A rodent model of protein turnover used to design an experiment for measuring the rates of channeling, recycling and protein synthesis.
We described previously a mechanistic model of whole-body protein turnover in rodents. Channeling was defined as the flow of amino acids from the extracellular compartment to aminoacyl tRNA and protein synthesis. Recycling was defined as the flow of amino acids from protein degradation to aminoacyl tRNA (protein synthesis) without mixing with the intracellular pool of amino acids. In this paper, the model is applied to tissues and whole body and is used to develop an experimental protocol for estimating protein fractional synthesis rate, recycling and channeling. Channeling, recycling and protein synthesis must be estimated simultaneously because changes in specific radioactivities over time are highly dependent on the rate of protein synthesis. Injection-specific radioactivities, body weights and experimental variation were used with the model to generate data at different rates of recycling and channeling. The data generated were then used to determine the best time points and experimental method to estimate percentages of recycling, channeling and protein synthesis rate by the iterative Method of Maximum Likelihood. Specific radioactivity at each time point was based on simulated data from three rodents at each of six time points. Predicted protein synthesis rates were within 5%/d of observed rates for all methods. Predicted rates of recycling and channeling were generally within 15% of observed rates except recycling in muscle at high channeling and high recycling. Standard deviations of the predictions of percentages of channeling and recycling were between 0.148 and 44.5% for the pulse dose method, 0.0655 and 197% for the continuous infusion method and 0.351 and 962% for the flooding dose method. The experimental design that yields the best estimates of channeling, recycling and protein synthesis is the pulse dose. Changes in amino acid specific radioactivities in the extracellular, aminoacyl tRNA and protein pools were greatest and should be measured at 2, 6, 10, 40, 70 and 100 min in the pulse method. (+info
Measurements of Rn-222, Rn-220 and their decay products in the environmental air of the high background radiation areas in Yangjiang, China.
For the renewal of dose estimation from internal irradiation in the high background radiation areas (HBRA) of Yangjiang, the measurements of radon, thoron and their decay products in the environmental air were conducted, including: (1) integrating measurements of Rn-222 and Rn-220 concentrations; (2) eqilibrium factor F for Rn-222 and alpha-potential energy value of Rn-220; (3) external gamma radiation in places where radon measurements were undertaken; (4) cumulative exposure to indoor radon for each family in a case-control study on lung cancer. The Rn-Tn cup monitor method was used for the integrating measurement of Rn-222 and Rn-220 concentration. An alpha track detector was used for the integration measurement of Rn-222 concentration in the case-control study on lung cancer. The results of measurements show that although the investigated areas are located between the Equator and the Tropic of Cancer, and that people live in well-ventilated dwellings, the concentrations of radon, especially of Rn-220 are significantly higher in the indoor air of HBRA than those in the control area. The value of equilibrium factors for Rn-222, the alpha potential energy of decay products from Rn-222 and Rn-220 are determined. (+info
Asymmetric distribution of glucose and indole-3-acetyl-myo-inositol in geostimulated Zea mays seedlings.
Indole-3-acetyl-myo-inositol occurs in both the kernel and vegetative shoot of germinating Zea mays seedlings. The effect of a gravitational stimulus on the transport of [3H]-5-indole-3-acetyl-myo-inositol and [U-14C]-D-glucose from the kernel to the seedling shoot was studied. Both labeled glucose and labeled indole-3-acetyl-myo-inositol become asymmetrically distributed in the mesocotyl cortex of the shoot with more radioactivity occurring in the bottom half of a horizontally placed seedling. Asymmetric distribution of [3H]indole-3-acetic acid, derived from the applied [3H]indole-3-acetyl-myo-inositol, occurred more rapidly than distribution of total 3H-radioactivity. These findings demonstrate that the gravitational stimulus can induce an asymmetric distribution of substances being transported from kernel to shoot. They also indicate that, in addition to the transport asymmetry, gravity affects the steady state amount of indole-3-acetic acid derived from indole-3-acetyl-myo-inositol. (+info
Sources of nonlinearity in cDNA microarray expression measurements.
BACKGROUND: A key assumption in the analysis of microarray data is that the quantified signal intensities are linearly related to the expression levels of the corresponding genes. To test this assumption, we experimentally examined the relationship between signal and expression for the two types of microarrays we most commonly encounter: radioactively labeled cDNAs on nylon membranes and fluorescently labeled cDNAs on glass slides. RESULTS: We uncovered two sources of nonlinearity. The first, which led to discrepancies in analysis affecting the fluorescent signals, was signal quenching associated with excessive dye concentrations. The second, affecting the radioactive signals, was a nonlinear transformation of the raw data introduced by the scanner. Correction for this transformation was made by some, but not all, image-quantification software packages. CONCLUSIONS: The second type of nonlinearity is more troublesome, because it could not have been predicted a priori. Both types of nonlinearities were detected by simple dilution series, which we recommend as a quality-control step. (+info
Application of extracorporeal immunoadsorption to reduce circulating blood radioactivity after intraperitoneal administration of indium-111-HMFG1-biotin.
BACKGROUND: Extracorporeal immunoadsorption (ECAT) is a method of reducing activity in radiosensitive organs by removing excess monoclonal antibodies (MAbs) from the blood. Previously, the authors experimentally evaluated ECAT based on the avidin-biotin concept after intravenous administration of radioimmunoconjugates. The aim of the current study was to determine whether ECAT could be used to reduce activity after intraperitoneal (i.p.) administration of indium-111((111)In)-HMFG1-biotin in rats, and to compare the pharmacokinetics of (111)In-HMFG1 with or without attached biotin after i.p. injection. METHODS: HMFG1, a murine immunoglobulin G(1) MAb that recognizes an epitope on the polymorphic epithelial mucin (PEM) antigen, was labeled with (111)In and then biotinylated. ECAT was explored from unseparated blood using an avidin-agarose adsorption column. Thirty rats were used as controls and 13 underwent ECAT. The whole-body (WB), blood, and organ activity were monitored. RESULTS: The binding capacity of (111)In-HMFG1-biotin to avidin was high. Biotinylation did not enhance the excretion of HMFG1. When ECAT was employed, the WB and blood radioactivity were reduced by 35-40% (P < 0.05) and 75--86% (P < 0.01), respectively. After the completion of ECAT, the activity uptake in organs was significantly decreased. CONCLUSIONS: ECAT was successfully applied after i.p. injection of the (111)In-HMFG-biotin MAb to reduce the radioactivity in the WB, blood, and radiosensitive organs. Due to redistribution of the radiolabeled MAbs during and after the completion of ECAT, the adsorption may have been prolonged or repeated. Biotinylation did not significantly change the biodistribution of the (111)In-HMFG1 in rats after intraperitoneal injection. (+info
Clinically useful detection criteria for sentinel nodes in patients with breast cancer using a radioisotope technique.
BACKGROUND: The radioisotope technique has been used to identify sentinel nodes in patients with breast cancer. However, quantitative analysis of the radioactivity for detecting the sentinel nodes was not previously examined. In this study, we considered a clinically useful criterion for detecting sentinel nodes by a detailed analysis of 312 sentinel nodes using the radioisotope technique. PATIENTS AND METHODS: Patients with T1-2, N0 breast cancer were eligible for this study. The nodes with the highest radioactivity after injection of technetium-labeled tin colloids were identified as hot nodes. The radioactivities of the hot nodes and the background counts of the axillary basin were examined in order to establish new criteria for detecting the sentinel nodes. RESULTS: Between May 1997 and December 2001, 312 hot nodes were detected in 183 of 186 patients (98.4%). Since the false-negative rate for metastasis in hot nodes was only 2.1% (1/48), they could serve as sentinel nodes to predict the nodal status. However, there was a wide distribution of the hot nodes and the background in terms of absolute counts and a criterion for the sentinel nodes could not be established in terms of the absolute counts. When we adopted the criterion of sentinel nodes with a >/=100 count ratio in relation to the background, only 169 hot nodes (54.3%) met our definition. When the criterion of a >or=10 count ratio was adopted, all hot nodes met our definition and all other nodes remained non-sentinel nodes. CONCLUSION: The criterion for defining sentinel nodes in our method is a node with a >or=10 count ratio with respect to the background. It is recommended that an analysis based on such objective data should be investigated in order to provide surgeons with more accurate and clinically useful criteria for detecting sentinel nodes. (+info
Specific activities of 60Co and 152Eu in samples collected from the Atomic-Bomb Dome in Hiroshima.
Neutron-induced activities 60Co and 152Eu have been measured for samples collected from the Atomic-Bomb Dome locating at 161 m from the hypocenter of the Hiroshima Bomb. Specific activities 60Co/Co and 152Eu/Eu at the time of the detonation have been determined as 10.0 +/- 1.0 Bq mg-1 (steel sample S4) and 80 +/- 9 Bq mg-1 (granite sample G1), respectively. Detailed measurements of 60Co and 152Eu activities for samples collected from various locations of the Dome show almost no directional dependence whether the sample faced to the epicenter or not, nor vertical height dependence between 17 m height and the ground level. In addition, 152Eu was not detected in the sample collected from the basement. It has been shown that the present 60Co activity value, the nearest steel one to the hypocenter, as well as other short distance data are systematically lower than the calculated values based on the neutron fluence of the DS86. (+info
IONIZING RADIATION AS AN INDUSTRIAL HEALTH PROBLEM.
Ionizing radiation, first as x-rays, later in natural form, was discovered in Europe in the late 1890's. Immediate practical uses were found for these discoveries, particularly in medicine. Unfortunately, because of the crude early equipment and ignorance of the harmful effects of radiation, many people were injured, some fatally. Because of these experiences, committees and regulatory bodies were set up to study the problem. These have built up an impressive fund of knowledge useful in radiation protection.With the recent development of the peaceful uses of atomic energy, sources of radioactivity have appeared cheaply and in abundance. A rapidly growing number are finding industrial application. Because of their potential risk to humans, the industrial physician must acquire new knowledge and skills so that he may give proper guidance in this new realm of preventive medicine.The Radiation Protection Program of one such industry, the Hydro-Electric Power Commission of Ontario, is summarized. (+info