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Biomedical subjects

X Ding

Publications and source records attributed to X Ding.

At least 19 recordsLinked to original sources

Risk factors of superinfection following imipenem/cilastatin therapy in hospitalised patients with acute exacerbations of severe chronic obstructive pulmonary disease.

Imipenem is often used in treatment of acute exacerbations of severe chronic obstructive pulmonary disease (COPD). Superinfection following imipenem therapy is a common cause of treatment failure and high economic burden. This study is aimed to explore any clinical factors which determine the risk of superinfection after imipenem treatment in acute exacerbations of severe COPD. A prospective observational study was conducted in a 5-bed respiratory intensive care unit of a Chinese University hospital. Fifty-one patients with acute exacerbations of severe COPD who were hospitalised and treated with imipenem for more than 3 days were enrolled during 1.5 year. The associations between the risk of superinfection and potential factors were analysed by logistic regression. Forty-seven out of 51 patients (92.2%) had their symptoms and signs improved at the end of imipenem treatment. Superinfections were developed in 12 patients, and the superinfection rate was as high as 30.8% (12 out of 39 patients with definite bacteriologic responses). The frequent superinfecting organisms were Stenotrophomonas maltophilia and Pseudomonas aeruginosa. Among a wide range of potential risk factors, we found that lower blood pH, previous cephalosporines treatment and longer period of imipenem treatment are independently associated with a higher risk of superinfection. The risk of superinfection following imipenem treatment in hospitalised patients with acute exacerbations of COPD was high. Lower blood pH, previous cephalosporines treatment and longer period of imipenem treatment all increased the risk of superinfection.

Acute Disease↗

Monte Carlo simulation of large electron fields.

Accurate simulation of large electron fields may lead to improved accuracy in Monte Carlo treatment planning while simplifying the commissioning procedure. We have used measurements made with wide-open jaws and no electron applicator to adjust simulation parameters. Central axis depth dose curves and profiles of 6-21 MeV electron beams measured in this geometry were used to estimate source and geometry parameters, including those that affect beam symmetry: incident beam direction and offset of the secondary scattering foil and monitor chamber from the beam axis. Parameter estimation relied on a comprehensive analysis of the sensitivity of the measured quantities, in the large field, to source and geometry parameters. Results demonstrate that the EGS4 Monte Carlo system is capable of matching dose distributions in the largest electron field to the least restrictive of 1 cGy or 1 mm, with D(max) of 100 cGy, over the full energy range. This match results in an underestimation of the bremsstrahlung dose of 10-20% at 15-21 MeV, exceeding the combined experimental and calculational uncertainty in this quantity of 3%. The simulation of electron scattering at energies of 15-21 MeV in EGS4 may be in error. The recently released EGSnrc/BEAMnrc system may provide a better match to measurement.

Computer Simulation↗

Neutron radiation area monitoring system for proton therapy facilities.

A neutron radiation area monitoring system has been developed for proton accelerator facilities dedicated to cancer therapy. The system comprises commercial measurement equipment, computer hardware and a suite of software applications that were developed specifically for use in a medical accelerator environment. The system is designed to record and display the neutron dose-equivalent readings from 16 to 24 locations (depending on the size of the proton therapy centre) throughout the facility. Additional software applications provide for convenient data analysis, plotting, radiation protection reporting, and system maintenance and administration tasks. The system performs with a mean time between failures of >6 months. Required data storage capabilities and application execution times are met with inexpensive off-the-shelf computer hardware.

Equipment Design↗

Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans.

BACKGROUND: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common. OBJECTIVE: To report the identification of a mutation in the human CRYGS gene. SUBJECTS AND METHODS: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out. RESULTS: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (theta = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G-->T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011). CONCLUSIONS: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.

Amino Acid Sequence↗

Structural features and hypoglycaemic activity of an exopolysaccharide produced by Sorangium cellulosum.

AIMS: To investigate the structural features and hypoglycaemic activity of an exopolysaccharide (EPS) produced by Sorangium cellulosum NUST06. METHODS AND RESULTS: The chemical structure of the EPS from S. cellulosum NUST06 was determined by gas-liquid chromatography, gas chromatography (GC), GC-mass spectrometry and nuclear magnetic resonance. The EPS was composed of a beta-D-(1-->4)-glucose backbone with alpha-D-(1-->6)-mannose side chains. The molecular weight of the EPS was approx. 2x10(5) Da. Healthy and alloxan-induced diabetic mice were used in the study. Blood glucose levels of the experimental animals during the trial period were analysed by a glucose test kit based on the glucose oxidase method. When 100 and 200 mg kg(-1) day(-1) of purified EPS was orally administered for 7 days, the serum glucose in alloxan-induced diabetic mice was reduced by 35.9 and 41.4% (P<0.01), and the serum glucose in healthy mice was reduced by 27.3 and 30.1% (P<0.05), respectively. CONCLUSIONS: The EPS produced by S. cellulosum NUST06 decreased blood glucose levels distinctly in both healthy and alloxan-induced diabetic mice. SIGNIFICANCE AND IMPACT OF THE STUDY: To elucidated the chemical structure of the EPS from S. cellulosum NUST06 and exploited the anti-diabetic potential of the EPS.

Animals↗

Organochlorine pesticides and polychlorinated biphenyl residues in foodstuffs and human tissues from china: status of contamination, historical trend, and human dietary exposure.

Concentrations of persistent organochlorine pesticides such as DDTs, hexachlorocyclohexanes (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs), were determined in a wide variety of foodstuffs and human tissues collected from Shanghai and its vicinity in China in 2000-2001. Among the organochlorines analyzed, DDT and its metabolites were prominent compounds in most of the foodstuffs. In particular, mussels contained noticeable residues of DDTs (34,000 ng/g lipid weight), which are one to three orders greater than those reported levels in bivalves from other Asian countries. Concentrations of HCHs, CHLs, HCB, and PCBs in foodstuffs were generally low, suggesting small amounts of inputs into the environment. Temporal trends examined by comparing the results of previous studies of organochlorine levels in Chinese foodstuffs in 1970s and 1992 revealed a greater amounts of declines of DDTs and HCHs residues and the average daily intakes during the past 30 years. In contrast, very high concentrations of DDTs and HCHs were detected in human tissues from Shanghai, with the maximum values as high as 19,000 ng/g lipid weight (mean: 7,600 ng/g) and 17,000 ng/g (mean: 7,400 ng/g), respectively. Considering that foodstuffs are a main source of human exposure to contaminants, the greater concentrations of DDTs and HCHs in Chinese people might be due to past extensive usage of these compounds as agricultural pesticides. Continuous monitoring and epidemiological studies of organochlorine pesticides in humans are warranted in China. To our knowledge, this is the first report to present the residue levels of persistent organochlorine pesticides and PCBs in human tissues of China.

Aged↗

Activation of the NPTA element of the CYP2A3 gene by NFI-A2, a nasal mucosa-selective nuclear factor 1 isoform.

The aim of this study was to determine whether the NPTA element of the olfactory mucosa-predominant CYP2A3 gene can be activated by NFI-A2, a recently identified member of the nuclear factor 1 family of transcription factors. Isoform-specific RNA-PCR confirmed that NFI-A2 is mainly expressed in rat olfactory mucosa. A full-length NFI-A2 cDNA was isolated from a cDNA library of rat olfactory mucosa and was used for preparation of a construct encoding a fusion protein of NFI-A2 with the yeast GAL4 activation domain. Expression of the fusion protein in yeast was detected with an antibody to NFI-A. The fusion protein activated the expression of a LacZ reporter gene in yeast one-hybrid assays with a reporter construct containing the NPTA element, but not with other constructs lacking the NPTA element. These findings suggest that NFI-A2 may be involved in the tissue-selective transcriptional activation of the CYP2A3 gene in the olfactory mucosa.

Amino Acid Sequence↗

An interferon regulatory factor-like binding element restricts Xmyf-5 expression in the posterior somites during Xenopus myogenesis.

The expression of myf-5, a key component of myogenic regulatory genes, declines progressively in mature somitic cells during vertebrate myogenesis. Little is known about how this down-regulation takes place. Here we provide evidence that an interferon regulatory factor binding element (IRF element) within the Xenopus myf-5 promoter is responsible for the elimination of myf-5 transcription in mature somitic mesoderm of Xenopus embryos. We show that this IRF element mediates the down-regulation of Xmyf-5 transcription in gastrula embryos, and can specifically interact with nuclear proteins of early neurula. Moreover, deletion of this IRF element results in the anterior expansion of reporter gene transcripts within somitic mesoderm in transgenic embryos. Our results, therefore, provide insight into how the negative control of Xmyf-5 expression takes place.

Animals↗

Synthesis and biological evaluation of didemnin photoaffinity analogues.

The synthesis of four benzophenone-containing analogues of the antiproliferative natural product didemnin B is presented. In vitro protein biosynthesis inhibition potency and antitumor activity were evaluated. The results indicate that all four analogues are biologically active and could serve as photoaffinity reagents for the study of receptor-binding interactions of didemnins. These analogues could also be useful in studying antitumor effects of didemnins.

Antineoplastic Agents↗

Mouse cyp2g1 gene: promoter structure and tissue-specific expression of a cyp2g1-lacz fusion gene in transgenic mice.

The structure of the mouse Cyp2g1 gene was determined to identify regulatory regions important for its olfactory mucosa-specific expression. Two Cyp2g1 genomic clones were isolated and characterized. A 3.6-kilobase 5'-flanking sequence was used to prepare a Cyp2g1--LacZ fusion gene for transgenic mice production. Transgene expression, as determined by beta-galactosidase activity in tissue extracts, was detected in the olfactory mucosa, but not in any other tissues examined, in five different transgenic lines. Thus, the 3.6-kilobase fragment contained regulatory elements sufficient for olfactory mucosa-specific and proper developmental expression of the reporter gene. However, histological and immunohistochemical studies indicated that the expression of the transgene in the olfactory mucosa was patchy and the cellular expression patterns of the transgene did not exactly match that of the endogenous gene. These results implicate the presence of additional regulatory sequences that are necessary for the correct cell type-selectivity within the olfactory mucosa.

Animals↗

Design of near-infrared imaging probe with the assistance of ultrasound localization.

A total of 364 optical source-detector pairs were deployed uniformly over a 9 cm x 9 cm probe area initially, and then the total pairs were reduced gradually to 60 in experimental and simulation studies. For each source-detector configuration, three-dimensional (3-D) images of a 1-cm-diameter absorber of different contrasts were reconstructed from the measurements made with a frequency-domain system. The results have shown that more than 160 source-detector pairs are needed to reconstruct the absorption coefficient to within 60% of the true value and appropriate spatial and contrast resolution. However, the error in target depth estimated from 3-D images was more than 1 cm in all source-detector configurations. With the a priori target depth information provided by ultrasound, the accuracy of the reconstructed absorption coefficient was improved by 15% and 30% on average, and the beam width was improved by 24% and 41% on average for high- and low-contrast cases, respectively. The speed of reconstruction was improved by ten times on average.

Journal Article↗

Retention behavior of transition metals on a bifunctional ion-exchange column with oxalic acid as eluent.

The common eluents used with a bifunctional ion-exchange column (IonPac CS5A) for separating transition metals are pyridine-2,6-dicarboxylic acid and oxalic acid (Ox). When Ox is used, cadmium and manganese co-elute. Although much research has been done to overcome the Cd2+-Mn2+ co-elution problem, the role of lithium hydroxide in separating the transition metals has received little attention. In this study, it is found that when the Ox concentration is higher than 35 mM, Cu2+ elutes after Pb2+ and Ox plays a predominant role in the retention behavior of the seven metals. When Ox concentration is lower than 35 mM especially when its concentration (25 mM) is half of the usually used standard concentration (50 mM), Cu2+ elutes before Pb2+, and at the same time, Mn2+ and Cd2+ can also be baseline separated. Lithium hydroxide plays a predominant role in the separation of the metals separated by cation exchange. So, lithium hydroxide is used to adjust the pH of the eluent. The use of an isocratic elution (25 mM Ox/LiOH/2 mM Na2SO4, pH 3.88) allows the separation of seven metals (Cu2+, Pb2+, Co2+, Mn2+, Cd2+, Zn2+ and Ni2+) in a single run. The effects of inorganic modifiers such as NaNO3, Na2SO4 and Na4P3O7 on retention behavior of the metals are also investigated.

Chromatography, Ion Exchange↗

Role of SspA in the density-dependent expression of the transcriptional activator AarP in Providencia stuartii.

The AarP protein in Providencia stuartii encodes a small transcriptional activator which activates the chromosomal aminoglycoside acetyltransferase aac(2')-Ia gene. In addition, AarP activates genes involved in a multiple antibiotic resistance (Mar) phenotype. Expression of an aarP-lacZ fusion increased in a density-dependent manner and reached peak levels at stationary phase. The expression of an aarP-lacZ fusion could be prematurely activated in cells at early to mid-exponential phase by the addition of spent culture supernatants from stationary phase cultures or by ethyl acetate extracts of these supernatants. Nutrient starvation had a negligible effect on aarP expression. In a search for mutations that block aarP activation at stationary phase, a mini-Tn5Cm insertion has been identified within a gene whose product was 77% identical to SspA, a regulatory protein involved in stationary phase gene expression and virulence. An unmarked sspA null allele (sspA2) was created by allelic replacement to further examine the role of sspA in P. stuartii. The sspA2 allele resulted in substantial decrease in aarP mRNA accumulation at various phases of growth. Furthermore, in an sspA mutant background, the aarP-lacZ fusion was no longer activated by an extracellular signal.

Adhesins, Bacterial↗

Structure--activity relationships of side-chain modified didemnins.

The synthesis and antitumor activity of a novel didemnin B analogue containing a psi[CH2NH] amide bond surrogate between N-Me-D-Leu7 and Pro8 are reported. The analogue shows activity (GI50 = 4 nM) comparable to that of didemnin B (GI50 = 13 nM) in the NCI-60 tumor cell screen. This result, along with new data from previously reported synthetic didemnin analogues, is discussed within the context of the side-chain SAR for didemnins.

Antineoplastic Agents↗

[Lys3]Didemnins as potential affinity ligands.

The synthesis and biological activity of N(epsilon)-Z-[Lys3]didemnin B are reported. This novel analogue retains antiproliferative, cytotoxic, and protein biosynthesis inhibition activities, but at reduced levels. This result suggests the use of [Lys3]didemnin derivatives as potential affinity probes for studying the molecular target(s) of the didemnin class of natural products.

Affinity Labels↗

Expression of inhibitory "killer cell lectin-like receptor G1" identifies unique subpopulations of effector and memory CD8 T cells.

T cell and natural killer (NK) cell functions are regulated by triggering of activating and inhibitory cell surface receptors. Here, we have studied the expression profile and predicted inhibitory function of mouse "killer cell lectin-like receptor G1" (KLRG1) on CD8 T cells. KLRG1 was present on 1 - 3 % of adult splenic CD8 cells that expressed CD8alpha beta heterodimers as well as a polyclonal TCR Vbeta repertoire indicative of conventional CD8 cells. The majority of KLRG1(+) CD8 cells belonged to the memory pool as determined by extensive phenotypic marker analysis. Spontaneous IFN-gamma production by approximately 20 % of KLRG1(+) CD8 cells identified them as pro-inflammatory effector cells. In contrast to NK cells, Ly49 and KLRG1 expression on CD8cells was found to be mutually exclusive. Therefore, distinct programs regulate KLRG1 expression in CD8 and NK cells. Finally, we provide evidence that KLRG1 triggering interferes with TCRalpha beta-mediated Ca(++) mobilization and cytotoxicity, raising the possibility that KLRG1 functionally participates in down-regulation of CD8 T cell responses.

Animals↗

Primary malignant lymphoma of the brain: analysis of MMAC1 (PTEN) tumor suppressor gene.

With the use of RT-PCR (reverse transcriptase-polymerase chain reaction), Northern blot analysis, and Western blot analysis, seven primary brain lymphomas were examined for the state of the MMACI tumor suppressor gene. Nucleotide analysis of RT-PCR clones revealed no abnormality in the MMAC1 coding sequence in each case. Although Northern blot revealed variation among cases in the signal intensities for MMAC1 mRNA, Western blot revealed a distinct MMAC1 protein band in all cases, suggesting that the actual MMAC1 expressions were similar. In Western blot analysis of phosphorylated Akt (p-Akt), which is regulated positively by PI3K (phosphoinositide-3 kinase) and negatively by MMAC1, all the lymphomas revealed an Akt band but not a p-Akt band, suggesting that the MMAC1 phosphatase activity was maintained in each case. These findings suggest that the MMAC1 gene is normal in its coding sequence, gene expression, and phosphatase activity in the lymphomas. Thus, unlike the p16 and p15 tumor suppressor genes, which are frequently deleted and inactivated in brain lymphoma and represent a striking contrast to systemic lymphoma, MMAC1 may not play an important role in carcinogenesis in this tumor, as in the systemic counterpart.

Aged↗