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M R Nasca

Publications and source records attributed to M R Nasca.

At least 19 recordsLinked to original sources

Expression of functional mGlu5 metabotropic glutamate receptors in human melanocytes.

Cultured human melanocytes express mGlu5 metabotropic glutamate (mGlu) receptors, as shown by RT-PCR, immunocytochemistry, Western blot analysis, and measurement of agonist-stimulated polyphosphoinositide hydrolysis. The mGlu5 receptor agonists (S)-3, 5-dihydroxyphenylglycine and quisqualate increased [(3)H-methyl]thymidine incorporation and melanocyte proliferation in subconfluent cultures, but impaired cell viability in confluent cultures. Both effects were prevented by 2-methyl-6-(2-phenyl-1-ethynyl)-pyridine, a potent and highly selective mGlu5 receptor antagonist. Agonists of other mGlu receptor subtypes (such as the mGlu2/3 receptor agonist, 2S,2'R,3'R-2-2', 3'-dicarboxycyclopropylglycine, or the mGlu4/6/7/8 receptor agonist, L-2-amino-4-phosphonobutanoate) or selective agonists of ionotropic glutamate receptors (N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and kainate) did not affect melanocyte proliferation or viability. The presence of a receptor for glutamate, the major excitatory neurotransmitter, in human melanocytes is intriguing. mGlu5 receptors may be involved in the control of melanocyte proliferation (and perhaps in other functions), but harbor a potential toxicity and may therefore contribute to cell damage under pathological conditions.

Amino Acid Sequence↗

Penile cancer among patients with genital lichen sclerosus.

BACKGROUND: Genital lichen sclerosus (LS) has sporadically been reported to be associated with penile squamous cell carcinoma (SCC). OBJECTIVE: The purpose of this study was to assess the risk of malignant degeneration in a series of male patients affected by genital LS. METHODS: All cases of histologically proven epithelial malignancy associated with penile LS recorded in our pathology files over a 10-year period (1987-1997) were reviewed. Assessment for presence of human papillomavirus (HPV) was performed from paraffin-embedded tissues using polymerase chain reaction (PCR). RESULTS: Five of 86 white and uncircumcised men with genital LS (mean age at diagnosis, 53 years; range, 22-83 years) showed malignant or premalignant histopathologic features: 3 had SCC, one had erythroplasia of Queyrat (unifocal SCC in situ), and one verrucous carcinoma. The average lag time from onset of LS was 17 years (range, 10-23 years). Histologically, transition from LS to frank neoplastic foci was evident in all cases of SCC. In these SCC cases, areas of epithelial dysplasia were well evident at the tumor periphery. In the remaining cases, the histologic findings were consistent with erythroplasia of Queyrat and verrucous carcinoma. PCR detected HPV 16 infection in 4 of the 5 cases; one SCC patient was negative for HPV. CONCLUSION: Malignant changes were associated with 5.8% of the cases of penile LS in our series. Therefore patients with genital LS are at considerable risk of the development of penile SCC, as well as other epithelial and in situ carcinomas, namely verrucous carcinoma and erythroplasia of Queyrat. HPV infection probably plays a major role because 4 of 5 patients were positive for HPV. Histologically, epithelial dysplasia may represent a precancerous stage before the development of neoplasia in atrophic nonproliferative LS lesions, as its presence at the tumor periphery in our SCC biopsy samples seemed to suggest.

Adult↗

Thalidomide increases human keratinocyte migration and proliferation.

Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

Cell Division↗

Epidemiologic analysis and clinical course of 84 consecutive cases of pemphigus in eastern Sicily.

BACKGROUND: The purpose of this study was to examine the clinical and epidemiologic features of pemphigus in eastern Sicily. METHODS: All new cases of pemphigus seen in the Dermatology Clinic at the University of Catania during the period January 1982 to June 1996 were studied retrospectively. RESULTS: Eighty-four patients with pemphigus represented 1.3% of 6653 patients admitted to our clinic in a 13.5-year period, with an average annual incidence of six cases per year. The most common form of presentation was pemphigus vulgaris (PV) (75%), followed by pemphigus erythematosus (17%), pemphigus herpetiformis (6%), and pemphigus vegetans (2%). In 6% of PV patients, the oral lesions were not followed by skin involvement, and the lag time between the onset of illness and the final diagnosis in five PV cases was prolonged, ranging from 4 to 7 years, probably due to the mild clinical presentation of the disease. Two trauma-related PV cases were documented; in one case, the blisters were located in a surgical scar and in the other in a burn scar. CONCLUSIONS: Our findings showed that pemphigus has a relatively high prevalence in eastern Sicily compared with other Italian regions; PV is the most common variant, and may have a mild course not always requiring aggressive therapy.

Adult↗

Transient leucoderma appearing in an untreated area following contact immunotherapy for alopecia areata.

One of the possible unwanted side effects following contact immunotherapy of alopecia areata is skin hypopigmentation, either in the form of a transient, post-inflammatory hypopigmentation or as the development of a persistent, depigmented patch. A case of leucoderma occurring on the forehead of a 16-year-old girl following application of squaric acid dibutylester to the scalp for the treatment of alopecia areata is described. Past medical and family history were negative for vitiligo and autoimmune disorders. The hypopigmented patch was distant from the scalp area where squaric acid dibutylester had been applied, and it was not preceded by any sign of eczema, erythema or itch in the same area. Moreover, it faded as soon as treatment was discontinued. A 4-year follow-up revealed no evidence of vitiligo. In conclusion, the possible occurrence of a transient leucoderma in untreated areas should be included among the side effects of contact immunotherapy of alopecia areata with squaric acid dibutylester.

Adolescent↗

Squamous cell carcinoma of the penis.

Penile tumors, although not frequent, represent a difficult diagnostic and therapeutic challenge. Of the malignant penile neoplasms, the most frequent is penile carcinoma, which includes squamous cell carcinoma and its well-differentiated variant, verrucous carcinoma. Current concepts about classification, epidemiology, pathogenesis, histopathology, diagnosis, staging, prognosis, and treatment are presented.

Carcinoma in Situ↗

Treatment of alopecia areata with squaric acid dibutylester.

BACKGROUND: Among contact allergens that are frequently used in the treatment of alopecia areata (AA), squaric acid dibutylester (SADBE) stands out for its good tolerability and its mild side effects. METHODS: One hundred and forty-four patients with AA of varying degrees were treated with SADBE. Of these, 71 had AA affecting less than 50% of the scalp, and 73 had a severe form, including 13 patients with alopecia totalis (AT) and two with alopecia universalis (AU). The patients were treated using both traditional and nontraditional methods. RESULTS: In the less severe form, we obtained a 80% rate of regrowth, compared to the 49% of the more severe form including 13 cases of AT and the two of AU. The failure rate was higher for patients with the more severe form (29%) compared to a 7% rate only for patients with mild AA. We also observed four cases of initial regrowth on the side of the scalp opposite to the site of application ('castling phenomenon'). Among those patients who were treated with application of SADBE on the right side of the back, three displayed regrowth on the left side of the scalp, (i.e., on the opposite side) and in an area distant from the site of application; for two patients the regrowth began on the right side of the scalp and one of them also displayed growth of fine hairs in the right dorsal region, the site of application of the compound. CONCLUSIONS: Our data further support the hypothesis of a systemic action of SADBE; however, further confirmation on a larger sample of cases is needed.

Adolescent↗