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Biomedical subjects

P Stoebner

Publications and source records attributed to P Stoebner.

At least 19 recordsLinked to original sources

Ultraviolet AI exposure of human skin results in Langerhans cell depletion and reduction of epidermal antigen-presenting cell function: partial protection by a broad-spectrum sunscreen.

BACKGROUND: Ultraviolet (UV) B-induced effects on the skin immune system have been extensively investigated, but little is known regarding the immunological changes induced by UVA exposure of human skin. Recent data assessing the protection afforded by sunscreens against photoimmunosuppression stress the need for broad-spectrum sunscreens with an adequate UVA protection. OBJECTIVES: The purpose of this study was first to determine the changes observed in epidermal Langerhans cells (ELC) density and epidermal antigen-presenting cell (APC) activity after exposure of human skin to UVAI (340-400 nm) radiation, and secondly to assess the immune protection afforded in vivo by a sunscreen formulation containing a long wavelength UVA filter with a low UVA protection factor (UVA-PF = 3). METHODS: Epidermal cell (EC) suspensions were prepared from skin biopsies 3 days after exposure to a single dose of UVAI (either 30 or 60 J cm(-2)). RESULTS: Flow-cytometric analysis of EC suspensions revealed that exposure to 60 J cm(-2) UVAI resulted in a decreased number of ELC without infiltration of CD36+ DR+ CD1a- antigen-presenting macrophages into the epidermis, and a significant reduction of HLA-DR expression on viable ELC. In vivo exposure to both 30 and 60 J cm(-2) resulted in a decreased allogeneic CD4+ T-cell proliferation induced by UVAI-irradiated ECs. The sunscreen application partially prevented (57 +/- 9%) the decrease in epidermal allogeneic APC activity induced by 60 J cm(-2) UVAI. CONCLUSIONS: In vivo UVAI exposure of human skin results in a decreased number of ELC and in a downregulation of epidermal APC activity. This last effect is partially prevented by prior application of a sunscreen with a low UVAI-PF value. These results indicate that increasing the absorption of UV filters for long UVA wavelengths may lead to an improved immune protection.

Adult↗

[Extensive primary cutaneous mucinosis associated with refractory anemia with excess of blast].

BACKGROUND: We describe an original case of a primary cutaneous mucinosis, associated with a refractory anemia with excess of blast. CASE REPORT: A 65 year-old female consulted for erythematous-purple blush reticulated and large plaques that progressively developed on the trunk and limbs. Biopsies showed abundant dermis mucin deposits with a perivascular lymphocytic infiltrate. The epidermis was normal. Laboratory evaluation showed refractory anemia with excess of blast, associated with cytogenetic abnormalities. After two years course, the progressive aggravation of the myelodysplastic syndrome was associated with a progressive extension of the cutaneous mucinosis. DISCUSSION: This is the first report of an atypical primary diffuse and extensive cutaneous mucinosis. Primary cutaneous mucinosis may be associated with systemic diseases. To our knowledge, the association with refractory anemia with excess of blast has not been described previously. Mucine deposits may be considered as a consequence of neutrophilic dysfunction that are observed in myelodysplastic syndromes.

Aged↗

Morphometric analysis of the peripheral nerve: advantages of the semi-automated interactive method.

A semi-automated interactive method (BIOCOM) was developed for the morphometric analysis of the peripheral nerve in routine histopathological examination. The human superficial peroneal nerve was used for myelinated fibre measurements. The precision and reproducibility of the results were validated using a manual morphometric method on a digitalizing table. Having compared the two methods, we believe that the semi-automated method constitutes an interesting alternative to traditional methods.

Humans↗

Herpes simplex virus ICP0 and ICP4 immediate early proteins strongly enhance expression of a retrovirus harboured by a leptomeningeal cell line from a patient with multiple sclerosis.

A leptomeningeal cell line (LM7) harbouring an unknown retrovirus was recently isolated from the cerebrospinal fluid of a patient with multiple sclerosis. However, spontaneous expression of the LM7 retrovirus in this primary culture is quite low. We present results showing that in vitro infection of LM7 cells with herpes simplex virus type 1 (HSV-1), but not that of control cells, results in (i) potent stimulation of the specific reverse transcriptase (RT) activity detected in the culture supernatant and (ii) co-expression of both typical HSV-1 virions and abundant retrovirus-like particles. Transfection of LM7 cells with plasmids expressing HSV-1 immediate early (IE) ICP0 and ICP4 proteins produced a similar enhancement of RT activity in culture supernatants with retrovirus-like particles being identifiable by electron microscopy. These effects were not observed with a plasmid expressing ICP27 or with the parental plasmid in LM7 cells, nor with any of these four plasmids in control cells. These results show that HSV IE trans-activating proteins strongly enhance the expression of the latent retrovirus present in LM7 cells. The possible role in vivo of herpesviruses as 'triggering' cofactors in the retrovirus hypothesis for multiple sclerosis aetiology is also discussed.

Arachnoid↗

Enhanced chemiluminescence: a high-sensitivity detection system for in situ hybridization and immunohistochemistry.

The breakthrough of chemiluminescence in the field of solution immunoassays and transfer membranes prompted us to explore whether a light-based detection system could provide a gain in sensitivity over chromogenic and FITC markers for nucleic acid and protein detection on histological preparations. A Hamamatsu device and an enhanced chemiluminescence (ECL) luminol substrate of the peroxidase were used to detect epithelial and endothelial components by immunohistochemistry (IHC) and for in situ hybridization (ISH) of papilloma virus DNA. The accuracy of the signal was compared to that obtained with DAB-peroxidase, silver-enhanced DAB-peroxidase, NBT-BCIP-alkaline phosphatase, and FITC. Our results demonstrated the feasibility and high sensitivity of luminescence detection for histological preparations. In part due to the ultrasensitive videocamera and photon-counting imaging, interpretable and reproducible results were obtained within counting times shorter than 5 min, and with dilutions of the primary antibodies 100- to 10,000-fold greater than those used for chromogenic and FITC reactions. As for ISH, with identical concentrations of the HPV 18 DNA probe on HeLa cells, labeling was apparent by luminescence but undetectable with the chromogen. The morphological resolution allowed a discriminatory analysis of the signal. Therefore, at the light microscopic level, enhanced chemiluminescence offers an appealing alternative to FITC and chromogenic markers for detection and quantification of low-concentration molecules.

Antibodies, Monoclonal↗

[Cutaneous lesion associated with multiple endocrine neoplasms type 2A (Sipple's syndrome). An early clinical marker].

We report the association of a cutaneous lesion with multiple endocrine neoplasia type 2A (MEN 2A) in three patients from a French family. These lesions are very similar to those previously described in an Italian and an American MEN 2A family and called cutaneous lichen amyloidosis. In all three families the patients presented with a pruritic and pigmented cutaneous lesion localized unilaterally on the upper back. However, in the French family the patients also complained of paroxysmal pain in the same area, in which we could elicit a touch hypoesthesia and pain hyperesthesia. Such an association of cutaneous and neurological features in the upper back is known as Notalgia Paresthetica (NP). NP is believed to represent a neuropathy of the posterior dorsal nerve rami. Unlike the two previously reported families, the histological, immunohistochemical and ultrastructural analysis of the skin biopsies of the French patients did not show any amyloid material. This suggests that the presence of amyloid may not be a constant feature of the cutaneous lesions associated with MEN 2A. We consider these lesions as a form of dorsal neuropathy rather than a cutaneous lichen amyloidosis. Whatever their origin, these cutaneous lesion usually precede the appearance of the neoplastic lesions of MEN 2A. They may act as an early clinical marker that must be searched for in each subject at risk for MEN 2A. In addition, all patients presenting with NP should be screened for MEN 2A.

Adrenal Gland Neoplasms↗

Basal cell (basaloid) carcinoma of the lung: a new morphologic and phenotypic entity with separate prognostic significance.

On review of 115 poorly or undifferentiated lung cancers from 671 lung tumors resected over a 7-year period, we have found 38 cases of basaloid carcinoma. The cardinal histopathologic features distinguishing this tumor from other non-small cell lung cancers are a lobular growth pattern of small cells with moderately hyperchromatic nuclei, with no prominent nucleoli, and with scant cytoplasm, a high mitotic rate, and peripheral palisading. Basaloid carcinoma was present in a pure form in 19 cases and the other 19 tumors were of a mixed, but prominent, basaloid type associated with squamous cell carcinoma, large cell carcinoma, or adenocarcinoma. The immunophenotype of basaloid cancers was close to that of basal bronchial epithelial cells, with a low level of expression of low molecular weight cytokeratins. Staining for neuroendocrine markers was infrequent and inconsistent. Ultrastructural study showed an absence of neurosecretory granules and the presence of some squamous and/or glandular differentiation. This morphologic and immunologic phenotype suggests that basaloid carcinoma is derived from a pluripotent reserve cell or a basal bronchial epithelial stem cell. This unique histologic form of lung tumor has a poor prognosis, with a median survival rate of 22 months for stage I and II disease. This justifies classification of basaloid carcinoma as a distinct form of lung cancer, separate from small cell lung carcinoma.

Adult↗

Ultrastructural localization of the major components of the extracellular matrix in normal rat nerve.

In this study we determined the ultrastructural distribution of the various components of the extracellular matrix (laminin, fibronectin, Type I, III, and IV collagens) of the normal peripheral nerve in adult rat. The localization of these macromolecules was investigated in basement membranes as well as in different areas of epi-, peri-, and endoneurium, by use of a pre-embedding immunoperoxidase method.

Animals↗

Thymolipoma in association with myasthenia gravis.

A 52-year-old male presented with an anterior mediastinal tumor associated with a 2-year history of myasthenia gravis. The patient underwent thymectomy and a 185-g, 10 X 8 X 3.5 cm, well-delineated tumor was resected. On histologic examination the tumor proved to be a thymolipoma composed of mature adipose elements containing cords and nests of thymic tissue. The latter consisted mainly of cortical areas, the thymocytes of which displayed an immunohistochemical profile of cortical cells, i.e., CD 1+, CD 4+, CD 8+, and frequently Ki 67+. Ultrastructural study confirmed the predominant cortical differentiation of the thymic component. No germinal centers, dendritic reticulum cells, or myoid cells were detected by histologic, immunohistochemical, and ultrastructural studies. The association of thymolipoma with myasthenia gravis is rare; this case is the 10th reported. Our findings lead us to believe that (a) the cortical differentiation of the thymic component and the active thymocyte proliferation could represent a factor leading to myasthenia gravis; and (b) thymolipoma could be a peculiar form of thymoma rather than a mixed tumor of mesenchymal and entodermal origin, a lipoma, or a hamartoma of the thymic gland. The reported association of thymolipomas with other immune disturbances or with neoplastic conditions usually associated with true thymomas support these findings.

Antibodies, Monoclonal↗

Melanin in the inner ear. An experimental study with control and kanamycin-intoxicated colored guinea-pigs.

Following several studies on the effects of kanamycin toxicity on the inner ears of guinea pigs, we have studied the importance of melanin in this phenomenon. Transmission electron microscopy showed that, under the influence of kanamycin, the intermediate strial cells developed a secretory aspect similar to that seen in skin melanocytes. This aspect as yet has never been described for the inner ear cells. A planimetric, morphometric method was also used to determine the strial cell melanin status in control animals. Additional findings in the study confirmed an increase in the number of melanosomes during kanamycin poisoning. Statistical data are discussed.

Animals↗

Microangiopathy of endoneurial vessels in hypoxemic chronic obstructive pulmonary disease (COPD). A quantitative ultrastructural study.

A peripheral neuropathy has been reported in patients with chronic respiratory insufficiency due to chronic obstructive pulmonary disease (COPD). It is mainly characterized by axonal degeneration, secondary demyelination and abnormal endoneurial vessels. The pathogenesis of these lesions remains obscure. To investigate whether relationships exist between neuritic and vascular lesions, a qualitative and quantitative ultrastructural study was performed on nerve biopsies in 13 patients with chronic respiratory insufficiency due to COPD, and in 9 normal controls without pulmonary lesions. A computer-assisted multiple regression analysis taking into account clinical, electrophysiological, biological and morphometric parameters was performed. Statistically significant differences in the endoneurial structure of microvessels were: (1) thickening of the basement membrane; (2) narrowing of the lumen; (3) mural pericytic debris deposits, occurring in the COPD group. In the latter, hypercapnia correlated positively with nerve fibers lesions (P = 0.03) and endothelial area (P = 0.03). No correlations were found between age and other parameters. These findings highlight the fact that the microangiopathy in peripheral nerves in patients with COPD may be diffuse and essentially due to hypoxia and reduction in blood flow, as in diabetic neuropathy.

Aged↗

There is no simple adequate sampling scheme for estimating the myelinated fibre size distribution in human peripheral nerve: a statistical ultrastructural study.

Morphometric studies of peripheral nerves (PN) usually involve some sampling of the myelinated fibres (MF). In order to scrutinize the statistical properties of the sampling processes in common use and the reliability of the resulting estimates, a quantitative analysis of human superficial peroneal nerves from 8 different normal subjects was undertaken at the ultrastructural level, both in terms of MF spatial distribution and of their size distribution. This study used sampling rates involving more than 10% of the whole myelinated fibre population observed in each nerve fascicle. However, in nearly all the fascicles evaluated, the sampling fluctuations are so high that neither the number of axons nor their diameter distribution can be assessed with enough accuracy. A systematic study of the myelinated fibres shows that the spatial distribution of their size is not uniform. This marked heterogeneity in the MF size distribution imposes measurement of large enough samples (500 or 600 MFs usually represent about one-half or two-thirds of the whole MF population) in a way to secure a reliable enough estimate of the density and size distributions. However, the practical usefulness of sampling schemes requiring more than one-half of the whole MF population in a nerve fascicle, is questionable.

Adult↗

[Lipoblastic liposarcoma of the lung. Ultrastructural study of a case].

A case of fatal lipoblastic pulmonary liposarcoma in a 20 year-old female is reported. A thoracotomy was performed but failed to yield the pathological diagnosis. This diagnosis was obtained by ultrastructural study of a cerebral metastasis. To our knowledge, only seven cases of pulmonary liposarcoma have been previously described in the literature and the lipoblastic aspect was never mentioned.

Adult↗