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Biomedical subjects

W Eberhardt

Publications and source records attributed to W Eberhardt.

At least 109 records · Page 6Linked to original sources

K+ ion regulation in retina.

During onset and offset of illumination, considerable changes in extracellular K+ concentration ([K+]c) occur within particular retinal layers. There are two ways in which glial cells may control [K+]c: (1) by space-independent processes, for example, by K+ uptake due to the Na(+)-K+ ATPase, and (2) by space-dependent processes, that is, by spatial buffering currents flowing through K+ channels. Rabbit retinal Müller (glial) cells were studied for expression of mechanisms supporting both kinds of processes. This review demonstrates that rabbit Müller cells have Na-K pumps whose distribution and properties are highly adapted to meet the needs of efficient K+ clearance. Furthermore, spatial buffering currents through specialized K+ channels of Müller cells greatly accelerate retinal K+ clearance during and after stimulation.

Animals↗

Ifosfamide in non-small cell lung cancer: a review.

In recent years, ifosfamide has proven to be one of the most effective cytostatic drugs in the treatment of non-small cell lung cancer. Single-agent studies have demonstrated response rates of 15% to 30%. Combinations containing ifosfamide together with one or two other cytostatic agents yield overall response rates of 30% to 45%, with 5% to 10% complete remissions. For this purpose, ifosfamide has proven to be an ideal constituent, especially since the routine use of mesna uroprotection has significantly reduced its toxicity. As myelosuppression is now the primary dose-limiting toxicity, further investigations are directed toward the question of whether adjuvant administration of hematopoietic growth factors can improve treatment results by allowing increased dose intensity. This seems to be particularly important in patients with malignancies that respond poorly to cytostatic chemotherapy to determine whether survival can be significantly prolonged. Further studies with ifosfamide, moreover, should include neoadjuvant investigations in patients with stages II and III disease or its combination with other treatment modalities.

Antineoplastic Combined Chemotherapy Protocols↗

Development of the rabbit retina. IV. Tissue tensility and elasticity in dependence on topographic specializations.

A method is introduced for the quantification of specific compliance and the elasticity of small pieces of living retinal tissue. These pieces are fixed at their margins by means of tissue glue, and loaded with a small iron spherule the bending force of which can be gradually enhanced by the action of an electromagnet. Retinal bending caused by such calibrated forces is measured by a horizontal light microscope, and used for estimations of specific compliance and elasticity of the tissue. Three different particular regions of the rabbit retina--periphery, visual streak, and (prospective) medullary rays--were tested at several post-natal developmental stages. From very early stages on (day 2 p.p.) up to adulthood the peripheral retina was found to be significantly more tensile than the two other central regions. This can be shown to depend greatly on the thickness of the tissue which is lower in the retinal periphery. During early post-natal development, all retinal regions except the (prospective) medullary rays become thinner. The tensility of the tissue increases, with the exception of the medullary rays which reduce their compliance strongly. In the adult retina, however, the tensility of all retinal regions is reduced as compared with the neonatal tissue. This seems to be caused by a constant gradual increase of the elasticity of the retina during development which, in turn, may be caused by several developmental parameters, e.g. the formation of synapses, the outgrowth of glial side branches ensheathing neighbouring neuronal cells, or a reduction in extracellular clefts. It is proposed that these differences in tensility between different retinal regions, may be the cause for differential retinal expansion driven by the intraocular pressure. Thus, simple mechanical features of the tissue may contribute to the formation of important topographic specializations of the retina, e.g. the visual streak as the site of highest visual acuity.

Aging↗

Laminin and basement membrane-associated microfilaments in wild-type and mutant Drosophila ovarian follicles.

The localization of the extracellular matrix glycoprotein laminin was studied using polyclonal anti-laminin antibodies. The laminin patterns of the basement membranes of the muscular epithelial sheath that envelops the ovariole were conspicuously different from those of the basement membrane of the follicular epithelium. In the latter structure laminin was stained in a pattern of parallel stripes oriented perpendicular to the long axis of the follicle; microfilament bundles at the adjacent basal side of the follicle cells have the same orientation. At late vitellogenic stages the orientation of the microfilaments remained the same while the laminin stripes were no longer visible. The orientation of laminin and F-actin was abnormal in follicles of the egg-shape mutant kugel, which produces shorter and thicker eggs than wild-type flies. This phenotype might result from the disturbance of the normal circular microfilament and/or laminin pattern.

Actin Cytoskeleton↗

Membrane ultrastructure preservation and membrane potentials after isolation of rabbit retinal glial (Müller) cells by papain.

Enzymatically isolated retinal glial (Müller) cells have been the subject of many electrophysiological studies. Local high membrane conductivities for potassium ions have been speculated to correspond with local occurrence of orthogonal arrays of intramembranous particles (OAP) observed in freeze-fracture replicas of retinal Müller cells in situ. We studied whether such OAP are preserved after enzymatic digestion of the retinal tissue which is necessary for isolation of living cells for electrophysiology. We found that strong papain digestion leads not only to disturbances in the cell's ultrastructure as seen in ultrathin sections but evokes both a redistribution of intramembranous particles and a disappearance of OAP as seen in the freeze-fracture replica. Furthermore, such isolated cells have low membrane potentials and lose their topographical specialization in K+ conductance. If, however, the retinae were exposed to papain as short as possible to get just some isolated cells, their cytoplasmic and membranous ultrastructure was preserved very well, and high resting membrane potentials were recorded in cells with marked regional specialization of membrane conductivity. Our results show that indeed sites of high K+ conductance may correspond with the occurrence of OAP, even in isolated cells.

Animals↗

Determination of the extracellular tortuosity in nuclear layers of the central nervous system by resistance measurements on a geometrical model.

The electrical resistivity of nuclear layers within CNS tissues is simulated by a densely packed array of glass spherules with a thin silver layer on their surfaces. Various mean spherule diameters and different thicknesses of the silver layer are tested; the relations between spherule diameter and thickness of silver mantle are in the same range as those between cell soma diameters and width of the extracellular clefts. Measuring the contribution of the silver layers to the total volume--corresponding to the extracellular volume fraction alpha within CNS tissues--and the resistance of columns of silvered spherules, tortuosity factors lambda 2 are calculated. Means of lambda 2 are found to vary within 5.6 and 9.2, independent of both spherule diameters and thickness of the silver layer, but strongly dependent on the packing density of the spherules. This latter dependence is described by a simple formula. These results are used to calculate the resistivities of the nuclear layers of the retina and of the granular layer in the hippocampal area dentata, based on morphometric data gained from own studies and literature reports, respectively. It is shown that such layers with densely packed cells express very high resistivity because of both low extracellular volume fraction and high tortuosity. Implications for current source density analyses, and for pathological events like epileptogenesis, are discussed. In an appendix, an analytical solution of the problem is given for the case of a cubic array of surface-conducting spheres.

Animals↗

[Sequential induction chemotherapy and radiation treatment of inoperable small cell bronchial cancer. Results of a prospective randomized study].

To study the potential benefit of sequential chemotherapy in inoperable small cell lung cancer (SCLC), from 1982 to 1986 ninety-one patients with histologically proven and previously untreated SCLC (median age: 53 years; median Karnofsky status: 80%) were randomly assigned to an initial therapy with adriamycin (since 1984 epirubicin), cyclophosphamide, vincristine (ACO resp. EPICO) or etoposide/cisplatin (VP16/DDP). Treatment courses were repeated every 3 weeks for a total of less than or equal to 6 courses with a crossover after a maximum of 3 cycles of either regimen. Limited disease (LD) patients with bronchoscopical, computertomographical and (re-) mediastinoscopical complete remission (CR) randomly received either a thoracic irradiation with 40 Gy or observation only. Overall, 60 out of 85 evaluable patients achieved an objective remission. A CR was observed in 24/51 patients (47%) with limited disease, and in 8/34 patients (24%) with extensive disease. Both, ACO (EPICO) and VP16/DDP were equally effective as initial and second-line therapy. Moreover, after failure to the initial therapy an objective remission could be achieved in 13% of the patients following the alternative second line combination. In 28% of LD patients with an otherwise complete remission residual tumor was detected by (re-) mediastinoscopy. Median survival times were 14 (CR: 16) months in LD patients and 10 (CR: 15) months in ED patients. At present, median survival is significantly improved in irradiated versus non-irradiated LD patients (25 vs. 13 months, p less than 0.04). The remission rates and median survival times observed in this study are comparable to those of a historical control group treated with ACO plus radiotherapy alone.

Adult↗