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Biomedical subjects

Jun Yang

Publications and source records attributed to Jun Yang.

At least 235 records · Page 13Linked to original sources
PubMed2004

Blood pressure differences between northern and southern Chinese: role of dietary factors: the International Study on Macronutrients and Blood Pressure.

Blood pressure and prevalence of high blood pressure are greater for northern than southern Chinese. Reasons for these differences are unclear. Relationships of north-south blood pressure differences with multiple dietary factors were investigated in 839 Chinese participants, International Study on Macronutrients and Blood Pressure (INTERMAP), 561 northern, 278 southern, aged 40 to 59 years. Daily nutrient intakes were determined from four 24-hour dietary recalls and 2 timed 24-hour urine collections. Average systolic/diastolic pressure levels were 7.4/6.9 mm Hg higher for northern than southern participants. Southern participants had lower body mass index, sodium intake, sodium/potassium ratio, and higher intake of calcium, magnesium, phosphorus, and vitamins A and C. Considered singly, with control for age and gender, several dietary variables (eg, body mass index, urinary sodium/potassium ratio, urinary sodium, dietary phosphorus, and magnesium) reduced north-south blood pressure differences by > or =10%. Controlled for age and gender, nondietary variables had little effect on north-south blood pressure differences. With inclusion in regression models of multiple dietary variables (sodium, potassium, magnesium or phosphorus, body mass index), north-south blood pressure differences became much smaller (systolic -1.1, diastolic 1.6 mm Hg) and statistically nonsignificant. In conclusion, multiple dietary factors accounted importantly for north-south blood pressure differences. Efforts are needed to improve nutrition in China, especially in the north, as well as in other populations including those in the United States, for prevention and control of adverse blood pressure levels and major adult cardiovascular disease.

Adult↗
PubMed2004

Preparation and characterization of positively charged ruthenium nanoparticles.

Positively charged ruthenium nanoparticles were prepared by NaBH(4) reduction at room temperature and at pH values lower than 4.9. The ruthenium nanoparticles were characterized by zeta potential measurement, TEM, XPS, and XRD. Particles with a mean diameter of 1.8 nm and a standard deviation of 0.40 nm could be obtained under the experimental conditions. The surface charge on the particles is believed to originate from hydrated proton adsorption. The positively charged ruthenium nanoparticles could be used as the starting material for further functionalization by PVP, ethylenediamine, and dodecylamine.

Journal Article↗
PubMed2004

Synthesis and biological evaluations of novel benzimidazoles as potential antibacterial agents.

A series of novel benzimidazole derivatives were synthesized via parallel solution-phase chemistry. Many of these compounds were found to inhibit the growth of Staphylococcus aureus and Escherichia coli. Several analogues exhibited low micromolar minimal inhibitory concentrations (MIC) against both Gram-positive and Gram-negative bacteria of clinical relevance and could serve as leads for further optimizations for antibacterial research.

Anti-Bacterial Agents↗
PubMed2004

Involvement of anion channel(s) in the modulation of the transient outward K(+) channel in rat ventricular myocytes.

The cardiac Ca(2+)-independent transient outward K(+) current (I(to)), a major repolarizing ionic current, is markedly affected by Cl(-) substitution and anion channel blockers. We reexplored the mechanism of the action of anions on I(to) by using whole cell patch-clamp in single isolated rat cardiac ventricular myocytes. The transient outward current was sensitive to blockade by 4-aminopyridine (4-AP) and was abolished by Cs(+) substitution for intracellular K(+). Replacement of most of the extracellular Cl(-) with less permeant anions, aspartate (Asp(-)) and glutamate (Glu(-)), markedly suppressed the current. Removal of external Na(+) or stabilization of F-actin with phalloidin did not significantly affect the inhibitory action of less permeant anions on I(to). In contrast, the permeant Cl(-) substitute Br(-) did not markedly affect the current, whereas F(-) substitution for Cl(-) induced a slight inhibition. The I(to) elicited during Br(-) substitution for Cl(-) was also sensitive to blockade by 4-AP. The ability of Cl(-) substitutes to induce rightward shifts of the steady-state inactivation curve of I(to) was in the following sequence: NO(3)(-) > Cl(-) approximately Br(-) > gluconate(-) > Glu(-) > Asp(-). Depolymerization of actin filaments with cytochalasin D (CytD) induced an effect on the steady-state inactivation of I(to) similar to that of less permeant anions. Fluorescent phalloidin staining experiments revealed that CytD-pretreatment significantly decreased the intensity of FITC-phalloidin staining of F-actin, whereas Asp(-) substitution for Cl(-) was without significant effect on the intensity. These results suggest that the I(to) channel is modulated by anion channel(s), in which the actin cytoskeleton may be implicated.

Actins↗
PubMed2004

ATM and ATR: sensing DNA damage.

Cellular response to genotoxic stress is a very complex process, and it usually starts with the "sensing" or "detection" of the DNA damage, followed by a series of events that include signal transduction and activation of transcription factors. The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair, cell cycle arrest, and cell death. There have been extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process, including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood, human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.

Animals↗
PubMed2004

Proteomic analysis of cellular responses to low concentration N-methyl-N'-nitro-N-nitrosoguanidine in human amnion FL cells.

We have shown previously that exposure to a low concentration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces comprehensive changes in the protein expression profile of human amnion FL cells, including the induction, suppression, upregulation, and downregulation of various proteins. In addition, by proteomic analysis combining two-dimensional gel electrophoresis (2-DE) and mass spectrometry, some of the induced and suppressed proteins were identified. In this study, we identified an additional 18 proteins among those that were either up- or downregulated by MNNG treatment. The proteins identified were a heterogeneous group that included several zinc finger proteins, proteins involved in signal transduction, cytoskeletal proteins, cell-cycle regulation proteins, and proteins with unknown functions. The involvement of these proteins in the cellular responses to alkylating agents has not been reported before and their physiological relevance is not clear. Therefore, our findings may help better understand the global cellular stress responses to chemical carcinogens, and may lead to new studies on the functions of these MNNG-responsive proteins. Furthermore, some of these proteins may serve as biomarkers for detecting exposure of human populations to environmental carcinogens.

Amnion↗
PubMed2004

Temperature dependence and resonance assignment of 13C NMR spectra of selectively and uniformly labeled fusion peptides associated with membranes.

HIV-1 and influenza viral fusion peptides are biologically relevant model fusion systems and, in this study, their membrane-associated structures were probed by solid-state NMR (13)C chemical shift measurements. The influenza peptide IFP-L2CF3N contained a (13)C carbonyl label at Leu-2 and a (15)N label at Phe-3 while the HIV-1 peptide HFP-UF8L9G10 was uniformly (13)C and (15)N labeled at Phe-8, Leu-9 and Gly-10. The membrane composition of the IFP-L2CF3N sample was POPC-POPG (4:1) and the membrane composition of the HFP-UF8L9G10 sample was a mixture of lipids and cholesterol which approximately reflects the lipid headgroup and cholesterol composition of host cells of the HIV-1 virus. In one-dimensional magic angle spinning spectra, labeled backbone (13)C were selectively observed using a REDOR filter of the (13)C-(15)N dipolar coupling. Backbone chemical shifts were very similar at -50 and 20 degrees C, which suggests that low temperature does not appreciably change the peptide structure. Relative to -50 degrees C, the 20 degrees C spectra had narrower signals with lower integrated intensity, which is consistent with greater motion at the higher temperature. The Leu-2 chemical shift in the IFP-L2CF3N sample correlates with a helical structure at this residue and is consistent with detection of helical structure by other biophysical techniques. Two-dimensional (13)C-(13)C correlation spectra were obtained for the HFP-UF8L9G10 sample and were used to assign the chemical shifts of all of the (13)C labels in the peptide. Secondary shift analysis was consistent with a beta-strand structure over these three residues. The high signal-to-noise ratio of the 2D spectra suggests that membrane-associated fusion peptides with longer sequences of labeled amino acids can also be assigned with 2D and 3D methods.

Amino Acid Sequence↗
PubMed2004

Carboxyl terminus truncated human papillomavirus type 58 L1 protein maintains its bioactivity and ability to form virus-like particles.

To prepare carboxyl terminus truncated human papillomavirus type 58 L1 (HPV58L1) protein and evaluate its ability to form virus-like particles, the baculovirus and Sf-9 insect cells was used to express HPV58L1 protein, and pFastBac-Htb containing HPV58L1 gene sequence of carboxyl terminus truncation was generated. Then Sf-9 cells were infected with recombinant baculovirus. After being cultured, the post-infected cells expressing--HPV58L1 protein were harvested and analyzed by SDS-PAGE and Western blot. The ProBond purification system was used for protein purification. The bio-activity of purified protein was identified by mouse erythrocyte hemagglutination assay, and the VLP formation was examined with transmission electron microscope. Our results showed that the recombinant baculovirus was generated and the Sf-9 cells was infected with the recombinant baculovirus, and after collecting, total cellular proteins were extracted. Truncated HPV58L1 protein with MW 58KD was revealed by SDS-PAGE and confirmed by Western blot. The purified L1 proteins under native condition could cause mouse erythrocytes to agglutinate and form VLP. It is concluded that HPV58L1 protein with carboxyl terminus truncation could be efficiently expressed. In baculovirus Sf-9 cells expression system, the purified protein could self-assemble into virions in vitro, and induce agglutination of mouse erythrocytes, indicating that carboxyl terminus truncation does not interfere with the bioactivity of HPV58L1 protein.

Baculoviridae↗
PubMed2004

New ouabain-conjugated peptide found from phage displayed peptide library.

BACKGROUND: Recently, numerous investigations have shown that endogenous ouabain plays an important role in primary and secondary hypertension. The purpose of this study was to find ouabain-conjugated peptides (OCP) to block or to antagonize actions between endogenous ouabain (EO) and sodium pump, to serve as theoretical and experimental bases of EO in hypertension. METHODS: The study involved screening the phage displayed 12-peptide library by biopanning for OCP. The DNA sequence of each selected peptide was determined and the amino acid sequences were deduced. The highest consistent of the polypeptide was synthesized by peptide synthesizer. Synthetic OCP was identified, its binding activity determined by radioligand binding assay, and bioactivity of ouabain conjugated peptide was measured by erythrocyte 86Rb uptake. RESULTS: Three kinds of peptides were identified. Peptide A (12 peptide, Leu-Leu-Ala-Asp-Thr-Thr-His-His-Arg-Pro-Trp-Thr) was the highest consistence of peptide sequences, occupied in 66.7% (8/12). Peptide A was synthesized. The results verified that there was binding activity between synthetically OCP and 3H-ouabain, and that OCP was capable of suppressing the inhibition action between ouabain and sodium pump on the surface of erythrocyte. The results showed that efficacy was in a dose-dependent manner. CONCLUSION: It is important that the results not only obtain distinctive OCP, but also supply valuable experimental data in detection of ouabain and therapy in hypertension.

Dose-Response Relationship, Drug↗
PubMed2004

Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death.

Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA were measured in elastase-treated Kupffer cells. Hepatocytes were treated with FasL and their viability was assessed by monotetrazolium (MTT), apoptosis by flow cytometry, as well as caspase-3 and p38-mitogen-activated protein kinase (MAPK) by immunoblotting. Elastase increased aspartate aminotransferase and lactate dehydrogenase in cocultures of hepatocyte and Kupffer cells (P<0.040). Elastase increased FasL production from Kupffer cells (P=0.02) and upregulated FasL mRNA (FasL/beta-2 microglobulin (BMG): 0.23+/-0.03 vs. 0.11+/-0.003; P=0.04). FasL increased alanine aminotransferase and lactate dehydrogenase (P<0.03) and reduced hepatocyte viability by 45% (P=0.01). FasL increased the number of dually labeled cells with AnnexinV/7AAD (P=0.03) while upregulating cleavage of caspase-3 and the phosphorylation of p38-MAPK. FasL antibody attenuated the FasL-related increase in dually labeled cells (P=0.02), the cleavage of caspase-3, and phosphorylation of p38-MAPK. Pancreatic elastase upregulates FasL within Kupffer cells. FasL induces hepatocyte injury and death and upregulates p38-MAPK and caspase-3 within hepatocytes. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.

Animals↗
PubMed2004

Acute pancreatitis induces FasL gene expression and apoptosis in the liver.

BACKGROUND: Liver injury is an important prognostic indicator in acute pancreatitis. We previously demonstrated that Kupffer cell-derived cytokines mediate liver injury. In this work, we sought to characterize the role of Fas Ligand (FasL) in liver injury during acute pancreatitis. METHODS: Acute pancreatitis was induced in mice using cerulein; serum FasL, AST, ALT, liver FasL, p38-MAPK, and caspase-3 were measured. FasL mRNA and protein and its receptor (Fas) were determined in rat Kupffer cells treated with elastase (1 U/ml) to mimic acute pancreatitis. Apoptosis was measured by flow cytometry. RESULTS: Cerulein-induced pancreatitis increased serum AST, ALT, and FasL and up-regulated liver FasL (1315 +/- 111 versus 310 +/- 164 pg/ml, P = 0.002 versus sham), while inducing p38-MAPK phosphorylation (P < 0.01 versus sham) and cleavage of caspase-3 (P < 0.04 versus sham); all were attenuated by pretreatment with the Kupffer cell inhibitor, gadolinium (all P < 0.003). In vitro, elastase induced a time-dependent increase in Kupffer cell FasL protein (FasL = 404 +/- 94 versus 170 +/- 40, P = 0.02, versus control), a 100-fold increase in FasL mRNA, and up-regulated Fas (FasL receptor). Gadolinium significantly attenuated the elastase-induced increase in FasL and FasL mRNA (FasL = 230 +/- 20 versus 404 +/- 94, P = 0.01, versus elastase) but had little effect on Fas. Additionally, elastase-primed Kupffer cell media induced apoptosis in hepatocytes (29 +/- 1 versus 16% +/- 1%; versus control, P < 0.001). CONCLUSIONS: Acute pancreatitis induces liver injury and hepatocyte death while up-regulating FasL, p38-MAPK, and caspase-3. Fas is up-regulated within Kupffer cells, suggesting that FasL may autoregulate its production by inducing its originator-cell death. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.

Acute Disease↗
PubMed2004

Prognostic significance of gelsolin expression level and variability in non-small cell lung cancer.

BACKGROUND: Gelsolin is an actin-binding protein that mediates cellular motility and maintains the integrity of cytoskeletal structure. Diminished expression of gelsolin has been observed in human cancer cell lines and tumors. Studies of the prognostic effect of gelsolin expression (GE) in non-small cell lung cancer (NSCLC) are rare and results are inconsistent to date. The present study used immunohistochemistry to evaluate the prognostic effect of gelsolin expression in 155 patients with resectable NSCLC. METHODS: Detection of gelsolin in tumor cells was performed by immunohistochemistry, and two approaches to classification were used to describe expression: expression level (negative, reduced or high) and expression uniformity (uniform or variable). Expression level was determined by a weighted index of intensity of staining (i.e., overall tendency) in the specimen. Expression uniformity was based on the presence or absence of variability in immunostaining within the tumor section. Chi-square test, student t-test, Cox proportional hazards regression and Kaplan-Meier survival analysis were used in data analyses. RESULTS: After controlling for covariates, high level gelsolin expression was significantly associated with poor survival compared with negative gelsolin expression in NSCLC, and this adverse prognostic effect was specific to patients with stage II tumors and for patients with squamous cell carcinomas. Similarly, variable gelsolin expression was significantly associated with poor survival compared with uniform gelsolin expression and this adverse prognostic effect was also specific to patients with stage II tumors and for patients with squamous cell carcinomas. CONCLUSION: High level gelsolin expression and variable gelsolin expression are adverse prognostic factors for NSCLC in this study, which might manifest the high motility and heterogeneity of tumor cells, two distinguishing characteristics for tumors with potentially enhanced invasive and dissemination capabilities.

Aged↗
PubMed2004

Statistical parametric mapping applied to an autoradiographic study of cerebral activation during treadmill walking in rats.

Autoradiographs are conventionally analyzed by a region-of-interest (ROI) analysis. However, definition of ROIs on an image set is labor intensive, is subject to potential inter-rater bias, and is not well suited for anatomically variable structures that may not consistently correspond to specific ROIs. Most importantly, the ROI method is poorly suited for whole-brain analysis, where one wishes to detect all activations resulting from an experimental paradigm. A system developed for analysis of imaging data in humans, Statistical Parametric Mapping (SPM), avoids some of these limitations but has not previously been adapted as a tool for the analysis of autoradiographs. Here, we describe the application of SPM to an autoradiographic data set mapping cerebral activation in rats during treadmill walking. We studied freely moving, non-tethered rats that received injections of the cerebral blood flow tracer [14C]-iodoantipyrine, while they were performing a treadmill task (n = 7) or during a quiescent control condition (n = 6). Results obtained with SPM were compared to those previously reported using a standard ROI-based method of analysis [J. Cereb. Blood Flow Metab. 23(2003) 925]. The SPM method confirmed most areas detected as significant using the ROI approach. However, in the subcortex, SPM detected additional significant regions that, because of their irregular structures, fell short of statistical significance when analyzed by ROI. The SPM approach offers the ability to perform a semi-automated whole-brain analysis, and coupled with autoradiography, provides an effective means to globally localize functional activity in small animals.

Animals↗
PubMed2004

Early administration of nicotinamide prevents learning and memory impairment in mice induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine.

BACKGROUND AND PURPOSE: NAD has been reported to improve the dementia of the Alzheimer type or sensory register, short- and long-term memory loss in the aged. Although nicotinamide has been confirmed to decrease infarct volumes and neurological deficit findings in several animal stroke models, it is not clear whether its neuroprotective effects can prevent memory damage sequelae. METHODS: We have addressed this topic by designing two behavioral paradigms. A memory impairment and cognitive change model was used in mice following 1-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine (MPTP) exposure. Step-down and step-through tests were performed to examine the effects of nicotinamide on learning and memory impairment. RESULTS: It was found that the early administration of nicotinamide (2 h after the injection of MPTP) could decrease error numbers, lessen stimulation time and prolong residence duration on the safety platform in the step-down test. Delayed administration of nicotinamide resulted in decreased effects. Similar results were found in the step-through test. Nicotinamide administrated 12 h after the induction of a memory-impairment model still exerted its effects on memory dysfunction. CONCLUSIONS: The injection of MPTP can cause a loss of brain functions including learning and memory. Learning and memory dysfunction probably occurs secondary to damage to arterioles and dopaminergic neurons by MPTP. By inhibiting oxidative stress, increasing NAD synthesis and ATP production and inhibiting poly (ADP-ribose) polymerase, nicotinamide is known to rescue the still viable, but injured, cells. This rescue process may partially restore learning and memory.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

Changes of hypothalamic alpha-MSH and CART peptide expression in diet-induced obese rats.

Two hypothalamic peptides, cocaine and amphetamine-regulated transcript (CART) and alpha-melanocyte-stimulating hormone (alpha-MSH), recognized as anorexigenic neuropeptides to suppress the feeding behavior, were monitored in rats fed with a high-fat (HIF) diet for 14 weeks. While half of the rats developed obesity (diet-induced obese, DIO), some did not (diet resistant, DR). Compared to the DR rats and the control rats (fed with standard chow), DIO rats were accompanied by a markedly higher energy intake and a decrease in the number of neurons carrying alpha-MSH and CART peptide in the arcuate nucleus of the hypothalamus. Failure of hypothalamic anorexigenic peptides CART and alpha-MSH to increase their content in response to HIF diet may play a key role for overly high energy consumption, resulting in obesity.

Animals↗
PubMed2004

Measurement of cardiac output with indocyanine green transcutaneous fluorescence dilution technique.

BACKGROUND: Cardiac output is an essential parameter for the hemodynamic assessment of patients with cardiovascular disease. The authors tested in an animal model the feasibility of measuring cardiac output by transcutaneous fluorescence monitoring of an intravenous bolus injection of indocyanine green. METHODS: Fluorescence dilution cardiac output was measured in 10 anesthetized rabbits and compared with cardiac output measured with a pulmonary thermodilution catheter and to aortic velocity measured by Doppler ultrasound. Indocyanine green fluorescence was excited with a near-infrared laser and measured with an optical probe positioned on the central ear artery. Measurements were obtained during baseline conditions as well as during short-term decreases and increases of the cardiac output. RESULTS: The fluorescence of circulating indocyanine green detected transcutaneously varied proportionally to that of arterial blood samples, which allowed for calibration in terms of blood concentration of indocyanine green. Average values of fluorescence dilution cardiac output and thermodilution cardiac output measured in baseline conditions were 412 (+/- 13) and 366 (+/- 11) ml/min, respectively. Fluorescence dilution cardiac output showed a close, one-to-one linear relation with thermodilution cardiac output in each animal and in the pooled data from all animals (slope = 0.95 x 0.03; R = 0.94). Fluorescence dilution cardiac output overestimated thermodilution cardiac output by an average of 46 (+/- 6) ml/min during baseline conditions. Fluorescence dilution cardiac output was tightly correlated with aortic velocity. CONCLUSIONS: The proposed technique yielded accurate estimates of the cardiac output in experimental animals. This study should provide an initial framework for clinical testing of this new minimally invasive method for measuring cardiac output.

Animals↗
PubMed2004

Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin.

Acute renal failure secondary to ischemic injury remains a common problem, with limited and unsatisfactory therapeutic options. Neutrophil gelatinase-associated lipocalin (NGAL) was recently shown to be one of the maximally induced genes early in the postischemic kidney. In this study, the role of NGAL in ischemic renal injury was explored. Intravenous administration of purified recombinant NGAL in mice resulted in a rapid uptake of the protein predominantly by proximal tubule cells. In an established murine model of renal ischemia-reperfusion injury, intravenous NGAL administered before, during, or after ischemia resulted in marked amelioration of the morphologic and functional consequences, as evidenced by a significant decrease in the histopathologic damage to tubules and in serum creatinine measurements. NGAL-treated animals also displayed a reduction in the number of apoptotic tubule cells and an increase in proliferating proximal tubule cells after ischemic injury. The results indicate that NGAL may represent a novel therapeutic intervention in ischemic acute renal failure, based at least in part on its ability to tilt the balance of tubule cell fate toward survival.

Acute Kidney Injury↗