Biomedical subjects
Publications and source records attributed to F L Chang.
The course of callosal development in area 17 of rats suggests that, unlike immediately adjacent regions, axons of callosal origin do not normally gain access to upper cortical layers, and this results in the loss of an early exuberant callosal pathway. Removal of optic input, however, permits invasion of these layers of area 17 by callosal axons and results in survival of callosally projecting neurons in area 17.
Embryonic cerebral cortex transplanted to the occipito-parietal region of newborn rats makes connections with the host brain. Retrograde labeling studies after injection of HRP into transplants showed input from the contralateral cortex and ipsilateral thalamus of the host. Transplant projections to the host thalamus and striatum have also been identified.
A number of experimental approaches have indicated differential interneuronal connectivity following differential experience during both development and adulthood. In Golgi preparations, prolonged maze training was reported to alter dendritic branching of distal apical dendrites of Layer IV and V pyramidal neurons in adult rat occipital cortex. To determine the specificity of this effect to direct involvement in the visual aspects of training, the effects of monocular maze training, using a split-brain procedure and opaque contact occluders, was examined in the present study. Rats were maze trained with unilateral or alternating monocular occlusion, while nontrained rats with unilateral or alternating monocular occlusion were handled briefly and given water reward. There was no within-animal effect of fixed occluder position in non-trained controls. In unilaterally-occluded trained rats, Layer V pyramidal neurons in occipital cortex opposite the open eye had greater oblique dendritic length in the distal region of the apical dendrite than did those opposite the occluded eye. Similarly, rats trained with alternating occlusion had greater distal apical oblique dendritic length in Layer V occipital pyramidal neurons than did nontrained controls. This indicates that morphological sequelae of training are concentrated in areas processing information associated with visual aspects of the training and renders unlikely general metabolic or hormonal causation of such effects.
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Quantitative analysis of dendritic structure is widely used in assessing neural relationships in Golgi-stained tissue. Quantitative techniques are tedious and time-consuming. A computer-microscope system is described which speeds data acquisition and analysis. Three neuronal samples are analyzed both by this computerized system and by camera lucida techniques. We demonstrate that the computerized techniques result in far fewer errors in data transcription and analysis than the camera lucida procedure. In addition, we show that the amount of distortion in camera lucida drawings caused by collapsing 3 dimensions into 2 varies both with cell class and cell dendrite type. This prevents the use of any simple statistical procedures for deriving 3-dimensional information from 2-dimensional data.
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BACKGROUND: The influence of tumor suppressor gene p53 on the apoptosis of bladder cancer cells is not completely understood. In this study, the requirement for p53 in the cisplatin-induced apoptosis of human bladder cancer cells TSGH-8301 was investigated. MATERIALS AND METHODS: TSGH-8301 cells, which contain endogenous wild type p53 genes, were transfected with expression vectors containing p53 cDNA mutated at codon 173. Stable mutant p53 transfectant clones were confirmed by Southern blotting and Western blotting. The cellular response to cisplatin was determined on the basis of (a) cells viability, (b) apoptotic DNA fragmentation, and (c) nuclear condensation. RESULTS: Cells containing an exogenous mutant p53 sequence had increased sensitivity to cisplatin by undergoing apoptosis compared with parental TSGH8301 cells. In contrast, no difference was observed in those clones with rearranged or undetectable exogenous mutant p53 cDNA. However, analysis of p53 mRNA with RT-PCR sequencing indicated that none of the transfectant clones expressed exogenous mutant p53 mRNA. CONCLUSION: The transfectants had lost the expression of mutant p53 during selection; however, they could still enhance the expression of wild-type p53, which conferred sensitivity to cisplatin. IMPLICATION: Transient expression of mutant p53 protein in TSGH8301 cells may induce an irreversibly stabilization of p53 and increase the steady state of p53 expression.
To study the relationship between the p53 status and chemotherapeutic drug-induced apoptosis, we have assessed the extent of apoptosis in nine bladder cancer cell lines during the treatment of adriamycin, cisplatin and methotrexate. Apoptosis was measured by the DNA fragmentation and merocyanine 540 (MC540) staining methods. Among the nine human bladder cancer cell lines, both wt-p53- and mut-p53-expressing cell lines (p53+/-) underwent apoptosis in response to anticancer drugs treatment. While the J82 (p53-/-) and TCCSUP (p53+/+) cell lines showed little or no apoptosis to these agents. Similar results were obtained when subjected to low doses of anticancer drug treatment. Interestingly, our results suggested that bladder cancer cells heterozygous for mutant p53 (+/-) seem to be most susceptible to chemotherapeutic drug. We therefore postulate that p53 mutations do not always provide a selective advantage in the development of chemoresistance, at least in bladderer tumor cell lines.