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991.
S Padmanabhan MA Jiménez C Gonzalez JM Sanz G Giménez-Gallego M Rico 《Canadian Metallurgical Quarterly》1997,36(21):6424-6436
1H NMR resonances of the phage 434 Cro protein were assigned using standard 2D NMR methods, and its solution structure determined using 867 distance constraints in distance geometry (DIANA) calculations ultimately refined by restrained molecular dynamics (GROMOS). In the 20 best NMR structures, the average pairwise backbone and heavy atom RMSDs are 0.63 +/- 0.14 and 1.53 +/- 0.15 A, respectively, for the structurally well-defined residues 4-65. Residues 1-3 and 66-71 at the N- and C-termini are structurally disordered. The region 4-65 includes five alpha-helices and tight turns which define the hydrophobic core of the protein. The backbone and heavy atom RMSDs for residues 4-65 are 0.92 +/- 0.12 and 1.99 +/- 0.12 A, respectively, for the NMR versus the crystal structures, but there are significant differences in the side-chain conformations and solvent accessibilities for some core residues. Analytical ultracentrifugation experiments confirm that 434 Cro is monomeric even at the high NMR concentrations. 434 Cro folding under NMR solution conditions is two-state as indicated by coincident urea denaturation curves from circular dichroism and intrinsic fluorescence measurements. They yield values for 434 Cro stability which show good correspondence to the free energy for global unfolding determined by NMR hydrogen exchange measurements for the slowest exchanging amide protons. 相似文献
992.
JR Passweg G Socié W Hinterberger A Bacigalupo JC Biggs BM Camitta RE Champlin RP Gale E Gluckman EC Gordon-Smith JM Hows JP Klein ML Nugent R Pasquini PA Rowlings B Speck A Tichelli MJ Zhang MM Horowitz MM Bortin 《Canadian Metallurgical Quarterly》1997,90(2):858-864
Bone marrow transplants for severe aplastic anemia were first performed in the 1970s. Transplant regimens, supportive care, and patient selection have changed substantially since then. Our objective was to determine the impact of these changes on transplant outcome. We studied 1,305 recipients of HLA-identical sibling transplants for aplastic anemia between 1976 and 1992, reported to the IBMTR by 179 centers. We compared survival of transplants performed in three intervals (1976 through 1980 [n = 186], 1981 through 1987 [n = 648], and 1988 through 1992 [n = 471]) using Cox proportional hazards regression. Five-year survival (+/-95% confidence interval) increased from 48% +/- 7% in the 1976-1980 cohort to 66% +/- 6% in the 1988-1992 cohort (P < .0001). Risks of graft-versus-host disease (GVHD) and interstitial pneumonia decreased over time, but the risk of graft failure did not. Higher long-term survival resulted primarily from decreased mortality in the first 3 months posttransplantation. Late mortality risks were low and changed little over the intervals studied. In multivariate analysis, changes in transplantation strategies accounted for most but not all of the improved outcome. Use of cyclosporine to prevent GVHD was the most important factor. Changes in patient selection did not seem to explain improved survival. Survival after HLA-identical sibling bone marrow transplantations for aplastic anemia has improved since 1976. Changes in GVHD prophylaxis account for much of this improvement. Other changes may also operate. 相似文献
993.
994.
SF Quan BV Howard C Iber JP Kiley FJ Nieto GT O'Connor DM Rapoport S Redline J Robbins JM Samet PW Wahl 《Canadian Metallurgical Quarterly》1997,20(12):1077-1085
The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke. 相似文献
995.
SA Gould EE Moore FA Moore JB Haenel JM Burch H Sehgal L Sehgal R DeWoskin GS Moss 《Canadian Metallurgical Quarterly》1997,43(2):325-31; discussion 331-2
We have previously documented the safety of 1 unit (50 gram) of human polymerized hemoglobin (Poly SFH-P) in healthy volunteers. This report describes the first patient trial to assess the therapeutic benefit of Poly SFH-P in acute blood loss. Thirty-nine patients received 1 (n = 14), 2 (n = 2), 3 (n = 15), or 6 (n = 8) units of Poly SFH-P instead of red cells as part of their blood replacement after trauma and urgent surgery. There were no safety issues related to the infusion of Poly SFH-P. The plasma hemoglobin concentration ([Hb]) after the infusion of 6 units (300 gram) of Poly SFH-P was 4.8 +/- 0.8 g/dL (mean +/- SD). Although the red cell [Hb] fell to 2.9 +/- 1.2 g/dL, the total [Hb] was maintained at 7.5 +/- 1.2 g/dL. Poly SFH-P maintained total [Hb], despite the marked fall in red cell [Hb] due to blood loss. The utilization of O2 (extraction ratio) was 27 +/- 16% from the red cells and 37 +/- 13% from the Poly SFH-P. Twenty-three patients (59%) avoided allogeneic transfusions during the first 24 hours after blood loss. Poly SFH-P effectively loads and unloads O2 and maintains total hemoglobin in lieu of red cells after acute blood loss, thereby reducing allogeneic transfusions. Poly SFH-P seems to be a clinically useful blood substitute. 相似文献
996.
de Lamotte-Guery F; Pruvost C; Minard P; Delsuc MA; Miginiac-Maslow M; Schmitter JM; Stein M; Decottignies P 《Protein engineering, design & selection : PEDS》1997,10(12):1425-1432
Proline 40 in Escherichia coli thioredoxin is located close to the redox
active site (Cys32-Cys35) within the alpha2 helix. The conservation of this
residue among most of the thioredoxins suggests that it could play an
important role in the structure and/or function of this protein. We have
substituted Pro40 for Ala by using site- directed mutagenesis and expressed
the mutant P40A in E.coli. The effects of the mutation on the biophysical
and biological properties of thioredoxin have been analyzed and compared
with molecular dynamics simulations. Modeling predicted that the
replacement of Pro40 by Ala induced a displacement of the active site which
exposes Trp31 to the solvent and opens a cleft located between helices
alpha2 and alpha3. The solvation free energy (SFE) calculation also
indicated that P40A became more hydrophobic as W31 became more accessible.
These predictions were totally in agreement with the experimental results.
The mutant P40A exhibited chromatographic behavior and fluorescence
properties very different from those of the wild-type (WT) protein, in
relationship with the displacement of W31. The determination of the free
energy of unfolding of P40A showed that the mutant was globally
destabilized by 2.9 kcal/mol. However, the effect of the mutation on the
transition curve was highly unusual as the midpoint of the unfolding
transition increased, indicating that some local structures were actually
stabilized by the mutation. Despite these structural modifications, neither
the ability of the protein to reduce a chloroplastic enzyme nor its
reactivity with the bacterial reductase decreased. The only functional
difference was the higher stability of P40A in light activation of
NADP-malate dehydrogenase under air, which suggests that the mutant was
less rapidly re-oxidized than WT. Therefore, it can be concluded that Pro40
is not essential for maintaining the redox function of thioredoxin but
rather is required for the stability of the protein.
相似文献
997.
998.
999.
1000.
J Broto C Marhuenda JM Gil-Vernet M Asensio J Lloret J Boix Ochoa 《Canadian Metallurgical Quarterly》1997,10(3):101-103
The authors show their experience in the use of the laparoscopic approach in 18 cases of unilateral exploratory anorchia. They highlight the advantages that this method offers in efficiency, speed, security and minimal aggression compared with conventional exploration of the inguinal channel in the search of the undetectable testis. In the 18 cases studied through the insertion of 5 mm lense in the umbilical area, it was established that a testicular hypoplasia was present in 8 cases. In another 5 cases testicular agenesia was diagnosed, and in the remaining 5, intraabdominal testis were found. In four of these testicles, a laparoscopic approach helped in their correct placement and also in the removal of the fifth in a patient with recurrent leukemia. 相似文献