Biomedical subjects
Publications and source records attributed to J S Sun.
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Not only the surface morphology but also the surface chemistry can be changed during the fabrication of biomaterials. Therefore, the result of a biocompatibility test of one material may alter to a great extent, dependent on the fabrication process. In this paper, the in vitro interaction of myoblasts and EVAL membranes with different surface properties was investigated. It was observed that moderate contact angle and porous structure are favourable for the cell adhesion and growth. However, cell adhesion and growth were decreased on a porous structure with particulate morphology and higher contact angle.
The purpose of this study was to obtain quantitative measures of the influence of callosal input to cells at the area 17/18 border region where transcallosal axons terminate most densely. Single-cell recordings were performed at the area 17/18 border region of the right hemisphere, while gamma-aminobutyric acid (GABA) or its antagonist, bicuculline, were applied to the transcallosal projecting regions of the left hemisphere to either block or overactivate the cells which projected to the neurons at the recording site. The results showed that visually evoked responses of the cells at the area 17/18 border were affected by administration of GABA or bicuculline to the contralateral hemisphere. Blockade of transcallosal input by application of GABA in the left hemisphere diminished the visually evoked responses of 51% of the neurons in the right hemisphere, and led to an increase in response magnitude for 17% of the neurons. Disinhibition of transcallosal input by application of bicuculline increased the evoked activity of 40% of the neurons and diminished the response magnitude of 20% of the neurons in the right hemisphere. GABA and bicuculline failed to show antagonistic effects on some cells. Thirty-two percent of the cells were affected by only one type of drug administration, and 13% of the cells showed either an increase or a decrease in responses after both GABA and then bicuculline administration. This study demonstrated complex interactions between neurons connected by the transcallosal pathway. A model of the transcallosal circuitry was proposed to explain the results.
Tritiated proline and leucine were injected into areas 17 and 18 of intact cats and into the medial bank of the lateral suprasylvian (LS) cortex of intact cats and cats from which areas 17 and 18 had been removed on postnatal day 1 (P1), P28, or in adulthood (A). The density of label transported to the superior colliculus was quantified using image-analysis equipment. The results from the intact cats confirmed previous reports that areas 17 and 18 project most heavily to stratum zonale (SZ) and stratum griseum superficiale (SGS) and LS cortex projects most heavily to stratum opticum (SO) of the superior colliculus. However, in cats with lesions of areas 17 and 18, the projections from LS cortex showed an age-dependent reorganization. LS projections to SGS and SZ were enhanced following ablation of areas 17 and 18 on P1, and projections to SGS were enhanced following an ablation on P28. The pattern of LS-collicular projection following ablations incurred in adulthood was indistinguishable from the pattern presented by intact cats. This study demonstrates that the LS corticocollicular projection expands in SGS and possibly substitutes for inputs eliminated by the removal of areas 17 and 18 from the immature brain. This enhanced pathway may contribute to compensatory neuronal changes and to spared behaviors that accompany damage of immature cortex.
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Topoisomerase I is an ubiquitous DNA-cleaving enzyme and an important therapeutic target in cancer chemotherapy for camptothecins as well as for indolocarbazole antibiotics such as rebeccamycin. To achieve a sequence-specific cleavage of DNA by topoisomerase I, a triple helix-forming oligonucleotide was covalently linked to indolocarbazole-type topoisomerase I poisons. The three indolocarbazole-oligonucleotide conjugates investigated were able to direct topoisomerase I cleavage at a specific site based upon sequence recognition by triplex formation. The efficacy of topoisomerase I-mediated DNA cleavage depends markedly on the intrinsic potency of the drug. We show that DNA cleavage depends also upon the length of the linker arm between the triplex-forming oligonucleotide and the drug. Based on a known structure of the DNA-topoisomerase I complex, a molecular model of the oligonucleotide conjugates bound to the DNA-topoisomerase I complex was elaborated to facilitate the design of a potent topoisomerase I inhibitor-oligonucleotide conjugate with an optimized linker between the two moieties. The resulting oligonucleotide-indolocarbazole conjugate at 10 nM induced cleavage at the triple helix site 2-fold more efficiently than 5 microM of free indolocarbazole, while the other drug-sensitive sites were not cleaved. The rational design of drug-oligonucleotide conjugates carrying a DNA topoisomerase poison may be exploited to improve the efficacy and selectivity of chemotherapeutic cancer treatments by targeting specific genes and reducing drug toxicity.
A new concept is presented to design and synthesize modified oligonucleotides in order to extend the range of double-helical DNA sequences that can be recognized by oligonucleotides via triple helix formation. The DNA target is composed of adjacent oligopurine.oligopyrimidine domains where the oligopurine sequences alternate on the two DNA strands. Canonical (C,T)-motif triple helices are formed with each oligopurine.oligopyrimidine domain of the target sequence. The two third-strand oligonucleotides were joined together via an appropriate linker between the two terminal bases with either a 3'-3' or a 5'-5' polarity. Molecular modeling was used to predict the optimal length of the linker bridging two terminal bases. The interaction of DNA with such a modified oligonucleotide containing a C3'-3'U linkage was studied by thermal dissociation, footprinting, and gel retardation experiments. They provide experimental evidence that the oligonucleotide does form a switched triple helix on this extended DNA target sequence. The binding of the so-called "switch oligonucleotide" is enhanced as compared to the two unlinked parental oligonucleotides which form triple helices with each oligopurine.oligopyrimidine domain of the target sequence.