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1.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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Non-secretion of ABO blood group antigens as a host susceptibility factor in the spondyloarthropathies 总被引:1,自引:0,他引:1
R Shinebaum C C Blackwell P J Forster N P Hurst D M Weir G Nuki 《British medical journal (Clinical research ed.)》1987,294(6566):208-210
Gram negative bacteria precipitate reactive arthritis and may be concerned in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state, or both. The distribution of the ABO blood group or secretor state, or both, was therefore determined in 87 patients with ankylosing spondylitis and 32 with other forms of spondyloarthropathy. The prevalence of non-secretors was significantly increased in the total patient group (54/114; 47%) and in the subgroup with ankylosing spondylitis (41/84; 49%) compared with local controls (89/334; 27%) (p less than 0.001). Other subgroups of patients showed a similarly increased prevalence of non-secretion (33-47%). The distribution of ABO blood groups did not differ between patients and controls. The association between non-secretor state and ankylosing spondylitis strengthens the hypothesis that ankylosing spondylitis is a form of reactive arthritis. It also suggests several pathogenic mechanisms which may be relevant to the initial hostparasite interaction in ankylosing spondylitis. 相似文献
4.
G Tzanakaki C C Blackwell J Kremastinou C Kallergi G Kouppari D M Weir 《Epidemiology and infection》1992,108(3):449-455
Usage of antibiotics in southern Europe is less well regulated than in northern countries. The proportion (48%) of meningococci in Spain insensitive to pencillin (MIC greater than or equal to 0.1 mg/l) prompted this investigation of antibiotic sensitivities of isolates from Greek patients with meningitis (31) and carriers (47 school-children and 472 recruits). The agar dilution method was used to determine MIC to penicillin G (PN), sulphamethoxazole (SU), rifampicin (RF), cefaclor (CF) and ciprofloxacin (CP). The proportion of isolates insensitive to PN was 48% for isolates from patients, 19% from school-children and 36.6% from recruits. Resistance to SU (MIC greater than or equal to 16 mg/l) was found in 16% of those from patients, 10.6% from children and 40% from recruits. None of the isolates from patients was resistant to RF (greater than or equal to 1 mg/l) but 6% of those from carriers were. Resistance to CF (greater than or equal to 4 mg/l) was found in 9.2% of patient isolates, 6.4% from children and 23.7% from recruits. All isolates except one were sensitive to CP (MIC range less than 0.0015-0.125 mg/l). Resistances to PN, SU and RF were analysed by serogroup, serotype and subtype of the bacteria. The proportion of resistant isolates showed some variation between different areas of Greece, but it was not statistically significant. 相似文献
5.
M A Hirthler E Blackwell D Abbe R Doe-Chapman C LeClair Smith J Goldthorn P Canizaro 《Journal of pediatric surgery》1992,27(1):40-43
Extracorporeal membrane oxygenation (ECMO) has been used to treat over 2,000 neonates with severe respiratory distress due to a number of different diagnoses. Its application has been expanded into the pediatric population as well. Despite both technical advances and refinement of management techniques, intracranial hemorrhage remains a major cause of both morbidity and mortality during ECMO. We reviewed our ECMO experience with regard to the diagnosis of intracranial bleeding, and gave particular attention to the technicians' written records. Seven of 50 patients had a documented intracranial event during ECMO, and in all 7, the technicians noted increasing difficulty with control of the activated clotting time (ACT), platelet count, or both. This manifested itself as both inability to raise the ACT and/or platelet count, or inability to decrease the ACT, despite discontinuation of heparin. The patients with intracranial hemorrhages had a significantly greater number of changes in the rate of heparin infusion than matched controls. None of the patients with intracranial bleeding had any signs of extracranial hemorrhage, and none manifested any hemodynamic abnormalities. In 4 cases, the regularly scheduled echoencephalogram was obtained earlier in the day, and the patients were subsequently weaned and decannulated. We conclude from this review that instability of previously well-controlled coagulation parameters is an early predictor of an intracranial event. However, the impact of earlier diagnosis on outcome is less clear from this small number of patients. 相似文献
6.
M. Doyle B. L. W. Chapman G. Blackwell E. G. Walsh G. M. Pohost 《Magnetic resonance in medicine》1994,31(5):546-550
We introduce an image processing method which reduces white noise and random artifacts in sets of high resolution, time resolved images. At each pixel, the processing consists of: (1) the isolation of a time intensity curve (TIC), (2) Fourier transformation of each TIC, (3) application of a threshold to remove low intensity coefficients, (4) inverse transformation to generate noise reduced TICS which are recombined to form images with improved signal-to-noise ratio (SNR). Noise filtering by Fourier thresholding is demonstrated on a set of cardiac images, resulting in a reduction of the noise energy by approximately 90%. 相似文献
7.
Andrew J Lawrence Andrew D Blackwell Roger A Barker Francesca Spagnolo Luke Clark Michael R F Aitken Barbara J Sahakian 《Movement disorders》2007,22(16):2339-2345
Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD. 相似文献
8.
SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a). 相似文献
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Sepsis and cytokines: current status 总被引:26,自引:0,他引:26
Sepsis is a constellation of clinical signs and symptoms resulting from
excessive systemic host inflammatory response to infection. This
inflammatory response is largely mediated by cytokines, which are released
into the systemic circulation. Plasma concentrations of specific cytokines,
TNF alpha, IL-1 beta, IL-6 and IL-8 are frequently elevated in human sepsis
and cytokine concentrations correlate with severity and outcome of sepsis.
In addition to pro-inflammatory cytokines, soluble cytokine receptors,
cytokine receptor antagonists and counter-inflammatory cytokines are also
produced in large quantities in patients with sepsis; however, the specific
role of these molecules in sepsis remains undefined. A complex interaction
of cytokines and cytokine-neutralizing molecules probably determines the
clinical presentation and course of sepsis. Intervening in this sequence of
events to modify the host inflammatory responses may prove to be a
beneficial treatment strategy for sepsis, but currently tested anticytokine
therapies have been largely unsuccessful.
相似文献