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Biomedical subjects

D Wang

Publications and source records attributed to D Wang.

At least 55 records · Page 3Linked to original sources

Humanin delays apoptosis in K562 cells by downregulation of P38 MAP kinase.

Humanin (HN) is a newly identified neuroprotective peptide. In this study, we investigated its antiapoptotic effect and the potential mechanisms in K562 cells. Upon serum deprivation, expression of HN in K562 cells decreased and its intracellular distribution changed from cytoplasm to cell membrane. In HN stably transfected K562 cells, apoptosis was delayed compared with control vector transfected cells as measured by flow cytometry. Furthermore, analysis of different mitogen-activated protein (MAP) kinases activity revealed that extracellular signal-regulated kinase (ERK) pathway was inhibited while p38 signaling was activated following serum deprivation in K562 cells. And in HN transfected K562 cells, ERK downregulation was not affected, but p38 activation was suppressed, which may responsible for the delayed apoptosis in these cells. Activation of the ERK signaling pathway by phorbol myristate 13-acetate (PMA) and sorbitol protected K562 cells from serum deprivation induced apoptosis. Additionally, overexpression of HN reduced megakaryocytic differentiation of K562 cells. The present data outline the role of ERK and p38 MAP kinases in serum deprivation induced apoptosis in K562 cells and figure out p38 signaling pathway as molecular target for HN delaying apoptosis in K562 cells.

Apoptosis↗

Pulmonary atresia with intact ventricular septum: predictors of early and medium-term outcome in a population-based study.

OBJECTIVES: Pulmonary atresia with intact ventricular septum is a form of congenital heart disease usually associated with right-heart hypoplasia, with considerable morphologic heterogeneity and often poor outlook. Ascertainment of risk factors for poor outcome is an important step if an improvement in outcome is to be achieved. METHODS: The UK and Ireland Collaborative study of Pulmonary Atresia with Intact Ventricular Septum is an ongoing population-based study of all patients born with this disease from 1991 through 1995. All available clinical, morphologic, and investigative variables were directly reviewed, and risk factor analysis was performed for poor outcome. RESULTS: One hundred eighty-three patients presented with pulmonary atresia with intact ventricular septum. Fifteen underwent no procedure, and all died. Of the remainder, 67 underwent a right ventricular outflow tract procedure (catheter or surgical), 18 underwent an outflow tract procedure with shunt, and 81 underwent a systemic-to-pulmonary shunt alone. One- and 5-year survival was 70.8% and 63.8%, respectively. Results from Cox proportional hazards model analysis showed that low birth weight (P = .024), unipartite right ventricular morphology (P = .001), and the presence of a dilated right ventricle (P < .001) were independent risk factors for death. The presence of coronary artery fistulae, right ventricular dependence, or the tricuspid valvar z score did not prove to be risk factors for death. After up to 9 years of follow-up, 29% have achieved a biventricular repair, 3% a so-called one-and-a-half ventricular repair, and 10.5% a univentricular repair, with 16.5% still having a mixed circulation (41% died). CONCLUSIONS: This population-based study has shown which features at presentation place an infant in a high-risk group. This is important information for counseling in fetal life and for surgical strategy after birth.

Follow-Up Studies↗

Transfection of CD40Ig into liver prevents acute rejection in rat liver transplantation.

OBJECTIVE: To investigate the effect of CD40Ig upon acute rejection of rat liver transplants. METHODS: Thirty-two orthotopic liver transplants were performed using Lewis to BN rats with "the two-cuff technique". The rats were randomly divided into three groups. Group A served as controls (n = 10); group B (n = 11) and group C (n = 11); Lipofectamine2000-pcDNA3.1 or Lipofectamine2000-pcDNA3.1. CD40Ig complex was injected into Lewis portal vein ex vivo before cold storage of the liver. On the fifth day after transplantation, three rats in each group were killed to study the pathological changes and TUNEL immune histochemistry performed to examine CD40Ig expression. Lymphocytes were obtained from the spleen. The mixed lymphocyte reaction (MLR) was performed to determine tolerance and sheep anti-human immunoglobulin G (IgG)-FITC-labeled T cells counted by flow cytometry. Postoperative survival times of rats in each group were recorded. The pathological changes of dead rats were observed. RESULTS: The mean survival times of group A and B were 11.00 +/- 4.28 and 12.75 +/- 5.57 days, respectively. There were serious acute rejections in allograft liver in groups A and B. Apoptosis index was 33.67 +/- 5.69 versus 39.00 +/- 5.29. Group C mean survival time was 41.25 +/- 13.70 days (P < .01). Immune histochemistry showed CD40Ig-positive elements in the allograft liver, which revealed light acute rejection and apoptosis index was 0.27 +/- 0.21 (P < .01). The part of the allografted liver in a dead rat showed light acute rejection while the others displayed chronic rejection. Recipients were specifically tolerant to donors in the MLR assay. The IgG-FITC-labeled T cells accounted for 11.57% of all T cells in group C. CONCLUSIONS: CD40Ig transfection inhibited T-cell costimulatory pathway, prevented acute rejection, and prolonged graft survival.

Animals↗

Oxygen radicals and matrix metalloproteinases mediate reperfusion liver injury.

Many pathological processes involve the breakdown and remodeling of the extracellular matrix, which is mediated by the family of important enzymes known as matrix metalloproteinases (MMPs). One such process is warm ischemia/reperfusion (I/R) injury, the most important cause of dysfunction of liver allografts. We monitored protein expression of MMP-9 by Western blotting in rat liver after I/R. We also monitored changes in total MMP activity in the serum before and after I/R. Ischemia was induced by clamping the common hepatic artery and portal vein for 40 minutes and reperfusing for 90 minutes. Blood samples collected before ischemia and after reperfusion were analyzed for AST, hydroxyl radical, and tumor necrosis factor (TNFalpha). This protocol resulted in a high level of MMP-9 expression in liver tissue. Total MMP activity in serum was also significantly increased. Levels of AST, hydroxyl radicals, and TNF alpha were concomitantly increased. Ilomastat, an MMP inhibitor, attenuated the I/R-induced liver injury. After administration of the oxygen radical scavenger N-acetylcysteine (NAC), total MMP activity was suppressed, and liver injury was again attenuated. These results indicated that reperfusion liver injury induced an increase in MMP-9 protein expression and in serum MMP activity. The protective effects of an MMP inhibitor and NAC indicate that oxygen radical production is involved in MMP expression and liver injury associated with I/R.

Acetylcysteine↗

Diagnosis of tuberculous vertebral osteomyelitis (TVO) in a developed country and literature review.

STUDY DESIGN: Review of medical and radiological records and literature to study the diagnosis of tuberculous vertebral osteomyelitis (TVO) and the differential diagnosis between TVO and pyogenic vertebral osteomyelitis (PVO). OBJECTIVE: To identify the correct criteria for the diagnosis. SETTING: National Spinal Injuries Centre, UK. METHODS: (1) Medical and radiological records of 10 patients diagnosed as vertebral osteomyelitis and treated elsewhere but later admitted to the NSIC were reviewed retrospectively. (2) Medical literature on vertebral osteomyelitis were reviewed. RESULTS: (1) Case review: Before the study, four of the 10 patients TVO had been diagnosed based on positive bacteriology. Of the other six, the diagnosis of PVO had been made in one based on positive blood culture of staphylococcus while in another without any positive result of bacteriology. The diagnosis had been uncertain in four because of negative results of both bacteriology and histology on both tuberculous and pyogenic infection. The author made the diagnosis of TVO in all 10 cases based on clinical manifestations and plain radiographs. Highly raised ESR with moderate rise of or normal WBC in eight cases supported TVO. Computer tomography and magnetic resonance imaging did not contribute to the differential diagnosis. Laminectomy in five patients led to some clinical improvement. The five patients without surgery deteriorated. Two of them died. (2) LITERATURE REVIEW: A total of 188 articles were reviewed. The crucial role of plain radiographs in the diagnosis of TVO and the high incidence of false-negative of tuberculosis in both bacteriological and histological tests were neglected in most articles. Polymerase chain reaction (PCR) was more reliable in diagnosing tuberculosis. CONCLUSION: Clinical manifestations, discrepancy between ESR and WBC, plain radiographs and PCR are keys to a correct diagnosis of TVO.

Adult↗

Admiral Lord Nelson's death: known and unknown--a historical review of the anatomy.

STUDY DESIGN: Reviewing documents about Lord Admiral Nelson's wound inflicted at the Battle of Trafalgar and studying the collected data in connection with ballistics and human anatomy. OBJECTIVES: Attempting to find out the actual cause of death of Lord Nelson as soon as 4 h postinjury by a musket ball. SETTING: United Kingdom. METHODS: (1) Review of the original report of Mr W Beatty, Lord Nelson's surgeon, on his examination of His Lordship's wound. (2) Investigating the course of the musket ball in connection with an atlas of human anatomy. (3) Investigating the course of the musket ball on a cadaver by RP (one of the authors). (4) Reviewing modern medical literature. RESULTS: The report of Mr Beatty suggested that division of a large branch of the pulmonary artery was the cause of Lord Nelson's early death. Assuming the left pulmonary artery was injured, anatomical studies based on atlases and dissection on a cadaver failed to support a simple straight-line course of the musket ball that could have divided the artery and damage the spinal cord on its path forward. CONCLUSION: The question remains open as to how the musket ball following a relatively straight-line trajectory by entering the body at the acromion, could have divided the left pulmonary artery and damaged the spinal cord later in its course. The mechanism needs further investigation.

Blood Vessels↗

Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis.

Nicotine dependence is the most prevalent form of drug addiction in the US and throughout the world. Epidemiological studies demonstrate that genetics accounts for at least 50% of the liability to nicotine dependence. However, there have been very limited linkage studies providing convincing evidence of susceptibility genomic loci for this disorder. In this study, we conducted genome-wide permutation linkage analyses on the smoking data collected between 1970 and 1972 of the Framingham Heart Study (FHS) to account for the abnormality associated with the smoking quantity (defined as the number of cigarettes smoked per day). We used empirical thresholds obtained from permutation tests to determine the significance of each genomic region. The variance component method implemented in SOLAR was used for the analysis. Under the empirical genome-wide thresholds determined specifically for the FHS smoking data, we found two highly or near-highly significant linkages of nicotine dependence on chromosomes 1 and 4 (P=0.001) and eight significant linkages on chromosomes 3, 7, 8, 9, 11, 16, 17, and 20 (P<0.05). These findings strongly indicate that some of these regions may harbor susceptibility loci for nicotine dependence. Further analysis of these positive regions by fine mapping and/or association analysis is warranted. To our knowledge, this study presents the most convincing linkage evidence for nicotine dependence in the field.

Adult↗

Differential gene expression in liver of inbred chickens and their hybrid offspring.

Differential display of mRNA was used to analyse the differences of gene expression in liver between chicken hybrids and their parents in a 4 x 4 diallel crosses in order to study the molecular basis of heterosis in chickens. The results indicated that patterns of gene expression in hybrids differ significantly from their parents. Four patterns of differential gene expression were revealed, which included: (i) bands only detected in the hybrid F1s (UNF1); (ii) bands only absent in the hybrid F1s (ABF1); (iii) bands only detected in the parental P1 or P2 lines (UNP1 and UNP2) and (iv) bands absent in the parental P1 or P2 lines (ABP1 and ABP2). In addition, correlations between patterns of gene expression and heterosis percentages of nine carcass traits of 8-week-old chickens were evaluated. Statistical results showed that negative correlations between heterosis percentages and the percentage of F1-specific bands (UNF1) were significant at P < 0.01 for breast muscle yield, leg muscle yield, wing weight, eviscerated weight and eviscerated weight with giblet of 8-week-old chickens, and at P < 0.05 for intermuscular fat width. Heterosis percentage was negatively correlated with ABP (bands present in the hybrid F1s and one parental line but absent in the other parental line, ABP1 and ABP2) for breast muscle yield, leg muscle yield, wing weight, eviscerated weight and eviscerated weight with giblet of 8-week-old chickens (P < 0.01). Bands detected only in the hybrid F1s but not in either of the parental lines (UNF1) and bands absent in parental P1 or P2 lines (which includes ABP1 and ABP2) may play important roles in chicken heterosis.

Animals↗

LARALink: a web application for cytogenetic linkage analysis.

Genomic and expression data have increased dramatically over the last several years. This is primarily due to the completion of the human genome project as well as an upsurge in the use of various high-throughput technologies. Recent attempts to correlate genomic and expression data have stimulated the scientific community to determine how this data can be used within a clinical setting (P Khatri et al., Genomics 2002: 79: 266; LJ van't Veer et al., Nature 2002: 415: 530). LARALink (Loci Analysis for Rearrangements Link) is a database-driven web application that utilizes several public datasets to analyze clinical cytogenetic data to identify candidate genes. LARALink allows UniGene clusters or single-nucleotide polymorphisms (SNPs) to be queried for multiple patients by cytoband, chromosome marker, or base pair. The results can be further refined with the use of an anatomical site, developmental stage, pathology, or cell-type expression filter. Once a set of UniGene clusters (expressed genes) has been identified either for a single patient or for a shared region among multiple patients, the expression-distribution profile, expressed sequence tags (ESTs), or online mendelian inheritance in man (OMIM) entries are displayed. The utility of this tool is shown by its application to both research and clinical medicine. LARALink is a public resource available at: http://www.laralink.bioinformatics.wayne.edu:8080/unigene.

Alzheimer Disease↗

Identification of a novel HLA-DRB1 allele (HLA-DRB1*111902*).

In this paper, we report a new HLA-DRB1 allele identified in a male acute myeloid leukaemia Chinese patient. This sample was initially typed as DRB1*11XX using commercial polymerase chain reaction-sequence-specific primers kit. When it was typed using a chip-based sequence-specific oligonucleotide technique, a novel hybridization pattern that does not match any known alleles was observed. Through sequencing, we have identified this allele as a new HLA-DRB1 allele, which was later named HLA-DRB1*111902 by the WHO Nomenclature Committee. The sequence of this new allele differs from DRB1*111901 by one nucleotide (from G to C) at 203nt of exon 2 but does not cause any amino acid substitution.

Alleles↗

Elevated serum IgG titer and avidity to Actinobacillus actinomycetemcomitans serotype c in Japanese periodontitis patients.

AIM: The purpose of this study was to characterize serum antibody responses to different serotypes of Actinobacillus actinomycetemcomitans strains in various forms of periodontitis and to determine whether any specific type of A. actinomycetemcomitans was associated with any specific form of periodontitis in a Japanese population. METHODS: Sonicated whole cell and autoclaved serotype antigens of A. actinomycetemcomitans were used. Serum IgG titer and avidity to A. actinomycetemcomitans were measured by enzyme-linked immunoabsorbant assay (ELISA) and ammonium thiocyanate-dissociation ELISA, respectively, in 46 aggressive periodontitis patients (8 localized, 38 generalized), 28 chronic periodontitis patients, and 18 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction. RESULTS: Generalized aggressive and chronic periodontitis patients exhibited significantly higher IgG titers than healthy subjects to both sonicated and autoclaved antigens of serotype c strains, while IgG titer to serotype b (Y4) was significantly higher in localized aggressive periodontitis patients compared to healthy subjects. No A. actinomycetemcomitans was detected in localized aggressive periodontitis patients. A. actinomycetemcomitans-positive patients exhibited significantly higher IgG titer and avidity to serotype c than A. actinomycetemcomitans-negative patients. In A. actinomycetemcomitans-positive patients, a significantly positive correlation was observed between antibody titer and avidity to serotype c. A. actinomycetemcomitans-positive patients with generalized aggressive periodontitis showed lower IgG avidities to serotype c than those with chronic periodontitis, though no statistically significant difference was found. CONCLUSION: A. actinomycetemcomitans serotype c may play a significant role in chronic and generalized aggressive periodontitis, while A. actinomycetemcomitans serotype b may be associated with localized aggressive periodontitis in a Japanese population.

Actinobacillus Infections↗

Correlation between temperature satisfaction and unsolicited complaint rates in commercial buildings.

UNLABELLED: This paper analyzes the relation between temperature satisfaction ratings expressed on a questionnaire and unsolicited complaint rates recorded in a maintenance database. The key findings are as follows: (i) the satisfaction ratings and complaint rates are negatively correlated with a moderate magnitude (r(s) = -0.31 to -0.36), and the correlation is statistically significant (P = 0.01-0.005), and (ii) the percent dissatisfied with temperature and the complaint rate are positively correlated with moderate magnitude (r(s) = 0.31-0.36), and the correlation is statistically significant (P = 0.01-0.004). Both data sets contain 'real-world' measures of temperature satisfaction, with the complaints contributing directly to the cost of operations and maintenance. The relationship between two validates a new method of assessing the economic cost of thermal discomfort in commercial buildings. PRACTICAL IMPLICATIONS: Complaints in commercial buildings indicate occupants' dissatisfaction to their environments. It not only deteriorates occupants' performance and organization productivity, but also increases building maintenance and operating cost. Nailing economic consequences of complaints will enable monetary comparison of discomfort cost with building and operating costs. This comparison may be desirable for building owners and tenants to make well-informed decisions on construction, rental, and retrofit. It may also be used to evaluate complaint diagnostic and eliminating techniques.

Data Collection↗

Pregnancy alters nitric oxide synthase and natriuretic peptide systems in the rat left ventricle.

Cyclic guanosine monophosphate (cGMP), which is implicated in cardiac cell growth and function, is synthesized by cytoplasmic soluble guanylyl cyclase (GC) stimulated via nitric oxide (NO) and by particulate membrane-bound GC activated via natriuretic peptides. We investigated possible cGMP elevation in the left ventricle (LV) of rats developing physiologic LV hypertrophy during gestation. Furthermore, expression of estrogen receptors (ER) and oxytocin receptors (OTR) was evaluated because their activation stimulates NO and atrial natriuretic peptide (ANP) release from the heart. Compared with nonpregnant controls, Sprague-Dawley rats on day 7 of gestation had similar heart weights, but, on days 14 and 21, ventricular mass increased by 12% and 28% respectively (P< 0.05). LV cGMP concentration was elevated at day 14 of gestation (3.25 +/- 0.12 vs 4.65 +/- 0.17 pmol/g wet weight, P< 0.01) but decreased at day 21 (2.45 +/- 0.09 pmol/g, P< 0.05) to increase again on postpartum day 1 (6.01 +/- 0.15 pmol/g) and day 4 (9.21 +/- 1.79 pmol/g). Changes in endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), OTR and ERalpha, but not ERbeta, proteins paralleled the pregnancy-related cGMP changes in the LV. In contrast, ANP mRNA of the LV remained at control level throughout gestation but increased postpartum, whereas brain natriuretic peptide (BNP) expression declined at term and increased postpartum. The particulate GC natriuretic peptide receptors (GC-A and GC-B) transcripts were already lower at day 14 of gestation. Natriuretic peptide clearance receptor (NPR-C) transcript was not altered on days 7 and 14, but increased at term. We conclude that cGMP concentration in the rat LV is influenced by both NOS and natriuretic peptide systems and may be involved in the changes of LV contractility and hypertrophy that occur during rat gestation.

Animals↗

Photoassociative production and trapping of ultracold KRb molecules.

We have produced ultracold heteronuclear KRb molecules by the process of photoassociation in a two-species magneto-optical trap. Following decay of the photoassociated KRb*, the molecules are detected using two-photon ionization and time-of-flight mass spectroscopy of KRb+. A portion of the metastable triplet molecules thus formed are magnetically trapped. Photoassociative spectra down to 91 cm(-1) below the K(4s)+Rb(5p(1/2)) asymptote have been obtained. We have made assignments to all eight of the attractive Hund's case (c) KRb* potential curves in this spectral region.

Journal Article↗

Structural and functional characterization of the two human ThOX/Duox genes and their 5'-flanking regions.

A crucial step in thyroid hormone synthesis is the oxidative coupling of iodide to thyroglobulin that is catalyzed by thyroperoxidase. The limiting factor of this reaction is the supply of hydrogen peroxide. The generation of hydrogen peroxide has been linked to an enzymatic system located at the apical pole of thyrocytes. This enzymatic activity is assumed to be exerted by NADPH oxidases encoded by two recently cloned genes hThOX1 and hThOX2. Both genes are expressed at high levels in thyrocytes. In this study we report the chromosomal organization of these two genes and the functional characterization of their respective promoter regions. The two human ThOX genes are arranged in a head to head configuration and are separated by a 16 kb-long region. Human ThOX1 and ThOX2 genes span 75 kb and are composed of 35 and 34 exons, respectively. The promoters of both genes do not resemble each other and differ from promoters of other known thyroid-specific genes. No TATA box is present in either ThOX gene promoter. Functional studies confirm that both promoters display significant transcriptional activities after transfection in differentiated thyroid cell lines. However, in contrast to that of thyroglobulin or Na(+)/I(-) symporter gene promoter, hThOX promoter activity is not restricted to thyroid cells. Additionally, functional studies show that both hThOX promoters are not positively controlled by cAMP.

5' Flanking Region↗

Solution chemistry effects on orthophosphate adsorption by cationized solid wood residues.

Adsorption of orthophosphate anions in aqueous solution by cationized milled solid wood residues was characterized as a function of sorbate-to-sorbent ratio (approximately equal to 0.001-2.58 mmol of P/g substrate), pH (3-9), ionic strength, I (no I control; 0.001 and 0.01 M NaCl), reaction time (4 min to 24 h), and in the presence of other competing anions (0.08-50 mM SO4(2-); 0.08-250 mM NO3-). Sorption isotherms revealed the presence of two kinds of adsorption sites corresponding to high and low binding affinities for orthophosphate anions. Consequently, a two-site Langmuir equation was needed to adequately describe the data over a range of solution conditions. In addition to higher sorption capacity, cationized bark possessed a higher binding energy for orthophosphate anions compared to cationized wood. The sorption capacity and binding energy for bark were 0.47 mmol of P g(-1) and 295.7 L mmol(-1), respectively, and for wood, the corresponding values were 0.27 mmol g(-1) and 61.4 L mmol(-1). Both the sorption capacity and binding energy decreased with increasing I, due to competition from Cl- ions for the available anion-exchange sites. The surface charge characteristics of cationized bark (pHzpc = 7.9) acted in concert with orthophosphate speciation to create a pH-dependent sorption behavior. Orthophosphate uptake was quite rapid and attained equilibrium levels after 3 h. Both SO4(2-) and NO3- influenced percent removal but required high relative competing anion to H2PO4- molar ratios, i.e., 2.5-3 for SO4(2-) and 25 for NO3-, to cause appreciable reduction. These results support our hypothesis that adsorption of orthophosphate anions on cationized bark involves ion exchange and other specific Lewis acid-base interactions.

Adsorption↗

Molecular characterization of HMW glutenin subunit allele 1Bx14: further insights in to the evolution of Glu-B1-1 alleles in wheat and related species.

1Bx14 is a member of the high molecular weight (HMW) glutenin subunits specified by wheat Glu-B1-1 alleles. In this work, we found that the full-length amino acid sequence of 1Bx14 and 1Bx20, the last two of the three cysteine residues, which are conserved in 1Bx7, 1Bx17 and homologous 1Ax and 1Dx subunits, were replaced by tyrosine residues. In the 5' flanking regions (-900 to -1,200 bp relative to the start codon), a novel miniature inverted-repeat transposable element insertion was present in 1Bx12 and 1Bx20 but not 1Bx7 and 1Bx17. 1Bx14 and 1Bx20 like alleles were readily found in tetraploid wheat subspecies but not several S genome containing Aegilops species. Phylogenetic analysis showed that the four molecularly characterized Glu-B1-1 alleles (1Bx7, 1Bx14, 1Bx17, 1Bx20) could be divided into two allelic lineages. The lineage represented by 1Bx7 and 1Bx17 was more ancient than the one represented by 1Bx14 and 1Bx20. Combined, our data establish that 1Bx14 and 1Bx20 represent a novel subclass of Glu-B1-1 alleles. Based on current knowledge, potential mechanism involved in the differentiation of two Glu-B1-1 lineages is discussed.

Alleles↗