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Biomedical subjects

A Nikkels

Publications and source records attributed to A Nikkels.

11 recordsLinked to original sources

[Cutaneous melanomas, a spectrum of emerging cancers in women of Wallonia. Outlook by the Mosan Study Group of Pigmented Neoplasms].

The Mosan Study Group of Pigmented Neoplasms was founded about 15 years ago. It has collected more than 20,000 cutaneous malignancies including melanomas and basal and squamous cell carcinomas. The incidence of these cancers is on the rise in Wallonia. In particular, malignant melanomas represent a spectrum of emerging cancers characterized by a proteiform biological outcome. They mostly affect young women. The major risk factor appears to be iterative and unwise ultraviolet exposures. The prevention of melanomas is basically founded on such a dogma and accordingly relies on sunscreens. However, controversies about their beneficial effects are rife and fueled by axiomas and contradictory sophisms. At the exception of surgery, the therapeutic options for the diverse types of melanomas do not yet fulfill the scope of evidence-based medicine.

Carcinoma, Squamous Cell↗

Purification and characterization of a 315 kDa keratinolytic subtilisin-like serine protease from Microsporum canis and evidence of its secretion in naturally infected cats.

A keratinolytic protease, secreted as the major component by a feline clinical isolate of Microsporum canis cultivated in a minimal medium containing cat keratin, was purified by affinity chromatography on bacitracin agarose and gel filtration. The apparent molecular mass of the enzyme was 31.5 kDa and the pI was 11.8. The enzyme was not glycosylated and its first 15 N-terminal amino acids showed numerous similarities with other fungal subtilisins. The optimum pH was around 9 while inactivation of the enzyme was reversible at pH 4, but not at pH 11. The enzyme was stable at 37 degrees C with an apparent optimum temperature around 55 degrees C. PMSF, soybean trypsin inhibitor (SBTI) and chymostatin strongly inhibited the proteinase. The highest affinity (Km of 0.37 mM) and physiological efficiency (k(cat)/Km) were obtained for the synthetic substrate N-Suc-Ala-Ala-Pro-Phe-p-nitroanilide. These results indicate that the keratinase belongs to the subtilisin-like serine protease family. Purified rabbit immunoglobulins G prepared against the keratinase and used in an immunohistochemical test allowed the detection of the keratinase produced by the fungus invading hair structures in naturally infected cats. The in vitro keratinolytic activity of the enzyme and its production in vivo suggest that it may contribute to pathogenicity.

Amino Acid Sequence↗

Naevocyte triggering by recombinant human growth hormone.

The influence of growth hormone and insulin-like growth factor I on human melanocytes is being increasingly recognized. Clinical evidence has shown that when recombinant human growth hormone (hGH) is administered to children of short stature, the growth of melanocytic naevi is boosted. This study was conducted on 56 hGH-triggered naevi and nine similar lesions excised before or after hGH therapy for hypopituitarism and Turner's syndrome. A series of 40 naevi excised from age-matched healthy children served as controls. Atypicality of naevocytes was investigated using image analysis, AgNOR counts, immunohistochemistry (HMB-45, NKI-C3, Ki-67, anti-bcl-2-oncoprotein), and DNA flow cytometry. The data associate hGH treatment with anisokaryosis and increased AgNOR and Ki-67 counts in naevocytes. The same cells also show abnormal patterns of HMB-45 immunolabelling. These indications of naevocyte activation were not suggestive of malignant transformation. hGH-triggered melanocytomas should be added to the list of atypical melanocytic naevi. The long-term evolution of these lesions remains unknown and the potential risk of malignant transformation awaits careful evaluation.

Adolescent↗

Varicella-zoster virus latency in the adult rat is a useful model for human latent infection.

A model of latent infection by varicella-zoster virus (VZV) was obtained in the adult rat. Inoculation of VZV-infected cells in the skin led to infection of the peripheral nervous system. Latency was characterized by a long-lasting presence of the viral genome, of selected viral gene transcripts, and of at least one viral protein in the dorsal root ganglia. Reactivation has not been obtained in vivo, but has occurred ex vivo after repeated stresses. Many similarities with VZV latency in humans were found, making this model useful for vaccine and antiviral studies.

Animals↗

Detection of human papillomaviruses in paraffin-embedded biopsies of cervical intraepithelial lesions: analysis by immunohistochemistry, in situ hybridization, and the polymerase chain reaction.

One hundred and forty biopsies with an initial diagnosis of cervical intraepithelial lesion (CIL) were tested for the presence of human papillomavirus (HPV) by immunohistochemistry and in situ hybridization using commercial biotinylated probes (Vira-Type in situ assay; Digene Diagnostics, Silver Spring, MD) or probes labeled with digoxigenin by the random primer technique. Immunohistochemistry was more inferior to the in situ hybridization method, with a detection rate of 14% (20/140) compared to 61% (86/140) for the in situ assay with the digoxigenin-labeled probes. Biotinylated probes proved to be slightly less sensitive than digoxigenin-labeled probes, with a detection rate of 53% (74/140). Although less sensitive in our series taken as a whole, immunohistochemistry was positive in a few cases of CILs negative by in situ hybridization, so that the association of these techniques gave the highest detection rate (66%; 92/140). The CILs that remained negative with these methods (34%; 48/140) were investigated by the polymerase chain reaction (PCR) using consensus primers to determine definitively the presence of HPV in these lesions and were reviewed histologically to assess the diagnosis of CILs. The PCR method increased the detection rate of HPV in our series to 76% (107/140). The diagnosis of CILs was confirmed for all the biopsy specimens positive by PCR (15/15; 100%) and for all the HPV negative tissues with histological features of a high-grade lesions (7/7; 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis.

BACKGROUND: We studied the immunopathologic characteristics of five cases of toxic epidermal necrolysis by using a large panel of antibodies. OBSERVATIONS: The pattern and amount of the inflammatory cell infiltrate varied according to the stage of the disease. The main constant feature was the prominent involvement of the monocyte-macrophage lineage, including factor XIIIa+HLA-DR+ dendrocytes and CD68+ Mac 387+ macrophages, before and during the epidermal necrosis. The number of CD4+ and CD8+ lymphocytes was comparatively small. This was associated with a dense labeling of the epidermis for tumor necrosis factor alpha. CONCLUSIONS: Cells of the monocyte-macrophage lineage largely outnumber lymphocytes in the lesions of toxic epidermal necrolysis. Tumor necrosis factor alpha is likely a major cytokine that is responsible for necrosis.

Adolescent↗

Dermal dendrocytes and photochemotherapy.

We studied the fate of dermal dendrocytes in patients treated with psoralens and ultraviolet light by combining immunohistochemistry and computerized image analysis. Factor-XIIIa-positive dermal dendrocytes were found to be altered in these patients. When compared with controls, dermal dendrocytes were often increased in number and had an uneven size and tissue distribution. Their cytoplasm was occasionally fragmented. These changes were more pronounced when early photosclerosis was present. The alterations described probably reflect vascular changes, and may be responsible for immunomodulating actions and disorder of the connective tissue structure induced by ultraviolet light.

Adult↗

Comparative morphometric study of eruptive PUVA-induced and chronic sun-induced lentigines of the skin.

Computerized image analysis was used to compare lentigines (brown freckle-like cutaneous spots) induced by treatment with psoralens and ultraviolet light A (PUVA-induced lentigines) with those induced by solar exposure (actinic lentigines). For these conditions, which appear to be distinctive clinically and histologically, the number, size and shape of the macules were analyzed, revealing significant differences in the two latter parameters. This indicates that UV irradiations of different wave lengths act differently on melanocytes and/or on the interrelation between melanocytes and keratinocytes. The overall effect is much more self-limited in PUVA lentigines than in actinic lentigines, suggesting that the pathophysiology of these lesions is probably different.

Humans↗