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M Ast

Publications and source records attributed to M Ast.

10 recordsLinked to original sources

Upregulation of the cochaperone Mdg1 in endothelial cells is induced by stress and during in vitro angiogenesis.

Angiogenesis research has focused on receptors and ligands mediating endothelial cell proliferation and migration. Little is known about the molecular mechanisms that are involved in converting endothelial cells from a proliferative to a differentiated state. Microvascular differentiation gene 1 (Mdg1) has been isolated from differentiating microvascular endothelial cells that had been cultured in collagen type I gels (3D culture). In adult human tissue Mdg1 is expressed in endothelial and epithelial cells. Sequence analysis of the full-length cDNA revealed that the N-terminal region of the putative Mdg1-protein exhibits a high sequence similarity to the J-domain of Hsp40 chaperones. We show that this region functions as a bona fide J-domain as it can replace the J-domain of Escherichia coli DnaJ-protein. Mdg1 is also upregulated in primary endothelial and mesangial cells when subjected to various stress stimuli. GFP-Mdg1 fusion constructs showed the Mdg1-protein to be localized within the cytoplasm under control conditions. Stress induces the translocation of Mdg1 into the nucleus, where it accumulates in nucleoli. Costaining with Hdj1, Hdj2, Hsp70, and Hsc70 revealed that Mdg1 colocalizes with Hsp70 and Hdj1 in control and stressed HeLa cells. These data suggest that Mdg1 is involved in the control of cell cycle arrest taking place during terminal cell differentiation and under stress conditions.

Amino Acid Sequence↗

Morphologic fate of diencephalic prosomeres and their subdivisions revealed by mapping cadherin expression.

The expression of four cadherins (cadherin-6B, cadherin-7, R-cadherin, and N-cadherin) was mapped in the diencephalon of chicken embryos at 11 days and 15 days of incubation and was compared with Nissl stains and radial glial topology. Results showed that each cadherin is expressed in a restricted manner by a different set of embryonic divisions, brain nuclei, and their subregions. An analysis of the segmental organization based on the prosomeric model indicated that, in the mature diencephalon, each prosomere persists and forms a coherent domain of gray matter extending across the entire transverse dimension of the neural tube, from the ventricular surface to the pial surface. Moreover, the results suggest the presence of a novel set of secondary subdivisions for the dorsal thalamus (dorsal, intermediate, and ventral tiers and anteroventral subregion). They also confirm the presence of secondary subdivisions in the pretectum (commissural, juxtacommissural, and precommissural). At most of the borders between the prosomeres and their secondary subdivisions, changes in radial glial fiber density were observed. The diencephalic brain nuclei that derive from each of the subdivisions were determined. In addition, a number of previously less well-characterized gray matter regions of the diencephalon were defined in more detail based on the mapping of cadherin expression. The results demonstrate in detail how the divisions of the early embryonic diencephalon persist and transform into mature gray matter architecture during brain morphogenesis, and they support the hypothesis that cadherins play a role in this process by providing a framework of potentially adhesive specificities.

Animals↗

Combinatorial expression of cadherins in the tectum and the sorting of neurites in the tectofugal pathways of the chicken embryo.

The expression of four cadherins (N-cadherin, R-cadherin, cadherin-6B and cadherin-7) was mapped in the developing tectal system of the chicken embryo from four to 19 days of incubation. Each of the cadherins is expressed in a restricted fashion in specific tectal layers, with partial overlap between the cadherins. In some layers, subpopulations of neurons differentially express the cadherins, e.g., in the stratum griseum centrale. Double labeling demonstrates that many of the projection neurons in this layer co-express at least two cadherins. Fibers of the efferent (tectofugal) pathways originating in these neurons also differentially express the cadherins, most prominently at around 1 1 days of incubation. While the different subpopulations of cadherin-expressing projection neurons are dispersed and mixed within the tectum, their neurites sort out and fasciculate according to which cadherin they express, as they collect in the major output of the tectum, the brachium colliculi superioris. From here, cadherin-expressing fascicles follow separate paths to their respective target areas, some of which also express the respective cadherins, in a matching fashion. We propose that the preferentially homophilic binding of cadherins provides a potential adhesive basis for the sorting and selective fasciculation of specific subpopulations of neurites, similar to the well-established sorting and aggregation of cells expressing cadherins. The combinatorial expression of cadherins by the tectal projection neurons may contribute to the complexity and specificity of functional connections in this system.

Animals↗

Expression of the cell adhesion molecule axonin-1 in neuromeres of the chicken diencephalon.

Axonin-1/TAG-1, a member of the immunoglobulin (Ig) superfamily of adhesion molecules, has been shown to be selectively expressed by a subset of neurons and fiber tracts in the developing nervous system of vertebrates. Axonin-1/TAG-1 is thought to play a role in the outgrowth, guidance, and fasciculation of neurites. In the present study, we map the expression of axonin-1 in the diencephalon of the chicken brain at early and intermediate stages of development [2-8 days of incubation; embryonic day (E)2-E8] by immunohistochemical methods. Results show that axonin-1 is first expressed at about E2.5 by postmitotic neurons scattered throughout most of the diencephalon. During the neuromeric stage of brain development (about E3-E5), axonin-1+ nerve cell bodies are predominantly found in two neuromeric subdivisions: 1) in the alar plate of the precommissural pretectum and dorsal thalamus and 2) in the posterior preoptic region of the hypothalamus. The axonin-1+ fiber bundles emerging from these areas grow across segmental boundaries. For example, axonin-1+ neurites originating in the dorsal thalamus cross the zona limitans intrathalamica at a right angle to project to the striatum. Later, the axonin-1+ neuromere areas give rise to particular axonin-1+ gray and white matter structures. Most of these structures correspond to the structures described to express TAG-1 in rodents. In conclusion, axonin-1 can be used as a marker to study aspects of the transition from the early neuromeric structure to the mature anatomy of the chicken brain.

Animals↗

Bile acid sequestrants.

The bile acid sequestrants, cholestyramine and colestipol, are the drugs of choice for the treatment of patients with hypercholesterolemia caused by increases in LDL-cholesterol levels without concurrent hypertriglyceridemia (type IIA and type IIB hyperlipoproteinemia). Longitudinal clinical studies with these drugs have shown their ability to slow the progression of atherosclerosis and to limit the consequences of the disease. Bile acid sequestrants can be used with other lipid-lowering drugs such as nicotinic acid or HMG CoA reductase inhibitors, to maximize the cholesterol-lowering effects. The side effect profile of the bile acid sequestrants is tolerable, with most complaints related to effects on the gastrointestinal tract and the bulkiness of the resins.

Chemical Phenomena↗

Detection of presymptomatic carriers of Huntington's chorea.

Laterality of thumb opposition and handedness were determined in three groups of subjects: patients with Huntington's chorea (n = 18), asymptomatic offspring of patients (n = 40), and asymptomatic siblings of patients over 50 years of age termed 'escapees' (n = 17). 100% of patients and 55% of young at-risk offspring had crossed laterality of thumb opposition and handedness. Only 2 (11.8%) of the 'escapees' had crossed laterality. Crossed laterality may be associated with symptomatic presymptomatic Huntington's chorea.

Adolescent↗

Constitutional predisposition to central nervous system (CNS) disease determined by tests of lateral asymmetry. A preliminary report.

Three factors in combination cause diseases of the central nervous system (CNS): specific etiological agent, physical stress and a general constitutional predisposition to CNS diseases. Research has tended to focus on the first to the disregard of the second and third factors. A newly developed test of functional body asymmetry, however, may have application to the elucidation of the role of physical stress and the constitutional predisposition to CNS diseases. In the present study, neurophysioligcal tests of lateral asymmetry in hand preference and thumb opposition rotation divide the normal population equally into a pure dominant group and a cross-dominant group. Neurological interviews with each group show cross-dominant normal subjects to be more vulnerable to physical stress factors such as overexertion and sleep disturbance. In a previous sutdy applying the same tests, patients with manifest primary diseases of the CNS such as parkinsonism showed cross-dominance in more than 90% of cases. These results with cross-dominant normals and CNS disease patients suggest that cross-dominance indicates a constitutional predisposition to CNS diseases. They also suggest that cross-dominant normal individuals are vulnerable to pysical over-exertion and the specific etiological agent responsible for a distinct CNS syndrome. As far as temporal order is concerned, since it is present in 50% of the normal population, cross-dominant laterality would appear to be a condition prior to any disease process rather than a consequence of CNS disease.

Adolescent↗

Bipolar manic-depressives and unipolar depressives distinguished by tests of lateral asymmetry.

Tests of lateral asymmetry in hand preference and superiority in thumb opposition rotation (opposing the thumb's pulp surface to that of the little finger) have been applied to bipolar and unipolar affective patients in an attempt to evaluate the effectiveness of these tests in differentiating the bipolar and unipolar patient populations. Two comparison samples were also tested: nonpsychotic central nervous system (CNS) disease patients, and normal controls. The normals divided almost evenly into pure dominance (e.g., right-handed, and superior right thumb opposition) and cross-dominance (e.g., right-handed, but superior left thumb opposition). All but one of the CNS disease patients were cross-dominant; the bipolars were predominantly pure dominant; while the unipolars, in contrast to the pure dominant bipolars, were in the majority cross-dominant. This result is consistent with the view that there are two types of affective disorder, bipolar manic-depressive and unipolar depressive illness.

Bipolar Disorder↗

Lateral asymmetry in patients with nervous and mental disease. A preliminary study.

Hand preference and the performance of thumb-to-finger opposition by the right and left hands were tested in four samples: manic-depressives, schizophrenics, nonpsychotic patients with diseases of the central nervous system and normal control subjects. The schizophrenics and manic-depressives both showed significantly more pure dominance (e.g. right-handed, and superior right thumb opposition) than the normal controls, while the nonpsychotic patients with diseases of the central nervous system showed significantly more cross-dominance (e.g. right-handed, but superior left thumb opposition) than the normal control subjects.

Adult↗