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Biomedical subjects

T Horn

Publications and source records attributed to T Horn.

213 records · Page 12Linked to original sources

Alcoholic liver injury: defenestration in noncirrhotic livers--a scanning electron microscopic study.

The fenestration of hepatic sinusoidal endothelial cells in 15 needle biopsies obtained from chronic alcoholics without cirrhosis was studied by scanning electron microscopy. As compared to nonalcoholics, a significant reduction in the number of fenestrae and porosity of the sinusoidal lining wall (fractional area of fenestrae) was observed in acinar Zone 3, both in biopsies with and without Zone 3 fibrosis as judged by light microscopy. A significant reduction of porosity as shown in this study may influence the blood hepatocytic exchange and contribute to the alcohol-induced liver injury.

Biopsy, Needle↗

Subcellular distribution of urokinase and urokinase receptor in human neutrophils determined by immunoelectron microscopy.

A high-affinity receptor for urokinase-type plasminogen activator (uPAR) has been identified on the plasma membrane of a number of different cell types, and has been shown to be important for plasminogen activation, cell adhesion, and possibly signal transduction. uPAR and uPA cosediment with secretory vesicles and specific granules by subcellular fractionation and translocate to the plasma membrane upon activation of neutrophils. Here the subcellular distribution of uPAR and uPA is studied by electron microscopy of neutrophils using immunogold double labeling for uPAR and uPA and a set of markers for well-defined subtypes of granules: matrix metalloproteinase type-9 (MMP-9) for gelatinase granules, lactoferrin (LF) for specific granules, and myeloperoxidase (MPO) and neutrophil elastase (NE) for primary granules. With this technique uPAR colocalizes with uPA in 71% of labeled granules. In granules containing uPAR the degree of coexpression with MMP-9, MPO and NE was 19, 66, and 74%, respectively. In granules labeled for uPA the corresponding overlap with MMP-9, MPO and NE was 24, 64, and 51%, respectively. Low levels of co-localization were found for uPAR and LF (7%) and for uPA and lactoferrin (5%). The results indicate that uPAR and uPA are present in gelatinase granules and primary granules, but rarely in specific granules. The demonstration of uPAR and uPA in primary granules is of particular interest, and may indicate that uPAR and uPA participate in the activation of latent hepatocyte growth factor of neutrophils.

Biomarkers↗

Morphological effects of sodium fusidate (fusidin) on pancreatic islet cells: an electron microscopic study.

Fusidic acid has been shown to prevent the lymphocyte co-stimulatory activities of cytokines and seems--in preliminary trials--clinically effective as an immunoregulatory drug e.g. in insulin-dependent diabetes mellitus. A toxic effect of fusidic acid may however be suspected since a previous study showed a significant dilatation of rough endoplasmic reticulum in cultured pancreatic islet cells from normal rats. In this study we examined the ultrastructural effects of the sodium salt of fusidic acid (fusidin) on cultured rat islet cells (treatment period 3-5 days), and of islet cells from rats receiving fusidin for 6 days. Electron microscopically, fusidin treatment in vitro (3 to 30 micrograms/ml) showed a significant dilatation of the rough endoplasmic reticulum of islet cells. No dose dependent changes were found. In the in vivo model no changes were demonstrated in concentrations of fusidin up to 9.64 micrograms/ml of homogenated pancreatic tissue. It is concluded that treatment with fusidin gives no detectable ultrastructural changes in vivo.

Animals↗

Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ.

Surgical specimens from 62 patients with vulvar dysplasia and carcinoma in situ were morphologically investigated. Lesions were classified according to WHO (mild, moderate, severe dysplasia and carcinoma in situ) and according to Toki et al. (1991) (warty, basaloid, combined warty/basaloid or basaloid/warty types or mixed (warty, basaloid and simple) forms). Following the WHO classification, moderate dysplasia was shown in 4 cases, severe dysplasia in 47 and carcinoma in situ in 11 cases. Pure warty type was shown in 2 cases (both biopsy specimens). One case revealed pure simple dysplasia whereas no case of pure basaloid type was found. Various combinations of warty and basaloid types were shown in 52 cases and mixed forms in 7 cases. The results indicate that pure forms of warty and basaloid types probably do not exist. HPV DNA was detected by PCR in 51/58 cases (88%) (45 with HPV type 16 and 6 with HPV type 33) evenly distributed in all age groups and in all types of lesions (WHO and Toki et al. 1991). By ISH HPV was detected in 24/62 cases (39%) (21 with HPV type 16/18 and 3 with HPV type 31/33), nearly always in warty areas. All these cases were positive for the same virus type by PCR. No case revealed more than one type of HPV. HPV type 6, 11, 18, and 31 were not detected by PCR. The results indicate a correlation between HPV type 16 and 33 and dysplasia/carcinoma in situ in the vulva.

Adult↗

Interferon-gamma-dependent in vitro model for the putative keratin 17 autoimmune loop in psoriasis: exploration of pharmaco- and gene-therapeutic effects.

In 1999, A.S. Gudmundsdottir et al. have envisaged an epitope on keratin 17 (K17) as a putative psoriasis major autoantigen recognized by T cells. In a HaCaT keratinocyte model, we now demonstrate that IFN-gamma and to a less extent also TNF-alpha and TGF-alpha are able to induce K17 protein expression, in contrast to IL-1alpha, IL-1beta, IL-6, IL-8 and IL-18. This supports our hypothesis of an existing proinflammatory cytokine/K17 autoimmune loop as a presumptive positive feedback mechanism driving psoriasis etiopathogenesis. K17 overexpression was now found to also coincide with suppression of keratinocyte proliferation, e.g. induced by NF-kappa B inhibitors (Bay 11-7082 and Bay 11-7085), and thereby correlated hyperapoptosis to be encountered in psoriatic epidermis. Acitretin as an established antipsoriatic drug and the tyrosine kinase inhibitor imatinib decreased, whereas hydrocortisone as well as dexamethasone increased the IFN-gamma-induced K17 overexpression. The latter might be another mechanism explaining the well-known rebound phenomena after abrupt withdrawal of corticosteroids in psoriasis treatment. Finally, we defined a K17-directed and effective antisense oligodesoxynucleotide which may hold promise for future gene-therapeutic approaches in psoriasis.

Acitretin↗

Ultrastructural features of the interferon-treated adult laryngeal papilloma.

The ultrastructural features of the interferon-treated adult laryngeal papillomas are described. Compared with untreated papillomas, no differences in ultrastructure were found by transmission electron microscopy. By scanning electron microscopy, significant alterations comprising a smooth and oedematous surface with a uniform microvilli pattern of the superficial cells were observed after interferon therapy. Our observations suggest an increased cell adhesion and maturation of epithelial cells caused by interferon.

Adult↗

Ultrastructural features of the adult laryngeal papilloma.

The ultrastructural features of nine laryngeal papillomas of the adult type were examined by transmission and scanning electron microscopy. The surface was covered by numerous microvilli varying in size and shape and often arranged in parallel cords. Although we did not find virus-like particles, the ultrastructural characteristics of the adult type of laryngeal papilloma did not differ from those previously found on the juvenile type. The two types may in nature be one and the same lesion, differing in behaviour because of the different environments.

Adult↗

Lightmicroscopical features of interferon-alpha-treated laryngeal papillomatosis in adults.

Papillomatous tissue samples from 12 adult patients with laryngeal papillomatosis were examined by light microscopy before and after interferon-alpha (IFN) treatment. Increased atypia, a change in intra-epithelial differentiation, sclerosis of the underlying stroma and infiltration of especially plasma cells were found in tumour tissue removed after 3 weeks of IFN treatment. These morphological findings do not explain the effects exerted by IFN on the growth pattern of adult laryngeal papillomatosis, but provide a basis for further studies.

Adult↗

Solid and papillary neoplasm of the pancreas.

In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well as zymogenlike granules were demonstrated. Measurements of mean nuclear volume and volume-corrected mitotic index discriminated between SPN and well-differentiated ductal adenocarcinoma of the pancreas, with notably lower values being seen in SPN. Silver-stained nucleolar organizer region counts showed wide overlaps. The results suggest that SPN is a tumor with mixed endocrine and exocrine features. Its low malignant potential compared to ductal adenocarcinoma is reflected in the mean nuclear volume and volume-corrected mitotic index. The presence of estrogen receptors may prove therapeutically useful.

Adolescent↗

Iron particle-enhanced visualization of inflammatory central nervous system lesions by high resolution: preliminary data in an animal model.

BACKGROUND AND PURPOSE: The detection of cell infiltration is critical for the diagnosis and monitoring of inflammatory disorders, especially in the central nervous system (CNS). Superparamagnetic iron oxide (SPIO) particles have recently been introduced as a contrast agent to detect macrophage migration in vivo by MR imaging. We tested the hypothesis that focal hyperechogenicity due to SPIO-laden macrophages can also be visualized on high-resolution sonography. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced by myelin-oligodendrocyte glycoprotein (MOG) in congenic Lewis rats, an animal model mimicking many aspects of human multiple sclerosis. At the height of disease, rats underwent MR imaging with a 1.5T unit. Animals were injected with SPIO particles 24 hours before imaging. Control rats either received no contrast agent or were injected with SPIO particles without prior induction of EAE. Immediately after MR imaging, the rats were sacrificed, and the brains were removed and placed in saline. Sonography was performed directly after brain removal. Brains were embedded in paraffin, and sections were stained for iron with Perls stain and for macrophages with ED1 immunohistochemistry. RESULTS: SPIO-enhanced sonography of rat brains during a relapse of EAE specifically showed marked focal echogenicity in EAE-typical areas of the brain, including the periventricular region, the cerebellum, and the brain stem. The sonographic results corresponded to in vivo MR imaging findings of the respective animals as well to the clinical symptoms of EAE and to histology showing iron-laden macrophages in demyelinated lesions. CONCLUSION: SPIO particles allow the detection and demarcation of inflammatory CNS lesions on sonograms by specific macrophage imaging.

Animals↗