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Biomedical subjects

T C Yang

Publications and source records attributed to T C Yang.

At least 73 records · Page 4Linked to original sources

Three variant forms of subcortical aphasia in Chinese stroke patients.

Five right-handed patients with subcortical aphasia that involved the left hemisphere subcortical lesion sites were subjected to CT scans. Given their etiology, two cases were infarctions and the other three were hemorrhages. Two of the patients presented an involvement of the anterior limb of the internal capsule and of the basal ganglia and an anterior superior white-matter lesion extension. In both cases slow scanty dysarthric speech was noted; one had markedly impaired auditory comprehension, and the others were only partially impaired. The third patient presented an involvement of the posterior limb of the internal capsule and of the thalamus and a posterior paraventricular white-matter lesion extension. He had poor auditory comprehension, echolalia, and fluent speech. The last two patients presented an involvement of the internal capsule, the basal ganglia, and the thalamus and an anterior posterior paraventricular white-matter lesion extension. The latter two showed poor auditory comprehension with nonfluent and scanty spontaneous speech. The speech sounds were nonsensical monosyllabic words with a pattern similar to that of global aphasia. All patients had lasting right hemiplegia.

Aged↗

Neoplastic cell transformation by high-LET radiation: molecular mechanisms.

Experimental data on molecular mechanisms are essential for understanding the bioeffects of radiation and for developing biophysical models, which can help in determining the shape of dose-response curves at very low doses, e.g., doses less than 1 cGy. Although it has been shown that ionizing radiation can cause neoplastic cell transformation directly, that high-LET heavy ions in general can be more effective than photons in transforming cells, and that the radiogenic cell transformation is a multi-step process [correction of processes], we know very little about the molecular nature of lesions important for cell transformation, the relationship between lethal and transformational damages, and the evolution of initial damages into final chromosomal aberrations which alter the growth control of cells. Using cultured mouse embryo cells (C3H10T1/2) as a model system, we have collected quantitative data on dose-response curves for heavy ions with various charges and energies. An analysis of these quantitative data suggested that two DNA breaks formed within 80 angstroms may cause cell transformation and that two DNA breaks formed within 20 angstroms may be lethal. Through studies with restriction enzymes which produce DNA damages at specific sites, we have found that DNA double strand breaks, including both blunt- and cohesive-ended breaks, can cause cell transformation in vitro. These results indicate that DNA double strand breaks can be important primary lesions for radiogenic cell transformation and that blunt-ended double strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship is similar for HGPRT gene mutation, chromosomal deletion, and cell transformation, suggesting common lesions may be involved in these radiation effects. The high RBE of high-LET radiation for cell killing and neoplastic cell transformation is most likely related to its effectiveness in producing DNA double strand breaks in mammalian cells. At present the role of oncogenes in radiation cell transformation is unclear.

Animals↗

[Preliminary pathological observation on bone injury after inhalation of trifluoromethyl hypofluoride in rats].

This paper reports the relation between fluoride contents and pathologic changes of skeletal system in Wistar rats after inhalation of organofluoride compound-trifluoromethyl hypofluoride. The trifluoromethyl hypofluoride (CF3OF), purity greater than 95%, used in this study was produced and provided by the Chenguang Chemical Industrial Institute. Twenty-four Wistar rats, weighing between 200 and 250g, were divided into three groups: a control group and two test groups. They were exposure to the trifluoromethyl hypofluoride gas at a dosage of 0, 0.067 and 0.1 ppm respectively, in 1 m3 Plexiglass chamber, two hours a day, five days a week. The results showed that the fluoride levels of ilia in 0.067 and 0.1 ppm group rats were significantly higher than those in the control group (P less than 0.05). The osteogenic effect of CF3OF was confirmed by the histopathological examination of the skeletal tissues. The lesions were also mainly limited to the 0.1 ppm CF3OF group. A very marked osteogenic reaction was found in the periosteum and Haversian canals of ilia in the rats including focal active periosteous osteoblastic proliferations and bone or osteoid tissues forming with a little osteoclastic reactions. for 23 weeks.

Animals↗

Induction of proline prototrophs in CHO-K1 cells by heavy ions.

Using an established mammalian cell line, Chinese hamster ovary cells (CHO-K1), we have observed the induction of prototrophs by various heavy ions. This cell line requires proline for normal growth in medium with low serum concentration. X-rays, three types of heavy particles (600 MeV/u iron, 670 MeV/u neon, and 320 MeV/u silicon ions), ethylmethane sulphonate and 5-azacytidine were used to induce revertants which were proline independent. Log-phase cells treated with 5-azacytidine showed a very high reversion frequency. The induction frequency per viable cell appears to be dose dependent for these four types of radiation, and the dose-response curves are approximately linear. Our results also indicate that the effectiveness of high-LET particles in inducing proline prototrophs is much greater than that of low-LET radiation. The RBE value for the induction of prototrophs was calculated for neon, silicon, and iron particles and found to be about 1.3, 1.7 and 4.5, respectively. At equal survival level, the reversion frequency for X-rays and EMS was about the same.

Animals↗

Neoplastic cell transformation by heavy charged particles.

With confluent cultures of the C3H10T1/2 mammalian cell line, we have investigated the effects of heavy-ion radiation on neoplastic cell transformation. Our quantitative data obtained with high-energy carbon, neon, silicon, argon, iron, and uranium particles show that RBE is both dose- and LET-dependent for malignant cell transformation. RBE is higher at lower doses. There is an increase of RBE with LET, up to about 100-200 keV/micron, and a decrease of RBE with beams of higher LET values. Transformation lesions induced by heavy particles with LET values greater than 100 keV/micron may not be repairable in nonproliferating cells. RBE for slow and nonproliferating cells may be much higher than for actively growing cells.

Animals↗

Neoplastic cell transformation by energetic heavy ions and its modification with chemical agents.

For many years we have been interested in understanding the potential carcinogenic effects of cosmic rays. We have studied the oncogenic effects of cosmic rays with accelerator-produced heavy particle radiation and with a cultured mammalian cell system--C3H10T1/2 cells. Our quantitative data obtained with carbon, neon, silicon, and iron particles showed that RBE is both dose and LET dependent for neoplastic cell transformation. RBE is higher at lower dose, and RBE increases with LET up to about 200 keV/micrometer. In nonproliferation confluent cells, heavy-ion induced transformation damage may not be repairable, although a dose modifying factor of about 1.7 was observed for X-ray radiation. Our recent studies with super-heavy high-energy particles, e.g., 960 MeV/U U235 ions (LET = 1900 keV/micrometer), indicate that these ions with a high inactivation cross-section can cause neoplastic cell transformation. The induction of cell transformation by radiation can be modified with various chemicals. We have found that the presence of DMSO (either during or many days after irradiation) decreased the transformation frequency significantly. It is, therefore, potentially possible to reduce the oncogenic effect of cosmic rays in space through some chemical protection.

Animals↗

Effects of heavy ion radiation on the brain vascular system and embryonic development.

Using neonatal rats as a model system, we investigated the response of the brain vascular system to ionizing radiation and found that distinct petechial hemorrhages developed in the cerebral cortex within a few hours after irradiation, reached a maximum about 13 to 24 hours, and decreased exponentially with time. No brain hemorrhage was found in neonatal rats 12 days after irradiation. Our experimental results indicate that a dose of a few hundred rad of X rays can induce a significant number of hemorrhages in the brain, and the number of lesions increases exponentially with dose. Heavy ions induce more hemorrhages than X rays for a given dose, and the RBE for 670 MeV/u neon particles ranges from about 2.0 for low doses to about 1.4 for high doses. A histological study of the hemorrhages indicates that a large number of red blood cells leak from the blood vessels. The radiation-induced hemorrhages may be a result of some capillary membrane damages or reproductive death of some blood vessel epithelial cells. The fast onset of hemorrhage after irradiation suggest that some membrane damage may be involved. The effect of heavy-ion radiation on the embryonic development was studied with energetic iron particles. Pregnant mice were whole-body irradiated with 600 MeV/u iron particles on day 6 of gestation and were sacrificed 12 days after irradiation. Various physical abnormalities were observed, and embryos irradiated with 1 rad iron particles showed retardation of body development.

Abnormalities, Radiation-Induced↗

Response of cultured normal human mammary epithelial cells to X rays.

The effect of X rays on the reproductive death of cultured normal human mammary epithelial cells was examined. Techniques were developed for isolating and culturing normal human mammary epithelial cells which provide sufficient cells at second passage for radiation studies, and an efficient clonogenic assay suitable for measuring radiation survival curves. It was found that the survival curves for epithelial cells from normal breast tissue were exponential and had D0 values of about 109-148 rad for 225 kVp X rays. No consistent change in cell radiosensitivity with the age of donor was observed, and no sublethal damage repair in these cells could be detected with the split-dose technique.

Breast↗

Molecular and cellular radiobiology of heavy ions.

Quantitative studies at the BEVALAC have demonstrated some of the physical and radiobiological factors that promise to make accelerated heavy ions important for the therapy of cancer. The measured physical dose-biological effect relationships allow the safe and effective delivery of therapeutic schedules of heavy ions. Among the charged particle beams available, carbon, neon and helium ions in the "extended Bragg peak mode" have optimal physical and biological effectiveness for delivery of therapy to deep seated tumors. The depth-dose profiles of these beams protect intervening and adjacent tissues as well as tissues beyond the range of the particles. For the treatment of hypoxic tumors, silicon and argon beams are being considered because they significantly depress the radiobiological oxygen effect in the region of the extended Bragg ionization peak. The depth-effectiveness of the argon beam is somewhat limited, however, because of primary particle fragmentation. Silicon beams have a depth-dose profile which is intermediate between that of neon and argon, and are candidates to become the particle of choice for maximizing high LET particle effects. Heavy accelerated ions depress enzymatic repair mechanisms, decrease variations of radiosensitivity during the cell division cycle, cause greater than expected delays in cell division, and decrease the protective effects of neighboring cells in organized systems. Near the Bragg peak, enhancement of heavy particle effects are observed in split dose schedules. Late and carcinogenic effects are being studied. With the newly developed Repair-Misrepair theory we can quantitatively model most observations.

Animals↗

Some indications of structural damage in retina by heavy ion radiation.

At the Lawrence Berkeley Laboratory Bevalac Facility, iron nuclei were accelerated to an energy of 600 MeV/amu. The beam of iron thus obtained was used to irradiate living biological specimens in order to study possible microscopic tissue damage with the aid of SEM. The experiments involved total head irradiation of live rats which were subsequently returned to their cages to remain for 1 day and 30 days before further examination. After the 1 day and 30 day waits, both eyes were enucleated and placed in chemical fixative followed by ethanol dehydration and critical point drying. Retinas were carefully removed from the eye cups and loaded separately on aluminum stubs which were sputter coated. SEM of the 1 day and 30 day retinas revealed lesions which were not found at all in control retinas. The 1 day and 30 day retinas manifest regions where outer rod segments were missing or rearranged. A single energetic iron nucleus may be capable of generating a retinal lesion which becomes enlarged as biological processes intervene during the 1 day and 30 day waits. Being composed of highly specialized nerve cells, retinas cannot regenerate following irradiation which severely damages the rod cells. Thus one would expect the observed radiation induced retinal lesions to correspond to permanent tissue damage and possible loss of visual acuity in the intact animal.

Animals↗

Response of cultured mammalian cells to accelerated krypton particles.

One of the more interesting observations made in early studies with heavy ions is that the cross-section of the radiosensitive area in mammalian cells increases with LET of HZE particles. It is not certain, however, whether this radiosensitive area is limited to the nuclear area of cells. The successful acceleration of krypton ions to 8.5 MeV/amu at the HILAC Lawrence Berkeley Laboratory, has provided an opportunity to gain more information on this question. Cultured human kidney cells (T-1), growing in exponential phase, were exposed to 3 MeV/amu krypton particles and their colony-forming ability studied. The survival curve was found to be exponential with a mean lethal dose D0=720 rad. A calculation of the cross-section of the radio-sensitive area from the data obtained gives a value of about 145 micrometers2. Present results suggest that the inactivation cross-section stays about the same for heavy ions that have LET greater than 20,000 MeV cm2 g-1, that the nucleus is the only sensitive site for high LET radiation and that a single hit of a heavy ion with very high LET in the nuclear region of the cell can lead to lethal effects. Such particles are therefore extremely dangerous to proliferating living cells.

Cell Line↗