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61.
Christopher J. Long Jason Van Batavia Amy B. Wisniewski Christopher E. Aston Laurence Baskin Earl Y. Cheng Yegappan Lakshmanan Theresa Meyer Bradley Kropp Blake Palmer Natalie J. Nokoff Alethea Paradis Brian VanderBrink Kristy J. Scott Reyes Elizabeth Yerkes Dix P. Poppas Larry L. Mullins Thomas F. Kolon 《Journal of pediatric urology》2021,17(3):379-386
62.
Mehdi Nouraie Janet S. Lee Yingze Zhang Tamir Kanias Xuejun Zhao Zeyu Xiong Timothy B. Oriss Qilu Zeng Gregory J. Kato J. Simon R. Gibbs Mariana E. Hildesheim Vandana Sachdev Robyn J. Barst Roberto F. Machado Kathryn L. Hassell Jane A. Little Dean E. Schraufnagel Lakshmanan Krishnamurti Enrico Novelli Reda E. Girgis Claudia R. Morris Erika Berman Rosenzweig David B. Badesch Sophie Lanzkron Oswaldo L. Castro Jonathan C. Goldsmith Victor R. Gordeuk Mark T. Gladwin 《Haematologica》2013,98(3):464-472
The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study, we assessed the association of hemolysis with outcomes in sickle cell anemia. A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (P≤0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (P≤0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all P<0.0001). Two-year follow-up analysis showed that a high hemolytic component was associated with an increased risk of death (hazard ratio, HR 3.44; 95% confidence interval, CI: 1.2–9.5; P=0.02). The hemolytic component reflects direct markers of intravascular hemolysis in patients with sickle cell disease and allows for adjusted analysis of associations between hemolytic severity and clinical outcomes. These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality (Clinicaltrials.gov identifier: ). NCT00492531相似文献
63.
M. R. Lakshmanan Mildred Ezekiel Barbara S. Campbell Richard A. Muesing 《Alcoholism, clinical and experimental research》1986,10(4):412-418
Chylomicron remnants, but not lymph chylomicrons, showed a receptor-dependent high affinity saturable binding to normal rat hepatocytes. The Scatchard analysis of the specific binding data showed a high affinity binding site for the remnants with a dissociation constant of 0.61 nM, assuming a molecular weight of 50 X 10(6) for chylomicron remnants. Based on the heparin-releasable bound radioactivity, approximately 80% of the bound remnants seemed to be internalized. The binding process was markedly inhibited by pronase as well as by protein synthesis inhibitors. Competitive binding studies revealed that the order of competition for the binding of labeled remnants by homologous unlabeled lipoproteins was remnants greater than chylomicrons greater than very low density lipoproteins greater than high density lipoproteins. Human low density lipoproteins showed virtually no competition. Studies on the catabolism of triacylglycerol moiety of the remnants showed that 15.2% of the 14C label in the triacylglycerol moiety of the remnants was catabolized by the hepatocytes to 14CO2 due to specific interaction. This amounted to 93% of the total 14CO2 evolution. This was in sharp contrast to the catabolism of the triacylglycerol moiety of very low density lipoproteins from human and rat, where most of the 14CO2 evolution was due to pathways associated with nonspecific binding. Chronic ethanol feeding caused a 29% (p less than 0.02) decrease in the dissociation constant of the high affinity binding site of the liver cell for the remnants, whereas the extent of internalization was decreased by 19% (p less than 0.01) as compared to the pair-fed control animals.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
64.
S Baskar S Ostrand-Rosenberg N Nabavi L M Nadler G J Freeman L H Glimcher 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(12):5687-5690
The inability of the autologous host to reject resident tumor cells is frequently the result of inadequate generation of tumor-specific T cells. Specific activation of T cells occurs after delivery of two signals by the antigen-presenting cell. The first signal is antigen-specific and is the engagement of the T-cell antigen receptor by a specific major histocompatibility complex antigen-peptide complex. For some T cells, the second or costimulatory signal is the interaction of the T-cell CD28 receptor with the B7 activation molecule of the antigen-presenting cell. In the present study, we demonstrate that mouse sarcoma cells genetically engineered to provide both T-cell activation signals stimulate potent tumor-specific CD4+ T cells that cause rejection of both engineered and wild-type neoplastic cells. Two other recent studies have also demonstrated that costimulation via B7 can improve tumor immunity. However, our study differs from these reports by two important observations. (i) One of these studies utilized mouse tumor cells expressing xenogenic viral antigens, and hence, the results are not applicable to wild-type resident tumors. Our study, however, demonstrates that coexpression of B7 by major histocompatibility complex class II+ tumor cells induces immunity in the autologous host that is specific for naturally occurring tumor antigens of poorly immunogenic tumors. (ii) In both earlier studies, only CD8+ T cells were activated after coexpression of B7, whereas in the present report, tumor-specific CD4+ T cells are generated. This report therefore illustrates the role of B7 activation molecule in stimulating potent tumor-specific CD4+ T cells that mediate rejection of wild-type tumors and provides a theoretical basis for immunotherapy of established tumors. 相似文献
65.
Hindsight bias: an impediment to accurate probability estimation in clinicopathologic conferences 总被引:1,自引:0,他引:1
N V Dawson H R Arkes C Siciliano R Blinkhorn M Lakshmanan M Petrelli 《Medical decision making》1988,8(4):259-264
Although clinicopathologic conferences (CPCs) have been valued for teaching differential diagnosis, their instructional value may be compromised by hindsight bias. This bias occurs when those who know the actual diagnosis overestimate the likelihood that they would have been able to predict the correct diagnosis had they been asked to do so beforehand. Evidence for the presence of the hindsight bias was sought among 160 physicians and trainees attending four CPCs. Before the correct diagnosis was announced, half of the conference audience estimated the probability that each of five possible diagnoses was correct (foresight subjects). After the correct diagnosis was announced the remaining (hindsight) subjects estimated the probability they would have assigned to each of the five possible diagnoses had they been making the initial differential diagnosis. Only 30% of the foresight subjects ranked the correct diagnosis as first, versus 50% of the hindsight subjects (p less than 0.02). Although less experienced physicians consistently demonstrated the hindsight bias, more experienced physicians succumbed only on easier cases. 相似文献
66.
67.
PURPOSE: To study the optical coherence tomography (OCT) pattern of the fluorescein angiographic leakage in acute central serous chorioretinopathy (CSCR). METHODS: This is a non-interventional pilot case study. OCT line scan was performed over the fluorescein angiographic leak site in eyes clinically diagnosed acute CSCR. Clinical fundus photograph, site of leakage on fundus fluorescein angiography and corresponding OCT were analysed. RESULTS: The mean age of 10 consecutive patients was 38.8 +/- 6.9 years. Six patients were male and the mean duration of symptom was 7 days. Six eyes (60%) showed a characteristic dipping pattern of neurosensory retina with intervening hyper-reflective echoes suggestive of fibrin over the leakage site. All these eyes had ink-blot leak and subretinal fibrin. CONCLUSIONS: Ink-blot leak in acute CSCR with subretinal fibrin generates a dipping morphological pattern on OCT. 相似文献
68.
Therapeutic potential of Aurora kinase inhibitors in cancer 总被引:1,自引:0,他引:1
Naruganahalli KS Lakshmanan M Dastidar SG Ray A 《Current opinion in investigational drugs (London, England : 2000)》2006,7(12):1044-1051
Aurora kinases (AKs) represent a family of serine/threonine protein kinases that regulate mitotic processes during cell division. They are primarily involved in regulating the multiple steps of mitosis, including centrosome duplication, formation of bipolar mitotic spindle, chromosome alignment on the mitotic spindle, establishment and maintenance of the spindle checkpoint and cytokinesis. As AKs are key regulators of mitosis, several studies have indicated that they have a strong association with cancer and are overexpressed in numerous cancerous cell lines as well as human malignancies. Thus, AKs represent a promising therapeutic target for anticancer drug development. In this review, the role of AKs in cancer, and the current status and therapeutic potential of AK inhibitors is discussed. 相似文献
69.
70.
Baskar V Kamalakannan D Kiberd B Holland MR Singh BM 《QJM : monthly journal of the Association of Physicians》2005,98(6):427-433
BACKGROUND: Microalbuminuria screening to identify patients at risk of diabetic nephropathy is widely accepted. AIM: To investigate whether blood-pressure-based strategies can identify such patients without the need for microalbuminuria testing. METHODS: Spot urine for albumin/creatinine ratios was performed in all patients over an 18-month period. The performance of four combinations of clinical models, based on existing triggers for anti-hypertensive intervention (prior use and/or existing systolic BP exceeding 140 or 160 mmHg and/or dipstick proteinuria exceeding 1+ or 2+) was evaluated at microalbuminuria thresholds of 3.5 and 10 mg/mmol. The models were ranked 1 to 4, based on their escalating relative strengths in predicting need for intervention. RESULTS: Of 3748 patients, 1257 (34%) or 739 (20%) exceeded microalbuminuria thresholds of 3.5 or 10 mg/mmol. All four models predicted microalbuminuria risk (areas under ROC curves 0.60-0.77, all p < 0.001). The models (1-4) identified 2220, 2465, 2803 or 2937 for intervention, respectively, irrespective of microalbuminuria status, and missed 368, 232, 194 or 126 at 3.5 mg/mmol and 164, 87, 81 or 45 at 10 mg/mmol. DISCUSSION: Clinical models using routinely measured parameters reduced the target population for microalbuminuria screening by 60-80%, missing 3-10% of patients with albumin/creatinine ratios exceeding 3.5 mg/mmol or 1-4% of those exceeding 10 mg/mmol. 相似文献