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Biomedical subjects

B Thiele

Publications and source records attributed to B Thiele.

At least 19 recordsLinked to original sources

Effects of methylprednisolone and 21-aminosteroids on mitogen-induced interleukin-6 and tumor necrosis factor-alpha production in human peripheral blood mononuclear cells.

The compounds U-74389G (16-desmethyl tirilazad) and U-74500A are two of the novel series of nonglucocorticoid 21-aminosteroids (or lazaroids) which mimic the high-dose neuroprotective pharmacology of the glucocorticoid methylprednisolone (MP) in the injured CNS. Despite structural analogies to MP, it has been shown previously for a variety of endpoints that lazaroids are devoid of classical glucocorticoid effects. Our objective here was to measure the immunosuppressive effects of these lazaroids directly. Specifically, we have compared the in vitro effects of MP, U-74389G, and U-74500A on the mitogen-induced cytokine production in human peripheral blood mononuclear cells, which is known to be very sensitive and perhaps the most clinically relevant parameter reflecting immunomodulation. We show that, in contrast to the glucocorticoid MP, both lazaroids at therapeutically relevant concentrations have no significant inhibitory effects on stimulated interleukin-6 and tumor necrosis factor-alpha production, neither via residual glucocorticoid receptor-mediated activities nor via direct physicochemical effects on cellular membranes. These results strongly support the view that lazaroids lack glucocorticoid activities, but rather exert their tissue protective effects via mechanisms that are independent of glucocorticoid-receptor binding.

Cells, Cultured

[Integration of prior knowledge in speech comprehension in relation to age].

In a first study we confirm the general evidence concerning the influence of implicit knowledge structures on sentence and text comprehension. In addition the results suggest a differentiation in the availability of prior knowledge. The level of activation is dependent on the type of semantic relations between prior knowledge and the explicit sentence information. This result can be explained by a theoretical framework in which different levels of cognitive effort can be related to activation or production of such relations. The main point of our second experiment is to prove the influence of aging on the process of knowledge integration mentioned above. We compared the results of a subject group of young (25 years) with old adults (75 years) in a recognition task. The experimental data support a slowdown for primarily sensorical and motorical and nonlexical components for the higher age group but they do not confirm a deficit in the critical process of knowledge integration. Finally we discuss a differentiation of such integration procedures dependent on demand of memory capacities (activation vs. operations) and the advantage of such a classification on identification of specific cognitive deficits.

Adult

Phenotypic investigation of mononuclear phagocytes by flow cytometry.

A simple and rapid method for the phenotypic analysis of mononuclear phagocytes is described. Using flow cytometry, surface markers, as well as intracellular antigens and DNA content of peripheral blood monocytes, or differentiated monocytic cells could be analysed. Furthermore, the method has been of use in several species and is therefore not restricted to applications in humans. Different modes of data acquisition and analysis were compared and are discussed.

Antibodies, Monoclonal

The influence of methylprednisolone on the energy metabolism of Ehrlich ascites tumour cells.

Using Ehrlich ascites tumour cells, the short-term effects of the therapeutic glucocorticoid Methylprednisolone (MP) on the cellular energy metabolism were studied. ATP-consuming processes involved in the rapid MP effects were identified indirectly from the effects of MP on cellular oxygen consumption related to the inhibition of respiration by selective inhibitors of Ca(2+)-ATPase and protein synthesis. The effects of MP on plasma membrane permeability for Ca2+ ions and phospholipid turnover were studied directly by using confocal laser scanning microscopy and tracerkinetic measurements, respectively. MP inhibited cellular oxygen consumption, suppressed the inhibitory effect of lanthanum but not that of cycloheximide on oxygen consumption, blocked the [Ca2+]i rise in response to calcium ionophore A 23187, and decreased phospholipid turnover. MP acted instantly in a dose-dependent manner. The observed effects of MP are discussed in relation to the hypothesis that the drug has direct membrane effect affecting plasma membrane permeability and function.

Adenosine Triphosphate

Dextran sulphate induces a PKC and actin independent internalisation of CD4.

Internalisation of CD4 is a well-known phenomenon. It occurs in the presence of phorbol myristate acetate (PMA), TPA or gangliosides and is usually completed within 30 min. Here, we describe an internalisation of CD4 molecules induced by low concentrations of high molecular weight dextran sulfate (M(r) 500 kDa) which differs from the classical mode in several ways. Internalisation is demonstrated by flow cytometry after simultaneous and consecutive staining of extracellular and internalised CD4 molecules and by visualisation by electron micrographs. A simple blockage of antibody binding sites on the CD4 molecule (epitope masking) by DS500, as widely believed, is definitely not responsible for the observed effects. DS500-mediated internalisation is a slow and energy-dependent process, where CD4 but not CD 2, 3, 8, 16, 56 and HLA-DR molecules are involved. The reaction reveals a characteristic time and concentration dependency. It does not require activation of protein kinase C (PKC) and cannot be inhibited by cytochalasin D. These results provide some more insight in the behavior of CD4 on lymphoid cell surfaces in response to high molecular weight polyanions such as dextran sulfate.

Actins

Modulation of cytokine expression by hypericum extract.

The effect of hypericum extract LI 160 on the stimulated cytokine expression was investigated in vitro in a whole blood culture system. Blood samples were taken from five healthy volunteers and four depressive patients. The release of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) was measured quantitatively after an incubation time of 24 hours on microtiter plates. A massive suppression of the interleukin-6 release was found for PHA-stimulated hypericum extract. Possible relations to the antidepressive effects of hypericum extract are discussed.

Antidepressive Agents

[Photodynamic therapy of eyelid basalioma after topical administration of delta-aminolevulinic acid].

Delta-aminolevulinic acid (ALA) induced Protoporphyring IX photodynamic therapy (PDT) is a new method in the therapy of cutaneous malignancies. Topical application prevents photosensibilization of normal skin. Promising results in the treatment of superficial basal cell carcinomas have been reported. To evaluate the efficiency of this method in the therapy of basal cell carcinomas of the lid, 10 patients were treated by PDT 5 h after application of ALA. The lesions were irradiated by an argon-ion-laser-pumped dye laser at a wavelength of 630 or 635 nm and at cumulative radiant exposures of 50 and 100 J/cm2. After 5-8 weeks follow-up, the basal cell carcinomas were excised to assess histologic changes. In the first few days after PDT the lesions seemed clinically to regress, due to erythematous swelling, but after a few weeks all tumours showed the same configuration they had before irradiation. Histological examination revealed small areas of necrotic cells in all irradiated basal cell carcinomas, surrounded by residual tumour formations. The reason for the poor results may be limited penetration of ALA or light. Although ALA-induced Protoporphyrin-IX PDT is a promising approach in the therapy of dermal lesions, it is not yet an acceptable alternative method in the treatment of basal cell carcinomas of the lid.

Administration, Topical

The recognition of UV-irradiation melanocyte with HMB-45 monoclonal antibody.

Monoclonal antibody HMB-45 was previously thought to be melanoma specific antibody and was taken recently as a marker for melanocyte proliferation or activation. A single UV-irradiation system which may induce a functional activity change in melanocytes was used to test the irradiated epidermal melanocyte for expression of HMB-45. Melanocytes, in the epidermis of the biopsies taken 7 days after a single UV exposure, showed markedly stained HMB-45, accompanied by morphological changes such as enlarged size, rich cytoplasma and elongated dendrites. We conclude that since morphological changes in irradiated melanocytes may be interpreted as signs of functional activity changes, melanocytes are exposed to stimulatory factors induced by UV light and get into a functional activating state to produce melanosome and HMB-45 antigen. Besides, the presence of HMB-45 in a single UV exposed epidermal melanocyte may support the hypothesis that its expression is inducible and is closely related to the functional activity of melanocyte.

Adult

Influence of phospholipid liposomes (PLL) on UVB-induced erythema formation.

Application of liposomal phospholipids (Natipide II) caused a significant decrease in erythema induced by UVB (280-312 mm) in patients with skin types II and III (n = 31). In accordance with findings in other organs, e.g. liver, the present findings suggest that phospholipids are capable of reducing H2O2 formation and/or increasing glutathione synthesis in human skin, thus reducing erythema formation by preventing oxidative stress.

Adult

Development of a Langerhans cell phenotype from peripheral blood monocytes.

Epidermal Langerhans cells (ELC) are definitively primed to differentiate into dendritic cells (DC). It is unknown at what stage of monocyte development this priming occurs. In a culture system characterized by low paracrine stimulation, i.e. Iscove's modified Dulbecco medium (IMDM) with 2% FCS, we tested the ability of peripheral blood monocytes to turn to the route of the LC-DC lineage. In this system monocytes did not develop significant yeast cell phagocytosis, although mannose receptors were available. However, they became strong stimulators of mannan specific T cell proliferation. Phenotype development was analysed by flow cytometry using the monoclonal antibodies OKT6 (CD1a), IOT2 (HLA-DR), IOM2 (CD14) and the ligand Man-BSA-FITC. CD1a was the first marker which distinguished cultured monocytes from developing macrophages, obtained by addition of 8% human serum. Like cord blood Langerhans cells (CBLC) they internalized OKT6 in deep coated pits. They maintained a phenotype of monocyte derived Langerhans cells (MoLC) during eight days of in vitro culture, expressing CD1a, mannose receptors and HLA-DR and decreasing CD14, if left in their own conditioned medium. MoLC could be converted into macrophages by addition of human serum only within the first four days in vitro. Our data suggest that monocytes acquire an LC phenotype by autocrine stimulation.

Antigens, CD

[Scabies norvegica sive crustosa in a patient with AIDS].

We report the case of a 20-year-old homosexual man with HIV-1 infection presenting with AIDS. An erythemato-squamous, papulo-crustous, non-itching dermatosis of 4 months duration was finally diagnosed as Norwegian scabies in the immunosuppressed. For clinical and epidemiological reasons the high contagiosity of this rare entity requires an appropriate therapy without delay.

AIDS-Related Opportunistic Infections