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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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Richard B Thompson Ewout J van den Bos Bryce H Davis Yoshihisa Morimoto Damian Craig Brad S Sutton Donald D Glower Doris A Taylor 《The Journal of heart and lung transplantation》2005,24(2):205-214
BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction. 相似文献
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We present the findings of clean intermittent self-catheterisation (CISC) as a long term method of bladder management for 36 quadriplegic spinal cord injured patients, primarily at C6/C7 level, who were taught CISC between 1983 and 1987. Success in CISC was assessed by a mail survey, a telephone interview, and current sterile urine status. Twenty nine (81%) of 36 patients continued to use CISC after a mean discharge period of 2.9 years (p less than 0.001) with high levels of acceptance. Rao's V discriminant analysis showed success in CISC was affected by the interval between injury and initial self-catheterisation (Canonical Correlation Co-efficient = 1.34). Results of urinalysis for patients continuing CISC were obtained for 18 (62%) patients, 16 (88%) of whom had sterile urine. Implications of these and other findings along with reasons for cessation of CISC are discussed. 相似文献
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We graded the overall cosmetic outcome of 56 patients who required excision of the eye. Each patient was then subjected to a more detailed analysis of the specific abnormalities associated with excision of the eye in order to discover which are associated most consistently with a poor cosmetic result. The only factor showing a statistically significant variation with the overall cosmetic outcome was the degree of upper lid sulcus. Taken individually the other features showed no statistically significant correlation. When each finding was scored, the averaged sum of the scores was related to cosmetic outcome with statistical significance. A method of quantifying orbital volume loss is described. 相似文献
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A T Yachnis L B Rorke J A Biegel G Perilongo R A Zimmerman L N Sutton 《The American journal of surgical pathology》1992,16(10):998-1006
We report an unusual large, multicystic, posterior fossa neuroepithelial neoplasm involving the cerebellum, brain-stem, and quadrigeminal cistern of a 9-month-old girl. The neoplasm consisted of variably sized, sharply demarcated nests of small cells with a high nuclear-cytoplasmic ratio and moderately basophilic nuclei, embedded in a desmoplastic, immature-appearing, mesenchymal stroma. The nests contained mitoses but none were seen in the stroma. Glial fibrillary acidic protein (GFAP), neurofilament protein, synaptophysin, and cytokeratin (AE-1) were expressed in the nests. Mesenchymal cells were negative for neural markers but positive for vimentin and desmin. The neoplasm was interpreted as a mixed mesenchymal and primitive neuroectodermal tumor (PNET) with histologic features reminiscent of a recently described intraabdominal desmoplastic small cell tumor. The tumor responded poorly to chemotherapy and a second operation was performed 1 year later. The second specimen bore no resemblance to the original and consisted of epithelial-like nests and clusters of neoplastic cells frequently interrupted by sinusoidal vessels. Tumor cells had medium-sized vesicular nuclei with small nucleoli, and a granular cytoplasm. Occasional less cellular islands of neuropil-like tissue contained larger cells having eccentric, vesicular nuclei with prominent nucleoli and abundant pink cytoplasm. Mitoses were not conspicuous. Many cells expressed synaptophysin, neurofilament protein, and GFAP. Neurofilament protein was strongly positive in the larger, neuron-like cells and synaptophysin stained the neuropil-like areas strongly but was less prominent in the neuronal perikarya. Unexpectedly, the neuropil-like areas expressed epithelial membrane antigen, whereas the neuronal cells were negative for chromogranin A. The peculiar histologic picture, combination of phenotypic markers, and remarkable biologic behavior of this unusual tumor defies classification according to existing nomenclature and exemplifies the broad range of phenotypes expressed by primitive neuro-epithelial neoplasms. 相似文献
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L. T. Bilaniuk P. T. Molloy R. A. Zimmerman P. C. Phillips S. N. Vaughan G. T. Liu L. N. Sutton M. Needle 《Neuroradiology》1997,39(9):642-653
We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The
NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem
tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour
identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed
by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients)
and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15
% of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed
to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour
of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis
than patients with similar tumours without neurofibromatosis type 1.
Received: 21 November 1996 Accepted: 22 December 1996 相似文献
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