Biomedical subjects

Y Lin

Publications and source records attributed to Y Lin.

At least 19 recordsLinked to original sources

PubMed2007

c-Jun N-terminal kinase mediates hydrogen peroxide-induced cell death via sustained poly(ADP-ribose) polymerase-1 activation.

Reactive oxygen species (ROS) have been closely associated with both apoptotic and non-apoptotic/necrotic cell death. Our previous study has illustrated that c-Jun-N-terminal kinase 1 (JNK1) is the main executor in hydrogen peroxide (H(2)O(2))-induced nonapoptotic cell death. The main objective of this study is to further elucidate the molecular mechanisms downstream of JNK1 in H(2)O(2)-induced cell death. In this study, poly(ADP-ribose) polymerase-1 (PARP-1), a key DNA repair protein, was readily activated by H(2)O(2) and inhibition of PARP-1 activation by either a pharmacological or genetic approach offered significant protection against H(2)O(2)-induced cell death. More importantly, H(2)O(2)-mediated PARP-1 activation is subject to regulation by JNK1. Suppression of JNK1 activation by a chemical inhibitor or genetic deletion markedly suppressed the late-phase PARP-1 activation induced by H(2)O(2), suggesting that JNK1 contributes to the sustained activation of PARP-1. Such findings were supported by the temporal pattern of nuclear translocation of activated JNK and a direct protein-protein interaction between JNK1 and PARP-1 in H(2)O(2)-treated cells. Finally, in vitro kinase assay suggests that PARP-1 may serve as the direct phosphorylation target for JNK1. Taken together, data from our study reveal a novel underlying mechanism in H(2)O(2)-induced nonapoptotic cell death: JNK1 promotes a sustained PARP-1 activation via nuclear translocation, protein-protein interaction and PARP-1 phosphorylation.

Adenosine Triphosphate↗

PubMed2006

Odontogenic tumours: a retrospective study of 1642 cases in a Chinese population.

A total of 1642 odontogenic tumour cases retrieved from the files of the College of Stomatology, Sichuan University, China were retrospectively analyzed for gender, age, tumour site and relative frequency of various types, and the data compared with that of previous reports. The final diagnosis in each case was based on the WHO 2005 histopathological classification of odontogenic tumours. Of these tumours 1592 (97.0%) were benign and 50 (3.0%) were malignant. Ameloblastoma (40.3%) was the most frequent type, followed by keratocystic odontogenic tumour (35.8%), odontoma (4.7%) and odontogenic myxoma (4.6%). The mean age of the patients was 32.1, with a wide range (3-84 years). The male-female ratio and maxilla-mandible ratio were 1.4:1 and 1:4.0, respectively. Ameloblastoma and keratocystic odontogenic tumours, important indications of extensive surgical procedures, are not considered rare in this Chinese population, whereas odontoma is uncommon.

Adolescent↗

PubMed2006

Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase.

Target of Rapamycin (TOR), a giant protein kinase expressed by all eucaryotic cells, controls cell size in response to nutrient signals. In metazoans, cell and organismal growth is controlled by nutrients and the insulin/insulin-like growth factor (IGF) system, and the understanding of how these inputs coordinately regulate TOR signaling has advanced greatly in the past 5 years. In single-cell eucaryotes and Caenorhabditis elegans, TOR is a dominant regulator of overall mRNA translation, whereas in higher metazoans, TOR controls the expression of a smaller fraction of mRNAs that is especially important to cell growth. TOR signals through two physically distinct multiprotein complexes, and the control of cell growth is mediated primarily by TOR complex 1 (TORC1), which contains the polypeptides raptor and LST8. Raptor is the substrate binding element of TORC1, and the ability of raptor to properly present substrates, such as the translational regulators 4E-BP and p70 S6 kinase, to the TOR catalytic domain is essential for their TOR-catalysed phosphorylation, and is inhibited by the Rapamycin/FKBP-12 complex. The dominant proximal regulator of TORC1 signaling and kinase activity is the ras-like small GTPase Rheb. Rheb binds directly to the mTOR catalytic domain, and Rheb-GTP enables TORC1 to attain an active configuration. Insulin/IGF enhances Rheb GTP charging through the ability of activated Akt to inhibit the Rheb-GTPase-activating function of the tuberous sclerosis heterodimer (TSC1/TSC2). Conversely, energy depletion reduces Rheb-GTP charging through the ability of the adenosine monophosphate-activated protein kinase to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function, as well as by HIFalpha-mediated transcriptional responses that act upstream of the TSC1/2 complex. Amino-acid depletion inhibits TORC1 acting predominantly downstream of the TSC complex, by interfering with the ability of Rheb to bind to mTOR. The components of the insulin/IGF pathway to TORC1 are now well established, whereas the elements mediating the more ancient and functionally dominant input of amino acids remain largely unknown.

Animals↗

PubMed2006

Effects of electro-acupuncture on the expression of c-jun and c-fos in spared dorsal root ganglion and associated spinal laminae following removal of adjacent dorsal root ganglia in cats.

This study evaluated the plastic changes of c-jun and c-fos in the right sixth lumbar dorsal root ganglion (L6 DRG), Rexed's lamina II in representative spinal segments L3, L5, and L6 and in the nucleus dorsalis (ND) at L3 segments after electro-acupuncture (EA) in cats subjected to removal of L1-L5 and L7-S2 DRG. Following dorsal root ganglionectomy, there was a significant increase in the density of c-jun immunoreactivity in the neurons and glia in spinal lamina II and in the ND; there was also marked elevation in the expression of c-fos in ND. In both cases there was no change in the c-jun and c-fos immunoreactivity in the DRG. After EA in the operated animals, there was an up-regulation in the expression of c-jun in the L6 DRG and the associated spinal lamina II; however, increased c-fos expression was detected only in the L6 DRG. Western blot and RT-PCR were also performed to quantitatively explore the mRNA and protein expression changes in the spinal dorsal horn and associated DRG. Following partial deafferentation, there was a significant increase in the protein level of both c-jun and c-fos in the dorsal horn, while, in both cases there was no change in c-jun and c-fos protein and mRNA in the DRG. After EA in the operated animals, both c-jun protein and its mRNA in the L6 DRG as well as the associated dorsal horn of L6 spinal segment were upregulated, but increased c-fos protein and its mRNA was observed only in the L6 DRG. These findings suggested that c-jun and c-fos might be related to the acupuncture promoted spinal cord plasticity as reported previously.

Animals↗

PubMed2006

Disposition of lead (Pb) in saliva and blood of Sprague-Dawley rats following a single or repeated oral exposure to Pb-acetate.

Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100mg Pb-acetate/kg body weight in rats or approximately 1-week after 5 sequential daily oral gavage doses of 1, 10, or 100mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and alpha-amylase activity were also determined. At specified times post-dosing groups of animals were anesthetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to Pb-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r(2)=0.922) between the average Pb concentrations in these biological matrices, which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24h post-dosing and a decrease in alpha-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These results demonstrate a feasibility to rapidly detect Pb in saliva and suggest that saliva may correlate best with plasma Pb concentration.

Animals↗

PubMed2006

Pilot study using SELDI-TOF-MS based proteomic profile for the identification of diagnostic biomarkers of thyroid proliferative diseases.

Biomarkers for thyroid cancer (TCa) lack specificity. To develop TCa specific biomarkers, SELDI-TOF-MS was used to examine the proteomic profile of biopsies obtained from papillary TCa along with adjacent normal tissue. Sixty-three potential biomarkers were categorized by univariate analysis into single biomarker candidates and segregated by multivariate analysis into normal and cancerous groups. Our studies demonstrate the sensitivity and reproducibility of this approach to detect biomarkers for TCa.

Biomarkers, Tumor↗

PubMed2006

Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF.

Our previous study showed that DNA vaccination with a plasmid vector encoding a core peptide of mucin1 (PDTRP) provided modest protection against challenge with tumor cells that expressed mucin1 protein. We report here that a DNA vaccine comprising a modified PDTRP plasmid and GM-CSF coding sequence at the C-terminus induced better protection against tumor challenge. The increased protection was directly correlated with a stronger PDTRP-specific immune response induced by the GM-CSF fusion plasmid. The plasmid encoding GM-CSF and the target PDTRP antigen induced a greater PDTRP-specific Th proliferation, antibodies, and cytotoxicity. Interestingly, the modified plasmid vaccine predominantly enhanced the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and IFN-gamma mRNA in spleen cells from vaccinated mice. In addition, protection against tumor challenge in vaccinated mice showed that there was no significant change in mice survival after in vivo CD8+CTL depletion, indicating that antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene vaccine was dominated by Th2 immune response.

Animals↗

PubMed2006

Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in human malignant melanoma and their relation to angiogenesis.

BACKGROUND: Angiogenesis is the major and key factor for growth and invasion of tumours, including malignant melanoma (MM), but the factors that contribute to tumour angiogenesis are still unclear. OBJECTIVE: To study expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in human MM and their relation to angiogenesis. To investigate the correlation between eNOS and VEGF and the role of nitric oxide (NO) generated by eNOS in the process of mediating angiogenesis by VEGF. METHODS: Tissue sections from 31 patients with MM were examined using immunohistochemistry and morphological quantitative analysis for protein expression of eNOS and VEGF. Microvessel density (MVD) was counted in endothelial cells in immunostained by anti-FVIII:RAg antibody. RESULTS: Positive eNOS and VEGF immunostaining were observed in 77.4% and 83.9% of MM lesions, respectively, whereas pigmented naevi never expressed eNOS and VEGF. A positive correlation between eNOS and VEGF in MM was observed. Expression of eNOS and VEGF was positively correlated with MVD expression in MM, and MVD expression in MM was stronger than in pigmented naevi. Expression of eNOS and VEGF was not correlated with lymph node metastasis. CONCLUSIONS. On the basis of the current data showing that malignant melanocytic tumours displayed strong VEGF and eNOS expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF and eNOS, such expression may be used as a discriminating factor to distinguish malignant melanoma from pigmented naevi. Expression of eNOS and VEGF may contribute to angiogenesis of MM, eNOS probably plays an important role in mediating VEGF-induced angiogenesis.

Adult↗

PubMed2006

Novel IRF6 mutations in Chinese patients with Van der Woude syndrome.

Van der Woude syndrome (VWS) (OMIM 119300) is a dominantly inherited, developmental disorder that is characterized by pits and/or sinuses of the lower lip and a cleft lip and/or cleft palate. Mutations in the interferon regulatory factor 6 gene (IRF6) have been recently identified in patients with VWS, with more than 60 mutations reported. However, the VWS phenotype, IRF6 mutation genotypes, and their interrelationships in Chinese VWS patients have not been studied. Here, we report 11 Chinese families with variable clinical phenotypes of VWS and identified mutations in all patients. Of the 11 mutations, 8 appeared to be novel: CC5.6GT, T342A, 566delA, C748T, C756A, C989A, C1209G, and 1316delT. Seven mutations caused a change or loss of the IRF6 domain. The marked phenotypic variation may be caused by the action of certain modifier genes on IRF6 function.

Adult↗

PubMed2006

Osteopontin regulation by protein kinase B (Akt) in HepG2 cells.

AIM: The mechanism responsible for osteopontin regulation is not understood in HepG2 cells. The aim of this study was to investigate the relationship between protein kinase B (Akt), a key gene in PI3K signal transduction pathway, and osteopontin expression. METHODS: HepG2 cells were transfected with constitutively active Akt and dominant negative Akt using lipofectin. The Akt transfection was confirmed by Western blot analysis. Osteopontin expression was detected by both Northern blot and Western blot. RESULTS: Overexpression of exogenous Akt was detected in HepG2 cells by Western blot, indicating that HepG2 cells were successfully transfected with the Akt genes. In serum-free condition, the expression of osteopontin was either low or undetectable in HepG2 cells transfected with vector only, however, the expression increased after transfection of cells with constitutively active Akt. Osteopontin expression decreased when HepG2 cells were transfected with dominant negative Akt. CONCLUSION: Protein kinase B (Akt) gene regulated osteopontin expression in RNA level and protein level, suggesting that osteopontin synthesis can be blocked by inactivation of the Akt gene. This leads to a potential means of intervention for the inhibition of metastases in liver cancer.

Base Sequence↗

PubMed2005

Integrated optics ring-resonator sensors for protein detection.

Using an integrated optics ring-resonator biosensor, we have demonstrated the detection of protein in low concentrations. We detected 0.3 nM of avidin in a buffered saline solution; the calculated detection limit is 0.1 nM (6.8 ng/ml) for avidin, which compares favorably with those of other optical protein detection techniques. Further improvement is possible. Our ring resonator utilizes Si(x)N(y)/SiO2 waveguides, which, owing to evanescent field interaction, change the effective refractive index when target molecules are immobilized on their surfaces. The selectivity of the sensor depends on the biotin surface coating, which causes the specific binding and immobilization of avidin.

Biosensing Techniques↗

PubMed2005

Tear function and goblet cell density after pterygium excision.

PURPOSE: To evaluate the short-term effect of pterygium excision on tear function and conjunctival goblet cell density. METHODS: In all, 70 patients (70 eyes) with primary pterygia who underwent a bare-sclera procedure were enrolled in this study. Tear break-up time, Schirmer, and tear-ferning tests and conjunctival goblet cell density obtained by impression cytology were evaluated before and 1 month after surgery. RESULTS: At 1 month postoperation, the tear break-up time (11.49+/-3.76 s) was significantly prolonged when compared with the preoperation tear break-up time (9.74+/-3.43 s, P=0.002). Before surgery, only 17% of the patients showed normal crystallization in the tear-ferning test. This proportion was significantly increased to 90% 1 month after surgery (P<0.001). There is no significant difference in the Schirmer test value between pre- and postsurgery (P>0.05). The mean goblet cell density in conjunctival impression specimens before surgery was 41.82+/-18.29/10 fields, which was increased significantly 1 month after surgery (P<0.001) with a mean cell density of 50.67+/-18.71/10 fields. CONCLUSION: Tear function in patients with primary pterygium improves after pterygium excision, which indicates that pterygium has a close relationship with dry eye.

Adult↗

PubMed2005

Skin rash and good performance status predict improved survival with gefitinib in patients with advanced non-small cell lung cancer.

BACKGROUND: Gefitinib (Iressa) is active as a single agent in the treatment of select patients with recurrent non-small cell lung cancer (NSCLC). The clinical characteristics of patients treated with gefitinib on an Expanded Access Program (EAP) at our institution identified predictive variables associated with better outcome. PATIENTS AND METHODS: Patients (n=199) with advanced NSCLC were treated with gefitinib (250 mg) upon progression with chemotherapy. Baseline patient characteristics were: median age, 69 years; males, 57%; adenocarcinoma, 56%. RESULTS: Partial responses were noted in two patients (1%) and disease stabilization in 66 (35%) patients. The median survival (MS) was 5.9 months [95% confidence interval (CI) 4.1-7.1] and median time to progression was 3 months (95% CI 2.0-3.0). The predictive factors analyzed were gender, skin rash, diarrhea, tumor histology and performance status (PS). Patients who developed skin rash (any grade) had MS of 10.8 months versus 4.0 months for those without rash (P <0.0001, log rank test). Patients with PS 0, 1 and 2 had MS of 8.4, 6.2 and 2.8 months, respectively (P <0.0002). The other factors did not impact survival. CONCLUSIONS: Occurrence of skin rash and baseline PS of 0/1 were associated with improved survival with gefitinib for recurrent NSCLC patients at our institution.

Adult↗

PubMed2005

Determination of gene organization in the human IGHV region on single chromosomes.

Organization of the IGHV genes (n=108) on single human chromosomes has been determined by detecting these sequences in single sperm using multiplex PCR amplification followed by microarray detection. A total of 374 single sperm samples from five Caucasian males were studied. Three deletion/insertion polymorphisms (Del I-Del III) with deletion allele frequencies ranging from 0.1 to 0.3 were identified. Del I is a previously reported polymorphism affecting three IGHV genes (IGHV1-8, IGHV3-9, and IGHV2-10). Del II affects a region 2-18 kb containing two pseudogenes IGHV(II)-28.1 and IGHV3-29, and Del III spans approximately 21-53 kb involving genes IGHV4-39, IGHV7-40, IGHV(II)-40-1, and IGHV3-41. Deletion alleles of both Dels II and III were found in a heterozygous state, and therefore, could not be easily detected if haploid samples were not used in the study. Results of the present study indicate that deletions/insertions together with other possible chromosomal rearrangements may play an important role in forming the genetic structure of the IGHV region, and may significantly contribute to antibody diversity. Since these three polymorphisms are located within or next to the 3' half of the IGHV region, they may have an important role in the expressed IGHV gene repertoire during immune response.

Chromosomes, Human, Pair 14↗

PubMed2005

The comparison of Ca2+/CaM-independent and Ca2+/CaM-dependent phosphorylation of myosin light chains by MLCK.

The main regulatory mechanism of smooth muscle contraction involves Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin (CDPM), by myosin light chain kinase (MLCK). It is also known that the increase in intracellular Ca2+ and phosphorylation of myosin occurs within a short time under physiological conditions, but the muscle tension may persist for a longer period of time. However, the mechanism of this phenomenon is still not clear. We hypothesize that MLCK also phosphorylates myosin in a Ca2+/CaM-independent manner (CIPM). The difference between CIPM and CDPM are as follows. Firstly, the extent of CIPM by MLCK was temperature-independent, whereas CDPM by MLCK was apparently decreasing with increasing temperature. Secondly, in contrast to the decreased extent of CDPM, the prolongation of incubation time did not decrease the extent of CIPM. Thirdly, a high concentration of K+ influences CIPM less than CDPM. Furthermore, the MLCK inhibitor ML-9 significantly inhibited CDPM by MLCK but not CIPM by MLCK. Lastly, arachidonic acid selectively increased CIPM by MLCK but not CDPM by MLCK. Finally, the activity of Mg2+-ATPase of myosin followed the sequence as this: CDPM>CIPM>unphosphorylated myosin. Our results revealed some primary features of CIPM by MLCK.

Animals↗

PubMed2004

Polymer-assisted deposition of metal-oxide films.

Metal oxides are emerging as important materials for their versatile properties such as high-temperature superconductivity, ferroelectricity, ferromagnetism, piezoelectricity and semiconductivity. Metal-oxide films are conventionally grown by physical and chemical vapour deposition. However, the high cost of necessary equipment and restriction of coatings on a relatively small area have limited their potential applications. Chemical-solution depositions such as sol-gel are more cost-effective, but many metal oxides cannot be deposited and the control of stoichiometry is not always possible owing to differences in chemical reactivity among the metals. Here we report a novel process to grow metal-oxide films in large areas at low cost using polymer-assisted deposition (PAD), where the polymer controls the viscosity and binds metal ions, resulting in a homogeneous distribution of metal precursors in the solution and the formation of uniform metal-organic films. The latter feature makes it possible to grow simple and complex crack-free epitaxial metal-oxides.

Adsorption↗

PubMed2004

Normal age-related signal change in the laryngeal cartilages.

MRI may be used for detecting cartilage invasion in patients with laryngeal carcinoma. However, the normal laryngeal ossification pattern has not been studied. Our purpose was to examine the normal age-related signal patterns in the cricoid, thyroid and arytenoid cartilages on T1-weighted images. Signal in the cartilages was assessed by two radiologists in a blinded fashion using three-point scales for intensity and symmetry. Statistical analysis consisted of logistic and monotonic regression. There was excellent interobserver agreement (>85%) for all categories. The cartilages predominantly ossify symmetrically and the extent of high signal from all three increases with age. The latter may help in detection of cartilage invasion by tumor in older patients. Normal symmetry may be helpful when comparing sides for tumor invasion.

Adolescent↗

PubMed2004

Effect of raloxifene and its interaction with human PTH on bone formation.

We studied the of effects raloxifene alone or in combination with human PTH (hPTH) 1-34 in mineralizing cultures of SaOS-2 cells. Raloxifene (10(-8)-10(-6) M) increased bone nodule formation in cultures of SaOS-2 cells when added intermittently from day 8 to day 17. A single 24-h treatment with 10(-8) M hPTH (1-34) at day 8 reduced the nodule area by 75.6% at day 17, and raloxifene added concomitantly with hPTH (1-34) reduced this inhibitory effect in a dose-dependent manner. Raloxifene also reduced the hPTH (1-34)-induced inhibition of alkaline phosphatase (ALP) activity. The 10-fold stimulation of c-fos mRNA expression by hPTH (1-34) was not influenced by raloxifene co-treatment. The protein kinase A (PKA) inhibitor 6-22 amide (1.7 nM) and the protein kinase C (PKC) inhibitor-bisindolylmaleimide 1 (10 nM) did not influence the separate effects of PTH and raloxifene on mineralized bone nodule formation. This is the first report on the interaction of PTH and raloxifene in an osteoblast culture system.

Alkaline Phosphatase↗