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Biomedical subjects

Jie Wang

Publications and source records attributed to Jie Wang.

At least 37 records · Page 2Linked to original sources

Toxicity of microcystins in the isolated hepatocytes of common carp (Cyprinus carpio L.).

The toxicity of hepatotoxic microcystins produced mainly by Microcystis aeruginosa in mammals and fishes was well studied in recent years. However, there were scarcely reports in toxic effects of microcystins on isolated hepatocytes of fishes, especially investigation of microcystin-induced apoptosis and/or necrosis in carp hepatocytes. In the present study, the isolated hepatocytes of common carp were exposed to various concentrations of microcystins (0.01, 0.1, 1, 10, 100, 1000 microg L(-1)) for 2, 4, 8, 16 and 24h, respectively, and cytotoxicity of microcystins in the toxin-treated cells was determined. Results of this study showed that cytotoxicity of microcystins on carp hepatocytes was time and dose-dependent, and the approximate LC(50) of microcystins in carp hepatocytes was 169.2 microg L(-1). The morphological changes typical of apoptosis, such as blebbing of cell membrane, condensation and fragmentation of cell nucleus were observed in the hepatocytes exposed to microcystins (1, 10 and 100 microg L(-1)) using fluorescence and differential interference contrast microscopy. Agarose gel electrophoresis of DNA demonstrated a typical apoptotic "ladder pattern" in microcystin-treated hepatocytes after 16 h of exposure. Results of the present study indicated that the form of cell death in microcystin-treated hepatocytes depend on the exposure dose of toxin. When lower concentration of microcystins (10 and 100 microg L(-1)) was used for exposure, carp hepatocytes died in apoptosis while, when higher one used (1000 microg L(-1)), they died in the form of necrosis.

Animals↗

Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men.

BACKGROUND: Little is known about the clinical and virologic manifestations of human herpesvirus (HHV)-8 infection in immunocompetent persons in the absence of malignancy. METHODS: A total of 46 human immunodeficiency virus-negative, HHV-8-seropositive men collected saliva daily, and 25 recorded 15 common symptoms daily (gastrointestinal, constitutional, and oropharyngeal) and absences from work or school. Quantitative polymerase chain reaction measured HHV-8 DNA in saliva. RESULTS: Some 44 (96%) of 46 men reported having sex with men (MSM). Of the 44 MSM, 27 (61%) had HHV-8 detected in saliva on > or = 1 day; heterosexual men also shed HHV-8. In analyses restricted to MSM, HHV-8 DNA was detected on 636 (22%) of 2897 days. Among MSM with HHV-8 detected in saliva, the median rate was 20% (range, 1%-100%), with 30% shedding on > 50% of days, and the median quantity was 4.5 log10 copies/mL (range, 2.0-7.3 log10 copies/mL). The quantity of HHV-8 shed was lower in nonwhites (P<.001) and younger participants (P=.03). The frequency of HHV-8 detection and quantity were correlated (r=0.62; P<.001). Symptoms were reported on 10 (9%) of 114 days when HHV-8 was present, compared with 78 (9%) of 830 days without (odds ratio, 0.93 [95% confidence interval, 0.30-2.88]; P=.9). CONCLUSIONS: HHV-8 is detected frequently and intermittently in the saliva of chronically infected immunocompetent MSM, but this infection is asymptomatic.

Adult↗

Effect of passive cardiac containment on ventricular synchrony and cardiac function in awake dogs.

OBJECTIVE: Passive restraint of the left ventricle (LV) has been shown to have beneficial effects on acute hemodynamics and reverse remodeling in both animal and human models. The goals of this study were to test whether a left ventricular support device (LVSD) improves LV synchrony and/or affects cardiac performance. METHODS: Ten dogs were chronically instrumented to measure hemodynamics and LV volume (sonomicrometry). Congestive heart failure (CHF) was induced by repeated intracoronary microembolization via a chronically implanted coronary catheter. The LVSD was implanted after establishment of CHF in five animals, and five animals were observed as controls. All animals were then observed for 8 weeks. A mathematical model to measure LV synchrony was used to evaluate LV motion over time. RESULTS: Mean arterial pressure and LV pressures was significantly increased after LVSD therapy, and LV pressure-volume relationships were shifted leftwards, although no change was seen in ejection fraction, end-systolic elastance, or LV dP/dt versus control. There was no significant change in diastolic function in LVSD animals compared with control animals. End-diastolic volumes were reduced by 15% after 8 weeks with LVSD treatment, versus an increase of 8% in control animals (p<0.05). Synchrony was significantly improved with LVSD therapy compared with control (9% vs 76% of baseline) in 1 of 11 ventricular dimension axes (Anterior-Apex). CONCLUSIONS: LVSD therapy provided only minimal improvement in ventricular synchrony and partially improved hemodynamics. Further study into mechanisms of benefit are warranted.

Animals↗

Molecular level structures of poly(n-alkyl methacrylate)s with different side chain lengths at the polymer/air and polymer/water interfaces.

Sum frequency generation (SFG) vibrational spectroscopy has been successfully applied to study molecular structures of several poly(n-alkyl methacrylate)s (PAMAs) with different side chain lengths at the PAMA/air and PAMA/water interfaces. We have observed that the ester side chains from all PAMAs always dominate the interface, but the orientation information of the methyl end group on the side chains varies, depending on the length of the side chain. The contributions from methylene groups on the side chains have been evaluated, and the surface structures have been related to the surface tension of these polymers. Different water restructuring behaviors have been observed for different PAMAs. This phenomenon and its reversibility are strongly dependent on the glass transition temperature of each polymer, which is influenced by the side chain length. Detailed data fitting and analysis has been discussed.

Air↗

Integrons containing the VIM-2 metallo-beta-lactamase gene among imipenem-resistant Pseudomonas aeruginosa strains from different Chinese hospitals.

A total of 140 nonrepetitive strains of imipenem-resistant Pseudomonas aeruginosa were isolated from five different Chinese hospitals. Fourteen isolates were confirmed to contain the VIM-2 metallo-beta-lactamase gene. Twelve isolates harbored two kinds of class 1 integron, containing both VIM-2- and aminoglycoside-resistant genes.

Conjugation, Genetic↗

Expression of Delta DNMT3B variants and its association with promoter methylation of p16 and RASSF1A in primary non-small cell lung cancer.

Despite the role of DNMT3B in de novo DNA methylation, a correlation between DNMT3B expression and promoter DNA methylation has not being established in tumors. We recently reported DeltaDNMT3B, a subfamily of DNMT3B, with seven variants, as the predominant expression forms in non-small cell lung cancer (NSCLC). We hypothesized that expression of the DeltaDNMT3B variants plays a role in promoter methylation formation during lung tumorigenesis. Expression of seven DeltaDNMT3B variants was measured in 119 NSCLCs and the corresponding normal lungs using reverse transcription-PCR. The expression patterns of DeltaDNMT3B variants were analyzed with the status of p16 and RASSF1A promoter methylation in the tumors as well as in patients' clinical variables, including outcomes. Expression of DeltaDNMT3B variants was detected in 94 of 119 (80%) tumors but in only 22 (18%) of the corresponding normal lungs (P < 0.0001). DeltaDNMT3B1, DeltaDNMT3B2, and DeltaDNMT3B4 were the most frequently detected transcripts in the tumors (62%, 76%, and 46%, respectively). The expression of DeltaDNMT3B variants was associated with p16 and RASSF1A promoter methylation in the tumors, but the strongest association was between DeltaDNMT3B4 and RASSF1A. Forty-two of 46 (91%) tumors with RASSF1A promoter methylation expressed DeltaDNMT3B4 compared with only 13 of 73 (18%) tumors without the promoter methylation (P < 0.0001). Strong associations were also observed between expression of the variants in the tumors and in patients' clinical outcomes. Expression of DeltaDNMT3B variants is common in NSCLC and may play an important role in the development of promoter methylation.

Adult↗

Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization.

Left ventricular (LV) diastolic dysfunction is a fundamental impairment in congestive heart failure (CHF). This study examined LV diastolic function in the canine model of CHF induced by chronic coronary embolization (CCE). Dogs were implanted with coronary catheters (both left anterior descending and circumflex arteries) for CCE and instrumented for measurement of LV pressure and dimension. Heart failure was elicited by daily intracoronary injections of microspheres (1.2 million, 90- to 120-microm diameter) for 24 +/- 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dt(min)) decreased by 25 +/- 2% (P < 0.05) and LV isovolumic relaxation constant and duration increased by 19 +/- 5% and 25 +/- 6%, respectively (both P < 0.05), indicating an impairment of LV active relaxation, which was cardiac preload independent. LV passive viscoelastic properties were evaluated from the LV end-diastolic pressure (EDP)-volume (EDV) relationship (EDP = be(alpha*EDV)) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient (alpha) increased by 62 +/- 10% (P < 0.05) and the stiffness constant (k) increased by 66 +/- 13% after CCE. The regional myocardial diastolic stiffness in LV anterior and posterior walls was increased by 70 +/- 25% and 63 +/- 24% (both P < 0.05), respectively, after CCE, associated with marked fibrosis, increase in collagen I and III, and enhancement of plasminogen activator inhibitor-1 (PAI-1) protein expression. Thus along with depressed LV systolic function there is significant impairment of LV diastolic relaxation and increase in chamber stiffness, with development of myocardial fibrosis and activation of PAI-1, in the canine model of CHF induced by CCE.

Animals↗

Toward elucidating the membrane topology of helix two of the colicin E1 channel domain.

The membrane-bound closed state of the colicin E1 channel domain was investigated by site-directed fluorescence labeling using a bimane fluorophore attached to each single cysteine residue within helix 2 of each mutant protein. The fluorescence properties of the bimane fluorophore were measured for the membrane-associated form of the closed channel and included fluorescence emission maximum, fluorescence anisotropy, apparent polarity, surface accessibility, and membrane bilayer penetration depth. The fluorescence data show that helix 2 is an amphipathic alpha-helix that is situated parallel to the membrane surface, but it is less deeply embedded within the bilayer interfacial region than is helix 1 in the closed channel. A least squares fit of the various data sets to a harmonic wave function indicated that the periodicity and angular frequency for helix 2 in the membrane-bound state are typical for an amphipathic alpha-helix (3.8 +/- 0.1 residues per turn and 94 +/- 4 degrees, respectively) that is located at an interfacial region of a membrane bilayer. Dual quencher analysis also revealed that helix 2 is peripherally membrane associated, with one face of the helix dipping into the interfacial region of the lipid bilayer and the other face projecting outwardly into the aqueous solvent. Finally, our data show that helices 1 and 2 remain independent helices upon membrane association with a short connector link (Tyr(363)-Gly(364)) and that short amphipathic alpha-helices participate in the formation of a lipid-dependent, toroidal pore for this colicin.

Amino Acid Sequence↗

Topography of the hydrophilic helices of membrane-inserted diphtheria toxin T domain: TH1-TH3 as a hydrophilic tether.

After low pH-triggered membrane insertion, the T domain of diphtheria toxin helps translocate the catalytic domain of the toxin across membranes. In this study, the hydrophilic N-terminal helices of the T domain (TH1-TH3) were studied. The conformation triggered by exposure to low pH and changes in topography upon membrane insertion were studied. These experiments involved bimane or BODIPY labeling of single Cys introduced at various positions, followed by the measurement of bimane emission wavelength, bimane exposure to fluorescence quenchers, and antibody binding to BODIPY groups. Upon exposure of the T domain in solution to low pH, it was found that the hydrophobic face of TH1, which is buried in the native state at neutral pH, became exposed to solution. When the T domain was added externally to lipid vesicles at low pH, the hydrophobic face of TH1 became buried within the lipid bilayer. Helices TH2 and TH3 also inserted into the bilayer after exposure to low pH. However, in contrast to helices TH5-TH9, overall TH1-TH3 insertion was shallow and there was no significant change in TH1-TH3 insertion depth when the T domain switched from the shallowly inserting (P) to deeply inserting (TM) conformation. Binding of streptavidin to biotinylated Cys residues was used to investigate whether solution-exposed residues of membrane-inserted T domain were exposed on the external or internal surface of the bilayer. These experiments showed that when the T domain is externally added to vesicles, the entire TH1-TH3 segment remains on the cis (outer) side of the bilayer. The results of this study suggest that membrane-inserted TH1-TH3 form autonomous segments that neither deeply penetrate the bilayer nor interact tightly with the translocation-promoting structure formed by the hydrophobic TH5-TH9 subdomain. Instead, TH1-TH3 may aid translocation by acting as an A-chain-attached flexible tether.

Boron Compounds↗

Pancreatic beta cells lack a low glucose and O2-inducible mitochondrial protein that augments cell survival.

beta cell failure is a common denominator of diabetes. Susceptibility to stress-induced apoptosis may underlie beta cell failure and/or hamper islet transplantation therapy. The causal basis is not well understood. In efforts to identify important differences in gene expression in alpha vs. beta cells, a gene termed HIMP1 (Hypoglycemia/hypoxia Inducible Mitochondrial Protein, or HIG1) has been cloned from an alpha cell cDNA library. It is a member of a well conserved eukaryote protein family. In mice, its two alternatively spliced products each form a transmembrane loop, having an N(outside)-C(outside) orientation and are expressed highly in the mitochondrial inner membrane in several tissues including heart and pancreatic alpha cells, but not in beta cells. Ectopic expression of HIMP1 in MIN6 beta cells protects the cells from apoptosis induced by several stimuli and prolongs their survival. These results suggest an important role for HIMP1 in stress protective programs in mitochondria.

Animals↗

Irreducible representation and projection operator application to understanding nonlinear optical phenomena: hyper-Raman, sum frequency generation, and four-wave mixing spectroscopy.

Symmetry plays an essential role in understanding optical activities of a molecule in infrared and Raman vibrational spectroscopy as well as in nonlinear optical vibrational spectroscopy. Each vibrational mode belongs to an irreducible representation of the underlying symmetry group. In this paper, using the alpha-helical polypeptide symmetry as an example, we calculate all the third rank nonzero hyper-Raman tensors as well as the infrared and Raman tensors by applying the projection operators to each irreducible species. We demonstrate that the projection operator method provides selection rules for the infrared, Raman, and hyper-Raman vibrational transitions and also other nonlinear optical spectroscopy such as sum frequency generation and the four-, five-, and six-wave mixing coherent vibrational transitions. Specific expressions for all nonzero elements of the corresponding nonlinear susceptibility tensors in a laboratory-fixed coordinate frame are also deduced.

Optics and Photonics↗

Dynamic changes in subgraph preference profiles of crucial transcription factors.

Transcription factors with a large number of target genes--transcription hub(s), or THub(s)--are usually crucial components of the regulatory system of a cell, and the different patterns through which they transfer the transcriptional signal to downstream cascades are of great interest. By profiling normalized abundances (A(N)) of basic regulatory patterns of individual THubs in the yeast Saccharomyces cerevisiae transcriptional regulation network under five different cellular states and environmental conditions, we have investigated their preferences for different basic regulatory patterns. Subgraph-normalized abundances downstream of individual THubs often differ significantly from that of the network as a whole, and conversely, certain over-represented subgraphs are not preferred by any THub. The THub preferences changed substantially when the cellular or environmental conditions changed. This switching of regulatory pattern preferences suggests that a change in conditions does not only elicit a change in response by the regulatory network, but also a change in the mechanisms by which the response is mediated. The THub subgraph preference profile thus provides a novel tool for description of the structure and organization between the large-scale exponents and local regulatory patterns.

Cell Cycle↗

Integrated analysis of multiple data sources reveals modular structure of biological networks.

It has been a challenging task to integrate high-throughput data into investigations of the systematic and dynamic organization of biological networks. Here, we presented a simple hierarchical clustering algorithm that goes a long way to achieve this aim. Our method effectively reveals the modular structure of the yeast protein-protein interaction network and distinguishes protein complexes from functional modules by integrating high-throughput protein-protein interaction data with the added subcellular localization and expression profile data. Furthermore, we take advantage of the detected modules to provide a reliably functional context for the uncharacterized components within modules. On the other hand, the integration of various protein-protein association information makes our method robust to false-positives, especially for derived protein complexes. More importantly, this simple method can be extended naturally to other types of data fusion and provides a framework for the study of more comprehensive properties of the biological network and other forms of complex networks.

Algorithms↗

Exhaustion of the Frank-Starling mechanism in conscious dogs with heart failure induced by chronic coronary microembolization.

The role of the Frank-Starling mechanism in the regulation of cardiac systolic function in the ischemic failing heart was examined in conscious dogs. Left ventricular (LV) dimension, pressure and systolic function were assessed using surgically implanted instrumentations and non-invasive echocardiogram. Heart failure was induced by daily intra-coronary injections of microspheres for 3-4 weeks via implanted coronary catheters. Chronic coronary embolization resulted in a progressive dilation of the left ventricle (12+/-3%), increase in LV end-diastolic pressure (118+/-19%), depression of LV dP/dt(max) (-19+/-4%), fractional shortening (-36+/-7%), and cardiac work (-60+/-9%), and development of heart failure, while the LV contractile response to dobutamine was depressed. A brief inferior vena caval occlusion in dogs with heart failure decreased LV preload to match the levels attained in their control state and caused a further reduction of LV dP/dt(max), fractional shortening, stroke work and cardiac work. Moreover, in response to acute volume loading, the change in the LV end-diastolic dimension-pressure (DeltaLVEDD-DeltaLVEDP) curve in the failing heart became steeper and shifted significantly to the left, while the increases in LV stroke work and cardiac work were blunted. Thus, our results suggest that the Frank-Starling mechanism is exhausted in heart failure and unable to further respond to increasing volume while it plays an important compensatory role in adaptation to LV dysfunction in heart failure.

Animals↗

Neuroprotective effects of neuregulin-1 in rat models of focal cerebral ischemia.

The purpose of this study was to investigate the therapeutic efficacy and mechanism of recombinant human NRG-1 to attenuate ischemia/reperfusion brain injury. NRG-1(3.0 ng/kg) was applied intravascularly 10 min before middle cerebral artery occlusion (MCAO) and then focal cerebral ischemia for 90 min and reperfusion for 24 h. The rats were scored post-reperfusion for neurological deficits and infarct volume in the brain was assessed by 2,3,5-triphenyltetrazolium chloride(TTC). Apoptosis was evaluated by TUNEL staining. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure changes of caspase-3 mRNA. The level of TNF-alpha was determined using enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that recombinant human NRG-1 could reduce cerebral infarct volume by about 71% (P < 0.05) and TUNEL positive cells when given immediately before MCAO, and improved behavior of animals. Furthermore, we also showed that NRG-1 could also decrease the expression of caspase-3 mRNA and production of TNF-alpha protein. These data suggest that pre-administration of NRG-1 attenuates cerebral ischemia and reperfusion injury. This protective effect may be involved in the inhibition of caspase-3 and TNF-alpha.

Analysis of Variance↗

A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia.

The purpose of this study was to test if HBOC-201, a hemoglobin-based oxygen-carrying solution, can decrease infarct size (or Inf) during acute, severe myocardial ischemia and reperfusion. To test the impact of HBOC-201 on infarct size, ischemia was produced in 18 dogs by coronary stenosis to achieve 80-95% flow reduction for 195 min along with pacing 10% above the spontaneous heart rate, followed by 180 min of reperfusion. Animals were randomized to intravenous infusion of HBOC-201 (1 g/kg) (n=6), normal saline (NS) (n=6), or phenylephrine (Phe) (n=6, as a control for the increased blood pressure seen with HBOC-201), given 15 min after the start of ischemia. Amount of infarct was quantified as the ratio between area at risk (AAR) and Inf after Evans blue and 2,3,5-triphenyltetrazolium chloride staining. Hearts were divided into five layers from base (layer A) to apex (layer E) and photographed for digital image analysis of AAR and Inf. Regional myocardial function (RMF) was also measured after 60 min of ischemia and 15 min of reperfusion. Inf/AAR was significantly reduced after HBOC-201 therapy (4.4+/-2.2%) vs. NS (26.0+/-3.6%) and Phe (25.7+/-4.1%) (both, P<0.05). RMF after reperfusion was restored to 92% of baseline with HBOC-201 compared with 11% of baseline after NS (P<0.05) and 49% after Phe (P=not significant). HBOC-201 administration after induction of severe myocardial ischemia by acute coronary stenosis reduces infarct size and improves myocardial viability.

Animals↗

Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction.

The impact of hypertension on left ventricular (LV) structure, pump function, and heart failure in Dahl salt-sensitive rats is poorly characterized but hypothesized to yield insights into the pathophysiology of heart failure with normal or preserved ejection fraction. Eighty Dahl salt-sensitive rats were fed either a high-salt (HS) or low-salt (LS, controls) diet starting at age 7 weeks. Ventricular properties were measured by echocardiography, hemodynamics and end-systolic and end-diastolic pressure-volume relationships (ESPVR and EDPVR, respectively). Compared with LS controls, HS rats developed severe hypertension and LV hypertrophy. At week 12, HS rats developed passive diastolic dysfunction (leftward/upward shifted EDPVR, increased chamber stiffness) with reductions in end-diastolic volume. However, the ESPVR also shifted upward (enhanced end-systolic function) so that overall pump function was enhanced compared with LS, and there was no change in end-diastolic pressure (EDP). At 16 and 20 weeks, HS hearts enlarged so that end-diastolic volumes and EDPVRs became similar to the respective age-matched LS controls. Concomitantly, the ESPVRs and overall pump function curves also moved toward controls, and ejection fraction declined. Despite normal or enhanced overall pump function at these times, EDP and wet lung weight increased, indicative of development of heart failure. In the Dahl salt-sensitive rat, which pathophysiologically retains salt and water, the development of heart failure (increased EDP and wet lung weight) is dissociated from changes in passive diastolic and active systolic properties. These observations suggest that a volume overload sate plays an important pathophysiological role in development of heart failure despite preserved overall ventricular pump function in this model of chronic hypertension.

Animals↗

Prevalence of the metabolic syndrome and its relation to cardiovascular disease in an elderly Chinese population.

OBJECTIVES: This study sought to assess the prevalence of the metabolic syndrome (MetS) and its association with cardiovascular disease (CVD) in elderly Chinese people. BACKGROUND: The information available about the prevalence of MetS based on the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) in China is limited. METHODS: We conducted a population-based cross-sectional study in an urban Beijing sample of 2,334 participants age 60 to 95 years (943 men, 1,391 women). The CVD included diagnosed coronary heart disease (CHD), stroke, and peripheral arterial disease (PAD). RESULTS: The prevalence of MetS by the NCEP criteria was 30.5% (17.6% in men, 39.2% in women). Use of the new IDF definition significantly increased the prevalence to 46.3% (34.8% in men, 54.1% in women). Odds ratios (OR) for CHD, stroke, PAD, and CVD in those with MetS using the NCEP criteria were 1.43 (95% confidence interval [CI] 1.18 to 1.74), 1.45 (95% CI 1.14 to 1.85), 1.47 (95% CI 1.18 to 1.84), and 1.50 (95% CI 1.25 to 1.81), respectively. Corresponding ORs using new IDF criteria were 1.69 (95% CI 1.40 to 2.02), 1.58 (95% CI 1.26 to 2.00), 1.42 (95% CI 1.14 to 1.76), and 1.73 (95% CI 1.46 to 2.07), respectively. Those who met the IDF but not the NCEP criteria (n = 436, 18.7%) had significantly elevated ORs for CHD (1.66, 95% CI 1.31 to 2.10) and stroke (1.53, 95% CI 1.13 to 2.06). CONCLUSIONS: The MetS is highly prevalent in elderly people in Beijing, particularly among women. Individuals with MetS defined by either criteria are at significantly elevated ORs for CHD, stroke, and PAD. The IDF criteria seem to be better suited than the NCEP criteria for screening and estimating risk of MetS in Chinese people.

Aged↗