Search PubMed⌕ Search

Biomedical subjects

D Xu

Publications and source records attributed to D Xu.

At least 235 records · Page 13Linked to original sources

A new set of chemotaxis homologues is essential for Myxococcus xanthus social motility.

Myxococcus xanthus cells aggregate and develop into multicellular fruiting bodies in response to starvation. A new M. xanthus locus, designated diffor defective in fruiting, was identified by the characterization of a mutant defective in fruiting body formation. Molecular cloning, DNA sequencing and sequence analysis indicate that the dif locus encodes a new set of chemotaxis homologues of the bacterial chemotaxis proteins MCPs (methyl-accepting chemotaxis proteins), CheW, CheY and CheA. The dif genes are distinct genetically and functionally from the previously identified M. xanthus frz chemotaxis genes, suggesting that multiple chemotaxis-like systems are required for the developmental process of M. xanthus fruiting body formation. Genetic analysis and phenotypical characterization indicate that the M. xanthus dif locus is required for social (S) motility. This is the first report of a M. xanthus chemotaxis-like signal transduction pathway that could regulate or co-ordinate the movement of M. xanthus cells to bring about S motility.

Amino Acid Sequence↗

An efficient computational method for globally optimal threading.

Computational recognition of native-like folds of an anonymous amino acid sequence from a protein fold database is considered to be a promising approach to the three-dimensional (3D) fold prediction of the amino acid sequence. We present a new method for protein fold recognition through optimally aligning an amino acid sequence and a protein fold template (protein threading). The fitness of aligning an amino acid sequence with a fold template is measured by (1) the singleton fitness, representing the compatibility of substituting one amino acid by another and the combined preference of secondary structure and solvent accessibility for a particular amino acid, (2) the pairwise interaction, representing the contact preference between a pair of amino acids, and (3) alignment gap penalties. Though a protein threading problem so defined is known to be NP-hard in the most general sense, our algorithm runs efficiently if we place a cutoff distance on the pairwise interactions, as many of the existing threading programs do. For an amino acid sequence of size n and a fold template of size m with M core secondary structures, the algorithm finds an optimal alignment in O (Mn1.5C + 1 + mnC + 1) time and O (MnC + 1) space, where C is a (small) nonnegative integer, determined by a particular mathematical property of the pairwise interactions. As a case study, we have demonstrated that C is less than or equal to 4 for about 75% of the 293 unique folds in our protein database, when pairwise interactions are restricted to amino acids < or = 7 A apart (measured between their beta carbon atoms). An approximation scheme is developed for fold templates with C > 4, when threading requires too much memory and time to be practical on a typical workstation.

Algorithms↗

Assessing hepatitis A virus epidemic stochastic process in eight cities in China in 1990.

BACKGROUND: In The People's Republic of China in 1990, the age-specific seroprevalence of hepatitis A was investigated in eight large cities. METHODS: A stochastic model, the two-state Markov chain, was applied to hepatitis A virus seroprevalence data by age group. An age-specific risk rate, Markov Risk Rate (MRR), and its weighted sum, Total MRR, are defined and used as novel measure indices to prioritize age groups for allocating vaccine or to decide in which cities vaccine should be used to prevent hepatitis A. RESULTS: In 1990, the MRR1- in Xi'an, Jinan, Ha'erbin and Huhehaote, and the MRR10- in Chongqing were over 40. The MRR10- in Xi'an, Nanjing, Jinan and Ha'erbin and the MRR20- in Chongqing and Nanjing were over 20. The Total MRR in Chongqing and Ha'erbin were over 160, which was higher than the warning value. CONCLUSIONS: All age groups whose MRR was over 20 are strongly recommended to be vaccinated first. Chongqing and Ha'erbin are cities at high risk of a hepatitis A virus epidemic in the 1990s and therefore should be under close surveillance.

Adolescent↗

The relationships among nitric oxide production, bacterial translocation, and intestinal injury after endotoxin challenge in vivo.

BACKGROUND: This study examines the hypothesis that there is a relationship among endotoxin-induced bacterial translocation (BT) and increased nitric oxide (NO) production and that inhibition of excessive NO production with NG-monomethyl-L-arginine (L-NMMA) is beneficial. METHODS: Rats received 0, 1, or 4 mg/kg endotoxin intraperitoneally, and 6 or 18 hours later, they were killed and BT, NO production (as reflected in nitrite/nitrate levels), and calcium-dependent nitric oxide synthase and calcium-independent nitric oxide synthase (iNOS) activities were measured in tissues (ileum, liver, and mesenteric lymph nodes) and blood. In a second set of experiments, the animals received the NOS inhibitor L-NMMA (100 mg/kg) intravenously either 15 minutes before or 2 hours after endotoxin challenge (4 mg/kg) and the same parameters were measured. RESULTS: The incidence of BT was higher in rats receiving 4 mg/kg endotoxin (62.5%) than in the control group (0%, p < 0.05), and the 1 mg/kg endotoxin group had intermediate incidence (25%). The animals receiving 4 mg/kg endotoxin had higher tissue (mesenteric lymph nodes, liver) and blood nitrite/nitrate levels than the control or 1 mg/kg endotoxin groups. The increased NO production was mainly attributable to an elevated level of iNOS activity. The administration of L-NMMA before but not after endotoxin challenge reduced iNOS activity, NO production, and BT to control levels at 6 hours but not 18 hours after endotoxin administration. CONCLUSION: Endotoxin-induced mucosal injury and BT are associated with iNOS activity and increased NO production. Inhibition of iNOS activity with L-NMMA before treatment prevented endotoxin-induced ileal mucosal injury and BT.

Animals↗

Post-hemorrhagic shock mesenteric lymph is cytotoxic to endothelial cells and activates neutrophils.

The goal of these experiments was to test the hypothesis that after a nonlethal episode of hemorrhagic shock, factors carried in the mesenteric lymph would promote endothelial cell injury and activate neutrophils to a greater extent than portal vein plasma. Catheters were placed in the efferent lymphatic duct draining the mesenteric lymph node complex, after which male rats were subjected to sham or actual shock (30 mmHg for 90 min), and lymph was collected. Portal vein plasma was collected from the sham-shock and shocked rats at 6 h post-shock or sham-shock. When the effect of lymph or portal blood plasma was tested on endothelial cell (HUVEC) monolayer permeability, it was found that post-shock lymph, but not post-shock portal vein plasma, increased HUVEC permeability to both 10 kDa and 40 kDa permeability probes. Subsequent experiments documented that only post-shock lymph was cytotoxic to endothelial cells as manifest both by decreased trypan blue dye exclusion and the increased release of Chromium-51 from chromium-loaded endothelial cells. Furthermore post-shock lymph induced a greater increase in neutrophil superoxide formation than pre-shock lymph, pre-shock, or post-shock portal vein plasma. Lastly, neutrophil-mediated endothelial cell injury was potentiated by the presence of post-shock lymph, and the magnitude of HUVEC injury was greater in endothelial cells incubated with post-shock lymph plus neutrophils than in monolayers incubated with post-shock lymph or neutrophils alone. These results suggest that post-shock lymph is cytotoxic to endothelial cells and activates neutrophils. Since the lung is the first organ that is exposed to mesenteric lymph, lung injury after hemorrhagic shock may be mediated by factors contained in mesenteric lymph.

Animals↗

Myxococcus xanthus sasN encodes a regulator that prevents developmental gene expression during growth.

Myxococcus xanthus multicellular fruiting body development is initiated by nutrient limitation at high cell density. Five clustered point mutations (sasB5, -14, -15, -16, and -17) can bypass the starvation and high-cell-density requirements for expression of the 4521 developmental reporter gene. These mutants express 4521 at high levels during growth and development in an asgB background, which is defective in generation of the cell density signal, A signal. A 1.3-kb region of the sasB locus cloned from the wild-type chromosome restored the SasB+ phenotype to the five mutants. DNA sequence analysis of the 1.3-kb region predicted an open reading frame, designated SasN. The N terminus of SasN appears to contain a strongly hydrophobic region and a leucine zipper motif. SasN showed no significant sequence similarities to known proteins. A strain containing a newly constructed sasN-null mutation and Omega4521 Tn5lac in an otherwise wild-type background expressed 4521 at a high level during growth and development. A similar sasN-null mutant formed abnormal fruiting bodies and sporulated at about 10% the level of wild type. These data indicate that the wild-type sasN gene product is necessary for normal M. xanthus fruiting body development and functions as a critical regulator that prevents 4521 expression during growth.

Alleles↗

Synthetic lethality of yeast slt mutations with U2 small nuclear RNA mutations suggests functional interactions between U2 and U5 snRNPs that are important for both steps of pre-mRNA splicing.

A genetic screen was devised to identify Saccharomyces cerevisiae splicing factors that are important for the function of the 5' end of U2 snRNA. Six slt (stands for synthetic lethality with U2) mutants were isolated on the basis of synthetic lethality with a U2 snRNA mutation that perturbs the U2-U6 snRNA helix II interaction. SLT11 encodes a new splicing factor and SLT22 encodes a new RNA-dependent ATPase RNA helicase (D. Xu, S. Nouraini, D. Field, S. J. Tang, and J. D. Friesen, Nature 381:709-713, 1996). The remaining four slt mutations are new alleles of previously identified splicing genes: slt15, previously identified as prp17 (slt15/prp17-100), slt16/smd3-1, slt17/slu7-100, and slt21/prp8-21. slt11-1 and slt22-1 are synthetically lethal with mutations in the 3' end of U6 snRNA, a region that affects U2-U6 snRNA helix II; however, slt17/slu7-100 and slt21/prp8-21 are not. This difference suggests that the latter two factors are unlikely to be involved in interactions with U2-U6 snRNA helix II but rather are specific to interactions with U2 snRNA. Pairwise synthetic lethality was observed among slt11-1 (which affects the first step of splicing) and several second-step factors, including slt15/prp17-100, slt17/slu7-100, and prp16-1. Mutations in loop 1 of U5 snRNA, a region that is implicated in the alignment of the two exons, are synthetically lethal with slu4/prp17-2 and slu7-1 (D. Frank, B. Patterson, and C. Guthrie, Mol. Cell. Biol. 12:5179-5205, 1992), as well as with slt11-1, slt15/prp17-100, slt17/slu7-100, and slt21/prp8-21. These same U5 snRNA mutations also interact genetically with certain U2 snRNA mutations that lie in the helix I and helix II regions of the U2-U6 snRNA structure. Our results suggest interactions among U2 snRNA, U5 snRNA, and Slt protein factors that may be responsible for coupling and coordination of the two reactions of pre-mRNA splicing.

Base Sequence↗

Carbon monoxide inhibition of regulatory pathways in myocardium.

The 1H nuclear magnetic resonance (NMR) myoglobin (Mb) Val E11 signal provides a unique opportunity to assess the functional role of Mb in the cell. On CO infusion in perfused myocardium, the MbO2 signal at -2.76 parts per million (ppm) gradually disappears, whereas the corresponding MbCO signal emerges at -2.26 ppm, reflecting the state of Mb inhibition. Up to 76.8% MbCO saturation, myocardial O2 consumption (MVO2) remains constant, whereas the rate-pressure product (RPP) has already dropped to 92% of the control level. At 87.6% MbCO saturation, the lactate formation rate has increased by a factor of two, and MVO2 begins to decline. However, the ratio CO/O2 is still 1/10, well below the inhibition threshold for cytochrome oxidase activity. The MVO2 decline in the face of an adequate O2 supply and an unperturbed high-energy phosphate level implies that Mb may play a role in directly regulating respiration, mediated potentially by a shift in NADH/NAD. Although nitrite inhibits Mb, nitrite also directly affects the myocardial function.

Adenosine Triphosphate↗

Ultrarapid delayed rectifier current inactivation in human atrial myocytes: properties and consequences.

The ultrarapid delayed rectifier current (IK,ur) plays a significant role in human atrial repolarization and is generally believed to show little rate dependence because of slow and partial inactivation. This study was designed to evaluate in detail the properties and consequences of IK,ur inactivation in isolated human atrial myocytes. IK,ur inactivated with a biexponential time course and a half-inactivation voltage of -7.5 +/- 0.6 mV (mean +/- SE), with complete inactivation during 50-s pulses to voltages positive to +10 mV (37 degreesC). Recovery from inactivation proceeded slowly, with time constants of 0.42 +/- 0.06 and 7.9 +/- 0.9 s at -80 mV (37 degreesC). Substantial frequency dependence was observed at 37 degreesC over a clinically relevant range of frequencies. Inactivation was faster and occurred at more positive voltages at 37 degreesC compared with room temperature. The voltage and time dependencies of Kv1.5 inactivation were studied in Xenopus oocytes to avoid overlapping currents and strongly resembled those of IK,ur in native myocytes. We conclude that, while IK,ur inactivation is slow, it is extensive, and slow recovery from inactivation confers important frequency dependence with significant consequences for understanding the role of IK,ur in human atrial repolarization.

Action Potentials↗

[A molecular epidemiologic study on the mechanism of intrauterine transmission of hepatitis B virus].

A case-control study with examination of placentas using immunohistochemistry stain was reported in this paper. In the Maternal and Children Health Hospital of Shanxi Province, 242 consecutive HBsAg positive mothers and their babies were selected as subjects and 110 placentas of HBsAg positive mothers and 25 placentas of HBsAg negative mothers during the different period of pregnancy were collected for laboratory test. The results showed that maternal HBeAg positivity (OR = 32.63) and history of threatened premature labor (OR = 22.80) were important risk factors. Among full-term placentas with HBsAg positivity, HBsAg (biomarker of HBV infection) positive rates were 100% in decidual cell, 59.38% in trophoblastic cell, 65.50% in villous mesenchyme cell, and 39.38% in villous capillary endothelial cell (VCEC) with a decreasing trend (trend test, chi 2 = 30.5, P < 0.01) from mothers to fetus whereas HBsAg positive in VCEC was significantly related to intrauterine infection (OR = 20.86, P < 0.01). Results suggested that there might be two transmission routes on the mechanism of HBV intrauterine transmission, hemogenous by damage of placental vessels and cellular through placental cellular transfer of HBV.

Adult↗

Treatment of atrophic cholecystitis by regulating the function of the spleen--a report of 50 cases.

Fifty cases of atrophic cholecystitis were treated mainly by regulation of the function of the spleen. Of them, 21 cases were cured, 18 markedly effective, and 7 effective. The total effective rate was 92.0%. By comparison of results of ultrasonography B performed before and after treatment, it was shown that both the longitudinal and transverse inner diameters of gallbladder cross section increased evidently, and the condition of atrophy was improved remarkably after treatment.

Adolescent↗

[Development of emission models for volatile organic compounds from indoor materials].

Volatile organic compounds (VOCs) emitted from indoor materials was a major cause of indoor air pollution. The characteristics of VOCs emission was an important part of research programs on indoor air quality. The technology of test chambers with exactly controllable conditions has been successfully used in studies of VOCs emissions. The technology could be used to model the chamber VOCs concentration level vs time profile C(t), which could in turn be used to estimate the sample emission rate vs time profile R(t). The emission models of VOCs from indoor materials were presented in this review. The principal of emission process, parameters and the applications of emission models were introduced. The application of diffusion model, dilution model and vapor pressure (VP) model were limited due to the existence of sink effect. Sink model is the most promising model at present.

Air Pollution, Indoor↗

[Renal aquaporin-2 water channel expression in congestive heart failure rat].

OBJECTIVE: To study aquaporin-2 (AQP2) that mediates vasopressin-regulated collecting duct water permeability. METHODS: Male Sprague-Dawley rats (200-250 g) underwent either a left coronary artery ligation, a model of CHF, or a shamoperation (Sham-Op). Five weeks after surgery, mean blood pressure (MBP) and cardiac output (CO) were measured by catheterization in the conscious animal. The rats were sacrificed 24 hours later. Left ventricular myocardial infarction size (LVMI) was estimated and the rats were divided into two groups according to the size of infarction. Total RNA and protein were extracted from whole kidney. AQP2 and GAPDH mRNA were measured by Northern blot and AQP2 protein expression by Western blot. RESULTS: AQP2/GAPDH mRNA densities of Sham-Op, LVMI < 20% rats and LVMI > or = 20% rats were 1.385 +/- 0.023, 1.523 +/- 0.036, and 1.779 +/- 0.072 (P < 0.01). AQP2 protein Western blot densities were 100% +/- 10%, 157% +/- 13% and 202% +/- 25% (P < 0.01). CONCLUSION: Both mRNA and protein of AQP2 gene expression are increased in CHF rat and this upregulation is present in the compensated (LVMI < 20% rats) and decompensated (LVMI > or = 20% rats) stage of CHF. This contributes to water retention associated with CHF.

Animals↗

[Cloning and expressing of HCV NS5 partial gene and dynamic changes of anti-NS5].

OBJECTIVE: To study antigenicity of HCV NS5 protein and dynamic changes of anti-NS5 in post-transfusion hepatitis C (PT-HC). METHODS: Epitopes of HCV NS5 protein were analyzed by Goldkey Program. NS5 gene fragment was amplified by reverse transcription and polymerize chain reaction (RT-PCR) from sera of PT-HC patients. Sequence analysis was performed, and recombinant strain was constructed. Series sera from PT-HC were detected for anti-NS5, ALT and HCV RNA. RESULTS: The homology of nucleotide and amino acid with genotype II in the same region was 91.8% and 92.4%, respectively. SDS-PAGE analysis showed an expressing band around 50 kD, the fusion protein represented about 21.4% of total bacterial protein. Western blot result proved the expressing band could specifically react with sera from hepatitis C patients. Detection results of series blood samples from PT-HC showed that the antibody against NS5 appeared relatively late, the positive conversion time was 182.9 +/- 168.5 day. Dynamic changes of anti-NS5 were correlated with serum ALT in most cases. The types of dynamic change of anti-NS5 were passing positive; intermittent positive; persistent positive, and persistent negative in two years. CONCLUSION: Antibody against NS5 may reflect the disease activity to some extent. It appears relatively late, and is of no value in early stage diagnosis.

Cloning, Molecular↗

Long-term efficacy of recombinant interferon alpha 2a in the treatment of chronic hepatitis C: a randomized prospective study comparing two dose schedules in Chinese patients.

OBJECTIVE: To compare the long-term efficacy of a dose of 3 million units (MU) of r-IFN alpha 2a (IFN-alpha 2a) three times a week (t.i.w.) for 6 months with a starting dose 6 MU for 3 months and subsequent reduction to 3 MU t.i.w for further 3 months. METHODS: Sixty-eight serological and histological chronic hepatitis C patients with elevated serum alanine aminotransferase (ALT) were enrolled and randomized into two groups. Sixty-three patients were completed with full course of treatment. Five patients were withdrawn from trial (2 due to personal reasons and 3 due to adverse drug reactions during treatment). Thirty patients received 6 MU IFN-alpha 2a t.i.w., 3 months followed by 3 MU t.i.w. for another 3 months (Group A). Thirty-three patients received 3 MU IFN-alpha 2a t.i.w. for 6 months (Group B). RESULTS: The sex, age, baseline serum bilirubin, ALT and aspartate aminotransferase (AST) levels were matched in both groups. At the end of the 6th month, the complete and partial response rates in Group A were 60.0% and 16.7% respectively, and the clearance of serum HCV-RNA was 53.3%. In Group B, the complete and partial response rates were 72.7% and 6.1% respectively, and the clearance of HCV-RNA was 61.3%. The patients were followed up for 6, 12, and 18 months after stopping treatment. In Group A, the rates of complete normalization of ALT and clearance of serum HCV-RNA at 24 months were 50.0% and 60.0% respectively. In Group B, the rates of normalization of ALT and clearance of HCV-RNA at 24 months were 54.4% and 41.9% respectively. The efficacy between the two groups showed no statistically significant difference. The response rates of treatment were similar to those in the patients with HCV genotype 1b and 2a. Six patients (10.8% of the study population) developed neutralization antibodies to IFN-alpha 2a during treatment, and four of them were responded to the treatment. Adverse drug reactions (ADR), were common, but most of them were tolerable, and the incidence of ADR was in both groups, but the severity was higher in Group A. CONCLUSIONS: IFN-alpha 2a is effective in the treatment of Chinese patients with chronic hepatitis C. The sustained response rates and adverse drug reactions among two dose schedule groups are similar.

Adolescent↗

[Determination of uric acid, creatinine and pseudouridine in human urine by high performance capillary zone electrophoresis].

A simultaneous determination of uric acid, creatinine and pseudouridine in human urine by high performance capillary zone electrophoresis(HPCZE) is described. The urine samples were refrigerated and filtered. Then the samples were directly introduced into the capillary and a phosphate buffer solution(pH 6.1) was employed. The capillary used was 36 cm x 50 microns i.d. and detection was carried out with a UV monitor at 210 nm. The calibration curve showed a good linearity for uric acid, creatinine, and pseudouridine in the concentration range of 2-80 mg/L and their correlation coefficients were 0.996, 0.996 and 0.999 respectively. Within day CV for assaying the urine samples of uric acid, creatinine and pseudouridine were 5.0%, 3.0%, and 4.4%, and the corresponding between day data were 6.5%, 5.9%, and 5.3%, respectively. The recoveries of uric acid, creatinine and pseudouridine were 99.0%, 102.%, 92.2%, respectively. The total time for separation and determination was within 10 min. This method is characterized by direct assay of urine samples without any pretreatment. The results show that HPCZE is a simple, rapid, sensitive and reliable assay method.

Creatinine↗

[Preliminary studies on chemical constituents and pharmacological action of Eclipta prostrata L].

OBJECTIVE: To study the pharmacologically active components of Eclipta prostrata. METHOD: The components were extracted by alcohol and isolated by silica gel column and subjected to pharmacological screening. RESULT: Four compounds were isolated from E. prostrata, of which two were identified as stigmasterol and alpha-terthienyl. CONCLUSION: alpha-Terthienyl was isolated from the plant for the first time. The EtOAc part of alcoholic extraction exhibits significant hepatoprotective activity against carbon terachloride-induced liver injury in rats.

Alanine Transaminase↗

[Synthesis and antiinflammatory activity of 2-(E)-(4-hydroxy-3-methoxybenzylidene)-5-(N-substituted aminomethyl) cyclopentanones].

In search for new antiinflammatory agents, a series of 2-(E)-(4-hydroxy-3-methoxybenzylidene)-5-(N-substituted aminomethyl) cyclopentanones was synthesized via Stork reaction, Mannich reaction and amine exchange reaction. All of the fifteen target compounds were characterized by spectral analysis and elemental analysis. Preliminary pharmacological tests showed that several target compounds exerted appreciable effect on xylene-induced ear edema in mice and that alteration of the substituents of anilines showed significant influence on antiinflammatory potency.

Animals↗