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PubMedDate not supplied

Genealogical memory to perinatal iodine-131 exposure in rats: I. Alteration in natural immunity.

A heritable alteration in the natural immunity as measured by changes in the natural killer (NK) cell activities of peripheral blood lymphoid-cells was found to occur in rats upon an in utero exposure to iodine-131. The model that was employed for the measurements consisted of Fischer F344 inbred rats exposed to iodine-131 (sodium) during their 16th to 18th day of gestation. The natural immunity of the animals was evaluated by determining the NK cell activities of peripheral blood lymphoid cells of the offsprings when they reached 2 months of age. Immediately following determination of the natural immunity, brother and sister matings were carried out for evolution of the families. Study of these pedigrees revealed an impairment in the natural immunity to persist through two generations (F1, and F2) of the male animals. The hematological profiles of the animals suggest that the insult may alter the numbers of red and white blood cells in the succeeding generations, but has little noticeable effect upon the percentage of lymphocytes. The interpretation of the results indicate that a perinatal insult by iodine-131 during late gestation can result in both somatic and germ cell changes in the immunological system. Thus, there appears to be a genealogical memory to an in utero radionuclide insult which may adversely affect the offspring's immunological competency to respond to subsequent insults.

Animals↗
PubMed1980

Production of 7.6-minute potassium-38 for medical use.

A method is described for generating 20--30 mCi of 7.6-min potassium-38 by means of a small cyclotron. Sodium chloride is mounted on a water-cooled tantalum plate, by evaporation from an aqueous solution. It is bombarded with 14.7 MeV helium-4 ions, at 50 microA. The K-38 is produced free of other radionuclides. For intravenous injection the bombarded NaCl is dissolved in sufficient pyrogen-free water to make an isotonic saline solution, which then is sterilized by filtration. Other methods of production investigated were the bombardment of: carbon tetrachloride with He-4 ions; calcium oxide with 7.8-MeV deuterons; and potassium chloride with 23-MeV He-3 ions. These gave products that were unsuitable for clinical applications. Chiefly because of the short half-life of K-38, the whole-body radiation exposure is estimated to be only about 12 mrad/mCi, and exposures to the heart and kidneys are approximately ten times greater.

Animals↗
PubMed2004

Standardization and quantification of radionuclide solid gastric-emptying studies.

UNLABELLED: The purposes of this investigation were to standardize and validate a simple quantitative method for performing radionuclide solid gastric emptying that can be used for any dual-head gamma-camera and to establish reference values. METHODS: After eating a solid meal (egg sandwich) labeled with a radionuclide, 20 healthy volunteers (9 male, 11 female) underwent a 90-min gastric-emptying study performed with a triple-head gamma-camera. Two sets of 3 simultaneous projections were acquired sequentially for 30 s each: anterior, right posterior oblique (RPO), left posterior oblique (LPO), posterior, left anterior oblique (LAO), and right anterior oblique (RAO), and this sequence was repeated continuously for 90 min. Time-activity curves were generated using a gastric region of interest for each of the views as well as the conjugate-view geometric mean (GM) data for the anterior/posterior, LAO/RPO, and RAO/LPO combinations. Quantitative parameters were determined: percentage gastric emptying (%GE) at 90 min, half-time (min) based on an exponential fit, and clearance rate (%/min) based on a linear fit. Reference values were determined on the basis of a 95% confidence interval of the t distribution. The results were statistically analyzed and compared. RESULTS: The %GE reference values were greater for the anterior/posterior GM (>or=33%) than for the LAO (>or=31%) and anterior (>or=30%) GMs. The 3 %GE GM methods, the 3 exponential-fit GM methods, and the 3 linear-fit GM methods had high correlation coefficients (r >or= 0.874), and with only a single exception, there was no statistical difference among them. The LAO method and LAO/RPO GM mean method correlated strongly (r = 0.900) and had similar mean values (52% vs. 51%) and reference values (29% vs. 30%). All 3 methods of GM quantification also correlated strongly, and there was no significant difference among them. CONCLUSION: We have described and validated a simple method for radionuclide solid gastric emptying that can be used with a dual-head gamma-camera. We recommend the anterior/posterior GM method and have established reference values (>or=33%).

Adult↗
PubMed1984

Relation between marked changes in left ventricular outflow tract gradient and disease progression in hypertrophic cardiomyopathy.

Spontaneous and persistent changes in left ventricular (LV) outflow gradient have been observed occasionally in patients with hypertrophic cardiomyopathy (HC). However, the significance and frequency of such hemodynamic alterations have not been established. In this study, the serial preoperative hemodynamic status of 409 patients with HC was analyzed. Basal LV outflow tract obstruction either spontaneously appeared (or increased) or disappeared (or decreased) in 19 nonoperated patients (about 5%). Changes in hemodynamic state were shown by serial cardiac catheterization in 17 patients and by catheterization and M-mode echocardiography in 2 patients. In most patients (12 of 19), subaortic obstruction under basal conditions appeared or increased; 8 became more symptomatic and in 4 the condition remained stable. Reduction or loss of LV outflow gradient occurred in 7 patients; in 5 of these the condition deteriorated clinically and in 2 it did not change. Hence, in 13 of the 19 patients (70%), spontaneous changes in the magnitude of the basal LV outflow gradient were associated with symptomatic progression. The mechanism of the decrease or disappearance of subaortic obstruction in those patients who deteriorated clinically appeared to be related in 4 patients to impaired global and/or segmental LV function. Chronic atrial fibrillation probably contributed to the worsening clinical condition in 2 of these patients as well as in 2 others. In conclusion, substantial changes in the magnitude of basal subaortic obstruction may occur in a small proportion of patients with HC as part of the natural history of their disease, and such hemodynamic alterations are usually associated with clinical deterioration. It is exceedingly rare for the hemodynamic state of a patient with HC to change from totally nonobstructive to obstructive or vice versa, because such patients usually retain the capacity to generate gradients with provocative maneuvers.

Adult↗
PubMed2001

Cloning, sequencing, and characterization of a gene cluster involved in EDTA degradation from the bacterium BNC1.

EDTA is a chelating agent, widely used in many industries. Because of its ability to mobilize heavy metals and radionuclides, it can be an environmental pollutant. The EDTA monooxygenases that initiate EDTA degradation have been purified and characterized in bacterial strains BNC1 and DSM 9103. However, the genes encoding the enzymes have not been reported. The EDTA monooxygenase gene was cloned by probing a genomic library of strain BNC1 with a probe generated from the N-terminal amino acid sequence of the monooxygenase. Sequencing of the cloned DNA fragment revealed a gene cluster containing eight genes. Two of the genes, emoA and emoB, were expressed in Escherichia coli, and the gene products, EmoA and EmoB, were purified and characterized. Both experimental data and sequence analysis showed that EmoA is a reduced flavin mononucleotide-utilizing monooxygenase and that EmoB is an NADH:flavin mononucleotide oxidoreductase. The two-enzyme system oxidized EDTA to ethylenediaminediacetate (EDDA) and nitrilotriacetate (NTA) to iminodiacetate (IDA) with the production of glyoxylate. The emoA and emoB genes were cotranscribed when BNC1 cells were grown on EDTA. Other genes in the cluster encoded a hypothetical transport system, a putative regulatory protein, and IDA oxidase that oxidizes IDA and EDDA. We concluded that this gene cluster is responsible for the initial steps of EDTA and NTA degradation.

Bacterial Proteins↗
PubMed1991

[Non-invasive assessment of the left ventricular pressure to volume relationships during ejection period using a single cardiac probe system and tonometric measurement of radial arterial pressure].

The left ventricular (LV) pressure to volume relationships are very sensitive parameters for the evaluation of the LV function. For measurement of LV pressure in an entire cardiac cycle, an invasive method is always needed. However, on the assumption that the LV pressure is similar to that of aorta and radial artery during ejection period, we have developed a new system for simple and non-invasive assessment of the LV pressure to volume relationships. The LV volume is estimated by ECG-gated radionuclide ventriculography using a single cardiac probe system and the data were collected every 10 msec. The radial arterial pressure was measured simultaneously every 10 msec by a tonometry system. These data were transferred to the personal computer through RS-232c cable. Then the pressure to volume curves during ejection phase was generated automatically. Emax was calculated from these curves. Moreover, the new parameter called the ejection rate of change of power (ERCP) can be calculated. These parameters are very useful for the evaluation of the effect of the drugs on the LV performance.

Adult↗
PubMed2006

Electron- and positron-emitting radiolanthanides for therapy: aspects of dosimetry and production.

UNLABELLED: All lanthanides have similar chemical properties regarding labeling. Therefore, radiolanthanides that have been used for therapy, such as (153)Sm and (177)Lu, might easily be replaced with other radiolanthanides. The aim of this work was to investigate the suitability of electron- and positron-emitting radiolanthanides for radionuclide therapy with reference to dosimetry and production possibilities. METHODS: Radiolanthanides with half-lives of 1 h to 15 d, stable or long-lived daughters, and limited photon emission were selected. The ratio of the absorbed dose rate to the tumors and the normal tissue (TND) was calculated for different tumor sizes and compared with the TND values for (90)Y and (131)I. The normal tissue and tumors were simulated as an ellipsoid and spheres, respectively. The TND values depend on the physical parameters of the radionuclides, the tumor size, and the ratio between the activity concentrations in the tumor and normal tissue (TNC). RESULTS: (153)Sm, (161)Tb, (169)Er, (175)Yb, and (177)Lu had the highest TND values for most of the tumor sizes studied. Among these radiolanthanides, (161)Tb and (177)Lu are the only ones that can be produced no-carrier-added (nca) and with high specific activities. The Auger-electron emitters (161)Ho and (167)Tm had high TND values for tumors weighing less than 1 mg and can be produced nca and with high specific activities. (142)Pr, (145)Pr, and (166)Ho showed TND values similar to those of (90)Y. (166)Ho is generator produced and can be obtained nca and at high specific activities. (143)Pr, (149)Pm, (150)Eu, (159)Gd, (165)Dy, (176m)Lu, and (179)Lu had higher TND values than did (90)Y for all tumor sizes studied, but only (149)Pm can be produced nca and at high specific activities. The other electron-emitting radiolanthanides and the positron-emitting radiolanthanides showed low TND values for all tumor sizes because of the high photon contribution. CONCLUSION: The low-energy electron emitters (161)Tb, (177)Lu, and (167)Tm might be suitable for radionuclide therapy. The Auger-electron emitter (161)Ho might not be suitable for systemic radionuclide therapy (intravenous injection) because of its short half-life but might be suitable for local therapy (e.g., in body cavities). If higher electron energy is needed, (149)Pm or (166)Ho might be suitable for radionuclide therapy.

Electrons↗
PubMed2004

Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression.

RATIONALE: Impulsive aggressive personality disordered patients have been shown to have decreased relative glucose metabolism in orbito-frontal cortex and anterior cingulate gyrus compared with normal subjects. In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment. OBJECTIVES: The goals of the present study were to attempt to replicate the finding of improvement in impulsive aggression in borderline personality disorder with SSRIs and to investigate the specific cortical areas modified by medication, which might underlie the observed clinical improvement using (18)FDG-PET. METHODS: Ten impulsive aggressive patients with borderline personality disorder were imaged with (18)F-deoxyglucose positron emission tomography at baseline and after receiving fluoxetine at 20 mg/day for 12 weeks. Anatomical MRIs were coregistered to PET and relative metabolic rates were obtained in 39 Brodmann areas. RESULTS: Brodmann areas 11 and 12 in the orbito-frontal cortex showed significant increases in relative metabolic rate. Significant clinical improvement was also observed as assessed by the Overt Aggression Scale-Modified. CONCLUSIONS: These changes are consistent with a normalizing effect of fluoxetine on prefrontal cortex metabolism in impulsive aggressive disorder.

Adult↗
PubMed2001

Foggy scintillation counting technique.

A new "foggy scintillator" was developed for the measurement of low-energy beta-emitters in air. By the use of an ultrasonic wave generator, a liquid scintillator can be converted into the "foggy scintillator". In order to obtain reasonable detection efficiency, it is necessary to prepare a liquid scintillator with a very high concentration of the first solute (PPO). The foggy scintillation counting technique avoids the trouble of the sample preparation usually necessary for the measurement of radionuclides in air, since the radionuclide in the air can be measured directly.

Journal Article↗
PubMedDate not supplied

Doxorubicin-induced cardiac neurotoxicity: study with iodine 123-labeled metaiodobenzylguanidine scintigraphy.

BACKGROUND: Iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) can be used to generate a scintigraphic image of the adrenergic nervous innervation of the heart. METHODS AND RESULTS: To test the hypothesis that doxorubicin may lead to damage of cardiac neurons, we examined 37 patients with various malignant neoplasms, 14 of whom were on therapy with doxorubicin. All patients were examined with 123I-MIBG scintigraphy and radionuclide ventriculography. Cardiac 123I-MIBG uptake was assessed by means of a heart to mediastinum activity ratio (H/M). Left ventricular ejection fraction was not different in patients with or without doxorubicin. In patients receiving doxorubicin, the H/M ratio was significantly lower (1.73 +/- 0.25 vs 2.13 +/- 0.25, p < 0.001) and correlated with doxorubicin cumulative dose (r = -0.51, p < 0.001). By using a H/M ratio of 1.73 as a cutoff point, 123I-MIBG uptake was abnormal in none of the 23 patients not receiving and 6 of 14 patients receiving doxorubicin therapy (p < 0.001). In 10 patients initially not receiving doxorubicin, 123I-MIBG scintigraphy was repeated after receiving 236 +/- 47 mg/m2 of doxorubicin. The H/M became abnormal in 3 of 10 patients, whereas the ejection fraction became abnormal in 2 of 10 patients. CONCLUSION: 123I-MIBG cardiac uptake decreases in a doxorubicin dose-dependent way, indicating a cardiac adrenergic neurotoxic effect of doxorubicin. This phenomenon appears early and generally before deterioration of the ejection fraction.

3-Iodobenzylguanidine↗
PubMed2006

Measurement of gastric emptying by the 13C-octanoate breath test--rationalization with scintigraphy.

The (13)C-octanoate breath test has not achieved universal acceptance for the measurement of solid phase gastric emptying, largely because the results are not comparable with those from direct methods such as scintigraphy. To convert breath-test data to their scintigraphic equivalent scale corrections are applied which have been obtained from population studies, but there is no guarantee that these are applicable in all cases. We propose an alternative method applicable on an individual basis based upon a simple physiological model which does not require any change to the breath-test protocol. It is demonstrated by comparison with scintigraphy and the octanoate saliva test. Results from an existing dataset of simultaneous breath test, saliva test and scintigraphic determinations of solid phase gastric emptying from nine healthy subjects were re-analysed. The corrected breath tests gave gastric emptying curves which were shown to be not significantly different to those obtained from scintigraphy. The method provides a simple but effective way of generating gastric emptying curves from breath-test data that are directly comparable with direct measurement methods, which is advantageous since it allows the whole of the gastric emptying profile to be generated, not just values for the lag phase and half-emptying times.

Algorithms↗
PubMed2001

Evaluation of pulmonary absorption using pharmacokinetic methods.

When assessing inhaled drug absorption, standard pharmacokinetic analyses cannot differentiate drug that reaches the systemic circulation from the lungs from that of the gut. Pulmonary absorption kinetics can be assessed for drugs with negligible gastrointestinal absorption or for drugs that are eliminated via first-pass metabolism. For other drugs, pulmonary absorption kinetics can be studied by blocking gastrointestinal absorption with charcoal, or by studying absorption during the first 30 minutes post inhalation before appreciable oral absorption has occurred. Pharmacokinetic data generally agree well with pulmonary deposition data derived by measuring inhaled radiotracer-labelled drug using gamma-scintigraphy. Monitoring pulmonary and oral absorption also provides information on total systemic exposure and therefore safety. Furthermore, the duration of action of different inhaled drugs and the degree of pulmonary targeting can be obtained by determining the corticosteroid occupancy of lung and systemic glucocorticoid receptors. Pharmacokinetic data from healthy volunteers cannot be extrapolated to patients with asthma, as systemic exposure to inhaled drugs can be markedly less in patients than in healthy volunteers. This correlates with the observed differences in side effects in these two groups. Although pharmacokinetic methods do not provide information on regional deposition, they do generate data on systemic and pulmonary exposure, and so play a role in the development of delivery systems.

Administration, Inhalation↗
PubMed2005

Radiogenic therapy: novel approaches for enhancing tumor radiosensitivity.

Radiotherapy (RT) is a well established modality for treating many forms of cancer. However, despite many improvements in treatment planning and delivery, the total radiation dose is often too low for tumor cure, because of the risk of normal tissue damage. Gene therapy provides a new adjunctive strategy to enhance the effectiveness of RT, offering the potential for preferential killing of cancer cells and sparing of normal tissues. This specificity can be achieved at several levels including restricted vector delivery, transcriptional targeting and specificity of the transgene product. This review will focus on those gene therapy strategies that are currently being evaluated in combination with RT, including the use of radiation sensitive promoters to control the timing and location of gene expression specifically within tumors. Therapeutic transgenes chosen for their radiosensitizing properties will also be reviewed, these include: gene correction therapy, in which normal copies of genes responsible for radiation-induced apoptosis are transfected to compensate for the deletions or mutated variants in tumor cells (p53 is the most widely studied example). enzymes that synergize the radiation effect, by generation of a toxic species from endogenous precursors (e.g., inducible nitric oxide synthase) or by activation of non toxic prodrugs to toxic species (e.g., herpes simplex virus thymidine kinase/ganciclovir) within the target tissue. conditionally replicating oncolytic adenoviruses that synergize the radiation effect. membrane transport proteins (e.g., sodium iodide symporter) to facilitate uptake of cytotoxic radionuclides. The evidence indicates that many of these approaches are successful for augmenting radiation induced tumor cell killing with clinical trials currently underway.

Adenoviridae↗
PubMed1982

Reconstruction and imaging of the beating heart.

Computer methods are discussed which have been developed by the Medical Image processing Group (formerly at SUNY/Buffalo, now at the University of Pennsylvania) for the reconstruction of the beating human heart from x-ray projections. Two data collection modes are emphasized: the dynamic spatial reconstructor and gated cardiac scanning with a rotate-only (third-generation) computed tomography scanner. How the reconstructed beating heart can be displayed by means of dynamic computer graphics is also illustrated.

Animals↗
PubMed1982

Nuclear medicine--an overview.

A radioactive isotope behaves chemically and biologically like its non-radioactive counterpart. The application of this principle to medical diagnosis has evolved into a whole specialty called nuclear medicine. The development of the rectilinear scanner and gamma camera has extended the study of molecular pathways into an exciting imaging modality while developments in radiopharmaceuticals have made radionuclide imaging of many organ systems widely available. The most significant improvements have occurred in bone, hepatobiliary and cardiac imaging. Today, however, nuclear medicine is evolving into a more dynamic study of physiological processes in the body and how these processes may be affected by disease and medical treatment. Emission tomography with a new generation of both gamma and positron emitters will be integral part of nuclear medicine in the future. The challenge to develop radio-labelled antibodies for immunotherapy and immunodetection remains while many of the older techniques like radioimmunoassay, and even the simple colloid liver scan, will continue to contribute significantly to health care.

Humans↗
PubMed1997

Use of radioactive tracers in the evaluation of penile hemodynamics: history, methodology and measurements.

Radionuclide tracer techniques are intimately associated with some of the early ground-breaking investigations in erectile dysfunction and have evolved along with the field. At the present time, the various investigations can be grouped into four categories: labeled blood-pool; tracer washout; tracer washin and combined blood-pool/tracer and tracer washout examinations. Blood pool studies are most useful in assessing the integrity of arterial inflow, but may also be used to generate indices of venous leak. A non-imaging version of the blood-pool test may represent a simple and cost-effective alternative. Washout of intracavernosal xenon during erection seems the most rigorous method of testing venous integrity. Washout using 99mTc-labeled substances may emerge as a convenient alternative to the more technically difficult xenon examinations. Dual-isotope blood pool and washout examinations, though complicated, represent an ideal method of analyzing penile hemodynamics, with potential to contribute significantly to the understanding of penile physiology. Development of improved pharmacologic stimuli and augmentation of testing protocols by intracavernosal pressure monitoring may further improve the utility of quantitative and physiologic nuclear medicine examinations in erectile dysfunction.

Animals↗
PubMed1998

New modular delivery system for diagnostic and therapeutic pre-targeting using tautomer-specific monoclonal antibody EM-6-47 and 3-substituted adenines.

We have developed a new modular affinity system for the 2-step delivery of functional molecules to target cells. The system is based on the tautomer-specific monoclonal antibody (MAb) EM-6-47, which binds to 3- and 3,8-substituted adenines with high affinity (Ka > 10(9) l/mol) without cross-reacting with naturally occurring purine derivatives. This MAb serves as the hapten-specific fusion partner to produce bispecific MAbs (bs-MAbs) recognizing a target cell antigen and a low-m.w. hapten as carrier molecule for, e.g., radionuclides. Either the C-8 or the N-3 position of adenines can be used for conjugation with effector molecules; the remaining position may be substituted with different moieties to modulate the pharmacokinetics of the haptens. Different 3- and 3,8-substituted adenines conjugated to the chelates DOTA and DTPA or to the drug daunomycin were synthesized. Adenine-chelate derivatives were efficiently labeled with (111)In and 90Y, while high-affinity binding of 3-substituted adenines to MAb EM-6-47 remained almost unaffected by the conjugation to radiochelates. To confirm the validity of the delivery system, a prototype bs-MAb, EM-168-47, was generated by somatic cell fusion of MAb EM-6-47 and MAb EM-168-2, the latter recognizing a surface antigen on canine hematopoietic cells. Two-step targeting assays in vitro verified the bs-MAb-mediated, dose-dependent delivery of (111)In-labeled adenine-chelate derivatives to myeloid cells. This system represents a powerful tool for new pre-targeting approaches relying on bs-MAbs and low-m.w. haptens. Suitable cellular antigens can be targeted by fusing the appropriate MAbs with hapten-specific MAb EM-6-47, and tailor-made 3-substituted adenines may be labeled with diagnostic or therapeutic radionuclides, cytotoxic drugs or other functional molecules.

Adenine↗
PubMed2003

Modelling of nonreactive tracer dipole tests in a shear zone at the Grimsel test site.

The investigation of the migration of a high pH plume in a fractured shear zone is foreseen by a long-term experiment at the Grimsel rock laboratory. In order to characterise the initial conditions for the long-term experiment and to evaluate an optimal hydraulic in situ set-up, several dipole experiments with nonreacting tracers have been performed. The dipole experiments differ in geometry, pumping rates and orientation to the background water flow. Several single and double-porosity models have been applied to fit the results of these dipole tracer tests in order to extract values for some transport parameters and discriminate for certain transport processes. A two-dimensional porous medium approach was successfully used to fit tracer breakthrough curves measured for a dipole experiment. A model based on a one-dimensional dual porous medium approach was also successful, although the applied hydraulic dipole, with similar injection and extraction rates, suggests the existence of an extended two-dimensional flow field. For the two-dimensional porous medium approach, tracer breakthrough could only be fitted with a complex flow field geometry within the heterogeneous fractured shear zone. The heterogeneity was generated by heterogeneous porosity and hydraulic permeability distributions. Predictions for further dipole geometries and a sorbing tracer have been calculated by means of both models using the flow and transport parameters deduced from fits for a single dipole experiment. This allows for comparison with the measured breakthrough of sorbing tracers. The foreseen experiment with sorbing (radionuclide) tracers will help decide on the appropriate approach that should be used to describe such dipole experiments in this shear zone. Additionally, the migration and spreading of a solution with high pH has been calculated taking into account mineral dissolution and precipitation in a two-dimensional porous medium approach in order to estimate the amount and character of the mineral reactions induced by the interaction between the high pH solution and the rock.

Geological Phenomena↗