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)

Dysbaric osteonecrosis was induced successfully in adult sheep after 12 to 13, 24-hour exposures to compressed air (2.6-2.9 atmospheres absolute) during a 2-month period. All exposed sheep had decompression sickness and extensive bone and marrow necrosis in their long bones. Radiographic analysis of these progressive lesions showed mottled to distinct medullary opacities and endosteal thickening characteristic of dysbaric osteonecrosis. Six months after the last hyperbaric exposure, neovascularization of once ischemic fatty marrow was centripetal from the diaphyseal cortex. Proliferating endosteal new bone, fatty marrow calcification, and appositional new bone formation were widespread. Juxtaarticular osteonecrosis involved marrow fibrosis and loss of osteocytes in subchondral cortical bone. Tidemark reduplication in juxtaarticular bone and cartilage thinning suggested possible early osteoarthritis induction by recurrent episodes of transient ischemia after multiple hyperbaric exposures. Dysbaric osteonecrosis appears to involve a bone compartment syndrome of elevated intramedullary pressure initiated by decompression induced N2 bubble formation in the fatty marrow of the long bones. An animal model that can be used to investigate the pathogenesis, diagnosis, and treatment of dysbaric osteonecrosis is discussed.
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PMID:Dysbaric osteonecrosis in divers and caisson workers. An animal model. 937 84

The murine hair coat consists of four different hair types that are characterised by hair length, the number of medulla columns, and the presence and number of bends. The molecular mechanisms underlying the establishment and maintenance of distinct hair follicle fates are unknown. We identify Igfbp5 as the first molecular marker that distinguishes among different hair follicle types. High-resolution expression analysis revealed that its expression in the medulla of hair shafts is associated with the bend-forming zones of zigzag hairs. To directly examine the functional importance of segmental gene expression in the hair follicle, we have generated transgenic mice expressing Igfbp5 in differentiating keratinocytes of the medulla and inner root sheath. Ectopic expression of Igfbp5 resulted in the appearance of remarkable curvatures and thinning of hair shafts, two hallmarks of hair bends. Both effects and the natural bending process are under negative control of IGF signalling. Thus, our data identify Igfbp5 as a central regulator of hair shaft differentiation and hair type determination.
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PMID:Segmental Igfbp5 expression is specifically associated with the bent structure of zigzag hairs. 1602 35

We present detailed results for the motion of a finite sized gas bubble in a blood vessel. The bubble (dispersed phase) size is taken to be such as to nearly occlude the vessel. The bulk medium is treated as a shear thinning Casson fluid and contains a soluble surfactant that adsorbs and desorbs from the interface. Three different vessel sizes, corresponding to a small artery, a large arteriole, and a small arteriole, in normal humans, are considered. The hematocrit (volume fraction of RBCs) has been taken to be 0.45. For arteriolar flow, where relevant, the Fahraeus-Lindqvist effect is taken into account. Bubble motion cause temporal and spatial gradients of shear stress at the cell surface lining the vessel wall as the bubble approaches the cell, moves over it and passes it by. Rapid reversals occur in the sign of the shear stress imparted to the cell surface during this motion. Shear stress gradients together with sign reversals are associated with a recirculation vortex at the rear of the moving bubble. The presence of the surfactant reduces the level of the shear stress gradients imparted to the cell surface as compared to an equivalent surfactant-free system. Our numerical results for bubble shapes and wall shear stresses may help explain phenomena observed in experimental studies related to gas embolism, a significant problem in cardiac surgery and decompression sickness.
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PMID:Effect of a soluble surfactant on a finite sized bubble motion in a blood vessel. 2030 44

Endophilin A is a key player in clathrin-mediated endocytosis at nerve terminals and is essential for the maintenance of synaptic transmission. Endophilin consists of two regions: an SH3 domain that interacts with other endocytotic proteins and an N-BAR domain that binds and bends membranes. Here, we used atomic force microscopy (AFM) under fluid to examine the interaction of the endophilin N-BAR domain with planar supported lipid bilayers, under conditions that closely mimic the environment in which this protein normally operates. We found that when bound to lipid bilayers, the N-BAR domain formed aggregates of various sizes. The N-BAR domain also perturbed the structure of the planar bilayer, at a low concentration (0.15 microM) causing bilayer thinning, and at a 10-fold higher concentration (1.5 microM) forming thin slivers from the bilayer sheet. This bilayer sculpting effect crucially involved the central appendage domain. Reduced hydrophobicity in this domain, caused by the A66D mutation, almost abolished the ability of the endophilin N-BAR domain to bind to supported bilayers. In contrast, increased hydrophobicity, caused by the A66W mutation, switched the bilayer sculpting effect of the N-BAR domain from sliver formation to vesiculation. By following the action of the endophilin N-BAR domain under near-physiological conditions, we have been able to provide additional insights into its membrane binding and bending mechanism.
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PMID:The endophilin N-BAR domain perturbs the structure of lipid bilayers. 2052 5

The transmembrane protein 16 (TMEM16) family of membrane proteins includes both lipid scramblases and ion channels involved in olfaction, nociception, and blood coagulation. The crystal structure of the fungal Nectria haematococca TMEM16 (nhTMEM16) scramblase suggested a putative mechanism of lipid transport, whereby polar and charged lipid headgroups move through the low-dielectric environment of the membrane by traversing a hydrophilic groove on the membrane-spanning surface of the protein. Here, we use computational methods to explore the membrane-protein interactions involved in lipid scrambling. Fast, continuum membrane-bending calculations reveal a global pattern of charged and hydrophobic surface residues that bends the membrane in a large-amplitude sinusoidal wave, resulting in bilayer thinning across the hydrophilic groove. Atomic simulations uncover two lipid headgroup-interaction sites flanking the groove. The cytoplasmic site nucleates headgroup-dipole stacking interactions that form a chain of lipid molecules that penetrate into the groove. In two instances, a cytoplasmic lipid interdigitates into this chain, crosses the bilayer, and enters the extracellular leaflet, and the reverse process happens twice as well. Continuum membrane-bending analysis carried out on homology models of mammalian homologs shows that these family members also bend the membrane-even those that lack scramblase activity. Sequence alignments show that the lipid-interaction sites are conserved in many family members but less so in those with reduced scrambling ability. Our analysis provides insight into how large-scale membrane bending and protein chemistry facilitate lipid permeation in the TMEM16 family, and we hypothesize that membrane interactions also affect ion permeation.
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PMID:Atomistic insight into lipid translocation by a TMEM16 scramblase. 2787 8