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Biomedical subjects

T K Johnson

Publications and source records attributed to T K Johnson.

35 records · Page 2Linked to original sources

An improved radiolabeling technique of ivalon and its use for dynamic monitoring of complications during therapeutic transcatheter embolization.

Transcatheter embolization by Ivalon particles for treatment of arteriovenous malformations has been an accepted therapeutic technique for many years. We describe a new and efficient radiolabeling technique of Ivalon particles using [99mTc]sulfur colloid. Continuous and dynamic monitoring of injected radiolabeled Ivalon particles is made possible by viewing the persistence scope of a portable gamma camera whose head is positioned over the patient undergoing therapeutic embolization. Therefore, if inadvertent pulmonary embolism or reflux migration of radiolabeled Ivalon particles has occurred, the angiographer is immediately aware of this potentially serious or fatal complication and can take corrective action. We describe two patients, each with an arteriovenous malformation, who had therapeutic embolization with radiolabeled Ivalon particles, one resulting in reflux migration and the other resulting in inadvertent pulmonary embolism.

Adult↗

Ribosomal protein S14 is encoded by a pair of highly conserved, adjacent genes on the X chromosome of Drosophila melanogaster.

We describe a Drosophila DNA clone of tandemly duplicated genes encoding an amino acid sequence nearly identical to human ribosomal protein S14 and yeast rp59. Despite their remarkably similar exons, the locations and sizes of introns differ radically among the Drosophila, human, and yeast (Saccharomyces cerevisiae) ribosomal protein genes. Transcripts of both Drosophila RPS14 genes were detected in embryonic and adult tissues and are the same length as mammalian S14 message. Drosophila RPS14 was mapped to region 7C5-9 on the X chromosome. This interval also encodes a previously characterized Minute locus, M(1)7C.

Animals↗

Clinical comparison of high-resolution with high-sensitivity collimators in low-count cardiac gated blood pool studies.

We compared high-sensitivity (HS) and high-resolution (HR) collimators for 2.5-minute low-count acquisitions in 13 patients undergoing cardiac gated blood pool studies. High-count acquisitions served as standards. Ejection fractions calculated from low-count acquisitions were plotted against high-count acquisitions for each collimator; the variance of the HS plot was lower, and HS images were superior.

Adult↗

Efficient transfer of proteins from acetic acid-urea and isoelectric-focusing gels to nitrocellulose membrane filters with retention of protein antigenicity.

A method which facilitates the rapid and quantitative electrophoretic transfer of proteins from gels not containing sodium dodecyl sulfate (SDS) to nitrocellulose membranes is described. The equilibration of non-SDS-polyacrylamide gel electrophoretic gels in a buffer containing SDS confers a net negative charge to the proteins present, presumably as a result of the formation of SDS-protein complexes. Proteins from gels equilibrated in the SDS buffer and then electroblotted in a Tris-glycine buffer at pH 8.3 are transferred with much greater efficiency than are proteins from untreated gels. The method has been shown to significantly enhance the electrophoretic transfer of polyoma viral proteins resolved in either acetic acid-urea or isoelectric-focusing gels to nitrocellulose membranes, and it is suggested that the method should have universal applicability to all gel electrophoresis systems currently employed. The proteins from isoelectric-focusing gels treated with SDS and transferred to nitrocellulose membranes were found to retain antigenicity to antisera prepared against either denatured or native viral proteins.

Acetates↗

Eighteen-month clinical experience with extended wear silicone contact lenses on 400 patients.

Four hundred patients wearing silicone elastomer contact lenses for extended wear were monitored over an 18-month period. Safety and efficacy were evaluated as related to corneal physiology and lens performance. These lenses proved to be reasonably durable and the lens material and design characteristics did not interfere with ocular physiology but permitted good visual acuity and comfort. The authors' clinical experiences, when compared with other reports of extended-wear lens designs and materials, indicate that this silicone elastomer lens provides superior performance characteristics.

Adolescent↗

Hybrid dysgenesis in Drosophila: the mechanism of T-007-induced male recombination.

The term "hybrid dysgenesis" describes a syndrome of genetic effects which sometimes results when Drosophila melanogaster from wild populations are outcrossed; this syndrome often includes male recombination as well as enhanced rates of genic and chromosomal mutation, sterility, and transmission ratio distortion. In this study, we have examined the mechanism of T-007-induced male recombination by genetically characterizing third chromosomes generated by an exchange in a well-marked euchromatic region. Most recombinant chromosomes were sequentially normal, and no recessive lethal events at the point of exchange were recovered. The results demonstrate that although some recombinants may be generated by nonhomologous chromosome (or chromatid) breakage and reunion, the predominant effect of T-007 is through an enhanced rate of normal mitotic exchange. The rate of mitotic exchange is also increased by ionizing radiation and chemical mutagens; we suggest that the common factor in all three cases is the induction of single strand breaks.

Animals↗

MABDOS: a generalized program for internal radionuclide dosimetry.

Dosimetry calculations of monoclonal antibodies (MABs) are made difficult because the focus of radioactivity is targeted for a nonstandard volume in a nonstandard geometry, precluding straightforward application of the MIRD formalism. MABDOS, a program for performing internal radionuclide dosimetry, addresses this shortcoming. It accounts for the perturbations introduced by the inclusion of tumor(s) as additional source/target of radiation. Biodistribution data are conformed to a compartmental model, allowing the forward simulation of compartmental activity. Integration of the resultant time-activity curves yields cumulative activities for each compartment. Allowing compartments to represent physical organ spaces, cumulative activities are loaded into a column vector representing radionuclide source organs. A matrix multiplication between column vector and the appropriate S table is carried out. S factors for tumors as source and target organ are calculated by treating the tumor as a spherical perturbation to Standard Man geometry, and carrying out a Monte Carlo simulation on-the-fly. The software presents an integrated modeling/dosimetry environment and offers a viable methodology for performing prospective treatment planning.

Antibodies, Monoclonal↗

Photon contribution to tumor dose from considerations of 131I radiolabeled antibody uptake in liver, spleen, and whole body.

The contribution of penetrating photon energy to tumor dose is usually ignored because of the difficulty in calculating absorbed fractions and because it is frequently assumed to represent a small proportion of the total energy. The MABDOSE software--written explicitly to simulate photon transport for the calculation of penetrating radiation absorbed fractions--was used to simulate the 131I photon spectrum originating from the liver, spleen, and whole body source organs. Specific absorbed fractions were calculated for tumors of radius 1.0, 1.5, and 2.0 cm placed near the liver and spleen in the Reference Man geometry. Cumulated activities were estimated using values reported from the literature. Dosimetry estimates from the combined cumulated activity and specific absorbed fractions indicate that neglecting the photon contribution underestimates the tumor dose by 10%-25%.

Antibodies, Monoclonal↗

Pharmacokinetic modeling.

For radiation dosimetry calculations of radiolabeled monoclonal antibodies, (MAB), pharmacokinetics are critical. Specifically, pharmacokinetic modeling is a useful component of estimation of cumulated activity in various source organs in the body. It is thus important to formulate general methods of pharmacokinetic modeling and of pharmacokinetic data reduction, leading to cumulated activities. In this paper different types of models are characterized as "empirical," "analytical," and "compartmental" pharmacokinetic models. There remains a pressing need for quantitative studies in man for a proper understanding of the pharmacokinetics of MAb. Pharmacokinetic modeling of radiolabeled MAb in vivo has relied on relatively limited studies in man and complementary detailed measurements in animals. In either case, any model chosen for analysis of such data is inevitably based on measurements of limited accuracy and precision as well as assumptions regarding human physiology. Very few macroscopic compartmental pharmacokinetic models for MAb, have been tested over a range of conditions to determine their predictive ability. Extracorporeal immunoadsorption represents one approach for drastically altering the biokinetics of antibody distribution, and may serve to validate a given pharmacokinetic model. In addition to macroscopic modeling, the microscopic evaluation of the time-dependent distribution of radiolabeled MAb in tissues is of utmost importance for a proper understanding of the kinetics and radiobiologic effect. Many tumors do not exhibit homogeneous uptake. A mathematical understanding of that distribution is thus essential for accurate tumor dosimetry estimates. This review summarizes methodologies for pharmacokinetic modeling, critically reviews specific pharmacokinetic models and demonstrates the capability of modeling for predictive calculations of altered pharmacokinetics, emphasizing its use in dosimetric calculations.

Animals↗

Dosimetry of solid tumors.

Dosimetry data arising from a decade of radioimmunotherapy are summarized along with techniques utilized to arrive at the reported dose estimates. Generality of the MIRD methodology allows it to serve as a vehicle for the calculation of solid tumor dosimetry although several limitations exist. Nonstandard geometries of solid tumors will ultimately necessitate determination of absorbed fractions for the individual tumors. Several approaches currently under investigation are described. For reasons of practicality, solid tumor dosimetry estimates continue to use the assumption of homogeneous activity distribution in a source organ, accounting for either all radiation or only nonpenetrating radiation. As computation tools become available for incorporating inhomogeneous cellular level data, the currently used "average dose" as an index of tumor sterilization will likely be replaced with a statistical distribution based on the number of viable cells in the tumor volume. Estimates of a tumor control dose would be based upon a linear extension of dose coupled with a threshold dose for cell sterilization.

Humans↗