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81.
I Dix CS Russell RT O'Keefe AJ Newman JD Beggs 《Canadian Metallurgical Quarterly》1998,4(12):1675-1686
We present here the first insights into the organization of proteins on the RNA in the U5 snRNP of Saccharomyces cerevisiae. Photo-crosslinking with uniformly labeled U5 RNA in snRNPs reconstituted in vitro revealed five contacting proteins, Prp8p, Snu114p, p30, p16, and p10, contact by the three smaller proteins requiring an intact Sm site. Site-specific crosslinking showed that Snu114p contacts the 5' side of internal loop 1, whereas Prp8p interacts with five different regions of the 5' stem-loop, but not with the Sm site or 3' stem-loop. Both internal loops in the 5' domain are essential for Prp8p to associate with the snRNP, but the conserved loop 1 is not, although this is the region to which Prp8p crosslinks most strongly. The extensive contacts between Prp8p and the 5' stem-loop of U5 RNA support the hypothesis that, in spliceosomes, Prp8p stabilizes loop 1-exon interactions. Moreover, data showing that Prp8p contacts the exons even in the absence of loop 1 indicate that Prp8p may be the principal anchoring factor for exons in the spliceosome. This and the close proximity of the spliceosomal translocase, Snu114p, to U5 loop 1 and Prp8p support and extend the proposal that Snu114p mimics U5 loop 1 during a translocation event in the spliceosome. 相似文献
82.
In Part 1 of this work, we formulated and analyzed a mathematical model for our fibroblast-populated collagen microsphere (FPCM) assay of cell traction forces (Moon and Tranquillo, 1993). In this assay, the FPCM diameter decreases with time as the cells compact the gel by exerting traction on collagen fibrils. In Part 1 we demonstrated that the diameter reduction profiles for varied initial cell concentration and varied initial FPCM diameter are qualitatively consistent with the model predictions. We show here in Part 2 how predictions of a model similar to that of Part 1, along with the determination of the growth parameters of the cells and the viscoelastic parameters of the gel, allow us to estimate the magnitude of a cell traction parameter, the desired objective index of cell traction forces. The model is based on a monophasic continuum-mechanical theory of cell-extracellular matrix (ECM) mechanical interactions, with a species conservation equation for cells (1), a mass conservation equation for ECM (2), and a mechanical force balance for the cell/ECM composite (3). Using a constant-stress rheometer and a fluids spectrometer in creep and oscillatory shear modes, respectively, we establish and characterize the linear viscoelastic regime for the reconstituted type 1 collagen gel used in our FPCM traction assay and in other assays of cell-collagen mechanical interactions. Creep tests are performed on collagen gel specimens in a state resembling that in our FPCM traction assay (initially uncompacted, and therefore nearly isotropic and at a relatively low collagen concentration of 2.1 mg/ml), yielding measurements of the zero shear viscosity, mu 0 7.4 x 10(6) Poise), and the steady-state creep compliance, J0e. The shear modulus, G (155 dynes/cm2), is then determined from the inverse of J0e in the linear viscoelastic regime. Oscillatory shear tests are performed in strain sweep mode, indicating linear viscoelastic behavior up to shear strains of approximately 10 percent. We discuss the estimation of Poisson's ratio, v, which along with G and mu 0 specifies the assumed isotropic, linear viscoelastic stress tensor for the cell/collagen gel composite which appears in (3). The proliferation rate of fibroblasts in free floating collagen gel (appearing in (1)) is characterized by direct cell counting, yielding an estimate of the first-order growth rate constant, k (5.3 x 10(-6) s-1). These independently measured and estimated parameter values allow us to estimate that the cell traction parameter, tau 0, defined in the active stress tensor which also appears in (3), is in the range of 0.00007-0.0002 dyne.cm4/mg collagen.cell.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
83.
RT Wille K Krishnan KA Cooney DS Bach F Martinez 《Canadian Metallurgical Quarterly》1996,109(3):848-850
A Hungarian-American kindred with familial primary pulmonary hypertension (PPH) and a new, low-oxygen affinity beta-chain variant hemoglobin, Hb Washtenaw, is described. The index case presented with severe PPH and was found to have the abnormal hemoglobin. Two siblings with the abnormal hemoglobin also demonstrated increased pulmonary artery pressures on exercise echocardiography suggestive of early PPH. The occurrence of PPH and the abnormal hemoglobin could be due to genetic or biochemical factors or simply coincidental. A previous study had described a possible association of an abnormal beta-chain variant hemoglobin, Hb Warsaw, and PPH. It was suggested that the putative gene for familial PPH may be located near the beta-globin gene on chromosome 11. The association of PPH and the beta-chain variant hemoglobin in this kindred adds further support to this hypothesis. 相似文献
84.
RT van Domburg AJ van Miltenburg-van Zijl RJ Veerhoek ML Simoons 《Canadian Metallurgical Quarterly》1998,31(7):1534-1539
OBJECTIVES: This study was performed to investigate the long-term outcome of patients with unstable angina within subgroups of the Braunwald classification. BACKGROUND: Long-term follow-up studies of patients with unstable angina are rare and date from more than two decades ago. This study was performed to establish the prognosis of different subgroups of patients with unstable angina (Braunwald criteria) during a 7-year follow-up period. METHODS: We registered a well defined group of 417 consecutive patients, admitted to the hospital for suspected unstable angina. The definite diagnosis was unstable angina in 282 patients (68%) and evolving myocardial infarction in 26; in 109 patients (26%), the symptoms were attributed to other or nonspecific causes. Patients with definite unstable angina were subclassified according to the Braunwald classification. Survival, survival without infarction and survival without infarction or intervention were determined for each class. RESULTS: After a median follow-up period of 94 months, the mortality rate in the first year was 6% and 2% to 3% in the following years. The frequency of revascularization was 47% in the first year, and that for myocardial infarction was 11% in the first year and 1% to 3% thereafter. The Braunwald classification appeared to be appropriate for risk stratification in the first year. However, at 7 years the event rates in all classes were similar. In particular, the Braunwald classification had no long-term impact on mortality or infarction rates. However, patients with acute angina at rest or postinfarction angina and patients with extensive anginal treatment had high intervention rates. CONCLUSIONS: To our knowledge, this study is the first to demonstrate that despite a complicated course during the first year, current management results in good long-term outcome in patients with unstable angina. 相似文献
85.
QY He AB Mason RC Woodworth BM Tam RT MacGillivray JK Grady ND Chasteen 《Canadian Metallurgical Quarterly》1997,36(48):14853-14860
Human serum transferrin N-lobe (hTF/2N) has four iron-binding ligands, including one histidine, one aspartate, and two tyrosines. The present report elucidates the inequivalence of the two tyrosine ligands (Tyr 95 and Tyr 188) on the metal-binding properties of hTF/2N by means of site-directed mutagenesis, metal release kinetics, and absorption and electron paramagnetic resonance (EPR) spectroscopies. When the liganding tyrosines were mutated individually to phenylalanine, the resulting mutant Y95F showed a weak binding affinity for iron and no affinity for copper, whereas, mutant Y188F completely lost the ability to bind iron but formed a stable complex with copper. Since other studies have demonstrated that mutations of the other two ligands, histidine and aspartate, did not completely abolish iron binding, the present findings suggest that the tyrosine ligand at position 188 is essential for binding of iron to occur. Replacement of Tyr 188 with phenylalanine created a favorable chemical environment for copper coordination but a fatal situation for iron binding. The positions of the two liganding tyrosines in the metal-binding cleft suggest a reason for the inequivalence. 相似文献
86.
DG Kent Q Peng RT Isaacs SB Whiteside DL Barker DJ Apple 《Canadian Metallurgical Quarterly》1997,23(9):1371-1375
PURPOSE: To assess the effect of relatively large positioning holes on the security of capsular bag fixation of plate-haptic silicone intraocular lenses (IOLs). SETTING: Center for Research on Ocular Therapeutics and Biodevices, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: This study tested the hypothesis that larger holes allow ingrowth of lens material, fibrous tissue, or both through them, which helps fixate the lens more firmly in the capsular bag. Five rabbits had bilateral continuous curvilinear capsulorhexis, phacoemulsification, and implantation of a plate-haptic silicone IOL. An IOL with a small, round positioning hole (Staar AA-4203V) was implanted in the right eye in each rabbit, and a large-hole IOL (Staar AA-4203VF) was implanted in the left eye. After 2 months, all rabbits were killed. The force required to extract one haptic from the capsular bag was measured with a digital force meter. All eyes had histopathological analysis. RESULTS: It was slightly more difficult to extract a large-hole IOL from the capsular bag, although this trend was not statistically significant. However, histopathological analysis consistently showed 360 degree synechia formation through the holes, showing that the IOL could be securely fixed in position. CONCLUSIONS: Proliferation of lens epithelial cells through a large positioning hole in a plate-haptic silicone IOL may improve the long-term security of capsular bag fixation. This will help reduce the incidence of IOL decentration and dislocation. 相似文献
87.
PS Gill RT Mitsuyasu T Montgomery J Huang S Cabriales M Testa BM Espina AM Levine SA Miles 《Canadian Metallurgical Quarterly》1997,3(5):278-283
The aim of this study was to evaluate psychosocial quality of life after heart transplantation. We examined 29 patients (25 M and 4 F), average age was 43.5 y (18-62 y). The age at time of heart transplantation was 43 years (17-55 y). The time after heart transplantation was 3.3 year (0.3-9 y). Spielberger's Questionnaire of Anxiety, Knobloch's inventory of neuroticism, Freiburg's Personality Inventory and Quality of Life Inventory were used, 33% of patients demonstrated increasing frequency and 29% of patients increasing intensity of neurotic symptoms. 23% of patients presented increasing levels of anxiety (as a state). The personality dimensions (depression, excitability and low emotional stability) displayed high frequency. The results showed that patients were more satisfied with family support, with sexual activities, and less satisfied with financial situation, social activities, social isolations, sleep, memory, excitability, fatigue. 41.5% of patients returned back to work. The results indicate that these psychosocial factors play an important role in quality of life after heart transplantation. That is why if is necessary to dedicate an increasing attention to them. (Tab. 1, Fig. 6, Ref. 14.) 相似文献
88.
89.
ML Geleijnse A Elhendy RT van Domburg R Rambaldi AE Reijs JR Roelandt PM Fioretti 《Canadian Metallurgical Quarterly》1997,79(8):1031-1035
To investigate the prognostic value of dobutamine stress-induced changes in systolic blood pressure (BP) 418 patients (mean age 60 years, 238 men) with chest pain and known or suspected coronary artery disease, who underwent a dobutamine-atropine stress technetium-99m sestamibi myocardial perfusion scintigraphic study, were followed up for 25 +/- 15 months. Blood pressure was measured by automatic sphygmomanometry every 3 minutes. A marked decrease and increase in systolic BP from rest to peak were defined as changes of > or = 20 mm Hg, and > or = 30 mm Hg, respectively. Worst outcome events were cardiac death (n = 30), nonfatal myocardial infarction (n = 17), and hospitalization for congestive heart failure (n = 8). A decrease in systolic BP (prevalence 16%) was associated with older age and higher baseline systolic BP. Fixed and reversible sestamibi perfusion defects and follow-up results were similar to patients without a systolic BP decrease. In contrast, an increase in systolic BP (prevalence 24%) was associated with younger age, lower baseline systolic BP, and with absence of a history of prior congestive heart failure or treatment with angiotensin-converting enzyme inhibitors. Furthermore, these patients had fewer fixed perfusion defects and tended to have fewer annual event rates (3.5% vs 7.5%, p < 0.10). In a multivariate model, an increase in systolic BP was not an independent predictor for subsequent events. In conclusion, a dobutamine-induced decrease in systolic BP is not associated with fixed or reversible sestamibi defects or adverse prognosis. An increase in systolic BP, however, is associated with less fixed sestamibi defects and a tendency toward less annual event rates. 相似文献
90.
There are six major steps in the management of patients with neuroendocrine tumors (NETs) (carcinoids and pancreatic endocrine tumors). One of the steps that is increasing in its importance is the need to assess primary tumor location and tumor extent in these patients. Without such information, it is not possible to adequately manage these patients. Conventional imaging studies (CT scan, MRI, ultrasound, angiography), functional localization studies measuring hormonal gradients, endoscopic ultrasound, and most recently, somatostatin receptor scintigraphy (SRS) with [125I-DTPA-DPhe1]-octreotide have all been advocated to localize NETs in different studies. Whereas it is now established that for all NETs, except insulinomas, SRS has the greatest sensitivity, it remains unclear whether this increased sensitivity translates into increased clinical usefulness. It, therefore, remains unclear based on fiscal and clinical considerations what should be the recommended algorithm for the use of the different localization methods. To address this issue, we have recently performed two prospective studies on patients with gastrinomas. In this paper, the methods and results of each are summarized and based on these results, an algorithm for localization studies in NETs is proposed. One study assessed the role of SRS in management in 122 patients and shows that the use of SRS changed management in 47 percent of patients according to six different criteria when the patients were stratified according to their principal management problem. Determining whether liver metastases were present is one of the major goals of tumor localization studies and is frequently a source of confusion because of the difficulty in distinguishing small NETs liver metastases from hemangiomas. In the second study, the ability of SRS and other tumor localization methods to distinguish these two possibilities was assessed in 15 patients with small hemangiomas and 15 patients with small hepatic metastases (mean size 1.3 cm). SRS correctly identified 93 percent of the patients with liver metastases and was not positive in any patient with a hemangioma, suggesting it was not a liver metastases. SRS had greater negative and positive predictive value than conventional studies. Based on these two studies, and SRS's greater sensitivity and fiscal considerations, it is proposed that SRS should be the initial tumor imaging study in all NETs except insulinomas, and algorithms for the use of other localization studies in both NETs and insulinomas are proposed. 相似文献