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Biomedical subjects

J Micka

Publications and source records attributed to J Micka.

5 recordsLinked to original sources
PubMed1999

Physics of rotating gamma systems for stereotactic radiosurgery.

PURPOSE: The purpose of this study was to evaluate the characteristics of a new rotating gamma system for stereotactic radiosurgery by comparison with a well accepted system. METHODS AND MATERIALS: A novel gamma unit for stereotactic radiosurgery has been developed and distributed to 15 hospitals in China. The unit contains 30 cobalt-60 gamma radiation sources with initial activity of 200 Ci (7.4 x 10(12) Bq) each. The sources are positioned along 30 arcs, and rotate continuously as a group in an axis orthogonal to the patient's body. Measurements have been made on a representative unit installed in the Auhai Radiosurgery Center at the Beijing Navy General Hospital in the People's Republic of China. Ionization chambers calibrated by an American accredited dosimetry calibration laboratory were used for these measurements, as well as radiochromic film and thermoluminescent dosimeters. The unit tested utilizes collimators of nominal diameters of 4, 8, 14, and 18 mm. Radiochromic film samples from a Leksell Model U Gamma Knife were evaluated by the same laboratory and are presented for comparison. The treatment planning system was not evaluated. RESULTS: Radiation-absorbed dose rates and profiles measured for this unit are comparable to those previously measured with the same techniques for the Leksell Model U Gamma Knife units in San Diego and Atlanta. CONCLUSION: This unit is capable of producing well collimated beams of high energy photons, suitable for stereotactic radiosurgery. It has similar physical characteristics to those previously reported for the Leksell Model U Gamma Knife unit.

Cobalt Radioisotopes↗
PubMed1998

Aromatic hydrocarbon receptor polymorphism: development of new methods to correlate genotype with phenotype.

Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon receptor (AHR) affinity among inbred mouse strains, is an important determinant of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6 and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for the rapid identification of DNA sequence differences between Ahr alleles. Oligonucleotides containing single-base changes at polymorphic sites were immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA radiolabeled probes. The observed hybridization patterns demonstrate that this approach can be used to detect nucleotide differences in the Ahr coding region with very high accuracy. In parallel experiments, we used a yeast two-hybrid system to assess phenotypic differences in AHR function. AHR activation, as measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae strain SFY526, was determined following treatment with varying doses of the AHR ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15-fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with results reported for whole-animal studies than the values observed by in vitro ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also confirmed the previously reported observation that an A375V change is principally responsible for the high- to low-affinity AHR phenotype. There has been no straightforward method to reliably and reproducibly phenotype large numbers of humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by oligonucleotide-hybridization and yeast two-hybrid methodologies will be invaluable for the rapid and unequivocal determination of changes in DNA sequence and receptor-ligand affinities associated with human AHR polymorphisms.

Animals↗
PubMed1997

Human Ah receptor (AHR) gene: localization to 7p15 and suggestive correlation of polymorphism with CYP1A1 inducibility.

The mammalian aromatic hydrocarbon receptor (AHR) is a ubiquitous ligand-activated transcription factor. AHR ligands include 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), benzo[a]pyrene, and polychlorinated and polybrominated biphenyls; the endogenous ligand is not yet known. Following ligand binding, the AHR transcriptionally activates genes encoding drug-metabolizing enzymes important in both the metabolic potentiation of substrates to genotoxic reactive intermediates and ultimate carcinogens, and the detoxification of toxic or carcinogenic drugs and other environmental pollutants. AHR-mediated gene expression is also involved in many critical life processes (e.g. cell type-specific differentiation, cell division, apoptosis) by signal transduction mechanisms. Similar to mice, human populations exhibit a > 20-fold range of the CYP1A1 inducibility/AHR affinity phenotype. In the present study, we localized the human AHR gene to chromosome 7p15, using fluorescence in situ hybridization (FISH). Performing linkage analysis in a three-generation family, we show with good probability that the high CYP1A1 inducibility phenotype segregates with the 7p15 region. Sequencing 93 nt (31 amino acids) of the human AHR gene's exon 9, which is the region correlated with the mouse A375V polymorphism responsible for the major portion of high vs low CYP1A1 inducibility/AHR affinity, we found no nucleotide differences; Val-381 was present in all five individuals examined (four related and one unrelated), two of whom show "high' and three of whom show "low' CYP1A1 inducibility. These data indicate that the "high' and "low' CYP1A1 inducibility trait, in the population studied, cannot be explained by a difference among these 31 amino acids in exon 9 of the AHR gene.

Amino Acid Sequence↗
PubMed1994

A comparison of methods for calibrating parallel-plate chambers/.

All dosimetry protocols for calibrating the output of electron beams recommend the use of parallel-plate ionization chambers, but the method of determining their value of Ngas is a matter of concern. The AAPM Protocol (TG 21) recommends a direct comparison with a calibrated cylindrical chamber in phantom at dmax with the highest available electron energy beam. This must be done by the user. Since all calibration laboratories traditionally use 60Co for megavoltage chamber calibrations, two alternate procedures based on exposures in-air, or in-phantom, have been proposed. All methods use correction factors in the data reduction. To verify the consistency of the three methods, we have measured Ngas using each of these techniques for six of the most commonly used and commercially-available parallel-plate ionization chambers. The paired cylindrical and parallel-plate ionization chambers, and phantom materials/buildup caps were matched to the wall composition of the plane chambers, as recommended in TG 39. A 22 MeV electron beam was used for the electron irradiations. The ionization chambers were then taken to an Accredited Dosimetry Calibration Laboratory (ADCL), where 60Co calibrations were performed. The results demonstrate that, by using the appropriate correction factors for the chambers described in this work, all three methods yield values for Ngas that are within 1% of each other.

Biophysical Phenomena↗