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81.
L Madlensky TC Berk BV Bapat RS McLeod J Couture D Baron T Hiruki M Redston Z Cohen S Gallinger 《Canadian Metallurgical Quarterly》1995,5(2):355-360
Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic disorder characterized by a strong family history of colorectal and extracolonic cancers, usually at a young age. This article presents a new provincial service for families with HNPCC. The Steve Atanas Stavro Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital is accruing patients that meet a set of criteria establishing a putative diagnosis of HNPCC. The objectives of the Registry are to develop and assess patient pedigrees, to coordinate screening procedures for at-risk persons, to maintain a prospective database of patient information, to provide education and support for families and to contribute to research. To date, surgeons and patients are the most common referral sources, while oncologists and geneticists are the least common. The ultimate goal of the HNPCC service is the secondary prevention of cancer and a corresponding decrease in mortality for HNPCC family members. 相似文献
82.
JG Wilcox FZ Stanczyk RS Morris E Gentzschein RA Lobo 《Canadian Metallurgical Quarterly》1996,66(5):748-752
OBJECTIVE: To determine the independent biologic effects of 17 alpha-dihydroequilin sulfate. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENTS(S): Twenty-one postmenopausal women, mean age 50 +/- 2 (+/-SEM) years, and mean body mass index 27 +/- 2. INTERVENTION(S): Women were randomized to receive daily oral doses of either 1.25 mg of estrone sulfate (E1S), 0.2 mg of 17 alpha-dihydroequilin sulfate, or a combination. Three blood and urine samples were obtained before and after 30 and 90 days of treatment. RESULT(S): After 30 and 90 days of treatment, E1S alone increased sex hormone-binding globulin (SHBG) levels significantly, 19.7% +/- 6.0% and 61.3% +/- 13.0%, whereas 17 alpha-dihydroequilin sulfate reduced SHBG levels, 20.8% +/- 68% and 12.4% +/- 7.5%, respectively. Nevertheless, the combination of E1S and 17 alpha-dihydroequilin sulfate significantly increased SHBG levels, 103% +/- 27.9% and 98.2% +/- 19.1%, compared with baseline at 30 and 90 days. Fewer changes were evident with corticosteroid-binding globulin (CBG). After 90 days of treatment, CBG levels significantly increased 30.9% +/- 5.5% with E1S, decreased by 7.2% +/- 5.0% with 17 alpha-dihydroequilin sulfate, and, with the combination, significantly increased by 10.5% +/- 2.4% compared with baseline. Changes in lipids and lipoproteins were more variable. However, high-density-lipoprotein cholesterol increased significantly with E1S at 30 and 90 days compared with baseline, 96.5% +/- 39% and 91.5% +/- 22.6%, and with the combination increased 66.4% +/- 13.3% and 79.2% +/- 24.4%, respectively. Fewer changes were evident with 17 alpha-dihydroequilin sulfate alone, decreasing 4.4% +/- 22% and 2.6% +/- 21.3%. Urinary ratios of bone collagen equivalents-creatinine and calcium-creatinine decreased in all three groups. However, the combination group resulted in a significantly greater percentage decrease in bone collagen equivalents-creatinine than with E1S alone. CONCLUSIONS(S): 17 alpha-Dihydroequilin sulfate could modify some of the first-pass effects of conjugated equine estrogens and act synergistically with other conjugated equine estrogens to reduce bone resorption. 相似文献
83.
IK Temple RJ Gardner DO Robinson MS Kibirige AW Ferguson JD Baum JC Barber RS James JP Shield 《Canadian Metallurgical Quarterly》1996,5(8):1117-1121
Transient neonatal diabetes mellitus (TNDM) is a rare form of childhood diabetes which usually resolves in the first 6 months of life but which predisposes to type 2 diabetes of adult onset. We recently reported paternal uniparental isodisomy of chromosome 6 (UPD6) in two children with TNDM and proposed that there may be an imprinted gene important in the aetiology of diabetes on chromosome 6. We now describe two unrelated families which independently suggest that the gene is imprinted, is paternally expressed and maps to 6q22-q23. One family has a duplication while the other, with familial TNDM, shows linkage to a marker in this region. 相似文献
84.
RD Howard RS Martens SA Innis JM Drnevich J Hale 《Canadian Metallurgical Quarterly》1998,55(5):1151-1163
A sexual size dimorphism usually occurs when size-dependent reproductive advantages exist in only one sex. Studies on Japanese medaka, Oryzias latipes, have demonstrated reproductive size advantages in females but not in males, even though males and females are similar in body size. We conducted mate-choice and mate-copying tests in which a female could first associate with, then mate with, either a large (>/=1 sd+X standard length) or a small male (=1 sd-X standard length). Large males obtained a mating advantage in both tests, and both mate choice and mate competition influenced their mating success. In the majority of trials, females associated with large males. Association preferences of females corresponded to their mating preferences when mate competition between males was weak; however, when mate competition was strong, large males obtained almost every mating regardless of female association preference. Preference for large males may provide females with a reproductive advantage if males mate multiply because small males become sperm-depleted sooner than large males. We found no indication that females copied the mating decisions of other females. Repeatability of female mating preference was low, not because females mated at random with respect to male size, but because most females consistently preferred large males. We also conducted mating tests at four density levels and found that large males maintained their mating advantage relative to small males at all densities. Thus, male and female medaka may be similar in body size because large size provides a fecundity advantage for females, as demonstrated in previous studies, and large size provides a mating advantage for males, as demonstrated in our study. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour. 相似文献
85.
Objective. To assess the role of coronal and sagittal vertebral clefts in diagnosing skeletal dysplasias. Material and Methods. A search in the database at the International Skeletal Dysplasia Registry revealed 40 different diagnoses in which coronal or sagittal clefts were present, the major groups being: atelosteogenesis, chondrodysplasia punctata, dyssegmental dysplasia, Kniest dysplasia and short rib polydactyly syndrome. We reviewed all firm cases with both AP and lateral films of the spine in these major groups (n = 143), with patients' ages ranging from 20 weeks of gestation up to 26 years of age. Results. Ninety-four percent of all clefts were found in children less than 1 year of age, mainly located in the thoracolumbar region. Fifty-six percent of the clefts were observed in boys. Coronal clefts were more common than sagittal clefts. Clefts were most frequently observed in atelosteogenesis (88%), followed by chondrodysplasia punctata (79%), dyssegmental dysplasia (73%), Kniest dysplasia (63%) and short rib polydactyly syndrome (53%). Conclusion. Vertebral clefts are of major diagnostic value in the groups mentioned above, especially before 1 year of age. The search did not come up with new entities in which vertebral clefts are of major diagnostic value. 相似文献
86.
CA Porr DS Kronfeld LA Lawrence RS Pleasant PA Harris 《Canadian Metallurgical Quarterly》1998,76(7):1875-1879
Diet and exercise are two management factors that affect bone density and strength. We proposed that bone density and calcium status would be affected by deconditioning for 12 wk and by dietary Ca concentration. Eleven highly conditioned Arabian horses were taken out of training and placed in stalls for 12 wk. Horses were walked on a mechanical walker in two 30-min sessions, 7 d/wk. Diets were designated CC (.36% Ca) and HC (.62% Ca). Data were collected every 21 d. Serum or plasma were analyzed for total and ionized Ca, parathyroid hormone, osteocalcin, hydroxyproline, electrolytes, and blood gases. Bone mineral content (BMC) of the left third metacarpal bone was estimated by radiographic photometry using an aluminum step wedge, which was exposed in each radiograph, as a reference standard for an image analysis system. During deconditioning, BMC decreased by approximately 1.1 g/2 cm, or .45% per week. This decrease was unaffected by dietary Ca. Serum Ca concentration increased with deconditioning. The results suggest that dietary Ca at twice the currently recommended level did not prevent the loss of BMC in response to deconditioning. Loss of BMC during 12 wk of stall confinement may weaken bones, increasing the risk of skeletal injuries when training is resumed. 相似文献
87.
Although sequences within the C terminus of apolipoprotein B (apoB) have been implicated in the formation of covalent lipoprotein(a) [Lp(a)] particles, sequences in apoB that mediate initial noncovalent interaction with apo(a) remain to be characterized. To address this question, we have used an affinity chromatography method in which 2 recombinant forms of apo(a) [r-apo(a); either a 17-kringle form (17K) or a derivative containing apo(a) kringle IV types 5-8] have been immobilized onto Sepharose beads. Conditioned media from rat hepatoma (McA-RH7777) cell lines stably expressing various carboxyl-terminally truncated forms of human apoB (ranging from full-length apoB to apoB15) were applied to the r-apo(a) affinity columns; the columns were subsequently washed and eluted with epsilon-aminocaproic acid (epsilon-ACA). Specific binding was quantified by Western blot analysis of column fractions. Of the apoB truncations examined, apoB94, apoB42, apoB37, and apoB29 exhibited complete specific binding to 17K r-apo(a). Only approximately 50% binding was observed for apoB18, whereas essentially no detectable binding was observed with apoB15. In all cases, similar results were obtained when the r-apo(a) kringle IV types 5-8-Sepharose column was used. Additionally, substitution of proline for epsilon-ACA as the eluent resulted in similar column profiles with either r-apo(a) affinity column. We also demonstrated that apoB48 present in chylomicrons bound completely to the 17K column in an epsilon-ACA-dependent manner. Taken together, these results represent the first demonstration that N-terminal sequences in apoB between amino acid residues 680 (apoB15) and 781 (apoB18) are essential for noncovalent association with apo(a) and that these sequences interact with domain(s) present within apo(a) kringle IV types 5-8. 相似文献
88.
RS Vander Heide LM Schwartz RB Jennings KA Reimer 《Canadian Metallurgical Quarterly》1995,30(5):656-662
OBJECTIVES: Cardioprotective adaptation to brief periods of ischemia and reperfusion is termed ischemic preconditioning (PC). Limitation of infarct size by preconditioning is associated with marked slowing of ischemic metabolism. The cause of metabolic slowing has not been determined but may involve either pro- or anti-adrenergic mechanisms. Hypothetically, adrenergic stimulation could signal the adaptive response. Alternatively, metabolic slowing during the sustained ischemic challenge could occur through a reduction in beta-adrenergic stimulation. This study was designed to test the role of cardiac norepinephrine (NE) in PC. METHODS: The effect of PC on myocardial infarct size was studied in control dogs and dogs depleted of catecholamines by pretreatment with reserpine (RES; 0.25 mg/kg i.v.). PC was induced by four cycles of 5 min of ischemia and 5 min of reperfusion. Infarcts were produced by 60 min of ischemia and 3 h of reperfusion. Cardiac NE depletion was verified by radioimmunoassay of tissue samples and by absence of hemodynamic response to a tyramine bolus (1.4 mg/kg) administered at the end of each experiment. Infarct size, expressed as percent of area at risk, was controlled for variation in collateral blood flow using analysis of covariance (ANCOVA). RESULTS: Adjusted mean infarct size was 25.5 +/- 3.2% in untreated controls vs. 19.1 +/- 3.3% in RES-treated controls (P = NS). PC limited infarct size in untreated dogs (7.4 +/- 1.8 vs. 25.5 +/- 3.2%; PC vs. control; P < 0.01) but not in RES-treated dogs (15.7 +/- 3.0% vs. 19.1 +/- 3.3%; RES + PC vs. RES; P = NS). Infarct size was larger in dogs with RES + PC than with PC alone, even though there was a trend toward a slight beneficial effect with RES alone. CONCLUSION: The cardioprotective effect of ischemic preconditioning cannot be explained entirely as an anti-adrenergic effect. On the contrary, adrenergic receptor stimulation may be required for the full expression of ischemic preconditioning in canine myocardium. 相似文献
89.
FTIR difference spectroscopy has been established as a new tool to study the GTPase reaction of H-ras p21 (Ras) in a time-resolved mode at atomic resolution without crystallization. The phosphate vibrations were analyzed using site specifically 18O-labeled caged GTP isotopomers. One nonbridging oxygen per nucleotide was replaced for an 18O isotope in the alpha-, beta-, or gamma-position of the phosphate chain. In photolysis experiments with free caged GTP, strong vibrational coupling was observed among all phosphate groups. The investigation of Ras*caged GTP photolysis and the subsequent hydrolysis reaction of Ras*GTP showed that the phosphate vibrations are largely decoupled by interaction with the protein in contrast to free GTP. The characteristic isotope shifts allow band assignments to isolated alpha-, beta-, and gamma-phosphate vibrations of caged GTP, GTP, and the liberated inorganic phosphate. The unusually low frequency of the beta (PO2-) vibration of Ras-bound GTP, as compared to free GTP, indicates a large decrease in the P-O bond order. The bond order decrease reveals that the oxygen atoms of the beta (PO2-) group interact much more strongly with the protein environment than the gamma-oxygen atoms. Thereby, electrons are withdrawn from the beta-phosphorus, and thus also from the beta/gamma-bridging oxygen. This leads to partial bond breakage or at least weakening of the bond between the beta/gamma-bridging oxygen and the gamma-phosphorus atom as a putative early step of the GTP hydrolysis. Based on these results, we propose a key role of the beta-phosphate for GTP hydrolysis. The assignments of phosphate bands provide a crucial marker for further time-resolved FTIR studies of the GTPase reaction of Ras. 相似文献
90.
Host recognition and disposal of LPS, an important Gram-negative bacterial signal molecule, may involve intracellular processes. We have therefore analyzed the initial pathways by which LPS, a natural ligand of glycosylphosphatidylinositol (GPI)-anchored CD14 (CD14-GPI), enters CD14-expressing THP-1 cells and normal human monocytes. Exposure of the cells to hypertonic medium obliterated coated pits and blocked 125I-labeled transferrin internalization, but failed to inhibit CD14-mediated internalization of [3H]LPS monomers or aggregates. Immunogold electron microscope analysis found that CD14-bound LPS moved principally into noncoated structures (mostly tubular invaginations, intracellular tubules, and vacuoles), whereas relatively little moved into coated pits and vesicles. When studied using two-color laser confocal microscopy, internalized Texas Red-LPS and BODIPY-transferrin were found in different locations and failed to overlap completely even after extended incubation. In contrast, in THP-1 cells that expressed CD14 fused to the transmembrane and cytosolic domains of the low-density lipoprotein receptor, a much larger fraction of the cell-associated LPS moved into coated pits and colocalized with intracellular transferrin. These results suggest that CD14 (GPI)-dependent internalization of LPS occurs predominantly via noncoated plasma membrane invaginations that direct LPS into vesicles that are distinct from transferrin-containing early endosomes. A smaller fraction of the LPS enters via coated pits. Aggregation, which greatly increases LPS internalization, accelerates its entry into the nonclathrin-mediated pathway. 相似文献