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J Farrar S Portolano N Willcox A Vincent L Jacobson J Newsom-Davis B Rapoport SM McLachlan 《Canadian Metallurgical Quarterly》1997,9(9):1311-1318
The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies. 相似文献
14.
Eighty beef crossbred steers with an average weight of 493 kg (4·66 kg SD) were allocated at random to one of five treatments to assess the effects of withholding feed and water on carcass shrinkage and meat quality. The five treatments were: slaughter from the feedlot (T1); and 12, 24, 36 and 48 h periods without feed and water prior to slaughter (T2-5).Weights were taken of the live animal and the carcass to monitor shrinkage along with relevant meat quality measurements. There were no treatment differences (P > 0·05) in initial farm weight, but plant weight shrinkage increased from 31gkg(-1) for T1 to 106 g kg(-1) for T5. Warm carcass weight decreased (P < 0·05) from 278·8 kg for T1, to 270·7 kg for T3 and 261·9 kg for T5. Liver, alimentary tract components, hide and head decreased as a proportion of farm weight as time without feed and water increased. Muscle pH at 6 days post mortem was increased (P < 0·05) in T3-5 compared to T1, with the result that muscle colour became darker, and steaks had less drip loss. Shear values increased (P < 0·05) from 6·3 kg in T1 to 7·7 kg in T4 and T5 indicating an increase in muscle toughness as time without feed and water increased. It was concluded that steers lose live weight rapidly within the first 24 h without feed and water, and that these relatively short periods of time (24 h) can have detrimental effects on carcass shrinkage and muscle quality. 相似文献
15.
Lejla Medzikovic Hylja Heese Pieter B. van Loenen Cindy P. A. A. van Roomen Ingeborg B. Hooijkaas Vincent M. Christoffels Esther E. Creemers Carlie J. M. de Vries Vivian de Waard 《International journal of molecular sciences》2021,22(4)
Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis. 相似文献
16.
This paper introduces Voronoi squared distance minimization (VSDM), an algorithm that fits a surface to an input mesh. VSDM minimizes an objective function that corresponds to a Voronoi-based approximation of the overall squared distance function between the surface and the input mesh (SDM). This objective function is a generalization of the one minimized by centroidal Voronoi tessellation, and can be minimized by a quasi-Newton solver. VSDM naturally adapts the orientation of the mesh elements to best approximate the input, without estimating any differential quantities. Therefore, it can be applied to triangle soups or surfaces with degenerate triangles, topological noise and sharp features. Applications of fitting quad meshes and polynomial surfaces to input triangular meshes are demonstrated. 相似文献
17.
This study, which deals with the distribution of hydrocarbons in seven types of rabbit tissues, was done for the purpose of
providing information that might help shed light on the biological relevance of the hydrocarbons in mammalian metabolism.
Liver, kidneys, brain, spleen, skeletal muscle, perinephric adipose, and a sample of blood serum were collected from a single
animal for analysis of their hydrocarbon composition. The analytical methodology consisted of solvent extraction, saponification
(adipose), elution chromatography on hydrated alumina, and combined gas chromatography-mass spectrometry. Hydrocarbons were
detected in all of the tissues examined at concentrations estimated to range from 0.1 to 0.01% of the total lipid extracted.
Three quite distinct distribution modes were recognized. The bulk of the identified components consisted of normal, saturated,
nonterpenoid hydrocarbons in the C16 to C33 range. Squalene, phytene, phytadiene, and pristane were the only terpenoids detected. Nonterepenoid branched (iso andanteiso) hydrocarbons were identified unequivocally and in significant amounts in the muscle only. The adipose was the only tissue
which was relatively rich in monoalkenes, and its overall hydrocarbon composition closely resembled that of the feed. The
results of the study are not consistent with metabolic inertness. The observed qualitative and quantitative differences might
reflect function and metabolic activities of the individual organs in a way yet to be elucidated.
Presented in part at the AOCS Spring Meeting, New Orleans, April, 1976. 相似文献
18.
Both confocal Raman microspectroscopy and atomic force microscopy (AFM) have been undertaken to study the crystalline and the morphological aspects of cast PA 6 films at a sub-microscopic scale. The percentages of the different crystalline structures present within PA 6 cast films, i.e. the monoclinic α, the pseudo-hexagonal β, and the monoclinic γ, have been measured by confocal Raman microspectroscopy. In cast films, the prevailing structure is the β one. AFM has been used to characterize the morphology of the PA 6 films. Simultaneously, the deformed state has been considered as well. Our main interest has been to follow the evolution of the percentage of each crystalline structure as a function of the plastic deformation mechanisms which are responsible of the yielding of PA 6 films: shear banding for temperatures T lower than 160 °C and formation of fibrils for 相似文献
19.
Blends of unsaturated polyester resin and polyvinylacetate (PVAc) were cured between two glass slides. In this case, the low-profile
effect arises by fissuring with a fractal geometry. This paper shows how the fractal dimension of the fissures depends on
the PVAc amount and on the cure temperature. These results are discussed with the present knowledge about the polyester network
morphology in two phases more or less co-continuous. 相似文献
20.
Vincent J. Senn 《Journal of the American Oil Chemists' Society》1969,46(9):476-478
Cold-pressed peanut oil was separated into chromatographically homogeneous fractions by column chromatography. The fatty acid
composition of the major fractions was determined by gas chromatography. The phosphatides, and especially the cephalins, had
a higher palmitate content than did the triglycerides. Palmitate was the dominant fatty acid in the phosphatidyl-serines. 相似文献