing in clusterin-null mice were on average better differentiated. These data suggest that clusterin not only suppresses epithelial cell proliferation in vitro but also interferes with the promotion stage of skin carcinogenesis.

Animals↗
PubMed2004

Purpura fulminans in a child as a complication of chickenpox infection.

Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation or in the context of an acquired or congenital protein C or S deficiency. Here we report the case of a 4-year-old child who developed, 5 days after a chickenpox infection, large painful ecchymotic, necrotizing and retiform plaques on the lower extremities. Laboratory analyses revealed very low protein S levels as well as anticardiolipin antibodies. Aggressive treatment by low-molecular-weight heparin, steroids, intravenous immunoglobulins and fresh frozen plasma was able to prevent the extension of the lesions and to correct the coagulation abnormalities. No lesions required skin grafting. As in our patient, an acquired protein S deficiency is probably responsible for most cases of purpura fulminans occurring after varicella, but the concomitant presence of antiphospholipid antibodies may also play a role.

Antibodies, Anticardiolipin↗
PubMed2004

Nephrogenic fibrosing dermopathy in a renal transplant recipient with tubulointerstitial nephritis and uveitis.

We report a patient with nephrogenic fibrosing dermopathy. He had chronic renal failure with arthritis, uveitis and histologically severe tubulointerstitial nephritis for which he received a renal transplant from a family relative. After an episode of acute renal failure with the transplant he developed painful, erythematous, firm papules and plaques with geographic borders on the legs, anterior thorax and elbow. A skin biopsy revealed increased fibroblast and collagen fiber content of the dermis and subcutaneous septae. Mucin deposition, sparse smooth-muscle-actin-positive cells and an increased number of CD34-positive cells in the deep dermis were found. After several weeks of hemodialysis, the lesions changed from an inflammatory to a purely sclerotic phase. The fibrocyte, a recently described circulating cell type, that is deposited in scar tissue may be involved in the pathogenesis of this novel pseudosclerodermatous skin disorder.

Diagnosis, Differential↗
PubMed2003

Histopathologic correlation in dermoscopy: a micropunch technique.

BACKGROUND: Dermoscopy is a simple-to-use, in vivo method for the diagnosis of malignant melanoma and the differential diagnosis of pigmented skin lesions. It uses an immersion technique and optical magnification to visualize structures not visible to the naked eye. The anatomoclinical correlation of dermoscopic with histopathologic findings is important, and while many articles have described different techniques to achieve this goal, no direct correlation with a visual control has been described. We recently developed a micropunch technique that allows for the first time this direct correlation. OBSERVATIONS: After applying local anesthesia, the physician makes a superficial round incision using a 1-mm micropunch in the area of interest and leaves the punch in place. The lesion is documented using digital dermoscopy before and after surgery. Using these images, the laboratory technicians can easily visualize the precise site of the punch and its correlation with the initial dermoscopic image, and the sections are chosen in a way that they pass through the punch incision. The punch incision can be easily identified in the histopathologic slides because of its clear-cut borders. Since the punch always stays in place, this technique does not interfere with the interpretation of the slides (eg, measurement of the Breslow thickness). CONCLUSIONS: The advantages of our technique are that it is easy to perform by any clinician in any setting after a short setup and training period for the clinician and the laboratory technicians. Unlike with other techniques, the physician need not be present at the laboratory at the moment of the step sectioning. It can be performed in private practice and for many other indications besides pigmented skin lesions. Finally, since this technique allows for the first time a direct correlation between dermoscopic and histopathologic findings, the clinician will be able to "guide" the pathologist and indicate the precise areas of interest or suspicion.

Biopsy↗
PubMed2003

CD44 and hyaluronate in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans.

The histological distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) may be extremely difficult. CD34 and Factor XIIIa have been used to differentiate DF from DFSP. However, there is an overlap and relative lack of specificity of their expressions. CD44 is a widely distributed integral membrane glycoprotein, which is expressed as a multitude of isoforms generated by alternative splicing of at least 10 different variant exons and post-translational modifications. CD44 is currently thought to be the principal cell surface receptor for hyaluronate (HA), the major component of the extracellular matrix. In this study we aimed to assess the expression of standard CD44 (CD44s) and its isoforms (CD44v3, CD44v4, CD44v5, CD44v6, CD44v7, CD44v7v8, and CD44v10), and HA in DF and DFSP. Immunohistochemical staining was performed on the biopsy specimens of 15 cases of DF and four cases of DFSP, using antibodies that recognize the CD44s, different CD44 isoforms and the hyaluronate binding protein (HABP). Tumor cells displayed a strong CD44s immunoreactivity in all cases of DF whereas a faint HA positivity was observed in the tumor stroma. The DF cells were negative for CD44v3, CD44v4, CD44v6, CD44v7 and CD44v7v8 but showed a strong reactivity for CD44v5 and CD44v10. In contrast, CD44s' expression was significantly reduced or absent in all DFSP lesions and the tumor stroma displayed strong staining for HA. Our results indicate that CD44 and HA can be used as additional diagnostic markers to distinguish DF from DFSP.

Dermatofibrosarcoma↗
PubMed2003

Decreased CD44 expression and stromal hyaluronate accumulation in myxoid dermatofibroma.

BACKGROUND: Dermatofibroma (DF) is a common benign histiocytic tumor, which has several clinicopathological variants. Myxoid DF is one of these variants, which is characterized by a stromal mucin deposition. CD44 is a polymorphic transmembrane glycoprotein and the principal cell surface receptor of hyaluronate (HA), the major component of the extracellular matrix. In a recent study, we have observed an abnormal accumulation of HA in the superficial dermis of transgenic mice with a keratinocyte-specific CD44 expression defect. We have also shown that HA was accumulated in large amounts in the superficial dermis of lichen sclerosus et atrophicus (LSA) lesions and that the epidermal CD44 expression of LSA skin was significantly decreased or lost. In an another study, we have suggested that a decrease in CD44 expression in follicular epithelial proliferations might be correlated with an abnormal HA accumulation in perifollicular solitary cutaneous myxoma. Recently we have also demonstrated that classical DF lesions displayed a strong CD44 expression in tumor cells and a weak HA positivity in tumor stroma whereas CD44 expression was significantly reduced or absent in dermatofibrosarcoma lesions and the tumor stroma showed strong HA staining. OBJECTIVE AND METHODS: Here we present 3 cases of myxoid DF, in which we explored the nature of the mucinous material in myxoid stroma by colloidal iron and hyaluronic acid binding protein stainings, as well as the expression of CD44 in the tumor cells by immunohistochemistry. RESULTS: We show that HA is accumulated in the stroma of all myxoid DF lesions with a significant decrease in CD44 expression in the tumor cells. CONCLUSION: Our results suggest that a decrease in CD44 expression in the tumor cells may result in stromal myxoid changes characterized by an abnormal HA accumulation in myxoid DF.

Adult↗
PubMed2002

Basal cell carcinoma of the earlobe after auricular acupuncture.

The genesis of familial and sporadic basal cell carcinomas involves activation of the Sonic hedgehog signal transduction pathway. Other known factors for the development of basal cell carcinoma are ultraviolet exposure, X-rays, race, age, gender and decreased DNA repair capacity. We here report the case of a right earlobe sporadic basal cell carcinoma in a 65-year-old woman. This case is unusual because of its earlobe localization and its association with multiple auricular acupuncture treatments. This observation suggests a connection between local traumas, which occur in the course of acupuncture treatment and ear piercing, and the genesis of basal cell carcinoma. The incidence of minor adverse events associated with acupuncture is high, but serious events are uncommon. Acupuncture is not known to date for promoting the development of tumors. This connection remains to be elucidated.

Acupuncture, Ear↗
PubMed2002

Hyaluronate accumulation and decreased CD44 expression in perifollicular solitary cutaneous myxoma.

BACKGROUND: Myxomas are rare cutaneous tumors which may be solitary or associated with Carney's complex, NAME or LAMB syndromes. The mucinous material which constitutes the stroma of cutaneous myxomas is predominantly composed of hyaluronate (HA), the major component of the extracellular matrix. CD44 is a polymorphic integral membrane glycoprotein which serves as the principal cell surface receptor for HA. OBJECTIVE AND METHODS: Here we present 2 cases of solitary cutaneous myxomas displaying microscopically a perifollicular localization, in which we explored the nature of the accumulated mucinous material by colloidal iron and HA-binding protein stainings, as well as the epidermal expression of CD44 protein by immunohistochemistry. RESULTS: We show that HA is accumulated in the stroma of the cutaneous myxoma lesions and that the protein expression of CD44 in the keratinocytes of the trichofolliculoma-like epithelial buds projecting from the hair follicle centering these lesions is significantly decreased. CONCLUSIONS: Our results suggest that a decrease in CD44 expression in follicular epithelial proliferations may be correlated with an abnormal HA accumulation in cutaneous myxoma.

Adult↗