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Biomedical subjects

Y Jin

Publications and source records attributed to Y Jin.

At least 37 records · Page 2Linked to original sources

Extracellular ATP opposes thrombin-induced myosin light chain phosphorylation and loss of barrier integrity in corneal endothelial cells.

Increased contractility of the actin cytoskeleton by phosphorylation of the regulatory myosin light chain (MLC) results in a loss of barrier integrity in corneal endothelial cells. This study has investigated the effect of extracellular ATP, which may influence both Ca2+ and cAMP signalling, on MLC phosphorylation and barrier integrity in cultured bovine corneal endothelial cells (BCEC) known to express A2B and P2Y purinergic receptors, and ecto-nucleotidases. Extracellular ATP (100 microM) promoted MLC dephosphorylation (pMLC=61.8% at 18 min; n=9). Pre-exposure to ARL-67156, an ecto-nucleotidase inhibitor, prevented ATP-induced dephosphorylation. Other P2Y agonists, UTP and ATPgammaS, also induced MLC dephosphorylation but to a lesser degree compared to ATP. Thrombin (2 U/ml), which activate Rho kinase through PAR-1 receptors in the endothelium, induced MLC phosphorylation (pMLC=129.2%; n=14). This phosphorylation was completely abolished by concomitant exposure to ATP. When cells were pretreated with adenosine (100 microM; A2B agonist) or forskolin (10 microM), thrombin-induced phosphorylation was suppressed. ATP also led to a significant increase in cAMP (> 3-fold compared to 10 microM adenosine). Thrombin-induced increase in trans-endothelial flux of horseradish peroxidase (44 kDa) and disruption of the cortical actin were suppressed by ATP. These findings indicate that in BCEC (1) ATP induces elevated cAMP through its metabolite adenosine leading to MLC dephosphorylation, (2) Stimulation of P2Y2 receptors also leads to activation of MLCP since UTP- and ATPgammaS caused MLC dephosphorylation, and (3) ATP is antagonistic to thrombin since the latter inhibits MLCP through increased activity of Rho kinase. These findings further emphasize the role of contractility of the actin cytoskeleton in regulating the barrier integrity of corneal endothelium.

Actins↗

Identification of a novel HLA-A*0278 allele in a Chinese family.

A novel human leukocyte antigen-A (HLA-A) allele, A*0278, has been identified in a Chinese family using DNA-based typing and molecular cloning methods. The alleles A*0278 differs from its closest matching HLA sequence of A*0256 by a silent substitution at 102 A > C and by two replacement substitutions, 98T > A and 292 C > G in exon 2, resulting in a change of codon 33 from Phe (TTC) to Tyr (TAC) and codon 98 from His (CAC) to Asp (GAC). Serology study revealed that A*0278 is associated with HLA-A2 broad specificity. A polymerase chain reaction-sequence-specific primers-based assay was developed to identify A*0278. Family study indicated that the propositus inhered his father's HLA haplotype A*0278, B*35, DRB1*15. No further individuals of A*0278 were found in 5000 Chinese bone marrow donor volunteers.

Alleles↗

Nanoscopic modeling of fracture of 2D graphene systems.

Macroscopic fracture parameters are investigated on 2D graphene systems containing atomic-scale cracks. In the discrete atomistic simulations the interatomic forces are described by the Tersoff-Brenner potential. Two methods to calculate the elastic energy release rates in atomic systems, the global energy method and the local force method, are developed. The values of energy release rates of several graphene systems in symmetric (mode I) and antisymmetric (mode II) small deformation are obtained from atomistic simulations and then compared with the results obtained through homogenized material properties based on linear elastic fracture mechanics. The results show good agreement between discrete atomistic and continuum mechanics modeling for fracture. Meanwhile, atomic stress fields in front of crack tips are investigated through molecular mechanics simulation by applying remote K-field deformation. The atomic stress distributions match very well with those of linear elastic solutions. These establish connections of fracture parameters between microscopic and macroscopic description of fracture in covalently bonded solids.

Carbon↗

Atomistic simulations of J-integral in 2D graphene nanosystems.

The J-integral is investigated in discrete atomic systems using molecular mechanics simulations. A method of calculating J-integral in specified atomic domains is developed. Two cases, a semiinfinite crack in an infinite domain under the remote K-field deformation and a finite crack length in a finite geometry under the tensile and shear deformation prescribed on the boundary, are studied in the two-dimensional graphene sheets and the values of J-integral are obtained under small-strain deformation. The comparison with energy release rates in Mode I and Mode II based on continuum theory of linear elastic fracture mechanics show good agreements. Meanwhile, the nonlinear strain and stress relation of a 2D graphene sheet is evaluated and is fitted with a power law curve. With necessary modifications on the Tersoff-Brenner potential, the critical values of J-integral of 2D graphene systems, which denoted as Jc, are eventually obtained. The results are then compared with those from the relevant references.

Models, Theoretical↗

The participation of myofibroblasts in the capsular formation of human conventional and chromophobe renal cell carcinomas.

The presence of myofibroblasts has been elucidated in neoplastic capsules of various organs. In the present article, we examine the presence of myofibroblasts in the capsule of renal cell carcinoma (RCC) and discuss the origin of the myofibroblasts. Nineteen renal tumors (conventional RCC, n=17; chromophobe RCC, n=2) with evident and totally surrounded fibrous capsule were selected. Abundant myofibroblasts were immunohistochemically observed in the capsule of the RCCs. These findings were confirmed by electron and immunoelectron microscopic studies of three conventional RCCs. Type III and I collagens were predominant in the outer and inner layers of the RCC capsule, respectively. The cytoplasm of the tubular epithelial cells in the tissue surrounding the neoplastic capsule stained positively for transforming growth factor (TGF)-beta 1. In situ hybridization detected type I collagen mRNA in myofibroblasts of the capsule. Myofibroblasts may participate in the capsular formation of conventional and chromophobe RCCs through the collagen production.

Carcinoma, Renal Cell↗

Observation of a threshold enhancement in the plambda invariant-mass spectrum.

An enhancement near the m(p)+M(Lambda) mass threshold is observed in the combined pLambda and pLambda invariant-mass spectrum from J/psi-->pK(-)Lambda;+c.c. decays. It can be fit with an S-wave Breit-Wigner resonance with a mass m=2075+/-12(stat)+/-5(syst) MeV and a width of Gamma=90+/-35(stat)+/-9(syst) MeV; it can also be fit with a P-wave Breit-Wigner resonance. Evidence for a similar enhancement is also observed in psi(')-->pK(-)Lambda;+c.c. decays. The analysis is based on samples of 5.8x10(7)J/psi and 1.4x10(7)psi(') decays accumulated in the BES II detector at the Beijing Electron-Positron Collider.

Journal Article↗

A genetic linkage map of grape, utilizing Vitis rupestris and Vitis arizonica.

A genetic linkage map of grape was constructed, utilizing 116 progeny derived from a cross of two Vitis rupestris x V. arizonica interspecific hybrids, using the pseudo-testcross strategy. A total of 475 DNA markers-410 amplified fragment length polymorphism, 24 inter-simple sequence repeat, 32 random amplified polymorphic DNA, and nine simple sequence repeat markers-were used to construct the parental maps. Markers segregating 1:1 were used to construct parental framework maps with confidence levels >90% with the Plant Genome Research Initiative mapping program. In the maternal (D8909-15) map, 105 framework markers and 55 accessory markers were ordered in 17 linkage groups (756 cM). The paternal (F8909-17) map had 111 framework markers and 33 accessory markers ordered in 19 linkage groups (1,082 cM). One hundred eighty-one markers segregating 3:1 were used to connect the two parental maps' parents. This moderately dense map will be useful for the initial mapping of genes and/or QTL for resistance to the dagger nematode, Xiphinema index, and Xylella fastidiosa, the bacterial causal agent of Pierce's disease.

Base Sequence↗

Structure-function of human 3 alpha-hydroxysteroid dehydrogenases: genes and proteins.

Four soluble human 3 alpha-hydroxysteroid dehydrogenase (HSD) isoforms exist which are aldo-keto reductase (AKR) superfamily members. They share 86% sequence identity and correspond to: AKR1C1 (20 alpha(3 alpha)-HSD); AKR1C2 (type 3 3 alpha-HSD and bile-acid binding protein); AKR1C3 (type 2 3 alpha-HSD and type 5 17 beta-HSD); and AKR1C4 (type 1 3 alpha-HSD). Each of the homogeneous recombinant enzymes are plastic and display 3-, 17- and 20-ketosteroid reductase and 3 alpha- 17 beta- and 20 alpha-hydroxysteroid oxidase activities with different k(cat)/K(m) ratios in vitro. The crystal structure of the AKR1C2.NADP(+).ursodeoxycholate complex provides an explanation for this functional plasticity. Ursodeoxycholate is bound backwards (D-ring in the A-ring position) and upside down (beta-face of steroid inverted) relative to the position of 3-ketosteroids in the related rat liver 3 alpha-HSD (AKR1C9) structure. Transient transfection indicates that in COS-1 cells, AKR1C enzymes function as ketosteroid reductases due to potent inhibition of their oxidase activity by NADPH. By acting as ketosteroid reductases they may regulate the occupancy of the androgen, estrogen and progesterone receptors. RT-PCR showed that AKRs are discretely localized. AKR1C4 is virtually liver specific, while AKR1C2 and AKR1C3 are dominantly expressed in prostate and mammary gland. AKR1C genes are highly conserved in structure and may be transcriptionally regulated by steroid hormones and stress.

3-Hydroxysteroid Dehydrogenases↗

Observation of the decay psi(2S)-->K0SK0L.

The decay psi(2S)-->K(0)(S)K(0)(L) is observed using psi(2S) data collected with the Beijing Spectrometer at the Beijing Electron-Positron Collider; the branching fraction is determined to be B(psi(2S)-->K(0)(S)K(0)(L))=(5.24+/-0.47+/-0.48)x10(-5). Compared with J/psi-->K(0)(S)K(0)(L), the psi(2S) branching fraction is enhanced relative to the prediction of the perturbative QCD "12%" rule. The result, together with the branching fractions of psi(2S) decays to other pseudoscalar meson pairs (pi(+)pi(-) and K+K-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.

Journal Article↗

Simultaneous stimulation of Fas-mediated apoptosis and blockade of costimulation prevent autoimmune diabetes in mice induced by multiple low-dose streptozotocin.

Type I diabetes is the result of a selective destruction of insulin-producing beta cells in pancreatic islets by autoreactive T cells. Depletion of autoreactive T cells through apoptosis may be a potential strategy for the prevention of autoimmune diabetes. Simultaneous stimulation of the Fas-mediated pathway and blockade of costimulation by a CTLA4-Fas ligand (FasL) fusion protein has been reported to lead to enhanced in vitro apoptosis of peripheral lymphocytes. To test the feasibility of CTLA4-FasL-based gene therapy to prevent autoimmune diabetes, we developed a recombinant adenovirus containing the human CTLA4-FasL gene (AdCTLA4-FasL). A single injection of 2 x 10(8) plaque-forming units of AdCTLA4-FasL via the tail vein of mice greatly reduced the incidence of autoimmune diabetes (13%, n=15) induced by multiple low-dose streptozotocin. AdCTLA4-FasL administration abrogated pancreatic insulitis, significantly increased apoptosis of pancreatic T-lymphocytes, and altered splenocyte response to mitogenic and antigenic stimulation. These results indicate the therapeutic potential of simultaneous stimulation of the Fas-mediated pathway and blockade of costimulation by adenovirus-mediated CTLA4-FasL gene transfer in the prevention of autoimmune diabetes.

Adoptive Transfer↗

Interferon-gamma mediates neuronal killing of intracellular bacteria.

Neurons can be targets for microbes, which could kill the neurons. Just in reverse, we, in this study, report that bacteria can be killed when entering a neuron. Primary cultures of foetal mouse hippocampal neurons and a neuronal cell line derived from mouse hypothalamus were infected by Listeria monocytogenes. Treatment with interferon-gamma (IFN-gamma) did not affect bacterial uptake, but resulted in increased killing of intracellular bacteria, whereas the neuronal cell remained intact. The IFN-gamma-mediated bacterial killing was mapped to the neuronal cytosol, before listerial actin tail formation. Treatment with IFN-gamma induced phosphorylation of the transcription factor STAT-1 in neurons and IFN-gamma-mediated listerial killing was not observed in STAT-1(-/-) neurons or neurons treated with IFN regulatory factor-1 antisense oligonucleotides. IFN-gamma-treated neuronal cells showed increased levels of inducible nitric oxide synthase (iNOS) mRNA, and antisense iNOS oligonucleotides hampered the bacterial killing by neurons upon IFN-gamma treatment. This novel neuronal function - i.e., that of a microbe killer - could play a crucial role in the control of infections in the immuno-privileged nervous system.

Animals↗

Appropriate antibiotic utilization in seniors prior to hospitalization for community-acquired pneumonia is associated with decreased in-hospital mortality.

BACKGROUND: We analysed the association of mortality and prescription of antibiotics prior to hospitalization for community-acquired pneumonia. METHODS: We used administrative data (hospital abstracts, physician claims, prescriptions) for seniors (age 61 years and over) for Alberta, Canada from 1 April 1994 to 31 March 1999. RESULTS: Hospitalization of 21 191 seniors occurred during the study period. In about 43% of hospitalizations (n = 9034), a physician was consulted prior to hospital admission. Antibiotics were dispensed to 31% of those with a prior physician visit and in about 72%, the antibiotic choice was deemed appropriate. The odds for mortality were significantly decreased in those with prior physician visits (OR = 0.87, P < 0.01), with any antibiotic prescription (OR = 0.66, P < 0.0001), and with an appropriate antibiotic (OR = 0.68, P = 0.03). The choice of an appropriate antibiotic as opposed to an inappropriate antibiotic resulted in a 2.6% absolute and 38% relative mortality reduction. CONCLUSION: Choosing an appropriate outpatient antibiotic in accordance with published expert opinion guidelines compared with inappropriate antibiotic prescriptions decreased hospital mortality in patients subsequently hospitalized for community-acquired pneumonia.

Aged↗

Structure-based design, synthesis, and pharmacologic evaluation of peptide RGS4 inhibitors.

Regulators of G-protein signaling (RGS) proteins form a multifunctional signaling family. A key role of RGS proteins is binding to the G-protein Galpha-subunit and acting as GTPase-activating proteins (GAPs), thereby rapidly terminating G protein-coupled receptor (GPCR) signaling. Using the published RGS4-Gialpha1 X-ray structure we have designed and synthesized a series of cyclic peptides, modeled on the Gialpha Switch I region, that inhibit RGS4 GAP activity. These compounds should prove useful for elucidating RGS-mediated activity and serve as a starting point for the development of a novel class of therapeutic agent.

Animals↗

Percutaneous pulmonary vein isolation for treatment of atrial fibrillation.

BACKGROUND: Transvenous catheter ablation for the treatment of atrial fibrillation is an evolving technique. AIM: The purpose of this study was to identify subgroups of patients most likely to benefit from pulmonary vein electrical isolation. METHODS: Patients with symptomatic atrial fibrillation resistant to pharmacological therapy were studied. Mapping-guided segmental application of radio-frequency energy was used to electrically isolate the pulmonary veins in 74 patients. Ischaemic or dilated cardiomyopathy was present in 34% of patients. Atrial fibrillation had been present for a mean time (+/- standard deviation) of 6.6 +/- 6.1 years. It was paroxysmal in 53 patients (72%). RESULTS: The mean number of procedures was 1.6/patient. After 6 +/- 6 months, 73% of patients (54/74) were in sinus rhythm. Thirteen of those in sinus rhythm were using anti-arrhythmic medications (25%). Recurrence of atrial fibrillation soon after pulmonary vein isolation occurred in 50%. Patients with persistent/permanent atrial fibrillation were less likely to be in sinus rhythm at follow up (11/21 (52%) vs 43/53 (81%); P = 0.01). However, the rate of early recurrence was similar in the intermittent and the persistent/permanent groups (26/53 (49%) vs 11/21(52%), respectively; P-value not significant). Patients with persistent atrial fibrillation were more likely to experience a recurrence of atrial fibril-lation (89%; P = 0.04). No other baseline factors predicted procedural success. Cardiac tamponade occurred in two patients and moderate pulmonary vein stenosis (>50% diameter narrowing) occurred in three patients. CONCLUSIONS: Pulmonary vein isolation is an effective curative treatment for a broad group of patients with atrial fibrillation. However, the procedure is only suitable for patients with problematic atrial fibrillation resistant to other therapies because of the small risk of serious complications.

Adult↗

Overexpression of iNOS and down-regulation of BMPs-2, 4 and 7 in retinoic acid induced cleft palate formation.

The present work studied the induction of cleft palate formation in embryos developed from pregnant BALB/c mice treated orally with retinoic acid (RA). Previous studies on mature somatic cell types showed that RA exerted inhibitory effects on inducible nitric oxide synthase (iNOS) production. For the first time, our study has shown that RA actually stimulates significant expression of iNOS at specific zones of the affected embryonic palatal tissues at three consecutive stages, from gestation day 13 (GD13) to day 16 (GD16). Enzymatically, iNOS facilitates intracellular nitric oxide (NO) synthesis from L-arginine. When NO reacts with reactive superoxides it may result in irreparable cell injury. NO was also reported to induce apoptosis in some mammalian cell systems. Based on our findings, we propose that such an increase in NO production might be associated with apoptosis in the embryonic palatal tissues in the RA-treated mice. The detrimental effects of NO resulted in a reduction in proliferating palatal cells and therefore disturbed the normal plasticity of the palatal shelves. With iNOS overexpression, our findings also showed that there was significant concomitant down-regulation in the expressions of Bone Morphogenetic Proteins (BMPs) -2, 4, and 7 with regional variations particularly in the palatal mesenchymal cells for those embryos developing cleft palate. Since specific spatial and temporal expressions of BMPs -2, 4, and 7 are critical during normal palatal morphogenesis, any deficiency in the epithelial-mesenchymal interaction may result in retarding growth at the embryonic palatal shelves. Taken together, our study has demonstrated cleft palate formation in the BALB/c embryos involved overexpression of iNOS and down-regulation of BMPs-2, 4 and 7.

Animals↗

[Expression of nerve growth factor mRNA and nerve regeneration after discontinuous injection of phorbol-12-myristate-13-acetate into silicone chamber].

OBJECTIVE: To study the mRNA expressions of protein kinase C(PKC) and nerve growth factor (NGF) in rat sciatic nerve and the number of axons after phorbol-12-myristate-13-acetate (PMA) was injected into silicone chamber. METHODS: Forty-two SD adult rats were divided into six groups depending on the time of injury (1 day, 3 days, 1 week, 2 weeks, 3 weeks and 4 weeks). A 0.5 cm nerve was cut in double rat sciatic nerves and "T" type silicone chamber was sutured. PMA at the concentration of 1 x 10(-9) mol/L was injected discontinuously into the right side of T type silicone chamber (PMA group) and saline was injected into the left side (control group). Nucleic acid in situ hybridization histochemistry technique and the computer imagine analysis were employed to detect dynamic changes of PKC mRNA and NGF mRNA in rat sciatic nerves. The number of axons was measured. RESULTS: The expressions of PKC mRNA and NGF mRNA increased after injury, and the expressions of PKC mRNA and NGF mRNA reached the peak 2 weeks and 3 weeks after injury respectively in control group. The expressions of PKC mRNA and NGF mRNA in PMA group were significantly increased than those in control group 2,3 and 4 weeks after injury (P < 0.01). The number of axons in PMA group significantly increased than that in control group (P < 0.01). CONCLUSION: PKC involved in the expression of NGF mRNA and nerve regeneration after injury. During the regenerated course, PMA can promote the expression of NGF mRNA and the number of axons after injury.

Animals↗

Production of a fusion protein consisting of the enterotoxigenic Escherichia coli heat-labile toxin B subunit and a tuberculosis antigen in Arabidopsis thaliana.

Transgenic plants are potentially safe and inexpensive vehicles to produce and mucosally deliver protective antigens. However, the application of this technology is limited by the poor response of the immune system to non-particulate, subunit vaccines. Co-delivery of therapeutic proteins with carrier proteins could increase the effectiveness of the antigen. This paper reports the ability of transgenic Arabidopsis thaliana plants to produce a fusion protein consisting of the B subunit of the Escherichia coli heat-labile enterotoxin and a 6 kDa tuberculosis antigen, the early secretory antigenic target ESAT-6. Both components of the fusion protein were detected using GM1-ganglioside-dependent enzyme-linked immunosorbant assay. This suggested the fusion protein retained both its native antigenicity and the ability to form pentamers.

Amino Acid Sequence↗

Observation of a near-threshold enhancement in the pp mass spectrum from radiative J/psi-->gammapp decays.

We observe a narrow enhancement near 2m(p) in the invariant mass spectrum of pp pairs from radiative J/psi-->gammapp decays. No similar structure is seen in J/psi-->pi(0)pp decays. The results are based on an analysis of a 58 x 10(6) event sample of J/psi decays accumulated with the BESII detector at the Beijing electron-positron collider. The enhancement can be fit with either an S- or P-wave Breit-Wigner resonance function. In the case of the S-wave fit, the peak mass is below 2m(p) at M=1859(+3)(-10) (stat)+5-25(syst) MeV/c(2) and the total width is Gamma<30 MeV/c(2) at the 90% confidence level. These mass and width values are not consistent with the properties of any known particle.

Journal Article↗