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31.
Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25-30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long-lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor. 相似文献
32.
In Experiment 1, a group of listeners with substantial hearing loss due to presbyacusis and a group of listeners with normal hearing were given three localization tests: a frontal plane test in which they judged whether sounds came from the left, overhead, or the right; a sagittal plane test in which they judged whether sounds came from directly in front, overhead, or behind; and an elevation test in which they judged the vertical position of sounds coming from in front. The two groups performed similarly on the frontal plane test, which chiefly depended upon their ability to use binaural localization cues. They performed differently on the sagittal plane and elevation tests, for which the predominant localization cues were spectral. The listeners with presbyacusis were substantially less accurate than those with normal hearing in both of these instances. They had particular difficulty judging source elevation, rarely scoring much above chance. Follow-up testing of a group of subjects in the early stages of presbyacusis showed localization performance that was intermediate to the other two groups, but far more like that of the normal-hearing listeners. In Experiment 2, additional tests were run with the following conditions designed to encourage improved performance by listeners with presbyacusic hearing loss: (1) filtering of stimuli to preclude masking of more informative high-frequency components by low frequencies; (2) simplification of the elevation test and greater spatial separation of its loudspeaker sources; and (3) use of hearing aids. Conditions 1 and 2 had no appreciable effect on performance; condition 3 significantly improved presbyacusic listeners' ability to localize in the sagittal plane, particularly when sounds came from the front. 相似文献
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RM Bionta G Blewitt CB Bratton D Casper A Ciocio R Claus M Crouch ST Dye S Errede GW Foster W Gajewski KS Ganezer M Goldhaber TJ Haines TW Jones D Kielczewska WR Kropp JG Learned JM LoSecco J Matthews HS Park LR Price F Reines J Schulz S Seidel E Shumard D Sinclair HW Sobel JL Stone L Sulak R Svoboda G Thornton van der Velde JC C Wuest 《Canadian Metallurgical Quarterly》1987,36(1):30-36
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F Zindy H Soares KH Herzog J Morgan CJ Sherr MF Roussel 《Canadian Metallurgical Quarterly》1997,8(11):1139-1150
In situ hybridization of mouse embryo sections demonstrated expression of mRNAs encoding two polypeptide inhibitors (p18INK4c and p19INK4d) of cyclin D-dependent kinase (CDK) 4 and CDK6 in the central nervous system. No expression of two other INK4 members, p16INK4a and p15INK4b, was observed. The p19INK4d and p18INK4c proteins formed complexes with either CDK4 or CDK6 in a temporal pattern consistent with the results of in situ hybridization. Expression of INK4c was observed at embryonic day 13.5 in neuroepithelial zones of the developing brain, being restricted to dividing neuroblasts but absent from differentiating postmitotic neurons. In the neocortex, p18INK4c was expressed precisely at those developmental stages when neuroblasts switch from a symmetric to an asymmetric pattern of cell division with concomitant increases in their G1 interval. INK4d RNA was detected from embryonic day 11.5 onward, at higher levels than INK4c and with a distinctly different spatial and temporal pattern. Marked INK4d expression was seen in dorsal root ganglia, spinal cord, and focally throughout the brain, but primarily in postmitotic neurons. Neural expression of INK4d continued postnatally into adulthood in postmitotic cells of the dentate gyrus, the pyramidal layer of the hippocampus, and in discrete regions of the cerebral cortex, cerebellum, thalamus, and brainstem. Downregulation of p19INK4d in the dentate gyrus after kainic acid-induced seizures indicated that its expression could also be modified in nondividing cells by excitotoxic stress. Therefore, p19INK4d may contribute to maintaining the quiescent state, acting as a buffer to prevent reactivation of cyclin D-dependent kinases in terminally differentiated cells. 相似文献
37.
C Vayssettes-Courchay AA Cordi JM Lacoste M Laubie TJ Verbeuren 《Canadian Metallurgical Quarterly》1997,122(7):1361-1366
BACKGROUND AND PURPOSE: Studies on risk factors for stroke have been less intensive than those for coronary disease. Only a few studies have addressed the question of the role of heredity in the occurrence of stroke. We analyzed whether a positive parental history of cardiovascular disease predicts the risk of stroke independently from other risk factors and whether the role of parental history varies by age and stroke subtypes. METHODS: This study was a prospective follow-up of 14371 middle-aged men and women. A positive parental history of cardiovascular disease was defined as either stroke or coronary disease before the age of 60 years. The end point of the follow-up was an incident case of stroke. Multivariate analyses were performed with the Cox proportional hazards model. RESULTS: The risk ratio of stroke after multifactorial adjustment (age, smoking, blood pressure, cholesterol, diabetes, and education) associated with a positive parental history of stroke was 1.89 (P = .004) in men and 1.80 (P = .007) in women. The association between parental history of stroke and the risk of stroke was stronger among subjects aged 25 to 49 years than among older subjects. Parental history of coronary disease was not associated with the risk of stroke in men, but in women it had a borderline significant association with the risk of ischemic stroke. CONCLUSIONS: A positive parental history of stroke predicted the risk of stroke independently from the other risk factors. 相似文献
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MI Verkhovsky JE Morgan A Puustein M Wikstr?m 《Canadian Metallurgical Quarterly》1996,380(6571):268-270
Cell respiration in eukaryotes is catalysed by mitochondrial enzyme cytochrome c oxidase. In bacteria there are many variants of this enzyme, all of which have a binuclear haem iron-copper centre at which O2 reduction occurs, and a low-spin haem, which serves as the immediate electron donor to this centre. It is essential that the components of the cell respiratory system have a high affinity for oxygen because of the low concentration of dissolved O2 in the tissues; however, the binding of O2 to the respiratory haem-copper oxidases is very weak. This paradox has been attributed to kinetic trapping during fast reaction of O2 bound within the enzyme's binuclear haem iron-copper centre. Our earlier work indicated that electron transfer from the low-spin haem to the oxygen-bound nuclear centre may be necessary for such kinetic oxygen trapping. Here we show that specific decrease of the haem-haem electron transfer rate in the respiratory haem-copper oxidase from Escherichia coli leads to a corresponding decrease in the enzyme's operational steady-state affinity for O2. This demonstrates directly that fast electron transfer between the haem groups is a key process in achieving the high affinity for oxygen in cell respiration. 相似文献
40.