Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Involvement of the cervical spine by rheumatoid disease is common, but lateral subluxation at the atlanto-axial level has not been recorded previously. The condition is due to asymmetrical erosion of the lateral atlanto-axial facet joint, and may be complicated by collapse of the lateral mass of the axis. The condition should be suspected in patients with rheumatoid arthritis (RA) who present with occipital, auricular, and/or facial pain.
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PMID:Lateral subluxation of the atlanto-axial joint in rheumatoid arthritis. 74 97

Structural chromosome aberrations were evaluated in peripheral blood samples obtained from three populations exposed to partial-body irradiation. These included 143 persons who received radiotherapy for enlarged thymus glands during infancy and 50 sibling controls; 79 persons irradiated for enlarged tonsils and 81 persons surgically treated for the same condition during childhood; and 77 women frequently exposed as young adults to fluoroscopic chest X rays during lung collapse treatment for tuberculosis (TB) and 66 women of similar ages treated for TB with other therapies. Radiation exposures occurred 30 and more years before blood was drawn. Doses to active bone marrow averaged over the entire body were 21, 6, and 14 cGy for the exposed thymic, tonsil, and TB subjects, respectively. Two hundred metaphases were scored for each subject, and the frequencies of symmetrical (stable) and asymmetrical (unstable) chromosome aberrations were quantified in 97,200 metaphases. Cells with stable aberrations were detected with greater frequency in the irradiated subjects compared with nonirradiated subjects in all three populations, and an overall test for an association between stable aberrations and partial-body ionizing radiation was highly significant (P less than 0.001). We found no evidence that radiation-induced aberrations varied by age at exposure. These data show that exposure of children or young adults to partial-body fractionated radiation can result in detectable increased frequencies of stable chromosome aberrations in circulating lymphocytes 30 years later, and that these aberrations appear to be informative as biological markers of population exposure.
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PMID:Chromosome aberrations in relation to radiation dose following partial-body exposures in three populations. 237 85

We report the neuropathologic findings in a 63-year-old white male with a history of birth asphyxia, cerebral palsy, seizures and mild mental retardation in conjunction with similar brain pathologic findings in animal models of perinatal asphyxia. The human case showed a left cerebral hemispheric hemiatrophy associated with an extensive ulegyria involving all cerebral lobes on that side and a single microscopic focus of cortical atrophy in the right hemisphere. Among a large number of experimental perinatal asphyctic exposures only an occasional animal, like the human case described, showed unilateral hemispheric injury with softening and necrosis if examined early and ulegyria with hemispheric hemiatrophy if examined late. The present paper suggests that perinatal asphyxia under specific pathophysiologic conditions may cause unilateral brain injury. Our experimental studies suggest the specific condition of perinatal asphyxia potentially causing unilateral or asymmetrical brain damage is marked hypoxemia combined with substantial reductions in blood pressure but without circulatory collapse. Given these conditions, the asymmetry of the brain damage likely reflects fetal head position within the gravitational field relative to the heart. With disturbed cerebral blood flow autoregulation from asphyxia, the gravitational field likely accentuates the ischemia of those brain areas most elevated above the level of the heart. Thus, we postulate head position may play a pivotal role in defining brain regions that are damaged in hypotensive perinatal asphyxia. This interpretation may affect the intensive care of hypoxemic, hypotensive newborns aimed at minimizing the risk of brain damage.
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PMID:Cerebral hemiatrophy--correlation of human with animal experimental data. 325 12

Thrombin generation is the culminating event of the coagulation cascade. It is initiated after the expression of tissue factor by endothelial cells and monocytes exposed to thrombogenic stimuli. Anionic phospholipids, chiefly phosphatidylserine, are necessary for the optimal activity of tissue factor and completion of the clotting process. They display a catalytic potential by allowing the formation of the characteristic enzyme complexes at the membrane surface. Platelets are viewed as the main source of procoagulant phospholipid referred to as platelet factor 3. The plasma membrane of resting cells presents an asymmetrical distribution of phospholipids, aminophospholipids being sequestered in the inner leaflet. Procoagulant phospholipids become available at the outer surface after cell stimulation. The collapse of the membrane asymmetry is thought to promote a phospholipid scrambling accompanied by the shedding of microparticles. The plasma membranes of such vesicles bear irreversibly externalized procoagulant phosphatidylserine and contain glycoproteins that testify to their tissue origin. Hence, microparticles could disseminate a dual procoagulant and adhesive potential. Thrombin autoamplification is exerted through feedback activation loops involving either coagulation factors or platelets. This article details the mechanisms by which procoagulant phospholipids promote the generation of an excess of thrombin. A new pharmacological approach of thrombosis is presented, based on the control of the exposure of procoagulant phospholipids and membrane microparticle shedding.
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PMID:Physiopathological significance of catalytic phospholipids in the generation of thrombin. 880 13

It is commonly believed that growth cone turning during pathfinding is initiated by reorganization of actin filaments in response to guidance cues, which then affects microtubule structure to complete the turning process. However, a major unanswered question is how changes in actin cytoskeleton are induced by guidance cues and how these changes are then translated into microtubule rearrangement. Here, we report that local and specific disruption of actin bundles from the growth cone peripheral domain induced repulsive growth cone turning. Meanwhile, dynamic microtubules within the peripheral domain were oriented into areas where actin bundles remained and were lost from areas where actin bundles disappeared. This resulted in directional microtubule extension leading to axon bending and growth cone turning. In addition, this local actin bundle loss coincided with localized growth cone collapse, as well as asymmetrical lamellipodial protrusion. Our results provide direct evidence, for the first time, that regional actin bundle reorganization can steer the growth cone by coordinating actin reorganization with microtubule dynamics. This suggests that actin bundles can be potential targets of signaling pathways downstream of guidance cues, providing a mechanism for coupling changes in leading edge actin with microtubules at the central domain during turning.
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PMID:Focal loss of actin bundles causes microtubule redistribution and growth cone turning. 1203 75

Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 microm in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 microm in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.
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PMID:Dynamics and fragmentation of thick-shelled microbubbles. 1240 41

A theoretical study specifically addresses the question of whether nucleophilic addition to the carbonyl groups of acid chlorides, esters, and anhydrides involves an addition-elimination pathway or proceeds by a concerted S(N)2-like mechanism in the absence of the generally assumed tetrahedral intermediate. Density functional calculations [B3LYP/6-31+G(d,p)] establish that chloride ion exchange reactions with both formyl and acetyl chloride proceed by a pi attack on the C=O bond. No discernible tetrahedral intermediate typical of an addition-elimination pathway was found in either case. While a tetrahedral intermediate does exist for the addition of fluoride ion to (Cl)(2)C=O, halide exchange of LiCl with both ClFC=O and (Cl)(2)C=O also proceeds by a concerted S(N)2-like pathway. The formation of a tetrahedral intermediate from the addition of methanol to acetyl chloride is slightly exothermic (4.4 kcal/mol). The ion-dipole complex of methanol weakly bonded to the carbonyl carbon of protonated acetyl chloride is stabilized by 13.8 kcal/mol but does not collapse to a tetrahedral intermediate. When four CH(3)OH molecules are H-bonded to protonated acetyl chloride, a tetrahedral intermediate is not completely formed and this solvated complex more closely resembles the precursor to an S(N)1-type ionization of Cl(-). With six H-bonding methanol molecules, a methanol adds to the carbonyl carbon and a proton relay occurs with formation of a tetrahedral-like structure that immediately loses chloride ion in an S(N)1-like solvolysis. These results corroborate earlier suggestions (Bentley et al. J. Org. Chem. 1996, 61, 7927) that the methanolysis of acetyl chloride does not proceed through the generally assumed addition-elimination pathway with a discrete tetrahedral intermediate but is consistent with ionization of Cl(-). The reaction of methoxide ion with methyl acetate proceeds via a multiple-well energy surface and involves the intermediacy of an asymmetrical species with differing C-OMe bond lengths. Models of synthetic applications of acyl transfer reactions involving anhydrides that form N-acyloxazolidinones also proceed by a concerted S(N)2-type pathway even with the carboxylate leaving group. Concerted transition states were observed for the reactions of each enantiomer of a 1,3-diphenylcycloprop-2-ene carboxylic anhydride by S-3-lithio-4-phenyloxazolidinone. Despite close structural similarities between the diastereomeric transition states, the relative energies correlated closely with the experimental results.
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PMID:Computational studies of nucleophilic substitution at carbonyl carbon: the S(N)2 mechanism versus the tetrahedral intermediate in organic synthesis. 1547 86

We have investigated the effect of sphingomyelin (SM) to ceramide enzymatic conversion on lipid bilayers using Giant Unilamellar Vesicles (GUVs). Sphingomyelinase was added externally to GUVs containing various proportions of SM. In situ asymmetrical SM conversion to ceramide reduced the area of one leaflet. In the absence of equilibration of all the lipids between the two leaflets, a mismatch between the two monolayers was generated. The tension generated by this mismatch was sufficient to trigger the formation of membrane defects and total vesicle collapse at relatively low percentage of SM ( approximately 5% mol). The formation of nanometric size defects was visualised by AFM in supported bilayers. Vesicle rupture was prevented in two circumstances: (a) in GUVs containing a mixture of l(d) and l(o) domains and (b) in GUVs containing 5% lyso-phosphatidylcholine. In both cases, the accumulation of enough ceramide (at initial SM concentration of 10%) allowed the formation of ceramide-rich domains. The coupling between the two asymmetrical monolayers and the condensing effect produced by the newly formed ceramide generated a tension that could underlie the mechanism through which ceramide formation induces membrane modifications observed during the late stages of apoptosis.
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PMID:Surface tension induced by sphingomyelin to ceramide conversion in lipid membranes. 1729 25

During corticogenesis, progenitors divide within the ventricular zone where they rely on radial process extensions, formed by radial glial cell (RG) scaffolds, along which they migrate to the proper layers of the cerebral cortex. Although the microtubule-associated proteins doublecortin (DCX) and doublecortin-like kinase (DCLK) are critically involved in dynamic rearrangement of the cytoskeletal machinery that allow migration, little is known about their role in early corticogenesis. Here we have functionally characterized a mouse splice-variant of DCLK, doublecortin-like (DCL), exhibiting 73% amino acid sequence identity with DCX over its entire length. Unlike DCX, DCL is expressed from embryonic day 8 onwards throughout the early neuroepithelium. It is localized in mitotic cells, RGs and radial processes. DCL knockdown using siRNA in vitro induces spindle collapse in dividing neuroblastoma cells, whereas overexpression results in elongated and asymmetrical mitotic spindles. In vivo knockdown of the DCLK gene by in utero electroporation significantly reduced cell numbers in the inner proliferative zones and dramatically disrupted most radial processes. Our data emphasize the unique role of the DCLK gene in mitotic spindle integrity during early neurogenesis. In addition, they indicate crucial involvement of DCLK in RG proliferation and their radial process stability, a finding that has thus far not been attributed to DCX or DCLK.
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PMID:Doublecortin-like, a microtubule-associated protein expressed in radial glia, is crucial for neuronal precursor division and radial process stability. 1731 68

Many thousands of contrast ultrasound studies have been conducted in clinics around the world. In addition, the microbubbles employed in these examinations are being widely investigated to deliver drugs and genes. Here, for the first time, the oscillation of these microbubbles in small vessels is directly observed and shown to be substantially different than that predicted by previous models and imaged within large fluid volumes. Using pulsed ultrasound with a center frequency of 1 MHz and peak rarefactional pressure of 0.8 or 2.0 MPa, microbubble expansion was significantly reduced when microbubbles were constrained within small vessels in the rat cecum (p<0.05). A model for microbubble oscillation within compliant vessels is presented that accurately predicts oscillation and vessel displacement within small vessels. As a result of the decreased oscillation in small vessels, a large resting microbubble diameter resulting from agent fusion or a high mechanical index was required to bring the agent shell into contact with the endothelium. Also, contact with the endothelium was observed during asymmetrical collapse, not during expansion. These results will be used to improve the design of drug delivery techniques using microbubbles.
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PMID:Direct observations of ultrasound microbubble contrast agent interaction with the microvessel wall. 1767 65


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