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K Papadakis FI Luks ME De Paepe GJ Piasecki CW Wesselhoeft 《Canadian Metallurgical Quarterly》1997,32(2):347-351
We investigated cell proliferation and cell death in the olfactory epithelium (OE) of mice from birth to maturity using bromodeoxyuridine and terminal deoxynucleotidyl transferase nick end labeling. We show that cell death events and proliferative activity diminish concomitantly with age in the OE. Thus, the age-dependent and coordinate diminution in cell proliferative activity and cell death events may serve to maintain the thickness of the OE as mice mature and age. 相似文献
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TL Tomusiak FI Mamchur NV Zeliak LT Kisilevich ZR Matsun IN Gurvits 《Canadian Metallurgical Quarterly》1993,(3):11-13
Long-term (1-10 years) results of wandering kidney surgery were followed-up for 118 patients. The outcomes were found dependent on the duration of the disease, variety and severity of the lesion, age of the patients. The response appeared better in younger patients, in those with shorter duration of the disease and with unessential changes in the kidney. Recommendations are provided on the regimens, jobs, outpatient and inpatient follow-up for the subjects treated surgically for wandering kidney to reinforce the correction results achieved. 相似文献
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JB Thomas MJ Fall JB Cooper RB Rothman SW Mascarella H Xu JS Partilla CM Dersch KB McCullough BE Cantrell DM Zimmerman FI Carroll 《Canadian Metallurgical Quarterly》1998,41(26):5188-5197
A three-component library of compounds was prepared in parallel using multiple simultaneous solution-phase synthetic methodology. The compounds were biased toward opioid receptor antagonist activity by incorporating (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (a potent, nonselective opioid pure antagonist) as one of the monomers. The other two monomers, which included N-substituted or unsubstituted Boc-protected amino acids and a range of substituted aryl carboxylic acids, were selected to add chemical diversity. Screening of these compounds in competitive binding experiments with the kappa opioid receptor selective ligand [3H]U69,593 led to the discovery of a novel kappa opioid receptor selective ligand, N-?(2'S)-[3-(4-hydroxyphenyl)propanamido]-3'-methylbutyl?-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (8, RTI-5989-29). Additional structure-activity relationship studies suggested that 8 possesses lipophilic and hydrogen-bonding sites that are important to its opioid receptor potency and selectivity. These sites appear to exist predominantly within the kappa receptor since the selectivity arises from a 530-fold loss of affinity of 8 for the mu receptor and an 18-fold increase in affinity for the kappa receptor relative to the mu-selective ligand, (+)-N-[trans-4-phenyl-2-butenyl]-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (5a). The degree of selectivity observed in the radioligand binding experiments was not observed in the functional assay. According to its ability to inhibit agonist stimulated binding of [35S]GTPgammaS at all three opioid receptors, compound 8 behaves as a mu/kappa opioid receptor pure antagonist with negligible affinity for the delta receptor. 相似文献
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SA Nachman FI Chasalow M Navaie-Waliser SL Blethen P Tropper 《Canadian Metallurgical Quarterly》1996,16(6):449-454
We measured human chorionic gonadotropin (hCG) in cord sera of 22 infants born to women infected with the human immunodeficiency virus-1 (HIV-1). hCG was also determined in cord sera from 173 infants born at a suburban hospital to HIV-1-seronegative women. The findings indicate that 16 (9%) of 173 HIV-1-seronegative samples had hCG levels greater than 90 IU/L (values were distributed as a Poisson curve). In contrast, 8 (36%) of the 22 infants born to HIV-1-infected women had hCG levels in excess of 90 IU/L, and 7 (88%) of these were shown to be HIV-infected. The remaining 14 infants born to HIV-1-infected women had low hCG levels, and 3 (21%) of the 14 had HIV infection. Mean follow-up time for HIV-uninfected infants was 17.5 months (range 9 months to 3 years). A statistically significant association between maternal-fetal HIV-1 transmission and hCG levels > or = 90 IU/L in cord sera was observed (p = 0.02). The difference between CD4 counts among mothers who transmitted HIV and those who did not was also statistically significant (p = 0.025). On the basis of this study's findings, we propose that cord blood hCG may serve as a surrogate marker for HIV-1 infection. Testing hCG levels in cord sera is an inexpensive and readily available screening test for early identification of infants at increased risk for getting HIV-1 from their mothers. 相似文献
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BACKGROUND: Staff development experts in a tertiary-care hospital were searching for a holistic approach to facilitating improved outcomes. METHOD: Staff development experts, clinical nurse specialists, and clinical managers developed a model that provides a framework for educators to integrate their energies with those of other leaders in order to create a holistic approach to the goal of achieving excellence. RESULTS: The model that is proposed links strategies for change with outcome evaluation. CONCLUSIONS: The model provides a conceptual lens that helps nurse leaders focus on organizational assessment, strategies to improve the work environment, and the evaluation of outcomes. The model is useful for guiding practice as well as research. 相似文献
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In addition to classical steroids, which have cholesterol as a precursor, there are steroids with 7-dehydrocholesterol as a precursor. This review describes the identification of these steroids, their biosynthesis, and some aspects of their function. There are three classes of these compounds, distinguished by the number of their carbon atoms, 23, 24, and 25. Each class has a spiral steroid and is a phosphodiester. Up until these investigations, no spiral steroids or steroid phosphodiesters were known. There are at least 13 compounds, of which six have been purified to near homogeneity; each one has been characterized by its mass and proposed composition, and they function by regulating the NaK-ATPase. Based on the tissues in which they have been detected, each class of compound seems to regulate a different isoform of the NaK-ATPase. This is an important site of endocrine regulation. 相似文献
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FI Meredith RT Riley CW Bacon DE Williams DB Carlson 《Canadian Metallurgical Quarterly》1998,61(8):1034-1038
The purpose of this study was (i) to determine whether pure fumonisin B1 could be incorporated into, recovered, and detected by high-pressure liquid chromatographic analysis from the semipurified Oregon test diet (OTD) used in rainbow trout feeding studies, and (ii) to determine if the incorporated fumonisin B1 was biologically available using the change in free sphingoid bases in liver, kidney, and serum as a mechanism-based biomarker. The results indicate that fumonisin is not easily quantified in the OTD. Recoveries ranged from 12 to 81% of the calculated concentrations based on the fumonisin B1 added to the OTD. However, the fumonisin B1 in the OTD was readily absorbed and biologically active as evidenced by marked increases in free sphinganine in liver, kidney, and serum. The magnitude of the increase in free sphinganine at 100 ppm in the OTD was comparable to that known to be associated with liver toxicity in rats, pigs, and ponies. 相似文献
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JB Thomas SW Mascarella RB Rothman JS Partilla H Xu KB McCullough CM Dersch BE Cantrell DM Zimmerman FI Carroll 《Canadian Metallurgical Quarterly》1998,41(11):1980-1990
A study of the binding site requirements associated with the N-substituent of (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) derivatives was undertaken using a set of rigid vs flexible N-substituents. The study showed that compounds 7-9 bearing the trans-cinnamyl N-substituent most closely reproduced the potency at the opioid receptor of the flexible N-propylphenyl or N-propylcyclohexyl analogues previously reported. Neither the N-substituted cis-cinnamyl nor the cis-phenylcyclopropylmethyl compounds 10 and 11, respectively, showed high affinity for the opioid receptor. However, the N-trans-phenylcyclopropylmethyl compound 12 closely approximated the affinity of compounds 7-9. Additionally, we found that free rotation of the phenyl ring is necessary for high affinity binding and mu receptor subtype selectivity as the planar N-substituted thianaphthylmethyl and benzofuranylmethyl compounds 13 and 14 had significantly lower binding affinities. Altogether, these findings suggest that the high binding affinity, selectivity, and antagonist potency of N-propylphenyl or N-propylcyclohexyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) are achieved via a conformation wherein the connecting chain of the N-substituents is extended away from piperidine nitrogen with the appended ring system rotated out-of-plane relative to the connecting chain atoms. This conformation is quite similar to that observed in the solid state for 5, as determined by single crystal X-ray analysis. Additionally, it was found that, unlike naltrexone, N-substituents bearing secondary carbons attached directly to the piperidine nitrogen of 4 suffer dramatic losses of potency vs analogues not substituted in this manner. Using a functional assay which measured stimulation or inhibition of [35S]GTP-gamma-S binding, we show that the trans-cinnamyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) retain opioid pure antagonist activity and possess picomolar antagonist potency at the mu receptor. 相似文献