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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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To ascertain the range of neurological problems in patients with systemic cancer, we prospectively evaluated neurological symptoms, neurological diagnoses, and primary tumors in all patients with a history of systemic cancer examined by the Department of Neurology at the Memorial Sloan-Kettering Cancer Center, from Jul 1, 1990, to Dec 31, 1990. Of the 815 patients seen for neurological symptoms, less than half (45.2%) had metastatic involvement of the nervous system. The three most common symptoms were back pain (18.2%), altered mental status (17.1%), and headache (15.4%). The most common neurological diagnosis was brain metastasis (15.9%), followed by metabolic encephalopathy (10.2%), pain associated with bone metastases only (9.9%), and epidural extension or metastasis of tumor (8.4%). Of 133 patients with undiagnosed back or neck pain, 44 (33%) had epidural extension or metastases from tumor and 40 (30%) had pain associated with vertebral metastases only. In 15 (11%) the cause for the back pain was unrelated to metastatic disease. Of 132 patients seen on initial consultation for altered mental status, metabolic encephalopathy was the major neurological diagnosis (80; 61%); 20 (15%) had intracranial metastases. Of 97 patients with undiagnosed headache, 59 (61%) had a nonstructural cause. Fifty-three of these patients had either migraine, tension headache, or headache related to systemic illness (e.g., fever, sepsis). These results indicate that even in patients with systemic cancer, a group particularly prone to developing neurological disease that can be diagnosed radiologically, the role of clinicians remains important in helping distinguish noncancer-related and nonmetastatic neurological problems. 相似文献
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Vincent DeAngelis 《American journal of orthodontics and dentofacial orthopedics》2003,124(4):19A-20A, author reply 20A
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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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1. The response to an optimally oriented stimulus of both simple and complex cells in the cat's striate visual cortex (area 17) can be suppressed by the superposition of an orthogonally oriented drifting grating. This effect is referred to as cross-orientation suppression. We have examined the spatial organization and tuning characteristics of this suppressive effect with the use of extracellular recording techniques. 2. For a total of 75 neurons, we have measured the size of each cell's excitatory receptive field by use of rectangular patches of drifting sinusoidal gratings presented at the optimal orientation and spatial frequency. The length and width of these grating patches are varied independently. Receptive-field length and width are determined from the dimensions of the smallest grating patch required to elicit a maximal response. 3. The extent of the area from which cross-orientation suppression originates has been measured in an analogous manner. Each neuron is excited by a patch of drifting grating the same size as the receptive field. The response to this stimulus is modulated by a superimposed patch of grating having an orthogonal orientation. After selecting the spatial frequency that produces maximal suppression, the response of each cell is examined as a function of the length and width of the orthogonal (suppressive) grating patch. Results from 29 cells show that the dimensions of the orthogonal grating patch required to elicit maximal suppression are similar to, or smaller than, the dimensions of the excitatory receptive field. Thus cross-orientation suppression originates from within the receptive field. 4. For some cells the spatial frequency tuning of the suppressive effect is much broader than the spatial frequency tuning for excitation. In these cases it is possible to find a spatial frequency that produces suppression but not excitation. With the use of a suppressive stimulus having this spatial frequency, we examined the strength of suppression as a function of orientation for 11 cells. These tests show that suppression occurs at all orientations, including the preferred orientation for excitation. In some cases, suppression is somewhat stronger at the preferred orientation for excitation than at any other orientation. 5. For 12 cells we varied the relative spatial phase between the optimally oriented and orthogonal gratings. In all cases the magnitude of suppression is largely independent of the relative spatial phase. 6. For three binocular cells we examined whether the suppressive effect of a grating oriented orthogonal to the optimum could be mediated dichoptically.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献