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Biomedical subjects

J Li

Publications and source records attributed to J Li.

At least 73 records · Page 4Linked to original sources

Gene transfer of RANTES and MCP-1 chemokine antagonists prolongs cardiac allograft survival.

Vascularized organ allografts are rapidly destroyed by host immune cells that are recruited along chemokine gradients. Among chemokines, Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) CC chemokine ligand (CCL5) and monocyte chemoattractant protein (MCP)-1 (CCL2) are upregulated in rejecting cardiac allografts. To antagonize these chemokines, we constructed adenoviral vectors expressing NH(2)-terminal deletion (8ND) mutants of the respective genes. Using the F344-to-LEW rat model, intragraft gene transfer of chemokine analogs prolonged cardiac allograft survival from 10.1+/-0.7 and 10.4+/-0.7 days using non-coding adenovirus and vehicle alone, respectively, to 17.0+/-0.7 days for 8ND-RANTES (P<0.001) and 14.2+/-0.8 days for 8ND-MCP-1 (P<0.01). 8ND-RANTES reduced graft infiltration by monocytes/macrophages, cluster of differentiation (CD) 8alpha(+) and T-cell receptor alphabeta(+) cells, while 8ND-MCP-1 reduced monocytes/macrophages. In mixed leukocyte reactions in vitro, proliferation of host lymphocytes from regional lymph nodes in response to donor splenocytes was unaffected by 8ND-RANTES gene transfer. Using a two-gene approach, the contribution of 8ND-MCP-1 was negligible, consistent with available evidence that 8ND-RANTES inhibits both RANTES and MCP-1 activities. 8ND-RANTES gene transfer and a short course of low-dose cyclosporine A synergistically prolonged graft survival to 37.8+/-5.5 vs 15.4+/-0.5 days with cyclosporine alone (P<0.001). These results suggest a role for anti-chemokine gene therapy as an adjuvant therapy in heart transplantation.

Animals↗

Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers.

Methods to permit more precise delineation of astrocytomas of different grades may have therapeutic utility. The authors selectively microdissected pure populations of cells from normal brain and astrocytomas. They performed two-dimensional protein gel electrophoresis (2DGE) followed by protein sequencing. Differential expression was confirmed immunohistochemically. 2DGE identified proteomic patterns and proteins that differentiated normal brain from tumor and distinguished astrocytomas of increasing grade.

Astrocytoma↗

Measurement of sigma(e+e- -->psi(3770)-->hadrons) at Ec.m.=3773 MeV.

We measure the cross section for e+e- -->psi(3770) -->hadrons at Ec.m.=3773 MeV to be (6.38+/-0.08(+0.41)(-0.30) nb using the CLEO detector at the CESR e+e- collider. The difference between this and the e+e- -->psi(3770) -->DD cross section at the same energy is found to be (-0.01+/-0.08(+0.41)(-0.30) nb. With the observed total cross section, we extract Gamma(ee)(psi(3770))=(0.204+/-0.003(+0.041)(-0.027) keV. Uncertainties shown are statistical and systematic, respectively.

Journal Article↗

Observation of a chi(c2)' candidate in gamma gamma --> DD production at belle.

We report on a search for new resonant states in the process gamma gamma --> DD. A candidate C-even charmonium state is observed in the vicinity of 3.93 GeV/c2. The production rate and the angular distribution in the gamma gamma center-of-mass frame suggest that this state is the previously unobserved chi(c2)', the 2(3)P2 charmonium state.

Journal Article↗

New measurements of Cabibbo-suppressed decays of mesons with the CLEO-c detector.

Using of data collected with the CLEO-c detector, we report on first observations and measurements of Cabibbo-suppressed decays of D mesons in the following six decay modes: pi+ pi- pi0 pi0, pi+ pi+ pi- pi- pi0, pi+ pi0 pi0, pi+ pi+ pi- pi0, eta pi0, and omega pi+ pi-. Improved branching fraction measurements in eight other multipion decay modes are also presented. The measured D --> pi pi rates allow us to extract the ratio of isospin amplitudes A(DeltaI = (3/2) / A(DeltaI = (1/2)) = 0.420 +/- 0.014(stat) +/- 0.016(syst) and the strong phase shift of delta1 = (86.4 +/- 2.8 +/- 3.3) degrees, which is quite large and now more precisely determined.

Journal Article↗

DSS1 is required for the stability of BRCA2.

DSS1 is an evolutionarily conserved acidic protein that binds to BRCA2. However, study of the function of DSS1 in mammalian cells has been hampered because endogenous DSS1 has not been detectable by Western blotting. Here, we developed a modified Western blotting protocol that detects endogenous DSS1 protein, and used it to study the function of DSS1 and its interaction with BRCA2 in mammalian cells. We found that essentially all BRCA2 in human cell lines is associated with DSS1. Importantly, we found that RNAi knockdown of DSS1 in human cell lines led to dramatic loss of BRCA2 protein, mainly due to its increased degradation. Furthermore, the stability of BRCA2 mutant devoid of the DSS1-binding domain is unaffected by the depletion of DSS1. Most notably, like BRCA2 depletion, DSS1 depletion also led to hypersensitivity to DNA damage. These results demonstrated that the stability of BRCA2 protein in mammalian cells depends on the presence of DSS1. Deletion or mutation of DSS1 or suppression of its expression by other mechanisms are therefore potential causative mechanisms for human breast and ovarian cancer. Such mechanisms may be relevant to sporadic as well as familiar breast cancer where BRCA1 and BRCA2 mutations are not present.

BRCA2 Protein↗

Investigation of MR image distortion for radiotherapy treatment planning of prostate cancer.

MR imaging based treatment planning for radiotherapy of prostate cancer is limited due to MR imaging system related geometrical distortions, especially for patients with large body sizes. On our 0.23 T open scanner equipped with the gradient distortion correction (GDC) software, the residual image distortions after the GDC were <5 mm within the central 36 cm x 36 cm area for a standard 48 cm field of view (FOV). In order to use MR imaging alone for treatment planning the effect of residual MR distortions on external patient contour determination, especially for the peripheral regions outside the 36 cm x 36 cm area, must be investigated and corrected. In this work, we performed phantom measurements to quantify MR system related residual geometric distortions after the GDC and the effective FOV. Our results show that for patients with larger lateral dimensions (>36 cm), the differences in patient external contours between distortion-free CT images and GDC-corrected MR images were 1-2 cm because of the combination of greater gradient distortion and loss of field homogeneity away from the isocentre and the uncertainties in patient setup during CT and MRI scans. The measured distortion maps were used to perform point-by-point corrections for patients with large dimensions inside the effective FOV. Using the point-by-point method, the geometrical distortion after the GDC were reduced to <3 mm for external contour determination and the effective FOV was expanded from 36 cm to 42 cm.

Humans↗

Study of PMS777, a new type of acetylcholinesterase inhibitor, in human HepG2 cells. Comparison with tacrine and galanthamine on oxidative stress and mitochondrial impairment.

Acetylcholinesterase inhibitors are commonly used as cognitive enhancers for dementia in aged people. Among them, tacrine (THA) but not galanthamine, was shown to exhibit hepatotoxicity which reduces its clinical use. PMS777, both a PAF antagonist and a new potent acetylcholinesterase inhibitor was recently demonstrated to reverse scopolamine-induced amnesia in mice without toxicity. In the present study, the effects of THA, galanthamine and PMS777 were compared in HepG2 cells on the oxidative parameters involved in the reported hepatotoxicity of THA. THA (> or = 10 microM) induced an oxidative stress as shown by elevated ROS and MDA production and by a decrease in GSH level. Moreover, mitochondrial membrane potential and redox status were decreased. At low concentrations (< or =10 microM), there was no significant disturbance. None of the oxidative stress markers was affected by PMS777 up to the maximum concentration tested and it is suggested that PMS777 is not cytotoxic for HepG2 cells. Galanthamine was also without cytotoxicity. Our results suggest that the toxic effect of THA above 10 microM may be caused by drug-induced mitochondrial energization impairment and destabilisation of membrane phospholipids associated with an oxidative stress. In contrast by preventing these dysfunctions, PMS777 could be safer than THA.

Cell Survival↗

Search for exclusive multibody non- decays at the resonance.

Using data collected at the psi(3770) resonance with the CLEO-c detector at the Cornell e+e- storage ring, we present searches for 25 charmless decay modes of the psi(3770), mostly multibody final states. No evidence for charmless decays is found.

Journal Article↗

Novel approach to tuning the physical properties of organic-inorganic hybrid semiconductors.

We discuss theoretically a novel approach to tailoring the properties of a new family of organic-inorganic hybrid superlattices, using two isostructural materials, ZnSe(en)0.5 and ZnTe(en)0.5, as examples. Replacing Se with Te leads to a number of nontrivial changes: the conduction band parity, singularity type, conductivity in the superlattice direction, and the p-type dopability. Experimentally, we report the first unambiguous observation of exciton-polariton emission in a hybrid semiconductor, i.e., ZnTe(en)0.5 . The band-edge excitonic transitions in both emission and absorption are explained by the calculated electronic structures.

Journal Article↗

Artificial 'spin ice' in a geometrically frustrated lattice of nanoscale ferromagnetic islands.

Frustration, defined as a competition between interactions such that not all of them can be satisfied, is important in systems ranging from neural networks to structural glasses. Geometrical frustration, which arises from the topology of a well-ordered structure rather than from disorder, has recently become a topic of considerable interest. In particular, geometrical frustration among spins in magnetic materials can lead to exotic low-temperature states, including 'spin ice', in which the local moments mimic the frustration of hydrogen ion positions in frozen water. Here we report an artificial geometrically frustrated magnet based on an array of lithographically fabricated single-domain ferromagnetic islands. The islands are arranged such that the dipole interactions create a two-dimensional analogue to spin ice. Images of the magnetic moments of individual elements in this correlated system allow us to study the local accommodation of frustration. We see both ice-like short-range correlations and an absence of long-range correlations, behaviour which is strikingly similar to the low-temperature state of spin ice. These results demonstrate that artificial frustrated magnets can provide an uncharted arena in which the physics of frustration can be directly visualized.

Journal Article↗

Frizzled-related protein variants are risk factors for hip osteoarthritis.

OBJECTIVE: To examine the association of the Arg200Trp and Arg324Gly variants of FRZB with the risk and phenotype of radiographic osteoarthritis (OA) of the hip and serum levels of Frizzled-related protein (FRP) in a prospective cohort of elderly Caucasian women. METHODS: Radiographic hip OA status of patients was defined by the presence of severe joint space narrowing (JSN) (feature grade>or=3), a summary grade>or=3, or definite osteophytes (grade>or=2) and JSN (grade>or=2) in the same hip. Genotypes were obtained in 569 patients with radiographic OA of the hip and in 1,317 and 4,136 controls for the Arg200Trp and Arg324Gly variants, respectively. Serum FRP levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression was performed. RESULTS: The minor allele frequency for the Arg200Trp polymorphism was 0.12 in the control group compared with 0.14 in the group with radiographic OA of the hip (P=0.12), and the minor allele frequency for the Arg324Gly variant was 0.083 in the control group compared with 0.088 in the group with radiographic OA of the hip (P=0.63). The multilocus genotypes available in 1,886 subjects suggested that inheritance of both minor alleles was a risk factor for developing OA characterized by JSN (P<0.01). Patients with radiographic OA of the hip who were homozygous for the Arg200Trp minor allele had higher serum FRP levels than controls who were homozygous for the major allele. CONCLUSION: Our data confirm findings of another study, that a rare haplotype with both Arg200Trp and Arg324Gly FRZB variants contributes to the genetic susceptibility to hip OA among Caucasian women, and that these polymorphisms may contribute to increased serum levels of proteins as biomarkers of OA.

Aged↗

Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS.

The authors have previously shown that acute lung injury (ALI) produces a wide spectrum of pathological processes in patients who die of severe acute respiratory syndrome (SARS) and that the SARS coronavirus (SARS-CoV) nucleoprotein is detectable in the lungs, and other organs and tissues, in these patients. In the present study, immunohistochemistry (IHC) and in situ hybridization (ISH) assays were used to analyse the expression of angiotensin-converting enzyme 2 (ACE2), SARS-CoV spike (S) protein, and some pro-inflammatory cytokines (PICs) including MCP-1, TGF-beta1, TNF-alpha, IL-1beta, and IL-6 in autopsy tissues from four patients who died of SARS. SARS-CoV S protein and its RNA were only detected in ACE2+ cells in the lungs and other organs, indicating that ACE2-expressing cells are the primary targets for SARS-CoV infection in vivo in humans. High levels of PICs were expressed in the SARS-CoV-infected ACE2+ cells, but not in the uninfected cells. These results suggest that cells infected by SARS-CoV produce elevated levels of PICs which may cause immuno-mediated damage to the lungs and other organs, resulting in ALI and, subsequently, multi-organ dysfunction. Therefore application of PIC antagonists may reduce the severity and mortality of SARS.

Acute Disease↗

Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide.

Grape seed proanthocyanidin extract (GPSE) at high doses has been shown to exhibit cytotoxicity that is associated with increased apoptotic cell death. Nitric oxide (NO), being a regulator of apoptosis, can be increased in production by the administration of GSPE. In a chick cardiomyocyte study, we demonstrated that high-dose (500 microg/ml) GSPE produces a significantly high level of NO that contributes to increased apoptotic cell death detected by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. It is also associated with the depletion of intracellular glutathione (GSH), probably due to increased consumption by NO with the formation of S-nitrosoglutathione. Co-treatment with L-NAME, a NO synthase inhibitor, results in reduction of NO and apoptotic cell death. The decline in reduced GSH/oxidized GSH (GSSG) ratio is also reversed. N-Acetylcysteine, a thiol compound that reacts directly with NO, can reduce the increased NO generation and reverse the decreased GSH/GSSG ratio, thereby attenuating the cytotoxicity induced by high-dose GSPE. Taken together, these results suggest that endogenous NO synthase (NOS) activation and excessive NO production play a key role in the pathogenesis of high-dose GSPE-induced cytotoxicity.

Acetylcysteine↗

Observation of organochlorine pesticides in the air of the Mt. Everest region.

High mountains have been suggested to play an important role in the global transport of persistent organic pollutants, yet observation of these pollutants in high mountains is very limited. In the summer of 2002, air samples were collected at Dingri at a height of 4400 m above sea level (m a.s.l.) and at Rongbuk Valley (4976 m a.s.l.) in the Mt. Everest region and analyzed using large volume injection gas chromatography tandem mass spectrometry. The mean concentrations of organochlorine pesticides (OCPs) in the samples were 19.2, 11.2, 7.7, 8.9, 10.4, 27.6, 5.1, 5.1, and 3.7 pg m(-3) for alpha-HCH, beta-HCH, gamma-HCH, HCB, heptachlor, alpha-endosulfan, p,p'-DDE, o,p'-DDT, and p,p'-DDT, respectively. Backward trajectories were used to assess the association between source regions, transport paths, and observed OCP concentrations. During the sampling period, the o,p'-DDT/p,p'-DDT concentration ratios were observed to be between 1.23 and 1.41, much higher than that of technical DDT, indicating the existence of a DDT source other than technical DDTs in the source regions.

Air Pollutants↗

Recent advances on the complement system of teleost fish.

The complement system plays an essential role in alerting the host of the presence of potential pathogens, as well as in their clearing. In addition, activation of the complement system contributes significantly in the orchestration and development of an acquired immune response. Although the complement system has been studied extensively in mammals, considerably less is known about complement in lower vertebrates, in particular teleost fish. Here we review our current understanding of the role of fish complement in phagocytosis, respiratory burst, chemotaxis and cell lysis. We also thoroughly review the specific complement components characterized thus far in various teleost fish species. In addition, we provide a comprehensive compilation on complement host-pathogen interactions, in which we analyze the role of fish complement in host defense against bacteria, viruses, fungi and parasites. From a more physiological perspective, we evaluate the knowledge accumulated on the influence of stress, nutrition and environmental factors on levels of complement activity and components, and how the use of this knowledge can benefit the aquaculture industry. Finally, we propose future directions that are likely to advance our understanding of the molecular evolution, structure and function of complement proteins in teleosts. Such studies will be pivotal in providing new insights into complement-related mechanisms of recognition and defense that are essential to maintaining fish homeostasis.

Animals↗

Taurine protects against ischemia-reperfusion injury in rabbit livers.

Ischemia-reperfusion injury is of major clinical relevance during liver transplantation. In the present study, the therapeutic efficacy of taurine to protect against ischemia-reperfusion injury was investigated in rabbit livers. We demonstrated that intravenous injection of taurine attenuated liver dysfunction as evidenced by reductions in serum alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. The recovery of morphological and ultrastructural changes in the liver was also promoted by taurine. The mechanism of the protective effect of taurine seems at least to rely on antioxidation, since the lipoperoxides contents in liver tissues were significantly reduced among taurine-treated rabbits. These results suggest that taurine is a potent useful reagent to protect the rabbit liver from ischemia-reperfusion injury.

Animals↗