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991.
The fast alkali myosin light chain 1f/3f (MLC1f/3f) gene is developmentally regulated, muscle specific, and preferentially expressed in fast-twitch fibers. A transgene containing an MLC1f promoter plus a downstream enhancer replicates this pattern of expression in transgenic mice. Unexpectedly, this transgene is also expressed in a striking (approximately 100-fold) rostrocaudal gradient in axial muscles (reviewed by J. R. Sanes, M. J. Donoghue, M. C. Wallace, and J. P. Merlie, Cold Spring Harbor Symp. Quant. Biol. 57:451-460, 1992). Here, we analyzed the expression of mutated transgenes to map sites necessary for muscle-specific, fiber-type-selective, and axially graded expression. We show that two E boxes (myogenic factor binding sites), a homeodomain (hox) protein binding site, and an MEF2 site, which are clustered in an approximately 170-bp core enhancer, are all necessary for maximal transgene activity in muscle but not for fiber-type- or position-dependent expression. A distinct region within the core enhancer promotes selective expression of the transgene in fast-twitch muscles. Sequences that flank the core enhancer are also necessary for high-level activity in transgenic mice but have little influence on activity in transfected cells, suggesting the presence of regions resembling matrix attachment sites. Truncations of the MLC1f promoter affected position-dependent expression of the transgene, revealing distinct regions that repress transgene activity in neck muscles and promote differential expression among intercostal muscles. Thus, the whole-body gradient of expression displayed by the complete transgene may reflect the integrated activities of discrete elements that regulate expression in subsets of muscles. Finally, we show that transgene activity is not significantly affected by deletion or overexpression of the myoD gene, suggesting that intermuscular differences in myogenic factor levels do not affect patterns of transgene expression. Together, our results provide evidence for at least nine distinct sites that exert major effects on the levels and patterns of MLC1f expression in adult muscles. 相似文献
992.
993.
994.
M Kopf S Herren MV Wiles MB Pepys MH Kosco-Vilbois 《Canadian Metallurgical Quarterly》1998,188(10):1895-1906
Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell-dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6-deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti-mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3-deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6-deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses. 相似文献
995.
GA Cook SL Elliott MV Skeljo AS Giraud ND Yeomans 《Canadian Metallurgical Quarterly》1997,42(3):654-660
Coadministration with the human immunodeficiency virus (HIV) protease inhibitor ritonavir was investigated as a method for enhancing the levels of other peptidomimetic HIV protease inhibitors in plasma. In rat and human liver microsomes, ritonavir potently inhibited the cytochrome P450 (CYP)-mediated metabolism of saquinavir, indinavir, nelfinavir, and VX-478. The structural features of ritonavir responsible for CYP binding and inhibition were examined. Coadministration of other protease inhibitors with ritonavir in rats and dogs produced elevated and sustained plasma drug levels 8 to 12 h after a single dose. Drug exposure in rats was elevated by 8- to 46-fold. A > 50-fold enhancement of the concentrations of saquinavir in plasma was observed in humans following a single codose of ritonavir (600 mg) and saquinavir (200 mg). These results indicate that ritonavir can favorably alter the pharmacokinetic profiles of other protease inhibitors. Combination regimens of ritonavir and other protease inhibitors may thus play a role in the treatment of HIV infection. Because of potentially substantial drug level increases, however, such combinations require further investigation to establish safe regimens for clinical use. 相似文献
996.
MV Ha 《Canadian Metallurgical Quarterly》1997,12(6):S45-S47
There are some differences between the spectrum of gastroenterological diseases in Vietnam compared with those of more developed countries. These may be due to different living standards, quality of nutrition, and different infection rates of intestinal parasites and hepatotropic viruses. Gastric carcinoma and hepatocellular carcinoma (HCC) are leading malignancies, while colorectal cancer is less frequent. Bile duct stones often have Ascaris eggs in the centre, and they prevail in incidence over gall-bladder stones. The majority of digestive cancers are detected at a very late stage. The Vietnamese Association of Gastroenterology aims to contribute to the development of modern gastroenterology (GE) in Vietnam, to study and apply recent advances in imaging technology, such as fibre-optic diagnostic and therapeutical endoscopy, ultrasonography, laparoscopic surgery etc. and to do further work in molecular biology. For this purpose, besides our self-reliance, we need, and ask for, support and assistance from the Japanese Society of GE (JSGE), the Asian Pacific Association of GE (APAGE) and the Organisation Mondiale de GE (OMEGE). At the same time, we suggest a choice be made among the different technologies, bearing in mind their cost-effectiveness, and to give preference to measures for the primary prevention and early detection of the diseases. Japanese experience in the early detection of gastric cancer and HCC, and in the Percutaneous Ethanol Injection Therapy (PEIT) for treatment of HCC, are highly appreciated. We recommend also a judicious and scientific combination of traditional medicine and modern technology in the research and the struggle against digestive diseases. 相似文献
997.
J Simó Mi?ana M Gaztambide Ganuza MV Morote Sanchís G Palazón Ferrer J Gálvez Candel ML Salto Sánchez D Pe?arroja González I Hernández Aguado 《Canadian Metallurgical Quarterly》1997,108(20):767-771
BACKGROUND: To know the utilization of the screening mammography among women from 25 to 65 years old in an urban health zone, where there is not an specific screening program for breast cancer. To detect the demographic and risk determinants that are involved in the mammography screening use. SUBJECTS AND METHODS: A sample of 1,240 women were interviewed consecutively as they visited their physician. Risk factors, sociodemographic variables and use of health services were analyzed. The associated variables with the use of mammography screening were determined by univariant analysis. A multiple logistic regression model was designed to identify the variables independently associated with the use of mammography screening. RESULTS: The percentage of interviewed women who have completed at least one mammography screening in the last three years has been 10.2 +/- 3% (confidence level: 95%), 68.3% of them were under 50 years old. The variables independently associated with the use of mammography screening were: age (OR = 1.08); routine visit to the gynecologist (OR = 8.13); educational level (primary: OR = 2.44, secondary: OR = 3.66, university: OR = 7.43, no schooling: reference level); and knowledge about the benefits of mammography screening (OR = 6.15). Family history of breast cancer and the other risk factors were found not to be associated with the use of mammography screening. CONCLUSIONS: The use of mammography screening among women from 25 to 65 years is inadequate according to the age and other risk factors. Mammography screening among women with a family history of breast cancer and those over 50 years old is underused, so it would be recommended and their use increased for these women. But women under 40 years old without family history of breast cancer have to be dissuaded from undertaking such a screening. 相似文献
998.
KE Moe PN Prinz LH Larsen MV Vitiello SO Reed GR Merriam 《Canadian Metallurgical Quarterly》1998,53(2):B117-B124
Studies of estrogen effects on growth hormone (GH) and its pulsatile release in postmenopausal women have typically utilized estrogen replacement therapy (ERT) of relatively short duration (days to weeks). The purpose of this study was to compare GH measures from healthy postmenopausal women who were on oral ERT for 3 years or more (n = 24; mean ERT duration = 16.1 years) with women not on ERT (NERT; n = 40). Blood samples were drawn remotely every 20 min for 24 h and then analyzed for mean 24-h GH, mean GH during sleep, and mean 24-h insulin-like growth factor-I (IGF-I). GH peak analyses were also performed. Mean 24-h GH and GH during sleep were significantly higher and IGF-I was significantly lower in ERT women compared with NERT women. In addition, use of long-term ERT was associated with more GH peaks relative to women not on ERT, but no change in GH peak amplitude or area. GH was not related to age in either group. GH was strongly and negatively correlated with measures of adiposity in NERT women but not in ERT women. In conclusion, long-term oral ERT is associated with increased circulating GH and decreased IGF-I levels, even after many years of treatment. 相似文献
999.
1000.
The alimentary tocopherol deficiency is accompanied by decreased hydroxylase, demethylase, NADH- and NADPH-reductase, aldehyde dehydrogenase, arylesterase and glutathione reductase activity in rat's liver. It decreased the reduced glutathione and increased it's oxidized form concentration in the tocopherol deficient animals. The stability of microsomal membrane is decreased to solubilizing action of deoxycholate and trypsin. This changes, possibly, caused elevation of alteration of function enzyme's and microsomal membrane after nitrosodimethylamine (NDMA) administration in deficient rats. The 7-days injection of tocopherol (20 and 100 mg/kg), dibunol (80 mg/kg), sodium selenite (30 mkg/kg) increased aldehyde dehydrogenase, esterase, glutathione-dependent enzymes activity and increased of reduced glutathione concentration in liver, suppressed lipid peroxidation and increased survival rats after lethal dose carcinogen treatment. Supplementation of tocopherol decreased harmful action of nitrosodimethylamine on microsomal membrane and enzymes activity. 相似文献