Biomedical subjects

Y Hu

Publications and source records attributed to Y Hu.

At least 19 recordsLinked to original sources

PubMed2007

PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies.

Programmed death-1 ligand-1 (PD-L1), a member of the B7 family of costimulatory molecules, plays an important role in the regulations of the cellular and humoral immune responses. In this study, two mouse anti-human PD-L1 monoclonal antibodies named 10E10 and 2H11 were successfully generated and further characterized. Monoclonal antibody 10E10 bound to distinct PD-L1 epitope comparing an available anti-PD-L1 monoclonal antibody on a series of malignant cell lines, activated T lymphocytes, B lymphocytes and dendritic cells. Then, by using immunohistochemistry staining with monoclonal antibody 2H11, the expression of PD-L1 was found in human gastric carcinoma specimens but not in normal or gastric adenoma tissues. Additional data show that PD-L1 can be regarded as a decisive factor in evaluating gastric carcinoma prognosis and anti-human PD-L1 monoclonal antibody 10E10 could inhibit T-cell apoptosis induced by tumor-associated PD-L1. Taken together, these results showed that the two functional mouse anti-human PD-L1 monoclonal antibodies we generated might be of great value for further exploration of the costimulatory molecule regulating network and immunointervention for tumor immunotherapy.

Animals↗

PubMed2006

Selective hair analysis of nicotine by molecular imprinted solid-phase extraction: an application for evaluating tobacco smoke exposure.

A method using a molecularly imprinted polymer (MIP) as the selective sorbent for solid-phase extraction (SPE) has been developed. Its application to the assay of hairy nicotine level among smokers and non-smokers with high-performance liquid chromatography (HPLC) and evaluation of exposures to the environmental tobacco smoke (ETS) were validated. The MIP was synthesized using nicotine as the template molecule and methacrylic acid (MAA) as the functional monomer. This MIP-SPE method provided inherent selectivity and a sensitive response to nicotine with a detection limit of 0.2 ng/ml hair at a signal-to-noise ratio of 3:1 and the limit of quantification was 0.5 ng/ml. The linearity was assessed in the range of 0.5-80 ng/ml hair, with a coefficient (r(2)) greater than 0.987. The amounts of nicotine determined in smokers and non-smokers hair were in the range of 5.1-69.5 ng/mg hair and 0.50-9.3 ng/mg hair, respectively. The reported measures of ETS exposure were significantly associated with hairy nicotine levels. This assay of nicotine in hair using MISPE provided a very selective and reliable method for the evaluation of the exposure to tobacco smoke.

Cotinine↗

PubMed2006

Effects of a 28-day "living high--training low" on T-lymphocyte subsets in soccer players.

The purpose of this study was to investigate the changes in T-lymphocyte subsets in soccer players during "living high--training low" (LHTL) for 28 days in comparison to equally trained control players. Sixteen male soccer players were randomly assigned into two groups. The LHTL group lived in normobaric hypoxic rooms, simulating an altitude of 3000 m for 10 hours per night for 28 days. The control group lived at sea level. Both LHTL and control groups trained together at sea level and completed the same training schedules. The blood samples were collected prior to the trial (baseline) and at 1, 14, 21 and 28 days of the trial, respectively. Lymphocyte subsets were quantitated using the recommended flow cytometry method. The results showed that the relative changes from the baseline in the CD4 (+)/CD8 (+) ratio, in both LHTL and control groups, followed a similar downward trend during the trial. However, the trend was more pronounced in the LHTL group. In the LHTL group, significant differences were seen at both 14 and 28 days compared to the baseline. In addition, a significant difference was also observed between the groups at 14 days. During LHTL, hypoxia may augment the effect which training may have on T-lymphocyte subsets after 14 days, even when training was not performed under hypoxic condition. The long term effect of LHTL was unknown at this time and needs further investigation.

Adult↗

PubMed2006

Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme.

OBJECTIVE: To investigate the association between muscle-specific creatine kinase (CKMM) gene polymorphism and the effects of endurance training on running economy. METHODS: 102 biologically unrelated male volunteers from northern China performed a 5000-m running programme, with an intensity of 95-105% ventilatory threshold. The protocol was undertaken three times per week and lasted for 18 weeks. Running economy indexes were determined by making the participants run on a treadmill before and after the protocol, and the A/G polymorphism in the 3' untranslated region of CKMM was detected by polymerase chain reaction-restricted fragment length polymorphism (NcoI restriction enzyme). RESULTS: Three expected genotypes for CKMM-NcoI (AA, AG and GG) were observed in the participants. After training, all running economy indexes declined markedly. Change in steady-state consumption of oxygen, change in steady-state consumption of oxygen by mean body weight, change in steady-state consumption of oxygen by mean lean body weight and change in ventilatory volume in AG groups were larger than those in AA and GG groups. CONCLUSIONS: The findings indicate that the CKMM gene polymorphism may contribute to individual running economy responses to endurance training.

Adolescent↗

PubMed2006

Polymorphisms in the HBB gene relate to individual cardiorespiratory adaptation in response to endurance training.

OBJECTIVE: The crucial role of haemoglobin in endurance performance has been well documented. We examined whether polymorphisms in the HBB gene modified aerobic capacity. METHODS: 102 recruits were trained by running 5000 m three times per week for 18 weeks. Exercise intensity progressively increased from an initial heart rate corresponding to 95% of the individual baseline ventilatory threshold during the first 10 weeks to 105% during the last 8 weeks. The phenotypes measured were running economy and VO(2)max. Running economy was determined by measuring submaximal VO(2) for 5 min at a constant running speed of 12 km.h(-1) and VO(2)max was obtained during an incremental test to exhaustion. Genomic DNA was extracted from white cells of peripheral blood and the -551C/T, intron2,+16C/G and +340 A/T genotypes were examined relative to the TAA site variants by PCR-RFLP. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium at three loci. None of the running economy and VO(2)max-related traits were associated with the three polymorphisms or haplotypes at baseline, while the training response of running economy was associated with -551C/T and intron2,+16C/G polymorphisms. Subjects homozygous for intron2,+16C/C or -551C/C had decreased oxygen cost of running compared to the other individuals. DISCUSSION: It was concluded that the -551C/C or intron2,+16C/C genotype might explain part of the individual variation in the cardiorespiratory adaptation to endurance training.

Adaptation, Physiological↗

PubMed2006

Arsenic sequestration in iron plaque, its accumulation and speciation in mature rice plants (Oryza sativa L.).

A compartmented soil-glass bead culture system was used to investigate characteristics of iron plaque and arsenic accumulation and speciation in mature rice plants with different capacities of forming iron plaque on their roots. X-ray absorption near-edge structure spectra and extended X-ray absorption fine structure were utilized to identify the mineralogical characteristics of iron plaque and arsenic sequestration in plaque on the rice roots. Iron plaque was dominated by (oxyhydr)oxides, which were composed of ferrihydrite (81-100%), with a minor amount of goethite (19%) fitted in one of the samples. Sequential extraction and XANES data showed that arsenic in iron plaque was sequestered mainly with amorphous and crystalline iron (oxyhydr)oxides, and that arsenate was the predominant species. There was significant variation in iron plaque formation between genotypes, and the distribution of arsenic in different components of mature rice plants followed the following order: iron plaque > root > straw > husk > grain for all genotypes. Arsenic accumulation in grain differed significantly among genotypes. Inorganic arsenic and dimethylarsinic acid (DMA) were the main arsenic species in rice grain for six genotypes, and there were large genotypic differences in levels of DMA and inorganic arsenic in grain.

Absorptiometry, Photon↗

PubMed2006

Murine models of myocardial and limb ischemia: diagnostic end-points and relevance to clinical problems.

Ischemic disease represents the new epidemic worldwide. Animal models of ischemic disease are useful because they can help us to understand the underlying pathogenetic mechanisms and develop new therapies. The present review article summarizes the results of a consensus conference on the status and future development of experimentation in the field of cardiovascular medicine using murine models of peripheral and myocardial ischemia. The starting point was to recognize the limits of the approach, which mainly derive from species- and disease-related differences in cardiovascular physiology. For instance, the mouse heart beats at a rate 10 times faster than the human heart. Furthermore, healing processes are more rapid in animals, as they rely on mechanisms that may have lost relevance in man. The main objective of the authors was to propose general guidelines, diagnostic end points and relevance to clinical problems.

Animal Experimentation↗

PubMed2006

Characterization of neointima lesions associated with arteriovenous fistulas in a mouse model.

Arteriovenous fistulas (AVFs) are usually used for vascular access in the provision of hemodialysis, but AVFs have a 1-year patency rate of only about 60% owing to stenosis. As the molecular mechanisms behind AVF neointimal hyperplasia remain largely unknown, representative models in transgenic mice could be useful to study this process at the genetic level. Hence, we characterized neointimal lesion formation in a model of AVF recently developed in the mouse, where the common carotid artery was end-to-side sutured to jugular vein in C57BL/6J mice. At the site of anastomosis, arterial wall thickening was observed as early as 1 week after surgery (fourfold) and progressed to six- and 10-fold original thickness in carotid arteries after 2 and 3 weeks, respectively. The lumen of the carotid artery was significantly narrowed owing to neointima hyperplasia, and thrombosis was observed in the vein wall opposite to the anastomosed artery. Histological and immunohistochemical analyses revealed that 3-week neointimal lesions consisted of abundant smooth muscle cells (alpha-actin(+)) and a small number of membrane attack complex-1+ macrophages. Furthermore, using chimeric mice receiving bone marrow from transgenic mice expressing the LacZ gene in smooth muscle (SM-LacZ), it was found that bone marrow stem cells did not contribute to smooth muscle cell accumulation in neointimal lesions of AVF arteries. Thus, this model, which reproduces many of the features of human AVF, should prove useful for our understanding of the mechanism of neointimal formation and to evaluate the effects of drugs and gene therapy on this disease.

Animals↗

PubMed2006

Some insights into the mode of action of butadiene by examining the genotoxicity of its metabolites.

1,3-Butadiene (BTD) is an important commodity chemical and air pollutant that has been shown to be a potent carcinogen in mice, and to a lesser extent, a carcinogen in rats. To better assess butadiene's carcinogenic risk to humans, it is important to understand its mode of action and how this relates to differences in responses among species. In a series of in vitro experiments, lymphocytes from rats, mice, and humans were exposed to 3,4-epoxy-1-butene (EB) or 1,2:3,4-diepoxybutane (DEB) for 1h at the G(0) stage of the cell cycle, stimulated to divide, and cultured to assess the ability of these metabolites to induce sister chromatid exchange (SCE) and chromosome aberrations (CAs). EB induced no increases in SCEs or CAs in the cells from the three species. DEB was a potent SCE- and CA-inducer, with the results being similar in each rodent species. The response for SCEs seen in the human cells was more complex, with genetic polymorphism for glutathione-S-transferases (GST) possibly modulating the response. The single cell gel electrophoresis assay was used on genetically engineered V79 cell lines to investigate a possible influence of GST status. Experiments were also conducted to investigate the reason for EB's failure to induce SCEs or CAs in G(0) cells. The results indicate that EB-induced DNA damage was repaired before DNA synthesis in unstimulated lymphocytes, but EB caused a large increase in SCEs if actively cycling cells were treated. Thus, the results indicate that DEB damage is persistent in G(0) cells, and DEB is a much more potent genotoxicant than EB. The carcinogenic effect of butadiene will most likely depend on the degree to which DEB is produced and reaches target tissues, and to a lesser extent on the ability of EB to reach actively dividing or repair deficient cells.

Animals↗

PubMed2006

SEA0400, a novel Na+/Ca2+ exchanger inhibitor, reduces calcium overload induced by ischemia and reperfusion in mouse ventricular myocytes.

Given the potential clinical benefit of inhibiting Na+/Ca2+ exchanger (NCX) activity during myocardial ischemia reperfusion (I/R), pharmacological approaches have been pursued to both inhibit and clarify the importance of this exchanger. SEA0400 was reported to have a potent NCX selectivity. Thus, we examined the effect of SEA0400 on NCX currents and I/R induced intracellular Ca2+ overload in mouse ventricular myocytes using patch clamp techniques and fluorescence measurements. Ischemia significantly inhibited inward and outward NCX current (from -0.04+/-0.01 nA to 0 nA at -100 mV; from 0.23+/-0.08 nA to 0.11+/-0.03 nA at +50 mV, n=7), Subsequent reperfusion not only restored the current rapidly but enhanced the current amplitude obviously, especially the outward currents (from 0.23+/-0.08 nA to 0.49+/-0.12 nA at +50 mV, n=7). [Ca2+]i, expressed as the ratio of Fura-2 fluorescence intensity, increased to 138+/-7% (P<0.01) during ischemia and to 210+/-11% (P<0.01) after reperfusion. The change of NCX current and the increase of [Ca2+]i during I/R can be blocked by SEA0400 in a dose-dependent manner with an EC50 value of 31 nM and 28 nM for the inward and outward NCX current, respectively. The results suggested that SEA0400 is a potent NCX inhibitor, which can protect mouse cardiac myocytes from Ca2+ overload during I/R injuries.

Aniline Compounds↗

PubMed2006

Increased risk of chronic obstructive pulmonary diseases in coke oven workers: interaction between occupational exposure and smoking.

BACKGROUND: Coke oven workers are regularly exposed to coke oven emissions (COE) and may be at risk of developing lung diseases. There is limited evidence for the link between exposure to COE and chronic obstructive pulmonary diseases (COPD). The aim of this study was to explore the dose-response relationship between COE exposure and COPD and to assess the interaction with cigarette smoking. METHODS: Seven hundred and twelve coke oven workers and 211 controls were investigated in southern China. Benzene soluble fraction (BSF) concentrations as a surrogate of COE were measured in representative personal samples and the individual cumulative COE exposure level was quantitatively estimated. Detailed information on smoking habits and respiratory symptoms was collected and spirometric tests were performed. RESULTS: The mean BSF levels at the top of two coking plants were 743.8 and 190.5 microg/m3, respectively, which exceed the OSHA standard (150 microg/m3). After adjusting for cigarette smoking and other risk factors, there was a significant dose-dependent reduction in lung function and increased risks of chronic cough/phlegm and COPD in coke oven workers. The odds ratio for COPD was 5.80 (95% confidence interval 3.13 to 10.76) for high level cumulative COE exposure (> or =1714.0 microg/m3-years) compared with controls. The interaction between COE exposure and smoking in COPD was significant. The risk of COPD in those with the highest cumulative exposure to COE and cigarette smoking was 58-fold compared with non-smokers not exposed to COE. CONCLUSION: Long term exposure to COE increases the risk of an interaction between COPD and cigarette smoking.

Adult↗

PubMed2006

Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses.

Three distinct isolates of Candida albicans were used to establish systemic and oral infections in inbred mice that are genetically resistant or susceptible to tissue damage. Patterns of infection differed significantly between both yeasts and mouse strains. Systemic infection conferred significant protection against re-challenge with the homologous, but not the heterologous yeast; however, the protective effect was more evident in the tissue-susceptible CBA/CaH mice than in the resistant BALB/c strain. In contrast, oral infection induced protection against both homologous and heterologous oral challenge, although this was significant only in the CBA/CaH mice. CBA/CaH mice produced antibodies of both IgG1 and IgG2a subclasses, whereas BALB/c mice produced predominantly IgG1. Western blotting demonstrated considerable differences between epitopes recognised by serum antibodies from mice of both strains after immunisation with each of the three yeasts. Thus, different strains of yeast show considerable specificity in antibody responses elicited by either systemic or oral infection.

Animals↗

PubMed2006

Partial-k-space acquisition method for improved SNR efficiency and temporal resolution in 3D fMRI.

Previous studies have shown the relative importance of physiological noise and thermal noise in 2D MR images. Since physiological noise is proportional to the signal, it can be the dominant component at the center of k-space. In this study we demonstrate that the signal-to-noise ratio (SNR) efficiency and temporal resolution for 3D functional MRI (fMRI) are increased by the use of a partial-k-space acquisition method. In partial-k-space methods, the high-spatial-frequency components are doubled in amplitude during reconstruction, resulting in twice as much noise from those components. However, in sum these contributions are relatively small compared to those at the low spatial frequencies, where physiological noise is dominant. Therefore, the effect on the final MR images is almost negligible due to the square summation rule. Thus, the partial-k-space 3D method sacrifices much less SNR than is expected from the thermal noise model, and the SNR efficiency is increased compared to a full-k-space acquisition since more time frames can be collected for the same scan time. Accordingly, the temporal resolution can be increased in 3D acquisitions because only partial coverage of k-space is necessary. Experimental results confirm that more activation with a higher average t-score is detected by this method.

Algorithms↗

PubMed2006

Regulation of adipose-derived adult stem cells differentiating into chondrocytes with the use of rhBMP-2.

BACKGROUND: Adipose tissue has been demonstrated to contain a population of progenitor cells that can differentiate into bone and cartilage. Studies have suggested that adipose-derived adult stem (ADAS) cells can be induced to differentiate into chondrocytes by transforming growth factor-beta (TGF-beta). In this study, we examined whether bone morphogenetic protein-2 (BMP-2), as a member of the TGF-beta superfamily, could regulate ADAS cells to differentiate into a chondrolineage. METHODS: ADAS cells were isolated and induced by rhBMP-2. These cells were cultured in pellets for 2 weeks, and the chondrogenic phenotype was observed in vitro and in vivo. ADAS cells cultured without BMP-2 were used as controls. RESULTS: After 2 weeks of culture, the differentiated ADAS cells reacted positively to Alcian blue and collagen II, and the content of collagen II protein was obviously up-regulated at day 14. Glycosaminoglycan (GAG) content gradually increased from day 2 to day 14 (P < 0.05). However, H&E staining and collagen II expression were weak, and there was a little collagen II protein and GAG detected in the control group. Additionally, the pellets of ADAS cells induced by rhBMP-2 were transplanted into BALB/C nude mice and formed cartilage lacuna at week 8 in vivo. DISCUSSION: These data demonstrate that rhBMP-2 induce ADAS cells to differentiate into chondrocytes in vitro and in vivo. This is useful for basic and clinical studies aimed at repairing cartilage damage. But in a control group, ADAS cells tended towards differentiation into chondrocytes, which was affected by ITS. We will be exploring the mechanism further.

Adipose Tissue↗

PubMed2006

Distinct roles for interleukin-12p40 and tumour necrosis factor in resistance to oral candidiasis defined by gene-targeting.

Cell-mediated immunity is important for anti-Candida host defence in mucosal tissues. In this study we used cytokine-specific gene knockout mice to investigate the requirement for T helper type 1 (Th1) and Th2 cytokines in recovery from oral candidiasis. Knockout mice used in this study included interleukin-4 (IL-4), IL-10, IL-12p40, interferon-gamma (IFN-gamma), and tumour necrosis factor (TNF). The mice were challenged either orally or systemically with Candida albicans yeasts, and levels of colonization were determined. IL-12p40 knockout mice developed chronic oropharyngeal candidiasis, but were not more susceptible to systemic challenge. On the other hand, TNF knockout mice displayed increased susceptibility to both oral and systemic challenge, but only in the acute stages of infection. TNF apparently has a protective effect in the acute stages of both oral and systemic candidiasis, whereas IL-12p40 is essential for recovery from oral but not systemic candidiasis. The role of IL-12p40, and its relation to T-cell-mediated responses remain to be determined.

Animals↗

PubMed2006

Ectopic cartilage formation induced by mesenchymal stem cells on porous gelatin-chondroitin-hyaluronate scaffold containing microspheres loaded with TGF-beta1.

The study aimed to produce a novel porous gelatin-chondroitin-hyaluronate scaffold in combination with a controlled release of TGF- beta1 and to evaluate its potentials in ectopic cartilage formation. The gelatin-chondroitin-hyaluronate scaffold was developed to mimic the natural extra cellular matrix of cartilage. Gelatin microspheres loaded with TGF- beta1 (MS-TGF beta1) showed a fast cytokine release at initial phase (37.4%) and the ultimate accumulated release was 83.1% by day 18. Then MS-TGF beta1 were incorporated into scaffold. The MSCs seeded on scaffold with or without MS-TGF beta1 were incubated in vitro or implanted subcutaneously in nude mice. In vitro study showed that, compared to the scaffold, the scaffold/MS-TGF beta1 significantly augmented the proliferation of MSCs and GAG synthesis. Three weeks postoperatively histology observation showed that in MSCs/scaffold/MS-TGF beta1 implantation group, cells of newly formed ectopic cartilage were located within typical lacunae and demonstrated morphological characteristics of chondrocytes. Six weeks later the ectopic cartilage grew more and islands of cartilage were observed. The matrix was extensively metachromatic by safranin-O/Fast green staining. Immunohistochemical staining also indicated ectopic cartilage was intensely stained for type II collagen. Instead, in the MSCs/scaffold implantation group, no cartilage-like tissue formed and matrix showed negative or weak positive staining. The percentage of positive staining area was significantly larger in MSCs/scaffold/MS-TGF beta1 group (p<0.05) at each time point. The results indicated that the novel gelatin-chondroitin-hyaluronate scaffold with MS-TGF beta1 could induce the chondral differentiation of MSCs to form cartilage and might serve as a new way to repair cartilage defects.

Animals↗

PubMed2006

Sterilising action of pyrazinamide in models of dormant and rifampicin-tolerant Mycobacterium tuberculosis.

SETTING: Pyrazinamide (PZA) is an effective sterilising drug in tuberculosis, but its mode of action is controversial. OBJECTIVE: To test the bactericidal activity of 1.56-100 microg/ml PZA in Hu/Coates models of dormant and rifampicin (RMP) tolerant Mycobacterium tuberculosis. METHODS: In model 1, bactericidal activity was tested in pH 5.5 medium against 4-day, 30-day or 100-day static, hypoxic cultures. In models 2 and 3, 100 microg/ml RMP was added to a 100-day culture and PZA was added either during incubation with RMP in model 3, or after resuspension in RMP-free medium in model 2. RESULTS: Model 1: cfu counts on the 100-day and 30-day cultures fell by a maximum of about 1.6 log cfu/ml with increasing culture age, PZA concentration and incubation period, while counts on the 4-day culture showed little change. Model 2: cfu counts at the end of 7 days of recovery showed little bactericidal activity. Model 3: viable bacilli were almost completely eliminated. Bactericidal activity in these models increased with decreasing metabolic bactericidal activity, as measured by the uptake of [3H] uridine into bacterial RNA. CONCLUSION: PZA differs from other anti-tuberculosis drugs in showing greater bactericidal activity the slower the bacillary metabolic activity, hence its great value as a sterilising drug, likely to remain as an effective companion drug with newer sterilising drugs.

Antibiotics, Antitubercular↗

PubMed2005

Approximation of flammability region for natural gas-air-diluent mixture.

The growing implementation of exhaust gas recirculation (EGR) in reducing NO(x) emissions of engine is of paramount motivation to perform a fundamental research on the flammability characteristics of fuel-air-diluent mixtures. In this work, the influences of EGR on the flammability region of natural gas-air-diluent flames were experimentally studied in a constant volume bomb. An assumption of critical burning velocity at flammability limit is proposed to approximately determine the flammability region of these mixtures. Based on this assumption, an estimation of the flammability map for natural gas-air-diluent mixtures was obtained by using the empirical formula of burning velocity data. The flammability regions of natural gas-air mixtures with EGR are plotted versus the EGR rate. From the comparison of estimated results and experimental measurements, it is suggested that the accuracy of prediction is largely dependent upon the formula of burning velocity used. Meanwhile, the influence of pressure on the critical burning velocity at flammability limit is also investigated. On the basis of the pressure dependence criterion, the estimation was performed for the circumstance of high temperature and pressure, and the prediction results still agree well with those of experiments.

Air↗