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91.
In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable. 相似文献
92.
Darwich L Coma G Peña R Bellido R Blanco EJ Este JA Borras FE Clotet B Ruiz L Rosell A Andreo F Parkhouse RM Bofill M 《Immunology》2009,126(3):386-393
The interferon (IFN)-gamma component of the immune response plays an essential role in combating infectious and non-infectious diseases. Induction of IFN-gamma secretion by human T and natural killer (NK) cells through synergistic costimulation with interleukin (IL)-12 and IL-18 in the adaptive immune responses against pathogens is well established, but induction of similar activity in macrophages is still controversial, with doubts largely focusing on contamination of macrophages with NK or T cells in the relevant experiments. The possible contribution of macrophages to the IFN response is, however, an important factor relevant to the pathogenesis of many diseases. To resolve this issue, we analysed the production of IFN-gamma at the single-cell level by immunohistochemistry and by enzyme-linked immunosorbent spot (ELISPOT) analysis and unequivocally demonstrated that human macrophages derived from monocytes in vitro through stimulation with a combination of IL-12 and IL-18 or with macrophage colony-stimulating factor (M-CSF) were able to produce IFN-gamma when further stimulated with a combination of IL-12 and IL-18. In addition, naturally activated alveolar macrophages immediately secreted IFN-gamma upon treatment with IL-12 and IL-18. Therefore, human macrophages in addition to lymphoid cells contribute to the IFN-gamma response, providing another link between the innate and acquired immune responses. 相似文献
93.
A comparison of the determination of absorbed dose to water in reference conditions with high-energy electron beams (Enominal of 6, 8, 10, 12, 15, and 18 MeV) following the recommendations given in the AAPM TG-51 and in the original TG-21 dosimetry protocols has been made. Six different ionization chamber types have been used, two Farmer-type cylindrical (PTW 30001, PMMA wall; NE 2571, graphite wall) and four plane parallel (PTW Markus, and Scanditronix-Wellh?fer NACP, PPC-05 and Roos PPC-40). Depending upon the cylindrical chamber type used and the beam energy, the doses at dmax determined with TG-51 were higher than with TG-21 by about 1%-3%. Approximately 1% of this difference is due to the differences in the data given in the two protocols; another 1.1%-1.2% difference is due to the change of standards, from air-kerma to absorbed dose to water. For plane-parallel chambers, absorbed doses were determined by using two chamber calibration methods: (i) direct use of the ADCL calibration factors N(60Co)D,w and Nx for each chamber type in the appropriate equations for dose determination recommended by each protocol, and (ii) cross-calibration techniques in a high-energy electron beam, as recommended by TG-21, TG-39, and TG-51. Depending upon the plane-parallel chamber type used and the beam energy, the doses at dmax determined with TG-51 were higher than with TG-21 by about 0.7%-2.9% for the direct calibration procedures and by 0.8%-3.2% for the cross-calibration techniques. Measured values of photon-electron conversion kecal, for the NACP and Markus chambers were found to be 0.3% higher and 1.7% lower than the corresponding values given in TG-51. For the PPC-05 and PPC-40 (Roos) chamber types, the values of kecal were measured to be 0.889 and 0.893, respectively. The uncertainty for the entire calibration chain, starting from the calibration of the ionization chamber in the standards laboratory to the determination of absorbed dose to water in the user beam, has been analyzed for the two formalisms. For cylindrical chambers, the observed differences between the two protocols are within the estimated combined uncertainty of the ratios of absorbed doses for 6 and 8 MeV; however, at higher energies (10< or =E< or =18 MeV), the differences are larger than the estimated combined uncertainties by about 1%. For plane-parallel chambers, the observed differences are within the estimated combined uncertainties for the direct calibration technique; for the cross-calibration technique the differences are within the uncertainty estimates at low energies whereas they are comparable to the uncertainty estimates at higher energies. A detailed analysis of the reasons for the discrepancies is made which includes comparing the formalisms, correction factors, and quantities in the two protocols, as well as the influence of the implementation of the different standards for chamber calibration. 相似文献
94.
Comparison of the IAEA TRS-398 and AAPM TG-51 absorbed dose to water protocols in the dosimetry of high-energy photon and electron beams. 总被引:1,自引:0,他引:1
The International Atomic Energy Agency (IAEA TRS-398) and the American Association of Physicists in Medicine (AAPM TG-51) have published new protocols for the calibration of radiotherapy beams. These protocols are based on the use of an ionization chamber calibrated in terms of absorbed dose to water in a standards laboratory's reference quality beam. This paper compares the recommendations of the two protocols in two ways: (i) by analysing in detail the differences in the basic data included in the two protocols for photon and electron beam dosimetry and (ii) by performing measurements in clinical photon and electron beams and determining the absorbed dose to water following the recommendations of the two protocols. Measurements were made with two Farmer-type ionization chambers and three plane-parallel ionization chamber types in 6, 18 and 25 MV photon beams and 6, 8, 10, 12, 15 and 18 MeV electron beams. The Farmer-type chambers used were NE 2571 and PTW 30001, and the plane-parallel chambers were a Scanditronix-Wellh?fer NACP and Roos, and a PTW Markus chamber. For photon beams, the measured ratios TG-51/TRS-398 of absorbed dose to water Dw ranged between 0.997 and 1.001, with a mean value of 0.999. The ratios for the beam quality correction factors kQ were found to agree to within about +/-0.2% despite significant differences in the method of beam quality specification for photon beams and in the basic data entering into kQ. For electron beams, dose measurements were made using direct N(D,w) calibrations of cylindrical and plane-parallel chambers in a 60Co gamma-ray beam, as well as cross-calibrations of plane-parallel chambers in a high-energy electron beam. For the direct N(D,w) calibrations the ratios TG-51/TRS-398 of absorbed dose to water Dw were found to lie between 0.994 and 1.018 depending upon the chamber and electron beam energy used, with mean values of 0.996, 1.006, and 1.017, respectively, for the cylindrical, well-guarded and not well-guarded plane-parallel chambers. The Dw ratios measured for the cross-calibration procedures varied between 0.993 and 0.997. The largest discrepancies for electron beams between the two protocols arise from the use of different data for the perturbation correction factors p(wall) and p(dis) of cylindrical and plane-parallel chambers, all in 60Co. A detailed analysis of the reasons for the discrepancies is made which includes comparing the formalisms, correction factors and the quantities in the two protocols. 相似文献
95.
Carmona-Bayonas A; Soler IO; Gomez FI; Billalabeitia EG; Saura HP; Tafalla MSA; Diaz MP 《Annals of oncology》2007,18(7):1281
Mitotane is often considered the front-line hormonal therapyof adrenocortical carcinoma (ACC). An illustrative case concerningthis issue and the rationale to ponder other alternatives isreported. A 69 year-old woman, diagnosed with ACC was admittedwith hypertensive crisis, supraventricular tachycardia, congestiveheart-failure, diarrhoea and rabdomyolisis. Two years earlier,she had undergone 相似文献
96.
97.
Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients 总被引:3,自引:1,他引:3
Nieken J; Mulder NH; Buter J; Vellenga E; Limburg PC; Piers DA; de Vries EG 《Blood》1995,86(3):900-905
Initial studies have shown that recombinant human interleukin-6 (rhIL- 6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II study. rhIL-6 was administered subcutaneously at 150 micrograms once daily for 6 consecutive weeks. Various hematologic and biochemical parameters were measured weekly during rhIL-6 treatment and 4 weeks after rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC) volume, radioisotope dilution assays with labeled autologous RBCs and with human serum albumin were performed before rhIL-6 administration and on day 8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7% +/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and 19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume increased 18% +/- 5% during the first week of rhIL-6 administration (P < .003), whereas RBC volume remained unaffected. The mean RBC corpuscular volume remained unchanged for 2 weeks and then began to decrease slowly, reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial baseline values. Erythropoietin levels increased rapidly up to 68% at week 3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of serum albumin, prealbumin, and transferrin decreased (P < .0001, P < .003, and P < .0001, respectively), whereas levels of serum amyloid A (P < .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P < .0001) increased during rhIL-6 treatment. All levels returned to pretreatment values after discontinuation of rhIL-6. No alterations in reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia. This anemia is reversible after the cessation of rhIL-6 treatment. 相似文献
98.
Ignasi Garcia-Olivé Eduard Xavier Valverde Forcada Felipe Andreo García José Sanz-Santos Eva Castellà Mariona Llatjós Julio Astudillo Eduard Monsó 《Archivos de bronconeumología》2009
Background and Objective
Linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven useful for sampling mediastinal masses and nodes and for staging lung cancer. The aim of this study was to assess the usefulness of this diagnostic tool in patients with indications of mediastinal disease that could not be diagnosed by noninvasive methods or white light bronchoscopy.Patients and Methods
All patients undergoing linear EBUS-TBNA for the diagnosis of mediastinal masses and/or adenopathy at our endoscopy unit were included in the study. Diagnoses obtained by linear EBUS-TBNA or any surgical technique performed after a nondiagnostic EBUS-TBNA were considered as final.Results
In the study population of 128 patients with a mean (SD) age of 62.0 (11.2) years, a total of 294 TBNAs were performed on 12 masses and 282 nodes. Satisfactory samples were obtained in 11 cases (91.7%) from masses and in 233 cases (82.6%) from nodes. Linear EBUS-TBNA was diagnostic, obviating the need for mediastinoscopy in 115 patients (diagnostic sensitivity, 89.8%). The technique confirmed the diagnosis in 85 of the 94 patients with cancer (90.4%), in 8 of the 10 patients with tuberculosis (80.0%), and in the 5 patients with sarcoidosis.Conclusions
Linear EBUS-TBNA is a useful diagnostic tool in patients with mediastinal disease for whom a pathologic diagnosis is not achieved by noninvasive methods or white light bronchoscopy. 相似文献99.
Vitamin K deficiency or administration of vitamin K antagonists results in the biosynthesis of abnormal des-gamma-carboxy forms of the vitamin K-dependent proteins. Monoclonal antibody H-11 binds several vitamin K- dependent proteins at a determinant that includes the first two residues of gamma-carboxyglutamic acid. Antibody H-11 binds fully carboxylated prothrombin and protein C in the presence of EDTA but binding is inhibited by the divalent metal ions, calcium, magnesium, and manganese. By contrast, des-gamma-carboxy prothrombin and protein C bind antibody H-11 the same in the presence of EDTA or calcium ion. Antibody H-11 thus appears to bind a conserved antigenic site containing gamma-carboxyglutamic acid that in the presence of divalent metal ion undergoes a conformational transition. This ability of antibody H-11 to bind des-gamma-carboxy prothrombin and protein C in the presence of calcium ion allowed the development of an immunoassay for these proteins in plasma. Prothrombin and protein C from stably anticoagulated individuals receiving warfarin were characterized by their ability to bind antibody H-11 in the presence of calcium ion. Binding of prothrombin and protein C to antibody H-11 in the presence of calcium correlated temporally with warfarin administration. The inability of calcium ion to inhibit binding of antibody H-11 to abnormal prothrombin and protein C in plasma suggests that the circulating forms of both proteins following warfarin administration cannot undergo the metal ion-dependent conformational transition that includes sequence residues 1 through 12. 相似文献
100.
William R Henderson Paolo B Dominelli Donald EG Griesdale Daniel Talmor A William Sheel 《Canadian respiratory journal》2014,21(2):107-111
High-frequency oscillation is a novel form of ventilation increasingly being used to treat refractory hypoxic respiratory failure resulting from acute lung injury or acute respiratory distress syndrome. Although there is no known relationship between airway pressure and transpulmonary pressure during conventional mechanical ventilation, no study has attempted to determine transpulmonary pressure during high-frequency oscillation.