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Monoclonal antibody-based therapy.

Monoclonal antibodies have been developed for cancer therapy because they specifically target tumor-related antigens. The current design of antibodies and delivery strategies seeks to overcome the obstacles encountered in delivering antibodies to their targets. Protein engineering techniques to humanize murine antibodies diminishes the immune response, which develops against murine monoclonal antibodies, allowing for multiple doses. Antibodies linked to vasoactive substances or conjugated to liposomes increase antibody and drug localization to tumors. Altering the sizes of antibodies and the methods by which they are conjugated to radioactive isotopes have delineated methods to increase efficacy and decrease toxicity. Tumor growth factors increasingly are being targeted by antibody-based therapeutics. To enhance immune activation of cytotoxic effector cells, bispecific antibodies and antibodies linked to superantigens are being examined. Prodrugs are being converted to their active compounds at the tumor site by antibodies conjugated to enzymes. Finally, intrabodies which can bind to intracellular proteins and are important for the malignant phenotype of the cell, are being developed.

Animals↗

Determination of single and repeated red cell volumes by the indicator dilution method using carbon monoxide as the indicator.

The use of radioactive isotopes limits clinical applications of blood volume measurement in the ICU. We measured red cell volumes with carbon monoxide-labeled RBC in six dogs and five human volunteers. The measured values obtained on the dogs were compared with the simultaneous measurements with the 51Cr method; the ratio of the carbon monoxide to 51Cr values ranged from 0.86 to 1.17, and the mean ratio was 1.0 +/- 0.1 (SD), r = .93. We infer from these results that the carbon monoxide method has several advantages over the 51Cr method: a) the short labeling time (about 1 min), b) rapidly decreasing background levels of carbon monoxide with FIO2 1.0, and c) repeatability at intervals of several hours.

Adult↗

An increase in laryngeal aerosol deposition by ultrasonic nebulizer therapy with intermittent vocalization.

In acute or chronic laryngitis as well as pharyngitis, nebulization with steroid and antibiotics is considered to be a safe and effective treatment. However, the optimal dose, frequency, duration, and method of administration by ultrasonic nebulization is not known. To evaluate whether there is continual improvement using ultrasonic nebulizer therapy, the deposition rate of aerosol particles into the upper airway was studied. We analyzed the deposition rate in the upper airway by a counting system of radioactive isotope (99mTc-diethylene triaminepentaacetic acid; 99mTc DTPA). Volunteers in good health inhaled an aerosol containing 99mTc DTPA under various conditions of inhalation. Deep and slow inhalation at a respiratory rate of 12 breaths/minute resulted in a high deposition rate of 99mTc DTPA in the lung and a low deposition rate in the larynx. In contrast, faster inhalation at a respiratory rate of 36 breaths/minute resulted in an increase in the isotope deposition rate in the larynx. Furthermore, when the volunteers vocalized intermittently during the fast inhalation at a respiratory rate of 36 breaths/minute, the isotope deposition rate in the volunteer's larynx was higher than in all other inhalation conditions. These results suggest that fast inhalation with intermittent vocalization is one of the important inhalation methods used to improve the deposition rate of aerosol particles into the upper airway with an ultrasonic nebulizer.

Administration, Inhalation↗

Utilization of a composite island flap employing omentum in organ reconstruction: an experimental investigation.

New methods for the reconstruction of the ear, nose, and breast using omentum to vascularize appropriate tissue composites of skin, bone, and cartilage are described. The initial investigation demonstrated that it is possible to obtain an island composite flap with omentum-costal cartilage-skin flap and preserve cartilage viability inside the omentum. The ear and nose were reconstructed in two stages. In the first stage, the appropriately carved cartilage and/or bony framework was covered with omentum and a skin graft, leaving the tissue composite buried subcutaneously. In the second stage, the newly reconstructed organ was exteriorized and diagnostic studies were done. The breast reconstruction was undertaken in two stages, first creating an omental island skin flap and subsequently either implanting a standard prosthesis under the flap or transferring the entire composite superiorly to better simulate the clinical reconstruction wherein the lower abdominal skin with omentum would be moved to the anterior chest. In each reconstruction a variety of diagnostic studies, including intravenous fluorescein dye, radioactive isotope uptake, and microangiography, were performed.

Animals↗

Is the hydrogen clearance technique a useful tool for measurements of pancreatic blood flow during acute experimental pancreatitis?

Changes of pancreatic blood flow (PBF) during acute pancreatitis (AP) have been under investigation by means of electromagnetic flowmeters, radioactive microspheres, isotope fractionation, radioactive gas clearance, and venous outflow techniques. All methods, however, have certain drawbacks, which make the application of other techniques desirable. In this study, the hydrogen clearance technique (HCT) was tested for the first time in a well-established foxhound model of AP. PBF, systemic blood pressure, and heart rate were monitored over 90 min after the onset of AP and 60 min after therapeutic infusion of Dextran-40 (10 ml/kg body wt). Our results fully agree with the data found by other techniques in this experimental model. Sixty-five of 73 electrodes implanted into the pancreas of eight foxhounds were found working. From 1,024 registered clearance curves, 876 were identified as monoexponential. In the other cases, and only then, we found either dislocation of the electrode tips (n = 6) or perielectrodal hemorrhage during histological examination (n = 4). We believe that the HCT is a feasible and reliable tool for measuring PBF in experimental settings like AP.

Acute Disease↗

Photoelectric plethysmography in monitoring skin circulation.

Photoelectric plethysmography is not new, but is a simple noninvasive technique to determine erythrocyte volume and oxygen saturation. The data are immediately available, accurate, repeatable, and recordable. Methods currently used for estimating microcirculation and oxygen saturation include clinical tests such as observation of skin color, temperature changes, capillary refill, and bleeding; chemical tests such as fluorscein injection; radioactive isotopes (24Na, 131I, 99mTc, and 133Xe); and instrumental methods (both invasive and noninvasive) such as temperature and infrared thermometry, thermocouples, oxygen probes, and/or the plethysmometer. None of these methods is entirely satisfactory.

Amplifiers, Electronic↗

Design and analysis of lipid tracer kinetic studies.

A fundamental problem in lipid metabolism is designing experiments to quantitate the kinetics of the plasma lipids and lipoproteins in the body. Tracers have been used extensively. In this review, we will combine our knowledge of the theory and application of tracer kinetic studies to discuss current state of the art methodologies for lipid metabolism. We will review the use of stable and radioactive isotopes pointing out the importance of the measurement variables, and the theory and application of noncompartmental and compartmental models to interpret the data.

Humans↗

Pigmented villonodular synovitis.

Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder that affects the synovium in young and middle-aged adults. Although most believe that it is an inflammatory process, some believe that it is a benign neoplasm. The optimal treatment is surgery. The local recurrence rate after marginal excision for localized PVNS is low. In contrast, the local recurrence rate after open synovectomy for diffuse PVNS is relatively high. The intra-articular instillation of radioactive isotopes or external beam radiotherapy (approximately 35 Gy in 14-15 fractions over 3 weeks) may significantly improve the likelihood of local control and long-term function in patients with incompletely resected diffuse PVNS. The probability of complications after moderate-dose radiotherapy (RT) is low.

Brachytherapy↗

Paternal investment directly affects female reproductive effort in an insect.

Female reproductive effort can be influenced by the quality of her mate. In some species, females increase their reproductive effort by differentially allocating resources after mating with high-quality males. Examination of female reproductive effort in relation to male quality has implications for estimating the evolvability of traits and for sexual-selection models. Accurate quantification of reproductive investment is not possible in many species. Butterflies are an exception, as most nectar-feeding species emerge with almost intact reproductive resources, and in some species males provide nutrients at mating that enhance female fecundity. By manipulating male donations and using radioactive isotopes, we quantified the effect of variation in nutrient provisioning on female reproductive effort in two butterfly species. In the greenveined white butterfly, Pieris napi, females increased their reproductive effort after receiving large male donations. By contrast, in the speckled wood, Pararge aegeria, where males do not provide nutrients, female reproductive effort was independent of male ejaculate. Increased reproductive effort in Pieris napi resulted from the production of more eggs, rather than from investing more resources per egg. In this species donating ability is heritable; hence females laying more eggs after mating with high-donating males benefit both through higher fecundity and through the production of high-donating sons.

Animals↗

Detection of bacterial interaction with lactoferrin by an enzyme-linked ligand binding assay (ELBA).

An enzyme-linked ligand binding assay (ELBA) was devised to measure the interaction between bacteria and human (H) or bovine (B) lactoferrin (Lf) linked to horseradish peroxidase. Reagents were calibrated for optimum colour development with o-phenylenediamine as chromophore and organisms that were either positive or negative in a radioisotope-labelled ligand binding assay (RLBA) with 125I-Lf. Good correlation of Lf binding (r = 0.89) was found between ELBA and RLBA with 169 randomly selected strains of Escherichia coli. A semi-quantitative scoring system for ELBA, corresponding to a similar system for RLBA, was established and shown to be valid for 517 strains from seven species of bacterial pathogens. ELBA was used to measure bacterial Lf binding-saturation and displacement kinetics and shown to be comparable with RLBA. ELBA may be a suitable method for examining the binding of Lf to bacteria without the need for radioactive isotopes.

Animals↗

Neutrality condition and response law for nonlinear reaction-diffusion equations, with application to population genetics.

We study a general class of nonlinear macroscopic evolution equations with "transport" and "reaction" terms which describe the dynamics of a species of moving individuals (atoms, molecules, quasiparticles, organisms, etc.). We consider that two types of individuals exist, "not marked" and "marked," respectively. We assume that the concentrations of both types of individuals are measurable and that they obey a neutrality condition, that is, the kinetic and transport properties of the "not marked" and "marked" individuals are identical. We suggest a response experiment, which consists in varying the fraction of "marked" individuals with the preservation of total fluxes, and show that the response of the system can be represented by a linear superposition law even though the underlying dynamics of the system is in general highly nonlinear. The linear response law is valid even for large perturbations and is not the result of a linearization procedure but rather a necessary consequence of the neutrality condition. First, we apply the response theorem to chemical kinetics, where the "marked species" is a molecule labeled with a radioactive isotope and there is no kinetic isotope effect. The susceptibility function of the response law can be related to the reaction mechanism of the process. Secondly we study the geographical distribution of the nonrecurrent, nonreversible neutral mutations of the nonrecombining portion of the Y chromosome from human populations and show that the fraction of mutants at a given point in space and time obeys a linear response law of the type introduced in this paper. The theory may be used for evaluating the geographic position and the moment in time where and when a mutation originated.

Biochemical Phenomena↗

Lattice location and stability of ion implanted Cu in Si

We report on the lattice location of ion implanted Cu in Si using the emission channeling technique. The angular distribution of beta(-) particles emitted by the radioactive isotope 67Cu was monitored following room temperature implantation into Si single crystals and annealing up to 600 degrees C. The majority of Cu was found close to substitutional sites, however, with a significant displacement, most likely 0.50(8) A along the <111> directions towards the bond center position. The activation energy for the dissociation of near-substitutional Cu is estimated to be 1.8-2.2 eV.

Journal Article↗

Lifetime measurements with a scanning positron microscope.

First lifetime results obtained with a scanning positron microscope will be presented. A pulsed positron beam with a variable energy from 0.5 to 20 keV, with a spot diameter of 2 microm, can be electronically scanned over an area of 0.6x0.6 mm(2). This beam is formed after a double-stage stochastic cooling (moderation) of positrons emitted from a radioactive isotope. Included in the system is a conventional scanning electron microprobe for surface analysis. Three-dimensional positron lifetime spectra of a GaAs sample with a small surface scratch reveal the range due to the mechanical damage.

Journal Article↗

A latex agglutination test for the detection of Mycoplasma pneumoniae in respiratory exudates: a comparative study with a commercially available DNA-probe test.

We prepared polyclonal antibody specific to Mycoplasma pneumoniae. Using this antibody, we developed a latex agglutination test (LAT) for detecting the organism in respiratory exudates as rapid diagnosis of M. pneumoniae infection. Further, LAT was compared with DNA-probe test (DP) which was the only commercially available test for the rapid detection of the organism. In LAT, both M. pneumoniae and M. genitalium give positive agglutination, but the titer of M. genitalium was significantly lower than that of M. pneumoniae. The detection limit of LAT was 2 x 10(5) CFU/ml and that of DP was 5 x 10(4) CFU/ml in vitro. It was considered that target molecules in LAT were accumulated in the pharyngeal portion of the patients, because of their long half-life at 37 C. However, ribosomal RNA which was target molecule in DP was destroyed at 37 C much sooner, and the accumulation could not be expected. Actually, positive rate in LAT was higher than that in DP among clinical specimens in which M. pneumoniae was detected by culture method. The procedure of LAT is much easier and more rapid than that of DP in which radioactive isotope is required. LAT could be the choice of test for rapid diagnosis of M. pneumoniae infection.

Antigens, Bacterial↗

Short-term distribution of Cs in relation to Cr-EDTA after intravenous dose in goats.

AIM: The aim of this study was to gather information about the short-term rate of caesium uptake (incorporation) in different animal tissues and explain them with known physiological mechanisms affecting ion distribution. METHODS: Six goats were given an intravenous bolus containing (134)Cs as a tracer and (51)Cr-EDTA as an extracellular marker. After 30 min, the animals were killed and the activity concentration of radioactive isotopes in different tissues and fluid compartments were measured. RESULTS: The highest relative activity concentration of (134)Cs was found in kidney cortex, with a tissue/plasma-ratio around 50. In urine, the ratio varied between 5 and 28. In the salivary gland, cardiac muscle and small intestine the ratio was around 11, 7 and 6, respectively. The contents of small intestine had an average activity concentration five times that of plasma. In skeletal muscle the terminal activity concentration was surprisingly low, with a tissue/plasma ratio mostly far less than unity. Even in connective tissue and cartilage the terminal activity concentration was generally higher than in skeletal muscle. CONCLUSION: The rate of uptake of caesium varies widely from tissue to tissue. Many of these differences can be explained with differences in Na,K-ATPase activity. Also, perfusion and accessibility play a role in some tissues, like brain and possibly part of the skeletal muscles. The short-term distribution of caesium differs distinctly from the long-term distribution reported in literature.

Animals↗

Cell kinetic study of human carcinomas using bromodeoxyuridine.

Cell kinetics in human malignant tumours were studied in vivo using bromodeoxyuridine (BrdU) and immunohistochemistry. BrdU was administered to twenty-four patients with gastric cancer at a dose of 1 g pre-operatively. Specimens were obtained during the operation, fixed in 70% ethanol and embedded in paraffin. BrdU-incorporating cells were detected by immunohistochemical staining using anti-BrdU monoclonal antibody. The labelling index (LI), determined by counting tumour cells microscopically, ranged from 4.0 to 41.4%. The LI was higher at the site of invasion than in the central area of the tumour, but no correlation was found between histological differentiation and LI. The LI of stage I gastric cancer was statistically lower than that of stage II, III and IV gastric cancers (P less than 0.005). This technique, which is less cumbersome and time-consuming than using radioactive isotopes of thymidine, appears to be useful for studying cell kinetics of human malignant tumours.

Antibodies, Monoclonal↗

Magnesium metabolism in patients with coronary heart disease.

1. The oral absorption of magnesium, its myocardial uptake and exchangeable magnesium have been studied in patients with coronary heart disease and controls using the radioactive isotope magnesium-28. 2. No significant difference in oral absorption or myocardial uptake was found between patients and controls. 3. The exchangeable magnesium per kg body weight was significantly lower in the patients than in the controls.

Adult↗

A study in vitro of threaded titanium pins used for retrograde obturation of root canals.

The microleakage of four retrograde filling materials was compared in vitro. Fifty-three single rooted teeth were instrumentated and root filled with resin chloroform and gutta-percha. The gutta-percha cones were left extruding from the access opening. All teeth were apicected and retrograde fillings placed. The materials used were a non gamma 2 amalgam (Amalcap), a glass ionomer cement (ChemFil II), threaded titanium pins cemented with a glass ionomer cement (ChemFil II) and identical titanium pins cemented with a silicone material (Adheseal). After removal of the gutta-percha with tweezers, a radioactive isotope solution was placed in the teeth. Extraradicular samples were taken at 3, 7, 28, 77 and 104 days. All retrograde fillings showed some microleakage. The group with titanium pins cemented with silicone showed the least leakage: significantly less than the teeth with glass ionomer cement (P < 0.01) and with amalgam (P < 0.01). No significant differences were found between other groups.

Dental Amalgam↗