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New mathematical models with associated equations for isotope dilution mass spectrometry (IDMS).

Vector models which progressively lead to a general model for isotope dilution mass spectrometry (IDMS) are presented for the case of two 'monitor isotopes' and one blend involved. They enable one to find the boundary conditions for performing IDMS, and cover the cases of highly enriched isotopes, radioactive isotopes and ratios that are given with different denominator. The models identify the key measurements in their simplest form as well as the conditions which minimise the measurement effort and in some cases the propagated measurement uncertainties. The equations are discussed and compared with other published IDMS equations. Combined with discussion on fundamental aspects of IDMS, this results in an even more 'general' but also more complex IDMS equation.

Journal Article↗

An assay for ribonuclease activity, based on ultraviolet absorption of RNA hydrolysate, using phosphotungstic acid.

In the method for the determination of ribonuclease activity that depends on the ultraviolet absorption of the RNA hydrolysate, the uranium reagent (25% perchloric acid solution containing 0.75% uranyl acetate) is commonly used for the efficient precipitation of the unhydrolyzed RNA. However, this reagent is always contaminated by the presence of radioactive isotopes. Radioactive uranium is one of the substances used for atomic nuclear fuel and therefore, at least in Japan, the use of uranium compounds requires permission from the government. We tried to find another efficient and non-radioactive precipitant of RNA to replace the uranium reagent, and have developed a phosphotungsten reagent (25% perchloric acid solution containing 0.75% phosphotungstic acid plus 0.6% bovine serum albumin solution) which functions as efficiently as the uranium reagent in the precipitation of RNA. A cell-free crude extract of Dictyostelium discoideum was used as the source of ribonuclease.

Chemical Precipitation↗

Germanium-68 as an adequate tracer for silicon transport in plants. Characterization of silicon uptake in different crop species.

A basic problem in silicon (Si) uptake studies in biology is the lack of an appropriate radioactive isotope. Radioactive germanium-68 ((68)Ge) has been used previously as a Si tracer in biological materials, but its suitability for the study of Si transport in higher plants is still untested. In this study, we investigated (68)Ge-traced Si uptake by four crop species differing widely in uptake capacity for Si, including rice (Oryza sativa), barley (Hordeum vulgare), cucumber (Cucumis sativus), and tomato (Lycopersicon esculentum). Maintenance of a (68)Ge:Si molar ratio that was similar in the plant tissues of all four plant species to that supplied in the nutrient solution over a wide range of Si concentrations demonstrated the absence of discrimination between (68)Ge and Si. Further, using the (68)Ge tracer, a typical Michaelis-Menten uptake kinetics for Si was found in rice, barley, and cucumber. Compared to rice, the relative proportion of root-to-shoot translocated Si was lower in barley and cucumber and especially in tomato (only 30%). Uptake and translocation of Si in rice, barley, and cucumber (Si accumulators) were strongly inhibited by 2,4-dinitrophenol and HgCl(2), but in tomato, as a Si-excluding species, both inhibitors produced the opposite effect. In conclusion, our results suggest the use of the (68)Ge tracer method as an appropriate choice for future studies of Si transport in plants. Our findings also indicate that the restriction of Si from symplast to apoplast in the cortex of Si excluders is a metabolically active process.

Biological Transport↗

Iodine isotopes in radiation hygiene.

Radioactive isotopes of iodine rank among the factors of anthropogenic contamination of the biosphere. The review presents a radiation-hygienic survey of literary data and the author's own results of studies of the metabolism and biological effect of radioactive isotopes of iodine. The risk of their intake by human organism is evaluated. Particular attention is paid to 132-135I and 129I. Data on biological danger of these isotopes are scarce in the literature.

Animals↗

[Peroperative detection probes. Evaluation and perspectives in endocrinology].

The principal primary endocrine tumors may be visualized scintigraphically by injection of highly specific radiopharmaceuticals. When surgery is indicated, the surgeon may be assisted in difficult cases by a probe detecting the radioactivity concentrated in tumoral tissue. A radiopharmaceutical consists of a vector molecule labeled with a radioactive isotope. Only radioactive emissions with a certain half life and energy are suitable for intraoperative detection; this limits the number of usable radionuclides. In practice, one uses iodine 123 (123I), iodine 125 (125I), and iodine 131 (131I) labeled metaiodobenzylguanidine mIBG or indium 111 (111In) labeled pentetreotide (Octreoscan) or bi-specific anti CEA antibody. During intra-operative detection, the probe is closely positioned to the tumor-tissue which is surrounded by radioactive background activity due to the non-specific binding in adjacent organs. In order to work with probes that are easily handled, and sensitive at the same time, one can opt for technology which uses either diodes or scintillating crystals. These probes can be used at room temperature and their choice depends upon the energy to be detected. Interesting results begin to be published concerning pheocyromocytomas, differentiated thyroid carcinomas, gastro-entero-pancreatic tumors and medullary thyroid carcinoma, especially for reintervention when conventional imaging modalities fail to localize tumors.

3-Iodobenzylguanidine↗

Studies of strontium biokinetics in humans. Part 1: optimisation of intrinsic labelling of foodstuffs with stable isotopes of strontium.

The radioactive isotopes of strontium, mainly (90)Sr, which are common fission products, may significantly contribute to the internal exposure of the population in case of their accidental release into the environment and transfer to the food chain. For (90)Sr, the internal radiation dose is significantly dependent on the fractional absorption of the ingested activity (f(1)-value). Human data on the absorption of dietary strontium and of soluble forms of the element give values ranging from about 0.15 to 0.45 (up to 1.0) for adults. The International Commission on Radiological Protection (ICRP) has adopted f(1)-values of 0.6 for children of less than 1 year of age, 0.4 for children between 1 and 15 years and 0.3 for adolescents above 15 years of age. This study was aimed at investigating how far these values correspond to the actual uptake of strontium from contaminated foodstuffs. A methodology is presented that has been developed for preparing foodstuffs intrinsically labelled with stable isotopes and that will be used in tracer kinetic investigations. The results show that cress and salad can be adequately labelled, i.e. a strontium concentration of 1.36+/-0.47 g per kg of cress (wet weight) and of 0.29+/-0.04 g per kg of salad (wet weight) may be obtained within 15 days and 24 days, respectively. For the biokinetic investigations on humans, applying stable isotopes of Sr as tracers, about 0.1-1 mg strontium is required per volunteer, i.e. a few grams of the edible parts of the labelled material are sufficient.

Air Pollutants, Radioactive↗

USAN assigned to radioactive pharmaceutical.

The United States Adopted Names (USAN) applicable to radioactive pharmaceuticals are composed of the names of the basic compound serving as the carrier for the radioactivity, the symbol for the radioactive isotope, and the atomic weight (since several radioactive isotopes of a given element may be in use--see listing under iodine). The following listing of nonproprietary names (shown in boldface type) is arranged in alphabetical order according to the English name of the radioactive element. The isotopes of hydrogen are listed under their specific names, deuterium and tritium. Radioactive pharmaceuticals are often supplied by the manufacturers under a designation equivalent to the adopted nonproprietary name and are listed as such; specific trademarks are given in brackets when they exist. Basic information relative to these lists was given in the editorial that accompanied the first such listing.

Pharmaceutical Preparations↗

Sentinel Lymph Node (SLN) laparoscopic assessment early stage in endometrial cancer.

BACKGROUND: The aim of the study was to demonstrate the validity of sentinel lymph node (SLN) detection after injection of radioactive isotope and patent blue dye in patients affected by early stage endometrial cancer. The second purpose was to compare radioactive isotope and patent blue dye migration. METHODS: Between September 2000 and May 2001, 11 patients with endometrial cancer FIGO stage Ib (n=10) and IIa (n=1) underwent laparoscopic SLN detection during laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and pelvic bilateral systematic lymphadenectomy. Radioactive isotope injection was performed 24 ours before surgery and blue dye injection was performed just before surgery in the cervix at 3, 6, 9 and 12 hours. A 350 mm laparoscopic gamma-scintiprobe MR 100 type 11, (99m)Tc setted (Pol.Hi.Tech.), was used intraoperatively for detecting SLN. RESULTS: Seventeen SLN were detected at lymphoscintigraphy (6 bilateral and 5 monolateral). At laparoscopic surgery the same locations were found belonging at internal iliac lymph nodes (the so called "Leveuf-Godard" area, lateral to the inferior vescical artery, ventral to the origin of uterine artery and medial or caudal to the external iliac vein). Fourteen SLN were negative at histological analysis and only 3 positive for micrometastasis (mean SLN sections = 60. All the other pelvic lymph nodes were negative at histological analysis. The same SLN locations detected with g-scintiprobe were observed during laparoscopy after patent blue dye injection. CONCLUSIONS: If the sensitivity of the assessment of SLN is confirmed to be 100%, this laparoscopic approach could change the management of early stage endometrial cancer. The clinical validity of this technique must be evaluated prospectively.

Adenocarcinoma↗

Liquid-scintillation-spectrometer data processing by desk-top computer.

A desk-top computing system has been programmed to store accurately the quench curves necessary for the calculation of total disintegrations/minute (d.p.m.) of samples containing either one or two radioactive isotopes. In producing d.p.m. values background counts are subtracted, and in binary-labelled samples the counts attributable to each radioactive isotope are separated. The programme also relates d.p.m. to the weight, volume and density of the sample. Each variable is easily recalled and adjustments can be made for different batches of samples without reprogramming. Equally easily changes of radioactive isotope, quenching agent, scintillator or window setting can be accommodated. Quadratic equations are used to express the quench curves. Counting efficiencies obtained when the coefficients in the quadratic equations are derived from three carefully chosen points on a quench curve are compared with those obtained when the coefficients are derived by the method of least squares. The results of both mathematical approximations are compared with the efficiencies read by the eye from graphs.

Carbon Isotopes↗

[The management of thyroid well-differentiated carcinoma invading the upper aerodigestive tract].

OBJECTIVE: To investigate the management and prognosis of thyroid well-differentiated carcinoma invading the upper aerodigestive tract. METHODS: A retrospective analysis of the management was performed done 62 patients with thyroid well-differentiated carcinoma invading the upper aerodigestive tract. The main method of surgery was shaving excision, and the other means including partial thyrochondrectomy, total laryngectomy, sleeve tracheal resection, sternocleidomastoid myoperiosteal flap and myodermal flap reconstruction, or simply palliative excision. Some patients received postoperative radioactive isotope therapy and radiotherapy. All patients were followed-up for 2 to 15 years with an average of 6.5 years. RESULTS: The best curative effect was proved in the patients with local invasion, with the lumen uninvolved and their locoregional control rate was 100.0% (17/17). And the second choice was in patients with more extensive involvement of the upper aerodigestive tract structures. For them, extensive surgical management was done attempting to remove all gross disease followed by reconstruction, their locoregional control rate was 87.5% (7/8). And the third place was designated to patients with local invasion for which shaving excision was performed even though minor residual disease was left, their locoregional control rate was 55.6% (5/9). The poorest result went to simple palliative excision. For 17 patients with minor residual tumor, the locoregional control rate of those who were given postoperative radioactive isotope therapy was significantly higher than those without. CONCLUSION: According to the limits and degree of invasion in the upper aerodigestive tract by thyroid well-differentiated carcinoma, different ways of surgery is indicated. For patients with residual disease, radioactive isotope therapy should be used to improve the result and life quality. Advanced lesions should be given postoperative radio therapy.

Adolescent↗

Nucleotide variation in the p53 tumor-suppressor gene of voles from Chernobyl, Ukraine.

The 1986 Chernobyl disaster contaminated vast regions of Ukraine and Belarus with a variety of radioactive isotopes and heavy metals. While over 90% of the radioactive isotopes have decayed into stable compounds, radiation levels in contaminated areas are still extraordinarily high. In fact, some rodents living near the reactor have internal 134,137Cs concentrations approaching 80 000 Bq/g. Several recent genetic analyses of vertebrates have illustrated that mutation rates of organisms exposed to radiation from Chernobyl are higher than in control groups, but none have studied DNA sequences. Nucleotide sequences of rodent mitochondrial genes were originally reported to have been hypervariable, but those results were subsequently retracted. Herein, I report the results of a pilot study to determine the extent of nucleotide variation at the p53 gene in four species of rodents (voles) from Chernobyl and from control sites. I sequenced a 788 bp region (coding and non-coding) of p53 in 30 different mice comprising four different species of Microtus. Nucleotide variation at the population level was due to deletions and substitutions; both were limited to introns. There were no significant differences between the number of haplotypes in radioactive and control populations (p=0.60). Rare or private alleles might have arisen due to unique mutational pressures at Chernobyl. Alternatively, natural selection might have favored one allele over others (i.e., a selective sweep). Neither scenario is strongly supported by these data. Thus, no apparent genetic effects of the Chernobyl disaster on the p53 gene of resident voles were revealed; more extensive surveys will be necessary to determine if mutation rates are indeed elevated in mice from Chernobyl. However, two salient points emerge; the first involves the utility of introns as markers for mutations in coding regions and the second considers the relative merits of cloning in mutation detection studies.

Animals↗

Determination of kinetic isotope effects for nucleoside hydrolases using gas chromatography/mass spectrometry.

Kinetic isotope effects are widely used to determine the transition state of chemical and enzymatic reactions. Radioactive isotopes are used most often to determine these kinetic isotope effects. However, stable isotopes offer a number of advantages over the use of radioactive isotopes. These advantages include ease of handling and disposal along with increased safety in the laboratory. [1'-(13)C]Inosine and [1'-(2)H]inosine kinetic isotope effects were determined using a gas chromatograph in conjunction with a mass selective detector for nucleoside hydrolase, a purine-metabolizing enzyme. Three ion pairs were used to determine kinetic isotope effects. These ion pairs were 158/159, 187/188, and 217/218. The average isotope effects for all ion pairs were 1.021 +/- 0.006 for [1'-(13)C]inosine and 1.113 +/- 0.008 for [1'-(2)H]inosine. The transition state consistent with these isotope effects is also consistent with the transition state proposed by Schramm and Horenstein using radioactive substrates.

Animals↗

Choice of monitoring isotope in double label radioimmunoassays with nonimmunological separation techniques.

We discuss the suitability of some radioactive isotopes as volume markers in radioimmunoassays, from a radiochemical point of view. For three eligible isotopes (22Na, 60Co, and 75Se) we studied the concentration of the marker in the precipitate formed in the separation phase of radioimmunoassays. For all those kinds of separations tested (charcoal, ammonium sulfate, polyethylene glycol, and ethanol), binding or coprecipitation was virtually absent or negligible with 22Na but 75Se was strongly concentrated in the precipitate. Concentration of 60Co occurred only with charcoal and ethanol precipitation. Because heavy metals tend to bind to serum proteins, we conclude that of all radioactive isotopes commercially available only 22Na should be used in radioimmunoassays with nonimmunological separation methods.

Charcoal↗

DNA synthesis of adult mammalian cardiac muscle cells in long-term culture.

Adult rat cardiac ventricular muscle cells were isolated and cultured in monolayer for 30-45 days. Most of the cardiac muscle cells undergo external and internal structural alterations, resembling embryonic/neonatal cardiac muscle cells in culture (Nag and Cheng, 1981; Nag et al., 1983). These cultured cells underwent DNA synthesis and mitosis as revealed by autoradiography studies that involved the exposure of the cells to [3H]-thymidine for 24 hr prior to the termination of the culture at selected intervals. During the first week of culture, cardiac muscle cells showed less than 5% labeled cells. The labeling index of myocytes attained a peak in the second week of culture, exhibiting approximately 23% labeled cells. The labeling indices of cardiac muscle cells declined over the period of 30 days of culture. During the end of the incubation period, approximately 4% of the myocytes were labeled. When the extent of the total cell population involved in DNA synthesis was examined by exposing the cells to [3H]-thymidine continuously for long periods of time, it was observed that approximately 26% of the cardiac muscle cells regained the capacity for DNA synthesis during 1-10 days of culture. From day 1 to day 14, approximately 29% of the total muscle cell population was labeled. When the cells were exposed to the radioactive isotope continuously for 30 days, approximately 31% of the cells incorporated radioactive isotope, showing their capacity for DNA synthesis. Approximately 90% of the cardiac muscle cells in long-term culture contained more than one nucleus. The nuclei were often observed in multiples of two. Labeled mitotic apparatus was observed in cardiac myocytes, indicating the replication of DNA, followed by karyokinesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗