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Biomedical subjects

S Y Lin

Publications and source records attributed to S Y Lin.

At least 19 recordsLinked to original sources
PubMed2000

Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression.

Beta-catenin can function as an oncogene when it is translocated to the nucleus, binds to T cell factor or lymphoid enhancer factor family members, and transactivates its target genes. In this study, we demonstrate that cyclin D1 is one of the targets of beta-catenin in breast cancer cells. Transactivation of beta-catenin correlated significantly with cyclin D1 expression both in eight breast cell lines in vitro and in 123 patient samples. More importantly, we found that high beta-catenin activity significantly correlated with poor prognosis of the patients and was a strong and independent prognostic factor in breast cancer. Our studies, therefore, indicated that beta-catenin can be involved in breast cancer formation and/or progression and may serve as a target for breast cancer therapy.

Adult↗
PubMed2000

HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway.

Overexpression of HER-2/neu correlates with poor survival of breast and ovarian cancer patients and induces resistance to tumor necrosis factor (TNF), which causes cancer cells to escape from host immune defenses. The mechanism of HER-2/neu-induced TNF resistance is unknown. Here we report that HER-2/neu activates Akt and NF-kappaB without extracellular stimulation. Blocking of the Akt pathway by a dominant-negative Akt sensitizes the HER-2/neu-overexpressing cells to TNF-induced apoptosis and inhibits IkappaB kinases, IkappaB phosphorylation, and NF-kappaB activation. Our results suggested that HER-2/neu constitutively activates the Akt/NF-kappaB anti-apoptotic cascade to confer resistance to TNF on cancer cells and reduce host defenses against neoplasia.

3T3 Cells↗
PubMed2000

Tumor suppression and sensitization to tumor necrosis factor alpha-induced apoptosis by an interferon-inducible protein, p202, in breast cancer cells.

p202, an IFN-inducible protein, interacts with several important regulatory proteins, leading to growth arrest or differentiation. In this report, we demonstrate that, in addition to inhibiting in vitro cell growth, p202 can also suppress the tumorigenicity of breast cancer cells in vivo. Furthermore, we found that p202 expression could sensitize breast cancer cells to apoptosis induced by tumor necrosis factor alpha treatment. One possible mechanism contributing to this sensitization is the inactivation of nuclear factor-kappaB by its interaction with p202. These results provide a scientific basis for a novel therapeutic strategy that combines p202 and tumor necrosis factor alpha treatment against breast cancer.

Apoptosis↗
PubMed2000

The surgical treatment for degenerative disease of the ankle.

Although a variety of surgical techniques are available for the surgical treatment of early degenerative disease of the ankle, arthrodesis remains the preferred treatment for severe cases. We studied 126 ankles with an average follow up of 39 months of whom 25 with early disease underwent debridement and cheilectomy, 18 with intermediate disease underwent lower tibial osteotomy and 83 with severe disease underwent either arthrodesis (78) or total ankle replacement (5). In 96% of cases there was a satisfactory functional outcome.

Adult↗
PubMed2000

Postero-medio-anterior approach of the ankle for the pilon fracture.

A good view of the operative field is important for better reduction and fixation in surgical treatment of fractures. The exposure of the ankle joint for the pilon fracture is commonly through the anterior approach, or combined with the medical approach. But sometimes it is still difficult to have complete viewing of the articular surface and to apply internal fixation by that approach. In recent years, we developed a "postero-medio-anterior" approach of the ankle joint by one incision. This approach provides an excellent exposure of the anterior, medial and posterior aspects of the ankle joint with a clear view of the articular surface. In our 45 cases of pilon fracture during 1991 to 1995, there was no incisional injury to the neurovascular bundle. Superficial wound edge necrosis was noted in two cases which healed later without further procedure. Therefore, we recommend this approach as a simple and reliable incision for open reduction of pilon fractures.

Adult↗
PubMed2000

Isothermal Fourier transform infrared microspectrosopic studies on the stability kinetics of solid-state intramolecular cyclization of aspartame sweetener.

A novel Fourier transform infrared (FT-IR) microspectrophotometer equipped with differential scanning calorimetry (DSC) was used to investigate the kinetics of intramolecular cyclization of aspartame (APM) sweetener in the solid state under isothermal conditions. The thermal-dependent changes in the peak intensity of IR spectra at 1543, 1283, and 1259 cm(-1) were examined to explore the reaction. The results support that the intramolecular cyclization process in APM proceeded in three steps: the methoxyl group of ester was first thermolyzed to release methanol, then an acyl cation was attacked by the lone pair of electrons available on nitrogen by an S(N)1 pathway, and finally ring-closure occurred. The intramolecular cyclization of APM determined by this microscopic FT-IR/DSC system was found to follow zero-order kinetics after a brief induction period. The bond cleavage energy (259.38 kJ/mol) of thermolysis for the leaving group of -OCH(3), the bond conversion energy (328.88 kJ/mol) for the amide II NH band to DKP NH band, and the CN bond formation energy (326.93 kJ/mol) of cyclization for the DKP in the APM molecule were also calculated from the Arrhenius equation. The total activation energy of the DKP formation via intramolecular cyclization was 261.33 kJ/mol, calculated by the above summation of the bond energy of cleavage, conversion, and formation, which was near to the value determined by the DSC or TGA method. This indicates that the microscopic FT-IR/DSC system is useful as a potential tool not only to investigate the degradation mechanism of drugs in the solid state but also to directly predict the bond energy of the reaction.

Aspartame↗
PubMed2000

Core decompression for osteonecrosis of the femoral head at pre-collapse stage.

Twenty-five patients (27 hips) were retrospectively studied for core decompression in the treatment of osteonecrosis of the femoral heads at pre-collapse stage, Ficat and Alert stages I and II, from Apr. 1984 to Jun. 1998 with follow-up period at least 1 yr (mean 28 months). Eleven hips (10 patients) were considered to have failed due to progressive collapsed more than 2 mm, severe pain or reoperation. We further analyzed the results with regard to the stages, the size of the necrotic area according to the Ohzono classification, the lateral head index (LHI) and the Kerboul combined necrotic angle. The survival rate according to the Ohzono classification was type 1B: 100%, 1C: 44%, 2: 25%, and 3B: 0%. Hips with Kerboul angle less than 250 degrees revealed satisfactory results in all except one hip. All hips with Kerboul angle more than 250 degrees collapsed. Fourteen of the 15 hips (93%) with lateral head index more than 20% did not collapse and all hips except one (7/8) with LHI less than 12% collapsed. We conclude core decompression yields satisfactory results in osteonecrotic femoral heads at pre-collapse stage and with small necrotic area or good lateral buttress.

Adult↗
PubMed1999

E1A sensitizes cells to tumor necrosis factor-induced apoptosis through inhibition of IkappaB kinases and nuclear factor kappaB activities.

The adenovirus E1A protein has been implicated in increasing cellular susceptibility to apoptosis induced by tumor necrosis factor (TNF); however, its mechanism of action is still unknown. Since activation of nuclear factor kappaB (NF-kappaB) has been shown to play an anti-apoptotic role in TNF-induced apoptosis, we examined apoptotic susceptibility and NF-kappaB activation induced by TNF in the E1A transfectants and their parental cells. Here, we reported that E1A inhibited activation of NF-kappaB and rendered cells more sensitive to TNF-induced apoptosis. We further showed that this inhibition was through suppression of IkappaB kinase (IKK) activity and IkappaB phosphorylation. Moreover, deletion of the p300 and Rb binding domains of E1A abolished its function in blocking IKK activity and IkappaB phosphorylation, suggesting that these domains are essential for the E1A function in down-regulating IKK activity and NF-kappaB signaling. However, the role of E1A in inhibiting IKK activity might be indirect. Nevertheless, our results suggest that inhibition of IKK activity by E1A is an important mechanism for the E1A-mediated sensitization of TNF-induced apoptosis.

Adenovirus E1A Proteins↗
PubMed1999

Brain-derived neurotrophic factor enhances association of protein tyrosine phosphatase PTP1D with the NMDA receptor subunit NR2B in the cortical postsynaptic density.

Our recent studies revealed that brain-derived neurotrophic factor (BDNF) rapidly enhances tyrosine phosphorylation and dephosphorylation of the NMDA receptor subunit, NR2B, in the postsynaptic density (PSD), potentially regulating synaptic plasticity. To explore the molecular mechanisms underlying synaptic NR2B signaling, we examined the protein tyrosine phosphatase, PTP1D; BDNF reportedly increases association of PTP1D with tyrosine phosphorylated proteins in cortical neurons and PC 12 cells. We now report that PTP1D is an intrinsic component of the rat cerebrocortical PSD, based on Western blot analysis using specific anti-PTP1D antibodies. In addition, NR2B was co-immunoprecipitated with PTP1D using anti-NR2B antibodies or anti-PTP1D antibodies, indicating physical association of the subunit with PTP1D. Moreover, treatment of the purified PSD with BDNF for 5 min elicited a two-fold increase in the association of NR2B with PTP1D. The BDNF action appeared to be specific, since nerve growth factor, another member of the neurotrophin gene family, did not alter the association. Finally, an overlay assay revealed that BDNF caused a two-fold increase in binding of blotted PSD NR2B proteins to PTP1D-SH2 domains, revealing molecular mechanisms mediating the PTP1D-NR2B binding. Taken together, our results raise the possibility that PTP1D participates in BDNF-mediated NR2B signaling cascades at the postsynaptic site, thereby regulating synaptic plasticity.

Animals↗
PubMed1999

Structural determinants for recognition and translocation by the anandamide transporter.

The biological actions of anandamide (arachidonylethanolamide), an endogenous cannabinoid lipid, are terminated by a two-step inactivation process consisting of carrier-mediated uptake and intracellular hydrolysis. Anandamide uptake in neurons and astrocytes is mediated by a high-affinity, Na+-independent transporter that is selectively inhibited by N-(4-hydroxyphenyl)-arachidonamide (AM404). In the present study, we examined the structural determinants governing recognition and translocation of substrates by the anandamide transporter constitutively expressed in a human astrocytoma cell line. Competition experiments with a select group of analogs suggest that substrate recognition by the transporter is favored by a polar nonionizable head group of defined stereochemical configuration containing a hydroxyl moiety at its distal end. The secondary carboxamide group interacts favorably with the transporter, but may be replaced with either a tertiary amide or an ester, suggesting that it may serve as hydrogen acceptor. Thus, 2-arachidonylglycerol, a putative endogenous cannabinoid ester, also may serve as a substrate for the transporter. Substrate recognition requires the presence of at least one cis double bond situated at the middle of the fatty acid carbon chain, indicating a preference for ligands whose hydrophobic tail can adopt a bent U-shaped conformation. On the other hand, uptake experiments with radioactively labeled substrates show that no fewer than four cis nonconjugated double bonds are required for optimal translocation across the cell membrane, suggesting that substrates are transported in a folded hairpin conformation. These results outline the general structural requisites for anandamide transport and may assist in the development of selective inhibitors with potential clinical applications.

Arachidonic Acids↗
PubMed1999

Growth/cell cycle regulation of Sp1 phosphorylation.

Sp1 sites can mediate growth/cell cycle induction of dihydrofolate reductase in late G1 (Jensen, D. E., Black, A. R. Swick, A. G., and Azizkhan, J. C. (1997) J. Cell. Biochem. 67, 24-31). To investigate mechanisms underlying this induction, effects of serum stimulation on regulation of Sp1 were examined. In Balb/c 3T3 cells, serum stimulation did not affect Sp1 synthesis or the relative binding of Sp1 family members to DNA; however, it did result in a rapid, approximately 2-fold increase in Sp1 levels and an approximately 3-fold increase in specific Sp1 phosphorylation in mid-G1. In normal human diploid fibroblasts, serum stimulation also increased Sp1 phosphorylation in mid-G1 but did not affect Sp1 levels. Therefore, Sp1 phosphorylation is regulated in a growth/cell cycle-dependent manner which correlates temporally with induction of dihydrofolate reductase transcription. Further studies revealed a kinase activity specifically associated with Sp1 in a growth-regulated manner. This activity is distinct from purified kinases previously shown to phosphorylate Sp1 in vitro and phosphorylates Sp1 between amino acids 612 and 678 in its C terminus, a region also phosphorylated in mid-G1 in vivo. Therefore, this study indicates that phosphorylation of the C terminus of Sp1 may play a role in the cell cycle regulation of its transcriptional activity.

3T3 Cells↗
PubMed1999

pH-dependent secondary conformation of bovine lens alpha-crystallin: ATR infrared spectroscopic study with second-derivative analysis.

BACKGROUND: In order to simulate the usage of different formulations of ophthalmic solution, the protein conformational changes of lens alpha-crystallin in buffer solutions of different pH were investigated. METHODS: The secondary structure of bovine lens alpha-crystallin in different Mcllvaine buffer solutions (pH 2.2, 4.0, 6.0, 7.2 and 8.0) was determined by attenuated total reflection (ATR)/Fourier transform infrared (FT-IR) spectrometry with second-derivative technique. The turbidity of alpha-crystallin in different buffer solutions was observed. RESULTS AND CONCLUSION: The results indicate that alpha-crystallin exists mainly in beta-sheet structure at 1627-1637 cm-1. The conformational components of alpha-crystallin may be closely similar in pH 7.2 buffer solution and in pH 8.0 buffer solution. Once alpha-crystallin dissolved in pH 6.0 and 4.0 buffer solution, the appearance of a component at 1618 or 1620 cm-1, associated with the presence of intermolecular beta-sheet structure or beta-turn structure or amino acid side chains, implied the denaturation of alpha-crystallin, which was even more marked in pH 4.0 buffer solution. Due to the effect of dissociation and stability of alpha-crystallin in pH 2.2 buffer solution, the secondary structure of the intact alpha-crystallin was difficult to evaluate. This study demonstrates that different pH can vary secondary conformational structure of alpha-crystallin, particularly if the pH is below 6.0. This suggests that the secondary structure of alpha-crystallin in buffer solution exhibits pH-dependent characteristics.

Acids↗
PubMed1999

Cannabinoid receptor and WIN-55,212-2-stimulated [35S]GTPgammaS binding and cannabinoid receptor mRNA levels in several brain structures of adult male rats chronically exposed to R-methanandamide.

We and others have recently demonstrated that the pharmacological tolerance observed after prolonged exposure to plant and synthetic cannabinoids in adult individuals seems to have a pharmacodynamic basis, based on the observed down-regulation of cannabinoid receptors in the brain of cannabinoid-tolerant rats. However, we were unable to elicit a similar receptor down-regulation after a chronic exposure to anandamide, the first discovered endogenous cannabinoid, possibly because of its rapid metabolic breakdown in arachidonic acid and ethanolamine. The present study was designed to progress in these previous studies, by using R-methanandamide, a more stable analog, instead anandamide. In addition, we examined not only cannabinoid receptor binding, but also WIN-55,212-2-stimulated [35S]-GTPgammaS binding, by autoradiography, and cannabinoid receptor mRNA levels, by in situ hybridization. Results were as follows. The daily administration of R-methanandamide for a period of five days produced decreases in cannabinoid receptor binding in the lateral caudate-putamen, cerebellum, entopeduncular nucleus and substantia nigra. The remaining areas, the medial caudate-putamen, globus pallidus, cerebral cortex (layers I and VI), hippocampus (dentate gyrus and Ammon's horn) and several limbic structures (nucleus accumbens, septum nuclei and basolateral amygdaloid nucleus), exhibited no changes in cannabinoid receptor binding. Similarly, the levels of cannabinoid receptor mRNA expression decreased in the lateral and medial caudate-putamen and in the CA1 and CA2 subfields of the Ammon's horn in the hippocampus after the chronic exposure to R-methanandamide, whereas the remaining areas showed no changes. WIN-55,212-2-stimulated [35S]-GTPgammaS binding did not change in the lateral caudate-putamen, cerebral cortex (layer I), septum nuclei and hippocampal structures (dentate gyrus and Ammon's horn) of animals chronically exposed to R-methanandamide, whereas a certain trend to decrease could be observed in the substantia nigra and deep layer (VI) of the cerebral cortex in these animals. In summary, as reported for other cannabinoid receptor agonists, the prolonged exposure of rats to R-methanandamide, a more stable analog of anandamide, was able to produce cannabinoid receptor-related changes in contrast with the absence of changes observed early with the metabolically labile anandamide. The observed changes exhibited an evident regional pattern with areas, such as basal ganglia, cerebellum and hippocampus, responding to chronic R-methanandamide treatment while regions, such as the cerebral cortex and limbic nuclei, not responding.

Animals↗
PubMed1999

Analysis of aberrant transcription of TSG101 in hepatocellular carcinomas.

A variety of studies suggest that tumour suppressor loci on chromosome 11p are important in various forms of human neoplasia. Recently, a gene located at the chromosome 11p 15.1-15.2 region called TSG101 was discovered and proposed as a candidate tumour suppressor gene in breast cancers. We evaluated the TSG101 gene in a panel of liver cancer cell lines and paired tumours and non-malignant tissues. In this study, four of the seven (57%) cell lines, eight of the 18 (44%) tumours and four of the 18 (22%) non-malignant liver tissues exhibited aberrant TSG101 transcripts by nested reverse transcription-polymerase chain reaction (RT-PCR) analysis. However, a normal-sized transcript without sequence abnormalities verified by single-stranded conformation polymorphism (SSCP) analysis was expressed at robust levels in all the cell lines and most of the tissue samples tested. In addition, Southern blot analysis could identify no genomic abnormalities of the gene. Our results suggest either that the TSG101 gene may not be involved in hepatocarcinogenesis or that it plays a role in the development and/or progress of hepatocellular carcinomas through an unusual mechanism.

Adult↗
PubMed1999

UV-B-induced secondary conformational changes in lens alpha-crystallin.

The changes in turbidity and protein secondary structure of alpha-crystallin after a 72 h UV-B (302 nm) irradiation in aqueous solution have been determined by UV spectrophotometry and Fourier transform infrared (FT-IR) microspectroscopy with reflection mode. The relative transmission of alpha-crystallin aqueous solution gradually decreases with the exposure time, indicating that the transparent alpha-crystallin aqueous solution becomes opaque with prolonged UV-B irradiation. The turbidity induced by UV-B shows first-order kinetics due to the photo-induced aggregation. The modification of the secondary structure of the alpha-crystallin molecule in aqueous solution caused by this aggregation might enhance the alpha-helix and beta-turn structures from 8.14 to 14.92% and from 24.46 to 35.54%, respectively; reduce the beta-sheet structure from 60.20% to 43.77%; and leave the random coil structure almost unaltered. The secondary conformation of alpha-crystallin changes gradually but evidently with its increase of turbidity during UV-B exposure.

Animals↗
PubMed1999

Double cartilage block ossiculoplasty in chronic ear surgery.

OBJECTIVES/HYPOTHESIS: Multiple techniques of ossicular reconstruction have been advocated for hearing rehabilitation in the setting of chronic otitis media No single method can adequately address the clinical spectrum of disease severity. In the situation of a severely diseased ear requiring a canal wall down (CWD) mastoidectomy in the presence of an intact stapes superstructure, the authors have employed a double cartilage block (DCB) ossiculoplasty. The technique and short-term results are reviewed. STUDY DESIGN: Retrospective chart review in a tertiary referral otologic practice. METHODS: Twenty-three patients underwent a CWD tympanomastoidectomy with DCB ossiculoplasty. Ages ranged from 6 to 85 years (mean, 36.1 y). The majority of ears were actively draining at the time of surgery (83%) and most procedures were revisions of prior mastoidectomies (74%). Audiometric data (mean postoperative follow-up, 19.5 mo) were calculated according to 1995 American Academy of Otolaryngology-Head and Neck Surgery guidelines. RESULTS: Audiometric results were available in 20 patients. The mean air-bone gap (ABG) was 23.8 dB after surgery. Closure of the ABG to within 20 dB was achieved in 10 of 20 patients (50%). No cases of DCB extrusion have occurred to date. CONCLUSIONS: The DCB represents an excellent alternative to biocompatible prostheses for ossicular reconstruction in the setting of severe chronic ear disease. As with all methods of ossiculoplasty, long-term follow-up will be necessary to determine if this technique remains stable in the hostile environment in which it has been employed.

Adolescent↗