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PubMed2003

Clarification of the three-body decay of 12C (12.71 MeV).

Using beta decays of a clean source of 12N produced at the IGISOL facility, we have measured the breakup of the 12C (12.71 MeV) state into three alpha particles with a segmented particle detector setup. The high quality of the data permits solving the question of the breakup mechanism of the 12.71 MeV state, a longstanding problem in few-body nuclear physics. Among existing models, a modified sequential model fits the data best, but systematic deviations indicate that a three-body description is needed.

Journal Article↗

PubMed2004

Destabilization of fast-ion-induced long sawteeth by localized current drive in the JET tokamak.

In a tokamak fusion reactor the energetic alpha particles will transiently stabilize the magnetohydrodynamic activity causing sawtooth oscillations. The crash events terminating long sawtooth free periods can provide seed islands for neoclassical tearing modes [Phys. Rev. Lett. 88, 105001 (2002)]]. To shorten the sawtooth periods localized current drive near the q=1 surface is a possibility. This Letter provides the first experimental evidence for the effectiveness of this method in the different physics regime associated with fast-ion-induced long sawteeth on the JET tokamak.

Journal Article↗

PubMed1994

Melanogenesis investigation leading to selective melanoma neutron capture therapy and diagnosis.

Basic investigation into the nature of melanin monomer and polymer synthesis in pigment cells has revealed many of the new underlying factors involved in its regulation and control by three melanogenesis-related genes, tyrosinase, TRP-1 and TRP-2, and other non-tyrosinase glycoproteins. Pigment cells can undergo clinically and biologically recognizable progressive multi-step carcinogenesis. Generally parallel to this progressive cancerization is accentuated melanogenesis. Using this accentuated melanogenesis to develop a specific diagnosis and cure for melanoma (Mm) has long been a challenge. However, until recently, no success was achieved. As an example, attempting to utilize the fact that dopa accumulates as a melanin substrate within Mm cells, hybrid compounds of dopa and cytotoxic drugs were developed. However, these compounds were found to have severe systemic side effects and were therefore unusable. Another newer Mm treatment involves high energy radiation such as fast neutrons. But this is quite non-selective, killing both the target cancer and the normal surrounding tissue. Since 1972, I have developed the idea of coupling the high energy releasing system of thermal neutron irradiation with the non-toxic 10B-dopa analogue, 10B1-L-p-boronophenylalanine (10B1-L-BPA). Thermal neutrons are essentially harmless, but, after specific absorption by 10B, release high LET alpha-particles and 7Li-atoms with an energy of 2.33 MeV up to a distance of 14 mu, the diameter of Mm cells, thus selectively killing them without damaging surrounding normal tissue. After the synthesis of 10B1-L-BPA, exhaustive in vitro and in vivo radiological studies on its enhanced killing effect were done to develop optimal Mm Boron Neutron Capture Therapy (NCT).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Flow cytometric measurements of somatic cell mutations in Thorotrast patients.

Exposure to ionizing radiation has long been well-recognized as a risk factor for cancer development. Since ionizing radiation can induce mutations, an accurate way of measuring somatic mutation frequencies could be a useful tool for evaluating cancer risks. In the present study, we have examined in vivo somatic mutation frequencies at the erythrocyte glycophorin A (GPA) and T-cell receptor (TCR) loci in 18 Thorotrast patients who have been continuously irradiated with alpha-particles emitted from the internal deposition of thorium dioxide and who thus have increased risks of certain malignant tumors. When compared with controls, the results showed a significantly higher frequency of mutants at the lymphocyte TCR loci but not at the erythrocyte GPA loci in the Thorotrast patients. The discrepancy between the results of the two assays is discussed.

Aged↗

PubMed1989

Structural and functional studies on rabbit liver glycogenin.

Glycogenin, the protein primer required for the biogenesis of muscle glycogen, has been isolated from rabbit liver glycogen. The protein comprised 0.0025% of liver glycogen by mass, 200-fold lower than the glycogenin content of muscle glycogen. Structural analyses, including determination of the amino acid sequence surrounding the glucosylated-tyrosine residue, showed identity with muscle glycogenin. Catalytically active liver glycogenin was partially purified and, like the skeletal muscle protein, catalysed an intramolecular, Mn2+- and UDP-Glc-dependent autoglucosylation reaction, forming a primer on which glycogen synthase could act. The results demonstrate that hepatic and muscle glycogenins are almost certainly identical proteins and that liver and skeletal muscle share a common mechanism for the biogenesis of glycogen molecules. The results also indicate that there is about one glycogenin molecule/liver glycogen alpha particle.

Amino Acid Sequence↗

PubMedDate not supplied

Bicuculline methiodide in the blood-brain barrier-epileptogen model of epilepsy.

Focal epilepsy can be produced by a blood-brain barrier (BBB)-excluded systemic convulsant (penicillin, folic acid, etc.) in the presence of a focal BBB lesion. Bicuculline methiodide, a gamma-aminobutyric acid blocking epileptogen, crosses the normal BBB of rats poorly and produces no consistent abnormality behaviorally or on EEG at 36 mg/kg. When the BBB is opened in 0.25 ml of cortex by 6,000 rad of alpha particles, by a pin trauma lesion, or by a heat lesion, the rats are normal clinically and on EEG. When these lesioned rats are challenged with bicuculline methiodide, 36 mg/kg, an intense, highly localized epileptiform discharge results that begins approximately 20 min after injection and lasts 30-90 min. The plausibility and experimental utility of the BBB-epileptogen model of epilepsy are enhanced by these observations.

Animals↗

PubMed1980

Unusual clinical and ultrastructural features in a boy with biochemically typical mannosidosis.

A 4 1/2-year-old boy with a history of recurring respiratory tract infections and seizures, and evidence of severe retardation of psychomotor development and growth, lacked the coarse facial features, skeletal changes and other clinical stigmata generally associated with mannosidosis, but the total alpha-mannosidase activity in his leukocytes, cultured fibroblasts and liver were no more than 10% of the control mean. Studies of the residual alpha-mannosidase enzyme suggest a specific deficiency of the thermostable isoenzyme with an acidic pH optimum. The alpha-mannosidase in the fibroblasts of our and another (control) patient with mannosidosis had a reduced affinity for the substrate 4-methylumbelliferyl-alpha-D-mannoside. Light microscopy of the liver biopsy showed an increase in connective tissue often distorting the hepatic architecture; numerous tiny vacuoles, small dense and lipid bodies in most hepatocytes, and similar but more extensive changes in sinusoidal cells; and sinusoidal pools of hepatocytic debris. Electron microscopy of hepatocytes revealed vacuoles similar but not identical to those described in reported mannosidosis patients, and in addition several forms of secondary lysosomes; prominent peroxisomes (microbodies); increased numbers of profiles of smooth endoplasmic reticulum; dilated rough endoplasmic reticulum containing traces of fine granulo-fibrillar material; increased numbers of rosettes of alpha particles of glycogen and reduced numbers of mitochondria with alterations in their distribution, size and configuration. It is believed that the usual clinical and hepatic ultrastructural features in our patient reflect another variant of mannosidosis.

Abnormalities, Multiple↗

PubMed1994

Dosimetry of Auger-electron-emitting radionuclides: report no. 3 of AAPM Nuclear Medicine Task Group No. 6.

The biological effects of Auger-electron-emitting radionuclides can be as severe as those of alpha particles of high linear energy transfer. A great deal of effort has been expended in exploring the biological effects of Auger electron emitters. Much of this effort has been devoted to improving theoretical and experimental techniques required to calculate absorbed doses and correlate them with the observed biological effects. Given that the main purpose of dosimetry is to obtain a physical descriptor with which to correlate radiation toxicity, then nowhere is this challenge greater than when biological specimens are subject to Auger electron cascades. The dense shower of short-range Auger electrons released by radionuclides, which decay by electron capture or internal conversion, results in biological damage that is highly dependent on the location of the decay site within the cell. In this report, different approaches to Auger electron dosimetry are described and compared. Methods to calculate the absorbed dose from Auger electron emitters at the DNA, cellular, multicellular, and organ levels are described as they relate to the biological effects. The concept of a radiation weighting factor for Auger electrons to be used in the calculation of equivalent dose is reviewed. The importance of subcellular distribution of Auger emitters in determining the biological effects of these radionuclides is emphasized and incorporated into the equivalent dose formalism. The Task Group recommends that a preliminary radiation weighting factor of 10 be used for deterministic effects of Auger electrons, and a value of 20 for stochastic effects.

Biophysical Phenomena↗

PubMed1995

Rutherford's curriculum vitae, 1894-1907.

A single page, handwritten document was discovered when the Macdonald Physics building of McGill University in Montreal was gutted in 1978. This proved to be the draft of Ernest Rutherford's curriculum vitae (C.V.) covering the years 1894-1907, probably written in the autumn of 1906 when Rutherford was preparing to leave McGill. The C.V. contains 21 headings in chronological order, referring to research and other activities of Rutherford and his coauthors (especially Soddy and Barnes), plus a further set of headings relating to the associated investigations of Rutherford's team, including Eve and Hahn. A transcript of the document is provided, although in several places, Rutherford's handwriting is difficult to interpret, and the significance of his abbreviations is not always clear. Each of the items in the C.V. is discussed briefly in this review, in the light both of Rutherford's personal career and of the contribution of his team to the development and understanding of radioactivity. This contribution included the cause and nature of radioactivity (with Soddy), energy aspects of radioactive decay (with Barnes), elucidation of the uranium-radium, thorium and actinium series (Godlewski and Hahn), the radioactivity of the earth and atmosphere (Eve), the nature of the gamma rays (Eve) and, perhaps most important of all, the nature and properties of the alpha particle (Rutherford himself). The latter investigations led directly to Rutherford's later work in Manchester, including the nuclear model of the atom and artificial disintegration of the nucleus.

England↗

PubMed2000

High resolution computed tomography and MRI for monitoring lung tumor growth in mice undergoing radioimmunotherapy: correlation with histology.

A model lung tumor system has been developed in mice for the evaluation of vascular targeted radioimmunotherapy. In this model, EMT-6 mammary carcinoma tumors growing in the lung are treated with 213Bi, an alpha particle emitter, which is targeted to lung blood vessels using a monoclonal antibody. Smaller tumors (< 100 microm in diameter) are cured, but larger tumors undergo a period of regression and then regrow and ultimately prove lethal. The goal of this work was to determine if external imaging with MRI or CT could be used routinely to monitor the growth/ regression of lung tumors in live mice. To attempt to evaluate individual tumors in vivo, animals were initially imaged with magnetic resonance imaging (MRI). High resolution MRI images could be obtained only after sacrifice when lungs were not moving. In contrast, high resolution computed tomography (CT) produced evaluable images from anesthetized animals. Serial CT images (up to 5/animal) were collected over a 17 day period of tumor growth and treatment. When tumored animals became moribund, animals were sacrificed and lungs were inflated with fixative, embedded in paraffin, and then sectioned serially to compare the detection of tumors by high resolution CT with detection by histology. CT proved most useful in detecting lung tumors located in the hilar area and least useful in detecting serosal surface and anterior lobe tumor foci. Overall, CT images of live animals revealed tumors in approximately 2/3 of cases detected in histologic serial sections when relatively few tumors were present per lung. Detection of lesions and their resolution post therapy were complicated due to residual hemorrhagic, regressing tumor nodules and the development of lung edema both of which appeared as high density areas in the CT scans. We conclude that the microCT method used could identify some lung tumors as small as 100 microm in diameter; however, no concrete evaluation of therapy induced regression of the tumors could be made with CT analyses alone.

Animals↗

PubMed2004

Basaltic rocks analyzed by the Spirit Rover in Gusev Crater.

The Spirit landing site in Gusev Crater on Mars contains dark, fine-grained, vesicular rocks interpreted as lavas. Pancam and Mini-Thermal Emission Spectrometer (Mini-TES) spectra suggest that all of these rocks are similar but have variable coatings and dust mantles. Magnified images of brushed and abraded rock surfaces show alteration rinds and veins. Rock interiors contain </=25% megacrysts. Chemical analyses of rocks by the Alpha Particle X-ray Spectrometer are consistent with picritic basalts, containing normative olivine, pyroxenes, plagioclase, and accessory FeTi oxides. Mössbauer, Pancam, and Mini-TES spectra confirm the presence of olivine, magnetite, and probably pyroxene. These basalts extend the known range of rock compositions composing the martian crust.

Extraterrestrial Environment↗

PubMed1964

POLONIUM-210: A VOLATILE RADIOELEMENT IN CIGARETTES.

Polonium-210, which emits alpha particles, is a natural contaminant of tobacco. For an individual smoking two packages of cigarettes a day, the radiation dose to bronchial epithelium from Po(210) inhaled in cigarette smoke probably is at least seven times that from background sources, and in localized areas may be up to 1000 rem or more in 25 years. Radiation from this source may, therefore, be significant in the genesis of bronchial cancer in smokers.

Humans↗

PubMed1997

Detection of soft X-rays and a sensitive search for noble gases in comet Hale-Bopp.

An image of comet Hale-Bopp (C/1995 O1) in soft x-rays reveals a central emission offset from the nucleus, as well as an extended emission feature that does not correlate with the dust jets seen at optical wavelengths. Neon was found to be depleted in the cometary ice by more than a factor of 25 relative to solar abundance, which suggests that ices in Hale-Bopp formed at (or later experienced) temperatures higher than 25 kelvin. A helium line emission at a wavelength of 584 angstroms was detected and may be attributable to charge transfer of solar wind alpha particles in the cometary coma. Ionized oxygen and another helium line contribute to an emission observed at 538 angstroms.

Cosmic Dust↗

PubMed2004

Feasibility of radioimmunotherapy of experimental pneumococcal infection.

Streptococcus pneumoniae is an important cause of community-acquired pneumonia, meningitis, and bacteremia. The problem of pneumococcal disease is exacerbated by increasing drug resistance. Furthermore, patients with impaired immunity are at high risk for invasive pneumococcal infections. Thus, there is an urgent need for new approaches to antimicrobial therapy. Antibody therapies take advantage of the specificity and high affinity of the antigen-antibody interaction to deliver antibacterial compounds to a site of infection in the form of naked or conjugated antibodies. We have recently established that radioimmunotherapy (RIT) can be used to treat experimental fungal infections in mice. In the present study, we investigated the feasibility of applying a RIT approach to the treatment of S. pneumoniae infection by evaluating the susceptibility of S. pneumoniae to radiolabeled antibody in vitro and in an animal infection model. For the specific antibody carrier, we used human monoclonal antibody D11, which binds to pneumococcal capsular polysaccharide 8. We have selected the alpha particle emitter (213)Bi as the radionuclide for conjugation to the antibody. Incubation of serotype 8 S. pneumoniae with (213)Bi-D11 resulted in dose-dependent killing of bacteria. RIT of S. pneumoniae infection in C57BL/6 mice showed that 60% more mice survived in the (213)Bi-D11-treated group (80 micro Ci) than in the untreated group (P < 0.01). The treatment did not cause hematological toxicity, as demonstrated by platelet counts. This feasibility study establishes that RIT can be applied to the treatment of bacterial infections.

Animals↗

PubMed2005

Boron neutron capture therapy of cancer: current status and future prospects.

BACKGROUND: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. BORON DELIVERY AGENTS: Two boron drugs have been used clinically, sodium borocaptate (Na(2)B(12)H(11)SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations ( approximately 20 microg/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boron-containing amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. CLINICAL TRIALS: Current or recently completed clinical trials have been carried out in Japan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of "debulking" surgery to remove as much of the tumor as possible, followed by BNCT at varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v. have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. CONCLUSIONS: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCT could move forward as a treatment modality.

Boron Neutron Capture Therapy↗

PubMed2004

Models of chromosome aberration induction: an example based on radiation track structure.

A few examples of models of chromosome aberration induction are summarised and discussed on the basis of the three main theories of aberration formation, that is "breakage-and-reunion", "exchange" and "one-hit". A model and code developed at the Universities of Milan and Pavia is then presented in detail. The model provides dose-response curves for different aberration types (dicentrics, translocations, rings, complex exchanges and deletions) induced in human lymphocytes by gamma rays, protons and alpha particles of different energies, both as monochromatic fields and as mixed fields. The main assumptions are that only clustered - and thus severe - DNA breaks ("Complex Lesions", CL) can participate in the production of aberrations, and that only break free ends in neighbouring chromosome territories can interact and form exchanges. The yields of CLs induced by the various radiation types of interest are taken from a previous modelling work. These lesions are distributed within a sphere representing the cell nucleus according to the radiation track structure, e.g. randomly for gamma rays and along straight lines for light ions. Interphase chromosome territories are explicitly simulated and configurations are obtained in which each chromosome occupies an intranuclear domain with volume proportional to its DNA content. In order to allow direct comparisons with experimental data, small fragments can be neglected since usually they cannot be detected in experiments. The presence of a background level of aberrations is also taken into account. The results of the simulations are in good agreement with experimental dose-response curves available in the literature, that provides a validation of the model both in terms of the adopted assumptions and in terms of the simulation techniques. To address the question of "true" incompleteness, simulations were also run in which all fragments were assumed to be visible.

Animals↗

PubMed1976

Failure of cyprohepatdine to inhibit vasopressin-stimulated cortisol release in a patient with Cushing's disease.

A case of a 21-year-old woman with Cushing's disease due to a pituitary tumor is described. The patient was treated with cyprohepatadine for 4 weeks immediately following pituitary alpha-particle irradiation. A standard vasopressin test to measure ACTH-mediated cortisol release was performed four times: prior to pituitary irradiation, after irradiation, after 4 weeks of cyproheptadine therapy, and off cyproheptadine for 2 weeks. Cyproheptadine failed to modify vasopressin-stimulated cortisol release in the patient described. This study suggests that cyproheptadine, which has previously been shown to decrease ACTH secretion, probably acts principally at the hypothalamic, rather than at the pituitary level.

Adult↗

PubMed1988

Toxicity of astatine-211 in the mouse.

The toxicity of the alpha particle emitting halogen astatine-211 was examined in male and female mice. Pathological changes were seen in mice killed at 14 days and/or at 56 days following a single injection of 61 kBq211 At per g body weight. The tissues affected, in order of severity were: spleen, lymph nodes, bone marrow, gonads, thyroid, salivary glands and stomach.

Animals↗