Particle-mediated gene transfer of PDGF isoforms promotes wound repair.
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Several techniques for cutaneous gene transfer have been investigated for either in vitro or in vivo applications. In the present study, we investigated whether the direct delivery of platelet-derived growth factor cDNA into skin results in improvement in tissue repair. Cutaneous transfections were carried out in rats using a particle-bombardment device (Accell). As revealed by reverse transcriptase-polymerase chain reaction, transgene expression in vivo was transient, with low level expression by day 5. When compared with wounds transfected with a control cytomegalovirus-luciferase plasmid, wounds transfected with platelet-derived growth factor A or B in the MFG vector showed a significant increase in wound tensile strength 7 and 14 d after transfection. At both time points platelet-derived growth factor A transfected wounds exhibited the highest increase in tensile strength over controls, resulting in a 3.5-fold increase at day 7 and a 1.5-fold increase at day 14. The degree of stimulation was not remarkably different between wounds transfected with platelet-derived growth factor B, which is predominantly cell associated, or a truncation mutant, platelet-derived growth factor B211, which is predominantly secreted. These findings demonstrate that in vivo gene transfer by particle bombardment can be used to improve the tissue repair response. This approach provides a robust tool to assess the biologic activity of various proteins and will aid in the development of therapeutic cutaneous gene delivery. (+info)
[18F]-labeled 3-deoxy-3-fluoro-D-glucose: synthesis and preliminary biodistribution data.
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A cyclotron target system for the production of anhydrous [18F] fluoride ion has been developed and used for the synthesis of carrier-free [18F]-3-deoxy-3fluoro-D-glucose (3-FDG). The synthesis is sufficiently rapid and efficient to allow production of usable amounts of 3-FDG with a 6-MeV cyclotron. Preliminary animal studies show that 3-FDG is in fact a glucose analog. (+info)
Concurrent chemotherapy and radiotherapy in invasive cervical cancer patients with high risk factors.
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The aim of this study was to evaluate the survival of 395 previously untreated cervical cancer patients with at least one high risk factor following concurrent chemoradiation and to assess the toxicities. Two different chemotherapy regimens were used for concurrent chemoradiation. In the patients with squamous cell carcinoma, 100 mg/m2 of cisplatin was infused intravenously, followed immediately by five consecutive daily administrations of 5-fluorouracil, 1,000 mg/m2/day, each infused intravenously over 24 hr. As for the patients with adenocarcinoma, 70 mg/m2 of cisplatin, 250 mg/m2 of cytoxan and 45 mg/m2 of adriamycin were administered intravenously on days 1, 2, and 3, respectively. The 5-year survival rate was 54.4% with stage III and IV, 62.6% with lymph node metastasis on computed tomogram or MRI, 77.9% with stage I-II disease with lesion size > or =4 cm, and 50.3% with small cell carcinoma or adenocarcinoma. Side effects from concurrent chemoradiation such as nausea, vomiting, and alopecia were present in all 395 cases. Anemia, leukopenia, thrombocytopenia, hepatotoxicity, and nephrotoxicity were observed to varying degrees, but there was no toxic death. This study suggests that cisplatin-based concurrent chemoradiation in treating cervical cancer patients with high risk factors is effective and relatively well tolerated, with acceptable toxicity. (+info)
Functional redundancy of ventral spinal locomotor pathways.
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Identification of long tracts responsible for the initiation of spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. Pathways derived from the mesencephalic locomotor region and pontomedullary medial reticular formation responsible for fictive locomotion in decerebrate preparations project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the ventrolateral funiculus (VLF). However, white matter regions critical for spontaneous over-ground locomotion remain unclear because cats, monkeys, and humans display varying degrees of locomotor recovery after ventral SCIs. We studied the contributions of myelinated tracts in the VLF and ventral columns (VC) to spontaneous over-ground locomotion in the adult rat using demyelinating lesions. Animals received ethidium bromide plus photon irradiation producing discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, VC, VLF-VC, or complete ventral white matter (CV). Behavior [open-field Basso, Beattie, and Bresnahan (BBB) scores and grid walking] and transcranial magnetic motor-evoked potentials (tcMMEP) were studied at 1, 2, and 4 weeks after lesion. VLF lesions resulted in complete loss or severe attenuation of tcMMEPs, with mean BBB scores of 18.0, and no grid walking deficits. VC lesions produced behavior similar to VLF-lesioned animals but did not significantly affect tcMMEPs. VC-VLF and CV lesions resulted in complete loss of tcMMEP signals with mean BBB scores of 12.7 and 6.5, respectively. Our data support a diffuse arrangement of axons within the ventral white matter that may comprise a system of multiple descending pathways subserving spontaneous over-ground locomotion in the intact animal. (+info)
Image display for collision avoidance of radiation therapy: treatment planning.
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Patient treatment in a medical linear accelerator is characterized by many angular and translational movements of the gantry and couch. The direction and orientation of each treatment beam is specified by a set of gantry, turntable, and collimator angles. It is possible that some selected treatment field configurations will result in gantry/couch or gantry/patient collisions that remain undetected during the treatment planning process. In this work, a digital camera has been used to record all the workable gantry/ patient set-up images, and a Windows programming language is used to edit and display these images on a personal computer for the treatment planner to screen the treatment plans. These graphical displays enable the planner to be aware of any potential collision hazards by an actual visualization of each selected gantry/turntable or gantry/patient angle configuration. (+info)
Evaluation of accelerator mass spectrometry in a human mass balance and pharmacokinetic study-experience with 14C-labeled (R)-6-[amino(4- chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1- methyl-2(1H)-quinolinone (R115777), a farnesyl transferase inhibitor.
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Accelerator mass spectrometry (AMS) has been used in a human mass balance and metabolism study to analyze samples taken from four healthy male adult subjects administered nanoCurie doses of the farnesyl transferase inhibitor 14C-labeled (R)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl) -1-methyl-2(1H)-quinolinone ([14C]R115777). Plasma, urine, and feces samples were collected at fixed timepoints after oral administration of 50 mg [14C]R115777 (25.4 Bq/mg or 687 pCi/mg i.e., equivalent to 76.257 x 10(3) dpm) per subject. AMS analysis showed that drug-related (14)C was present in the plasma samples with C(max) values ranging from 1.6055 to 2.9074 dpm/ml (1.0525-1.9047 microg/ml) at t(max) = 2 to 3 h. The C(max) values for acetonitrile extracts of plasma samples ranged from 0.3724 to 0.7490 dpm/ml in the four male subjects. Drug-related 14C was eliminated from the body both in the urine and the feces, with a mean total recovery of 79.8 +/- 12.9% in the feces and 13.7 +/- 6.2% in the urine. The majority of drug-related radioactivity in urine and feces was excreted within the first 48 h. High-performance liquid chromatography (HPLC)-AMS profiles were generated from radioactive parent drug plus metabolites from pooled diluted urine, plasma, and methanolic feces extracts and matched to retention times of synthetic reference substances, postulated as metabolites. All HPLC separations used no more than 5 dpm injected on-column. The radioactive metabolite profiles obtained compared well with those obtained using liquid chromatography/tandem mass spectometry. This study demonstrates the use of AMS in a human phase I study in which the administered radioactive dose was at least 1000-fold lower than that used for conventional radioactive studies. (+info)
Stability of electron-beam energy monitor for quality assurance of the electron-beam energy from radiotherapy accelerators.
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Information on electron energy is important in planning radiation therapy using electrons. The Geske 3405 electron beam energy monitor (Geske monitor, PTW Nuclear Associates, Carle Place, NY, USA) is a device containing nine ionization chambers for checking the energy of the electron beams produced by radiotherapy accelerators. We wondered whether this might increase the likelihood of ionization chamber trouble. In spite of the importance of the stability of such a quality assurance (QA) device, there are no reports on the stability of values measured with a Geske monitor. The purpose of this paper was therefore to describe the stability of a Geske monitor. It was found that the largest coefficient of variation (CV) of the Geske monitor measurements was approximately 0.96% over a 21-week period. In conclusion, the stability of Geske monitor measurements of the energy of electron beams from a linear accelerator was excellent. (+info)
Mutagenic effects of heavy charged particles.
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Heavy charged particles constitute the most important radiation risk in space. Since mutations can give rise to cancer the investigation of their induction may be helpful for risk quantification. This paper describes experiments in a number of mammalian cells performed with a large range of linear energy transfer (LET). RBE values are always found to increase with LET up to about 100 keV/microm and are similar to those suggested by ICRP. Molecular analyses demonstrate that heavy charged particles not only lead to sometimes very large deletions but also to smaller changes which might represent point mutations. Recent evidence shows that repair phenomena play an important role in the processing of initial DNA lesions to mutagenic alterations. (+info)