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Biomedical subjects

J Lindner

Publications and source records attributed to J Lindner.

At least 73 records · Page 4Linked to original sources

Experimental modification of postnatal cerebellar granule cell migration in vitro.

Histotypic migration of [3H]thymidine pulse-labeled granule cell neurons in cerebellar folium explants was monitored in the presence of antibodies to cell adhesion molecules and quantified by automatic image analysis. When explants were cultured in the presence of monovalent antibody fragments to cell adhesion molecules L1 and N-CAM, an inhibition of cell migration of 33.3 +/- 4.4% and 13.9 +/- 2.1%, respectively, was observed. In the presence of an equimolar mixture of monovalent antibody fragments to L1 antigen and N-CAM no additive effects in inhibition of cell migration were seen. Antibodies to the L2 carbohydrate epitope which is common to L1, N-CAM and other cell surface glycoproteins showed a similarly small effect on cell migration as antibodies to N-CAM. Monoclonal antibodies to cell surface antigen M2 and polyclonal antibodies to mouse liver membranes reacting with the surface of all cerebellar cell types did not alter the migratory behavior of granule cells. Cultivation of explants in the presence of neuraminidase, ganglioside binding toxins, as well as glycosaminoglycans and glycosaminoglycan degrading enzymes, also did not modify the extent of cell migration under the culture conditions used.

Animals↗

Malignant melanoma--its precursors and its topography of proliferation. DNA-Feulgen-cytophotometry and mitosis index.

DNA-content and size of the nuclear areas in different zones of malignant melanomas of different histological types and in dysplastic naevi were measured in order to provide information on the histogenesis and proliferative behaviour of human malignant melanoma. The results were compared with those from normal epidermis, common naevi, and reactive melanocytic hyperplasias. The mitotic index of melanomas--divided into different topographic zones in an analogous way--was also determined. The DNA-histographs of all naevi and reactive melanocytic hyperplasias showed a diploid maximum, but the dysplastic naevi had a larger proportion of nuclei with hyperdiploid and tetraploid DNA-content, indicating an increased proliferative activity. The mean values (X) of nuclear areas in dysplastic naevi (DN) were about the same as in common naevi (CN) and slightly lower than in superficial spreading melanomas (SSM). The coefficient of variability (cv) as an indicator of anisokaryosis was markedly higher in DN (27.8) and SSM (29.3) than in CN (20.2). In DNA-content we found similar results: almost no difference in mean values, but DN taking an intermediate position between CN and SSM with respect to cv (CN: 12.3; DN: 21.0; SSM: 36.6). There was no unequivocal evidence in these data for DN being a precancerous stage. Superficial melanomas with a nodular component ("SSM/NM") differed from SSM and NM by increased DNA-content and greater variability of nuclear areas and showed the clearest features of malignancy in their DNA-histographs. The mitotic indices had rather low values in SSM and intraepidermal marginal zones of "SSM/NM" on one hand and markedly higher values in NM and nodular parts of "SSM/NM" on the other. The highest mitotic counts were found in the three investigated metastases.

Cell Cycle↗

Modulation of granule cell migration by a glia-derived protein.

Cultured explants from early postnatal mouse cerebellum were used to examine the influence of a 43-kDa glia-derived neurite-promoting factor (GdNPF) on the migration of [3H]thymidine-labeled granule cell neurons. GdNPF, which is a potent serine protease inhibitor, significantly reduced the extent of granule cell migration in a dose-dependent manner. This effect could be neutralized by addition of thrombin, which binds GdNPF. Other protease inhibitors such as aprotinin, hirudin, soybean trypsin inhibitor, leupeptin, 6-aminocaproic acid, and D-Phe-Pro-ArgCH2Cl do not show this inhibitory effect. These results demonstrate that a glia-derived protein can regulate the migration of postmitotic neurons, an important cellular event in the development of the nervous system.

Animals↗

Histotypic pattern formation in cerebellar reaggregate cultures in the presence of antibodies to L1 cell surface antigen.

Reaggregate cultures of cerebella from 5-day-old C57BL/6J mice were cultured in the presence of Fab fragments of polyclonal antibodies against the cell surface adhesion molecule L1. Light microscopic examination showed that histotypic differentiation, as observed by the appearance of radially oriented glial processes and the sorting out of mature and immature neurons, was not affected by the antibody. Electron microscopic observation showed no effect on the synapse formation and the packing density of fasciculated neurites. These observations show that under the culture conditions used, L1 antibodies do not alter the particular cell interactions investigated in this study.

Animals↗

Cell type specificity and developmental expression of the L2/HNK-1 epitopes in mouse cerebellum.

The developmental expression of carbohydrate epitopes recognized by monoclonal antibodies HNK-1 and L2 was studied in tissue sections and cultures of mouse cerebellum. At all ages studied the 2 antibodies had identical staining patterns. In cultures of embryonic and early postnatal mice some, but not all cells of all 3 major neural cell types, neurons, astrocytes and oligodendrocytes, but not fibronectin-positive fibroblast-like cells were labeled by the antibodies. The most intensely labeled cells were those with antigenic marker profiles characteristic of immature glia. L2/HNK-1 epitope expression on neuron precursors was detected most convincingly in sections, where the band of migrating granule cell precursors in the external granular layer of the embryo and outer part of the external granular layer at early postnatal ages were strongly labeled by the antibodies. In sections of adult cerebella an overall reduced, but detectable level of L2/HNK-1 epitope expression was seen in all layers, but slightly more prominently in granular layer and white matter. At embryonic ages ventricular cells did not express detectable levels of epitopes. Most of the present data support the notion that the L2/HNK-1 epitopes are most strongly expressed on cell types with properties of glial and neuronal precursor cells.

Animals↗

New morphological and biochemical aspects of atherosclerosis.

According to morphological and biochemical findings, disturbances of metabolism (turnover) and function of smooth muscle cells and proteoglycans/GAG are decisive for the development of early and progressive atherosclerotic changes. The feedback dependencies between the smooth muscle cells and the components of the extracellular substance demonstrated, permit to call primary target points of atherogenic injuries of al constituents of this regulating circle system. If the increased turnovers of the arterial components do not return to a normal equilibrium, the result is hyperplasia of the cellular and intercellular constituents. The early atherosclerotic lesions can progress or relapse. In late and regressive lesions, the cell content as well as the anabolic and esp. the catabolic processes decrease. There result scars rich in collagen fibres and poorer in cells, ground substance, and elastin. The healing of atherosclerotic lesions can take place in any stage, the later the more difficult and insufficient. Disturbances of the fat metabolism, the own synthesis, and the intake of substances by smooth muscle and hematogenic cells are secondary sequels of the primary early atherosclerotic alterations and might be regarded as metabolic lesion of the smooth muscle cells. Other secondary and tertiary processes (calcification, fibrous degeneration, esp. of elastin) support the hypothesis that the early atherosclerotic lesions and their progress may finally start and perpetuate a metabolic insufficiency of the arterial wall.

Animals↗

Specificity of histiotypic organization and synaptogenesis in reaggregating cell cultures of mouse cerebellum.

The fine structure of reaggregating cultures of cells from 6- to 7-day-old mouse cerebellum was studied at intervals between 3 and 21 days in vitro (DIV). The resulting aggregates consisted mainly of small neurons (granule, stellate and basket cells), neuroglial cells and their processes. Large neurons were rarely present. By 7 DIV the previously loosely packed components had tightened into a more compact mass. A peripheral plexiform layer had formed which had many fine axons arranged into fascicles of parallel fibers. Deep to this zone was a cellular region containing clusters of neurons interspersed with small areas of neuropil. Axosomatic synapses appeared on neurons which resembled stellate or basket cells but not on granule cells. Axo-dendritic synapses formed in the neuropil of the cellular zone and, less frequently, in the outer plexiform layer. After 3 weeks glial cell processes had increased in volume at the expense of neurons. When cerebellar cells were cultured with cells from pons and medulla, which are normal sources of mossy fiber input, aggregates formed in which synaptic glomeruli were found. They were not seen in aggregates containing cells from retina and olfactory bulb cultured with cerebellum. Our observations suggest: that natural histogenetic mechanisms persist after dissociation and reaggregation of cerebellar cells resulting in a separation of an outer, 'molecular'-like layer from an inner granule cell layer and that neurons retain specificity of their synaptogenic capabilities both with regard to appropriate cell types and the morphological form that the synapses take.

Animals↗

A luteinizing hormone-releasing hormone agonist decreases biological activity and modifies chromatographic behavior of luteinizing hormone in man.

The effect of the luteinizing hormone-releasing hormone (LHRH) agonist, [D-Trp6,Pro9-NEth]LHRH (LHRHA), on luteinizing hormone (LH) bioactivity was assessed with a rat interstitial cell assay in four men during a 14-d treatment period. Biologic/immunologic (B/I) ratios were unchanged initially with treatment but by day 12 had fallen to levels lower than basal values. Frequent sampling on day 12 revealed blunted gonadotropin responsiveness to LHRHA and absence of spontaneous LH pulsations. Despite continued administration of LHRHA, human chorionic gonadotropin administration resulted in elevated B/I ratios and testosterone levels. Further characterization of the serum immunoreactive LH by Sephadex chromatography revealed a later elution profile during treatment with LHRHA. Thus, LHRHA appears to act, in part, by modification of the bioactivity of LH in man.

Adult↗

[Forme fruste of progressive lipodystrophy or multiple symmetrical surface lipomatosis?].

It is reported on a 44-year-old patient who has a peculiar form of the disturbance of the distribution of fatty tissue. Apart from clear superficial hypertrophies at upper arms, shoulders, thorax and hypogastrium as well as plum-sized nodes at the left femor and retroauricularly discrete atrophies are found in the face, at forearms and lower legs. In very inconspicuous paraclinical findings special forms of the progressive lipodystrophy and of the indolent symmetrical lipomatosis are discussed.

Adult↗