Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The radiological features of 10 cases of primitive neuroectodermal tumour (primary cerebral neuroblastoma) are presented. The angiographic and CT appearances were similar to those previously described in the literature. However, not previously documented was evidence on plain skull radiographs and CT scans of thinning and expansion of the overlying vault in 6 of the 10 cases.
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PMID:Radiological features of the neuroectodermal tumours of childhood. 650 15

The MARK protein kinases were originally identified by their ability to phosphorylate a serine motif in the microtubule-binding domain of tau that is critical for microtubule binding. Here, we report the cloning and expression of a novel human paralog, MARK4, which shares 75% overall homology with MARK1-3 and is predominantly expressed in brain. Homology is most pronounced in the catalytic domain (90%), and MARK4 readily phosphorylates tau and the related microtubule-associated protein 2 (MAP2) and MAP4. In contrast to the three paralogs that all exhibit uniform cytoplasmic localization, MARK4 colocalizes with the centrosome and with microtubules in cultured cells. Overexpression of MARK4 causes thinning out of the microtubule network, concomitant with a reorganization of microtubules into bundles. In line with these findings, we show that a tandem affinity-purified MARK4 protein complex contains alpha-, beta-, and gamma-tubulin. In differentiated neuroblastoma cells, MARK4 is localized prominently at the tips of neurite-like processes. We suggest that although the four MARK/PAR-1 kinases might play multiple cellular roles in concert with different targets, MARK4 is likely to be directly involved in microtubule organization in neuronal cells and may contribute to the pathological phosphorylation of tau in Alzheimer's disease.
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PMID:MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes. 1459 45

The p190 RhoGAPs, p190A and p190B, are highly related GTPase-activating proteins for the Rho GTPases. Rho GTPases and p190A reportedly control various aspects of brain development, and we hypothesized that p190B would be likewise involved in neuronal development. We find that like p190A, p190B is prominently expressed in the developing and adult brain. Unlike p190A, p190B is not abundantly tyrosine phosphorylated. We further demonstrate, using p190B-deficient mice, that p190B is required for normal brain development. Mice lacking p190B display several major defects, including (1) deficits in the formation of major forebrain commissures, including the corpus callosum and anterior commissure, (2) dilation of the lateral ventricles, suggesting inhibition of neurogenesis and/or survival, (3) thinning of the neocortical intermediate zone, suggesting defects in neuronal differentiation and/or axonal outgrowth, and (4) impaired neuronal differentiation. These defects are similar to, but distinct from, those described in p190A-deficient mice. RNA interference-mediated knockdown of neither p190 protein results in significant inhibition of neurite outgrowth in neuroblastoma cells, despite an apparent increase in RhoA activity. We conclude that p190 RhoGAPs control pivotal aspects of neural development, including neuronal differentiation and process outgrowth, and that these effects are mediated by signaling systems that include, but are not limited to, RhoA.
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PMID:Distinct but overlapping functions for the closely related p190 RhoGAPs in neural development. 1702 31

Siblings of non-consanguineous Jewish-Ethiopian ancestry presented with congenital axial hypotonia, weakness of the abducens nerve, psychomotor developmental delay with brain ventriculomegaly, variable thinning of corpus callosum and cardiac septal defects. Homozygosity mapping identified a single disease-associated locus of 3.5 Mb on chromosome 3. Studies of a Bedouin consanguineous kindred affected with a similar recessive phenotype identified a single disease-associated 18 Mb homozygosity locus encompassing the entire 3.5 Mb locus. Whole exome sequencing demonstrated only two homozygous mutations within a shared identical haplotype of 0.6 Mb, common to both Bedouin and Ethiopian affected individuals, suggesting an ancient common founder. Only one of the mutations segregated as expected in both kindreds and was not found in Bedouin and Jewish-Ethiopian controls: c.1404A>G, p.[*468Trpext*6] in CCDC174. We showed that CCDC174 is ubiquitous, restricted to the cell nucleus and co-localized with EIF4A3. In fact, yeast-two-hybrid assay demonstrated interaction of CCDC174 with EIF4A3, a component of exon junction complex. Knockdown of the CCDC174 ortholog in Xenopus laevis embryos resulted in poor neural fold closure at the neurula stage with later embryonic lethality. Knockdown embryos exhibited a sharp reduction in expression of n-tubulin, a marker for differentiating primary neurons, and of hindbrain markers krox20 and hoxb3. The Xenopus phenotype could be rescued by the human normal, yet not the mutant CCDC174 transcripts. Moreover, overexpression of mutant but not normal CCDC174 in neuroblastoma cells caused rapid apoptosis. In line with the hypotonia phenotype, the CCDC174 mutation caused depletion of RYR1 and marked myopathic changes in skeletal muscle of affected individuals.
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PMID:CDC174, a novel component of the exon junction complex whose mutation underlies a syndrome of hypotonia and psychomotor developmental delay. 2635 78

Recently, a large number of physiological studies on stress and hibernation had described an unusual morphological phenomenon of the rapid disappearance and reapperance of apical dendrites of pyramidal neurons of the hippocampus, prefrontal cortex and other parts of the brain. In this article an attempt is maid to explain this phenomenon on the basis of morphological analysis of natural elastic properties of neuroplasm and structural kinetics of partially preserved processes of the living isolated neurons. The neuroplasm displacement with its bidirectional flow was identified in the processes. A new physiological phenomenon is described--the isometric retraction of nerve cell processes, during which the neuroplasm fluxes were directed to the opposite sides, leading to abrupt thinning of middle parts of the processes and to a thickening of both ends. It is suggested that the extremely attenuated processes can reach the submicroscopic sizes, becoming invisible in the light microscope. The repeated reversible "disappearance" and "appearance" of the processes was demonstrated supravitally in the culture of neurons and of C-1300 neuroblastoma cells. Reduction of the diameter of the processes to a limit of their visibility was demonstrated by the example of their natural stretching. The same effect was observed in the areas between the reversible varicosities of the processes. These areas became extremely thin, and then invisible. Becoming thinner, the processes were capable of sharp extension. A review of the available literature and our own data allow to conclude that the phenomenon of the disappearance of the apical dendrites was due to their isometric retraction, which lead to the emergence of "invisible processes".
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PMID:[ISOMETRIC RETRACTION AND THE INVISIBLE PROCESSES OF NERVE CELLS]. 2714 78