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21.
Bakos E T Hegedüs Z Holló E Welker GE Tusnády GJ Zaman MJ Flens A Váradi B Sarkadi 《Canadian Metallurgical Quarterly》1996,271(21):12322-12326
The membrane topology of the human multidrug resistance-associated protein (MRP) was examined by flow cytometry phenotyping, immunoblotting, and limited proteolysis in drug-resistant human and baculovirus-infected insect cells, expressing either the glycosylated or the underglycosylated forms of this protein. Inhibition of N-linked glycosylation in human cells by tunicamycin did not inhibit the transport function or the antibody recognition of MRP, although its apparent molecular mass was reduced from 180 kDa to 150 kDa. Extracellular addition of trypsin or chymotrypsin had no effect either on the function or on the molecular mass of MRP, while in isolated membranes limited proteolysis produced three large membrane-bound fragments. These experiments and the alignment of the MRP sequence with the human cystic fibrosis transmembrane conductance regulator (CFTR) suggest that human MRP, similarly to CFTR, contains a tandem repeat of six transmembrane helices, each followed by a nucleotide binding domain, and that the C-terminal membrane-bound region is glycosylated. However, the N-terminal region of MRP contains an additional membrane-bound, glycosylated area with four or five transmembrane helices, which seems to be a characteristic feature of MRP-like ATP-binding cassette transporters. 相似文献
22.
L Silva-Carvalho JF Paton I Rocha GE Goldsmith KM Spyer 《Canadian Metallurgical Quarterly》1998,79(5):2374-2382
The convergence pattern of cardiac receptors, pulmonary C-fibers, carotid chemoreceptor, and baroreceptor afferents onto neurons within the nucleus of the solitary tract (NTS) was studied in the anesthetized (pentobarbitone sodium, 40 mg/kg,) paralyzed and artificially ventilated cat. Extra- and intracellular recordings were made from NTS neurons while stimulating both cardiac receptors by aortic root injections of veratridine (1-3 micrograms/kg) and pulmonary C-fibers by a right atrial injection of phenylbiguanide (10-20 micrograms/kg). The ipsilateral carotid body was stimulated by using arterial injection of CO2-saturated bicarbonate solution, whereas inflation of the ipsilateral carotid sinus was used to activate baroreceptors. The ipsilateral cardiac vagal branch, cervical vagus, and carotid sinus nerves were stimulated electrically (1 Hz, 0.2-1 ms, 1-35 V). In 78 NTS neurons recorded either extracellularly (n = 47) or intracellularly (n = 31), electrical stimulation of the cardiac branch of the vagus nerve evoked synaptic potentials (spikes and/or excitatory postsynaptic potentials) with an onset latency between 4 and 220 ms. Some neurons displayed both short and long latency inputs(15.5 +/- 1.8 and 160.0 +/- 8.5 ms; n = 14). Of these 78 neurons, 24 responded to veratridine stimulation of cardiac receptors (i.e., cardioreceptive neurons) by exhibiting an augmenting-decrementing discharge of 37 +/- 4 s in duration with a peak frequency of 30 +/- 5 Hz. Convergence from other cardiorespiratory receptors was noted involving either carotid chemoreceptors (n = 7) or pulmonary C-fibers (n = 4) or from both carotid chemoreceptors and pulmonary C-fibers (n = 6). In contrast, only one cardioreceptive NTS neuron was activated by distension of the carotid sinus. Recording sites recovered were confined to the medial NTS at the level of the area postrema and extended caudally into the commissural subnucleus. Our results indicate a convergence of carotid chemoreceptor and pulmonary C-fiber afferent inputs to cardioreceptive NTS neurons. With the paucity of baroreceptor inputs to these neurons it is suggested that sensory integration within the NTS may reflect regulatory versus defensive or protective reflex control. 相似文献
23.
BACKGROUND AND PURPOSE: The aim of our study was to characterize the patient profile and prognostic value associated with high positive IgG (>100 GPL) anticardiolipin antibodies (aCL). METHODS: We studied the clinical, laboratory, radiological, and prospective historical features of ischemic cerebrovascular disease in patients with >100 GPL titers. From our neurology department, 27 consecutive patients were prospectively identified and followed up (mean follow-up time, 34 months). RESULTS: The mean age of our cohort was 41 years. Lupuslike illness occurred in 3; 23 had primary antiphospholipid syndrome, including 3 who met criteria for Sneddon's syndrome; 1 patient had progressive systemic sclerosis. Cerebral infarcts occurred in 74% and were recurrent in 37%. Systemic ischemic events, most commonly deep vein thrombosis, occurred in 37%. Tobacco use was documented in 85%, hyperlipidemia in 74%, hypertension in 44%, and diabetes mellitus in 7% of patients. A prominent headache history was present in 67%. Lupus anticoagulant (LA) was present in 72%, approximately one half had positive antinuclear antibodies and thrombocytopenia, and one quarter had a false-positive VDRL. We compared mean GPL levels in patients testing positive for specific laboratory features of antiphospholipid syndrome with those testing negative for these parameters. Only the LA(+) group had a significantly higher mean GPL than the LA(-) group (P=0.006). Brain imaging showed nonlacunar infarcts in 73% and lacunes in 12%. Of 19 cerebral angiograms, 5 (26%) showed large-vessel occlusive disease and 6 (32%) branch obstruction. Echocardiograms were abnormal in 75%: thickened left-sided valves in 33% and vegetations in 12%. Recurrent cerebrovascular ischemic events were observed in 96%, with transient events (mean rate, 25%/y) occurring 5 times more frequently than strokes (mean rate, 5%/y). Using a standardized disability scale blinded to aCL titer, neurological impairment was severe in 7%, moderate in 30%, and mild or nonexistent in 63%, and unrelated to mean GPL value (P=0.567). Titers fluctuated greatly for individual patients, and most did not consistently test as highly positive. An analysis of fluctuation in symptom severity with concurrent GPL values did not show a statistically significant correlation. Compared with historical controls having a wide range of positive titers, the presence of high IgG aCL titers did not confer a worse prognosis for disability and recurrent ischemic events. CONCLUSIONS: Our data suggest that cerebrovascular events associated with high positive GPL are frequently multiple and minor (with no disability-titer correlation), present in relatively young patients, and often associated with tobacco abuse, hyperlipidemia, LA, systemic ischemic events, and occult cardiac disease. 相似文献
24.
WR Bishai NM Graham S Harrington DS Pope N Hooper J Astemborski L Sheely D Vlahov GE Glass RE Chaisson 《Canadian Metallurgical Quarterly》1998,280(19):1679-1684
Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used as a substitute for non-alcoholic sweetener. It has previously been shown to reduce blood pressure in studies in animals and human. The effect of intravenous stevioside on the blood pressure was studied in spontaneously hypertensive rats (SHR). The hypotensive effect on both systolic and diastolic blood pressure was dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious SHR. The maximum reductions in systolic and diastolic blood pressure were 31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg. Serum dopamine, norepinephrine and epinephrine levels were not changed significantly 60 min after intravenous injection of stevioside 100 mg/kg in anesthetized SHR. The present data show that stevioside given intravenously to conscious SHR was effective in blood pressure reduction and there was no change in serum catecholamines in anaesthetized animals with this natural compound. 相似文献
25.
By using perfusions and bolus administration, coupled with postembedding immunocytochemical procedures, we have identified the structures involved in the transport of derivatized orosomucoid (alpha1-acidic glycoprotein) across the continuous microvascular endothelium of the murine myocardium. Our findings indicate that: (i) monomeric orosomucoid binds to the luminal surface of the endothelium; (ii) it is restricted to caveolae during its transport across the endothelium; (iii) it is detected in the perivascular spaces at early time points (by 1 min) and in larger quantities at later time points (>5 min) from the beginning of its perfusion or its intravascular administration; (iv) no orosomucoid molecules are found in the intercellular junctions or at the abluminal exits of interendothelial spaces; and (v) the vesicular transport of orosomucoid is strongly inhibited by N-ethylmaleimide (>80%). Because, by size and shape, the orosomucoid qualifies as a preferential probe for the postulated small pore system, our results are discussed in relation to the pore theory of capillary permeability. 相似文献
26.
Endotoxaemia is a leading cause of death among horses. Thrombocytopenia is a common finding in clinical and experimentally-induced cases of endotoxaemia and can lead to coagulopathies, including disseminated intravascular coagulopathy which is usually fatal. In this study it was shown that endotoxin (3 ng ml-1 to 25 micrograms ml-1) can aggregate equine platelets in heparinised whole blood in vitro. The endotoxin-induced aggregation (EIA) was shown to be dependent on the presence of leucocytes in the blood and did not occur when detoxified endotoxin was used, suggesting that lipid A was necessary for the response. Aspirin (1 mmol litre-1) had no effect on EIA whereas apyrase (40 micrograms ml-1) completely abolished it and CV3988 (3 to 30 mumol litre-1) (a competitive antagonist of platelet-activating factor) inhibited the response in a concentration-dependent manner. It is concluded that endotoxin activates equine platelets at low concentrations through an indirect mechanism that involves calcium, leucocytes, adenine nucleotides and platelet-activating factor. 相似文献
27.
EK Runge RC Albers NE Christensen GE Zwicknagl 《Canadian Metallurgical Quarterly》1995,51(16):10375-10385
28.
游艇概念设计方法与技术研究 总被引:1,自引:0,他引:1
针对游艇的概念设计方法与技术展开研究,从创意设计思维层面入手,建立了游艇设计概念引入、意象及内涵深化的设计创意库,包括海洋生物库、东方文化符号库、其它类产品创意库等三大类;分析了游艇概念设计从抽象到具体的过程,提出了游艇创意概念设计的底影套模法;探讨了游艇设计的参数化、模块化实现技术。 相似文献
29.
针对某型控制器设计的双余度DSP数据采集装置,采用以双端口RAM方式进行数据交换。结果表明,此数据采集装置既能快速完成模拟数据的采样,又能快速地在DSP间进行高速数据交换,同时,还能够满足基于DSP数据采集装置的高精度与小型化要求。 相似文献
30.