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Biomedical subjects

J Feng

Publications and source records attributed to J Feng.

At least 91 records · Page 5Linked to original sources

Transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor-gamma.

CD36, the macrophage type B scavenger receptor, binds and internalizes oxidized low density lipoprotein, a key event in the development of macrophage foam cells within atherosclerotic lesions. Expression of CD36 in monocyte/macrophages is dependent on differentiation status and exposure to soluble mediators. In this study, we investigated the effect of transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 on the expression of CD36 in macrophages. Treatment of phorbol ester-differentiated THP-1 macrophages with TGF-beta1 or TGF-beta2 significantly decreased expression of CD36 mRNA and surface protein. TGF-beta1/TGF-beta2 also inhibited CD36 mRNA expression induced by oxidized low density lipoprotein and 15-deoxyDelta(12,14) prostaglandin J(2), a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, suggesting that the TGF-beta1/TGF-beta2 down-regulated CD36 expression by inactivating PPAR-gamma-mediated signaling. TGF-beta1/TGF-beta2 increased phosphorylation of both mitogen-activated protein (MAP) kinase and PPAR-gamma, whereas MAP kinase inhibitors reversed suppression of CD36 and inhibited PPAR-gamma phosphorylation induced by TGF-beta1/TGF-beta2. Finally, MAP kinase inhibitors alone increased expression of CD36 mRNA and surface protein but had no effect on PPAR-gamma protein levels. Our data demonstrate for the first time that TGF-beta1 and TGF-beta2 decrease expression of CD36 by a mechanism involving phosphorylation of MAP kinase, subsequent MAP kinase phosphorylation of PPAR-gamma, and a decrease in CD36 gene transcription by phosphorylated PPAR-gamma.

CD36 Antigens↗

Integrate-and-fire models with nonlinear leakage.

Can we express biophysical neuronal models as integrate-and-fire (IF) models with leakage coefficients which are no longer constant, as in the conventional leaky IF model, but functions of membrane potential and other biophysical variables? We illustrate the answer to this question using the FitzHugh-Nagumo (FHN) model as an example. A novel IF type model, the IF-FHN model, which approximates to the FHN model, is obtained. The leakage coefficient derived in the IF-FHN model has nonmonotonic relationship with membrane potential, revealing at least in part the intrinsic mechanisms underlying the FHN models. The IF-FHN model correspondingly exhibits more complex behaviour than the standard IF model. For example, in some parameter regions, the IF-FHN model has a coefficient of variation of the output interspike interval which is independent of the number of inhibitory inputs, being close to unity over the whole range, comparable to the FHN model as we noted previously (Brown et al., 1999).

Computer Simulation↗

Construction and analysis of three-dimensional graphic model of single-chain Fv derived from an anti-human placental acidic isoferritin monoclonal antibody by computer.

A three-dimensional (3D) graphic model of a single-chain Fv (scFv) which was derived from an anti-human placental acidic isoferritin (PAF) monoclonal antibody (MAb) was constructed by a homologous protein-predicting computer algorithm on Silicon graphic computer station. The structure, surface static electricity and hydrophobicity of scFv were investigated. Computer graphic modelling indicated that all regions of scFv including the inker, variable regions of the heavy (VH) and light (VL) chains were suitable. The VH region and the VL region were involved in composing the "hydrophobic pocket". The linker was drifted away VH and VL regions. The complementarity determining regions (CDRs) of VH and VL regions surrounded the "hydrophobic pocket". This study provides a theory basis for improving antibody affinity, investigating antibody structure and analyzing the functions of VH and VL regions in antibody activity.

Amino Acid Sequence↗

Aortic root replacement by ministernotomy: technique and potential benefit.

BACKGROUND: Although minimally invasive surgical procedures have aroused much interest in cardiac surgery, difficulty still exists with its application in most of the operations on great arteries. This report summarizes our initial experience of aortic root replacement by a superior ministernotomy in terms of operative indications, operative techniques, and potential benefits. METHODS: Between July 1999 and September 1999, 8 patients who were diagnosed with Marfan syndrome with aortic valve regurgitation underwent aortic root replacements with composite grafts. Clinical characteristics, in-hospital outcomes, and postoperative stay of these patients were compared with data of patients who had undergone Bentall procedure by standard median sternotomy from January to September 1999. RESULTS: There was no death in either group of patients. Demographics were similar between the two groups of patients. In the mini-incision group, the mediastinal drainage was significantly less than the standard incision group. The mean operating time was significantly longer than that in the standard incision group. The cardiopulmonary bypass time and aortic cross-clamping time were similar in both groups of patients. The mean intubation time, postoperative blood transfusion amount, duration of intensive care unit stay and postoperative hospital stay were less than that of the standard incision group; however, they all showed no statistical significant difference. CONCLUSIONS: Aortic root replacement by a superior ministernotomy in cardiopulmonary bypass with cannulas through the femoral artery and femoral vein or right atrium is a safe, reliable procedure with excellent exposure. The procedure provides a potential benefit of less trauma, quick recovery, and reduction of mediastinal drainage and reduction of blood transfusion.

Adult↗

Bradykinin protects the rabbit heart after cardioplegic ischemia via NO-dependent pathways.

BACKGROUND: Depressed myocardial performance is an important clinical problem after open heart surgery. We hypothesized pretreating with bradykinin would pharmacologically precondition the heart and improve post-ischemic performance, and induce myocardial preconditioning by activating nitric oxide synthase. METHODS: Thirty-three rabbit hearts underwent retrograde perfusion with Krebs-Henseleit buffer (KHB) followed by 50 minutes of 37 degrees C cardioplegic ischemia with St. Thomas' cardioplegia solution (StTCP). Ten control hearts received no pretreatment. Ten bradykinin-pretreated hearts received a 10-minute infusion of 0.1 microMol/L bradykinin-enriched KHB and cardioplegic arrest with 0.1 microMol/L bradykinin-enriched StTCP. Six other hearts received 0.1 microMol/L HOE 140, a selective B2 receptor antagonist, added to both the 0.1 microMol/L bradykinin-enriched KHB and 0.1 microMol/L bradykinin-enriched StTCP solutions. Finally, six other hearts received 100 microMol/L of N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, added to both the 0.1 microMol/L bradykinin-enriched KHB and 0.1 microMol/L bradykinin-enriched StTCP solutions. RESULTS: Bradykinin pretreatment significantly improved postischemic performance and coronary flow (CF) compared with control (LVDP: 53 +/- 5* vs 27 +/- 4 mm Hg; +dP/dtmax: 1,025 +/- 93* vs 507 +/- 85 mm Hg/s; CF: 31 +/- 3* vs 22 +/- 2 mL/min; *p < 0.05). Both HOE 140 and L-NAME abolished bradykinin-induced protection, resulting in recovery equivalent to untreated controls. CONCLUSIONS: Bradykinin pretreatment improves recovery of ventricular and coronary vascular function via nitric oxide-dependent mechanisms. Pharmacologic preconditioning by bradykinin pretreatment may be an important new strategy for improving myocardial protection during heart surgery.

Animals↗

Polychlorinated organic compounds in Yangtse River sediments.

Polychlorinated organic compounds (PCOCs) were analyzed in Yangtse River sediments. The results show that the concentrations of PCOCs in Yangtse River sediments followed the order of DDTs > HCB > HCHs > PCBs. High PCOCs concentrations were detected in sediments from station Y02a and Y02b, which are located in the main input of the Yangtse River (Nanjing section). Results also show that the PCOCs values were highly correlated with organic carbon content and heavy metal contamination.

China↗

Photoelectric measurements of s-BLM/nucleoli: a new technique for studying apoptosis.

A new method based on photoelectric measurement for analyzing apoptosis of cell-free MCF-7 nucleoli is reported. Supported bilayer lipid membrane (s-BLM) was used to enclose nucleoli in biological environment. The s-BLM was self-assembled on the wall of a super-thin cell. During the apoptosis induced by Taxol, the photoelectric current of the self-assembled s-BLM/nucleoli was found decreasing with time, suggesting the degradation of nucleus DNA. Electron transfer along the DNA double helix and along nuclear skeleton is assumed in the interpretation. This novel photoelectric analytical method may provide a rapid and sensitive technique to evaluate apoptosis.

Apoptosis↗

Nutraceutical interventions may delay aging and the age-related diseases.

Largely due to better control of infectious diseases and to year-round access to a more nutritious diet, life expectancy in developed countries has increased dramatically in the twentieth century. However, as the average age of the population has risen, the incidence of chronic age-related diseases such as Alzheimer's, Parkinson's, cardiovascular disease, cancer, arthritis, osteoporosis, benign prostatic hyperplasia, late-onset diabetes, and macular degeneration have increased. To obtain further significant improvements in both lifespan and the quality of life in this century, treatments and nutritional changes that address the age-related diseases and the aging process itself need to be examined and validated. There are many reports suggesting that oxidative stress and certain nutritional deficiencies may contribute to the aging process and to many age-related diseases. In this article, we report on two human clinical trials using novel antioxidant supplements in which urinary oxidative stress is significantly reduced. We also discuss the conceptual basis and existing literature for several nutritional supplements that may have beneficial effects on aging and age-related diseases. Based on the available data, we suggest that human life expectancy can be significantly increased in the twenty-first century by optimizing diet and using nutritional supplements.

Aging↗

Fabrication and photoelectric properties of self-assembled bilayer lipid membranes on conducting glass.

Supported bilayer lipid membranes (s-BLMs with and without the doping of fullerene C60) self-assembled on indium-tin oxide (ITO) glass were fabricated and characterized by cyclic voltammetry and electrochemical impedance spectroscopy using a three-electrode system. The photoelectric properties of the ITO supported planar lipid bilayers were studied. Light intensity of irradiation, bias voltage, and concentration of donors have been found to be limiting factors of the transmembrane photocurrent. The facilitation effect of C60 doping in s-BLMs on the photoinduced electron transfer across s-BLM is discussed. This novel self-assembled ITO/s-BLM system may provide a simple and mechanically stable model for the study of the photoelectric and photodynamic properties of biomembranes.

Electric Conductivity↗

Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi.

BACKGROUND: Currently, only two drugs are recommended for treatment of infection with Trypanosoma cruzi, the etiologic agent of Chagas' disease. These compounds kill the trypomastigote forms of the parasite circulating in the bloodstream, but are relatively ineffective against the intracellular stage of the parasite life cycle. Neither drug is approved by the FDA for use in the US. The hypoxanthine phosphoribosyltransferase (HPRT) from T. cruzi is a possible new target for antiparasite chemotherapy. The crystal structure of the HPRT in a conformation approximating the transition state reveals a closed active site that provides a well-defined target for computational structure-based drug discovery. RESULTS: A flexible ligand docking program incorporating a desolvation correction was used to screen the Available Chemicals Directory for inhibitors targeted to the closed conformation of the trypanosomal HPRT. Of 22 potential inhibitors identified, acquired and tested, 16 yielded K(i)'s between 0.5 and 17 microM versus the substrate phosphoribosylpyrophosphate. Surprisingly, three of eight compounds tested were effective in inhibiting the growth of parasites in infected mammalian cells. CONCLUSIONS: This structure-based docking method provided a remarkably efficient path for the identification of inhibitors targeting the closed conformation of the trypanosomal HPRT. The inhibition constants of the lead inhibitors identified are unusually favorable, and the trypanostatic activity of three of the compounds in cell culture suggests that they may provide useful starting points for drug design for the treatment of Chagas' disease.

Animals↗

Phospholipase Cgamma2 is essential in the functions of B cell and several Fc receptors.

Many receptors activate phospholipase Cgamma1 or -gamma2. To assess the role of PLCgamma2, we derived enzyme-deficient mice. The mice are viable but have decreased mature B cells, a block in pro-B cell differentiation, and B1 B cell deficiency. IgM receptor-induced Ca2+ flux and proliferation to B cell mitogens are absent. IgM, IgG2a, and IgG3 levels are reduced, and T cell-independent antibody production is absent. The similarity to Btk- or Blnk-deficient mice demonstrates that PLCgamma2 is downstream in Btk/Blnk signaling. FcRgamma signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell FcepsilonR function, and NK cell FcgammaRIII and 2B4 function. The results define a signal transduction pathway broadly utilized by immunoglobulin superfamily receptors.

Adaptor Proteins, Signal Transducing↗

Influence of extracellular potassium on the antiarrhythmic effect of global preconditioning in isolated perfused rat hearts.

The objective of this study was to investigate if a variation in extracellular-K+ concentrations alters the effects of global pre-conditioning on ischemia-induced arrhythmias. Rat hearts were Langendorff-perfused with Krebs-Henseleit solution and randomised in 8 groups (n = 12/group): four control groups (K+: 2, 4, 6, or 8 mmol/L) which underwent 30-min coronary artery occlusion and four preconditioned groups (K+: 2, 4, 6, or 8 mmol/L) in which the 30-min regional ischemia was preceded by 2 cycles of 3 min global ischemia. In the presence of low K+ (2 mmol/L), there were no differences between control and preconditioning groups in the number of ventricular premature beats (VPBs): 194 +/- 64 vs. 217 +/- 81, the incidence of ventricular tachycardia (VT): 100% vs. 100% and of ventricular fibrillation (VF): 100% vs. 100%. In the presence of normal K+ concentration (4 mmol/L), ischemic preconditioning reduced the number of VPBs from 88 +/- 26 to 25 +/- 10, (p < 0.05), the incidence of VT from 100 to 50% (p < 0.05), and of VF from 67 to 16% (p < 0.05). In the condition of higher K+ concentration (6 mmol/ L), VPBs (34 +/- 8 vs. 11 +/- 4), the incidence of VT (100% vs. 25%; p < 0.05 ) and VF (25% vs. 8%) were further reduced in preconditioned hearts. In the condition of K+ concentration (8 mmol/L), there were no differences in VPBs (11 +/- 3 vs. 7 +/- 2), the incidence of VT (8% vs. 0%) and VF (8% vs. 0%) between control and preconditioned hearts. Our data show that ischemic preconditioning affords protection against arrhythmias during coronary artery occlusion in the isolated rat heart and that hypokalemia abolishes the antiarrhythmic effects of global preconditioning.

Animals↗

Photoelectrochemistry as a novel strategy for DNA hybridization detection.

The special properties of ssDNA and dsDNA molecules in structure and electric behavior, may offer us some new ideas for the fabrication of genosensors and DNA-chips. In this work, the photoelectrochemical method was firstly employed to characterize the photoelectric behavior of a ssDNA probe electrode, which was prepared with the self-assembly technique, and its resulting dsDNA electrode. The obvious decrease in the photocurrent of the dsDNA modified electrode at open potential or a bias voltage indicated that photoelectrochemistry was another useful method for DNA hybridization detection. Using the special design of ssDNA probes, we attempt to discuss further the relationship between the properties of DNA molecules and their photoelectric behaviors. In addition, the electrochemical impedance method was employed to verify the occurrence of some modifications over the electrode interface before and after the hybridization event.

DNA↗

Optimizing the window size for multiple least squares fitting of electron energy loss spectra.

The purpose of this study was to determine the effect of the fitting window size used with the linear least squares fit method when quantitating trace elements with electron energy loss spectroscopy. Theory and computer simulation with a simple model of two 'signals' show that, when the background underlying the signal is slowly varying and the signal is localized, there exists a minimum window optimal for fitting raw spectra. The width of the minimum fitting window can be determined directly from the reference standard spectrum of the signal alone and the estimates of signal and background are related. Use of narrower than the minimum window will increase the fitting uncertainty of the signal and yield less reliable results. More complicated experimental spectra must be fitted to more than two standards and a simple analytical expression of the minimum fitting window cannot be derived, but can be determined empirically. Our study shows that the empirical value obtained from experimental spectra is only slightly larger than the theoretical value derived from the simple model, indicating that this conclusion is still valid. When fitting difference spectra with a slowly varying background, the estimates of signal and background are independent and windows wider than the size of the signal will yield the same fitting uncertainty. In the presence of a non-slowly varying background, common in difference spectra, the minimum window size depends on the fine structure of the signal and the background.

Calcium↗

Four-day multimedia diet records underestimate energy needs in middle-aged and elderly women as determined by doubly-labeled water.

Systematic problems exist in the quantification of food intake in populations using traditional self-reported measures. The objective of this study was to determine the effectiveness of an innovative multimedia diet record (MMDR) for dietary energy intake assessment. Dietary intake was estimated by combining the use of a microcassette tape recorder and 35-mm camera in 53 women whose ages ranged from 50 to 93 y (64.9 +/- 11.3 y), with body weights of 62.4 +/- 12.2 kg and body mass indexes (BMI) of 24.4 +/- 4.0 kg/m(2). Using household measures, subjects voice-recorded and photographed all food and beverages consumed for four consecutive days. A two-point doubly-labeled water (DLW) method was used over 13 d to calculate carbon dioxide production, total body water, and subsequently, total energy expenditure (TEE) through the use of a food quotient. Mean body weight did not change between d 1 and 14. TEE and reported energy intake were compared using MMDR. Mean reported energy intakes 7.5 +/- 1.9 MJ/d (1774 +/- 476 kcal/d) were lower (P < 0.01) than TEE by 10.4 +/- 3.1 MJ/d (2477 +/- 736 kcal/d), indicating underreporting of food intake. Reporting accuracy (reported energy intake/TEE' 100%) was 76.0 +/- 22.9%. Mean energy expenditure (MJ/d), as determined by doubly-labeled water, was higher (P < 0.01) in each stratified age range when compared to reported energy intake by MMDR. There were no significant differences in reporting accuracy among the stratified age groups. Using the MMDR method, this population of weight-stable women underreported their food intakes compared to their determined energy expenditure estimated by DLW.

Aged↗

Synchronization due to common pulsed input in Stein's model.

It is known that stimulus-evoked oscillatory synchronization among neurones occurs in widely separated cortical regions. In this paper we provide a possible mechanism to explain the phenomenon. When a common, random input is presented, we find that a group of neurones-of Stein's (integrate-and-fire) model type with or without reversal potentials-are capable of quickly synchronizing their firing. Interestingly the optimal average synchronization time occurs when the common input has a high coefficient of variation of interspike intervals (greater than 0.5) for this model with or without reversal potentials. The model with reversal potentials more quickly synchronizes than that without reversal potentials.

Animals↗