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Ionic permeability and electrical potential differences in Necturus kidney cells.

The cellular concentrations of Na, K, and Cl have been measured in kidney slices of the amphibian, Necturus maculosus. Permeability coefficients have been determined for Na, K, Cl, Rb, Cs, and choline, from studies both of the uptake of radioactive isotopes and the rate of cell swelling in anisotonic solutions. The results of both methods were found to agree well. Measurements were also made of electrical potential differences across the peritubular face of the kidney cells using bathing solutions in which the electrolyte composition and concentrations could be varied. The data obtained are consistent with a model cell in which the potential difference arises as a result of differences in Na permeability relative to K on the two faces of the cell. The intracellular Na concentration is considered to be regulated by a Na-K coupled pump located at the peritubular face of the cell.

Animals↗

INFLUENCE OF LITHIUM IONS ON THE TRANSMEMBRANE POTENTIAL AND CATION CONTENT OF CARDIAC CELLS.

The effect of lithium ions on cardiac cells was investigated by recording the changes in transmembrane potential and by following the movement of Li, Na, and K across the cell membrane. Isolated preparations of calf Purkinje fibers and cat ventricular muscles were used. Potentials were measured by intracellular microelectrodes; ion transport was estimated by flame photometric analysis and by using the radioactive isotopes of Na and K. It was shown (a) that Li ions can replace Na ions in the mechanism generating the cardiac action potential but that they also cause a marked depolarization and pronounced changes in action potential configuration; (b) that the resting permeability to Li ions is high and that these ions accumulate in the cell interior as if they were not actively pumped outwards. In Li-Tyrode [K](i) decreases markedly while the K permeability seems to be increased. In a kinetic study of net K and Na fluxes, the outward movement of each ion was found to be proportional to the second power of its intracellular concentration. The effect on the transmembrane potential is explained in terms of changes in ion movement and intracellular ion concentration.

Animals↗

Long duration responses in squid giant axons injected with 134cesium sulfate solutions.

Giant axons from the squid were injected with 1.5 M cesium sulfate solutions containing the radioactive isotopes 42K and 134Cs. These axons, when stimulated, gave characteristic long duration action potentials lasting between 5 and 45 msec. The effluxes of 42K and 134Cs were measured both under resting conditions and during periods of repetitive stimulation. During the lengthened responses there were considerable increases in potassium efflux but only small increases in cesium efflux. The selectivity of the delayed rectification process was about 9 times greater for potassium ions than for cesium ions. The data suggest that internal cesium ions inhibit the outward potassium movement occurring during an action potential. The extra potassium effluxes taking place during excitation appear to be reduced in the presence of cesium ions to values between 7 and 22% of those expected in the absence of cesium inhibition.

Action Potentials↗

Food irradiation: a public health challenge for the 21st century.

Although the United States food supply is generally considered one of the safest in the world, foodborne illnesses remain a concern. Each year, millions of Americans become ill and as many as 5000 die from foodborne infections. The United States Department of Agriculture estimates that medical treatment and productivity losses associated with foodborne illnesses cost as much as $37 billion annually. Irradiation, which involves exposing food briefly to radiant energy, can reduce or eliminate microorganisms that contaminate food or cause spoilage. So far, only limited quantities of irradiated foods--spices, herbs, dry vegetable seasonings, and some fresh fruits, vegetables, and poultry--have been available in the United States. Major purchasers are health care and food service establishments. The World Health Organization reviewed 500 studies and concluded that food irradiation poses no toxicological, microbiological, or nutritional problems. In more than 40 years, there have been no accidents in North America involving transport of the types of radioactive isotopes used for irradiation.

Food Irradiation↗

A biological approach to the platelet survival curve with criticism of previous interpretations.

The biological mechanisms of platelet destruction must be correctly identified before platelet survival curves can be interpreted. This report develops a theory of platelet destruction which is compared with experiments performed on platelets labelled with the radioactive isotope 51Cr. Platelet destruction rate is a complicated function of platelet number and the thrombokinetic destruction state of the body. A linear approximation of this function shows that destruction is dominated by constant and random consumption. A second order non-linear approximation shows the effect of 'platelet crowding'. This theoretical study explains the difference between predicting the complete platelet survival curve from only two experimental points (in the linear approximation) and the methods of curve fitting currently recommended by the International Committee for Standardization in Haematology. It indicates that the curve fitting of known functional forms to experimental data usually results in an under interpretation of the observations and dilutes the diagnostic potential of the platelet survival curve.

Animals↗

In situ measurement of iron overload in liver tissue by dual-energy methods.

The errors for determining liver iron content by dual-energy computed tomography (dual-energy CT) are calculated for the ideal case where only monochromatic x-ray beams are used. Because of the strong influence of spatial resolution on the radiation dose needed to reduce the error to a given level, we have also calculated the error in dual-energy transmission measurements alone, where the spatial information along the beam path is lost. The prediction of error was tested by simulations and measurements using x-rays emitted by radioactive isotopes and synchrotron radiation. Good agreement between calculation, simulation and measurement was found. It is shown that concentrations of liver iron content (disregarding variation of tissue composition) can be studied with a skin dose of about 30 mGy using dual-energy CT and even with much lower dose using dual-energy transmission measurements. However, there are sources of error besides photon noise, especially errors caused by variation of tissue composition. For example dual-energy CT, although suggested to avoid artifacts caused by fat in the case of a fatty liver, still is affected by fat. The magnitude of these errors is discussed qualitatively, and possibilities for their reduction are suggested. For a definitive estimate of errors of iron content measurements with optimized apparatus more experimental data for well defined variations of body tissue, especially in the case of haemochromatosis, are needed.

Artifacts↗

Characterization of monoclonal antibody to the Epstein-Barr virus BHRF1 protein, a homologue of Bcl-2.

A monoclonal antibody (MAb), designated 3E8, was produced against the Epstein-Barr virus BHRF1 which is a viral homologue of the anti-apoptotic protein Bcl-2. The MAb recognized the BHRF1 protein in extracts from EBV-containing cell lines after activation and EBV-negative cell lines transfected by the BHRF1 gene. Epitope mapping by Western blot analysis revealed that the antibody bound region encompassing amino acid residues 28-33 of the BHRF1. In addition to immunoblotting, the MAb could be applied widely in detection of the BHRF1 in many assays, including immunofluorescence assay, immunohistochemistry, enzyme-linked immunosorbent assay and immunoprecipitation. Most of all, when used in immunoprecipitation experiments, the MAb 3E8 showed a better effect than the existing anti-BHRF1 MAbs since radioactive isotopes were not required to intensify signals of its target antigen. Based on its great use in a variety of immunological reactions, it is a powerful tool to elucidate the biological functions of BHRF1.

Animals↗

Strontium chloride Sr 89 for treating pain from metastatic bone disease.

The role of strontium chloride Sr 89 in the palliative treatment of pain associated with metastatic bone disease is reviewed. Conventional therapies to relieve metastatic bone pain include nonopioid and opioid analgesics, hormonal therapy, external-beam irradiation, and chemotherapy. Limitations in the long-term safety and effectiveness of these treatments have increased interest in using systemic radioactive isotopes for palliation of pain. Strontium chloride Sr 89 is a relatively new bone-seeking radiopharmaceutical that has FDA-approved labeling for use in relieving pain associated with skeletal metastases. An analogue of calcium, strontium chloride Sr 89 is rapidly cleared from the blood after i.v. injection. The agent selectively irradiates metastatic sites while generally sparing normal soft-bone tissue. In clinical studies, a majority of patients with prostate or breast cancer obtained substantial relief from bone pain after receiving strontium chloride Sr 89 alone or in combination with external-beam irradiation. Adverse effects tend to be mild, but patients should be monitored for possible hematologic toxicity. Patients should discontinue any calcium-containing products before receiving the agent. The typical dose is 4 mCi (148 MBq) administered by slow i.v. push over one to two minutes; doses can be repeated at three-month intervals. Pain relief usually begins in 10-20 days and lasts up to six months. Radiation safety measures are necessary in handling strontium chloride Sr 89 and the wastes of patients. Strontium chloride Sr 89 is costly, but preliminary analysis indicates that it may reduce management expenditures overall.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms↗

Preservation of the pulmonary vasoconstrictor response to alveolar hypoxia during the administration of halothane to dogs.

The action of halothane on the pulmonary vasoconstrictor response to unilateral alveolar hypoxia was studied in two groups of dogs. In the first group the redistribution of blood flow between the two lungs was studied with a radioactive isotope method, which provided intermittent measurements, whilst in the second group the distribution of blood flow was observed continuously. In both groups there was no significant alteration of the hypoxic vasoconstrictor response with inspired halothane concentrations varying from 0.5 to 1.5%.

Animals↗

Transport of radioactive oxygen, nitrogen and xenon into the rabbit thoracic aorta in situ.

An in situ preparation of the rabbit thoracic aorta has been used to study the transport of short-lived radioactive isotopes of oxygen (15O16O), nitrogen (13N14N) and an isotope of xenon (133Xe) from 0.9% NaCl into the artery wall. At a luminal hydrostatic pressure of 2 kPa the uptake of all three isotopes by the intima-media increased with time in experiments of up to 15 min duration. Uptake of labelled oxygen was an order of magnitude higher than that of xenon and almost two orders of magnitude higher than nitrogen uptake. Adventitial uptake was similar for all three species. For a perfusion time of 2 1/2 min, the intimal-medial uptake of all three gases increased by almost an order of magnitude as luminal pressure increased from 2 to 13 kPa. Adventitial uptake increased rapidly and at a similar rate for all three gases. The studies were limited in depth and accuracy by the small quantities of isotope available.

Animals↗

Measurement of anterior-posterior diameter of inferior vena cava by ultrasonography: a new non-invasive method to assess acute changes in vascular filling state.

OBJECTIVE: The aim was to determine whether measurement of the anterior-posterior diameter of the inferior vena cava (IVC) by ultrasonography, before and during deep inspiration, allows indirect information on baseline blood volume and changes in vascular filling state to be obtained in healthy subjects. METHODS: Blood volume was measured in 12 volunteers by a standard radioactive isotope method. The IVC dimensions were measured by ultrasound in various positions. In addition, in 10 male subjects the effect on the IVC dimensions of volume loading was evaluated by rapid infusion of plasma expander. During and immediately following volume loading, the IVC dimensions and blood volume were remeasured. RESULTS: Neither the baseline IVC diameters nor any combination of these variables correlated with the concomitant blood volume. Volume loading increased the anterior-posterior IVC dimensions linearly, the largest increase being observed with the maximum IVC diameter and the subject in supine position. CONCLUSIONS: It follows that ultrasonic IVC indices cannot be used as accurate indirect estimate of baseline blood volume, but provide reliable information on acute changes of the subjects' vascular filling state.

Adult↗

Aromatic amino acids are utilized and protein synthesis is stimulated during amino acid infusion in the ovine fetus.

The purpose of this study was to determine whether the ovine fetus is capable of increased disposal of an amino acid load; if so, would it respond by increased protein synthesis, amino acid catabolism or both? A further purpose of the study was to determine whether the pathways of aromatic amino acid catabolism are functional in the fetus. Late gestation ovine fetuses of well-nourished ewes received an infusion of Aminosyn PF alone (APF), and Aminosyn PF + glycyl-L-tyrosine (APF+GT) at rates estimated to double the intake of these amino acids. The initial study, using APF, was performed at 126 +/- 1.4 d; the APF+GT study was performed at 132 +/- 1.7 d (term = 150 d). Phenylalanine and tyrosine kinetics were determined using both stable and radioactive isotopes. Plasma concentrations of most amino acids, but not tyrosine, increased during both studies; tyrosine concentration increased only during the APF+GT study. Phenylalanine rate of appearance and phenylalanine hydroxylation increased during both studies. Tyrosine rate of appearance increased only during the APF+GT study; tyrosine oxidation did not increase during either study. Fetal protein synthesis increased significantly during both studies, producing a significant increase in fetal protein accretion. Fetal proteolysis was unchanged in response to either amino acid infusion. These results indicate that the fetus responds to an acute increase in amino acid supply primarily by increasing protein synthesis and accretion, with a smaller but significant increase in amino acid catabolism also. Both phenylalanine hydroxylation and tyrosine oxidation are active in the fetus, and the fetus is able to increase phenylalanine hydroxylation rapidly in response to increased supply.

Amino Acids↗

New approaches for designing and evaluating food fortification programs.

Historically, food fortification programs were often undertaken with little attention to issues such as micronutrient bioavailability, optimal levels of addition, or efficacy or to monitoring impact on nutritional status, health, and human function. Several developments in recent years have enabled substantial progress to be made in the design and evaluation of fortification programs. The methodology for estimating the prevalence of inadequate nutrient intakes in a population and tolerable upper intake levels has been established and can be used as the basis for estimating desirable amounts of nutrient addition. More attention is being paid to assessing the bioavailability of nutrients (especially minerals) using stable and radioactive isotopes, and bioavailability of iron compounds can be estimated from changes in total body iron calculated from the ratio of transferrin receptors to serum ferritin. Procedures for quality control of the fortification process have been established. New approaches to monitoring the impact of fortification over time include assessment of liver retinol stores using retinol isotope dilution. In summary, the design and evaluation of food fortification programs now requires a series of formative research procedures on the part of nutritionists, which were not often expected or conducted in the past.

Biological Availability↗

Radiation protection system at the RIKEN RI beam factory.

The RIKEN RI (radioactive isotope) Beam Factory is scheduled to commence operations in 2006, and its maximum energy will be 400 MeV u(-1) for ions lighter than Ar and 350 MeV u(-1) for uranium. The beam intensity will be 1 pmicroA (6 x 10(12) particles s(-1)) for any element at the goal. For the hands-on-maintenance and the rational shield thickness of the building, the beam loss must be controlled with several kinds of monitors. Three types of radiation monitors will be installed. The first one consists of a neutron dose equivalent monitor and an ionisation chamber, which are commercially available area monitors. The second one is a conventional hand-held dose equivalent monitor wherein the logarithmic signal is read by a programmable logic controller based on the radiation safety interlock system (HIS). The third one is a simple plastic scintillator called a beam loss monitor. All the monitors have threshold levels for alarm and beam stop, and HIS reads all these signals.

Equipment Design↗

CT-guided stereotaxic biopsy of brain tumors: new technology for an old problem.

On 63 patients, we used stereotaxic surgery combined with computer tomographic (CT) technology, for reasonably safe and precise biopsy of brain lesions. Histological confirmation was possible in 97% of the cases. More recently, we have also been using the CT-guided stereotaxic technique for brachytherapy, consisting of introduction of an array of radioactive isotope seeds (192Ir). The after-loading cannulas used for the isotope seeds are now also being used for introduction of probes for localized hyperthermia of brain tumors. CT-guided stereotaxic technique is proving to be a major technological advance both diagnostically and therapeutically.

Adolescent↗

Episcleral radioactive plaque therapy: initial clinical experience with 56 patients.

Between 1983 and 1987, 56 patients with choroidal melanoma were treated at the University of Southern California with episcleral plaque (RPT). There were 29 female and 27 male patients, with a mean age of 59 years. Tumor stage at diagnosis was T2 in 18 (32%) and T3 in 38 (68%) patients. The tumor height ranged from 2.9 to 15 mm (mean 6.8 mm). Radial dimensions ranged from 5 to 25 mm (mean 13.2 mm), and circumference ranged from 7 to 23 mm (mean 12.3 mm). Most (77%) patients had posteriorly located tumors, including 18% that were juxtapapillary. Custom-designed gold plaques were utilized in this study. Radioactive isotopes used were 125I for 26 procedures or 192Ir for 31 procedures. A total of 56 patients were treated, with one patient having two procedures. Radiation doses at the tumor apex ranged from 29.8 to 165.4 Gy (mean 94.5 Gy), with the dose at 5-mm depth ranging from 70.5 to 430 Gy (mean 161.5 Gy). Follow-up ranged from 29 to 57 months (mean 39 months). The overall 4-year survival was 96%, with a 91% incidence of free-of-disease progression at 4 years. The majority (84%) of patients experienced a decrease in tumor height, with 27 (48%) patients having greater than 50% decrease. Increase in tumor height was noted in 5 (9%) and no change in 4 (7%) patients. Useful vision (greater than 5/200) was observed in 59% of patients, including 21% who had improved vision. Metastatic tumor occurred in 5 (9%) patients, with a mean time to metastases of 14 months. There was a good correlation between radial tumor dimension and metastatic disease, p less than 0.001. Treatment complications were observed in 34 (61%) patients, with cataract and retinopathy being the most common. Enucleation was performed in 11 (20%) patients, with a mean time to enucleation of 14.5 months. Causative factors for enucleation were treatment complications in 6 and tumor progression in 5 patients. Enucleations were required primarily in patients with tumors greater than 8 mm in height (p = 0.009). Improved RPT techniques with three-dimensional dosimetry are needed to reduce the overall incidence of treatment complications. Adjuvant hyperthermia is being investigated in an attempt to improve tumor control in patients with larger tumors.

Adult↗

Sequential changes in cerebral blood flow and distribution of flow within the brain during hemorrhagic shock.

Sequential changes in cerebral blood flow as well as in regional blood flow to the brain (brain stem, cerebellum, hypothalamus, white matter and grey matter) were measured in unanesthetized dogs subjected to gradual prolonged hemorrhage according to a protocol which stimulates the most commonly encountered type of clinical hemorrhagic shock. Microspheres labeled with five different radioactive isotopes were injected into a left atrial catheter at five different times: control, early hypotension (immediately after hemorrhage), late hypotension (just before reinfusion of the shed blood), as well as one and eight hours after reinfusion of the shed blood. Immediately after hemorrhage, the total cerebral blood flow decreased slightly, but increased when calculated as a percent of the cardiac output. In the late hypotensive, hypovolemic stage, there was decreased flow calculated both as percentages of cardiac output and absolute flow as compared with the initial response to hemorrhage. Immediately after reinfusion of the shed blood, there were further reductions of flow. Eight hours subsequently, flow rose to values slightly above control. The patterns of each region was almost identical to that of the total cerebral flow. Since each of the major regions of the brain are approximately equally affected, changes in the level of consciousness and other cerebral functions occurring with hypovolemic shock may reflect circulation of the white matter as well as that of the whole brain.

Animals↗

A valved hepatic portoduodenal intestinal conduit for biliary atresia.

Forty-six consecutive patients with biliary atresia were operated on at our institution during the 11-year period between 1978 and 1989. Their ages at operation ranged from 18 to 153 days (mean, 59 days). After dissecting the porta hepatis structures by Kasai operation, a biliointestinal anastomosis was constructed with a valved hepatic portoduodenal intestinal conduit in all cases. The intestinal valve is an intussuscepted muscular valve. Valvular function was examined radiologically. The upper gastrointestinal series demonstrated no reflux of contrast material into the conduit proximal to the valve and liver scintigraphy demonstrated that radioactive isotope drained readily into the duodenum through the valve. Thirty-nine of the forty-six patients (85%) had bile drainage after initial operation. At present 30 patients (65%) are alive without jaundice, 6 (13%) are alive with jaundice, and 10 (22%) are dead. The 5-year jaundice-free survival rate was 64%. Cholangitis occurred in 9 of 39 patients (23%) who had obtained apparent bile drainage: 5 had tractable cholangitis and 4 had refractory cholangitis. Reoperation restored bile flow in 2 of 8 patients who abruptly ceased to have bile drainage without cholangitis. In conclusion, with a valved hepatic portoduodenal intestinal conduit, the incidence of cholangitis was decreased, its medical control became easier, and the survival rate was improved.

Biliary Atresia↗