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Biomedical subjects

Q Wu

Publications and source records attributed to Q Wu.

At least 379 records · Page 21Linked to original sources

[The indication and technique in total correction of tetralogy of Fallot: experiences in 212 patients].

Two hundred and twelve consecutive patients underwent total correction of tetralogy of Fallot at Fuwai Hospital in Beijing between Sept. 1987 to Dec. 1993. They were 131 males and 81 females. Their age ranged from 1 year and 6 months to 37 years. 53 patients were more than 16 years old. Most of them had a typical symptoms and manifestations like cyanosis and clubbing fingers etc. Their HB ranged 155 to 325g/L (mean 21.2 +/- 3g/L). It was more thant 180g/L in 134 patients. SBE was complicated in one patient and reoperation was performed in 3 patients. Maldevelopment or hypoplasia of pulmonary artery and left ventricle were found in 52 patients. Only 2 patients died from nonsurgical cause postoperatively. The mortality was 0.9%. The remaining patients recovered uneventfully. The results suggested that hypoplastic pulmonary artery and left ventricle were not a absolute contraindication of total correction of tetralogy of Fallot. The high hematocrit was also not a high risk factor for death. The key was to correct the pathology completely and manage the complications properly.

Adolescent↗

[A comparative study on the chemical constituents of cultivated and wild fructus Gardeniae].

Studies have been made on the preliminary tests of the chemical constituents of cultivated and wild Fructus Gardeniae on the comparative analysis of the thin-layer chromatograms, IR and UV spectra of 95% ethanolic extracts as well as extracts obtained with four different solvents, and on the content determination of gardenosides. The results reveal that the cultivated and wild Fructus Gardeniae have similar chemical constituents, but differ in the contents of some constituents.

Chromatography, Thin Layer↗

[An electron microscopic histochemical study on proteoglycans in salivary gland myoepithelioma].

Four myoepitheliomas and four parotid gland were studied histochemically be electron microscopy after stain with ruthenium red. It was found that the normal myoepithelial cells of parotid gland had no secretion function, whereas the myoepithelioma cells were capable of secreting proteoglycans and might form the myxoid region in this tumor. The authors propose that in the pathological diagnosis and differentiat diagnosis of salivary gland epithelial tumors, the appearance of the myxoid region is not only the pathological feature of pleomorphic adenoma, but also the pathological change of myoepithelioma.

Humans↗

Coordination of transcription factors, NF-Y and C/EBP beta, in the regulation of the mdr1b promoter.

The expression of mdr genes that encode P-glycoprotein, an integral membrane drug transporter, has been associated with the emergence of the multidrug resistance phenotype during treatment with cancer chemotherapeutic drugs. To understand the regulation of the mdr genes, the murine mdr1b promoter has been isolated and characterized in our laboratory. Three nuclear protein binding sites that interact with nuclear proteins present in both drug-sensitive and -resistant murine macrophage-like 1774.2 cells have been localized to the promoter. In this report, transcription factor NF-Y has been identified as binding to the Y-box sequence in site 1 and as a major factor in the regulation of the murine mdr1b promoter in the mouse adrenal cell line, Y-1, that endogenously expresses the mdr1b gene. The expression of CCAAT/enhancer binding protein beta (C/EBP beta) in Y-1 cells augmented mdr1b promoter activity and resulted in an increased level of mdr1b mRNA. The effect of C/EBP beta expression on mdr1b promoter activity was sensitive to mutations in the Y-box, suggesting that coordination of NF-Y with C/EBP beta is required for further activation of the mdr1b promoter. Our studies have indicated that NF-Y is a critical factor for the mdr1b promoter, and its coordination with other factors, such as C/EBP beta, could be an important mechanism involved in mdr1b gene expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Antiproliferative properties of polyamine analogues: a structure-activity study.

A basis set of polyamine analogues was designed and synthesized. These compounds were used to initiate a systematic investigation of the role of chain length, terminal nitrogen alkyl group size, and symmetry of the methylene backbone in the antineoplastic properties of polyamine analogues. New synthetic methods predicated on our earlier polyamine fragment synthesis are described for accessing the tetraamines of interest. An unsymmetrically substituted diamine reagent, N-(tert-butoxycarbonyl)-N,N'-bis(mesitylenesulfonyl)-1,4-diaminobu tane, was developed for entry into unsymmetrical tetraamines. All of the tetraamines synthesized were first evaluated in a murine leukemia L1210 cell IC50 assay at 48 and 96 h. In an attempt to correlate this behavior with some aspect of polyamine metabolism, each compound was tested for its ability to compete with spermidine for the polyamine uptake apparatus, its impact on the polyamine biosynthetic enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), and its effect on the polyamine-catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) and on polyamine pools. While there was no obvious correlation between the 48 and 96 h IC50's and the impact of the analogues on polyamine metabolism, there were other structure-activity relationships. Correlations were observed to exist between chain length and IC50's and between terminal alkyl substituents and impact on Ki, ODC, and AdoMetDC. Also, preliminary studies suggest a relationship may exist between the 48 and 96 h IC50 activities and the analogue's chronic toxicity in vivo. Finally, when the overall length of the polyamine backbone was held constant, the symmetry of the methylene chains of the polyamine fragments was shown to be unimportant to the compound's activity.

Acetyltransferases↗

Protein kinase C activation inhibits cytokine-induced nitric oxide synthesis in vascular smooth muscle cells.

Vascular smooth muscle cells (SMC) respond by relaxation to nitric oxide (NO) released from the endothelium which expresses a constitutive, Ca(2+)-dependent NO synthase (cNOS). SMC can, however, produce NO themselves upon stimulation by proinflammatory cytokines which induce expression of an inducible, Ca(2+)-independent NO synthase (iNOS). Protein kinase C represents another important second messenger system involved in the regulation of SMC contraction. We have investigated iNOS expression and NO synthesis in rat vascular SMC treated with the cytokines, IFN gamma and TNF alpha, in the presence or absence of the activator of protein kinase C, beta-phorbol-12-myristate 13-acetate (PMA). Treatment with PMA did not induce any significant accumulation of nitrite, a major stable metabolite of NO, in SMC. When added simultaneously with the cytokines, PMA significantly reduced nitrite accumulation induced by cytokine stimulation in a dose-dependent fashion. This inhibitory effect was mediated by activation of PKC since calphostin C, a specific PKC inhibitor, abolished the PMA effect. Further analysis of iNOS mRNA with a rat iNOS cDNA probe demonstrated that addition of PMA reduced expression of SMC iNOS mRNA, indicating that the antagonism in induction of NO synthesis between PMA and the proinflammatory cytokines acts on the transcriptional level. The inhibitory effect of PMA may be mediated via induction of a suppressor of iNOS expression, since pretreatment with PMA reduced NO production after subsequent treatment with cytokines. These observations suggest that activation of the PKC pathway is involved in a negative regulation of iNOS gene expression and this is compatible with the observation that vascular SMC contraction can be induced by PKC activation.

Amino Acid Oxidoreductases↗

Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains.

Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic propeptide from trypsinogen to yield active trypsin. This cleavage initiates a cascade of proteolytic reactions leading to the activation of many pancreatic zymogens. The full-length cDNA sequence for bovine enterokinase and partial cDNA sequence for human enterokinase were determined. The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor. Membrane association may be mediated by a potential signal-anchor sequence near the amino terminus. The amino terminus of bovine enterokinase also meets the known sequence requirements for protein N-myristoylation. The amino-terminal heavy chain contains domains that are homologous to segments of the low density lipoprotein receptor, complement components C1r and C1s, the macrophage scavenger receptor, and a recently described motif shared by the metalloprotease meprin and the Xenopus A5 neuronal recognition protein. The carboxyl-terminal light chain is homologous to the trypsin-like serine proteases. Thus, enterokinase is a mosaic protein with a complex evolutionary history. The amino acid sequence surrounding the amino terminus of the enterokinase light chain is ITPK-IVGG (human) or VSPK-IVGG (bovine), suggesting that single-chain enterokinase is activated by an unidentified trypsin-like protease that cleaves the indicated Lys-Ile bond. Therefore, enterokinase may not be the "first" enzyme of the intestinal digestive hydrolase cascade. The specificity of enterokinase for the DDDDK-I sequence of trypsinogen may be explained by complementary basic-amino acid residues clustered in potential S2-S5 subsites.

Amino Acid Sequence↗

Role of the NH2-terminal domain of angiotensin II (ANG II) and [Sar1]angiotensin II on conformation and activity. NMR evidence for aromatic ring clustering and peptide backbone folding compared with [des-1,2,3]angiotensin II.

The role of the NH2 termini of angiotensin II (ANG II) and [Sar1]ANG II on conformation and activity were examined by proton NMR two-dimensional-J-correlated spectroscopy and one-dimensional nuclear Overhauser effect studies in the relatively nonpolar "receptor-simulating" environment provided by dimethyl sulfoxide-d6, using the biologically inactive COOH-terminal pentapeptide [des1,2,3]ANG II as control. Irradiation of C alpha H, C2H, and C4H proton resonances in ANG II and [Sar1]ANG II resulted in enhancements of Tyr and Phe ring proton resonances, indicating that the three aromatic rings cluster together. Very strong enhancements (17-22%) of the C alpha Y proton resonance in ANG II and [Sar1]ANG II upon irradiation of the C alpha H proton resonance, and vice versa, revealed that a Tyr-Ile-His bend is a predominant feature of the conformation of the two agonists. In contrast, saturation of the C alpha H and C alpha Y proton resonances in the control pentapeptide [des-1,2,3]ANG II did not produce, respectively, any C alpha Y or C alpha H proton nuclear Overhauser effect enhancement, illustrating the absence of a Tyr-Ile-His bend in the truncated ANG II peptide. The present findings indicate that the NH2-terminal domain of ANG II appears to have an essential role in generating the biologically active charge relay conformation of the hormone.

Algorithms↗

Activation-induced exposure of the thrombin anion-binding exosite. Interactions of recombinant mutant prothrombins with thrombomodulin and a thrombin exosite-specific antibody.

The activation of serine protease zymogens involves conformational changes that increase the affinity of substrate binding and the activity of the catalytic center. The activation of prothrombin is particularly complex and requires several cleavages in the proenzyme region in addition to the conserved activation cleavage after Arg320. To understand how these cleavages lead to the exposure of the thrombin anion-binding exosite, a major macromolecular recognition site, interactions of recombinant human prothrombin derivatives with thrombomodulin, and an exosite-specific antibody were studied by competition binding and immunoprecipitation. By either method, the anion-binding exosite is not functional on prethrombin 2, which is cleaved after Arg271 and lacks fragment 1.2, nor on meizothrombin, which is cleaved only after Arg320. In contrast, the exosite is fully exposed on meizothrombin des-F1, which is cleaved after both Arg320 and Arg155 and therefore lacks amino-terminal fragment 1 (F1). Thus, two events are required to create the exosite. First, cleavage after Arg320 causes conformational changes that are much more extensive than those accompanying the activation of trypsinogen. Second, removal of amino-terminal F1 is necessary, perhaps to relieve steric hindrance. These results indicate that the F1 fragment regulates access to the thrombin exosite. The properties of meizothrombin des-F1 suggest that this prothrombin derivative could have a biological function.

Amino Acid Sequence↗

Charge state specific facile gas-phase cleavage of Asp 75-Met 76 peptide bond in the alpha-chain of human apohemoglobin probed by electrospray ionization mass spectrometry.

Herein, we present the first example of charge state specific facile gas-phase cleavage of an aspartic acid-methionine peptide linkage. This cleavage (Asp 75-Met 76) was observed in the alpha-chain of human adult hemoglobin (Hb) and was probed by electrospray ionization mass spectrometry. This specific conformational and/or charge density dependent dissociation was observed primarily in the [M + 11H]11+ and [M + 12H]12+ species. A mechanism involving an intramolecular proton transfer from the protonated carboxyl side chain of Asp 75 to the neighboring Met 76 residue yielding an anhydride moiety at the C-terminal of the Asp 75 is proposed. Dramatic differences in dissociation of [M + 13H]13+ and [M + 14H]14+ species were observed.

Amino Acid Sequence↗

Construction and characterization of a human chromosome 2-specific BAC library.

We have constructed a human chromosome 2-specific bacterial artificial chromosome (BAC) library using DNA from the somatic cell hybrid GM10826. The average size of the clones is about 63 kb. The coverage and distribution of the library were estimated by screening with known polymorphic genetic markers and fluorescence in situ hybridization (FISH). Twenty-one markers tested positive when DNA pools prepared from approximately one-sixth of the library were screened with 33 known markers. This is consistent with the theoretical calculation of 63% coverage at one genomic equivalent. This suggested that the coverage of the library is approximately 5-6x. FISH analysis with 54 BACs revealed single site hybridization to chromosome 2, and the clones were distributed randomly on the chromosome. We have also performed direct sequencing of the BAC insert ends to generate sequence-tagged sites suitable for mapping and chromosome walking. This is the first reported human chromosome 2-specific BAC library and should provide a resource for physical mapping and disease searching for this chromosome.

Base Sequence↗

Cellular regulation of nitrate uptake in denitrifying Flexibacter canadensis.

Nitrate uptake and its regulation were investigated using an ion-specific nitrate electrode for denitrifying Flexibacter canadensis under anaerobic conditions. Glucose supported a greater rate of nitrate uptake than did glycerol, glutamate, lactose, cellobiose, or ethanol. Nitrate uptake closely approximated Michaelis--Menten kinetics; the estimated Ks(glucose) and apparent Km(nitrate) for nitrate uptake were 21 and 44 microM, respectively. Nitrate disappearance was correlated with nitrite accumulation, and nitrate had an inhibitory effect on nitrite reduction. Oxygen inhibition of nitrate uptake increased as the percent air saturation increased, and reversed readily as the percent air saturation decreased. The minimal air saturation showing inhibition of nitrate uptake was about 2-4%. Azide and cyanide completely inhibited nitrate uptake. No nitrate uptake was observed in cells grown in the presence of 1 or 5 mM tungstate (no added molybdate). When molybdate (100-200 microM) was present in the medium, nitrate uptake was exhibited by organisms grown with 1 mM, but not with 5 mM, tungstate, indicating that nitrate uptake was dependent on the presence of an active nitrate reductase, and that competition between tungsten and molybdenum occurred during the formation of nitrate reductase. Nitrite production from nitrate by whole cells but not cell-free extracts was inhibited by 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone, indicating that nitrate and (or) nitrite transport depended upon the electrochemical proton gradient.

Bacteroidetes↗

Integration of traditional and modern methods in the identification of AFB cultures isolated from clinical specimens of patients with skin diseases.

This article reports the identification of 57 AFB cultures isolated from clinical specimens by using traditional methods (TM, including biochemical and cultural methods) and modern ELISA with monoclonal antibody (McAb-ELISA) and nested primer gene amplification assay (NPGAA). The representive AFB culture M. A1, A7, A19, A21 and A22) isolated from human lepromas were identified as new species by TM and it was shown that they were not identical to M. leprae by McAb-ELISA and NPGAA. Among another set of samples (M. S17, S1, S2, S2R, S7, S29), M. S17 was identical to M. scrofulaceum as assessed by TM only, while the others were found to be similar to M. tuberculosis and different from M. leprae using TM and McAb-ELISA, and identical to M. tuberculosis with NPGAA. The authors conclude that TM and MM are very useful for identifying mycobacteria, while MM was much more sensitive and specific than TM. The selection and use of these methods depends on practical need.

Base Sequence↗

[Evaluation of two glycolipids from M. tuberculosis in the serodiagnosis of tuberculosis].

Sera from 112 healthy controls and 120 pulmonary tuberculous patients (61 untreated patients and 59 active patients) were assayed, by ELISA, to test the activity of IgG and IgM antibodies against antigen of 2, 3-diacyl-trehalose-2'-sulphate (SL IV) a phenolglycolipid antigen (PGLTb1) and purified protein derivative (PPD) from M. tuberculosis. Respectively, for SL IV-IgG-ELISA, SL IV-IgM-ELISA, PGLTb1-IgG-ELISA, PGLTb1-IgM-ELISA, PPD-IgG-ELISA, the specificities were of 96.43, 96.43, 96.43, 96.43 and 95.53%; the sensitivities were of 51.67, 32.50, 14.17, 18.33 and 33.33%; the efficiencies were of 73.28, 63.36, 53.88, 56.03 and 62.93%; the predictive values for a positive result were of 96.87, 86.67, 80.95, 84.62 and 88.64%. Among the three antigens tested, SL IV was found to be better than PGLTb1 and PPD.

Antibodies, Bacterial↗

[Study on antibacterial protein from human urinary bladder mucosa].

Acid-soluble extract of human bladder mucosal surface was obtained by washing out the bladder of accidentally dead male human with 1% acetic acid in the presence of proteinase inhibitors. Acid urea polyacrylamide gel electrophoresis (AU-PAGE) indicated that the acid-soluble extract had more than 10 main protein bands, but the currently known antibiotic peptides, e. g., Lysozyme and defensins, were not found in this extract. The quantitation assay of lysozyme showed that lysozyme only amounted to 2.2 microgram per milligram protein. When tested for antibacterial activity by using ultrasensitive radial diffusion assay, the acid-soluble extract effectively killed E. coli ML-35P. The antibacterial activity of the acid-soluble extract was further analysed by gel overlay technique and the result showed that one main protein band, which was referred to as human bladder protein (HBP), was potently antibacterial against E. coli ML-35P. The HBP accounted for 4% of the total acid-soluble extract protein. These results suggest that the presence of antibacterial protein in the bladder mucosa may be the molecular base of the bladder antibacterial defence mechanisms.

Adult↗

Cardiorespiratory responses to low-intensity heart rate-controlled exercise in female subjects.

This study compares selected cardiorespiratory responses of six healthy females during exercise on rowing (R), cycle (C) and arm (A) ergometers. Their mean +/- sd age, mass and height were 22.3 +/- 3.0 years, 55.3 +/- 6.3 kg and 161.5 +/- 7.4 cm, respectively. Subjects reported to the laboratory on three separate days without engaging in intense physical activity the day prior to testing. Subjects sat quietly for five minutes on an ergometer prior to a 15 minute, steady-state exercise bout. Target heart rate during the exercise period was set at 115 bpm, and was monitored continually with workload adjustments applied to the ergometers to ensure that the target rate was maintained. CO2 rebreathing using the Sensormedics Horizon MMC was performed twice at steady-state exercise and averaged to examine changes in Q and SV. A one-way repeated measures ANOVA revealed that at similar levels of heart rate (R = 114.0 +/- 2.8; C = 116.0 +/- 2.8; A = 114.8 +/- 6.9 bpm) there were significantly lower Q and SV during arm ergometry (8.43 +/- 0.93 l/min and 72.61 +/- 7.82 ml) than rowing (13.01 +/- 1.61 l/min and 111.57 +/- 13.52 ml) and cycle (11.10 +/- 2.19 l/min and 88.23 +/- 21.94 ml) ergometry, and there were no significant differences in Q and SV between rowing and cycling. These results suggest that arm work during low intensity steady-state aerobic exercise is associated with a reduced stroke volume which is probably related to a reduced venous return during arm work in comparison to other types of exercise.

Adult↗