[Synthesis of hemoglobin, RNA and DNA in hemolytic anemia, thalassemia and acute anemia following hemorrhage].
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Biomedical subjects
Publications and source records attributed to E Hahn.
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Cultures of normal tissue are relatively insensitive to heat, while malignant cells in culture are highly sensitive to thermal treatment. This differential thermal sensitivity is most pronounced when the cells of normal and neoplastic tissues are exposed to heat in their exponential growth phase. Dose survival curves of HeLa and 3T3 cells with and without postirradiation thermal treatment showed that the neoplastic HeLa line exhibited significant enhancement of radiosensitivity when the irradiated cells were exposed to elevated temperatures (42C. for 3 hours). Similar heat treatment of irradiated 3T3 fibroblasts did not appreciably enhance the radiation response. The potential significance of these findings for clinical radiotherapy is discussed.
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Because not all laboratories use the monitoring and stimulation protocols used in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, we reanalyzed the ESVEM patients' data using alternative, commonly used Holter monitor (HM) and programmed stimulation efficacy criteria to determine if different criteria would have changed the trial's conclusions. Also, because beta-blocker use and coronary artery disease frequency were not equally distributed between the two limbs in ESVEM, we reanalyzed the ESVEM data adjusting for the possible effect of these variables. In the HM limb, drug efficacy in the original ESVEM analysis was declared by reduction of total premature ventricular complexes (PVCs) by 70%, pairs by 80%, runs of 3 to 15 beats by 90%, and all ventricular tachycardia (VT) more than 15 beats by 100%. In this analysis, we examine outcome in subjects meeting two more stringent sets of criteria, (1) reduction of total PVCs by 70%, of pairs by 80%, and of all VT by 100% (new criteria set 1) and (2) reduction of total PVCs by 80%, of pairs by 90%, and of all VT by 100% (new criteria set 2). In electrophysiology (EPS) limb patients, we compared arrhythmia recurrence when efficacy was declared with triple extrastimuli as compared with maximally testing with double extrastimuli, and arrhythmia recurrence was compared in patients tested with identical versus any more aggressive protocol on drug than was used before drug. We also compared the predictive accuracy of zero versus 3 to 15, and 0 to 5, 6 to 10, and more than 10 induced beats on drug. Additionally, we compared predictive accuracy of the HM- and EP-guided limbs excluding patients on beta blockers and those with noncoronary disease. Lastly, to determine whether concordant results on HM and EPS testing would provide more accurate efficacy predictions than EP testing alone, HM recordings obtained in EPS-limb patients but not processed or used during the course of the EVSEM study were analyzed. The original ESVEM HM criteria, new set 1, and new set 2 yielded predicted drug efficacy rates of 77%, 68%, and 58%, respectively; however, arrhythmia recurrence rates were unchanged. Similarly, arrhythmia recurrence rates for patients tested with triple versus less than triple extrastimuli (p=.238), more aggressive versus identical protocols (p=.955), and 0 to 5 v 6 to 10 v more than 10 induced beats (p=.263) or 0 v 3 to 15 induced beats (p=.106) were unchanged. in the 215 (of 286) patients with coronary disease and not receiving beta blockers, there was still no difference in arrhythmia recurrence or mortality between the noninvasive and invasive limbs in ESVEM. Lastly, in patients with drug efficacy predictions by EPS testing, there was no difference in outcome in patients who had concordant versus discordant efficacy prediction by simultaneously obtained HMs. The use of more stringent testing methods and efficacy criteria would not have significantly improved the predictive accuracy of drug assessment by HM or EPS in the ESVEM trial. Additionally, excess noncoronary disease in EP-guided patients and excess beta-blocker used in HM-guided patients did not influence the results in the ESVEM trial.
Recent studies have demonstrated that neutrophils have the capacity to produce a variety of cytokines after stimulation. The synthesis and release of prostaglandin E2 (PGE2) via the cyclooxygenase (COX) pathway has been reported to occur in activated neutrophils. In the present study, we sought to determine the status of COX protein synthesis and PGE2 production in murine neutrophils after burn injury. The effect of burn injury on neutrophil COX and PGE2 response to infection or lipopolysaccharide (LPS) was also examined. Peritoneal neutrophils were obtained from BDF1 mice at 4, 18, 24, and 36 hours after a 15% TBSA full-thickness scald burn or sham burn. We found that neutrophils from healthy mice express a low level of COX-2 protein. Neutrophil COX-2 protein expression in burn animals was significantly increased at 4 hours and dramatically decreased at 36 hours after burn injury. Animals 36 hours after burn and topically infected with Pseudomonas Aeruginosa had neutrophil COX-2 expression almost identical to burn injury only. Neutrophils harvested from healthy mice cocultured with LPS (1 microg/ml) had a marked induction of COX-2 protein. Neutrophils 24 hours after burn were unresponsive to LPS-stimulated COX-2 enhancement. COX-1 protein was strongly expressed constitutively and not affected further by burn injury or LPS. The production of PGE2 corresponded with the changes in COX-2 expression for all groups of mice. Our data suggested that neutrophils express both COX-1 and COX-2 and produce PGE2. The effects of burn injury on neutrophil COX-2 protein synthesis and PGE2 production suggest that after burn there is a time-dependent response. Insights into not only the global cellular response to injury and infection but also temporal nature of the response are important in the development of the therapeutic treatment strategies for burn patients.
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