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61.
Arteriosclerotic intimal proliferation is one of the main long-term complications of organ transplantation. Low-molecular-weight, heparin-like molecules prevent myointimal proliferation in arterial wall injury and limit rejection in skin allografts. Cyclosporin limits rejection but has no major effect on intimal proliferation. Therefore, an experimental protocol was designed to test whether heparin-like molecules interacted with low doses of cyclosporin to prevent arterial wall immune system injury and response in a model of arterial graft rejection in normotensive and hypertensive rats. Aortic allografts were performed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) normotensive control rats. Four groups of 10 allografted (SHR and WKY) rats were used: one group was treated with placebo, one with low doses of cyclosporin (2 mg/kg body wt per day), one with low-molecular-weight, heparin-like molecule (1 mg/kg body wt per hour), and one with low doses of cyclosporin plus low-molecular-weight, heparin-like molecule. Ten SHRs and 10 WKYs were isografted and served as the control groups. All rats were killed 8 weeks after aortic grafting. Structural parameters of the grafted segment were measured by morphometric analysis on formalin-fixed sections with specific stains. The classical signs of immune system injury and response were present in the untreated allografts in SHRs and WKYs: inflammatory infiltration of the adventitia, medial injury, and intimal proliferative response. Low doses of cyclosporin had a significant beneficial effect on immune medial injury by increasing medial thickness and the number of remaining smooth muscle cells and decreasing the extracellular matrix injury. Cyclosporin had no protective effect on intimal proliferation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
62.
X Meng X Lu Z Li ED Green H Massa BJ Trask CA Morris MT Keating 《Canadian Metallurgical Quarterly》1998,103(5):590-599
Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS. 相似文献
63.
The plastic deformation produced crack tips in polycarbonate (PC) films stretched in tension, has been characterized by optical and transmission electron microscopy. An extensive and diffuse region of deformation is formed in unannealed specimens. Within this zone the ratio (v
f) of local film thickness to the (undeformed) thickness far away from the crack varies gradually both along and across the zone. The minimum ratio of 0.5 occurs at the crack tip. In contrast to this behaviour, films annealed for a short time just below the glass transition temperature T
g showed a highly localized response, the plastic strain being confined to a well-defined flame shaped deformation zone (DZ) ahead of the crack. Within most of this DZ, v
f is constant at 0.7, rising to 1 over a distance of 10 m at the zone tip, and falling to 0.5 over a distance of 4 m around the crack tip. Bi-refringence measurements show that a high degree of molecular orientation occurs within the zone. These experiments support the idea that an increase in the localization of the plastic strain response upon annealing below T
g is responsible for the embrittlement of PC by such heat treatment. 相似文献
64.
Rosanne Hertzberger Ali May Gertjan Kramer Isabelle van Vondelen Douwe Molenaar Remco Kort 《International journal of molecular sciences》2022,23(10)
Glycogen in the female lower reproductive tract is a major carbon source for colonization and acidification by common vaginal Lactobacillus species, such as Lactobacillus crispatus. Previously, we identified the amylopullulanase encoding gene pulA of Lactobacillus crispatus to correlate with the ability to autonomously utilize glycogen for growth. Here, we further characterize genetic variation and differential regulation of pulA affecting the presence of its gene product on the outer surface layer. We show that alpha-glucan degrading activity dissipates when Lactobacillus crispatus is grown on glucose, maltose and maltotriose, in agreement with carbon catabolite repression elements flanking the pulA gene. Proteome analysis of the S-layer confirmed that the amylopullulanase protein is highly abundant in an S-layer enriched fraction, but not in a strain with a defective amylopullulanase variant or in an amylopullulanase-sufficient strain grown on glucose. In addition, we provide evidence that Lactobacillus crispatus pulA mutants are relevant in vivo, as they are commonly observed in metagenome datasets of human vaginal microbial communities. Analysis of the largest publicly available dataset of 1507 human vaginal metagenomes indicates that among the 270 samples that contain a Lactobacillus crispatus pulA gene, 62 samples (23%) had a defective variant of this gene. Taken together, these results demonstrate that both environmental, as well as genetic factors explain the variation of Lactobacillus crispatus alpha-glucosidases in the vaginal environment. 相似文献
65.
Charavana K. Gurumurthy Edward J. Kramer Chung-Yuen Hui 《International Journal of Fracture》2001,109(1):1-28
Direct chip attach (DCA) microelectronic packaging technology is gaining prominence due to its numerous advantages. Delamination (debonding) of the underfill epoxy/ polyimide passivation interface of a DCA during hydro-thermal reliability testing has always been one of the salient problems. We have studied the water-assisted sub-critical crack growth along this interface and our measurement offers important clues as to the origins of the poor hydro-thermal testing results for these interfaces. A modified asymmetric double cantilever beam (ADCB) testing technique has been used to measure the sub-critical crack growth velocity v at various relative humidities and temperatures as a function of the crack driving force (strain energy release rate) G
*. The presence of a significant partial pressure of water p
H2O
produces a marked decrease (by up to a factor of 12) in the threshold G
* for crack growth at measurable velocities. Above the threshold log v rises linearly with
but then enters a regime where the crack velocity (v=v
*) is almost independent of
. Finally, at the values of G
* corresponding to rapid crack propagation in the absence of water, log v increases very rapidly with G
*. By analogy to the classic work on water-assisted sub-critical crack growth in silica-based glasses, where very similar features are observed, we believe that the sub-critical crack growth along the polyimide-epoxy interface results from stress-assisted hydrolysis of primary covalent bonds, in our case ester bonds across the interface. The regime of
just above the threshold corresponds to a physicochemical situation where the water activity (p
H
2O
) at the crack tip is the same as that of the gaseous environment. In the regime where v=v
* constant, the water activity at the crack tip is below that in the environment and the crack growth velocity is limited by the transport of water vapor to the bonds ahead of the crack tip. We develop a model of this crack growth following Wiederhorn 1967 that allows us to predict the sub-critical crack growth as a function of G
* for arbitrary relative humidity and temperature conditions. 相似文献
66.
67.
Yan-Ruide Li Yang Zhou Matthew Wilson Adam Kramer Ryan Hon Yichen Zhu Ying Fang Lili Yang 《International journal of molecular sciences》2022,23(14)
Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively transferring human iNKT cells into tumor-bearing humanized NSG mice and administering a single dose of tumor-localized α-GalCer, we demonstrated the rapid recruitment of human iNKT cells into solid tumors in as little as one day and a significantly enhanced tumor killing ability. Using firefly luciferase-labeled iNKT cells, we monitored the tissue biodistribution and pharmacokinetics/pharmacodynamics (PK/PD) of human iNKT cells in tumor-bearing NSG mice. Collectively, these preclinical studies demonstrate the promise of an αGC-driven iNKT cell-based immunotherapy to target solid tumors with higher efficacy and precision. 相似文献
68.
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