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Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice 总被引:15,自引:0,他引:15
Williamson RA; Henry MD; Daniels KJ; Hrstka RF; Lee JC; Sunada Y; Ibraghimov- Beskrovnaya O; Campbell KP 《Human molecular genetics》1997,6(6):831-841
Dystroglycan is a central component of the dystrophin-glycoprotein complex
(DGC), a protein assembly that plays a critical role in a variety of
muscular dystrophies. In order to better understand the function of
dystroglycan in development and disease, we have generated a null allele of
dystroglycan (Dag1neo2) in mice. Heterozygous Dag1neo2 mice are viable and
fertile. In contrast, homozygous Dag1neo2 embryos exhibit gross
developmental abnormalities beginning around 6.5 days of gestation.
Analysis of the mutant phenotype indicates that an early defect in the
development of homozygous Dag1neo2 embryos is a disruption of Reichert's
membrane, an extra-embryonic basement membrane. Consistent with the
functional defects observed in Reichert's membrane, dystroglycan protein is
localized in apposition to this structure in normal egg cylinder stage
embryos. We also show that the localization of two critical structural
elements of Reichert's membrane- -laminin and collagen IV--are specifically
disrupted in the homozygous Dag1neo2 embryos. Taken together, the data
indicate that dystroglycan is required for the development of Reichert's
membrane. Furthermore, these results suggest that disruption of basement
membrane organization might be a common feature of muscular dystrophies
linked to the DGC.
相似文献
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This study was undertaken to compare tropolone with oxine (8-hydroxy-quinoline) for labeling human neutrophils with In-111. Exposure of neutrophils to tropolone at concentrations required for efficient labeling resulted in a marked impairment of chemotaxis. In contrast, no impairment of neutrophil chemotaxis was observed using In-111 oxine. Labeling efficiencies obtained with In-111 tropolone under optimal conditions were consistently less than those obtained with In-111 oxine. We evaluated cells labeled by the two methods using chemotaxis radioassay to assess the chemotatic potential of labeled cells. The results led to the conclusion that the oxine technique is preferable to tropolone for labeling human neutrophils with In-111. 相似文献
86.
An emerging clinical modality called proton magnetic resonance spectroscopy (1H-MRS) enables the non-invasive in vivo assessment of tissue metabolism and is demonstrating applications in improving the specificity of MR breast lesion diagnosis and monitoring tumour responsiveness to neoadjuvant chemotherapies. Variations in the concentration of choline-based cellular metabolites, detectable with 1H-MRS, have shown an association with malignant transformation of tissue in in vivo and in vitro studies. 1H-MRS exists as an adjunct to the current routine clinical breast MR examination. This review serves as an introduction to the field of breast 1H-MRS, discusses modern high-field strength and quantitative approaches and technical considerations, and reviews the literature with respect to the application of 1H-MRS for breast cancer. 相似文献
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The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02). 相似文献
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EV Loftus Jr BA Olivares-Pakzad KP Batts MC Adkins DH Stephens MG Sarr EP DiMagno 《Gastroenterology》1996,110(6):1909-1918
BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreatic ducts is increasingly recognized. This study investigated if clinical, imaging, or, histological features predicated outcome, formulated a treatment algorithm, and clarified relationships among IPMT, mucinous cystic neoplasms of the pancreas (MCN), and chronic pancreatitis. METHODS: The medical records, radiographs, and pathological specimens of 15 patients with IPMT (dilated main pancreatic duct or branch ducts with mucin overproduction) who were evaluated between October 1983 and January 1994 were reviewed. RESULTS: One patient had hepatic metastases. Fourteen underwent an operation (6 distal pancreatectomy, 4 total pancreatectomy, and 4 pancreaticoduodenectomy); all had dysplastic intraductal epithelium and chronic pancreatitis, whereas 3 had invasive adenocarcinoma. After a median of 25 months, 10 patients were alive; 3 of 4 with malignant and 2 of 11 with benign IPMT died (P < 0.05). Patients with or without carcinoma had similar clinical and radiographic features. A clinical diagnosis of chronic pancreatitis had been made in 9 patients with benign IMPT and in none with malignant IPMT (P < 0.05). CONCLUSIONS: IPMT is a dysplastic and likely precancerous lesion that is frequently diagnosed as chronic pancreatitis and is separate from MCN. Because it is not possible to distinguish noninvasive from invasive IPMT preoperatively, complete surgical excision of the dysplastic process is our treatment of choice whenever appropriate. (Gastroenterology 1996 Jun;110(6):1909-18) 相似文献