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Biomedical subjects

Mosaad Megahed

Publications and source records attributed to Mosaad Megahed.

16 recordsLinked to original sources

Skin retinoid concentrations are modulated by CYP26AI expression restricted to basal keratinocytes in normal human skin and differentiated 3D skin models.

Cellular levels of all-trans retinoic acid (RA) are meticulously regulated utilizing an array of systems to balance uptake, biosynthesis, catabolism, and efflux transport. Metabolic transformation of all-trans RA to 4-hydroxylated RA appears to be primarily catalyzed by the cytochrome P450 (CYP) 26AI. Analysis of monolayer cultures of normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts by quantitative real-time PCR and reverse transcription-PCR revealed no basal levels of CYP26AI mRNA expression, whereas specific transcripts were detectable following addition of 10(-6) M all-trans RA. Immunofluorescence and Western blot analysis showed a weak expression of CYP26AI in NHEK, which was increased by stimulation with all-trans RA. Using a newly developed peptide antibody, we further examined the localization of CYP26AI expression in normal skin and three-dimensional (3D) skin models. In contrast to cell culture monolayers where CYP26AI was only weakly detectable, strong constitutive expression of CYP26AI in vivo and in organotypic culture was found to be restricted to basal epidermal keratinocytes, as well as eccrine sweat glands and sebaceous glands. These studies verify the capacity of human skin to metabolize RA, although substantial differences exist in CYP expression between normal skin and 3D skin models compared to monolayer cultures. Complex metabolic processes that maintain retinoid homeostasis may therefore be better studied in model systems more closely resembling in vivo skin. In light of our prior studies documenting the functional activity of RA metabolites, expression of CYP26 in the sebaceous gland epithelium supports the suggestion that altered RA metabolism may be involved in the pathogenesis of acne.

Blotting, Western↗

Painful rash and swelling of the limbs after recurrent infections in a teenager: polyarteritis nodosa.

UNLABELLED: Polyarteritis nodosa is a rare disease in childhood and adolescence that is difficult to diagnose clinically. We report on a 17-y-old girl presenting with a history of recurrent infections of the upper respiratory tract and conjunctivitis followed by a painful rash on the upper and lower extremities resembling erythema nodosum. The diagnosis of polyarteritis nodosa was proven by skin biopsy. Therapy with intravenous immunoglobulins failed, but with systemic steroids she responded promptly. CONCLUSION: Polyarteritis nodosa is a differential diagnosis in adolescents presenting with fever and an erythema nodosum-like rash.

Adolescent↗

Cytologic and DNA-cytometric examination of oral lesions in lichen planus.

BACKGROUND: The aim of the present study was to evaluate the diagnostic value of exfoliative cytology (EC) and DNA image cytometry applied to oral lesions of lichen planus (LP; n = 56), in order to detect or exclude malignant transformation. METHODS: Brush and excisional biopsies were obtained from 56 patients. In cases of oral LP in which brush biopsies were suspicious for tumor cells, nuclear DNA contents were measured, using a TV Image Analysis System. RESULTS: In 50 patients EC yielded tumor cell-negative, doubtful in four cases and suspicious results obtained in two cases. DNA image cytometry revealed DNA-aneuploidy only in the two suspicious cases. The comparison between cytologic/DNA-cytometric diagnosis and biopsy histology resulted in a total agreement (LP without dysplasia: 54 and squamous cell carcinoma in LP: two cases). CONCLUSIONS: In conclusion, cytology with DNA-cytometry is a highly sensitive, specific, and non-invasive method, which can be used for periodical follow up of oral LP lesions in order to early detect or exclude malignancy.

Adult↗

Verrucous carcinoma of the buccal mucosa: histopathological, cytological and DNA-cytometric features.

We describe a patient with an exophytic oral lesion diagnosed as verrucous carcinoma. The lesion existed without metastases, at least 5 years. Local excisions led to recurrences and continuous expansion. Scalpel biopsies for histopathological and polymerase chain reaction examination were obtained from characteristic regions of the lesion. Brush biopsies for exfoliative cytology (EC) were taken, in order to screen the mucosal area covered by the lesion. After Feulgen restaining of the smears, nuclear DNA contents were measured using a TV image analysis system. An exophytic lesion of the buccal mucosa was diagnosed as low-grade malignant through histopathology and EC combined with DNA-image cytometry (peritetraploid DNA-aneuploidy). Due to almost normal microscopic appearance of the epithelium of verrucous carcinoma, thorough cytological/DNA-cytometric and histological examinations are needed. Brush biopsies of such neoplastic oral lesions showing DNA-aneuploidy with peritetraploid stemlines should be used for diagnosis and follow-up examination of these patients.

Aged↗

Linear arrangement of multiple deep penetrating nevi: report of first case and review of literature.

BACKGROUND: Deep penetrating nevus is a recently described variant of melanocytic nevi with clinical and histopathological features that may be confused with malignant melanoma, blue nevus, pigmented Spitz nevus, or congenital melanocytic nevus. We report a case with linear arrangement of multiple deep penetrating nevi. To our knowledge, such presentation has never been reported in the literature. OBSERVATIONS: We describe a patient with multiple darkly pigmented lesions in the right periauricular area, above and behind the ear. The histopathological features of these lesions were consistent with deep penetrating nevus. CONCLUSIONS: To our knowledge, this is the first report of linear arrangement of multiple deep penetrating nevi. We consider this case a unique presentation of deep penetrating nevus.

Adult↗

Histopathologic findings in lupus erythematosus tumidus: review of 80 patients.

BACKGROUND: In a recent study, we demonstrated that lupus erythematosus (LE) tumidus (LET) is a distinct subset of cutaneous LE (CLE), which is clinically characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed areas. OBJECTIVE: Our purpose was to analyze skin biopsy specimens from 80 patients with this disease and to determine whether it could be differentiated from other variants of CLE on histopathologic grounds. METHODS: Skin biopsy specimens from 53 primary and 38 UVA- and/or UVB-induced lesions of 80 patients with LET were examined and compared with skin biopsy specimens from patients with discoid LE (DLE) and subacute CLE (SCLE). RESULTS: Specimens from LET lesions showed a characteristic and diagnostic pattern of perivascular and periadnexal cellular infiltrates in the papillary and reticular dermis composed almost entirely of lymphocytes. In some cases, few scattered neutrophils were present. Furthermore, interstitial mucin deposition was observed in all specimens, as confirmed by colloidal iron staining. In contrast to discoid LE and subacute CLE lesions, epidermal atrophy or alteration at the dermoepidermal junction was not detected. CONCLUSION: Skin lesions of patients with LET present with specific histopathologic features, and the differences compared with subacute CLE and discoid LE further support the concept to consider LET as a separate entity of CLE.

Dermis↗

Tacrolimus ointment for the treatment of vulvar lichen sclerosus.

The treatment of vulvar lichen sclerosus is generally considered difficult. Ultrapotent corticosteroids represent the most effective topical treatment, but carry the risk of side effects such as skin atrophy. We describe a 71-year-old woman with long-standing vulvar lichen sclerosus refractory to conventional treatment. After 6 consecutive weeks of treatment with tacrolimus ointment 0.1% (Protopic) twice daily, signs and symptoms of lichen sclerosus resolved. To our knowledge, this is the first report of the use of topical tacrolimus, which does not induce skin atrophy, in the treatment of vulvar lichen sclerosus.

Aged↗

Papulonodular mucinosis associated with subacute cutaneous lupus erythematosus.

Mucin deposition is a common histopathologic finding in lupus erythematosus (LE) but is rarely present in sufficient quantity to produce clinically apparent skin lesions. Until now, fewer than 40 cases of papulonodular mucinosis associated with LE have been reported in the literature, and it was associated with either systemic LE or discoid LE. For the first time, to our knowledge, we describe 2 patients with subacute cutaneous LE who presented with papulonodular mucinosis as a major clinical manifestation of their disease.

Adult↗

Lupus erythematosus tumidus in childhood. Report of 3 patients.

Lupus erythematosus (LE) is a rare disorder in childhood. Most patients reported in the literature present with systemic manifestations, and, to date, fewer than 20 children with chronic cutaneous LE have been documented. In this article, we describe 3 patients with childhood LE tumidus, an uncommon but distinct subtype of chronic cutaneous LE. The lesions are characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed areas and, unlike in other variants of chronic cutaneous LE, there is no epidermal involvement. The clinical, photobiological, and histologic features as well as the differential diagnoses of childhood LE tumidus are discussed and compared with the adult form of this disease.

Child↗

Reliability of diagnosis of melanoma in situ.

Early and correct diagnosis of malignant melanoma is of utmost importance to ensure adequate treatment and the best outcome. Prompted by the death of a patient with an apparent metastasising melanoma in situ, we reassessed 104 people with this malignant disorder, whose diagnosis had been histopathologically verified. We did immunohistochemical analysis of cells with the melanocytic marker melan-A/MART-1, and results of this analysis showed that 30 (29%) of 104 patients had invasive melanomas. One patient died of distant metastases, and the tumour recurred in another. Our finding could be relevant for diagnosis and treatment of melanoma in situ.

Antigens, Neoplasm↗

Characterization of the inflammatory infiltrate and expression of endothelial cell adhesion molecules in lupus erythematosus tumidus.

Lupus erythematosus tumidus (LET) is a disease with characteristic clinical and histopathologic features that has not always been considered a subset of cutaneous lupus erythematosus (CLE). Although LET was first mentioned in the literature in 1930, it has rarely been documented, and immunohistochemical studies have never been performed. The aim of the present study was to characterize the inflammatory infiltrate and to analyze the expression of endothelial cell adhesion molecules in skin specimens from patients with LET and to compare the results with those from patients with other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Cryostat sections of lesional skin specimens from ten patients with LET demonstrated an infiltrate composed of more than 75% CD4+, CD8+, and HLA-DR+ cells. Interestingly, CD45RO+ cells, in contrast to CD45RA+ cells, were the prevailing inflammatory cell population. Compared with skin specimens from patients with DLE and SCLE, the mean expression of CD4+ and CD8+ cells was higher (but not significantly so) in LET, and no differences were observed with the other three antibodies. Furthermore, in contrast to controls, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and P-selectin showed the same expression pattern in skin specimens from patients with DLE, SCLE, and LET. In conclusion, the inflammatory infiltrate of LET primarily consists of CD4+/CD8+ lymphocytes. Furthermore, expression of endothelial cell adhesion molecules was equally upregulated in LET compared with the expression in DLE and SCLE, suggesting a similar immunopathomechanism of these subtypes of CLE.

Amine Oxidase (Copper-Containing)↗

Synergism of RAD and cyclosporin A in prevention of acute rat corneal allograft rejection.

PURPOSE: The novel immunosuppressant RAD, 40-0-(2-hydroxy-ethyl)-rapamycin, has synergistic effects with cyclosporin A. The aim of this study was to evaluate the combined effect of RAD and cyclosporin A in the prevention of acute allograft rejection after murine corneal transplantation. METHODS: Fisher donor corneas were implanted into Lewis recipients. Postoperative evaluation included slit-lamp biomicroscopy and immunohistology. Treatment groups were comprised of rats treated orally with RAD 2.5 mg/kg/day, cyclosporin A 10 mg/kg/day, RAD 1.5 mg/kg/day plus cyclosporin A 5 mg/kg/day. RESULTS: Therapy with RAD 2.5 mg/kg and cyclosporin A 10 mg/kg led to a statistically significant and comparable prolongation of transplant survival. However. combination therapy was significantly superior. There was a significant reduction in the number of infiltrating cells in the animals treated with RAD and cyclosporin A. CONCLUSIONS: This is the first study on the efficacy of a double drug regimen with RAD and cyclosporin A for the control of acute corneal allograft rejection. Combination therapy resulted in superior graft survival.

Acute Disease↗

Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2-year results from an ongoing 5-year follow-up study in Europe.

Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses. This ongoing phase III, open-label study conducted in Europe is evaluating the long-term (5 year) clinical efficacy and safety of imiquimod 5% cream applied once daily 5 times per week (5 x/week) for 6 weeks for the treatment of superficial basal cell carcinoma (sBCC). A total of 182 subjects were enrolled. The initial sBCC clearance rate was 90% (12-week post treatment), whereas the proportion of subjects who were clinically clear at 2 years (current time point) was estimated to be 79.4%. Local skin/application site reactions were the most frequently reported safety findings. Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC. The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod.

Adjuvants, Immunologic↗