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Biomedical subjects

I Sommer

Publications and source records attributed to I Sommer.

At least 37 records · Page 2Linked to original sources

Effect of optic nerve transection upon myelin protein gene expression by oligodendrocytes: evidence for axonal influences on gene expression.

The effect of optic nerve transection on myelin protein gene expression was studied in rats following axotomy at two ages: during active myelination (17 days of age) and after peak expression of the genes (35 days of age). mRNA levels for proteolipid protein, myelin basic protein and myelin-associated glycoprotein were assessed by northern and dot blotting and by in situ hybridization using tissue sections and cultured individual oligodendrocytes. Transection at 17 days caused down-regulation of mRNAs for proteolipid protein, myelin basic protein and myelin-associated glycoprotein by 5 days after axotomy with an increase in GFAP mRNA. A more protracted change followed axotomy at 35 days of age. The abundance of mRNAs for proteolipid protein and myelin basic protein was significantly reduced by 28 days after transection in the affected nerve. Quantification of proteolipid protein mRNA expression in individual oligodendrocytes confirmed the down-regulation. However, in contrast to the effects on the major myelin proteins, the abundance of myelin-associated glycoprotein mRNA increased in the affected nerve for at least the initial month after lesioning at 35 days. The results show that optic nerve transection has significant effects on myelin protein mRNA expression in oligodendrocytes of optic nerve. However, the changes in myelin protein gene activity are relatively small and more protracted than those seen in Schwann cells after peripheral nerve section. Because axotomy also causes marked changes in the glial population of the optic nerve it is not possible unequivocally to ascribe the alteration in gene expression to loss of axons. However, the data may provide evidence that axons do influence myelin protein genes in oligodendrocytes and are necessary for them to develop their full expression.

Animals↗

Ultrastructural features of cultured oligodendrocytes expressing stage-specific cell-surface antigens.

This study was designed to correlate cytological features that had previously been established for oligodendrocytes at different developmental stages in vivo and cytological criteria in vitro with the expression of stage-specific cell-surface antigens of cultured oligodendrocytes. Cells obtained from the corpus callosum of 10-day-old C57BL/6J mice were maintained in monolayer cultures and stained with monoclonal antibodies 01 through 012 by indirect immunofluorescence or immunoperoxidase methods. 0 antigen-positive cells were classified according to two criteria: (a) cell shape (type I-III); and (b) cytoplasmic features at the ultrastructural level (class 1-3). Approximately 95% of all 0 antigen-positive cells could be identified as oligodendrocytes by established cytological criteria, thus supporting previous evidence of their glial character from electrophysiological and cell type-specific marker studies. After 12 days in vitro approximately 90% of all morphologically identified oligodendrocytes expressed antigens 03, 04, 05 or 06, which are the first to appear during development in vivo, whereas only 30-40% expressed antigens 011 or 012 which are the last to appear during development in vivo. 01 through 010 antigen-positive oligodendrocytes belong to 3 morphologically distinct cell types: (1) with small (approximately 10 micron in diameter) round cell bodies and few slender processes; (2) with 'hairy eyeball' morphology with a network of processes; and (3) with large, sometimes bipolar cell bodies (up to 30 micron in diameter) surrounded by high amounts of membranous material devoid of cytoplasm. By cytoplasmic criteria at least 90% of all 0 antigen-positive cells fit the description by Mori and Leblond of 'light' to 'medium' oligodendrocytes in vivo, although a clear-cut correlation with expression of early or late appearing 0 antigens was not observed. Typically 'dark' oligodendrocytes were rarely seen in our cultures. 011 and 012 antigen-positive cells are restricted to the group of large oligodendrocytes with high amounts of membranous material, often organized in more or less compact structures (type III). In contrast to the more uniform localization of antigens 01 through 010 over the whole cell surface, antigens 011 and 012 are less strongly detectable on cell bodies than on processes and membranous whirls.

Animals↗

Stage-specific cell-surface antigens of oligodendrocytes in the peripheral nervous system. Expression during development and regeneration and in myelin-deficient mutants.

Monoclonal antibodies to stage-specific cell surface antigens of oligodendrocytes have been used to investigate the expression of antigens 05 through 011 in the peripheral nervous system of the mouse by immunohistology. In the adult sciatic nerve antigens 05 through 09 and 011 were diffusely positive. 010 antigen was not detectable in the peripheral nervous system at any age tested. During development antigens 05, 06 and 07 were first detectable at birth in tracts at the proximal part of the sciatic nerve. At day 2 the whole diameter of the nerve was positive for 05 antigen, while antigens 06 and 07 were detectable only in part of the nerve and antigens 08 and 09 were just about to appear. At day 4 antigen 011 was the last to appear. At day 7 all antigens were strongly detectable throughout the nerve. After transection of adult sciatic nerve expression of antigens 05 through 09 and 011 was studied at the proximal and distal ends of the cut. Three days after transection all antigens were fully detectable in the degenerating myelin and its debris. After 15 days residual debris was still distinctly positive, while Schwann cells in the bands of Bünger were antigen-negative. At approximately two weeks a connecting bridge between proximal and distal ends of the cut nerve had developed, but the 0 antigens were not detectable in this bridge until day 21. At day 42 all antigens were again fully detectable in the regenerating nerve. In hypomyelinating mouse mutants no difference to the normal control littermates was seen in staining pattern and intensity for jimpy and shiverer, while quaking showed an increase in staining intensity for 05 through 08 antigens. In trembler antigens 05, 06 and 07, but not 08, 09 and 011 appeared associated with non-myelin-forming Schwann cells, while the few recognizable myelin-forming Schwann cells expressed all antigens. These observations show that we have characterized 4 new monoclonal antibodies as further reagents to look at developmentally distinct steps in myelination of the peripheral nervous system.

Animals↗

Postnatal development of rat peripheral nerves: an immunohistochemical study of membrane lipids common to non-myelin forming Schwann cells, myelin forming Schwann cells and oligodendrocytes.

Interest in the role of membrane lipids in Schwann cell function prompted this study of lipid antigens on myelin- and non-myelin forming Schwann cells. Using the monoclonal antibodies 07, which recognises galactocerebroside, 08, 09 and 011, the distribution and time course of expression of the 4 membrane lipids have been determined in Schwann cells of the rat sciatic nerve and sympathetic trunk, derived from 1-60-day-old rats. The proportion of Schwann cells binding each monoclonal antibody was found by dissociating the nerves and allowing 3 h for the cells to attach to coverslips, prior to double label immunofluorescence, using the monoclonal antibody in conjunction with antibodies to S100 as a general Schwann cell marker, or P0 to distinguish cells which had formed myelin. All 4 lipid antigens were expressed by myelin forming Schwann cells, appearing just before, or at the time that the cells started to form myelin. Only 011 was restricted to myelin forming Schwann cells. Non-myelin forming Schwann cells expressed 07, 08 and 09. In the cervical sympathetic trunk, the developmental expression of these 3 lipids was essentially complete by postnatal day 20, whereas in the sciatic nerve, expression was not complete until days 40-60. The results show that the biochemical maturation in non-myelin forming Schwann cells differs greatly between different nerves, and may not be completed until several weeks postnatally. The results also demonstrate that in addition to galactocerebroside, other similarities exist in the lipid composition of myelin and the plasma membrane of non-myelin forming Schwann cells since the lipids defined by 08 and 09 antibodies are found among both Schwann cell variants.

Age Factors↗

Multifocal contact dermatitis to nitroderm TTS 5 with extensive postinflammatory hypermelanosis.

Allergic contact dermatitis to nitroglycerin has been previously reported. A localized cutaneous burn-like reaction due to the transdermal device was recently described. We are presenting a case of recurrent allergic contact dermatitis due to nitroglycerin as well as to its delivery device, resulting in numerous patches of postinflammatory hypermelanosis at the sites of application.

Administration, Cutaneous↗

Monoclonal cell surface antibodies do not produce short-term effects on electrical properties of mouse oligodendrocytes in culture.

Eleven monoclonal antibodies (O1-O11) directed against the surface of oligodendrocytes were applied individually or in combination during measurement of membrane potential, input resistance and K+-pump activity in explant cultures of mouse spinal cord. Antibody binding to oligodendrocytes was verified by indirect immunofluorescence. None of the antibodies affected the electrical properties studied. On the basis of these observations, it is possible to identify oligodendrocytes immunocytologically prior to electrophysiological characterization.

Animals↗

Coexistence of nonsecreting and nonproducing light chain multiple myeloma.

A 61-year-old female patient presented with osteolytic skeletal lesions. Open rib biopsy disclosed tumor tissue which consisted of two types of cells: massive infiltrates of poorly differentiated lymphoplasmacytic cells were surrounded by large deposits of differentiated plasma cells. Serum immunoglobulins were normal. No light chains could be found in the urine. An immunoperoxidase technique was employed to detect intracellular immunoglobulins. While the partially differentiated cells were negative, the plasma cells were stained strongly positive for kappa light chains.

Female↗

Intestinal Buerger's disease.

We describe a 50-year-old man who, at 26 years of age, underwent a hemicolectomy on the right side of the abdomen due to infarction of the right colon. At 35 years of age, a stenotic, ischemic segment of distal jejunum was resected. Later he had had intermittent claudication, migratory thrombophlebitis, and recurrent cerebral infarctions. The mesenteric and mural blood vessels of both resected specimens of bowel showed an occlusive process with organized and recent thrombi and marked transmural inflammation. The internal elastic lamina and media in the arteries were preserved and there was no evidence of atheroma or calcification. The histologic findings were consistent with thromboangiitis obliterans. We suggest that the same mechanism may be responsible for intestinal peripheral and cerebrovascular involvement.

Colon↗

Expression of glial antigens C1 and M1 in the peripheral nervous system during development and regeneration.

The expression of C1 and M1 antigens was studied by indirect immunofluorescence methods in histological sections of peripheral nerves and ganglia of C57BL/6J mice during development and regeneration. In sciatic nerves of adult mice, C1 but not M1 antigen is found in vimentin- and glial fibrillary acidic protein (GFAP)-positive Schwann cells. A similar distribution is also seen in trigeminal nerve, dorsal root and superior cervical ganglia, and olfactory nerve. In all cases vimentin-positive structures outnumber GFAP- or C1 antigen-positive ones. At birth, C1 antigen and vimentin are expressed in sciatic nerves, but GFAP is not yet detectable. M1 antigen cannot be detected in Schwann cells. In monolayer cultures of neonatal mouse dorsal root ganglia, C1 antigen is expressed in a fibrillary staining pattern in some, but not all morphologically identified Schwann cells. In vitro, M1 antigen is not detectable in Schwann cells. After lesioning sciatic nerves of adult mice by cut or crush, detectable levels of C1 antigen rise after 4-6 days: The number of immunofluorescently labeled structures and their relative intensities are drastically augmented, first distally more so than proximally, over control values from non-lesioned, i.e. contralateral nerves. A similar augmentation is also observed for vimentin and GFAP. M1 antigen expression does not reach detectable levels in Schwann cells under these conditions. The increased detectability of C1 antigen persists up to 150 days after lesioning, the longest time period tested.

Animals↗

Simultaneous expression of neuronal and glial properties by chick ciliary ganglion cells during development.

Autoradiographic methods were used to show that non-neuronal cells from dissociated chick ciliary ganglia grown in cell culture for 1 day exhibit high affinity uptake for norepinephrine (NE) and/or specific receptors for nerve growth factor (NGF). Using immunofluorescence procedures, it was demonstrated that these cells reacted neither with the neuron-specific marker tetanus toxin nor with antibodies to the fibroblast marker fibronectin. The cells were, however, positive for 04 antigen, which is present on Schwann cells and oligodendrocytes and is recognized by a monoclonal antibody (Schachner, M., S. K. KIm, and R. Zehnle (1981) Dev. Biol. 83: 328-338). At all stages studied between embryonic day 6 (E6) and embryonic day 14 (E14), about 80% of the non-neuronal cells were positive for 04 antigen, the other non-neuronal cells being identified as fibroblasts or fibroblast-like cells by staining with antibodies to fibronectin. The proportion of cells with NGF receptors and cells with NE uptake decreased during development between E6 and E14. The percentage of 04-positive cells which have NGF receptors decreased from about 95% at E6 to about 35% at E14. The proportion of 04-positive cells with NE uptake decreased from about 57% at E6 to about 15% at E14. Thus, a considerable proportion of the non-neuronal cell population in embryonic ciliary ganglia displays neuronal properties. We suggest that those cells exhibiting biochemical properties of both differentiated glial cells and neurons are precursor cells which have the potential to develop either into glial cells or neurons.

Animals↗

Cell that are O4 antigen-positive and O1 antigen-negative differentiate into O1 antigen-positive oligodendrocytes.

In freshly dissociated viable cells of early postnatal mouse cerebellum, O1 antigen-positive oligodendrocytes have been eliminated by complement dependent immunocytolysis. Before seeding residual cells in culture, O4 antigen-positive cells were immunolabeled by O4 antibody which had been directly conjugated with rhodamine. After various periods of time in culture, cells were treated with fluorescein conjugated O1 antibody, in order to assay for the appearance of O1-positive oligodendrocytes. After 6.5 h in vitro, the first cells carrying both the previously applied rhodamine label and the freshly applied fluorescein label were seen. The simultaneous appearance of both labels indicates tha O4-positive and O1-negative cells are direct precursors of O1 antigen-positive oligodendrocytes.

Animals↗

Expression of glial antigens C1 and M1 in developing and adult neurologically mutant mice.

The distribution of two glial antigens (C1 and M1) has been studied by indirect immunofluorescence during postnatal development of the cerebella of normal and neurologically mutant mice (weaver, staggerer, reeler, Purkinje cell degeneration, and wobbler). During the first postnatal week of normal development, C1 antigen is expressed in ependyma. Bergmann glial fibers (BG), and astrocytes of the internal granular layer and white matter. After day 10, C1 antigen is restricted to BG and ependymal cells. During the second and third week. BG undergo a transient loss of C1 antigen that starts in medioventral areas and spreads in a gradient dorsally and laterally. In reeler, weaver, and staggerer, C1 antigen expression is normal during the first postnatal week, and subsides in BG in a similar spatial gradient as described for the normal littermates. However, the loss of C1 antigen in BG occurs earlier (first in reeler, then in weaver, and last in staggerer) and is not reversible as it is in normal mice. In Purkinje cell degeneration, C1 antigen expression is diminished in BG after the onset of behavioral abnormalities. Wobbler is normal with respect to C1 antigen expression at adult ages. M1 antigen is detectable in white matter astrocytes from postnatal day 7 on, and persists in these cells into adulthood. Astrocytes if the internal granular layer and BG express M1 antigen only transiently in normal mice during the second and third weeks. The appearance of M1 antigen in BG occurs in a spatiotemporal gradient, matching the one in which C1 antigen disappears. M1 antigen expression is abnormally maintained in BG of reeler, staggerer, and weaver. In Purkinje cell degeneration. M1 antigen is expressed abnormally at the onset of behavioral abnormalities first in astrocytes of the internal granular layer and, with growing age, increasingly also in BG. In wobbler, BG do not express M1 antigen. However, astrocytes of the granular layer are abnormally M1 antigen-positive.

Aging↗

Recognition of Bergmann glial and ependymal cells in the mouse nervous system by monoclonal antibody.

A monoclonal antibody designated anti-Cl was obtained from a hybridoma clone isolated from a fusion of NS1 myeloma with spleen cells from BALB/c mice injected with homogenate of white matter from bovine corpus callosum. In the adult mouse neuroectoderm, C1 antigen is detectable by indirect immunohistology in the processes of Bergmann glial cells (also called Golgi epithelial cells) in the cerebellum and of Müller cells in the retina, whereas other astrocytes that express glial fibrillary acidic protein in these brain areas are negative for C1. In addition, C1 antigen is expressed in most, if not all, ependymal cells and in large blood vessels, but not capillaries. In the developing, early postnatal cerebellum, C1 antigen is not confined to Bergmann glial and ependymal cells but is additionally present in astrocytes of presumptive white matter and Purkinje cell layer. In the embryonic neuroectoderm, C1 antigen is already expressed at day 10, the earliest stage tested so far. The antigen is distinguished in radially oriented structures in telencephalon, pons, pituitary anlage, and retina. Ventricular cells are not labeled by C1 antibody at this stage. C1 antigen is not detectable in astrocytes of adult or nearly adult cerebella from the neurological mutant mice staggerer, reeler, and weaver, but is present in ependymal cells and large blood vessels. C1 antigen is expressed not only in the intact animal but also in cultured cerebellar astrocytes and fibroblastlike cells. It is localized intracellularly.

Animals↗