Editorial: The lancet. Nuclear emergencies and accidents.
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This article is a summary of laboratory methods for the hepatic drug metabolizing enzymes which are reliable, sensitive, and reasonably straightforward to perform. Assay conditions are given for which the enzyme rate determinations are linear with respect to time and protein concentration for hepatic tissue preparations from Charles River Sprague Dawley CD male rats. In selecting these particular assay methods, factors such as disposal of radioactive wastes, safety of laboratory personnel, and cost of required equipment were considered. Thus 9 of the 10 hepatic parameters utilize simple spectrophotometric techniques; the remaining assay (ethoxyresorufin O-deethylase) requires a spectrophotofluorometer. The hepatic toxification/detoxification assays are cytochrome P-450 and reduced glutathione content, NADPH-cytochrome C reductase, aminopyrine N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase (3 substrates) and UDP-glucuronyltransferase (2 substrates).
The clinical laboratory has achieved an enviable record for safety even though the opportunities for accident and misfortune are ever present. This article provides an overview of what constitutes an adequate safety program for a laboratory, as well as a list of sources from which more detailed information can be obtained.
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A comparison of labelling compounds with chloramine-T and with 1, 3, 4, 6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril (Iodogen) has been carried out. For human transferrin, human calcitonin, 1-84 bovine parathyrin, fibrinopeptide-A, human thyrotropin and F-CB3, a cyanogen bromide cleavage peptide of human fibrinogen, the quality of tracer produced by the Iodogen method was better. For rat lutropin, human growth hormone and human prolactin, labelling with Iodogen produced a tracer of unsatisfactory quality. For a further 13 peptides, the results from both methods were comparable. Optimal reaction times using Iodogen were of the magnitude of two to three times longer than when using chloramine-T. Reduction of the volume of radioactive waste by up to 90% could be achieved when the Iodogen method was coupled with a short cation-exchange column to separate unreacted iodide from the labelled compound. Data is presented on the quality of tracer, expressed in terms of elution profiles and radioimmunoassay standard curves. A novel "combi-method" of labelling proteins without tyrosine or histidine moieties is presented where N-succinimidyl-3-(4-hydroxyphenyl)-propionate is labelled at pH 7.5 using Iodogen to give "Bolton-Hunter" reagent, which is then transferred to a vessel containing the peptide to be labelled at ph 8.6.
Mononuclear phagocytes play a role in immunologic phenomena as well as in the defense reactions of the organism. Therefore, clinicians should have at their disposal methods of evaluating their function. A simple and reproducible method was set up to evaluate mononuclear phagocytosis and catabolism. The test described in this paper is performed using peripheral monocytes. Mononuclear phagocytes were incubated with opsonized Cr51-labelled sheep erythrocytes. The mononuclear cells phagocytosed the opsonized erythrocytes, and any remaining red cells were lysed. The degree of phagocytosis was determined by the intensity of radioactivity within the monocytes. Catabolism was determined by measuring the amount of radioactive waste excreted by the phagocyte after 18 hours incubation. Thus, this method evaluates the afferent limb of the immune response, as well as the capacity of mononuclear phagocytes to remove and destroy foreign material. Levels of phagocyte catabolism, measured in 30 normal subjects, did not vary appreciably neither in the autologous or homologous serum, nor in the presence or absence of complement.
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A procedure has been proposed to reduce the volume of radon salt in the radon generators used in the laboratories for artificial preparation of radon procedures. This permits work to be done remotely under the conditions of a radon laboratory without manipulations just with radon solution and without radioactive waste.
Tumor necrosis factor alpha (TNF alpha) is a polypeptide cytokine produced primarily by monocytes and macrophages. It is involved in a wide variety of immune reactions. Measurement of TNF alpha originally depended upon bioassays that are of varying reliability and reproducibility. Early immunoassays for TNF alpha required handling of radioisotopes and costly disposal of radioactive waste. Subsequent use of enzymes as reporter molecules in enzyme immunoassay (EIA) has eliminated the burden of radioisotope handling and its associated costs. However, EIA has presented new challenges. Use of thimerosal as a preservative in EIAs may require high disposal costs due to its mercury content. In addition, many EIAs lack the sensitivity achievable in radioimmunoassay (RIA). We have developed a simple microplate enzyme-linked immunosorbent assay (ELISA) for the detection of TNF alpha in serum, plasma and culture supernatants. Our high affinity capture antibody has enabled us to achieve a sensitivity of 1.5 pg/mL. The assay is calibrated to the World Health Organization (W.H.O.) first international standard for TNF alpha (87/650) and exhibits excellent precision and reproducibility. Tetramethylbenzidine is used to generate the colored end product of the reaction, and thimerosal has been removed from all components.
The diminished probability of strategic nuclear confrontation alleviates some of the global concerns about large numbers of radiation casualties in the event of a nuclear war. As a result of the protection of the environment, the management of smaller numbers of radiation casualties assumes a more predictable and more specific role confined to accidents in nuclear energy projects, industry, technology and science. Recent experience of the consequences of accidents in nuclear power plants, in the field of radiotherapy and in the disposal of radioactive waste and spent fuel, present the medical and scientific communities with formidable problems if such events are to lead to minimal adverse effects on the biosphere. Whereas it is not possible to predict a nuclear or radiation accident, radioprotection is hardly an issue of health science alone, but rather an issue of the strictest quality assurance in all aspects of the utilization of nuclear energy and ionizing radiation. Thus, the medical community concerned with radioprotection will have to confine its emphasis on the management of radiation-induced alterations of the human organism from acute radiation syndromes to the stochastic concepts of chronic alterations of radiosensitive organic systems. Current multidisciplinary research in the field of radioprotection involves all aspects of basic and clinical research ranging from the subatomic mechanisms of free radical formation, macromolecular and intracellular radiation-induced alterations, biochemical and physiological homeostatic mechanisms and organ level manifestations to the clinical management of radiation casualties in a controlled hospital environment. Radioprotective agents, although widely studied in the past four decades and including several thousand agents, have not reached the level of providing the field of medicine with an agent that conforms to all criteria of an optimal radioprotectant, including effectiveness, toxicity, availability, specificity and tolerance. This article discusses the current state of radioprotection in medical therapy, and emphasizes a need for continued research in the area of medical management of radiation casualties from the viewpoint of a realistic probability of nuclear incidents or accidents in the nuclear energy-dependent world at the end of the millennium.
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Pacific rockfish from Cordell Bank, off central California (United States), were collected and histologically examined from 1985 to 1990. Hyperplastic and neoplastic cutaneous lesions, involving dermal chromatophores, were observed in five species; yellowtail rockfish (Sebastes flavidus), bocaccio (S. paucispinis), olive rockfish (S. serranoides), widow rockfish (S. entomelas), and chilipepper rockfish (S. goodei). Yearly prevalences were highest in S. paucispinis (29-38%). Prevalence was initially low in S. flavidus, but increased more than 3-fold from 1985 (7.5%) to 1990 (25%). The majority of lesions were black, but white, yellow, orange, red, and mixed-color variants were also seen. Lesions were found in skin, fins, lips, gingiva, tongue, urogenital papilla, conjunctiva, and cornea of the eye. Flat lesions were consistent with melanophore (black), xanthophore (yellow or orange), and erythrophore (red) hyperplasia. Neoplastic lesions included melanophoromas, amelanotic melanophoromas, xanthophoromas, erythrophoromas, and mixed chromatophoromas. Although etiology has not been determined, interest is currently focused on potential exposure to chemical and radioactive carcinogens from the Farallon Island Radioactive Waste Dump, 30 km to the south.