Electron beam therapy with transverse magnetic fields.

Detailed Monte Carlo electron transport simulations were carried out for the purpose of investigating the possibility of improving electron dose distribution for therapeutic applications, by using transverse magnetic fields. The case studied here is that of a 15 MeV electron beam of 6 cm diameter. The electrons pass through 4 cm of field-free tissue and a transverse magnetic field is applied for depth greater than 4 cm. A field of 3 T was found to improve the skin sparing factor by a factor of 2, when compared to field-free irradiation. A field of 2 T could also have a significant effect although less pronounced than 3 T while, for the case at hand, a magnetic field of only 1 T is not effective. The results here include detailed energy deposition contours in three dimensions.

The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a functional ligand for the axonal cell recognition molecule contactin.

Receptor-type protein tyrosine phosphatase beta (RPTP beta) is expressed in the developing nervous system and contains a carbonic anhydrase (CAH) domain as well as a fibronectin type III repeat in its extracellular domain. Fusion proteins containing these domains were used to search for ligands of RPTP beta. The CAH domain bound specifically to a 140 kDa protein expressed on the surface of neuronal cells. Expression cloning in COS7 cells revealed that this protein is contactin, a GPI membrane-anchored neuronal cell recognition molecule. The CAH domain of RPTP beta induced cell adhesion and neurite growth of primary tectal neurons, and differentiation of neuroblastoma cells. These responses were blocked by antibodies against contactin, demonstrating that contactin is a neuronal receptor for RPTP beta. These experiments show that an individual domain of RPTP beta acts as a functional ligand for the neuronal receptor contactin. The interaction between contactin and RPTP beta may generate unidirectional or bidirectional signals during neural development.

Receptor tyrosine phosphatase beta is expressed in the form of proteoglycan and binds to the extracellular matrix protein tenascin.

The extracellular domain of receptor type protein tyrosine phosphatase beta (RPTP beta) exhibits striking sequence similarity with a soluble, rat brain chondroitin sulfate proteoglycan (3F8 PG). Immunoprecipitation experiments of cells transfected with RPTP beta expression vector and metabolically labeled with [35S]sulfate and [35S]methionine indicate that the transmembrane form of RPTP beta is indeed a chondroitin sulfate proteoglycan. The 3F8 PG is therefore a variant form composed of the entire extracellular domain of RPTP beta probably generated by alternative RNA splicing. Previous immunohistochemical studies indicated that both RPTP beta and the extracellular matrix protein tenascin are localized in similar regions of the central nervous system. We have performed co-aggregation assays with red and green Co-vaspheres coated with tenascin and 3F8 PG, respectively, showing that the extracellular domain of RPTP beta (3F8 PG) binds specifically to tenascin. The interaction between a receptor tyrosine phosphatase and an extracellular matrix protein may have a role in development of the mammalian central nervous system.

The expression of a novel receptor-type tyrosine phosphatase suggests a role in morphogenesis and plasticity of the nervous system.

Analysis of the localization of receptor-type protein tyrosine phosphatase-beta (RPTP-beta) by in situ hybridization and immunocytochemistry indicates that it is predominantly expressed in the developing central nervous system (CNS). RPTP-beta is highly expressed in radial glia and other forms of glial cells that play an important role during development. The immunoreactivity localizes to the radial processes of these cells, which act as guides during neuronal migration and axonal elongation. The pattern of RPTP-beta expression changes with the progression of glial cell differentiation. In the adult, high levels of RPTP-beta are seen in regions of the brain where there is continued neurogenesis and neurite outgrowth. The spatial and temporal patterns of RPTP-beta expression suggest that this receptor phosphatase plays a role in morphogenesis and plasticity of the nervous system.

Detailed genetic and physical map of the 3p chromosome region surrounding the familial renal cell carcinoma chromosome translocation, t(3;8)(p14.2;q24.1).

Extensive studies of loss of heterozygosity of 3p markers in renal cell carcinomas (RCCs) have established that there are at least three regions critical in kidney tumorigenesis, one most likely coincident with the von Hippel-Lindau gene at 3p25.3, one in 3p21 which may also be critical in small cell lung carcinomas, and one in 3p13-p14.2, a region which includes the 3p chromosome translocation break of familial RCC with the t(3;8)(p14.2;q24.1) translocation. A panel of rodent-human hybrids carrying portions of 3p, including a hybrid carrying the derivative 8 (der(8)(8pter-->8q24.1::3p14.2-->3pter)) from the RCC family, have been characterized using 3p anchor probes and cytogenetic methods. This 3p panel was then used to map a large number of genetically mapped probes into seven physical intervals between 3p12 and 3pter defined by the hybrid panel. Markers have been physically, and some genetically, placed relative to the t(3;8) break, such that positional cloning of the break is feasible.

Monte Carlo optimization of metal/phosphor screens at megavoltage energies.

The physics of imaging with metal/phosphor (Gd2O2S:Tb on brass) screens at megavoltage energies has been investigated using Monte Carlo simulation. It has been found that pair production is a significant contributor to energy deposition for Bremsstrahlung beams with energies greater than 6 MV. The effects of different thicknesses of phosphor and metal have been studied, and it is shown that the metal plays a significant role in establishing electronic equilibrium in the phosphor. The transport of optical photons through the phosphor has been modeled, and was found that only 10% to 20% of the light created in the phosphor escapes from the surface, with much of the loss being due to total internal reflection at the surface. Calculated results have been compared with experimental measurements of screen brightness for different phosphor and metal thicknesses. The SNR of a video electronic portal imaging device (VEPID) has been calculated as a function of x-ray and optical photon detection efficiency. The non-Poisson distribution of energy deposition in the phosphor is an important contributor to the SNR. The results of this paper should serve as a useful guide to the engineering design of future electronic portal imaging systems.

The cloning of a receptor-type protein tyrosine phosphatase expressed in the central nervous system.

We have isolated cDNA clones and deduced the complete amino acid sequence of a large receptor-type protein tyrosine phosphatase containing 2307 amino acids. The human gene encoding this phosphatase, denoted RPTP beta (or PTP zeta), has been localized to chromosome 7q31-33. RPTP beta is composed of a large extracellular domain, a single transmembrane domain, and a cytoplasmic portion with two tandem catalytic domains. We have also cloned a variant of RPTP beta lacking 859 amino acids from the extracellular domain but with intact transmembrane and cytoplasmic domains. Interestingly, the amino-terminal region of the extracellular domain of RPTP beta contains a stretch of 266 amino acids with striking homology to the enzyme carbonic anhydrase. Immunoprecipitation experiments from a human neuroblastoma cell line indicate that the apparent molecular mass of the core and glycosylated forms of RPTP beta are approximately 250 and 300 kDa, respectively. Northern blot analysis shows that RPTP beta is strictly expressed in the central nervous system. In situ hybridization was used to further localize the expression to different regions of the adult brain including the Purkinje cell layer of the cerebellum, the dentate gyrus, and the subependymal layer of the anterior horn of the lateral ventricle. Hence, RPTP beta represents the first mammalian tyrosine phosphatase whose expression is restricted to the nervous system. The high level of expression of RPTP beta transcripts in the ventricular and subventricular zones of the embryonic mouse brain suggests the importance of this tyrosine phosphatase in the development of the central nervous system.

Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases.

The tyrosine phosphatase RPTP gamma is a candidate tumor suppressor gene since it is located on human chromosome 3p14.2-p21 in a region frequently deleted in certain types of renal and lung carcinomas. In order to evaluate its oncogenic potential and to explore its normal in vivo functions, we have isolated cDNAs and deduced the complete sequences of both human and murine RPTP gamma. The murine RPTP gamma gene has been localized to chromosome 14 to a region syntenic to the location of the human gene. Northern (RNA) blot analysis reveals the presence of two major transcripts of 5.5 and 8.5 kb in a variety of murine tissues. In situ hybridization analysis reveals that RPTP gamma mRNA is expressed in specific regions of the brain and that the localization of RPTP gamma changes during brain development. RPTP gamma is composed of a putative extracellular domain, a single transmembrane domain, and a cytoplasmic portion with two tandem catalytic tyrosine phosphatase domains. The extracellular domain contains a stretch of 266 amino acids with striking homology to the zinc-containing enzyme carbonic anhydrase (CAH), indicating that RPTP gamma and RPTP beta (HPTP zeta) represent a subfamily of receptor tyrosine phosphatases. We have constructed a model for the CAH-like domain of RPTP gamma based upon the crystal structure of CAH. It appears that 11 of the 19 residues that form the active site of CAH are conserved in RPTP gamma. Yet only one of the three His residues that ligate the zinc atom and are required for catalytic activity is conserved. On the basis of this model we propose that the CAH-like domain of RPTP gamma may have a function other than catalysis of hydration of metabolic CO2.

Measurement of the source size of a 6- and 18-MV radiotherapy linac.

The quality of portal imaging is strongly affected by the source size of the radiotherapy machine. The effective source size of the dual-energy clinac 1800 (6 and 18 MV) was measured with a 50 microns wide and 120 mm long slit formed by two tungsten-copper alloy blocks. A series of slit images were obtained by translating the slit horizontally. The images were analyzed using a microdensitometer. The measured data was simulated using an analytical model of the source and its size was derived by a best-fit analysis. For both energies the FWHM was found to be 1.5 +/- 0.1 mm.

Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.

PTPG, the gene for protein-tyrosine phosphatase gamma (PTP gamma), maps to a region of human chromosome 3, 3p21, that is frequently deleted in renal cell carcinoma and lung carcinoma. One of the functions of protein-tyrosine phosphatases is to reverse the effect of protein-tyrosine kinases, many of which are oncogenes, suggesting that some protein-tyrosine phosphatase genes may act as tumor suppressor genes. A hallmark of tumor suppressor genes is that they are deleted in tumors in which their inactivation contributes to the malignant phenotype. In this study, one PTP gamma allele was lost in 3 of 5 renal carcinoma cell lines and 5 of 10 lung carcinoma tumor samples tested. Importantly, one PTP gamma allele was lost in three lung tumors that had not lost flanking loci. PTP gamma mRNA was expressed in kidney cell lines and lung cell lines but not expressed in several hematopoietic cell lines tested. Thus, the PTP gamma gene has characteristics that suggest it as a candidate tumor suppressor gene at 3p21.

Use of storage phosphor imaging plates in portal imaging and high-energy radiography: the intensifying effect of metallic screens on the sensitivity.

The sensitivity of storage phosphor imaging plates (SPIP) at megavolt photon energies (60Co, 6-, 10-, and 18-MV radiotherapy beams) is studied both experimentally and by Monte Carlo radiation transport calculations. In addition, the same techniques are used to investigate the intensifying effect of metal screens on the sensitivity of the SPIP. The results provide evidence that the sensitivity of the SPIPs is proportional to the absorbed energy in the phosphor layer per cGy. The spectral sensitivity is calculated for photon energies between 10 keV and 20 MeV for various SPIP-screen combinations.

Intensifying effect of metallic screens on the sensitivity of x-ray films for 400-kV bremsstrahlung photons.

Measurements are carried out to determine the relative photographic effect produced by electrons emanating from metallic screens on a typical radiographic film. The electrons are produced in metal foils of aluminum, copper, and lead by the interaction of photons in a 400-kV bremsstrahlung beam. Intensification factors of up to 1.65, 2.05, and 5.90 aluminum, copper, and lead screens, respectively, are determined as a function of the foil thickness. The equilibrium thickness screens are determined to be 20 mg/cm2 for aluminum and 30 mg/cm2 for copper and lead. These results are compared with the absorbed dose in the film emulsions, calculated by Monte Carlo methods. The results of the present work are compared with those for 60Co and 137Cs photon beams. The dependence of the equilibrium thickness and the intensification factor on photon energy and the atomic number of the screen material is summarized and explained.

Tinnitus with normal hearing sensitivity: extended high-frequency audiometry and auditory-nerve brain-stem-evoked responses.

Extended high-frequency (HF) audiometry and auditory-nerve brain-stem-evoked responses (ABR) were carried out on two groups of subjects with normal hearing sensitivity. The experimental group comprised 17 subjects with tinnitus, while the control group consisted of age- and sex-matched subjects, not suffering from tinnitus. The aim of the study was to determine whether extended HF audiometry or ABR might reveal significant differences between these two groups of subjects with normal hearing sensitivity. In addition, the characteristics of tinnitus in subjects with normal audiograms were discussed. The results of extended HF audiometry showed no significant differences between the subjects with and without tinnitus. The ABR parameters considered were also within normal limits bilaterally. Based on the methods employed in this study, tinnitus in normal listeners does not appear to reflect appreciable damage in the cochlea or in the brain-stem auditory pathways. The authors present some suggestions for future research.

Monte Carlo studies of x-ray scattering in transmission diagnostic radiology.

Monte Carlo methods have been used to simulate the scattering of x rays in polystyrene and water phantoms. In particular, the ratio of the scattered to total x-ray fluence (scatter fraction) has been calculated for monoenergetic x-ray beams in the energy region relevant to diagnostic radiology and nuclear medicine (30-660 keV). Simulations have been made for representative values of the pertinent geometrical factors; phantom thickness from 5 to 21 cm, x-ray beam diameters of 10 and 25 cm, and scatterer-to-image-plane separations from 0 to 20 cm. As a function of x-ray energy, the scatter fraction was found to vary slowly between 30 and 100 keV, and to decrease between 100 and 660 keV. The present results were generated with a special transport code which included the effects of special geometries and the response of the x-ray detector. With the inclusion of these effects, the results resolved inconsistencies and showed good agreement with previous measured and calculated data.