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Biomedical subjects

W Meng

Publications and source records attributed to W Meng.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Study on diarrhea disease and Escherichia coli strains harboring HPI pathogenicity island of Yersinia enterolitica in Shandong province].

OBJECTIVE: It was found that some E. coli strains previously identified as entero SLTs-producing and invasive E. coli (ESIEC), harboring HPI pathogenicity island of Yersinia enterolitica. This research was designed to reveal prevalence, susceptible group and clinical features it caused. METHODS: All of the diarrhea patients were from the out-patient units of four hospitals in Shandong province from June to November of 1997. Stool specimen were collected before administration of antibiotics for isolation of enteric bacterial pathogen. Clinical symptoms were recorded at the same time. RESULTS: A total number of 449 enteric pathogenic bacteria strains were detected among stool samples from 671 patients, with isolation rates of Shigella species and diarrheagenic E. coli 25.48% and 15.05% respectively. When irp-2 and ipaB gene fragments were used as DNA probes, 42 of 176 un-identifiable strains were found irp-2(+) and ipaB(-), which were identified as HPI-harboring E. coli. Typical symptoms of the diarrhea caused by HPI-harboring E. coli were described as mild, including abdominal pain, shiver and vapidity. Temperature of the patients was usually normal. Over 6 times of bowel movements per day was frequently observed, of which most were unformed stools with mucous. CONCLUSION: HIP-harboring E. coli was an important diarrheagenic pathogen identified from 671 patients with diarrhea. Shigella was found to be the majority strain.

China↗
PubMed2001

[The effects of thrombopoietin and interleukin-11 on bone marrow megakaryocytic progenitors in patients with chronic idiopathic thrombocytopenic purpura in vitro].

OBJECTIVE: To observe the effects of recombinant human thrombopoietin (rhTPO) and rhTPO in combination with recombinant human interleukin-11(rhIL-11) on the megakaryocyte (MK) colony growth and maturation in patients with chronic idiopathic thrombocytopenic purpura (CITP) in vitro. METHODS: Bone marrow (BM) mononuclear cells of 21 patients with CITP were cultured in plasma clot culture systems, to which were added rhTPO alone or rhTPO plus rhIL-11 over a range of concentrations. After 14 days, the MK colonies were stained by GP III a Mc Ab(SZ-21) and ABC-Kit and counted. The diameters and areas of the positive cells of GP III a were measured by BM-cell analysis system of MCDS-2010. RESULTS: The diameters and areas of MK in CITP group were significantly lower than that in control group, P < 0.05. The addition of rhTPO to culture systems increased CFU-MK, total colonies and diameters and areas of MK in CITP patients. And this promoting effect was not dose-dependent. The optimal concentration of rhTPO was 10 ng/ml; in the group where 10 ng/ml rhTPO was used in combination with 20 ng/ml rhIL-11, the counts of CFU-MK, total colonies and the measurements of areas and diameters of MK increased significantly, compared with those in the group where rhTPO was used alone. CONCLUSION: There are maturation dysfunctions of MK progenitors in patients with CITP. rhTPO alone or in combination with rhIL-11 can promote the proliferation and maturation of MK progenitors in patients with CITP and, moreover, the combination of the two cytokines has more significant promoting effects, compared to rhTPO alone.

Adolescent↗
PubMed2001

Localization of cathepsins G and L in spontaneous resorption of intervertebral discs in a rat experimental model.

To determine the involvement of cathepsins G and L in the mechanism of spontaneous resorption of herniated intervertebral discs, localization of these cathepsins in this process was examined immunohistochemically using a rat model of autologous transplantation of coccygeal discs. Rat coccygeal discs were resected and autotransplanted into the subcutaneous space of the skin of the back. Paraffin-embedded sections of intervertebral disc tissue, harvested at various post-transplantational periods, were immunohistochemically stained with antibodies for cathepsin G, cathepsin L, MMP-1, MMP-3 and ED-2. The number of positive cells was counted in each part of the transplanted discs. Immunolocalization of cathepsins G and L in various types of disc cells was first observed early in the post-transplantation period. From two days after the operation, histology showed invasion by granulation tissue, with many macrophages, in all sections. Subsequently, the number of macrophages in granulation tissue was observed to increase, along with a gradual increase in the percentage of cells positive for MMP-1 and MMP-3. In addition to the ability of cathepsins G and L to degrade major extracellular matrix components of intervertebral discs, cathepsin G is capable of activating latent pro-MMPs. The up-regulation of cathepsins G and L in the intervertebral disc tissue in this spontaneous resorption model suggests that these proteinases may be involved in degradation of extracellular matrix, leading to the natural resorption of herniated discs.

Journal Article↗
PubMed2000

Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch.

The p21-activated kinases (PAKs), stimulated by binding with GTP-liganded forms of Cdc42 or Rac, modulate cytoskeletal actin assembly and activate MAP-kinase pathways. The 2.3 A resolution crystal structure of a complex between the N-terminal autoregulatory fragment and the C-terminal kinase domain of PAK1 shows that GTPase binding will trigger a series of conformational changes, beginning with disruption of a PAK1 dimer and ending with rearrangement of the kinase active site into a catalytically competent state. An inhibitory switch (IS) domain, which overlaps the GTPase binding region of PAK1, positions a polypeptide segment across the kinase cleft. GTPase binding will refold part of the IS domain and unfold the rest. A related switch has been seen in the Wiskott-Aldrich syndrome protein (WASP).

Amino Acid Sequence↗
PubMed2000

The inhibitory effect of prostaglandin E1 on oxidative stress-induced hepatocyte injury evaluated by calpain-mu activation.

BACKGROUND: Prostaglandin E1 (PGE1) is known to inhibit ischemia-reperfusion injury of the liver. The calcium-dependent neutral proteinase, calpain-mu, is involved in oxidative stress-induced hepatocyte injury. We investigated the mechanisms of cytoprotection by PGE1, focusing on the elevation of intracellular calcium ([Ca2+]i), activation of calpain-mu, and calpain-mu-mediated activation of protein kinase C-alpha (PKC-alpha). METHODS: Cultured hepatocytes were treated with various amounts of PGE1 (0, 0.1, 1.0, 10, and 100 ng/ml) for 30 min and subsequently with 0.5 mM tert-butyl hydroperoxide (TBHP). Cell injury was evaluated by the release of lactate dehydrogenase. Plasma membrane bleb formation was examined by phase contrast microscopy. Activation of calpain-mu and limited degradation of PKC-alpha was evaluated by Western blotting using antibodies that specifically recognize the amino-terminal regions of calpain-mu and PKC-alpha. [Ca2+]i was measured by confocal microscopy using Fluo-3AM. RESULTS: LDH release from cells treated with 10 ng/ml PGE1 was significantly lower than from untreated cells (135 +/- 12 vs. 258 +/- 18 IU/L, respectively; P < 0.05). Morphologically, many blebs were observed in untreated cells, but very few were seen in those treated with 10 ng/ml PGE1. Western blotting revealed that the amount of activated calpain-mu and [Ca2+]i increased up to 1,300 nM at 35 min after the addition of TBHP (0.5 mmol/L) in control experiments (without PGE1). PGE1 (10 ng/ml) delayed the rise in [Ca2+]i for about 30 min, but did not suppress it completely. PKC-alpha decreased in experiments using PGE1 (10 ng/ml). CONCLUSION: PGE1 exerts its cytoprotective effect in TBHP-induced hepatocyte injury partly by inhibiting Ca2+-calpain-mu-mediated mechanisms.

Alprostadil↗
PubMed2000

The Escherichia coli RNA polymerase alpha subunit linker: length requirements for transcription activation at CRP-dependent promoters.

The C-terminal domain of the Escherichia coli RNA polymerase alpha subunit (alphaCTD) plays a key role in transcription initiation at many activator-dependent promoters. This domain is connected to the N-terminal domain by an unstructured linker, which is proposed to confer a high degree of mobility on alphaCTD. To investigate the role of this linker in transcription activation we tested the effect of altering the linker length on promoters dependent on the cyclic AMP receptor protein (CRP). Short deletions within the alpha linker decrease CRP-dependent transcription at a Class I promoter while increasing the activity of a Class II promoter. Linker extension impairs CRP-dependent transcription from both promoters, with short extensions exerting a more marked effect on the Class II promoter. Activation at both classes of promoter was shown to remain dependent upon activating region 1 of CRP. These results show that the response to CRP of RNA polymerase containing linker-modified alpha subunits is class specific. These observations have important implications for the architecture of transcription initiation complexes at CRP-dependent promoters.

Amino Acid Sequence↗
PubMed2000

Evidence for apoptosis after intercerebral hemorrhage in rat striatum.

The overall hypothesis that cell death after intracerebral hemorrhage is mediated in part by apoptotic mechanisms was tested. Intracerebral hemorrhage was induced in rats using stereotactic infusions of 0.5 U of collagenase (1-microL volume) into the striatum. After 24 hours, large numbers of TUNEL-positive stained cells with morphologies suggestive of apoptosis were present in the center and periphery of the hemorrhage. Double staining with Nissl and immunocytochemical labeling with antibodies against neuronal nuclei and glial fibrillary acidic protein suggested that these TUNEL-positive cells were mostly neurons and astrocytes. Electrophoresis of hemorrhagic brain extracts showed evidence of DNA laddering into approximately 200-bp fragments. Western blots showed cleavage of the cytosolic caspase substrate gelsolin. The density of TUNEL-positive cells at 24 and 48 hours after hemorrhage was significantly reduced by treatment with the broad-spectrum caspase inhibitor zVADfmk. It was unlikely that apoptotic changes were due to neurotoxicity of injected collagenase because TUNEL-positive cells and DNA laddering were also obtained in an alternative model of hemorrhage where autologous blood was infused into the striatum. Furthermore, equivalent doses of collagenase did not induce cell death in primary neuronal cultures. These results provide initial evidence that apoptotic mechanisms may mediate some of the injury in brain after intracerebral hemorrhage.

Amino Acid Chloromethyl Ketones↗
PubMed2000

[The association and linkage analysis between the FcgammaR II a-131 and system lupus erythematosus].

OBJECTIVE: To shed light on the relationship between FcgammaR II a-131 and systemic lupus erythematosus(SLE) in southern Chinese Han population. METHODS: A population-based and family-based study was carried out. FcgammaR II a-131 of each subject was measured by using PCR-allele specific oligonucleotide hybridization(ASO) method. RESULTS: (1) The distribution of FcgammaR II A-131 genotype in cases is significantly different from that in controls (P<0.05). So is the frequency of FcgammaR II aR-131 allele (P < 0.01) which suggests that subjects who have R131 allele tend to be more susceptible to SLE. The subjects with R/R131 homozygous genotype have a higher risk of suffering from SLE. (2) The distribution of FcgammaR II a-131 varies in different races, with identical distribution type among Chinese and Japanese. (3) The results of family-based association analysis and transmitted/disequilibrium test(TDT) suggest that there is not any linkage evidence between FcgammaR II a-131 and SLE. Possibly, the sample size was too small to get positive result. CONCLUSION: This study suggests that FcgammaR II a-131 is a major factor predisposing to the development of SLE in southern Chinese Han population.

Alleles↗
PubMed2000

[Evaluation of performance and blood compatibility of polyethersulfone hollow fiber plasma separator].

In this study, we evaluated the performance and blood compatibility of polyethersulfone hollow fiber membrane plasma separator by animal experiment. Hemolysis did not occur under the usual conditions of plasma separation. The sieving coefficients of total protein, albumin and globulin were over 95%, and about 60% of total plasma were extracted from the whole blood. White blood cells, platelets, fibrinogen, and coagulation factors were decreased during the early stage of plasma separation and appeared to be within acceptable ranges for clinical use.

Animals↗
PubMed2000

[Acute promyelocytic leukemia cell differentiation induced by tanshinone II A and its molecular mechanism].

OBJECTIVE: To investigate APL cell differentiation induced by tanshinone II (Tan II A) and its molecular mechanism. METHODS: In vitro incubation of NB4 cells with Tan II A at the concentration of 0.5 microg/ml for 5 days, the cell differentiation was observed by cytomorphology, and nitroblue tetrazolium (NBT) test. Cell cycle, membrane CD(33), CD(11b) antigens and gene expressions (c-myc, c-fos, p53 and bcl-2) were analysed by flow cytometry. RESULTS: (91.3 +/- 2.1)% of NB4 cells were induced into morphologically and functionally more differentiated cells including 0.26 of myelocytes and metamyelocytes, and 0.68 of band form and neutrophils. Cell growth curve showed that growth of NB4 cells were inhibited. NBT reduction was significantly increased. Expression of CD(33) decreased and CD(11b) increased. The degrees of cell differentiation and growth inhibition induced by Tan II A or ATRA were no difference. Flow cytometry analysis showed that Tan II A arrested NB4 cell in G(0)/G(1) phase, inhibited cellular DNA synthesis, down-regulated c-myc and bcl-2 genes expression, and up-regulated c-fos and p53 genes expression. CONCLUSION: Tan II A can induce differentiation and growth inhibition of NB4 cells. Its possible molecular mechanism might relate to modulation of gene expressions associated proliferation and differentiation, and to inhibition of DNA synthesis.

Abietanes↗
PubMed2000

[A three-dimensional finite element analysis of the correlation between lengths and diameters of the implants of fixed bridges with proper stress distribution].

OBJECTIVE: The study is designed to investigate the correlation between lengths and diameters of the implants of fixed bridges with proper stress distribution. Meanwhile, the correlation between the diameter of the implants and the size of a mandible bone is evaluated by stress analysis. METHODS: According to the stress around the implants of an implant fixed bridge with proper stress distribution, especially peak stress, a three-dimensional finite element method was used to determine the correlation between diameters and lengths of implants with their diameters or lengths changing. RESULTS: The peak stress surrounding the implants in fixed bridge supported by clinical implants that were commonly used was figured out, and the correlated amount of diameters or lengths of the implants were achieved. Furthermore, a correlation curve of diameter and length of the implants was made. But the correlated amount of diameters or lengths of the implants were not found in this model. CONCLUSION: The proper stress distribution of implants with different implant sizes can be achieved by adjusting diameters or/and lengths of implants. The selection of the implant size is related to the limited model size. Being a preliminary theory, the results will be proved to be clinically acceptable to the size selection of implants.

Adult↗
PubMed2000

[Clinical study on interferon treatment of chronic idiopathic thrombocytopenic purpura].

The efficacy and mechanism of interferon alpha-2a (IFN alpha-2a) were assessed in the treatment of chronic idiopathic thrombocytopenic purpura (cITP). 20 patients with cITP (treatment group) were treated with IFN alpha-2a 3MIU i.m. once a week for 8 weeks; 28 patients with cITP (control group) were treated with prednisone 1 mg/(kg.d) for 4 weeks. Blood platelet counts (BPC), megakaryocyte number, immunnological parameters, percent and absolute counts of reticulated platelets (RPs) and megakaryocyte colony formation units were observed before and after therapy. The results showed that the efficacy of IFN alpha-2a was better than that of corticosteroid, P < 0.05. The RPs% decreased and the platelet-producing megakaryocyte percentage increased from 11.43% to 33.19% significantly after IFN alpha-2a therapy, but there were no significant changes in immunnological parameters. These indicate that IFN alpha-2a is effective in treating cITP, the mechanism may be based on promoting the megakaryocyte development and activating the production of platelets.

Adolescent↗
PubMed1999

[Iodine therapy for iodine deficiency goiter and autoimmune thyroiditis. A prospective study].

PROBLEM: There is epidemiological and clinical evidence that iodine may induce or promote the manifestation of autoimmune thyroiditis. For this reason it is important to know if substitution of alimentary iodine deficiency or iodine treatment of endemic goitre can cause formation of thyroid antibodies. On the other hand the practical importance of this phenomenon should be evaluated. PATIENTS AND METHODS: During a prospective study we examined 209 patients with endemic non-toxic goitre and 53 healthy people. For treatment were used 200 micrograms iodine/d (n = 119), 500 micrograms iodine/d (n = 27), 1.5 mg iodine/week (n = 41), 150 micrograms iodine/d plus 75 to 100 micrograms T4/d (n = 26), 100 micrograms iodine plus 100 micrograms T4/d (n = 24). The observation took 1 year with a 3-month interval for check ups including clinical examination, ultrasound, TSH, T3, fT4, TPO- and thyreoglobuline antibodies and urinary iodine. RESULTS: After 12 months 7.5% of iodine treated persons had produced antibodies, most of them at low levels. In healthy people we found increased antibody-levels in 3.8%, in patients with goitre in 9.0%, in patients with nodular goitres in 11.1%. 500 micrograms iodine caused the most antibody reaction in 14.8%. People treated with 200 micrograms iodine/d showed positive antibody levels in 5%. T4 seems to reduce antibody-reactions. Pathological antibody-levels were not found in patients with combined iodine/T4- and single-T4 therapy. Among the 22 primary pathological antibody levels only 4 increased further (18.2%). Three of them belonged to the group of 5 persons treated with 500 micrograms iodine/d. Primary high antibody values were normalized in 5 patients (22.7%). Hypothyroid disturbances were not found. Ultrasound did not show any alterations, and the reduction of thyroid volumes in antibody-positive patients was not affected. Median urinary iodine excretion during the observation-interval was 5.2 to 7.2 micrograms/dl. CONCLUSIONS: Possible antibody reactions have no clinical importance at all. Individual cases must be observed. Low iodine doses should be preferred. Combined iodine/T4 treatment seems to have an advantage regarding immunological thyroidal reactions.

Adult↗
PubMed1999

Generation of human T-cell responses to an HLA-A2.1-restricted peptide epitope derived from alpha-fetoprotein.

Alpha-fetoprotein (AFP) is often derepressed in human hepatocellular carcinoma. Peptide fragments of AFP presented in the context of major histocompatibility molecules could serve as potential recognition targets by CD8 T cells, provided these lymphocytes were not clonally deleted in ontogeny. We therefore wished to determine whether the human T-cell repertoire could recognize AFP-derived peptide epitopes in the context of a common class I allele, HLA-A2.1. Dendritic cells genetically engineered to express AFP were capable of generating AFP-specific T-cell responses in autologous human lymphocyte cultures and in HLA-A2.1/Kb transgenic mice. These T cells recognize a 9-mer peptide derived from the AFP protein hAFP(542-550) (GVALQTMKQ). Identified as a potential A2.1-restricted peptide epitope from a computer analysis of the AFP sequence, hAFP(542-550) proved to have low binding affinity to A2.1, but slow off-kinetics. AFP-specific CTL- and IFN-gamma-producing cells recognize hAFP(542-550)-pulsed targets. Conversely, hAFP(542-550) peptide-generated T cells from both human lymphocyte cultures and A2.1/Kb transgenic mice recognized AFP-transfected targets in both cytotoxicity assays and cytokine release assays. These lines of evidence clearly demonstrate that AFP-reactive clones have not been deleted from the human T-cell repertoire and identify one immunodominant A2.1-restricted epitope. These findings also clearly establish AFP as a potential target for T-cell-based immunotherapy.

Amino Acid Sequence↗
PubMed1999

Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase.

Cbl is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface. The evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to phosphorylated tyrosine residues and has cell-transforming activity. Point mutations in Cbl that disrupt its recognition of phosphotyrosine also interfere with its negative regulatory function and, in the case of v-cbl, with its oncogenic potential. In T cells, Cbl-N binds to the tyrosine-phosphorylated inhibitory site of the protein tyrosine kinase ZAP-70. Here we describe the crystal structure of Cbl-N, both alone and in complex with a phosphopeptide that represents its binding site in ZAP-70. The structures show that Cbl-N is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium-binding domain, and a divergent SH2 domain that was not recognizable from the amino-acid sequence of the protein. The calcium-bound EF hand wedges between the 4H and SH2 domains and roughly determines their relative orientation. In the ligand-occupied structure, the 4H domain packs against the SH2 domain and completes its phosphotyrosine-recognition pocket. Disruption of this binding to ZAP-70 as a result of structure-based mutations in the 4H, EF-hand and SH2 domains confirms that the three domains together form an integrated phosphoprotein-recognition module.

Amino Acid Sequence↗
PubMed1999

Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats.

Tissue type plasminogen activator (tPA) can be effective therapy for embolic stroke by restoring cerebral perfusion. However, a recent experimental study showed that tPA increased infarct size in a mouse model of transient focal ischemia, suggesting a possible adverse effect of tPA on ischemic tissue per se. In this report, the effects of tPA in two rat models of cerebral ischemia were compared. In experiment 1, rats were subjected to focal ischemia via injection of autologous clots into the middle cerebral artery territory. Two hours after clot injection, rats were treated with 10 mg/kg tPA or normal saline. Perfusion-sensitive computed tomography scanning showed that tPA restored cerebral perfusion in this thromboembolic model. Treatment with tPA significantly reduced ischemic lesion volumes measured at 24 hours by >60%. In experiment 2, three groups of rats were subjected to focal ischemia via a mechanical approach in which a silicon-coated filament was used intraluminally to occlude the origin of the middle cerebral artery. In two groups, the filament was withdrawn after 2 hours to allow for reperfusion, and then rats were randomly treated with 10 mg/kg tPA or normal saline. In the third group, rats were not treated and the filament was not withdrawn so that permanent focal ischemia was present. In this experiment, tPA did not significantly alter lesion volumes after 2 hours of transient focal ischemia. In contrast, permanent ischemia significantly increased lesion volumes by 55% compared with transient ischemia. These results indicate that in these rat models of focal cerebral ischemia, tPA did not have detectable negative effects. Other potentially negative effects of tPA may be dependent on choice of animal species and model systems.

Animals↗