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Biomedical subjects

Sélim Aractingi

Publications and source records attributed to Sélim Aractingi.

13 recordsLinked to original sources

Skin carcinoma arising from donor cells in a kidney transplant recipient.

The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.

Bowen's Disease↗

Vaccination-induced cutaneous pseudolymphoma.

BACKGROUND: Although mild early cutaneous transient reactions to vaccinations are common, late-onset chronic lesions have been scarcely reported. We report herein a series of 9 patients presenting with cutaneous and subcutaneous pseudolymphoma. OBSERVATIONS: Nine patients presenting with late-onset, chronic skin lesions occurring at the site of antihepatitis B (8 cases) and antihepatitis A (one case) vaccination were reported. Histopathologic and immunohistochemic studies, and molecular analysis of clonality of skin biopsy specimens, were performed. Furthermore, the presence of vaccine products was investigated in skin lesions by using histochemical, microanalytic, and electronic microscopy techniques. RESULTS: Histopathologic studies showed dermal and hypodermal lymphocytic follicular infiltrates with germinal center formation. The center of follicles was mostly composed of B cells without atypia, whereas CD4+ T cells were predominant at the periphery. Molecular analysis of clonality revealed a polyclonal pattern of B-cell and T-cell subsets. Aluminium deposits were evidenced in all cases by using histochemical staining in all cases, and by microanalysis and ultrastructural studies in one case. Associated manifestations were vitiligo (one case) and chronic fatigue with myalgia (two cases). CONCLUSION: Cutaneous lymphoid hyperplasia is a potential adverse effect of vaccinations including aluminium hydroxide as an adjuvant. Further prospective studies are warranted to evaluate the incidence of this complication in the immunized population.

Adolescent↗

Cetuximab-induced acne.

BACKGROUND: Cetuximab is a member of a new family of antineoplastic agents that inhibit epidermal growth factor receptor (EGFR). These molecules may induce acneiform eruptions. In this study, we aimed at evaluating (a) the characteristics of acne and (b) whether these acneiform eruptions could be improved by classical anti-acne treatments. METHODS: All patients treated with cetuximab in a single institution from October 2003 to May 2004 were prospectively evaluated. The presence of acne, its severity, need for a treatment and response to this treatment were recorded. RESULTS: 13 patients were included: 11 (85%) developed acneiform eruptions after a mean interval of 10 days. It was severe in 4/13 (31%). Comedones were never found and acne involved nonclassical sites in 3/11. Antibiotic treatment was given to 4 and local treatment to 2 patients: it was always efficient. CONCLUSION: Cetuximab-induced acne is frequent, differs from classical acne and may be treated effectively with classical modalities.

Acne Vulgaris↗

Analysis of HLA antigen expression in benign and malignant melanocytic lesions reveals that upregulation of HLA-G expression correlates with malignant transformation, high inflammatory infiltration and HLA-A1 genotype.

Previous studies indicate that the nonclassical class I HLA-G antigen, whose physiologic expression is mainly restricted to placenta, is upregulated in melanoma, renal carcinoma, lung carcinoma, glioblastoma and ovarian carcinoma, where its inhibitory effect on cytotoxic effector cells function is thought to participate in immune evasion by tumor cells. To define whether this expression was a specific feature of melanocytic malignant transformation, 174 paraffin-embedded melanocytic lesions including naevi, lentigo, primary and metastatic melanomas were analyzed for HLA-G and other HLA class I and class II antigen expression. HLA-G antigen expression in melanocytic cells was found to be significantly higher (p < 0.0003) in melanoma (22/79, 28%) than in naevi (1/70, 1.4%), suggesting that upregulation of HLA-G is associated with malignant transformation in this cell type. Further identification of HLA-G antigen expression in inflammatory infiltrating cells results in an overall frequency of HLA-G expressing cells that is higher in melanoma (28/79, 35.5%) than in naevi (5/60, 8.3%) or lentigo (2/23, 8.7%). Upregulation of HLA-G or HLA class II molecules in melanocytic cells thus appears as a better predictor of malignancy than classical HLA class I antigen defects, which are often described as an important mechanism used by tumor cells to evade immune surveillance. Furthermore, HLA-G expression was electively found in lesions that exhibited a high inflammatory infiltrate as well as in patients displaying HLA-A1 genotype. These findings may provide new insights in the comprehension of tumor progression and design of therapeutic approaches aimed at enhancing antitumor immune responses in melanoma patients.

Cell Transformation, Neoplastic↗

Topical effectiveness of molgramostim (GM-CSF) in sickle cell leg ulcers.

BACKGROUND: Leg ulcers are a frequently neglected, severe complication of sickle cell disease (SCD), responsible for significant altering quality of life. The management of leg ulcers remains disappointing. Local application of recombinant human granulocyte-macrophage colony-stimulating factor has been shown to be effective in several types of chronic wound healing. METHODS: We report 5 homozygous sickle cell patients with 14 leg ulcers lasting from 1 month to 6 years, treated with topical dripping of molgramostim solution. RESULTS: Healing was obtained for 9/14 ulcers, with no local or systemic adverse reactions. COMMENTS: Molgramostim solution appears to be an adequate therapy for SCD leg ulcers but a more conclusive evaluation will depend on larger series of patients and other types of formulations for topical applications could be even more effective in the future.

Administration, Topical↗

Selective expression of HLA-G in malignant and premalignant skin specimens in kidney transplant recipients.

The HLA-G molecule has been implicated in the escape from the host antitumor immune response. Besides, this molecule appears also to be detected in transplant recipient's tissues, mainly those with fewer rejection episodes. Since skin carcinomas develop frequently in organ transplant recipients, we asked whether HLA-G could be expressed in these lesions, therefore allowing tumor development in such patients. Immunohistochemical analysis of kidney transplant recipients presenting various types of epithelial malignant tumor and benign cutaneous lesion was done using a specific anti-HLA-G antibody. HLA-G was expressed in 35% of specimens of SCC, 47% of in situ carcinoma, 27% of AK and 14% of BCC but never in the 24 benign lesions studied. Many benign specimens were obtained from the same patients who had tumors, demonstrating that HLA-G expression was restricted to the malignant sites. Interestingly, HLA-G was expressed by proliferative keratinocytes, inflammatory infiltrates and even endothelial cells. Cytokines triggered in the course of organ transplantation include IL-10. This molecule may induce expression of HLA-G, which in turn may be implicated in tumor development in transplanted recipients.

Bowen's Disease↗

Presence of microchimerism in labial salivary glands in systemic sclerosis but not in Sjögren's syndrome.

OBJECTIVE: To determine whether microchimerism can be implicated in Sjögren's syndrome (SS) by studying minor salivary glands, one of the targets of the disease. METHODS: Labial salivary gland (LSG) biopsy specimens from 16 female patients with primary SS and 11 with systemic sclerosis (SSc) (a disease in which microchimerism is frequently detected) were analyzed. All 27 women had a history of pregnancy with a male baby. Specimens were microdissected, and polymerase chain reaction (PCR) was performed using the unique sex-determining region Y gene probe. RESULTS: The sensitivity of PCR for detecting male cells in LSG was high; the presence of 3 male cells was consistently detected in DNA extracted from a normal female LSG specimen to which male DNA had been added, and 1 male cell was detected in 50% of specimens analyzed. Male DNA was not found in any of the specimens from the 16 SS patients but was detected in 5 (45%) of 11 SSc specimens (P = 0.006). No differences in the rate of detection were found between patients with diffuse and limited SSc (male DNA detected in 2 of 3 and 3 of 8, respectively; P = 0.55) or between patients with and those without secondary SS (1 of 6 and 4 of 5, respectively; P = 0.08). CONCLUSION: The results of our study strengthen the possibility that microchimerism is implicated in SSc. This is the first study to demonstrate the presence of chimeric cells in LSG from 45% of SSc patients, independent of the presence of secondary SS. However, microchimerism was not detected in LSG from patients with primary SS, suggesting that the pathogenesis of the 2 diseases is different.

Adult↗

Necrotic cutaneous lesions induced by hypereosinophilic syndrome secondary to a T-cell lymphoma.

Cutaneous lesions of hypereosinophilic syndrome (HES) may display various presentations. These are important to recognize to allow early diagnosis. We report an unusual case of a young man with HES secondary to a splenic T-cell lymphoma, revealed by diffuse necrotic cutaneous lesions. Later on, brain and heart infarctions developed, leading to the patient's death. Analysis of skin biopsy specimens showed occluded dermal vessels surrounded by activated eosinophils. Because a complete analysis of hemostasis was unremarkable, these findings suggest that dermal vessel thrombosis was the direct consequence of the migration of activated eosinophils. Cutaneous lesions of HES are protean and probably reflect the differences between the lesional events induced in situ by activated eosinophils.

Adult↗

Prospective evaluation of risk factors of cutaneous drug reactions to sulfonamides in patients with AIDS.

BACKGROUND: Persons with HIV infection have increased rates of drug eruptions. OBJECTIVE: Our aim was to evaluate the risk factors of drug eruptions in response to sulfonamides in patients with AIDS, using a case-control analysis. METHODS: One hundred thirty-six patients who were hospitalized for pneumocystosis or toxoplasmosis were evaluated at the onset of treatment for various risk factors, which were then compared among patients with (48, 36%) and without (88, 64%) a drug eruption. RESULTS: In multivariate analysis, high CD8(+) cell count and age less than 36 years indicated a risk of drug eruption (respective odds ratios: 3.5 [95% CI 1.6-7.8], P =.002, and 2.1 [95% CI 1-4.6], P =.06). Markers of viral replication for HIV, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19, slow acetylation phenotype or genotype, and glutathione level were not associated with a risk. Administration of corticosteroids had no preventive effect. CONCLUSIONS: Our results challenge several current concepts regarding drug eruptions by discarding a strong association with glutathione deficiency, slow acetylation, or active viral infections and by showing no preventive effect of corticosteroids.

AIDS-Related Opportunistic Infections↗

[Microchimerisme in systemic sclerosis].

Several studies have shown an association between the presence of systemic sclerosis in females and the presence of fetal cells in peripheral blood. These results have led to the hypothesis that systemic sclerosis (SSc) may indeed be the consequence of an allogeneic fetomaternal reaction. However, certain normal female controls also exhibit microchimerism. In addition, there are several clinical and histological differences between SSc and sclerodermoid graft versus host reaction. If microchimerism plays a role in SSc, it would therefore comprise one step in a multistep process. This review focuses on recent papers targeting microchimerism and its evaluation in SSc.

Cell Movement↗