Biomedical subjects

Yang Li

Publications and source records attributed to Yang Li.

At least 73 records · Page 4Linked to original sources

PubMed2006

Novel inhibitors of hepatitis C virus RNA-dependent RNA polymerases.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide-and is the main cause of adult liver transplants in developed nations. We have identified a class of novel and specific inhibitors of HCV NS5B RNA-dependent RNA polymerase (RdRp) activity in vitro. Characterization of two such inhibitors, COMPOUND1 (5-(4-chlorophenylmethylene)-3-(benzenesulfonylamino)-4-oxxo-2-thionothiazolidine) and COMPOUND2 (5-(4-bromophenylmethylene)-3-(benzenesulfonylamino)-4-oxxo-2-thionothiazolidine), is reported here. With IC(50) values of 0.54muM and 0.44muM, respectively, they are reversible and non-competitive with nucleotides. Biochemical and structural studies have suggested that these compounds can inhibit the initiation of the RdRp reaction. Interestingly, these inhibitors appear to form a reversible covalent bond with the NS5B cysteine 366, a residue that is not only conserved among all HCV genotypes and a large family of viruses but also required for full NS5B RdRp activity. This may reduce the potential resistance of the viruses to this class of inhibitors.

Hepacivirus↗

PubMed2006

Inhibition of heat shock protein 90 function by 17-allylamino-17-demethoxy-geldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinase, dephosphorylates extracellular signal-regulated kinase, and induces cell cycle arrest and cell death.

PURPOSE: Heat shock protein 90 (HSP90) is a chaperone for several client proteins involved in transcriptional regulation, signal transduction, and cell cycle control. HSP90 is abundantly expressed by a variety of tumor types and has been recently targeted for cancer therapy. The objective of this study was to determine the role of HSP90 in promoting growth and survival of Hodgkin's lymphoma and to determine the molecular consequences of inhibiting HSP90 function by the small-molecule 17-allylamino-17-demethoxy-geldanamycin (17-AAG) in Hodgkin's lymphoma. EXPERIMENTAL DESIGN: HSP90 expression in Hodgkin's lymphoma cell lines was determined by Western blot and in primary lymph node sections from patients with Hodgkin's lymphoma by immunohistochemistry. Cell viability was determined by the 3-(4,5-dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Apoptosis and cell cycle fractions were determined by flow cytometry. Expression of intracellular proteins was determined by Western blot. RESULTS: HSP90 is overexpressed in primary and cultured Hodgkin's lymphoma cells. Inhibition of HSP90 function by 17-AAG showed a time- and dose-dependent growth inhibition of Hodgkin's lymphoma cell lines. 17-AAG induced cell cycle arrest and apoptosis, which were associated with a decrease in cyclin-dependent kinase (CDK) 4, CDK 6, and polo-like kinase 1 (PLK1), and induced apoptosis by caspase-dependent and caspase-independent mechanisms. Furthermore, 17-AAG depleted cellular contents of Akt, decreased extracellular signal-regulated kinase (ERK) phosphorylation, and reduced cellular FLICE-like inhibitory protein levels (FLIP), and thus enhanced the cytotoxic effect of doxorubicin and agonistic anti-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor antibodies. CONCLUSION: Inhibition of HSP90 function induces cell death and enhances the activity of chemotherapy and anti-tumor necrosis factor-related apoptosis-inducing ligand death receptor antibodies, suggesting that targeting HSP90 function might be of therapeutic value in Hodgkin's lymphoma.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Stress hormone-mediated invasion of ovarian cancer cells.

PURPOSE: There is growing evidence that stress and other behavioral factors may affect cancer progression and patient survival. The underlying mechanisms for this association are poorly understood. The purpose of this study is to determine the effects of stress-associated hormones norepinephrine, epinephrine, and cortisol on the invasive potential of ovarian cancer cells. EXPERIMENTAL DESIGN: The ovarian cancer cells EG, SKOV3, and 222 were exposed to increasing levels of either norepinephrine, epinephrine, or cortisol, and the in vitro invasive potential was determined using the membrane invasion culture system. Additionally, the effects of these stress hormones on matrix metalloproteinase-2 (MMP-2) and MMP-9 were determined by ELISA. The effects of the beta-adrenergic agonist isoproterenol on in vivo tumor growth were determined using nude mice. RESULTS: Stress levels of norepinephrine increased the in vitro invasiveness of ovarian cancer cells by 89% to 198%. Epinephrine also induced significant increases in invasion in all three cell lines ranging from 64% to 76%. Cortisol did not significantly affect invasiveness of the EG and 222 cell lines but increased invasion in the SKOV3 cell line (P = 0.01). We have previously shown that ovarian cancer cells express beta-adrenergic receptors. The beta-adrenergic antagonist propanolol (1 mumol/L) completely blocked the norepinephrine-induced increase in invasiveness. Norepinephrine also increased tumor cell expression of MMP-2 (P = 0.02 for both SKOV3 and EG cells) and MMP-9 (P = 0.01 and 0.04, respectively), and pharmacologic blockade of MMPs abrogated the effects of norepinephrine on tumor cell invasive potential. Isoproterenol treatment resulted in a significant increase in tumor volume and infiltration in the SKOV3ip1 in vivo model, which was blocked by propranolol. CONCLUSIONS: These findings provide direct experimental evidence that stress hormones can enhance the invasive potential of ovarian cancer cells. These effects are most likely mediated by stimulation of MMPs.

Animals↗

PubMed2006

Mediastinal node and diaphragmatic targeting after intracavitary injection of avidin/99mTc-blue-biotin-liposome system.

A method for delivering drugs to sites of disease extension in mediastinal nodes is described. Mediastinal node and lymphatic distributions were determined after intracavitary injection of the avidin/biotin-liposome system in normal rats. The effect of the injected dose on lymphatic targeting of liposomes after intraperitoneal injection of (99m)Tc-blue-biotin-liposomes and intrapleural injection of avidin, and vice versa, is presented. Scintigraphic imaging was used to follow the movement of (99m)Tc-blue-biotin-liposomes to determine the pharmacokinetics and organ uptake. Tissue biodistribution studies were performed 22 h after injection of the (99m)Tc-blue-biotin-liposomes. Results indicated that independent of the cavity in which each agent was injected, a dose of 5.0 mg of each agent results in higher mediastinal node targeting (8%-10% ID/Organ) as compared with the injection of a 0.5 mg dose (2%-5% ID/Organ, p < 0.05). Targeting of diaphragm and associated lymphatics was observed when (99m)Tc-blue-biotin-liposomes were injected in peritoneum and avidin in pleural space. In contrast, pleural, and pericardial lymphatic targeting was observed when (99m)Tc-blue-biotin-liposomes were injected in pleural space and avidin in peritoneum. Intracavitary injection of the avidin/biotin-liposome system could potentially be used for the delivery of prophylactic drugs that could reduce tumor metastasis and infection spread to mediastinal nodes.

Animals↗

PubMed2006

The HSP90 inhibitor 17-AAG synergizes with doxorubicin and U0126 in anaplastic large cell lymphoma irrespective of ALK expression.

OBJECTIVE: Heat shock protein 90 (HSP90) chaperones and maintains the molecular integrity of a variety of signal transduction proteins, including the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein, a genetic abnormality that is frequently observed in anaplastic large cell lymphoma (ALCL) cells. Here we demonstrate that HSP90 is overexpressed in primary and cultured ALK-positive and ALK-negative ALCL cells, and we evaluate the potential role of the small molecule inhibitor of HSP90, 17-allylamino-17-demethoxygeldanamycin (17-AAG) in treating ALCL. METHODS: The antiproliferative effect of 17-AAG-cultured cells was determined by MTS assay. Apoptosis and cell-cycle arrest were determined by Annexin-V/propidium iodide and propidium iodide staining, respectively, and fluorescein-activated cell sorting analysis. Expression of HSP90 was evaluated by immunohistochemistry, and molecular changes were determined by Western blot. RESULTS: Treatment of cultured ALCL cells with 17-AAG induced cell-cycle arrest and apoptosis, irrespective of ALK expression. At the molecular level, 17-AAG induced degradation of ALK and Akt proteins, dephosphorylated extracellular signal-regulated kinase, and degraded the cell-cycle regulatory protein cyclin D1 and its cyclin-dependent kinases, CDK4 and CDK6, but had a differential effect on p27 and p53 proteins. Inhibition of extracellular signal-regulated kinase phosphorylation by the mitogen activated protein kinase inhibitor U0126 induced cell death in all ALCL cell lines, and sublethal concentration 17-AAG showed synergistic antiproliferative effects when combined with U0126 or doxorubicin. CONCLUSION: Our data demonstrate that targeting HSP90 function by 17-AAG may offer a novel therapeutic strategy for ALCL, either as single-agent activity or by combining 17-AAG with conventional or targeted therapeutic schemes.

Anaplastic Lymphoma Kinase↗

PubMed2006

Amphiphilic poly(L-lactide)-b-dendritic poly(L-lysine)s synthesized with a metal-free catalyst and new dendron initiators: chemical preparation and characterization.

This study presents investigations on new approaches to novel biodegradable amphiphilic poly(L-lactide)-b-dendritic poly(L-lysine)s bearing well-defined structures. First, two new Boc-protected poly(L-lysine) dendron initiators G(2)OH 4 (generation = 2) and G(3)OH 6 (generation = 3) with hydroxyl end functional groups were efficiently derived from corresponding precursors 3 and 5 via methyl ester substitution with ethanolamine. Subsequently, two series of new diblock copolymers of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s (S1-S2, S3-S4) were prepared in chloroform through ring-opening copolymerization of poly(L-lactide)s with a metal-free catalyst of organic 4-(dimethylamino) pyridine (DMAP) in the presence of a corresponding new poly(L-lysine) dendron initiator. Further, molecular structures of the prepared new dendron initiators as well as those of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s bearing different dendron blocks and PLLA lengths were examined by means of nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), mass spectrometry (ESI-MS, MALDI-FTMS), and thermal gravimetric analysis (TGA). The results demonstrated successful formation of the synthetic precursors, functional dendron initiators, and new diblock copolymers. In addition, the very narrow molecular weight distributions (PDI = 1.10-1.14) of these poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s further indicated their well-defined molecular structures. After the efficient Boc-deprotection for the dendron amino groups with TFA/CH(2)Cl(2), new diblock poly(L-lactide)-b-dendritic poly(L-lysine)s bearing lipophilic PLLA and hydrophilic dendritic PLL were finally prepared. It was noteworthy that the MALDI-FTMS result showed that no appreciable intermolecular chain transesterification happened during the ROP of L-lactide catalyzed by the DMAP. Moreover, self-assembly of these new biodegradable amphiphilic copolymers in diverse solvents were also preliminarily studied.

Anthracenes↗

PubMed2006

New asymmetric AB(n)-shaped amphiphilic poly(ethylene glycol)-b-[poly(l-lactide)](n) (n = 2, 4, 8) bridged with dendritic ester linkages: I. Syntheses and their characterization.

This study presents new investigations on chemical syntheses and characterization of new asymmetric AB(n)-shaped amphiphilic diblock methoxy poly(ethylene glycol)-b-[poly(l-lactide)](n), MPEG-b-(PLLA)(n) (n = 2, 4, and 8), bridged with dendritic ester linkages. First, a new series of A(OH)(n)-shaped hydroxy end-capped MPEG-(OH)(2), MPEG-(OH)(4), and MPEG-(OH)(8) bearing corresponding one- to three-generation dendritic ester moieties were efficiently derived from the starting MPEG (M(n) = 2 KDa) and 2,2'-bis(hydroxymethyl)propionic acid (Bis-HMPA) via ester coupling and a facile hydroxy protection-deprotection cycle, and then, chemical structures of these functional MPEG-(OH)(n) were characterized by nuclear magnetic resonance spectrometry (NMR) and MALDI-FTMS. Subsequently, by employing these MPEG-(OH)(n) as functional macroinitiators, new asymmetric AB(n)()-shaped amphiphilic MPEG-b-(PLLA)(2) S1, MPEG-b-(PLLA)(4) S2, and MPEG-b-(PLLA)(8) S3 bridged with dendritic Bis-HMPA ester linkages of L1-L3 as well as linear structural MPEG-b-PLLA references (R1-R3) were synthesized through the SnOct(2)-catalyzed ring-opening polymerization (ROP) of l-lactide at 130 degrees C in m-xylene solution, and their structures were further examined by NMR and gel permeation chromatography (GPC). It was demonstrated that the functional MPEG-(OH)(n) efficiently initiated the ROP of LLA, finally leading to successful formation of the AB(n)-shaped amphiphilic MPEG-b-(PLLA)(n) (n = 2, 4, and 8) with each PLLA arm weight close to 2 KDa and very narrow molecular weight distribution. Moreover, thermal history, crystallization, and spherulite morphologies were studied by means of differential scanning calorimeter (DSC), thermal gravimetric analyzer (TGA), and polarized microscope (POM) for these new structural amphiphilic S1-S3 as well as the linear R1-R3, intriguingly indicating a strong molecular architecture dependence of segmental crystallizability, spherulite morphology, and apparent crystal growth rate. Due to the favorable biodegradability and biocompatibility of the PLLA and MPEG, these results may therefore create new possibilities for these novel structural AB(n)-shaped amphiphilic MPEG-b-(PLLA)(n) as potential biomaterials.

Cross-Linking Reagents↗

PubMed2006

Medium scale integration of molecular logic gates in an automaton.

The assembly of molecular automata that perform increasingly complex tasks, such as game playing, presents an unbiased test of molecular computation. We now report a second-generation deoxyribozyme-based automaton, MAYA-II, which plays a complete game of tic-tac-toe according to a perfect strategy. In silicon terminology, MAYA-II represents the first "medium-scale integrated molecular circuit", integrating 128 deoxyribozyme-based logic gates, 32 input DNA molecules, and 8 two-channel fluorescent outputs across 8 wells.

Algorithms↗

PubMed2006

Comparative study of maxillary growth and occlusal outcome after autogenous rib grafting in complete cleft palate defect.

Cleft palate is a congenital deformity with soft tissue and hard tissue defects. Normal cleft palate repairing surgery only repairs soft tissue defects, whereas bone defects in the hard palate still exist. Therefore, we conducted this study in beagles to observe the influence of bone grafting at primary surgery on craniofacial growth and occlusal relationships in individuals with complete cleft palate and to provide experimental evidence for optimal surgical procedures for cleft palate. Using 60 beagle puppies as subjects, we tested the effects of bone grafting in surgically induced palatal defect. The animals were randomly and equally divided into four groups: (1) unoperated controls; (2) surgically induced unilateral cleft palate, not repaired; (3) two-flap palatoplasty used to close the soft defect of the surgically induced cleft palate; (4) autogenous bone (a piece of rib bone) implanted into the palatal defect before two-flap palatoplasty was performed.Cephalometric roentgenography and plaster casts of the maxillary were taken preoperatively and every 4 weeks after surgery. Sixty metric cranial variables were measured directly from the cleaned skulls after the animals were killed the 34th week postoperatively. The measurement results indicated that bone grafting may reduce the disturbance of maxillary growth caused by the cleft palate and the denuded bone, but it may cause other maxillary deformities. This finding suggests that surgeons should be careful in choosing the method of primary bone grafting in repairing complete cleft palate.

Animals↗

PubMed2006

Identification and genome characterization of Heliothis armigera cypovirus types 5 and 14 and Heliothis assulta cypovirus type 14.

Genomic characterization of Heliothis armigera cypovirus (HaCPV) isolated from China showed that insects were co-infected with several cypoviruses (CPVs). One of the CPVs (HaCPV-5) could be separated from the others by changing the rearing conditions of the Heliothis armigera larvae. This finding was further confirmed by nucleotide sequencing analysis. Genomic sequences of segments S10-S7 from HaCPV-14, S10 and S7 from HaCPV-5, and S10 from Heliothis assulta CPV-14 were compared. Results from database searches showed that the nucleotide sequences and deduced amino acid sequences of the newly identified CPVs had high levels of identity with those of reported CPVs of the same type, but not with CPVs of different types. Putative amino acid sequences of HaCPV-5 S7 were similar to that of the protein from Rice ragged stunt virus (genus Oryzavirus, family Reoviridae), suggesting that CPVs and oryzaviruses are related more closely than other genera of the family Reoviridae. Conserved motifs were also identified at the ends of each RNA segment of the same virus type: type 14, 5'-AGAAUUU...CAGCU-3'; and type 5, 5'-AGUU...UUGC-3'. Our results are consistent with classification of CPV types based on the electrophoretic patterns of CPV double-stranded RNA.

Amino Acid Sequence↗

PubMed2006

Inhibition of the phosphatidylinositol-3 kinase/Akt promotes G1 cell cycle arrest and apoptosis in Hodgkin lymphoma.

Activation of the phosphatidylinositol 3-kinase (PI(3)K) pathway has been linked with tumour cell growth, survival and resistance to therapy in several cancer types. The active, phosphorylated form of Akt (pAkt) was found to be aberrantly expressed in Hodgkin lymphoma (HL)-derived cell lines and in Hodgkin-Reed-Sternberg (HRS) cells in 27 of 42 (64.3%) of primary lymph node sections of HL, indicative of PI(3)K activity. Akt phosphorylation was not associated with loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression, but with its phosphorylation in HL-cell lines, suggesting that its biological function is impaired. Akt phosphorylation was further induced by CD30 ligand (CD30L), CD40L and receptor activator of nuclear factor kappa B (RANK) ligand. The PI(3)K inhibitor LY294002 demonstrated antiproliferative effects in a dose- and time-dependent manner, which was associated with Akt dephosphorylation on Thr308 and Ser473 sites and dephosphorylation of the downstream ribosomal protein S6. LY209002 induced cell cycle arrest in the G0/G1 phase and apoptosis, which were associated with upregulation of MDM2, downregulation of cyclin D1, activation of caspase 9 and poly-ADP-ribose polymerase cleavage. The Akt inhibitor QLT394 also demonstrated antiproliferative effects in a dose- and time-dependent manner, dephosphorylated ribosomal S6 and cleaved caspase 9. Collectively, these data suggest that the aberrant activation of the PI(3)K/Akt survival pathway in HRS cells is not because of loss of PTEN expression. Our data suggest that PTEN phosphorylation and activation of CD30, CD40 and RANK may play a role in activating Akt in HRS cells.

Antigens, CD↗

PubMed2006

Characterization of a unique borreliacidal epitope on the outer surface protein C of Borrelia burgdorferi.

The outer surface protein C (OspC) of the Lyme disease agent, Borrelia burgdorferi, is an immunoprotective antigen in laboratory models of infection. However, to understand its protective effects, it is important to identify the key epitopes of this protein. We produced a borreliacidal anti-OspC monoclonal antibody specific to the B31 strain and identified its binding site. The specificity of MAb 16.22 was determined by Western blot reactivity using OspC derived from different Borrelia isolates which had varying amino acid sequences. Comparison of the OspC sequences and binding data suggested that MAb 16.22 binds to amino acids 133-147 of the OspC protein. To test this hypothesis, we synthesized a 15-amino acid peptide containing the target sequence and, using competition enzyme-linked immunosorbent assay (ELISA), we found that this peptide included the epitope of MAb 16.22. In addition, we determined that MAb 16.22 is able to kill of B. burgdorferi in a complement-independent fashion.

Antibodies, Bacterial↗

PubMed2006

SHP-1 dephosphorylates 3BP2 and potentially downregulates 3BP2-mediated T cell antigen receptor signaling.

Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-1 (SHP-1) is a critical inhibitory regulator in T cell-receptor (TCR) signaling. However, the exact molecular mechanism underlying this is poorly defined, largely because the physiological substrates for SHP-1 in T cells remain elusive. In this study, we showed that adaptor protein 3BP2 serves as a binding protein and a physiological substrate of SHP-1. 3BP2 is phosphorylated on tyrosyl residue 448 in response to TCR activation, and the phosphorylation is required for T cell signalling, as indicated by transcriptional activation of nuclear factor activated in T cells (NFAT). Concurrently, phosphorylation of Tyr566 at the C-terminus of SHP-1 causes specific recruitment of 3BP2 to the phosphatase through the SH2 domain of the adaptor protein. This leads to efficient dephosphorylation of 3BP2 and thereby termination of T cell signaling. The study thus defines a novel function of the C-terminal segment of SHP-1 and reveals a new mechanism by which T cell signaling is regulated.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Application of surface-enhanced laser desorption/ionization time-of-flight-based serum proteomic array technique for the early diagnosis of prostate cancer.

AIM: To identify the serum biomarkers of prostate cancer (PCa) by protein chip and bioinformatics. METHODS: Serum samples from 83 PCa patients and 95 healthy men were taken from a mass screening in Changchun, China. Protein profiling was carried out using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The data of spectra were analyzed using two bioinformatics tools. RESULTS: Eighteen serum differential proteins were identified in the PCa group compared with the control group (P < 0.01). There were four proteins at the higher serum level and 14 proteins at the lower serum level in the PCa group. A decision tree classification algorithm that used an eight-protein mass pattern was developed to correctly classify the samples. A sensitivity of 92.0% and a specificity of 96.7% for the study group were obtained by comparing the PCa and control groups. CONCLUSION: We identified new serum biomarkers of PCa. SELDI-TOF MS coupled with a decision tree classification algorithm will provide a highly accurate and innovative approach for the early diagnosis of PCa.

Aged↗

PubMed2006

Use of electrochemical DNA biosensors for rapid molecular identification of uropathogens in clinical urine specimens.

We describe the first species-specific detection of bacterial pathogens in human clinical fluid samples using a microfabricated electrochemical sensor array. Each of the 16 sensors in the array consisted of three single-layer gold electrodes-working, reference, and auxiliary. Each of the working electrodes contained one representative from a library of capture probes, each specific for a clinically relevant bacterial urinary pathogen. The library included probes for Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterocococcus spp., and the Klebsiella-Enterobacter group. A bacterial 16S rRNA target derived from single-step bacterial lysis was hybridized both to the biotin-modified capture probe on the sensor surface and to a second, fluorescein-modified detector probe. Detection of the target-probe hybrids was achieved through binding of a horseradish peroxidase (HRP)-conjugated anti-fluorescein antibody to the detector probe. Amperometric measurement of the catalyzed HRP reaction was obtained at a fixed potential of -200 mV between the working and reference electrodes. Species-specific detection of as few as 2,600 uropathogenic bacteria in culture, inoculated urine, and clinical urine samples was achieved within 45 min from the beginning of sample processing. In a feasibility study of this amperometric detection system using blinded clinical urine specimens, the sensor array had 100% sensitivity for direct detection of gram-negative bacteria without nucleic acid purification or amplification. Identification was demonstrated for 98% of gram-negative bacteria for which species-specific probes were available. When combined with a microfluidics-based sample preparation module, the integrated system could serve as a point-of-care device for rapid diagnosis of urinary tract infections.

Biosensing Techniques↗

PubMed2006

Retinal pigment epithelium damage enhances expression of chemoattractants and migration of bone marrow-derived stem cells.

PURPOSE: To characterize chemoattractants expressed by the retinal pigment epithelium (RPE) after sodium iodate (NaIO3)-induced damage and to investigate whether ocular-committed stem cells preexist in the bone marrow (BM) and migrate in response to the chemoattractive signals expressed by the damaged RPE. METHODS: C57/BL6 mice were treated with a single intravenous injection of NaIO3 (50 mg/kg) to create RPE damage. At different time points real-time RT-PCR, ELISA, and immunohistochemistry were used to identify chemoattractants secreted in the subretinal space. Conditioned medium from NaIO3-treated mouse RPE was used in an in vitro assay to assess chemotaxis of stem cell antigen-1 positive (Sca-1+) BM mononuclear cells (MNCs). The expression of early ocular markers (MITF, Pax-6, Six-3, Otx) in migrated cells and in MNCs isolated from granulocyte colony-stimulating factor (G-CSF) and Flt3 ligand (FL)-mobilized and nonmobilized peripheral blood (PB) was analyzed by real-time RT-PCR. RESULTS: mRNA for stromal cell-derived factor-1 (SDF-1), C3, hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF) was significantly increased, and higher SDF-1 and C3 protein secretion from the RPE was found after NaIO3 treatment. A higher number of BMMNCs expressing early ocular markers migrated to conditioned medium from damaged retina. There was also increased expression of early ocular markers in PBMNCs after mobilization. CONCLUSIONS: Damaged RPE secretes cytokines that have been shown to serve as chemoattractants for BM-derived stem cells (BMSCs). Retina-committed stem cells appear to reside in the BM and can be mobilized into the PB by G-CSF and FL. These stem cells may have the potential to serve as an endogenous source for tissue regeneration after RPE damage.

Animals↗

PubMed2006

Spectacle correction of heterophoria in hyperopic amblyopic children.

OBJECTIVE: To test the effects of corrective spectacles in hyperopic amblyopic children with heterophoria. METHODS: Visual acuity, refraction and the amount of heterophoria on near (33 cm) fixation were measured before and after 3 weeks of spectacle-wearing in 30 hyperopic amblyopic children with heterophoria. The control group consisted of 20 emmetropic children age-matched to the patients. RESULTS: Uncorrected eyes displayed hyperopic amblyopia accompanied by heterophoria. Corrective spectacles not only attenuated the hyperopia and amblyopia, but also changed the heterophoria to orthophoria. The amount of heterophoria before wearing spectacles was significantly different from that in emmetropic children; but after correction with spectacles, it was the same as that in the emmetropic controls. CONCLUSION: Correction with spectacles is effective for the treatment of heterophoria in hyperopic children with amblyopia.

Accommodation, Ocular↗

PubMed2006

[Lymphangiogenes and location of tumor lymphatic vessels induced by VEGF-C in primary breast carcer].

OBJECTIVE: To investigate the lymphangiogenesis and location of tumor lymphatic vessels induced by vascular endothelial growth factor C (VEGF-C) in primary breast cancer. METHODS: The expression of VEGF-C mRNA in 89 cases of primary breast cancer was detected by in situ hybridization, and lymphatic vessels with vascular endothelial growth factor receptor-3 (VEGFR-3) were labeled by immunohistochemistry SP method. RESULTS: VEGF-C mRNA expressed in 49 of all 89 cases of primary breast cancer, and the expression rate was 55.06%. The expression of VEGF-C mRNA was positively correlated with lymphatic vessel density (LVD) and axillary lymph node metastasis, LVD and the rate of axillary lymph node metastasis were significantly higher in VEGF-C mRNA positive group than those in the negative group (both P < 0.05). Different levels of lymphangiogenesis took place in all cases of breast cancer, but it was mainly located in tumor stroma, and apparently mature lymphatic vessels were not found in cancer nests. LVD was positive related with the clinical stage and axillary lymph node metastasis in breast cancer; the clinical stage, the LVD, the axillary lymph node metastasis in positive group were higher than those in the negative group (P < 0.05). CONCLUSION: The expression of VEGF-C mRNA is positively correlated with lymphangiogenesis and axillary lymph node metastasis in primary breast cancer. Lymphangiogenesis induced by VEGF-C predominantly takes place in the tumor stroma tissue, and mature lymphatic vessels are not found in cancer nests.

Adult↗