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151.
CT Dolphin DJ Beckett A Janmohamed TE Cullingford RL Smith EA Shephard IR Phillips 《Canadian Metallurgical Quarterly》1998,273(46):30599-30607
Flavin-containing monooxygenases (FMOs) are NADPH-dependent flavoenzymes that catalyze the oxidation of heteroatom centers in numerous drugs and xenobiotics. FMO2, or "pulmonary" FMO, one of five forms of the enzyme identified in mammals, is expressed predominantly in lung and differs from other FMOs in that it can catalyze the N-oxidation of certain primary alkylamines. We describe here the isolation and characterization of cDNAs for human FMO2. Analysis of the sequence of the cDNAs and of a section of the corresponding gene revealed that the major FMO2 allele of humans encodes a polypeptide that, compared with the orthologous protein of other mammals, lacks 64 amino acid residues from its C terminus. Heterologous expression of the cDNA revealed that the truncated polypeptide was catalytically inactive. The nonsense mutation that gave rise to the truncated polypeptide, a C --> T transition in codon 472, is not present in the FMO2 gene of closely related primates, including gorilla and chimpanzee, and must therefore have arisen in the human lineage after the divergence of the Homo and Pan clades. Possible mechanisms for the fixation of the mutation in the human population and the potential significance of the loss of functional FMO2 in humans are discussed. 相似文献
152.
Mibefradil is a new cardiovascular drug with peculiar Ca++ antagonistic properties. The most remarkable feature of mibefradil is its unique relative selectivity for T type calcium channels, a property that has been proposed to explain in part the beneficial pharmacological and clinical profiles of this drug. In adrenal glomerulosa cells, aldosterone biosynthesis and secretion in response to angiotensin II or extracellular potassium is dependent on a sustained influx of Ca++ through T type Ca++ channels. The effect of mibefradil on the steroidogenic function of glomerulosa cells was therefore investigated. Using the patch clamp technique, we found that mibefradil inhibits selectively and in a concentration-dependent manner (IC50 = 3 microM)++ T type currents in bovine glomerulosa cells. In addition to this tonic (voltage independent) inhibition, the drug also induced a shift of the steady-state inactivation curve of these channels toward hyperpolarized voltages, contributing to its efficacy to prevent Ca++ influx into the cell through T type channels. Concomitantly, mibefradil reduced the cytosolic calcium responses to potassium and angiotensin II (as assessed with fluorescent probes), without affecting the capacitative Ca++ influx, and inhibited pregnenolone and aldosterone formation. This inhibition of steroidogenesis was not exclusively due to mibefradil action on voltage-operated Ca++ channels, because this agent also partially reduced steroid synthesis induced by adrenocorticotropic hormone or forskolin, two activators of the cyclic AMP pathway. In conclusion, mibefradil is highly effective in adrenal glomerulosa cells in reducing T type channel activity and aldosterone biosynthesis, two actions that should contribute to the beneficial effect of the drug in the treatment of hypertension. 相似文献
153.
Maureen T. Ross Rena Cruz Trent L. Brooks-Richards Louise M. Hafner Sean K. Powell Maria A. Woodruff 《Virtual and Physical Prototyping》2018,13(4):255-265
Congenital facial anomalies, such as microtia (malformation of the external ear), lead to significant psychosocial effects starting from early childhood. Three-dimensional (3D) scanning and advanced manufacturing are being investigated as a cheaper and more personalised method of fabricating reconstructive treatments for patients compared to traditional approaches. To date, most case studies have used expensive 3D scanners, yet, there is potential for low-cost devices to provide comparable results. This study aimed to investigate these different approaches. Both ears of 16 adult participants were scanned with three devices: Artec Spider (Artec Group), Intel® RealSense? (Intel), and the Apple iPhone® 7 (Apple Inc.) combined with photogrammetry using 90, 60 and 30 photographs. The scanning time, processing time, accuracy, completeness, resolution and repeatability of each technique were assessed using the Artec Spider as a reference scanner. Our results show that the iPhone had the longest processing time however, this decreased nine-fold when reducing the number of photos from 90 to 30. There was no significant difference in the accuracy, completeness or repeatability of the iPhone scans with 90 photographs (1.4?±?0.6?mm, 79.9%, 1.0?±?0.1?mm), 60 photographs (1.2?±?0.2, 79.3%, 0.9?±?0.2?mm) or 30 photographs (1.2?±?0.3?mm, 74.3%, 1.0?±?0.2?mm). The Intel RealSesne performed significantly worse in each parameter (1.8?±?03?mm; 46.6%, 1.4?±?0.5). Additionally, the RealSense had significantly lower resolution with not enough detail captured for the application. These results demonstrate that the ear can be accurately 3D scanned using iPhone photographs. We would recommend capturing between 30 and 60 photographs of the ear to create a scan that is accurate but without the downfall of long processing time. Using these methods we aim to provide a more comfortable setting for the patient and a lower-cost and more personalised ear prosthesis. 相似文献
154.
DH Kang CL Coe DO McCarthy NN Jarjour EA Kelly RR Rodriguez WW Busse 《Canadian Metallurgical Quarterly》1997,17(8):481-487
T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation. 相似文献
155.
KR Solomon EA Kurt-Jones RA Saladino AM Stack IF Dunn M Ferretti D Golenbock GR Fleisher RW Finberg 《Canadian Metallurgical Quarterly》1998,102(11):2019-2027
Septic shock induced by lipopolysaccharide (LPS) triggering of cytokine production from monocytes/macrophages is a major cause of morbidity and mortality. The major monocyte/macrophage LPS receptor is the glycosylphosphatidylinositol (GPI)-anchored glycoprotein CD14. Here we demonstrate that CD14 coimmunoprecipitates with Gi/Go heterotrimeric G proteins. Furthermore, we demonstrate that heterotrimeric G proteins specifically regulate CD14-mediated, LPS-induced mitogen-activated protein kinase (MAPK) activation and cytokine production in normal human monocytes and cultured cells. We report here that a G protein binding peptide protects rats from LPS-induced mortality, suggesting a functional linkage between a GPI-anchored receptor and the intracellular signaling molecules with which it is physically associated. 相似文献
156.
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159.
TI Lezhen SA Kramarev EA Dmitrieva LA Palatnaia VN Blagodatny? 《Canadian Metallurgical Quarterly》1996,68(6):104-108
Practical application of turbidimetrical method for the diagnosis of haemostasis disorders in babies with acute intestinal infections (AII) is described. The results of plasma biochemical analysis show that disturbances in balance between coagulation and fibrinolytic systems takes place in patients with this pathology. The correlation between biochemical parameters and clinical characteristics is observed. As follows from our data, the phase of the haemostasis disorders in babies with AII does not depend on etiology of the disease, but indicates its severity. 相似文献
160.
Ten PD patients and ten age-matched normal controls learned a sequence of 3 or 4 different hand movements to a criterion of 5 consecutive correct trials. They also performed a control sequence of 3 or 4 movements which involved the repetition of the same hand posture. Trials to reach criterion, errors, total response time and its components, response time for each movement and inter-response time were examined. There were no group differences in trials to criterion or errors. Total movement time as well as response and inter-response times were significantly longer for the PD patients, however, but only for sequences involving different hand movements not for the repetitive sequences. The relative timing of the responses was also different with the PD patients spending proportionately more time on each response and the controls spending more time between responses. The implications of these findings for understanding the movement sequencing impairments in PD are discussed. 相似文献