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41.
Diffusion of nucleoside triphosphates and role of the entry site to the RNA polymerase II active center 下载免费PDF全文
Batada NN Westover KD Bushnell DA Levitt M Kornberg RD 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(50):17361-17364
Nucleoside triphosphates (NTPs) diffuse to the active center of RNA polymerase II through a funnel-shaped opening that narrows to a negatively charged pore. Computer simulation shows that the funnel and pore reduce the rate of diffusion by a factor of approximately 2 x 10(-7). The resulting limitation on the rate of RNA synthesis under conditions of low NTP concentration may be overcome by NTP binding to an entry site adjacent to the active center. Binding to the entry site greatly enhances the lifetime of an NTP in the active center region, and it prevents "backtracking" and the consequent occlusion of the active site. 相似文献
42.
43.
Perspective: ‘The forgotten children: National inquiry into children in immigration detention (2014)’ 下载免费PDF全文
Georgia Paxton Shidan Tosif Hamish Graham Andrea Smith Colette Reveley Jane Standish Kate McCloskey Grant Ferguson David Isaacs Hasantha Gunasekera Ben Marais Philip Britton Ameneh Khatami Karen Zwi Shanti Raman Elizabeth Elliott David Levitt Joshua Francis Paul Bauert Peter Morris Annie Whybourne Sarah Cherian Raewyn Mutch David Forbes David Rutherford Suzanne Packer 《Journal of paediatrics and child health》2015,51(4):365-368
44.
Cutaneous reactive hyperaemia is unaltered by dietary nitrate supplementation in healthy humans 下载免费PDF全文
Brett J. Wong Jeremy T. Keen Erica L. Levitt 《Clinical physiology and functional imaging》2018,38(5):772-778
The purpose of this study was to determine whether nitrate supplementation augments cutaneous reactive hyperaemia. Seven participants were tested pre‐ and postnitrate supplementation (25 ml beetroot juice); participants consumed one shot per day for 3 days. Participants were instrumented with two microdialysis fibres: control (Ringer's solution) and NO synthase inhibition (20 mM L‐NAME). Skin blood flow was measured via laser‐Doppler flowmetry (LDF). A blood pressure cuff was placed on the experimental arm and inflated to 250 mmHg for 5 mins to occlude arterial inflow. The cuff was released, and the resultant reactive hyperaemia was measured. Blood pressure was continuously measured via plethysmography from a finger on the non‐experimental arm. Cutaneous vascular conductance was calculated (LDF/MAP) and normalized to maximal vasodilatation (%CVCmax). Only diastolic blood pressure was reduced following nitrate supplementation (71 ± 2 vs. 66 ± 1 mmHg; P<0·05). There was no effect of nitrate supplementation on peak reactive hyperaemia at control (Pre: 52 ± 3 vs. Post: 57 ± 2%CVCmax) or L‐NAME (Pre: 52 ± 2 vs. Post: 59 ± 4%CVCmax) sites. There was no effect of nitrate supplementation on total reactive hyperaemia at either control (Pre: 4197 ± 943 vs. Post: 4523 ± 1040%CVCmax * sec) or L‐NAME (Pre: 5108 ± 997 vs. Post: 5694 ± 1002%CVCmax * sec) sites. These data suggest cutaneous reactive hyperaemia is unaffected by dietary nitrate supplementation in healthy humans. 相似文献
45.
T. M. Kajs Ph.D. J. A. Fitzgerald Ph.D. R. Y. Buckner B.S. G. A. Coyle B.S. B. S. Stinson B.S. J. G. Morel Ph.D. M. D. Levitt M.D. 《The American journal of gastroenterology》1997,92(1):89-94
Background and Objectives: We investigated the possibility that a variant of the normal colonic flora, a high concentration of methanogeas, influences the host's response to ingestion of nonabsorbable, fermentable materials. Methods: To better evaluate symptomatic and breath H2 and methane (CH4 ) responses, subjects were placed on a basal diet (primarily rice and hamburger) that contained minimal amounts of nonabsorbable, fermentable substrate. A breath CH4 /H2 ratio of greater or less than 1 on the second day of the basal diet was used to categorize subjects as high (N = 9) or low (N = 25) CH4 producers. After stabilization of the breath gas excretion (day 3 or 4 on the basal diet), the subjects ingested either sorbitol (8.8 g) or oat fiber (10.2 g). Results: The low CH4 producers had a signficantly higher ( p < 0.05) breath H2 concentration than the high producers on the basal diet and after ingestion of sorbitol (27.1 ± 2.7 ppm vs 15.8 ± 3.6 ppm) or oat fiber (13.1 ± 0.08 ppm vs 9.6 ± 1.2 ppm). Low producers of methane reported significantly increased bloating and cramping after sorbitol ingestion and increased bloating after fiber ingestion, whereas high CH4 producers reported no signficant increase in these symptoms. Conclusion: The presence of a methanogenic flora is associated with a reduced symptomatic response to ingestion of nonabsorbable, fermentable material in healthy subjects. Manipulation of the normal flora could be of therapeutic value in nonmethanogenic patients with irritable bowel syndrome. 相似文献
46.
Progression of more differentiated to less differentiated malignant phenotypes has been described infrequently during the natural evolution or at relapse of treated hematopoietic malignancies. This report describes an unusual instance of immunophenotypic transformation from an immunologically undifferentiated acute leukemia to a leukemia that at relapse possessed morphologic and immunologic markers characteristic of a Burkitt's-like acute lymphoblastic leukemia. A 26-year-old man initially presented with pancytopenia and a bone marrow diffusely replaced with blast cells morphologically most consistent with a French-American-British L2 subclassification. The surface immunophenotype of the blasts at diagnosis showed HLA-DR surface antigen but no myeloid, lymphoid, or immunoglobulin determinants. Despite successful induction and ongoing consolidation chemotherapy, the patient had a relapse five months after diagnosis; blast cells at relapse demonstrated marked cytoplasmic vacuolation consistent with a Burkitt's-like L3 acute lymphoblastic transformation. Immunophenotypic analysis revealed the presence of restricted immunoglobulin determinants (mu heavy chain and kappa light chain), as well as two separate B lineage surface determinants (BA-1 and B-1). Immunophenotypic transformations may reflect the presence of either a multiclonal or multipotent leukemic population; documentation of the frequency of such transformations and genomic analysis of the transformed subpopulations may be helpful in furthering the understanding of molecular mechanisms involved in leukemogenesis. 相似文献
47.
Marilyn W. Butler Doruk Ozgediz Dan Poenaru Emmanuel Ameh Safwat Andrawes Georges Azzie Eric Borgstein Daniel A. DeUgarte Essam Elhalaby Michael E. Ganey J. Ted Gerstle Erik N. Hansen Afua Hesse Kokila Lakhoo Sanjay Krishnaswami Monica Langer Marc Levitt Don Meier Ashish Minocha Benedict C. Nwomeh Lukman O. Abdur-Rahman David Rothstein John Sekabira 《World journal of surgery》2015,39(2):335-342
48.
Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young south african adults: early programming of cortisol axis 总被引:15,自引:0,他引:15
Levitt NS Lambert EV Woods D Hales CN Andrew R Seckl JR 《The Journal of clinical endocrinology and metabolism》2000,85(12):4611-4618
Low birth weight is associated with increased cardiovascular and metabolic disorders in adult life, although the mechanisms of this effect remain uncertain. There is one report of increased morning plasma cortisol levels in an elderly low birth weight cohort, but whether this is primary or secondary to other aspects of the phenotype is unclear. We investigated the association between low birth weight and glucose intolerance, blood pressure, and dyslipidemia in young, nonobese adults from a community undergoing the health transition with a high prevalence of both noncommunicable diseases and low birth weight. Additionally, we investigated whether altered basal and stimulated cortisol levels as a marker of hypothalamic-pituitary-adrenal responsiveness or cortisol metabolism were associated with low birth weight in these young adults. Twenty-year-old, historically disadvantaged, urbanized South Africans (n = 137) with birth weights either below the 10th percentile [underweight for age (UFA)] or between the 25th and 75th percentiles [appropriate for gestational age (AFA)] had anthropometry, blood pressure, lipid levels, and glucose tolerance measured. In a subset (n = 62), 0900 h plasma cortisol concentrations, cortisol responses to 1 microg ACTH, and urinary glucocorticoid metabolites were measured. The mothers of UFA infants were themselves lighter and had a lower body mass index (P: = 0. 0016). At age 20 yr, although the UFA group was still smaller and lighter, with a lower body mass index, they had higher fasting plasma glucose levels (P: = 0.047), and a greater proportion demonstrated glucose intolerance (11.9% vs. 0%; P: < 0.01). The UFA group also had higher systolic [UFA, 126.0 +/- 13.3 (+/-SD); AFA, 122.0 +/- 11.7 mm Hg; P: = 0.007] and diastolic (72.3 +/- 8.4 vs. 69. 5 +/- 8.7 mm Hg; P: = 0.02) blood pressures, after covarying for current weight and gender. Plasma cortisol levels determined at 0900 h were higher in the UFA group (484.9 +/- 166.3 vs. 418.6 +/- 160.6 nmol/L) and showed a greater plasma cortisol response to low dose ACTH stimulation (area under the curve for cortisol: UFA, 77,238 +/- 19,511; AFA, 66,597 +/- 16,064 nmol/L.min; P: = 0.04). In conclusion, the link between low birth weight and adult glucose intolerance and blood pressure elevation occurs in young adults in a high risk, disadvantaged population despite a lack of full catch-up growth. Moreover, cortisol axis activation is an early feature in the process linking low birth weight with adult cardiovascular and metabolic disease and is not dependent upon adult obesity or full catch-up growth, at least in this population undergoing the health transition. 相似文献
49.
An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane. 相似文献
50.
Cheryl Levitt Alan Katz Eric Mang Artem Safarov 《Canadian family physician Médecin de famille canadien》2015,61(6):523-527