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1.
Purpose:?Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined.

Materials and methods:?In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices (60Cobalt; 137Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically.

Results:?Acute GvHD was induced by a dose rate of 0.85 Gy/min (60Cobalt) and a total dose of 9 Gy and injection of 5×105 lymph node cells plus 5×106 bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with 137Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD.

Conclusions:?Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.  相似文献   

2.
Summary

Dose–response curves were determined for pulmonary adenomas and adenocarcinomas in mice after single acute doses of 200 kVp X-rays and cyclotron neutrons (E¯ = 7·5 MeV). A serial-killing experiment established that the radiation induction of chromosome aberrations. The validity of the concept of PLD neous cancers. The dose versus incidence (I) of tumours in male and female mice for X-ray doses between 0·25 and 7·5 Gy is ‘bell-shaped’ and best fitted with a purely quadratic induction and exponential inactivation terms, i.e. I = A + BD2e?αD. In contrast, the tumour dose–response after 0·1–4·0 Gy of neutrons is best fitted by I = A + BD e?αD and is steeply linear ≤ 1 Gy, peaks between 1 and 3 Gy and sharply declines at 4·0 Gy. The data for the female mice ≤ 1 Gy neutrons are best fitted to the square root of the dose.

A major objective of the experiments was to derive neutron RBE values. Because of the differences between the X-ray (quadratic) and neutron (linear) curves, the RBEn will vary inversely with decreasing X-ray dose. The RBE values at 1 Gy of X-rays derived from the B coefficients in the above equations are 7·4 ± 3·2 (male and female); 8·6 ± 3·6 (female) and 4·7 ± 1·8 (male). These are high values and imply even higher values at the doses of interest to radiation protection. If, however, one restricts the analysis to the initial, induction side of the response (≤ 1 Gy neutrons, ≤ 3 Gy X-rays) then good linear fits are obtainable for both radiations and indicate neutron RBE values of 7·4 ± 2·3 for female mice and 4·5 ± 1·8 for males, and these are independent of dose level.  相似文献   

3.
Summary

Exponential and density-inhibited cultures of C3H/10T1/2 cells were exposed to a single dose of 0·3 Gy of fission neutrons delivered at rates ranging from 0·005 to 0·1 Gy/min. No discernible effect upon cell survival or transformation was observed by a lowering of the fission neutron dose rate in either exponential or plateau cultures. At the level of 2·3 × 10?4 transformants per surviving cell, the RBE for neoplastic transformation was three at acute dose rates and ten at the lowest dose rate studied (0·005 Gy/min for neutrons and 0·01 Gy/min for X-rays).  相似文献   

4.
The aim of this study was to characterize Kenyan runners in regard to their oxygen uptake and blood and ammonia responses when running. Untrained Kenyan boys (14.2±0.2 years) and Scandinavian runners were included for comparison. The studies were performed at altitude (~2.000 m.a.s.l.) and, for several Kenyan and Scandinavian runners, at sea level as well. At altitude sedentary adolescent Kenyan boys had a mean maximal oxygen uptake (Vo2max) of 47 (44–51) ml · kg?1· min?1, whereas similarly aged boys regularly walking or running but not training for competition reached above 62 (58–71) ml · kg?1· min?1 in Vo2max. Kenyan runners in active training had 68±1.4 ml · kg?1· min?1 at altitude and 79.9±1.4 ml · kg?1· min?1 at sea level, with individuals reaching 85 ml · kg?1· min?1. The best Scandinavian runners were not significantly different from the Kenyan runners in Vo2max both at altitude and at sea level, but none of the Scandinavians reached as high individual values as observed for some Kenyan runners. The running efficiency, determined as the oxygen cost at a given running speed, was less in the Kenyan runners, and the difference became more pronounced when body weight was expressed in ml · kg?0.75 min?1. Blood lactate concentration was in general lower in the Kenyan than in the Scandinavian runners, and the Kenyans also had extremely low ammonia accumulation in the blood even at very high exercise intensities. It is concluded that it is the physical activity during childhood, combined with intense training as teenagers that brings about the high Vo2max observed in some Kenyan runners. Their high aerobic capacity, as well as their good running economy, makes them such superior runners. In addition, their low blood lactate and ammonia accumulation in blood when running may also be contributing factors.  相似文献   

5.
IntroductionThe kinetics of the bone marrow uptake of 3′-deoxy-3′-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer.MethodsFourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (KFLT) and the Patlak constant (KPatlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined.ResultsThere was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, KFLT=0.045±0.016 min?1 and KPatlak=0.039±0.013 min?1. After treatment, these values were SUV=0.74±0.19, KFLT=0.011±0.005 min?1 and KPatlak=0.005±0.002 min?1. Compartmental analysis revealed a significant drop in k3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease.ConclusionsThere is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.  相似文献   

6.
The radiation sensitivity of various subsets in the haemopoietic stem cell hierarchy was defined using a limiting dilution type long-term bone marrow culture technique that was previously shown to allow quantification of cells with spleen colony-forming potential (day-12 CFU-S) and in vivo marrow repopulating ability (MRA). Primitive stem cells that generate new in vitro clonable colony-forming cells (CFU-C) in the irradiated marrow (MRA) and have long-term repopulation ability (LTRA) in vitro (cobblestone area forming cell, CAFC day-28) had D0 values of 1·25 and 1·38 Gy, respectively. A lower D0 was found for the less primitive CFU-S day-12, CAFC day-12 and cells with erythroid repopulating ability (0·91, 1·08 and 0·97 Gy, respectively). CFU-S day-7 were the most radiosensitive (D0 equalling 0·79 Gy), while CFU-C and CAFC day-5 were relatively resistant to irradiation (D0 1·33 and 1·77 Gy). Split-dose irradiation with a 6 h interval gave dose sparing for stem cells with MRA and even more with in vitro LTRA, less for CFU-S day-12 and CAFC day-10 and none for CFU-S day-7. The cell survival data of the specified stem cell populations were compared with the ability of a fixed number of B6-Gpi-1a donor bone marrow cells to provide for short- and long-term engraftment in single- and split-dose irradiated cognenic B6-Gpi-1b mice. Serial blood glucose phosphate isomerase (Gpi) phenotyping showed less chimerism in the split as compared to the single radiation dose groups beyond 4 weeks after transplant. Radiation dose-response curves corresponding to stable chimerism at 12 weeks for single and fractionated doses revealed appreciable split-dose recovery (D2D1) in the order of 2 Gy. This was comparable to D2D1 estimates for MRA and late-developing CAFC (1·27 and 1·43 Gy, respectively), but differed from the poor dose recovery in cells corresponding to the committed CFU-S day-7/12 and CAFC day-10 population (0·14–0·33 Gy). These data are together consistent with differential radiosensitivity and repair in the haemopoietic stem cell hierarchy, and provide a cellular basis for explaining the dose-sparing effect of fractionated total-body irradiation conditioning on long-term host marrow repopulation.  相似文献   

7.
Summary

The one-electron reduction of 5-deazalumiflavin has been studied in aqueous solution in the acidity range H0 = ?1 to pH 13 using the reducing species CO2?, e?aq and (CH3)2?OH radicals. The spectral and other properties of the deazaflavin radicals formed were found to be independent of the reductant used. Four protolytic forms of the radical were distinguished with associated pKa values of 1·3 ± 0·3, 6·0 ± 0·3 and 10·7 ± 0·3.  相似文献   

8.
Summary

The one-electron reduction of 8-hydroxy-5-deazaisoalloxazine (HMDI) has been studied in aqueous solution in the acidity range pH0 to 13 using the reducing species CO2·?, e?aq and (CH3)2COH radicals. The spectral and other properties of the HMDI radicals were found to be independent of the reductant used. Four protolytic forms of the radical were distinguished with associated pKa values of 2·3 ± 0·3, 6·0 ± 0·3 and 10·1 ± 0·3.  相似文献   

9.
Summary

Clonogenic survival and neoplastic transformation of asynchronous cultures of C3H/10T½ cells were used to assay the effect of dose protraction of reactor-produced fission neutrons. Cells were exposed to eight neutron doses ranging from 0·05 to 0·9 Gy delivered at 11·7 or at 0·49 cGy/min. For each dose level, high and low dose rate irradiations were performed on the same day. At each dose a similar effectiveness of fission neutron irradiation at high or low dose rates was measured for both cell survival and transformation. The combined high and low dose-rate data were analysed by two- or three-parameter models. Depending on the model used, values of the effectiveness per unit dose derived as parameters of linear terms of the respective dose-response curves were 0·9–1·2 Gy?1 for clonogenic survival and 5–8 × 10?4 Gy?1 for neoplastic transformation. It is concluded that the modification of fission neutron dose-response curves by dose rate is negligible or absent in the range of doses and dose rates examined, in contrast to results with other sources of fission or fast neutrons.  相似文献   

10.
Summary

The kinetics of repair of sublethal damage in mouse lung was studied after fractionated doses of 137Cs γ-rays. A wide range of doses per fraction (1·7–12 Gy) was given with interfraction intervals ranging from 0·5 to 24 h. The data were analysed by a direct method of analysis using the incomplete repair model. The half-time of repair (T1/2) was 0·76 h for the pneumonitis phase of damage (up to 8 months) and 0·65 h for the later phase of damage up to 12 months. The rate of repair was dependent on fraction size for both phases of lung damage and was faster after large dose fractions than after small fractions. The T1/2 was 0·6 h (95 per cent c.1. 0·53, 0·69) for doses per fraction greater than 5 Gy and 0·83 h (95 per cent c.1. 0·76, 0·92) for doses per fraction of 2 Gy. Repair was nearly complete by 6 h, at least for the pneumonitis phase of damage. To the extent that extrapolation of these data to humans may be valid, these results imply that treatments with multiple fractions per day that involve the lung will not be limited by the necessity for interfraction intervals much longer than 6 h.  相似文献   

11.
Different mathematical models were used to evaluate if the maximal rate of heart rate (HR) increase (rHRI) was related to reductions in exercise performance resulting from acute fatigue. Fourteen triathletes completed testing before and after a 2-h run. rHRI was assessed during 5 min of 100-W cycling and a sigmoidal (rHRIsig) and exponential (rHRIexp) model were applied. Exercise performance was assessed using a 5-min cycling time-trial. The run elicited reductions in time-trial performance (1.34 ± 0.19 to 1.25 ± 0.18 kJ · kg?1, P < 0.001), rHRIsig (2.25 ± 1.0 to 1.14 ± 0.7 beats · min?1 · s?1, P < 0.001) and rHRIexp (3.79 ± 2.07 to 1.98 ± 1.05 beats · min?1 · s?1, P = 0.001), and increased pre-exercise HR (73.0 ± 8.4 to 90.5 ± 11.4 beats · min?1, P < 0.001). Pre-post run difference in time-trial performance was related to difference in rHRIsig (r = 0.58, P = 0.04 and r = 0.75, P = 0.003) but not rHRIexp (r = ?0.04, P = 0.9 and r = 0.27, P = 0.4) when controlling for differences in pre-exercise and steady-state HR. rHRIsig was reduced following acute exercise-induced fatigue, and correlated with difference in performance.  相似文献   

12.
Summary

The radiosensitization of Chinese hamster V79 cells in vitro by air and misonidazole at low X-ray doses (0·2–6·0 Gy) had been studied. These survival data, together with high-dose data, were fitted to the linear quadratic model ln S = ?(αD + βD2), deriving estimates of α and β by six different methods to illustrate the influence of the statistical treatment on the values so derived. This in vitro study clearly demonstrated that the survival parameters α and β are dependent to some degree on the method of analysis of the raw survival data; however, their ratios, the values of oxygen enhancement ratios (OERs) and radiosensitizer enhancement ratios (SERs) derived from the different methods, are similar. All methods of analysis give reduced OERs at low radiation doses for combined low- and high-dose X-ray data. However, the OERs are still appreciably high, ranging from 2·45 to 2·50 for an oxic dose of 2 Gy. All methods of analysis gave reduced SERs at low doses for combined low and high X-ray dose data for hypoxic cells irradiated in 1 mmol dm?3 misonidazole. At survival levels corresponding to doses of 2 Gy in the presence of 1 mmol dm?3 misonidazole and SERs ranged from 1·2 to 1·5.  相似文献   

13.
Summary

Human G0 lymphocytes were exposed to 220 kV X-radiation in the presence or absence of DMSO, an efficient selective scavenger of OH radicals. Our studies demonstrate that DMSO affects a concentration-dependent modulation of induced asymmetrical aberrations in human lymphocytes exposed to ~ 3·0 Gy, with maximum protectible fractions of approximately 70 percent at DMSO concentrations of ≥ 1 m. The dose dependency for dicentrics in lymphocytes acutely exposed to X-ray doses of 0·51 to 4·98 Gy in the absence of DMSO is adequately described by the linear-quadratic dose—response function Y = αD + βD2. Data from duplicate cultures exposed in the presence of 1 m DMSO produce an excellent fit to the regression function modified as follows: where the ‘dose modifying’ factor Δ = 0·501. We interpret these findings as providing evidence that OH radical-mediated lesions in DNA account for ~ 50 percent of the dose dependency for dicentrics resulting from either one-track or two-track events, following exposures of non-cycling cells to moderate-to-high doses of low LET radiation. These data may be used in additional calculations to derive an estimate of ~ 6 × 108 s?1 for the rate of reaction of OH radicals with DNA targets involved in aberration formation.  相似文献   

14.
A randomly selected group of 88 men and 115 women, aged 23–27 years in 1991, were tested as teenagers in 1983, and then followed-up in 1991. A mean increase of 15% in maximal voluntary isometric strength was found in men, and no change was found in women over the 8 years. Body weight increased 14% in men and 6% in women. Strength in relation to body weight (N · kg?1) did not change in men, but a small decrease of 3% was found in women. Strength in abdominal muscles decreased in blue-collar workers but increased in students. Maximal oxygen uptake (V?o2max (ml · min?1kg?1) decreased 9% in men and 3% in women. The values in 1991 were 47.9 and 39.5 ml · min?1kg?1 for men and women, respectively. Participation in leisure sport activities decreased 1.7 h · week?1 in men and 1.2 h · week?1 in women. Seventy percent of the men and 74% of the women participated in regular leisure sport activity, which was a marked increase from 8 years before, when only 54% of the men and 57% of the women were similarly active. The overall decrease in V?O2max in men was due primarily to a decrease among blue-collar workers and unemployed men: 19%vs 4% in other occupational groups. Only 20% of the blue-collar workers participated in sport activities for more than 4 h · week?1, and 47% did not participate at all. In women, changes in strength and V?O2max were related to motherhood. Abdominal muscle strength decreased, but arm flexor strength increased in women who had become mothers. V?O2max decreased 14% in mothers vs 2% in other women. Changes over 8 years in V?O2max and strength did not relate to changes in physical activity, but a significant relationship between decrease in physical activity and gain in body fat was found in men. Changes in body weight and body fat were the only variables that correlated with changes in strength. None of the observed changes related to changes in V?O2max (ml · min?1kg?1). For the 23- to 27-year-olds, the level of physical activity assessed in h · week?1 was almost as high in women as in men.  相似文献   

15.
Abstract Two series of experiments were carried out with similar techniques to assess the gross cost of running (CR), i.e. the ratio between O2 demand and speed. The two groups of male subjects differed in average maximal O2 uptake and variation coefficient (V̇O2 max = 70.9 ± 4.7 ml O2 • min –1 • kg–1 , VC = 6.6%; and 61.1±10.1 ml O2 • min–1 • kg–1, VC =16.5%). In the first series the O2 demand (VO2, mlO2 • min–1 • kg–1) was measured in the final 30 s of 4-min runs at 7 treadmill speeds (V, 166.7 to 366.7 m • min–1) in 12 well trained male marathon runners. After having added the anaerobic component of O2 demand, a mean linear regression was computed: VO2 = -11.5±4.0 + 0.232±0.018 * V , R2 = 0.992±0.004 (mean ± standard deviation). The intercepts (i.e. the apparent VO2 corresponding to V=0 or VO2 V0) were linearly related to the slopes (ΔVO2V; R=-0.71, p=0.0007). CR increased on average from 0.163±0.013 to 0.198±0.010 mlO2 • kg–1 • m–1 in the range of 166.7–333.3 m • min–1. The percent increase ranked from 10.1% to 37.4%. In the second series of experiments (18 subjects), VO2 V0 was inversely related to VO2 max while the opposite was true for ΔVO2V. Subjects with the lowest (VO2 max) presented positive values of VO2 V0. In conclusion, the widespread idea that gross CR is speed independent does not apply to all distance runners. Therefore, gross CR should be measured at race speed whenever gross CR is utilized to predict running performance.  相似文献   

16.
Summary

Phthalocyanines are photosensitizers evaluated for use in photodynamic therapy of cancer. As such, the dependence of the bioresponse on the light fluence rate may be of clinical importance. The effect of the fluence rate of white light from 0·165 to 3·3 kJ m?2 min?1 was studied in Chinese hamster cells and human lymphocytes, using as endpoints colony-forming ability and inhibition of [3H]thymidine incorporation following mitogenic stimulation and dye-photoactivation, respectively. Using Chinese hamster cells exposed to photoexcited chloroaluminium phthalocyanine tetrasulphonate in PBS solution, cytotoxicity was diminished as the fluence rate was reduced. In human lymphocytes changing the fluence rate between 0·33 and 3·3 kJ m?2 min?1 affected the response in a way similar to that of Chinese hamster cells. Human lymphocytes, when exposed to incremental increasing light fluences, 4 h after a conditioning dose, were able to recover from phthalocyanine-induced photo-damage, as evidenced by the reappearance of a shoulder on the dose-effect curve. This recovery process during a protracted light exposure, could explain the reduced sensitivity to phthalocyanine photosensitization, compared to exposure at high fluence rates.  相似文献   

17.
Summary

Considerable interest has been aroused in recent years by reports that the transforming and carcinogenic effectiveness of low doses of high LET radiations can be increased by reducing the dose rate, especially for transformation of 10T1/2 cells in vitro by fission-spectrum neutrons. We report on conditions which have been established for irradiation of 10T1/2 cells with high LET monoenergetic α-particles (energy of 3·2 MeV, LET of 124 keV μm?1) from 238Pu. The α-particle irradiator allows convenient irradiation of multiple dishes of cells at selectable high or low dose rates and temperatures. The survival curves of irradiated cells showed that the mean lethal dose of α-particles was 0·6 Gy and corresponded to an RBE, at high dose rates, of 7·9 at 80 per cent survival and 4·6 at 5 per cent survival, relative to 60Co γ-rays. The mean areas of the 10T1/2 nuclei, perpendicular to the incident α-particles, was measured as 201 μm2, from which it follows that, on average, only one in six of the α-particle traversals through a cell nucleus is lethal. Under the well-characterized conditions of these experiments the event frequency of α-particle traversals through cell nuclei is 9·8 Gy?1.  相似文献   

18.
Summary

Eggs of domestic chickens and black-headed gulls were continuously exposed to gamma-rays during incubation, using dose rates ranging from 0·004 to 0·08 Gy h?1 for 20 days. Acute-dose experiments were also conducted, and eggs were irradiated on day 10 of incubation with doses of between 1·92 and 28·8 Gy. Hatchability and numbers reaching full-term developed were affected only after chronic doses of 9·6 Gy and acute doses of 4·8 Gy or higher. Maximum embryo mortality occurred around days 10–11 of incubation and just before hatching, in all experiments. An increase in foot and limb deformities was observed above acute and chronic doses of 9·6 Gy.  相似文献   

19.
Summary

To characterize the potential role of high-l.e.t. radiation in respiratory carcinogenesis, the cytotoxic and transforming potency of 5·5 MeV α-particles from electroplated sources of 238Pu were determined using primary cultures of rat tracheal epithelial cells. The α-particle response was compared to the effects of 280 kVp X-rays and of the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. Increasing the α-particle dose caused an exponential decrease in survival with a D37 of 1·6 Gy. X-rays also caused a dose-dependent decrease in survival (D37 = 3·6 Gy) but the survival curve had a significant shoulder. The RBE for cell killing by α-particles versus X-rays varied with dose, and ranged between 4 and 1·5 for α doses in the range 0·2–4 Gy. At equally toxic doses (relative survival 0·18–0·2), all three agents induced similar frequencies of preneoplastic transformation. For preneoplastic transformation induced by doses of α- and X-radiations giving 80 per cent toxicity, an α RBE of 2·4 was derived. The similar RBEs for cell killing and for preneoplastic transformation suggest an association between the type or degree of radiation-induced damage responsible for both cell killing and cell transformation.  相似文献   

20.
Summary

In vitro effects of radiation were studied in two permanent cell lines (AGS and SII) from two patients with adenocarcinoma of the stomach and three permanent sublines from each cell line. Radiation survival parameters for AGS and SII parent cell lines and sublines were determined after in vitro irradiation of their cells with 0·5 to 10 Gy of 60Co gamma rays. The AGS and SII cell lines had different growth properties, DNA contents and radiation survival curves. Surviving fractions of SII parent cells (76 chromosomes) after 2·0 and 10 Gy were 1·22 and 17·8 times greater, respectively, than values for AGS parent cells (47 chromosomes). Sensitivities (D0) were 1·08 and 1·45 Gy for AGS and SII parent lines, respectively. The D0 values for AGS parent cells and sublines were similar (1·01 to 1·08 Gy), but SII parent cells and sublines had D0 values of 1·45, 1·36, 1·37 and 1·12 Gy (for SII-A). Also, the SII parent cells had survival fractions after 2·0 and 10 Gy that were 1·3 and 11·3 times greater, respectively, than values for the SII-A cells. These data show differences in radiation responses among stomach cancer cell lines and sublines that may relate to DNA content, but there was no consistent correlation between radiation response and a particular cell characteristic.  相似文献   

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