Biomedical subjects

Y Yu

Publications and source records attributed to Y Yu.

At least 361 records · Page 20Linked to original sources

PubMed1998

[Correction of mitral insufficiency with posterior annuloplasty].

OBJECTIVE: To summarize the experience in treating mitral insufficiency (MI), due to secondary annular dilation in the posterior portion of the annulus with mitral valve reconstruction. METHOD: Over the past 10 years, we performed mitral valvuloplasty with posterior annuloplasty in 35 patients, of which 27 patients were associated with congenital abnormalities, 3 patients had mild MI, 24 had moderate MI, and 8 had severe MI. Entire posterior annular plication was performed in 7 patients and partial posterior annular plication in 28. Associated subvalvulopasty was performed in 7 patients and leaflets repair reconstruction in 14. RESULT: There was no postoperative mortality. Complete correction was achieved in 21 patients (60.0%) and partial correction in 11 (31.4%). Mild and moderate insufficiency was found in 3 patients (8.6%) postoperatively. NYHA function class I was gained in 34 patients. One patient developed pulmonary hypertension and died due to right heart failure five years after operation. CONCLUSION: The results indicate that posterior annuloplasty is a safe, effective technique.

Adolescent↗

PubMed1998

[Ultrastructure changes of liver autolysis].

Ultra-structure changes of autolysis of hepatocyte were studied using transmission electron microscope(TEM). It was found that autolysis started 0.5 hour after death, with the heterochromatin of nuclei shrinking abnormally and smooth endoplasmic reticulum expanding. The changes developed to distinction after 1 h, and progressed continuously after 2 h, 3 h, 4 h and 5 h. It was found that (1) the mitochondria were swelling, its matrix density decreasing and flocculent dense bodies (FDB) emerging; (2) the rough endoplasmic reticulum and perinuclear cistern were expanding. It was suggested that ultra-structure changes of the autolysis be correlated to the postmortem time.

Autolysis↗

PubMed1998

[An optical model of axial reflection and its clinical application].

A developed optical model of axial reflection on retinal blood vessels has been presented in this paper. The loss of the transparency of retinal arterial vessel wall is a frequent expression of retinal vascular pathology. With the change of parameters, the model can simulate the progress of the axial reflection exactly during the onset and progression of hypertension. This non-invasive and quantitative method is useful for study in the relationship between hypertension and retinal vessel axial reflection. It can help doctors approach a diagnosis of hypertension.

Computer Simulation↗

PubMed1998

[A robust method for automated retinal vascular images mosaic based on phase correlation method and mathematical morphology].

Precise mosaic techniques are essential for quantitative evaluation of retinal images to make early detection of fundus anomalies feasible. Opening of a gray-scale image by a gray-scale structuring element(SE) can generate a background image. Image mosaic was achieved by subtraction this background image from the original image and then applying a phase correlation method to find translation difference. Because of the accuracy characteristics of the phase correlation method and the speed of the FFT hardware, this new algorithm can work very fast and accurately, compared to conventional techniques. The method was also characterized by an outstanding robustness against correlated noise and disturbances, such as those encountered with nonuniform illumination. The results confirm the robustness of the chosen approach.

Algorithms↗

PubMed1998

[Time resolved photoluminescence of PPV derivatives/C60 combination system].

We report the integrated and picosecond time-resolved photoluminescence (TRPL) measurement from two kinds of combination films: Poly(2-methoxy-5-(4-butenyloxy)phenylene vinylene) (MB-PPV)/C60 and Poly (2-methoxy-5-(4'-bromo-butoxy) phenylene vinylene) (MBB-PPV)/C60. Comparing with the pure MBB-PPV film, PL weakening and quenching of MBB-PPV were observed in the multilayer and mixed MBB-PPV/C60 films respectively. From TRPL spectra, the change of PL decay lifetime could be clearly seen, those could be attributed to the excitation transfer (ET) process between the excited MBB-PPV molecule and C60 molecule. Further measurements indicate that there is no noticeable dependence of the ET process on the temperature in the combination films.

English Abstract↗

PubMed1998

Cytokines and matrix metalloproteinases mRNA expression in archival human tissues from failed total hip arthroplasty using in situ hybridization and color video image analysis.

Reports on the histological and biochemical nature of periprosthetic fibrous/granulomatous tissue has, to date, been largely limited to frozen tissue sections. This study reports the cytokine and matrix metalloproteinase profiles found in periprosthetic interface tissues in THA which have failed due to aseptic loosening and in capsular tissues obtained at primary surgery. The study employs immunohistochemistry, in situ hybridization, and color video image analysis on formalin fixed and paraffin embedded sections.

Aged↗

PubMed1998

Hyperbaric oxygen as a signal transducer: upregulation of platelet derived growth factor-beta receptor in the presence of HBO2 and PDGF.

The purpose of this study was to test the hypothesis that hyperbaric oxygen (HBO2) may function by modifying the signal transduction pathway of growth factors or their receptors, or both. Studies were conducted with platelet derived growth factor (PDGF) and HBO2 using an established rabbit ear wound model. PDGF, a dimeric compound composed of A chain and B chain components, is found as PDGF-A, AB, and BB. It exerts its effects on cells by binding to one of two membrane-bound receptors, the alpha receptor or the beta receptor. Acutely ischemic wounds in rabbit ears were treated with saline or PDGF-BB and then animals were treated with hyperbaric air or oxygen at 2 atm abs (202.6 kPa). Hyperbaric air was without significant effect compared with control rabbits who breathed air at ambient pressure. Combined treatment with HBO2 plus PDGF-BB was synergistic in upregulating mRNA for PDGF-beta receptor. No treatments, whether alone or in combination, altered mRNA levels for PDGF-alpha receptor or for PGDF-A.

Animals↗

PubMed1997

Immunoisolation of adult porcine islets for the treatment of diabetes mellitus. The use of photopolymerizable polyethylene glycol in the conformal coating of mass-isolated porcine islets.

Functional porcine islets, free of known pathogens, can serve as a source of insulin producing cells for the treatment of experimentally induced insulin dependent Diabetes Mellitus. Porcine islets can be conformally coated (microencapsulated) with a covalently linked, stable permselective membrane while maintaining islet viability and function. The PEG conformal coating is immunoprotective in a discordant xenograft animal model (porcine islets to rat).

Animals↗

PubMed1997

GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family.

The receptor for glial cell line-derived neurotrophic factor (GDNF) consists of GFRalpha-1 and Ret. Neurturin is a GDNF-related neurotrophin whose receptor is presently unknown. Here we report that neurturin can bind to either GFRalpha-1 or GFRalpha-2, a novel receptor related to GFRalpha-1. Both GFRalpha-1 and GFRalpha-2 mediate neurturin-induced Ret phosphorylation. GDNF can also bind to either GFRalpha-1 or GFRalpha-2, and activate Ret in the presence of either binding receptor. Although both ligands interact with both receptors, cells expressing GFRalpha-1 bind GDNF more efficiently than neurturin, while cells expressing GFRalpha-2 bind neurturin preferentially. Cross-linking and Ret activation data also suggest that while there is cross-talk, GFRalpha-1 is the primary receptor for GDNF and GFRalpha-2 exhibits a preference for neurturin. We have also cloned a cDNA that apparently codes for a third member of the GFRalpha receptor family. This putative receptor, designated GFRalpha-3, is closely related in amino acid sequence and is nearly identical in the spacing of its cysteine residues to both GFRalpha-1 and GFRalpha-2. Analysis of the tissue distribution of GFRalpha-1, GFRalpha-2, GFRalpha-3, and Ret by Northern blot reveals overlapping but distinct patterns of expression. Consistent with a role in GDNF function, the GFRalphas and Ret are expressed in many of the same tissues, suggesting that GFRalphas mediate the action of GDNF family ligands in vivo.

Amino Acid Sequence↗

PubMed1997

Mu opioid receptor phosphorylation, desensitization, and ligand efficacy.

Mu opioid receptors are subject to phosphorylation and desensitization through actions of at least two distinct biochemical pathways: agonist-dependent mu receptor phosphorylation and desensitization induced by a biochemically distinct second pathway dependent on protein kinase C activation (1). To better understand the nature of the agonist-induced mu receptor phosphorylation events, we have investigated the effects of a variety of opiate ligands of varying potencies and intrinsic activities on mu receptor phosphorylation and desensitization. Exposure to the potent full agonists sufentanil, dihydroetorphine, etorphine, etonitazine, and [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) led to strong receptor phosphorylation, while methadone, l-alpha-acetylmethadone (LAAM), morphine, meperidine, DADL, beta-endorphin(1-31), enkephalins, and dynorphin A(1-17) produced intermediate effects. The partial agonist buprenorphine minimally enhanced receptor phosphorylation while antagonists failed to alter phosphorylation. Buprenorphine and full antagonists each antagonized the enhanced mu receptor phosphorylation induced by morphine or DAMGO. The rank order of opiate ligand efficacies in producing mu receptor-mediated functional desensitization generally paralleled their rank order of efficacies in producing receptor phosphorylation. Interestingly, the desensitization and phosphorylation mediated by methadone and LAAM were disproportionate to their efficacies in two distinct test systems. This generally good fit between the efficacies of opiates in mu receptor activation, phosphorylation, and desensitization supports the idea that activated receptor/agonist/G-protein complexes and/or receptor conformational changes induced by agonists are required for agonist-induced mu receptor phosphorylation. Data for methadone and LAAM suggest possible contribution from their enhanced desensitizing abilities to their therapeutic efficacies.

Analgesics, Opioid↗

PubMed1997

Functional dissection of systemic lupus erythematosus using congenic mouse strains.

We describe the in vivo phenotypes associated with three genomic intervals containing systemic lupus erythematosus (SLE)-susceptibility genes derived from the SLE-prone NZM2410 strain on a C57BL/6 genome. These intervals were identified previously via a genome-wide analysis of SLE susceptibility in a (NZM2410 x C57BL/6)F1 x NZM2410 backcross, and transferred independently on a C57BL/6 background to produce three congenic strains: B6.NZMc1 carrying Sle1, B6.NZMc4 carrying Sle2, and B6.NZMc7 carrying Sle3. B6.NZMc1 develops high titers of IgG anti-nuclear autoantibodies in the absence of any severe nephritis. B6.NZMc4 spontaneously develops elevated levels of IgM, but not IgG Abs against several Ags, indicative of polyclonal activation or polyreactivity affecting the B cell lineage. B6.NZMc7 causes the production of IgM and IgG Abs against both nuclear and non-nuclear Ags and the development of severe lupus nephritis. Therefore, our results show that three defined genomic intervals from the NZM2410 SLE-prone strain each contribute specific component phenotypes that have been associated with SLE, which in combination can mediate severe disease.

Animals↗

PubMed1997

Vitamin E inhibits apoptosis, DNA modification, and cancer incidence induced by iron-mediated peroxidation in Wistar rat kidney.

We have developed an experimental model of iron-induced oxidative nephrotoxicity and renal cancer. Using this model, the effect of vitamin E, a known antioxidant, was investigated. Three-week-old male Wistar rats were fed with vitamin E-sufficient (control) and vitamin E-supplemented diets throughout the experiment. After 1 month of feeding, iron-induced tissue lipid peroxidation, apoptosis, and formation of 8-hydroxydeoxyguanosine, a known DNA oxidative modification, were observed by cold Schiff staining, in situ labeling method (staining by terminal deoxynucleotidyl transferase-mediated nick end labeling), and high-performance liquid chromatography with electrochemical detection system, respectively, in the groups of rats treated with ferric nitrilotriacetate (Fe-NTA; Fe, 10 mg/kg body weight). For the vitamin E intervention study on Fe-NTA-induced renal carcinogenesis, two groups of rats fed vitamin E-sufficient and vitamin E-supplemented diets (30 and 20 rats, respectively) were treated with Fe-NTA (Fe, 7.5 mg/kg body weight once or twice a week) i.p. for 3 months and observed for 9 additional months. Five of the vitamin E-sufficient rats died during the first 3-month period. The results showed that vitamin E could inhibit tissue lipid peroxidation, apoptosis, 8-hydroxydeoxyguanosine formation, and the development of cancer [11 of 25 rats (44%) for vitamin E-sufficient versus 1 of 20 rats (5%) for vitamin E-supplemented rats, respectively]. These studies strongly suggest that in Fe-NTA-induced renal cancer, as with certain other types of cancer, oxidative stress plays an important role in carcinogenesis, and an antioxidant is an effective chemopreventive measure.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

1,2-Diarylimidazoles as potent, cyclooxygenase-2 selective, and orally active antiinflammatory agents.

Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mpk for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mpk) and hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

Animals↗

PubMed1997

1,2-Diarylpyrroles as potent and selective inhibitors of cyclooxygenase-2.

Series of 1,2-diarylpyrroles has been synthesized and found to contain very potent and selective inhibitors of the human cyclooxygenase-2 (COX-2) enzyme. The paper describes short and practical syntheses of the target molecules utilizing the Paal-Knorr reaction. Electrophilic substitution on 1 proceeds in a regioselective fashion, and the method was used to generate a number of tetrasubstituted pyrroles. Detailed SAR on the series has been studied by modifications of the aryl rings and the substituents in the pyrrole ring. Diarylpyrrole 1 is a very potent (COX-2, IC50 = 60 nm) and selective (COX-1/COX-2 = > 1700) inhibitor whereas the isomeric 2 is completely inactive against COX-2. Modifications of the substituents on the fluorophenyl ring in 1 yields very potent inhibitors of COX-2 (IC50 = 40-80 nm) with excellent selectivity (1200 to > 2500) vs COX-1. Analog 20 containing a sulfonamide group is an excellent inhibitor of COX-2 with an IC50 of 14 nm. Tetrasubstituted pyrroles containing groups such as COCF3, SO2CF3, or CH2OAr at position 3 in the pyrrole ring give excellent inhibitors (COX-2, IC50 = 30-120 nm). In vivo testing in the carrageenan-induced paw edema model in the rat establishes that the 1,2-diarylpyrroles are orally active antiinflammatory agents. Compound 3 is the most potent inhibitor of edema with an ED50 of 4.7 mpk.

Animals↗

PubMed1997

E2F4-RB and E2F4-p107 complexes suppress gene expression by transforming growth factor beta through E2F binding sites.

Transforming growth factor beta (TGF-beta) causes growth arrest in most cell types. TGF-beta induces hypophosphorylation of retinoblastoma susceptibility gene 1 product (RB), which sequesters E2F factors needed for progression into S phase of the cell cycle, thereby leading to cell cycle arrest at G1. It is possible, however, that the E2F-RB complex induced by TGF-beta may bind to E2F sites and suppress expression of specific genes whose promoters contain E2F binding sites. We show here that TGF-beta treatment of HaCaT cells induced the formation of E2F4-RB and E2F4-p107 complexes, which are capable of binding to E2F sites. Disruption of their binding to DNA with mutation in the E2F sites did not change the expression from promoters of E2F1, B-myb, or HsORC1 genes in cycling HaCaT cells. However, the same mutation stimulated 5- to 6-fold higher expression from all three promoters in cells treated with TGF-beta. These results suggest that E2F binding sites play an essential role in the transcription repression of these genes under TGF-beta treatment. Consistent with their repression of TGF-beta-induced gene expression, introduction of E2F sites into the promoter of cyclin-dependent kinase inhibitor p15(INK4B) gene effectively inhibited its induction by TGF-beta. Experiments utilizing Gal4-RB and Gal4-p107 chimeric constructs demonstrated that either RB or p107 could directly repress TGF-beta induction of p15(INK4B) gene when tethered to p15(INK4B) promoter through Gal4 DNA binding sites. Therefore, E2F functions to bring RB and p107 to E2F sites and represses gene expression by TGF-beta. These results define a specific function for E2F4-RB and E2F4-p107 complexes in gene repression under TGF-beta treatment, which may constitute an integral part of the TGF-beta-induced growth arrest program.

Base Sequence↗

PubMed1997

Abrogation of p53 function by HPV16 E6 gene delays apoptosis and enhances mutagenesis but does not alter radiosensitivity in TK6 human lymphoblast cells.

In order to gain a better understanding of the role of p53 in radiation-induced mitotic failure, apoptosis and mutagenesis, we introduced the HPV16 E6 gene via a retroviral vector into the TK6 human lymphoblast cell line which expresses wild type p53. Abrogation of p53 function by E6 resulted in a delayed and reduced apoptotic response and a moderate increase in the frequency of mutations at the thymidine kinase (tk) locus following gamma-irradiation, but failed to alter radiosensitivity. The apoptotic response of the E6-transduced line was intermediate between that of wild type TK6 and the WTK1 cell line. WTK1 is derived from the same parental cell line as TK6 but expresses mutant p53. The spontaneous and gamma-ray-induced mutation frequencies in E6-transduced TK6 cells, although higher than that of the parental TK6 cell line, were still much lower than that of the WTK1 line. No effect on apoptosis, radiosensitivity or mutability was observed when the HPV16 E6 gene was introduced into the WTK1 cells. These results indicate that p53 does not regulate the radiosensitivity of TK6 cells through the apoptotic pathway. Furthermore, the previously observed enhanced radioresistance and mutability in WTK1 cells must be attributed to a more complex mechanism than p53 status alone.

Apoptosis↗

PubMed1997

The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz.

Homeobox genes specify cell fate and positional identity in embryos throughout the animal kingdom. Paradoxically, although each has a specific function in vivo, the in vitro DNA-binding specificities of homeodomain proteins are overlapping and relatively weak. A current model is that homeodomain proteins interact with cofactors that increase specificity in vivo. Here we use a native binding site for the homeodomain protein Fushi tarazu (Ftz) to isolate Ftz-F1, a protein of the nuclear hormone-receptor superfamily and a new Ftz cofactor. Ftz and Ftz-F1 are present in a complex in Drosophila embryos. Ftz-F1 facilitates the binding of Ftz to DNA, allowing interactions with weak-affinity sites at concentrations of Ftz that alone bind only high-affinity sites. Embryos lacking Ftz-F1 display ftz-like pair-rule cuticular defects. This phenotype is a result of abnormal ftz function because it is expressed but fails to activate downstream target genes. Cooperative interaction between homeodomain proteins and cofactors of different classes may serve as a general mechanism to increase HOX protein specificity and to broaden the range of target sites they regulate.

Animals↗

PubMed1997

Differential dose delivery using a nondocking applicator for intraoperative radiation therapy.

PURPOSE: Although treatment of a field within a field to deliver a boost dose is quite common with external photon beam radiation therapy, the same is not always true with electron beam radiation or in intraoperative radiation therapy (IORT). The purpose of this work is to report the results and details of a new technique developed to treat a field within a field in intraoperative radiation therapy. METHODS AND MATERIALS: This technique makes use of the nondocking IORT system currently used at our institution. Treatment is given in two segments: the large field is first treated by using standard circular lucite cones; the second dose segment is delivered using a new circular brass cone designed to fit concentrically within the large lucite cone. RESULTS: Central axis depth dose, surface dose, output factors, and two-dimensional beam profiles have been measured for a 7 cm inner diameter (i.d.) flat lucite cone and 3.8 and 5 cm i.d. flat brass cones for electron beam energies ranging from 4-22 MeV. For different clinical target volumes, summed dose distributions differentially weighted in both energy and dose are presented. CONCLUSIONS: A simple technique for delivering differential dose in intraoperative radiation therapy is presented. The technique provides a method for escalating dose to higher values for a defined target volume.

Equipment Design↗