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91.
DH Vandorpe BE Shmukler L Jiang B Lim J Maylie JP Adelman L de Franceschi MD Cappellini C Brugnara SL Alper 《Canadian Metallurgical Quarterly》1998,273(34):21542-21553
We have cloned from murine erythroleukemia (MEL) cells, thymus, and stomach the cDNA encoding the Ca2+-gated K+ (KCa) channel, mIK1, the mouse homolog of hIK1 (Ishii, T. M., Silvia, C., Hirschberg, B., Bond, C. T., Adelman, J. P., and Maylie, J. (1997) Proc. Natl. Acad. Sci.(U. S. A. 94, 11651-11656). mIK1 mRNA was detected at varied levels in many tissue types. mIK1 KCa channel activity expressed in Xenopus oocytes closely resembled the Kca of red cells (Gardos channel) and MEL cells in its single channel conductance, lack of voltage-sensitivity of activation, inward rectification, and Ca2+ concentration dependence. mIK1 also resembled the erythroid channel in its pharmacological properties, mediating whole cell and unitary currents sensitive to low nM concentrations of both clotrimazole (CLT) and its des-imidazolyl metabolite, 2-chlorophenyl-bisphenyl-methanol, and to low nM concentrations of iodocharybdotoxin. Whereas control oocytes subjected to hypotonic swelling remained swollen, mIK1 expression conferred on oocytes a novel, Ca2+-dependent, CLT-sensitive regulatory volume decrease response. Hypotonic swelling of voltage-clamped mIK1-expressing oocytes increased outward currents that were Ca2+-dependent, CLT-sensitive, and reversed near the K+ equilibrium potential. mIK1 mRNA levels in ES cells increased steadily during erythroid differentiation in culture, in contrast to other KCa mRNAs examined. Low nanomolar concentrations of CLT inhibited proliferation and erythroid differentiation of peripheral blood stem cells in liquid culture. 相似文献
92.
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
93.
G Boerrigter M Mundhenke P Stark HD Schulte BE Strauer B Schwartzkopff 《Canadian Metallurgical Quarterly》1998,30(11):783-791
Collagen is an essential part of the cardiac interstitium. Collagen subtypes, their location, total amount and the architecture of the fibrillar network are of functional importance. Architecture in terms of density of the fibrillar network is assumed to be reflected by the intensity of immunohistochemical staining of collagen. The aim of this study was to evaluate a video-based microdensitometric method for quantifying density expressed as absorbance of collagen subtypes I and III stained with an indirect immunoperoxidase method in myectomy specimens of patients with hypertrophic obstructive cardiomyopathy. Various factors influencing the immunohistochemical staining product and the technical properties of the image analysis system were investigated. Linearity between collagen concentration and the absorbance of the immunohistochemical staining product was demonstrated for collagen I using a dot-blot technique. Immunohistochemical collagen staining and density measurement were easily reproducible. The cardiac disability of the patients was assessed according to the New York Heart Association (NYHA) criteria. There was a significant increase in collagen type I density with higher NYHA class, whereas no significant association was found for total collagen area fraction. Thus, video-based microdensitometry gives further insight into the structural remodelling of myocardial collagens and reveals their significance in the process of heart failure in hypertrophic cardiomyopathy. 相似文献
94.
H Okada J Woodcock-Mitchell J Mitchell T Sakamoto K Marutsuka BE Sobel S Fujii 《Canadian Metallurgical Quarterly》1998,97(21):2175-2182
BACKGROUND: Ischemia with or without reperfusion induces the release of diverse products from monocytes, including cytokines such as interleukin-1 (IL-1). To determine whether these phenomena modulate fibrinolysis and potentially exacerbate impairment of the macrocirculation, microcirculation, or both, we characterized the effects of IL-1 on the expression of fibrinolytic system and matrix proteins in rat cardiac microvascular endothelial cells (CMECs). METHODS AND RESULTS: Confluent CMECs were exposed to IL-1 in serum-free medium for 24 hours, and cell-conditioned medium was assayed for plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of plasminogen activators, and for type 1 collagen with Western blotting. IL-1 (2 ng/mL) specifically increased the accumulation of PAI-1 (4.4 +/- 0.6-fold; mean +/- SD; n = 9) without affecting tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA) levels, which remained unchanged. IL-1 increased the accumulation of collagen in conditioned media by 3.5 +/- 0.7-fold (n = 6). Conversely, the accumulation of both PAI-1 and collagen induced by IL-1 was inhibited with an IL-1 receptor antagonist (200 ng/mL; n = 6) and with cycloheximide (10 micrograms/mL; n = 6), implying that protein synthesis was a requirement for the effect. To determine whether the IL-1 effect was mediated by induction of oxygen-centered free radical production, known to be induced by IL-1, we exposed the cells to the hydroxyl radical scavenger tetramethylthiourea (10 mmol/L) and observed abolition of the IL-1-induced increase in the expression of PAI-1 and collagen (n = 6). Conversely, superoxides (generated with 10 mU/mL xanthine oxidase plus 0.6 mmol/L hypoxanthine, and 100 mumol/L hydrogen peroxide) induced the accumulation of PAI-1 and collagen (n = 6). IL-1 (1 microgram/kg body wt) and lipopolysaccharide (50 micrograms/kg body wt) administered in vivo increased PAI-1 protein in rat hearts as detected with Western blotting and PAI-1 immunostaining of rat heart microvessels, indicating the effects delineated in vitro were paralleled by effects in vivo. CONCLUSIONS: These results indicate that IL-1-induced oxygen-centered free radicals stimulate elaboration of PAI-1 and collagen by CMECs. Accordingly, microvascularly mediated inhibition of fibrinolysis may predispose to the persistence of microvascular thrombi, thereby contributing to impaired microcirculatory function, the no-reflow phenomenon, and cardiac dysfunction after ischemia and reperfusion. 相似文献
95.
Although the proposed regulations do not yet have the force and effect of law and HCFA is still seeking input in a variety of substantive areas, the regulations as proposed reflect HCFA's current view of enforcement of Stark II. Although simply complying with the statutory language and the Stark I regulations may be enough to avoid scrutiny until the proposed regulations are promulgated in final form, this approach may set physicians and physician groups up for significant disruption in their relationships in the future, particularly when proposed regulations have called certain practices into question. Clearly, every relationship between a physician (and his or her physician group) and any entity that provides DHS should be reexamined in light of the proposed regulations. In addition, arrangements under negotiation should be structured with the proposed new requirements in mind. 相似文献
96.
97.
Zhang D. Rahmat-Samii Y. Fetterman H.R. Prakash S. Bunshah F.R. Eddy M. Nilsson J.L. 《Microwave Theory and Techniques》1993,41(6):1032-1036
The use of YBa2Cu3O7-x and Tl2CaBa2Cu2O8 high-temperature superconducting thin films to fabricate frequency selective surfaces (FSS) at millimeter-wave frequencies (75-110 GHz) is discussed. An analytical/numerical model was applied, using a Floquet expansion and the method of moments, to analyze bandstop superconducting frequency selective surfaces. Experimental results were compared with the model, and showed agreement with resonant frequency prediction with an accuracy of better than 1%. The use of the superconducting frequency selective surfaces as quasi-optical millimeter-wave bandpass filters was also demonstrated 相似文献
98.
BE Hunte M Capone A Zlotnik D Rennick TA Moore 《Canadian Metallurgical Quarterly》1998,28(11):3850-3856
The present study describes three subsets of bone marrow-derived Lin CD43+B220(low) (B220(low)) progenitor cells which represent distinct stages in hematopoietic development. These populations differ in their expression of CD24 and ckit and the occurrence of IgH gene rearrangement. B220(low) CD24-ckit(hi) progenitors have their IgH loci in germ-line configuration and are multipotent since they can give rise to B cells, T cells and myeloid cells. B220lowckit(hi) cells which have acquired CD24 expression have retained IgH loci in germ-line configuration and the ability to generate B cells, however, they have lost the ability to generate T cells and myeloid cells. Thus acquisition of CD24 by B220(low) cells occurs concurrently with the transition from a multipotent to a lineage-restricted progenitor population. B220(low)CD24+ cells expressing low levels of ckit are also lineage restricted, giving rise to only B cells and have begun D-J(H) rearrangement, implying that initiation of IgH rearrangement coincides with the down-regulation of ckit expression. 相似文献
99.
100.
An electrical negative frequency feedback scheme is applied to a semiconductor laser to improve its direct frequency modulation performance in an FSK transmitter. An error signal caused by imperfect FM response is extracted through heterodyne discrimination detection with a stable master laser and fed back to the FM semiconductor laser. 相似文献