Biomedical subjects

Y Ling

Publications and source records attributed to Y Ling.

At least 19 recordsLinked to original sources

PubMed2006

Pseudoretinoblastoma in enucleated eyes of Asian patients.

INTRODUCTION: Retinoblastomas of the eye are a cause of childhood blindness and have a high rate of mortality, as well as a hereditary mode of transmission. Other conditions that mimic retinoblastomas are known as pseudoretinoblastomas, and are managed differently. Although pseudoretinoblastoma and the accuracy of retinoblastoma diagnosis have been reviewed in Caucasian patients, published studies in Asian patients are lacking. The purpose of this article is to report our experience with pseudoretinoblastomas in two major ophthalmological centres in Asia. METHODS: A case series of 28 enucleations carried out for suspected retinoblastoma at the Singapore National Eye Centre and KK Women's and Children's Hospital, Singapore, between January 1991 and December 2002, is reported. All cases were subjected to a detailed history from parents, followed by external ocular examination, slit-lamp biomicroscopy and binocular indirect ophthalmoscopy. Ancillary studies, such as B-scan ultrasonography and computed tomography, were employed as necessary to confirm the diagnosis. Histology was obtained on all cases. RESULTS: Of the 28 cases, 25 (89 percent) were found on histological analysis to be retinoblastomas. Three (11 percent) were pseudoretinoblastomas. There were two cases of Coat's disease and a case of presumed ocular toxocariasis. These three cases were described in detail. CONCLUSION: Although our sample size is small, the percentage of confirmed retinoblastomas was found to be only slightly higher than that found in western countries. Our findings are consistent with their findings that Coat's disease and presumed ocular toxocariasis are the more common causes of pseudoretinoblastoma.

Asian People↗

PubMed2005

Regeneration of dystrophin-expressing myocytes in the mdx heart by skeletal muscle stem cells.

Cell transplantation holds promise as a potential treatment for cardiac dysfunction. Our group has isolated populations of murine skeletal muscle-derived stem cells (MDSCs) that exhibit stem cell-like properties. Here, we investigated the fate of MDSCs after transplantation into the hearts of dystrophin-deficient mdx mice, which model Duchenne muscular dystrophy (DMD). Transplanted MDSCs generated large grafts consisting primarily of numerous dystrophin-positive myocytes and, to a lesser degree, dystrophin-negative non-myocytes that expressed an endothelial phenotype. Most of the dystrophin-positive myocytes expressed a skeletal muscle phenotype and did not express a cardiac phenotype. However, some donor myocytes, located at the graft-host myocardium border, were observed to express cardiac-specific markers. More than half of these donor cells that exhibited a cardiac phenotype still maintained a skeletal muscle phenotype, demonstrating a hybrid state. Sex-mismatched donors and hosts revealed that many donor-derived cells that acquired a cardiac phenotype did so through fusion with host cardiomyocytes. Connexin43 gap junctions were not expressed by donor-derived myocytes in the graft. Scar tissue formation in the border region may inhibit the fusion and gap junction connections between donor and host cells. This study demonstrates that MDSC transplantation warrants further investigation as a potential therapy for cardiac dysfunction in DMD.

Animals↗

PubMed2004

Experimental and computational studies of the desensitization process in the bovine rhodopsin-arrestin complex.

The deactivation of the bovine G-protein-coupled receptor, rhodopsin, is a two-step process consisting of the phosphorylation of specific serine and threonine residues in the cytoplasmic tail of rhodopsin by rhodopsin kinase. Subsequent binding of the regulatory protein arrestin follows this phosphorylation. Previous results find that at least three phosphorylatable sites on the rhodopsin tail (T340) and at least two of the S338, S334, or S343 sites are needed for complete arrestin-mediated deactivation. Thus, to elucidate the details of the interaction between rhodopsin with arrestin, we have employed both a computational and an in vitro experimental approach. In this work, we first simulated the interaction of the carboxy tail of rhodopsin with arrestin using a Monte Carlo simulated annealing method. Since at this time phosphorylation of specific serines and threonines is not possible in our simulations, we substitute either aspartic or glutamic acid residues for the negatively charged phosphorylated residues required for binding. A total of 17 simulations were performed and analysis of this shows specific charge-charge interactions of the carboxy tail of rhodopsin with arrestin. We then confirmed these computational results with assays of comparable constructed rhodopsin mutations using our in vitro assay. This dual computational/experimental approach indicates that sites S334, S338, and T340 in rhodopsin and K14 and K15 on arrestin are indeed important in the interaction of rhodopsin with arrestin, with a possible weaker S343 (rhodopsin)/K15 (arrestin) interaction.

Animals↗

PubMed2004

A phase I trial of a Bcl-2 antisense (G3139) and weekly docetaxel in patients with advanced breast cancer and other solid tumors.

PURPOSE: Expression of the Bcl-2 protein confers resistance to various apoptotic signals. G3139 [oblimersen sodium (Genasense)] is a phosphorothioate antisense oligodeoxynucleotide that targets Bcl-2 mRNA, downregulates Bcl-2 protein translation, and enhances the antitumor effects of subtherapeutic doses of docetaxel (Taxotere). PATIENTS AND METHODS: We performed a phase I trial to determine the maximum tolerated dose (MTD) and safety profile of combined therapy with G3139 and weekly docetaxel in patients with advanced Bcl-2-positive solid tumors. Cohorts of three to six patients were enrolled to escalating doses of G3139 and a fixed dose of weekly docetaxel using either of two schedules. In part I, G3139 was administered by continuous infusion for 21 days (D1-22), and docetaxel (35 mg/m2) was given weekly on days 8, 15 and 22. In part II, G3139 was given by continuous infusion for 5 days before the first weekly dose of docetaxel, and for 48 h before the second and third weekly docetaxel doses. For both schedules, cycles were repeated every 4 weeks. RESULTS: Twenty-two patients were enrolled. Thirteen patients were treated on the part I schedule with doses of G3139 escalated from 1 to 4 mg/kg/day. Nine patients were on the part II schedule of shorter G3139 infusion at G3139 doses of 5-9 mg/kg/day. Hematologic toxicities were mild, except for one case of persistent grade 3 thrombocytopenia in part I. The most common adverse events were cumulative fatigue and transaminase elevation, which prevented further dose escalation beyond 4 mg/kg/day for 21 days with the part I schedule. In part II of the study, using the abbreviated G3139 schedule, even the highest daily doses were tolerated without dose-limiting toxicity or the need for dose modification. Objective tumor response was observed in two patients with breast cancer, including one whose cancer previously progressed on trastuzumab plus paclitaxel. Four patients had stable disease. Pharmacokinetic results for G3139 were similar to those of other trials. CONCLUSIONS: G3139 in combination with standard-dose weekly docetaxel was well tolerated. The shortened and intermittent G3139 infusion had less cumulative toxicities and still allowed similar total G3139 delivery as the longer infusion. Further studies should examine the molecular effect of the regimen, as well as clinical activities in malignancies for which taxanes are indicated.

Adult↗

PubMed2003

Dynamic nonlinear effect on lasing in a random medium.

We have studied both experimentally and numerically the dynamic effect of nonlinearity on lasing in disordered medium. The third-order nonlinearity not only changes the frequency and size of lasing modes, but also modifies the laser emission intensity and laser pulse width. When the nonlinear response time is longer than the lifetime of the lasing mode, the nonlinearity changes the laser output through modifying the size of the lasing mode. When the nonlinear response is faster than the buildup of the lasing mode, positive nonlinearity always extracts more laser emission from the random medium due to the enhancement of single particle scattering.

Journal Article↗

PubMed2002

Probing localized states with spectrally resolved speckle techniques.

We have studied the spatial extent of localized states in random media using speckle correlation techniques. Optical gain is introduced to a local region of a random medium to induce lasing of the localized states. The far-field speckle pattern of laser emission from a localized state gives its spatial field correlation function at the surface of the random medium. The envelope of the spatial field correlation function decays exponentially with the transverse coordinate on the surface. The decay length is independent of the pumping rate and the excitation area. We demonstrate that localized states exist in a disordered system that does not reach the localization threshold.

Journal Article↗

PubMed2002

Bipedal stance exercise and prostaglandin E2 (PGE2) and its synergistic effect in increasing bone mass and in lowering the PGE2 dose required to prevent ovariectomized-induced cancellous bone loss in aged rats.

Previous reports have shown that bone loss was partially prevented by bipedal stance "exercise" following ovariectomy (ovx), and it was well documented that prostaglandin E2 (PGE(2)) had an anabolic effect on the rat skeleton. The aim of this study was to determine whether lower doses of PGE(2) could prevent ovx-induced cancellous bone loss with the combination of bipedal stance exercise. Seventy-eight 10-month-old female Sprague-Dawley rats were either ovariectomized or sham-operated on day 0 and then treated with PGE(2) (0, 0.3, or 1 mg/kg per day) and/or housed in normal height cages (NC, 28 cm) or raised cages (RC, 33 cm) for 8 weeks. Bone histomorphometry was performed on the double-fluorescent-labeled proximal tibial metaphysis. In sham rats, 1 mg/kg PGE(2) + RC had synergistic effects in increasing trabecular bone area, width, and number by stimulating mineral apposition rate and bone formation rate. As expected, ovx induced cancellous bone loss, accompanied by elevated activation frequency. Without RC, PGE(2) monotherapy prevented ovx-induced bone loss at the 1 mg/kg per day dose, whereas this prevention effect was observed at the 0.3 mg/kg per day dose when combined with RC. Similar to their effects in sham rats, PGE(2) and RC had synergistic effects in augmenting cancellous bone mass and architecture and maintaining the elevated bone formation but depressing bone resorption and activation frequency. We conclude that bipedal stance exercise lowers the PGE(2) dose required to prevent ovx-induced cancellous bone loss in the proximal tibial metaphysis in aged rats.

Animals↗

PubMed2001

Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening.

Bcl-2 belongs to a growing family of proteins which regulates programmed cell death (apoptosis). Overexpression of Bcl-2 has been observed in 70% of breast cancer, 30-60% of prostate cancer, 80% of B-cell lymphomas, 90% of colorectal adenocarcinomas, and many other forms of cancer. Thereby, Bcl-2 is an attractive new anti-cancer target. Herein, we describe the discovery of novel classes of small-molecule inhibitors targeted at the BH3 binding pocket in Bcl-2. The three-dimensional (3D) structure of Bcl-2 has been modeled on the basis of a high-resolution NMR solution structure of Bcl-X(L), which shares a high sequence homology with Bcl-2. A structure-based computer screening approach has been employed to search the National Cancer Institute 3D database of 206 876 organic compounds to identify potential Bcl-2 small-molecule inhibitors that bind to the BH3 binding site of Bcl-2. These potential Bcl-2 small-molecule inhibitors were first tested in an in vitro binding assay for their potency in inhibition of the binding of a Bak BH3 peptide to Bcl-2. Thirty-five potential inhibitors were tested in this binding assay, and seven of them were found to have a binding affinity (IC(50) value) from 1.6 to 14.0 microM. The anti-proliferative activity of these seven active compounds has been tested using a human myeloid leukemia cell line, HL-60, which expresses the highest level of Bcl-2 protein among all the cancer cell lines examined. Compound 6 was the most potent compound and had an IC(50) value of 4 microM in inhibition of cell growth using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Five other compounds had moderate activity in inhibition of cell growth. Compound 6 was further evaluated for its ability to induce apoptosis in cancer cells. It was found that 6 induces apoptosis in cancer cells with high Bcl-2 expression and its potency correlates with the Bcl-2 expression level in cancer cells. Furthermore, using NMR methods, we conclusively demonstrated that 6 binds to the BH3 binding site in Bcl-X(L). Our results showed that small-molecule inhibitors of Bcl-2 such as 6 modulate the biological function of Bcl-2, and induce apoptosis in cancer cells with high Bcl-2 expression, while they have little effect on cancer cells with low or undetectable levels of Bcl-2 expression. Therefore, compound 6 can be used as a valuable pharmacological tool to elucidate the function of Bcl-2 and also serves as a novel lead compound for further design and optimization. Our results suggest that the structure-based computer screening strategy employed in the study is effective for identifying novel, structurally diverse, nonpeptide small-molecule inhibitors that target the BH3 binding site of Bcl-2.

Amino Acid Sequence↗

PubMed2001

Photon statistics of random lasers with resonant feedback.

We have measured the photon statistics of random lasers with resonant feedback. With an increase of the pump intensity, the photon number distribution in a single mode changes continuously from Bose-Einstein distribution at the threshold to Poisson distribution well above the threshold. The second-order correlation coefficient drops gradually from 2 to 1. By comparing the photon statistics of a random laser with resonant feedback and that of a random laser with nonresonant feedback, we illustrate very different lasing mechanisms for the two types of random lasers.

Journal Article↗

PubMed2001

[Loss of heterozygosity on chromosome 3 in sporadic colorectal carcinoma].

OBJECTIVE: To study the loss of heterozygosity (LOH) on chromosome 3 in sporadic colorectal carcinoma (SCRC) and to explore the possible CRC related genes or loci. METHODS: LOH at 13 microsatellite loci spanning chromosome 3 were detected in 83 cases with SCRC. RESULTS: At least two loci LOH on chromosome 3 were detected in 29 of 74 (39%) cases. In 27 of 74 (37%) cases at least one locus LOH was detected on 3p, and in 39 of 74 (53%) cases at least one of 9 loci had LOH on 3q. Of the 13 loci examined, D3S1300 (3p14.2) was identified as the locus with most frequent LOH. 3q LOH was found to occur in distal CRCs more often than those proximal. Tumors with 3p and/or D3S1300 LOH had a tendency of local invasion, and occurred more often in patients older than 50 years. CONCLUSION: LOH on chromosome 3, dispersed with high frequency at several loci, was correlated with clinico-pathology of SCRC, indicating the existence of SCRC related genes on it. The discovery of D3S1300 locus with highly frequent LOH suggested that FHIT gene located in this region might act as a candidate tumor suppressor gene in the development of colorectal carcinoma.

Adult↗

PubMed2001

Apoptosis and Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

To investigate the roles of apoptosis and the Fas system (Fas, Fas ligand, soluble Fas) in the process of liver cirrhosis (LC) converting into hepatocellular carcinoma (HCC), expression of Fas and Fas ligand (FasL) in 49 LC and 36 HCC samples was detected by immunohistochemical method. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Serum soluble Fas (sFas) levels in 28 cases of LC and 27 cases of HCC were measured by enzyme-linked immunosorbent assay (ELISA) method. Compared with LC, apoptotic indices (AI) in HCC tissues were significantly reduced (P < 0.001), expression of Fas was decreased (P < 0.05), and that of FasL was increased (P < 0.05). Serum sFas levels in HCC patients were significantly higher than those in normal controls. Down-regulation of Fas expression, up-regulation of FasL expression in hepatocytes and elevation of sFas level in serum might contribute to tumor escape from immune surveillance of the body. Apoptosis and the Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

Adult↗

PubMed2001

Transparent morphology of the thoracoabdominal wall.

The transverse rectus abdominis myocutaneous (TRAM) flap has become the gold standard for autologous breast reconstruction in the last decade. The deep inferior epigastric perforator (DIEP) flap is a refinement of the conventional myocutaneous flap, which is based on anatomic studies of the abdominal wall. These authors have performed a transparent morphologic study of the abdominothoracic wall, in order to visualize the vessel architecture and relationships. The methodology of specimen processing, the anatomic findings, and modifications of surgical incisions are illustrated and discussed.

Abdominal Muscles↗

PubMed2001

Disruption of cell adhesion and caspase-mediated proteolysis of beta- and gamma-catenins and APC protein in paclitaxel-induced apoptosis.

Cell adhesion is important in the regulation of cell proliferation, migration, survival, and apoptosis. The major components of cell adhesion are the cadherin family of proteins, alpha-, beta- and gamma-catenins, and cytoskeletons. In addition, beta-catenin, when associated with adenomatous polyposis coli (APC) protein, an oncosuppressor, is implicated in the regulation of beta-catenin/APC-related signaling pathways. To examine the correlation between impairment of cell adhesion events and apoptosis, we used human non-small-cell lung cancer H460 and H520 cell lines as models to determine whether paclitaxel-induced apoptosis is associated with disruption of the components of cell adhesion and their functions. Paclitaxel treatment resulted in cells rounding up and losing contact with their neighboring cells, suggesting that the drug does indeed affect cell adhesion and related events. Western blot analysis revealed that paclitaxel caused a time- and concentration-dependent cleavage of beta-catenin, gamma-catenin, and APC protein, but not alpha-catenin or E-cadherin. These cleavages of beta-catenin and gamma-catenin were apoptosis-dependent, not mitosis-dependent. Paclitaxel treatment led to the proteolysis and activation of caspase-3 and -7, but not caspase-1. Furthermore, paclitaxel-induced apoptosis and cleavage of beta-catenin and gamma-catenin were inhibited by the pan-caspase inhibitor Z-VAD-FMK and partially inhibited by the caspase-3 inhibitor Z-DEVD-FMK but were not affected by the caspase-1 inhibitor AC-YVAD-CMK. Although the pan-caspase inhibitor blocked the cleavage of beta-catenin as well as DNA fragmentation, it did not affect paclitaxel-induced M-phase arrest and only partially prevented cell-growth inhibition. Biochemical studies revealed that cleaved beta-catenin was detected only in the Triton X-100 insoluble fraction, suggesting that it might localize in nuclear and/or membrane structures. Interestingly, the paclitaxel-induced beta-catenin fragment lost its ability to bind to E-cadherin, alpha-catenin, or APC protein and to serve as a substrate for tyrosine kinase. All our data demonstrate that the caspase-mediated cleavage of beta-catenin, gamma-catenin, and APC protein might contribute to paclitaxel-induced apoptosis.

Adenomatous Polyposis Coli Protein↗

PubMed2001

[Expression of telomerase reverse transcriptase and its relationship with tumor suppressor gene p53 in HCC].

OBJECTIVE: To explore the expression of human telomerase reverse transcriptase (HTERT) and its relationship with tumor suppressor gene p53. METHODS: RNA-RNA in situ hybridization (ISH) technique was applied to localize the expression of HTERT mRNA and immunohistochemistry (IHC) was used to observe the p53 protein expression in 34 specimens of HCC and their corresponding non-cancerous tissues. Both the significance of HTERT mRNA expression in the different histopathologic characters and its relationship with p53 protein were investigated. RESULTS: HTERT was detected in tumor tissue in 30 of 34 cases (88.2%), and all the 6 cases of small cancer (diameter<3cm) were positive. The positive rate of HTERT mRNA was higher in the tumor tissues with low-differentiation, extra- or intra-hepatic metastasis, uncompleted fibrotic capsule and/or the non-cancerous tissue with chronic active lesions or positive HBsAg. Intensive signal was seen both in the HCC cells along the front of invasive area and in a few non-cancerous liver cells with dysplasia. Of all 34 HCC, p53 protein was presented in 25 cases. There was a correlation between the expression of HTERT mRNA and of p53 protein. The coincidence rate of the expression (HTERT+/p53+ and HTERT-/p53-) was 79.4%. More intensity of HTERT signal could be seen in the cases of positive p53. HTERT mRNA was not found in normal liver tissues. CONCLUSIONS: High expression of HTERT mRNA is proved in most cases of HCCs. HTERT expression may relate to the pathogenesis and the invasion of HCC. p53 may play a role in regulating the expression of HTERT.

Adult↗

PubMed2001

[Treatment of syphilis in pregnancy and its perinatal prognosis].

OBJECTIVE: To investigate the effects of treatment of syphilis in pregnancy on perinatal prognosis. METHODS: Patients of syphilis in pregnancy from Hainan Provincial People's Hospital and Haikou Municipal Maternal and Child Health Center during 1995.1 to 2001.1 were collected for retrospective analysis. Pregnant women with syphilis were divided into treated group and untreated group according to whether they received penicillin anti-syphilis treatment or not during pregnancy. RESULTS: The total number of deliveries in the 2 hospitals during that period was 18,701, and 61 out of 9,805 women screened for syphilis were positive, giving an incidence of 6.2/1000. The perinatal mortality rates were 11.2% in treated group and 83.3% in untreated group, and incidences of congenital syphilis were 17.6% and 72.7% respectively. CONCLUSION: Syphilis in pregnancy is a serious complication to harm the fetus. Screening of syphilis during pregnancy is necessary, and penicillin treatment is effective which may reduce the perinatal mortality rate and the birth of congenital syphilis baby.

Adult↗

PubMed2001

Optical coherence tomography in measuring retinal nerve fiber layer thickness in normal subjects and patients with open-angle glaucoma.

OBJECTIVES: To investigate image characteristics and thickness of the retinal nerve fiber layer (RNFL) in normal and glaucomatous eyes using optical coherence tomography (OCT), and analyze the relationship between RNFL thickness and visual field index. METHODS: Eighty-three normal persons (150 eyes) and 83 patients with primary open angle glaucoma (POAG, 149 eyes) underwent OCT examinations with 3.4 mm diameter circle scan to calculate the RNFL thickness. Statistical analysis was used to compare differences in RNFL thickness in quadrants and means between the normal and glaucomatous groups and the different stages of POAG. Linear correlation and regression analysis were used to show the correlation between RNFL thickness and visual field index of 115 eyes in glaucomatous patients. Reproducibility, sensitivity and specificity of RNFL measurements using OCT were evaluated. RESULTS: RNFL thickness measured by OCT in normal subjects was thicker in superior and inferior, less in temporal, and thinnest in nasal quadrants. The curve showed double peaks. RNFL of glaucomatous patients showed local thinning or defect, diffuse thinning, or both. The mean RNFL thicknesses of the normal group in the temporal, superior, nasal and infelor quadrants were 90.1 +/- 10.8 microns, 140.4 +/- 10.5 microns, 85.2 +/- 14.0 microns, and 140.4 +/- 9.7 microns, respectively with a mean of 114.2 +/- 6.0 microns. The numbers for the glaucomatous group were respectively 56.0 +/- 31.0 microns, 81.0 +/- 36.3 microns, 47.1 +/- 27.5 microns, and 73.4 +/- 38.4 microns for the four quadrants, with a mean of 64.6 +/- 28.8 microns. There was a significant difference in RNFL thickness between the normal and glaucomatous groups (P < 0.000), and the three stages (early, developing and late) of glaucomatous groups (P < 0.000). There was a close negative relationship between RNFL thickness and visual field index (r = -0.796, P < 0.0001). The sensitivity and specificity of RNFL thickness in POAG measured using OCT were 93.3% and 92.0%, respectively. CONCLUSIONS: OCT can quantitatively measure RNFL thickness differences between normal persons and glaucomatous patients. RNFL thickness gradually decreases while visual field defect increases with the development of POAG.

Adolescent↗

PubMed2001

Effect of 0.2% brimonidine on retinal blood flow.

PURPOSE: To analyze the effect of 0.2% brimonidine eye drops on retinal blood flow of patients with glaucoma. METHODS: Using self-control method and Heidelberg Retina Flowmeter (HRF), we examined the volume, flow and velocity of the superior nasal and temporal, the inferior nasal and temporal artery of retina at baseline and 2 hours after single instillation of 0.2% brimonidine. RESULTS: There were no significant changes in volume, flow and velocity of four vessels before and after the administration of 0.2% brimonidine. CONCLUSIONS: There are no significant ocular haemodynamic benefits associated with Brimonidine therapy to the glaucoma patients.

Adrenergic alpha-Agonists↗

PubMed2000

Straight-line stabilization

For finite-dimensional maps, an unstable orbit in a neighborhood of an unstable fixed point can be stabilized by adjusting parameters so that the orbit goes to the fixed point along the straight line connecting the orbit (at a given time) and the fixed point [Yang Ling, Liu Zengrong and Jian-min Mao, Phys. Rev. Lett. 84, 67 (2000)]. This is called straight-line stabilization. In this paper, we derive the expression for the region of stabilization, i.e., the region within which the straight-line stabilization method is valid. For two-dimensional maps, the parameter adjustments needed by the stabilization method are explicitly given for nine cases. Stabilization of unstable flows, with or without introducing a Poincare map, is also investigated.

Journal Article↗