DN Burshtyn  AS Lam  M Weston  N Gupta  PA Warmerdam  EO Long 《Canadian Metallurgical Quarterly》1999,162(2):897-902

The heart has been recognized as a major target of thyroid hormone action. Our study investigates both the regulation of cardiac-specific genes and contractile behavior of the heart in the presence of a mutant thyroid hormone receptor beta1 (T3Rbeta1-delta337T) derived from the S kindred. The mutant receptor was originally identified in a patient with generalized resistance to thyroid hormone. Cardiac expression of the mutant receptor was achieved by a transgenic approach in mice. As the genes for myosin heavy chains (MHC alpha and MHC beta) and the cardiac sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) are known to be regulated by T3, their cardiac expression was analyzed. The messenger RNA levels for MHC alpha and SERCA2 were markedly down-regulated, MHC beta messenger RNA was up-regulated. Although T3 levels were normal in these animals, this pattern of cardiac gene expression mimics a hypothyroid phenotype. Cardiac muscle contraction was significantly prolonged in papillary muscles from transgenic mice. The electrocardiogram of transgenic mice showed a substantial prolongation of the QRS interval. Changes in cardiac gene expression, cardiac muscle contractility, and electrocardiogram are compatible with a hypothyroid cardiac phenotype despite normal T3 levels, indicating a dominant negative effect of the T3Rbeta mutant.  相似文献   

    

PA Smith  LE Ratner  FC Lynch  FM Corl  EK Fishman 《Canadian Metallurgical Quarterly》1998,18(3):589-601

Laparoscopic nephrectomy (LN) was recently introduced as a minimally invasive alternative to open nephrectomy in living related renal donation. Because of the limited field of view available with laparoscopic techniques, the role of preoperative radiologic evaluation in LN has expanded to include anatomic definition of the renal arteries, collecting system, renal parenchyma, and renal venous anatomy. Computed tomographic (CT) angiography has proved to be a minimally invasive alternative to conventional angiography in the preoperative evaluation of living related renal donors. CT angiography has been shown to have an accuracy comparable to that of conventional angiography in predicting renal arterial anatomy. In addition, CT angiography provides comprehensive definition of the renal vascular anatomy including the location, size, and length of the renal, adrenal, gonadal, and lumbar veins. Dual-phase spiral CT combined with three-dimensional CT angiography constitute a single, minimally invasive procedure that can provide a complete preoperative evaluation of potential living related renal donors prior to LN. Comprehensive anatomic depiction of the renal arterial and venous supplies aids in surgical planning and helps avoid potential complications.  相似文献   

    

WT Chang  PA Thomason  JD Gross  PC Neweil 《Canadian Metallurgical Quarterly》1998,17(10):2809-2816

We have isolated an insertional mutant of Dictyostelium discoideum that aggregated rapidly and formed spores and stalk cells within 14 h of development instead of the normal 24 h. We have shown by parasexual genetics that the insertion is in the rdeA locus and have cloned the gene. It encodes a predicted 28 kDa protein (RdeA) that is enriched in charged residues and is very hydrophilic. Constructs with the DNA for the c-Myc epitope or for the green fluorescent protein indicate that RdeA is not compartmentalized. RdeA displays homology around a histidine residue at amino acid 65 with members of the H2 module family of phosphotransferases that participate in multistep phosphoryl relays. Replacement of this histidine rendered the protein inactive. The mutant is complemented by transformation with the Ypd1 gene of Saccharomyces cerevisiae, itself an H2 module protein. We propose that RdeA is part of a multistep phosphorelay system that modulates the rate of development.  相似文献   

    

MW Church  KL Jen  MA Pellizzon  PA Holmes 《Canadian Metallurgical Quarterly》1998,59(3):577-584

Alcohol exposure and undernutrition during pregnancy have been associated with altered fetal body composition. Recent observations suggest that cocaine exposure during pregnancy may impair delivery of nutrients to the fetus and could thereby alter body growth and composition. Such effects are important because they can adversely influence physical and neural development. Consequently, we investigated the dose-dependent effects of cocaine on fetal body composition in an animal (rat) model and compared such effects with those caused by prenatal alcohol exposure and undernutrition. Pregnant Sprague-Dawley rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed (undernutrition) and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups (n = 11 to 14/group). Females were sacrificed on gestation day 20. One male and one female fetus was removed from each dam. The fetuses were minced, dehydrated, defatted, and analyzed for content of protein and the minerals Zn, Ca, Fe, Mg, K, and Na. In terms of concentration per unit of fat-free dry solids, male fetuses in the cocaine groups showed significant decreases in protein compared to untreated controls (15+/-3 to 20+/-2 mg/g vs. 24+/-4 mg/g, p = 0.01). There was a significant treatment effect for Ca (p < 0.05), reflecting a trend for decreased Ca concentrations in the fetuses of the cocaine and undernutrition groups. Male fetuses in the alcohol group had significantly elevated Mg levels compared to male fetuses in the other groups (3.0+/-0.8 vs. 1.0+/-0.2 to 2.3+/-0.7 mg/g, p < 0.05). There were some sex differences, with female fetuses having significantly lower concentrations of Mg, Fe, K, and higher protein concentrations than male fetuses. Although the effects were few and modest, these results suggest that prenatal cocaine, alcohol, and undernutrition can differentially alter fetal body weight and composition and, therefore, adversely influence fetal development.  相似文献   

    

DL Boger  J Zhou  B Winter  PA Kitos 《Canadian Metallurgical Quarterly》1995,3(12):1579-1593

The synthesis and evaluation of two key analogs 3 and 4 of the potent antitumor antibiotics deoxybouvardin (1) and RA-VII (2) which contain fundamental modifications in the tetrapeptide subunit are described. Unlike the natural products, these agents 3 and 4, which substitute (Gly)4 and (Gly)3 for the D-Ala-Ala-NMe-Tyr(OMe)-Ala tetrapeptide subunit, adopt conformations in which the central amide in the cycloisodityrosine subunit adopts its inherently preferred trans stereochemistry and both were found to be biologically inactive.  相似文献   

    

YB Kim  A Furusaki  XG Wen  PA Lee 《Canadian Metallurgical Quarterly》1994,50(24):17917-17932

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HJ Wenzel  TB Cole  DE Born  PA Schwartzkroin  RD Palmiter 《Canadian Metallurgical Quarterly》1997,94(23):12676-12681

Zinc transporter-3 (ZnT-3), a member of a growing family of mammalian zinc transporters, is expressed in regions of the brain that are rich in histochemically reactive zinc (as revealed by the Timm's stain), including entorhinal cortex, amygdala, and hippocampus. ZnT-3 protein is most abundant in the zinc-enriched mossy fibers that project from the dentate granule cells to hilar and CA3 pyramidal neurons. We show here by electron microscopy that ZnT-3 decorates the membranes of all clear, small, round synaptic vesicles (SVs) in the mossy fiber boutons of both mouse and monkey. Furthermore, up to 60-80% of these SVs contain Timm's-stainable zinc. The coincidence of ZnT-3 on the membranes of SVs that accumulate zinc, and its homology with known zinc transporters, suggest that ZnT-3 is responsible for the transport of zinc into SVs, and hence for the ability of these neurons to release zinc upon excitation.  相似文献   

    

RM Davidson  PA Lingenbrink  LA Norton 《Canadian Metallurgical Quarterly》1996,59(6):500-504

G292 osteoblastic cells were cultured in dishes made with a flexible base of polytetrafluoroethylene (PTFE) and stretched ( approximately 1% strain level) continuously for 48 hours. Patch-clamp recording techniques were then used to monitor single channel currents of mechanosensitive ion channels in these cells. To stimulate mechanosensitive channels, we applied suction to the membrane, expressed as -cm Hg, directly through the patch pipette. GigaOhm seals were obtained on a total of 33 osteoblasts that contained a high-conductance ( approximately 180 pS) mechanosensitive channel, all in the cell attached configuration. Of these, 18 were obtained from cells that had been stretched for either 1 (n = 6), 24 (n = 4), or 48 (n = 8) hours, and 15 were obtained in control (nonstretched) cells at either 1 (n = 2), 24 (n = 5), or 48 (n = 8) hours. For unstrained cells, applied pressures ranging from -1 to -5 cm Hg increased the probability of channel opening (Popen) from 0.05 +/- 0. 01 (mean + SEM) to 0.12 +/- 0.07. By contrast, for the same values of applied pressure in stretched cells, Popen ranged from 0.06 +/- 0. 01 to 0.49 +/- 0.15. Our results suggest that intrinsic properties of mechanosensitive ion channels in the G292 osteoblastic cell may be modulated by continuous mechanical loading of the cell itself.  相似文献   

    

CG Fairburn  SL Welch  PA Norman  ME O'Connor  HA Doll 《Canadian Metallurgical Quarterly》1996,153(3):386-391

OBJECTIVE: Since patients being treated for bulimia nervosa constitute only a minority of persons with the disorder, the cases seen in clinics may be subject to sampling bias. The aim of this study was to investigate sampling bias as it affects secondary referrals for bulimia nervosa. METHOD: The personal and family characteristics of a consecutive series of 60 women with secondary referrals for bulimia nervosa (clinic subjects) were compare with those of 83 subjects with bulimia who were recruited directly from the community. Most of the data were collected by interview. RESULTS: The demographic characteristics of the two groups were similar. The clinic subjects had a more severe eating disorder and much greater impairment of social functioning. There was no difference between the groups in duration of the eating disorder or level of general psychiatric disturbance. The community subjects were heavier and had stronger family histories of obesity. CONCLUSIONS: There is sampling bias among secondary referrals for bulimia nervosa. The relative absence of persons prone to obesity among secondary subjects is important, since there is evidence that vulnerability to obesity is a poor prognostic feature as well as being a risk factor for the development of bulimia nervosa. The greater social impairment among the clinic subjects is suggestive of greater personality disturbance in this group. Caution is warranted when generalizing from clinic cases to the disorder as a whole.  相似文献   

    

MD Brennan  PA Thorpe  J Hu  WJ Dickinson 《Canadian Metallurgical Quarterly》1996,181(1-2):51-55

A total of 71 Staphylococcus aureus strains isolated from bovine mammary glands were identified and subtyped. The methods used to differentiate between the S. aureus isolates were the DNA polymorphism pattern after amplification with a Polymerase Chain Reaction using several primer combinations and phage typing. The DNA fingerprinting technique using RAPD, ERIC1R and ERIC primers proved to be useful in differentiating isolates of S. aureus. Differentiation of isolates using phage typing gave no additional information compared to the DNA technique. The outbreak of S. aureus in the herd studied was mainly caused by one S. aureus strain. Other strains were only found on three occasions, twice in subclinical infections and once from a case of clinical mastitis. In the latter case the dominant strain was isolated from a different quarter of the same cow. Four of the ten cows studied suffered from clinical mastitis. From those four cows, three remained infected with the same S. aureus strain despite antibiotic treatment.  相似文献