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Biomedical subjects

Li Ding

Publications and source records attributed to Li Ding.

At least 55 records · Page 3Linked to original sources

[An experimental study of effects of active-heating-system for extravehicular spacesuit gloves on working performance].

OBJECTIVE: To observe the effects of active heating system for spacesuit gloves on extravehicular working performance. METHOD: After analyzing the factors with gloves influence on the working performance, the effects of active heating system for gloves were studied experimentally with aspects to fatigue, hand strength, dexterity and tactile sensing. RESULT: 1) Heating-system had not influence to grip; 2) Heating-system had 17% influence to fatigue except specific person; 3) Nut assembly and nipping pin showed that heating-system had little influence to dexterity; 4) Apperceiving shape of object and two-point distance showed heating-system had little influence to tactility. CONCLUSION: The active heating method is rational and has little influence on working performance.

Biomechanical Phenomena↗

[Spatial reconstruction of human motion utilizing two dimension images and a biomechanical model].

One of the key techniques in the research of human motion analysis is the reconstruction of human spatial motion utilizing the evaluation of the anatomic points positions that can uniquely define the position of all anatomical segments. Upon the bases of direct linear transform and human biomechanical model, the method to reconstruct an image sequence shot by a stationary camera was described. The result of the reconstruction process was a set of data that is kinematically consistent with the biomechanical model used. A new method to calibrate camera was developed which can be completed in any world coordination system according to the practical situation. A practical motion was selected as the investigated subject. The predicting and experimental results were in good agreement. The benefits and shortcoming of the methodology were discussed.

Biomechanical Phenomena↗

[Neurological complications following haploidentical bone marrow transplantation].

UNLABELLED: To explore the occurrence patterns of neurological complications following haploidentical bone marrow transplantation, a series of clinical data as the onset time, etiology, choices of therapies and prognosis in 10 patients with neurological disorders were summarized. The results showed that complications occurred in 10 out of 74 patients after bone marrow transplantation, which include 3 with encephalorrhagia, 3 infection, 1 epilepsy, 1 Guillian-Barr's syndrome, 1 encephalopathy and 1 schizophrenia. 4 patients died of neurological complications. IN CONCLUSION: neurological complications commonly occurred in haploidentical bone marrow transplantation, and encephalorrhagia might be the main indication that needs intensive care. Moreover, central nerve system infection and peripheral nerve diseases associated with slow immune reconstitution should have clinical interests.

Adolescent↗

[Pharmacokinetics of fudosteine in healthy volunteers].

AIM: To study the pharmacokinetics of fudosteine in healthy volunteers after the single and multiple dose administration. METHODS: Thirty-six volunteers were divided into three groups randomly, each group included six men and six women. In the single dose design, the volunteers received either a single dose of 600 mg, 400 mg or 200 mg fudosteine. After a one-week wash out period, the volunteers of 400 mg group participated in the multiple dose design in which each volunteer received 400 mg fudosteine three times a day for five consecutive days. The plasma concentrations were determined by pre-column derivatization HPLC-FL method and the pharmacokinetic parameters of fudosteine were calculated. RESULTS: The obtained pharmacokinetic parameters of fudosteine in single dose of 600 mg, 400 mg and 200 mg groups were as follows: T1/2 were (2.8 +/- 0.5), (2.7 +/- 0.5) and (3.2 +/- 0.6) h, respectively. T(max) were (0.51 +/- 0.22), (0.59 +/- 0.21) and (0.48 +/- 0.18) h, respectively. C(max) were (16 +/- 4), (11 +/- 3) and (6.1 +/- 1.5) microg x mL(-1), respectively. The AUC(0-10 h) and C(max) correlated linearly with doses, respectively (r > 0.99). The T(max), C(max) and AUC values of fudosteine in healthy male volunteers were smaller than those in female volunteers, and the T1/2 value was longer than that in female volunteers. The obtained multi-dose pharmacokinetic parameters of fudosteine were as follows: C(ss) was (4.1 +/- 0.8) microg x mL(-1); DF was 3.0 +/- 0.7; T1/2 was (2.5 +/- 0.4) h; T(max) was (0.6 +/- 0.3) h; C(max) was (13.2 +/- 1.3) microg x mL(-1). CONCLUSION: The values of pharmacokinetic parameters in healthy volunteers were linear in the range from 200 mg to 600 mg. Statistic analysis results showed that the differences of AUC and C(max) between men and women were not resulted from sexual differences, but from the weight differences. There was no significant difference in pharmacokinetic parameters between single dose and multi-dose.

Administration, Oral↗

Gene expression profiling of leiomyoma and myometrial smooth muscle cells in response to transforming growth factor-beta.

Altered expression of the TGF-beta system is recognized to play a central role in various fibrotic disorders, including leiomyoma. In this study we performed microarray analysis to characterize the gene expression profile of leiomyoma and matched myometrial smooth muscle cells (LSMC and MSMC, respectively) in response to the time-dependent action of TGF-beta and, after pretreatment with TGF-beta type II receptor (TGF-beta RII) antisense oligomer-blocking/reducing TGF-beta autocrine/paracrine actions. Unsupervised and supervised assessments of the gene expression values with a false discovery rate selected at P < or = 0.001 identified 310 genes as differentially expressed and regulated in LSMC and MSMC in a cell- and time-dependent manner by TGF-beta. Pretreatment with TGF-beta RII antisense resulted in changes in the expression of many of the 310 genes regulated by TGF-beta, with 54 genes displaying a response to TGF-beta treatment. Comparative analysis of the gene expression profile in TGF-beta RII antisense- and GnRH analog-treated cells indicated that these treatments target the expression of 222 genes in a cell-specific manner. Gene ontology assigned these genes functions as cell cycle regulators, transcription factors, signal transducers, tissue turnover, and apoptosis. We validated the expression and TGF-beta time-dependent regulation of IL-11, TGF-beta-induced factor, TGF-beta-inducible early gene response, early growth response 3, CITED2 (cAMP response element binding protein-binding protein/p300-interacting transactivator with ED-rich tail), Nur77, Runx1, Runx2, p27, p57, growth arrest-specific 1, and G protein-coupled receptor kinase 5 in LSMC and MSMC using real-time PCR. Together, the results provide the first comprehensive assessment of the LSMC and MSMC molecular environment targeted by autocrine/paracrine action of TGF-beta, highlighting potential involvement of specific genes whose products may influence the outcome of leiomyoma growth and fibrotic characteristics by regulating inflammatory response, cell growth, apoptosis, and tissue remodeling.

Apoptosis↗

Leiomyoma and myometrial gene expression profiles and their responses to gonadotropin-releasing hormone analog therapy.

Gene microarray was used to characterize the molecular environment of leiomyoma and matched myometrium during growth and in response to GnRH analog (GnRHa) therapy as well as GnRHa direct action on primary cultures of leiomyoma and myometrial smooth muscle cells (LSMC and MSMC). Unsupervised and supervised analysis of gene expression values and statistical analysis in R programming with a false discovery rate of P < or = 0.02 resulted in identification of 153 and 122 differentially expressed genes in leiomyoma and myometrium in untreated and GnRHa-treated cohorts, respectively. The expression of 170 and 164 genes was affected by GnRHa therapy in these tissues compared with their respective untreated group. GnRHa (0.1 microm), in a time-dependent manner (2, 6, and 12 h), targeted the expression of 281 genes (P < or = 0.005) in LSMC and MSMC, 48 of which genes were found in common with GnRHa-treated tissues. Functional annotations assigned these genes as key regulators of processes involving transcription, translational, signal transduction, structural activities, and apoptosis. We validated the expression of IL-11, early growth response 3, TGF-beta-induced factor, TGF-beta-inducible early gene response, CITED2 (cAMP response element binding protein-binding protein/p300-interacting transactivator with ED-rich tail), Nur77, growth arrest-specific 1, p27, p57, and G protein-coupled receptor kinase 5, representing cytokine, common transcription factors, cell cycle regulators, and signal transduction, at tissue levels and in LSMC and MSMC in response to GnRHa time-dependent action using real-time PCR, Western blotting, and immunohistochemistry. In conclusion, using different, complementary approaches, we characterized leiomyoma and myometrium molecular fingerprints and identified several previously unrecognized genes as targets of GnRHa action, implying that local expression and activation of these genes may represent features differentiating leiomyoma and myometrial environments during growth and GnRHa-induced regression.

Active Transport, Cell Nucleus↗

Gonadotropin-releasing hormone and TGF-beta activate MAP kinase and differentially regulate fibronectin expression in endometrial epithelial and stromal cells.

Gonadotropin-releasing hormone analog (GnRHa) is used for medical management of endometriosis and premature luteinizing hormone surge during controlled ovarian stimulation. Human endometrium expresses GnRH receptors, and GnRHa alters the expression of transforming growth factor-beta (TGF-beta) and receptors in endometrial cells. Because the diverse biological actions of GnRHa and TGF-beta are mediated in part through the MAPK pathway, we determined whether utilization of MAPK/ERK and transcriptional activation of immediate early genes c-fos and c-jun result in differential regulation of fibronectin, known as key regulator of embryo implantation and endometriosis progression. Using endometrial stromal cells (ESC) and the endometrial epithelial cell line HES, we demonstrated that GnRHa and TGF-beta, in a dose-, time-, and cell-dependent manner, increased the level of phosphorylated ERK1/2 (pERK1/2). GnRH antagonist Antide also increased pERK1/2 induction in ESC and HES, whereas pretreatment reduced GnRHa-induced pERK2 in ESC but not in HES. Cotreatments with GnRHa plus TGF-beta1 did not have an additive or an inhibitory effect on pERK1/2 induction compared with GnRHa or TGF-beta1 action alone. TGF-beta1 and GnRHa increased ERK1/2 nuclear accumulation and inversely regulated the expression of c-fos and c-jun and that of fibronectin in a cell-specific manner. Pretreatment with U-0126, a MEK1/2 inhibitor, blocked basal, as well as GnRHa- and TGF-beta1-induced pERK1/2; however, it differentially affected c-fos, c-jun, and fibronectin expression. In conclusion, the results indicate that GnRHa and TGF-beta signaling through MAPK/ERK results in differential regulation of fibronectin expression in endometrial cells, a molecular mechanism where short- and long-term GnRHa therapy and locally expressed TGF-beta could influence embryo implantation and endometriosis implants, respectively.

Cell Line↗

A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences.

The human Toll-like receptor 2 (TLR2) mediates responses of both innate and adaptive immunity to Gram-positive bacteria, including mycobacteria. We sought functional polymorphisms in the 5'-untranslated region (UTR) of TLR2. We found a highly polymorphic (GT)n dinucleotide repeat 100 bp upstream of the TLR2 translational start site in intron 2. The numbers of GT repeats varied from 12 to 28. There were significant differences in allele distribution between African Americans and Caucasians (P=0.008) and between African Americans and Koreans (P=0.0003). The promoter activities of recombinant promoter-intron2/reporter constructs including the shortest [GT)n=12] or longest [(GT)n=28] alleles were significantly more stimulated when exposed to 200 IU ml(-1) of interferon-gamma than when exposed to 100 IU ml(-1) of GM-CSF (P<==0.03). Since TLR2 plays a critical role in the human innate immune response, this functional microsatellite polymorphism may be important in the pathogenesis of infectious and inflammatory diseases.

Alleles↗

A digital ion trap mass spectrometer coupled with atmospheric pressure ion sources.

In a digital ion trap (DIT), the quadrupole trapping and excitation waveforms are generated by the rapid switching between discrete d.c. voltage levels. As the timing of the switch can be controlled precisely by digital circuitry, the approach provides an opportunity to generate mass spectra by means of a frequency scan in contrast to the conventional voltage scan, thus providing a wider mass range of analysis. An instrument has been constructed which employs a 'non-stretched' ion trap and the field fault around the aperture of the end-cap electrode can be corrected electronically using a field-adjusting electrode. The ion trap was coupled with electrospray ionization (ESI) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) sources to demonstrate the capability of the digital method. AP-MALDI mass spectra of singly charged ions with mass-to-charge ratios upto 17 000 Th were generated using a trapping voltage of only 1000 V. Forward and reverse mass scans at resolutions up to 19 000 and precursor ion isolation at resolutions up to 3500 with subsequent tandem mass spectrometric analysis were demonstrated. The method of generating the digital waveforms and period scan is described. Discussion of the issues of mass range, scan speed, ion trapping efficiency and collision-induced dissociation efficiency are also provided.

Animals↗

Cooperation between PKC-alpha and PKC-epsilon in the regulation of JNK activation in human lung cancer cells.

Phorbol esters can induce activation of two mitogen-activated protein kinase (MAPK) pathways, the extracellular signal-regulated kinase (ERK) pathway and the c-Jun N-terminal kinase (JNK) pathway. Unlike ERK activation, JNK activation by phorbol esters is somehow cell-specific. However, the mechanism(s) that contribute to the cell-specific JNK activation remain elusive. In this study, we found that phorbol 12-myristate 13-acetate (PMA) induced JNK activation only in non-small cell lung cancer (NSCLC) cells, but not in small cell lung cancer (SCLC) cells, whereas ERK activation was detected in both cell types. In NSCLC cells, PMA induced JNK activation in a time- and dose-dependent manner. JNK activation was attenuated by protein kinase C (PKC) down-regulation through prolonged pre-treatment with PMA and significantly inhibited by PKC inhibitors Gö6976 and GF109203X. Subcellular localization studies demonstrated that PMA induced translocation of PKC-alpha, -betaII, and -epsilon isoforms, but not PKC-delta, from the cytosol to the membrane. Analysis of various PKC isoforms revealed that PKC-epsilon was exclusively absent in the SCLC cell lines tested. Ectopic expression of PKC-epsilon in SCLC cells restored PMA activation of JNK signaling only in the presence of PKC-alpha, suggesting that PKC-alpha and PKC-epsilon act cooperatively in regulating JNK activation in response to PMA. Furthermore, using dominant negative mutants and pharmacological inhibitors, we define that a putative Rac1/Cdc42/PKC-alpha pathway is convergent with the PKC-epsilon/MEK1/2 pathway in terms of the activation of JNK by PMA.

Animals↗

Interferon-gamma receptor 1 promoter polymorphisms: population distribution and functional implications.

Different polymorphisms have been described in the minimal promoter region (MPR) of the interferon-gamma receptor 1 (IFNGR1), a molecule that plays a critical role in mycobacterial control. We sequenced the IFNGR1 MPR from African American, Caucasian and Korean controls, and from mycobacteria-infected patients. Six different single nucleotide polymorphisms (SNPs) were detected in the IFNGR1 MPR. The three ethnic groups showed different SNP distribution patterns, but no significant differences were detected between mycobacterial cases and controls. Two polymorphisms were found in all populations (G-611A, T-56C). We cloned the four allelic variants (var) of haplotype G-611A/T-56C into a luciferase reporter vector and determined their promoter activity. Polymorphisms at position -611 had a stronger effect on the promoter activity than those at position -56, and constructs carrying G-611 produced a stronger promoter activity than -611A constructs. The IFNGR1 MPR is a polymorphic region with at least two SNPs influencing its activity, but these are not associated with increased mycobacterial susceptibility.

Cloning, Molecular↗

EAnnot: a genome annotation tool using experimental evidence.

The sequence of any genome becomes most useful for biological experimentation when a complete and accurate gene set is available. Gene prediction programs offer an efficient way to generate an automated gene set. Manual annotation, when performed by experienced annotators, is more accurate and complete than automated annotation. However, it is a laborious and expensive process, and by its nature, introduces a degree of variability not found with automated annotation. EAnnot (Electronic Annotation) is a program originally developed for manually annotating the human genome. It combines the latest bioinformatics tools to extract and analyze a wide range of publicly available data in order to achieve fast and reliable automatic gene prediction and annotation. EAnnot builds gene models based on mRNA, EST, and protein alignments to genomic sequence, attaches supporting evidence to the corresponding genes, identifies pseudogenes, and locates poly(A) sites and signals. Here, we compare manual annotation of human chromosome 6 with annotation performed by EAnnot in order to assess the latter's accuracy. EAnnot can readily be applied to manual annotation of other eukaryotic genomes and can be used to rapidly obtain an automated gene set.

Algorithms↗

Gonadotropin releasing hormone and transforming growth factor beta activate mitogen-activated protein kinase/extracellularly regulated kinase and differentially regulate fibronectin, type I collagen, and plasminogen activator inhibitor-1 expression in leiomyoma and myometrial smooth muscle cells.

GnRH analog (GnRHa) and TGF-beta act directly on leiomyoma/myometrial smooth muscle cells (LSMCs and MSMCs) regulating diverse activities resulting in leiomyoma growth and regression. Because GnRH and TGF-beta receptor signaling is in part mediated through the MAPK pathway, we determined whether the contribution of MAPK/ERK and transcriptional activation of c-fos and c-jun, result in differential regulation of type I collagen, fibronectin, and plasminogen activator inhibitor 1 (PAI-1) gene expression, whose products are known to influence extracellular matrix turnover, which is critical in leiomyoma growth and GnRHa-induced regression. We found that GnRHa and TGF-beta in a dose- and time-dependent manner increased the level of phosphorylated ERK1/2 (pERK1/2) in LSMCs and MSMCs. GnRHa and TGF-beta increased ERK1/2 nuclear accumulation resulting in differential regulation of c-fos and c-jun mRNA expression via downstream signaling from MAPK kinase (MEK)1/2, because pretreatment with U0126, a synthetic inhibitor of MEK1/2, abolished basal and GnRHa- and TGF-beta-induced pERK1/2 and the expression of c-fos and c-jun. LSMCs and MSMCs also express fibronectin, type I collagen, and PAI-1 mRNA, and GnRHa and TGF-beta altered their expression in a cell-specific manner through MEK1/2. We concluded that GnRHa and TGF-beta acting through a MAPK/ERK pathway and transcriptional activation of c-fos/c-jun results in differential regulation of specific genes whose products may in part influence the outcome of leiomyoma growth and regression.

Collagen Type I↗

[Pharmacokinetics and bioequivalence of trimebutine dispersive tablet in healthy subjects].

AIM: To develop an HPLC-ESI-MS assay for determination of trimebutine in human plasma and to investigate the pharmacokinetics and bioequivalence of two trimebutine tablets in human. METHODS: After being made alkaline with saturated sodium bicarbonate, plasma was extracted by cyclohexane and separated by HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (pH 3.5)-methanol (18:82). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 388 for trimebutine and m/z 280 for the internal standard (sibutramine, IS). The fragmentor voltage was 50 V. A randomized cross-over design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer. RESULTS: Calibration curve was linear over the range of 0.3 - 150 microg x L(-1). The main pharmacokinetic parameters of T1/2, Tmax and Cmax were (9.2 +/- 2.8) h, (1.0 +/- 0.3) h and (40 +/- 20) microg x L(-1) for the reference tablet; (9.2 +/- 2.3) h, (0.9 +/- 0.4) h and (41 +/- 20) microg x L(-1) for the test tablet. The relative bioavalability of the test tablet was (97 +/- 13)%. The results of variance analysis and two one-sided t-test showed that there was no significant difference between the two formulations in the AUC and Cmax. CONCLUSION: The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.

Adult↗

[Pharmacokinetics and bioequivalence of eperisone hydrochloride tablet in healthy subjects].

AIM: To develop a HPLC-ESI-MS assay for determination of eperisone hydrochloride in human plasma and investigate the pharmacokinetics and bioequivalence of two eperisone hydrochloride tablets in human. METHODS: Buflomedil hydrochloride was used as the internal standard. After alkalized with saturated sodium bicarbonate solution, plasma was extracted with diethylether-cyclohexane (1:1) and separated using HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 3.88 with acetic acid)-methanol (20:80). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 260 for eperisone and m/z 308 for the internal standard. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer. RESULTS: Calibration curve was linear over the range of 0.02-20 microg x L(-1). The limit of quantification for eperisone hydrochloride in plasma was 0.02 microg x L(-1). The main pharmacokinetics parameters T1/2, Tmax and Cmax were (2.7 +/- 0.4) h, (1.1 +/- 0.5) h and (2.8 +/- 2.8) microg x L(-1) for the reference tablet; (2.8 +/- 0.5) h, (1.1 +/- 0.4) h and (3 +/- 4) microg x L(-1) for the test tablet, respectively. The relative bioavalability of the test tablet was (101 +/- 13)%. CONCLUSION: The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.

Adult↗

A comparison of cost and efficacy of three incontinence skin barrier products.

Maintaining healthy, intact perineal skin in nursing home residents with incontinence is a challenge. Their condition puts them at risk for developing incontinence dermatitis, possibly predisposing them to develop pressure ulcers. To examine the cost-effectiveness of three perineal skin barriers (a polymer-based barrier film and two petrolatum ointments) used to prevent incontinence dermatitis, a 6-month descriptive study was conducted among residents (N = 250) from four long-term care facilities (nursing homes) in the upper Midwestern US. All residents were incontinent and had intact perineal skin when they enrolled in the study. An economic analysis was performed using time-motion data from a convenience sample of enrolled residents and their caregivers. Residents had an average of 4.1 (+/-2.307) incontinent episodes per day, the occurrence of incontinence dermatitis was 3.3 % and not significantly different between the different protocols of care (P = 0.4448). Results of the economic analysis showed that daily barrier application costs ranged from $0.17 for the barrier film to $0.76 for the ointments evaluated. With labor included in the analysis, costs were also lower for the barrier film that required the least frequent application ($0.26) compared to ointments that required more frequent application ($1.40). Results of this study suggest that the daily or three times weekly barrier film protocols are affordable alternatives to using petrolatum ointments in the prevention of incontinence dermatitis.

Analysis of Variance↗

[Determination of the binding constants of four anti-HIV-1 active compounds with bovine serum albumin by capillary zone electrophoresis].

The binding constants (Kb) of four novel anti-HIV-1 active compounds with bovine serum albumin (BSA) were determined by capillary zone electrophoresis (CZE) with UV detection under condition of phosphate buffer (pH 8.0, 50 mmol/L) at 15 kV running voltage. These molecules were synthesized by computer-simulated design with the property of inhibiting the binding of HIV-1 Tat protein to trans-activation response region (TAR) RNA required for HIV-1 transcription and blocking the HIV replication cycle. The results showed that with the addition of different concentrations of BSA into the buffer solution, the binding constants of four active compounds (IG3, iso-C3, C3, MC3) with BSA could be measured by the change of migration time. The experimental values of Kb were 1.07 x 10(4), 1.34 x 10(4), 8.51 x 10(3) and 9.45 x 10(3) L/mol, respectively. It is an easy and simple method to estimate the interaction of small molecules with biomacromolecules with 1:1 molar binding ratio.

Animals↗