Biomedical subjects

Bing Li

Publications and source records attributed to Bing Li.

At least 37 records · Page 2Linked to original sources

PubMed2006

Potent antagonists of the Kv1.5 potassium channel: synthesis and evaluation of analogous N,N-diisopropyl-2-(pyridine-3-yl)acetamides.

This letter describes the discovery of a novel series of potent Kv1.5 ion channel antagonists based on a diisopropyl amide scaffold. Structure-activity relationships of functionalized analogs are discussed. Key compound 1-(3-(diisopropylcarbamoyl)-2-phenyl-3-(pyridin-3-yl)propyl)-3-(2-fluorobenzyl)urea (10) exhibits significant atrial-selective effects in an in vivo model.

Acetamides↗

PubMed2006

[Establishment of liver metastasis model of human gallbladder cancer and isolation of the subpopulation with high metastatic potential].

OBJECTIVE: To establish an experimental liver metastatic model of gallbladder cancer and isolate the subpopulation with high metastatic potential from the model, which may serve as a reliable tool in research on liver metastasis of gallbladder cancer in vivo and in vitro. METHODS: Human gallbladder cancer cells of the line GBC-SD were cultured. Ten nude athymic BALB/c mice, aged 4 approximately 5 weeks, underwent inoculation of suspension of GBC-SD cells into the spleens and then their spleens were resected. Three weeks later laparotomy was performed to observe if liver metastasis occurred. Once liver metastasis was discovered, the mice were killed and the livers were taken out to undergo microscopy, tumor cells were isolated from the metastatic foci and cultured in vitro, and then inoculated into other 10 mice in the same way as their parents cells for the second round of selection. The similar steps were repeated, altogether for three rounds of selection and a total 30 mice were inoculated in 3 rounds so as to find subpopulation with high metastatic potential. Another 10 mice underwent subcutaneous inoculation, 90 days later the mice were killed to observe if pulmonary metastasis occurred. PCR was used to detect the 3 microsatellite sequences D14S68, D18S69, and D20S199 in the DNA samples of the gallbladder cancer cells of the parent cell line GBC-SD, the isolated cells of the subpopulation with high metastatic potential, and the liver of experimental animal. RESULTS: 90% of the mice inoculated subcutaneously with the GBC-SD cells developed subcutaneous tumors, however, no mouse in this group died and no pulmonary metastasis was found. The liver metastatic rate was 65% in the 10 mice undergoing intrasplenic inoculation. Thus a metastatic model of human gallbladder cancer in nude mice was established. The liver metastatic tumors were uniformly distributed throughout the liver parenchyma with predominance to the periphery. Despite multiple sites of involvement, the left lobes were most commonly affected in all experimental animals. Histological examination of the metastatic lesion demonstrated adenocarcinoma. Gross hepatic metastasis was detected 10, 7, and 5 weeks after the inoculation respectively in the first, second, and third round selection respectively with an incidence rate of metastases of 60%, 70%, and 90% respectively. From the third round metastatic model a subpopulation with high metastatic potential was isolated and designated as GBC-SD/M, which exhibited the similar histological characteristics as its parent cell line GBC-SD under inverted light microscopy. The three amplified bands at the sites 14S68, D18S69, and D20S199, amplified with the three pairs of specific primers for the three homo-specific microsatellites, were detected in the GBC-SD cells and GBC-SD/M cells, but not in the liver of tumor-bearing animal. CONCLUSION: A liver metastasis model of human gallbladder cancer has been established, a reliable and efficient tool for study on the metastasis of gallbladder cancer to liver in vivo. Isolated from hepatic metastasis, the line of GBC-SD/M is a subpopulation with high metastatic potential, retaining the histological properties and identification of genetic background of its parent cell line GBC-SD.

Animals↗

PubMed2006

T-bet expression in the iris and spleen parallels disease expression during endotoxin-induced uveitis.

BACKGROUND: T lymphocytes have been implicated in the development of endotoxin-induced uveitis (EIU). T-bet is a Th1 cell-specific transcription factor that is involved in differentiation and effector functions. The aim of this study was to investigate kinetics of T-bet expression at the mRNA and protein levels during EIU using real-time PCR and whole-mount immunohistochemistry. METHODS: A single footpad injection of 200 mug of lipopolysaccharide (LPS) was administered to male Wistar rats in order to induce EIU. Clinical changes were followed by slit-lamp examination. The expression of T-bet mRNA in the spleen was evaluated 0, 8, 16, 24, 48, and 96 h after LPS injection using real-time PCR. Immunohistochemistry was performed on the iris whole-mounts as well as on frozen sections of the spleen to evaluate T-bet protein expression. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed on the iris whole-mounts to assay apoptotic cells. RESULTS: Uveitis was observed in all rats that received LPS. T-bet(+) cells and TUNEL(+) cells in the iris whole-mounts showed a similar pattern in cell number and distribution and both types of cells were observed at 8 h, significantly increased 24 h, and decreased 48 h after LPS injection. T-bet expression at both the mRNA and protein levels in spleen also paralleled ocular inflammation. It was weakly detectable after 0 h, increased after 8 h (index 1.3, T-bet(+) cells OD 17.43+/-2.15), reached its peak after 24 h (index 4.00, OD 53.52+/-4.00), and decreased 48 h following LPS injection (index 1.38, OD 25.75+/-2.45). CONCLUSIONS: The results show that T-bet expression in both the iris and the spleen, and in apoptotic cells in the iris parallel the severity of intraocular inflammation after systemic LPS administration. These results suggest that T-bet may play a significant role in the dynamics of EIU.

Animals↗

PubMed2006

Yeast beta-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway.

Anti-tumor mAbs hold promise for cancer therapy, but are relatively inefficient. Therefore, there is a need for agents that might amplify the effectiveness of these mAbs. One such agent is beta-glucan, a polysaccharide produced by fungi, yeast, and grains, but not mammalian cells. Beta-glucans are bound by C receptor 3 (CR3) and, in concert with target-associated complement fragment iC3b, elicit phagocytosis and killing of yeast. Beta-glucans may also promote killing of iC3b-opsonized tumor cells engendered by administration of anti-tumor mAbs. In this study, we report that tumor-bearing mice treated with a combination of beta-glucan and an anti-tumor mAb show almost complete cessation of tumor growth. This activity evidently derives from a 25-kDa fragment of beta-glucan released by macrophage processing of the parent polysaccharide. This fragment, but not parent beta-glucan, binds to neutrophil CR3, induces CBRM 1/5 neoepitope expression, and elicits CR3-dependent cytotoxicity. These events require phosphorylation of the tyrosine kinase, Syk, and consequent PI3K activation because beta-glucan-mediated CR3-dependent cytotoxicity is greatly decreased by inhibition of these signaling molecules. Thus, beta-glucan enhances tumor killing through a cascade of events, including in vivo macrophage cleavage of the polysaccharide, dual CR3 ligation, and CR3-Syk-PI3K signaling. These results are important inasmuch as beta-glucan, an agent without evident toxicity, may be used to amplify tumor cell killing and may open new opportunities in the immunotherapy of cancer.

Adjuvants, Immunologic↗

PubMed2006

Activation of the proapoptotic death receptor DR5 by oligomeric peptide and antibody agonists.

The cell-extrinsic apoptotic pathway triggers programmed cell death in response to certain ligands that bind to cell-surface death receptors. Apoptosis is essential for normal development and homeostasis in metazoans, and furthermore, selective activation of the cell-extrinsic pathway in tumor cells holds considerable promise for cancer therapy. We used phage display to identify peptides and synthetic antibodies that specifically bind to the human proapoptotic death receptor DR5. Despite great differences in overall size and structure, the DR5-binding peptides and antibodies shared a tripeptide motif, which was conserved within a disulfide-constrained loop of the peptides and the third complementarity determining region of the antibody heavy chains. The X-ray crystal structure of an antibody in complex with DR5 revealed that the tripeptide motif is buried at the core of the interface, confirming its central role in antigen recognition. We found that certain peptides and antibodies exhibited potent proapoptotic activity against DR5-expressing SK-MES-1 lung carcinoma cells. These phage-derived ligands may be useful for elucidating DR5 activation at the molecular level and for creating synthetic agonists of proapoptotic death receptors.

Amino Acid Sequence↗

PubMed2006

A highly efficient chemoenzymatic approach toward glycoprotein synthesis.

[reaction: see text] A highly efficient endoglycosidase-catalyzed synthesis of homogeneous glycoproteins is described. By using ribonuclease B as a model system, it was demonstrated that Endo-A could efficiently attach a preassembled oligosaccharide to a GlcNAc-containing protein in a regio- and stereospecific manner, when the corresponding sugar oxazoline was used as the donor substrate. The method allows the synthesis of both natural and tailor-made N-linked glycoproteins in excellent yield.

Carbohydrate Sequence↗

PubMed2006

Alternative splicing of delta-like 1 homolog (DLK1) in the pig and human.

Delta-like homolog 1 (DLK1), a paternally imprinted gene with several alternative splicing isoforms, is an important regulator of fetal and postnatal development. We report the sequence of porcine DLK1 (pDLK1) and examine the expression and alternative splicing isoforms in the pig (Sus scrofa) and human. DLK1-A was the sole isoform identified in human tissues and has been shown to be present in mouse and cattle. Surprisingly, DLK1-A was undetected in various tissues from fetal and postnatal pigs. Instead, DLK1-C2 was the most abundant isoform while DLK1-B was expressed to a lesser extent. In fractionated adipose tissue, pDLK1 was most highly expressed in the stromal-vascular cell fraction. In addition, total pDLK1 was highly expressed in fetal adipose tissue but dramatically decreased postnatally. Our data suggests that expression of DLK1-B and -C2 isoforms is sufficient for normal pig development. Furthermore, human and pig samples showed no alterations in species-specific splicing, but expression levels decreased with age, suggesting that regulation of expression, not splicing, is the most likely mechanism controlling the biological function of DLK1.

Adipocytes↗

PubMed2006

Role of T-cell receptor V beta 8.3 peptide vaccine in the prevention of experimental autoimmune uveoretinitis.

BACKGROUND: T-cell receptor (TCR) plays an important role in the development of autoimmune diseases. Recently, it was reported that immunization of animals with TCR peptide derived from the pathogenic cells could prevent autoimmune diseases. The aim of this study was to investigate whether vaccination with a synthetic peptide from the hypervariable region of TCR V(beta) 8.3, an experimental autoimmune uveoretinitis (EAU)-associated gene, was able to prevent the disease. METHODS: EAU was induced in Lewis rats by immunization with IRBP R16 peptide emulsified in complete Freund's adjuvant (CFA). The clinical and histological appearances were scored. Delayed type hypersensitivity (DTH) and lymphocyte proliferation were detected. Cytokine levels of aqueous humour, supernatants of cells from spleen and draining lymph nodes were measured by enzyme linked immunosorbent assay (ELISA). Gene expression of TCR V(beta) 8.3 on CD(4)(+) T cells was examined by real time quantitative polymerase chain reaction (PCR). RESULTS: After vaccination, the intraocular inflammation was significantly mitigated, antigen specific DTH and lymphocyte proliferation responses were suppressed, interleukin (IL)-2 in aqueous humour, interferon (IFN)-gamma and IL-2 produced by the spleen and draining lymph node cells were significantly decreased, whereas the production of IL-4 and IL-10 were increased. The response of draining lymph node cells to TCR V(beta) 8.3 peptide was enhanced after vaccination. Inoculation with CFA alone did not affect the severity of EAU and the above parameters. The suppression of EAU was much stronger in the group of four fold inoculations than the group of two fold inoculations. The expression of TCR V(beta) 8.3 gene was significantly reduced in the group of fourfold inoculations. CONCLUSION: Vaccination with the synthetic TCR V(beta) 8.3 peptide could remarkably inhibit the development of EAU.

Animals↗

PubMed2006

Glycopeptide synthesis through endo-glycosidase-catalyzed oligosaccharide transfer of sugar oxazolines: probing substrate structural requirement.

An array of sugar oxazolines was synthesized and tested as donor substrates for the Arthrobacter endo-beta-N-acetylglucosaminidase (Endo-A)-catalyzed glycopeptide synthesis. The experiments revealed that the minimum structure of the donor substrate required for Endo-A catalyzed transglycosylation is a Man beta1-->4-GlcNAc oxazoline moiety. Replacement of the beta-D-Man moiety with beta-D-Glc, beta-D-Gal, and beta-D-GlcNAc monosaccharides resulted in the loss of substrate activity for the disaccharide oxazoline. Despite this, the enzyme could tolerate modifications such as attachment of additional sugar residues or a functional group at the 3- and/or 6-positions of the beta-D-Man moiety, thus allowing a successful transfer of selectively modified oligosaccharides to the peptide acceptor. On the other hand, the enzyme has a great flexibility for the acceptor portion and could take both small and large GlcNAc-peptides as the acceptor. The studies implicate a great potential of the endoglycosidase-catalyzed transglycosylation for constructing both natural and selectively modified glycopeptides.

Amino Acid Sequence↗

PubMed2006

Effects of hypobaric hypoxia on adenine nucleotide pools, adenine nucleotide transporter activity and protein expression in rat liver.

AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver. METHODS: Adult male Wistar rats were exposed to a hypobaric chamber simulating 5,000 m high altitude for 23 h every day for 0 (H0), 1 (H1), 5 (H5), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by decapitation and liver was removed. Liver mitochondria were isolated by differential centrifugation program. The size of adenine nucleotide pool (ATP, ADP, and AMP) in tissue and mitochondria was separated and measured by high performance liquid chromatography (HPLC). The adenine nucleotide transporter (ANT) activity was determined by isotopic technique. The ANT total protein level was determined by Western blot. RESULTS: Compared with H0 group, intra-mitochondrial ATP content decreased in all hypoxia groups. However, the H5 group reached the lowest point (70.6%) (P<0.01) when compared to the control group. Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups and were significantly lower than that in H0 group. In addition, extra-mitochondrial ATP and ADP content decreased significantly in all hypoxia groups. Furthermore, extra-mitochondrial AMP in groups H5, H15 and H30 was significantly lower than that in H0 group, whereas H1 group had no marked change compared to the control situation. The activity of ANT in hypoxia groups decreased significantly, which was the lowest in H5 group (55.7%) (P<0.01) when compared to H0 group. ANT activity in H30 group was higher than in H15 group, but still lower than that in H0 group. ANT protein level in H5, H15, H30 groups, compared with H0 group decreased significantly, which in H5 group was the lowest, being 27.1% of that in H0 group (P<0.01). ANT protein level in H30 group was higher than in H15 group, but still lower than in H0 group. CONCLUSION: Hypobaric hypoxia decreases the mitochondrial ATP content in rat liver, while mitochondrial ATP level recovers during long-term hypoxia exposure. The lower level of extra-mitochondrial ATP may be related to the decrease of ANT activity during hypoxia exposure.

Adenine Nucleotides↗

PubMed2006

Assessing record linkage between health care and Vital Statistics databases using deterministic methods.

BACKGROUND: We assessed the linkage and correct linkage rate using deterministic record linkage among three commonly used Canadian databases, namely, the population registry, hospital discharge data and Vital Statistics registry. METHODS: Three combinations of four personal identifiers (surname, first name, sex and date of birth) were used to determine the optimal combination. The correct linkage rate was assessed using a unique personal health number available in all three databases. RESULTS: Among the three combinations, the combination of surname, sex, and date of birth had the highest linkage rate of 88.0% and 93.1%, and the second highest correct linkage rate of 96.9% and 98.9% between the population registry and Vital Statistics registry, and between the hospital discharge data and Vital Statistics registry in 2001, respectively. Adding the first name to the combination of the three identifiers above increased correct linkage by less than 1%, but at the cost of lowering the linkage rate almost by 10%. CONCLUSION: Our findings suggest that the combination of surname, sex and date of birth appears to be optimal using deterministic linkage. The linkage and correct linkage rates appear to vary by age and the type of database, but not by sex.

Adolescent↗

PubMed2006

Development and characterization of LLC-PK1 cells containing Sprague-Dawley rat Abcb1a (Mdr1a): comparison of rat P-glycoprotein transport to human and mouse.

INTRODUCTION: P-glycoprotein is localized in numerous tissues throughout the body and plays an important role in the disposition of many xenobiotics. The contribution of P-glycoprotein-mediated drug transport is being evaluated in early drug discovery stages, particularly for compounds targeted to the central nervous system, using in vitro tools including cell lines expressing P-glycoprotein. Previous work in our laboratory suggests there are species differences in P-glycoprotein transport activity between humans and animals. The rat Abcb1a form of P-glycoprotein (formerly known as Mdr1a), the predominate isoform in the brain, has not been described in a functional cell system. Here, we describe the development and characterization of LLC-PK1 cells expressing rat Abcb1. METHODS: We cloned rat Abcb1a and generated a stable LLC-PK1 cell line. Expression and function of the cells were evaluated by immunoblot analysis, cytotoxicity analysis, cellular accumulation assays, and transcellular transport of probe substrates. The transport ratios of structurally diverse compounds obtained from parental cells or cells stably transfected with human ABCB1, mouse Abcb1a or rat Abcb1a were compared. RESULTS: Two forms of rat Abcb1a were cloned from Sprague-Dawley cDNA that differ by six amino acids and a base pair deletion. The intact form was stably transfected in LLC-PK1 cells. Immunoblot analysis demonstrated expression of the protein. The cells demonstrated P-glycoprotein-mediated function by directional transport of dexamethasone, ritonavir, and vinblastine in a transwell assay that was inhibited in the presence of cyclosporin A, verapamil, or quinidine. Likewise, the cells showed reduced cellular accumulation of Rh123 by FACS analysis that was reversed in the presence of cyclosporin A. These cells showed >or=350-fold resistance to colchicine, doxorubicin, vinblastine, and taxol and were sensitized in the presence of verapamil or cyclosporin A. Of 179 chemically diverse compounds evaluated, approximately 20% of the compounds evaluated were predicted to be substrates in one species but not in other species. DISCUSSION: Taken together, these data suggest these cells will be useful for evaluation of rat Abcb1a-mediated transport and for evaluation of species-specific P-glycoprotein-mediated transport.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2006

OVA-specific CD8+ T cells do not express granzyme B during anterior chamber associated immune deviation.

PURPOSE: To examine antigen (Ag)-specific CTL response during anterior chamber associated immune deviation (ACAID). METHODS: OVA or OVA257-264 peptide was injected into the anterior chamber (AC) of C57BL/6 mice. There were 16 mice in each ACAID group induced with OVA or OVA257-264 peptide. The mice were primed by SC injection with OVA or OVA 257-264 peptide in complete Freund's adjuvant (CFA) on day 7. Ag-specific CD8+ T cells in spleens were analyzed on day 14 using Pentamer H-2K(b)-SIINFEKL(OVA257-264 peptide). IFN-gamma ELISPOT and intracellular granzyme B staining were used to characterize the CTL response. Twelve mice in each group immunized with OVA or OVA257-264 peptide in CFA served as positive controls. Twelve normal mice served as negative controls and 12 receiving injection of CFA as CFA controls for studying the influence of CFA on the Ag-specific CTL response. RESULT: The results showed that anterior chamber inoculation of OVA or OVA257-264 peptide could induce ACAID as evidenced by an impaired DTH response. The frequency of Ag-specific CD8+ T cells in ACAID mice was not different from that in mice challenged with Ags in CFA only (positive controls). IFN-gamma production by these cells in ACAID mice was not different compared to positive controls. However, Ag-specific CD8+ T cells in ACAID mice failed to secrete granzyme B. Mice challenged only with OVA peptide and CFA also showed a granzyme B negative CD8+ T cell response. Ag-specific CTL response induced by CFA alone was similar with the negative control. CONCLUSION: These results show that the frequency of Ag-specific CD8+ T cells is not altered during ACAID. The Ag-specific CTL response during ACAID is characterized by the absence of granzyme B expression.

Animals↗

PubMed2006

High-level expression, purification, and characterization of non-tagged Aspergillus flavus urate oxidase in Escherichia coli.

The entire encoding region for Aspergillus flavus uricase was cloned into pET-32a and expressed in Escherichia coli BL21 (DE3). The uricase was expressed in the E. coli cytoplasm in a completely soluble, biologically active form. A scalable process aimed to produce and purify multi-gram quantities of highly pure, recombinant urate oxidase (rUox) from E. coli was developed. The rUox protein was produced in a 30 L fermentor containing 25 L of 2x YT medium and purified to >99% purity using hydrophobic interaction, anion-exchange, and gel filtered chromatography. The final yield of purified rUox from fermentation resulted in approximately 27 g of highly pure, biologically active rUox per kg of cell paste (approximately 238 mg/8.8 g cell paste/L). The results presented here exhibit the ability to generate multi-gram quantities of rUox from E. coli that may be used for the development of pharmaceutics of reducing the hyperuricemia.

Aspergillus flavus↗

PubMed2006

Effects of sodium arsenite on catalase activity, gene and protein expression in HaCaT cells.

The objective of this research work is to study the effects of sodium arsenite on activity, mRNA and protein expression of catalase (CAT) in established human cell lines of keratinocytes (HaCaT). Based on the AlamarBlue assay, we found that a high level (100 micromol/l) of sodium arsenite inhibited cell viability. The reactive oxygen species (ROS) content in cells was increased in all treated cultures dose-dependently. CAT activity, mRNA expression and protein levels were decreased by 5-20 micromol/l of sodium arsenite. It is highly suggestive that CAT gene expression and protein levels are affected by arsenic.

Arsenites↗

PubMed2006

[Characteristics of adenine nucleotide translocator in mitochondria of rat cerebral cortex during hypobaric hypoxia exposure].

The purpose of the present study was to explore the effects of hypoxic exposure on mitochondrial adenine nucleotide translocator (ANT) activity and its characteristics. Male Wistar rats were exposed to hypoxia in a hypobaric chamber simulating high altitude at 5 000 m for 1, 5, 15 and 30 d. Control rats were fed outside the hypobaric chamber. Rats were sacrificed by decapitation and mitochondria from the cerebral cortex were isolated by differential centrifugation at each time point. The ANT activity was detected by the atractyloside (ATR)-inhibitor stop technique. Mitochondria was initiated by addition of (3)H-ADP and terminated after 12 s by quick addition of ATR. The radioactivity was measured in a liquid scintillation counter. Nonspecific binding of (3)H-ADP to mitochondria was estimated by incubation of mitochondrial samples with ATR prior to the addition of (3)H-ADP. This blank was substracted from the measured radioactivities. The activity of ANT was expressed as nanomoles (3)H-ADP per minute per milligram protein. The ANT density was determined by titrating the rate of state 3 respiration with increasing concentrations of carboxyatractyloside (CAT). Mitochondria were pre-incubated with CAT in a respiratory medium before ADP addition to initiate state 3 respiration. Plots of O2 consumption versus CAT appeared biphasic with an increasing inhibitory segment followed by a steady respiration, indicating that state 3 respiration was completely inhibited. The density of ANT was determined by the amount of CAT required to completely inhibit state 3 respiration, assuming a 1:1 binding stoichiometry, which was expressed as ANT density per milligram mitochondria protein. (ATP+ADP) in mitochondria was measured by high performance liquid chromatography (HPLC). The results showed that there was an obvious decrease in the ANT activity during hypoxic exposure. The lowest ANT activity was seen in 5 d group. Partial recovery of ANT activity was observed in 15 and 30 d groups, but ANT activity was still lower than that in the control group (P<0.01). Compared with that in normoxic control group, no change of ANT density in mitochondria was observed in hypoxia group (P>0.05). The turnover number of ANT in control, 1, 5, 15, 30 d groups were 16.67, 1.90, 0.40, 1.81, 4.73 pmol ADP/(min.pmol ANT), respectively. However, (ATP+ADP) in mitochondria in 1, 5, 15, 30 d groups were 63.37%, 48.44%, 52.73%, 60.16% of control group respectively. Therefore, the turnover number of energy production and expenditure were reduced. These observations suggest that the change of ANT activity may be one of the mechanisms of cellular oxidative phosphorylation dysfunction during hypoxic exposure.

Altitude↗

PubMed2006

Clinical features of Chinese patients with Fuchs' syndrome.

PURPOSE: To characterize the clinical features of Chinese patients with Fuchs' syndrome. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred eighteen eyes of 104 consecutive patients with Fuchs' syndrome initially examined between January 1999 and March 2005. METHODS: The history and clinical findings of all consecutive Fuchs' patients attending the Zhongshan Ophthalmic Center were reviewed. Auxiliary examinations, including laser flare-cell photometry, ultrasound biomicroscopy (UBM), fundus fluorescein angiography (FFA), and serologic tests for Toxoplasma gondii, were performed in certain cases. MAIN OUTCOME MEASURES: Patients' demographics, clinical presentation, and auxiliary examination findings. RESULTS: One hundred four patients (49 male, 55 female) were included in this study. Unilateral involvement was noted in 90 patients (86.5%). The most common symptom was blurred or decreased vision (86%). Stellate and medium-sized keratic precipitates (KPs) were noted in 108 eyes (91.5%). A mild anterior chamber (AC) reaction was observed in all the affected eyes. Heterochromia was observed in only 15 affected eyes, although there were varying degrees of iris depigmentation in all patients. Iris nodules, mostly Koeppe, were present in 28.0% of the affected eyes. Complicated cataract, vitreous opacity, and secondary glaucoma were observed in 84 of 118 eyes (70.7%), 31 eyes of 42 eyes (73.8%), and 24 of 118 eyes (23.1%), respectively. The mean laser flare photometry value (6.4+/-2.3 photon counts per millisecond) and the cell number in the AC (1.5+/-1.2 cells per 0.5 mm3) in 25 patients were both significantly higher than those in 25 healthy controls (5.3+/-2.3 photon counts per millisecond and 0.8+/-0.6 cells per 0.5 mm3) (P<0.05). Ultrasound biomicroscopy revealed exudates adjacent to the ciliary body in 18 of 24 patients (75%). Serological tests failed to confirm an association of Fuchs' syndrome with toxoplasmosis. Retinal capillary leakage in the midperipheral fundus and disc staining at the late stage were observed in most of the eyes examined by FFA. CONCLUSION: Fuchs' syndrome in Chinese patients is characterized by a mild uveitis with characteristic KPs, varying degrees of iris depigmentation, and, occasionally, heterochromia. Exudates adjacent to the ciliary body and subclinical retinal and optic nerve involvement were common in the patients who were studied by UBM and FFA.

Adolescent↗

PubMed2006

Inducible co-stimulator (ICOS) is upregulated in experimental autoimmune uveoretinitis.

PURPOSE: To study the expression of inducible co-stimulator (ICOS) and its association with T cell effector function in experimental autoimmune uveoretinitis (EAU). METHODS: Eighteen Lewis rats were immunized by retinal S-antigen (50 microg) emulsified in complete Freund's adjuvant (CFA). Twelve normal rats served as normal controls and 18 receiving injection of CFA and PBS as CFA controls for studying the influence of CFA on the expression of ICOS in CD4+CD25+ T cells. ICOS expression on cells from the spleens, inguinal nodes and retinae on day 0 (normal rats), 7, 13 and 21 was investigated using fluorescent quantitative real-time-PCR and Western blot. Expression of B7RP-1, an ICOS ligand, was also studied by Western blot. The phenotype of the cells from the aforementioned three tissues was identified with flow cytometry using antibodies to ICOS, CD4 and CD25. ICOS+ cells from the lymph nodes, and spleens on day 13 were magnetically sorted and cultured with S-antigen to study the cytokines production with enzyme-linked immunosorbent assay. RESULT: An obvious uveitis was induced in all the immunized rats on day 13 after S-antigen immunization. The mRNA and protein of ICOS were scarcely detectable in normal rat spleens. In EAU rats, an up-regulation of ICOS could be observed on day 7 and was very pronounced on day 13, followed by a decrease on day 21 in the spleens, draining nodes and retinae. Similarly, B7RP-1 expression seemed to be up-regulated during EAU. Flow cytometry showed that ICOS+ cells were mostly CD4 positive. Kinetics of ICOS+CD4+CD25+ T cells was similar to that of ICOS+ cells. CFA alone was also able to induce increased expression of ICOS in CD4+CD25+ T cells. IFN-gamma was secreted predominantly by ICOS+ T cells. CONCLUSION: ICOS expression is up-regulated in association with T cell effector capacity in EAU. It is presumed that the ICOS/B7RP-1 costimulatory pathway may play a role in the development of EAU.

Animals↗