Biomedical subjects

T Liu

Publications and source records attributed to T Liu.

At least 37 records · Page 2Linked to original sources

PubMed2004

A statistical model for functional mapping of quantitative trait loci regulating drug response.

Differential drug response, that is, pharmacodynamics, is most often likely to be a complex trait, controlled by the combined influences of multiple genes and environmental influences. Genetic mapping has proven to be a powerful tool for detecting and identifying specific genes affecting complex traits, that is, quantitative trait loci (QTL), based on polymorphic markers. In this article, we present a novel statistical model for genetic mapping of QTL governing pharmacodynamic processes. In principle, this model is a combination of functional mapping proposed to map function-valued traits and linkage disequilibrium mapping designed to provide high-resolution mapping of QTL by making use of recombination events created at a historic time. We implement a closed-form solution for the Expectation-Maximization algorithm to estimate the population genetic parameters of QTL and the simplex algorithm to estimate the curve parameters describing the pharmacodynamic changes of different QTL genotypes in response to drug dose or concentrations. Extensive simulations are performed to investigate the statistical properties of our model. The implications of our model in pharmacogenetic and pharmacogenomic research are discussed.

Algorithms↗

PubMed2004

Determinants of perioperative morbidity and mortality after pneumonectomy.

BACKGROUND: Pneumonectomy remains a relatively high-risk procedure. However, the underlying mechanism is still unknown. Thus, the effort to find out predisposing factors for surgical risks continues. We investigated the effect of both water-load control and sampling lymphadenectomy technique on perioperative morbidity and mortality after pneumonectomy. MATERIAL AND METHODS: A hundred and three consecutive patients undergoing simple pneumonectomy were included in the prospective study. Pneumonectomy was performed for lung cancer in 92 patients and for benign diseases in 11 cases; 81 patients were male and 22 female, and the mean age was 53.4 +/- 11.4 years. Both sampling and completion lymphadenectomy techniques were used randomly. Water-load was carefully limited to values as low as possible, depending on stable hemodynamics during and after operation. RESULTS: There were no deaths, and none of the patients needed postoperative mechanical ventilation. Major complications included dyspnea in 9 patients and supraventricular arrhythmias in 13 patients. Completion lymphadenectomy increased morbidity in both right and left pneumonectomy. CONCLUSIONS: Both water-load limitation and sampling lymphadenectomy technique may decrease morbidity and mortality after pneumonectomy.

Adult↗

PubMed2004

The status of structural genomics defined through the analysis of current targets and structures.

Structural genomics--large-scale macromolecular 3-dimenional structure determination--is unique in that major participants report scientific progress on a weekly basis. The target database (TargetDB) maintained by the Protein Data Bank (http://targetdb.pdb.org) reports this progress through the status of each protein sequence (target) under consideration by the major structural genomics centers worldwide. Hence, TargetDB provides a unique opportunity to analyze the potential impact that this major initiative provides to scientists interested in the sequence-structure-function-disease paradigm. Here we report such an analysis with a focus on: (i) temporal characteristics--how is the project doing and what can we expect in the future? (ii) target characteristics--what are the predicted functions of the proteins targeted by structural genomics and how biased is the target set when compared to the PDB and to predictions across complete genomes? (iii) structures solved--what are the characteristics of structures solved thus far and what do they contribute? The analysis required a more extensive database of structure predictions using different methods integrated with data from other sources. This database, associated tools and related data sources are available from http://spam.sdsc.edu.

Computational Biology↗

PubMed2004

Molecular characterization of Mycoplasma gallisepticum isolates from turkeys.

Mycoplasma gallisepticum was isolated from several turkey flocks at different locations in the United States that were clinically affected with respiratory disease. Five of these isolates from four series of outbreaks had patterns similar to the 6/85 vaccine strain of M. gallisepticum by random amplified polymorphic DNA (RAPD) analysis using three different primer sets, whereas with a fourth primer set (OPA13 and OPA14), only two of the isolates were similar to 6/85. Results obtained by sequencing portions of the pvpA, gapA, and mgc2 genes and an uncharacterized surface lipoprotein gene indicated that the field isolates had DNA sequences that ranged from 97.6% to 100%, similar to the 6/85 results. In some of the outbreaks there was an indirect association with the presence of commercial layers in the area that had been vaccinated with this vaccine strain, but there was no known close association with vaccinated birds in any of the outbreaks. Turkeys were challenged with two of the field isolates and with 6/85 vaccine strain. Turkeys challenged with the field isolates developed respiratory disease with airsacculitis and a typical M. gallisepticum antibody response, whereas birds challenged with 6/85 developed no respiratory signs or lesions and developed only a weak antibody response. Although these isolates were very similar to the 6/85 vaccine strain, it was not possible to prove that they originated from the vaccine strain-it is possible that they could be naturally occurring field isolates.

Adhesins, Bacterial↗

PubMed2003

Mapping the antigenicity of copper-treated cellular prion protein with the scrapie isoform.

When recombinant and cellular prion protein (PrP(C)) binds copper, it acquires properties resembling the scrapie isoform (PrP(Sc)), namely protease resistance, detergent insolubility and increased beta sheet content. However, whether the conformations of PrP(C) induced by copper and PrP(Sc) are similar has not been studied in great detail. Here, we use a panel of seven monoclonal antibodies to decipher the epitopes on full-length mouse PrP(C) that are affected by exogenous copper, and to compare the antigenicity of the copper-treated full-length PrP(C) with the full-length PrP(Sc) present in scrapie-infected mouse brains. In the presence of copper, we found that epitopes along residues 115-130 and 153-165 become more accessible on PrP(C). These regions correspond to the two beta sheet strands in recombinant PrP and they were proposed to be important for prion conversion. However, when we compared the antibody-binding patterns between full-length PrP(C) with full-length PrP(Sc) and between copper-treated full-length PrP(C) with full-length PrP(Sc), antibody binding to residues 143-155 and 175-185 was consistently increased on PrP(Sc). Collectively, our results suggest that copper-treated full-length PrP(C) does not resemble full-length PrP(Sc), despite acquiring PrP(Sc)-like properties. In addition, since each full-length protein reacts distinctively to some of the antibodies, this binding pattern could discriminate between PrP(C) and PrP(Sc).

Animals↗

PubMed2002

Measurement of B --> K*gamma branching fractions and charge asymmetries.

The branching fractions of the exclusive decays B0-->K(*0)gamma and B+-->K(*+)gamma are measured from a sample of (22.74+/-0.36)x10(6) BB decays collected with the BABAR detector at the PEP-II asymmetric e(+)e(-) collider. We find B (B0-->K(*0)gamma) = [4.23+/-0.40(stat)+/-0.22(syst)]x10(-5), B(B+-->K(*+)gamma) = [3.83+/-0.62(stat)+/-0.22(syst)]x10(-5) and constrain the CP-violating charge asymmetry to be -0.170 K(*)gamma)<0.082 at 90% C.L.

Journal Article↗

PubMed2002

Diversity of the apoptotic response to chemotherapy in childhood leukemia.

Apoptosis is the primary mechanism through which most chemotherapeutic agents induce tumor cell death. The purpose of this study was to determine the extent to which blasts from children with leukemia undergo a uniform apoptotic death pathway in vivo. The expression of pro- and anti-apoptotic proteins p53, p21, MDM-2, BCL-2, BCL-X(L), BCL-X(S), and BAX, and caspase-3 activity was determined in circulating blasts collected from the peripheral blood of children with leukemia prior to, and at serial time points following chemotherapy. Culturing blasts ex vivo for 12 h assessed spontaneous apoptosis and the increment induced by chemotherapy. Baseline apoptosis varied between 3% and 29%. Twenty-four hours following chemotherapy the increase in the percentage of cells undergoing apoptosis ranged from <1% to 38%. Eleven of 20 patients who received initial treatment with a p53-dependent drug showed an increase in p53 expression. In these patients, the levels of p53 target genes were also increased. A uniform pattern of BCL-2 family protein expression was not observed and only a minority of samples showed a change that would favor apoptosis. We conclude that that the initial apoptotic response to chemotherapy in children with leukemia is variable involving both p53-dependent and p53-independent pathways.

Adolescent↗

PubMed2002

Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection?

PURPOSE: The aim of this study was to determine the importance of pretreatment reexcision (PRE) of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) after initial unplanned resection. METHODS: The authors retrospectively reviewed the records of 116 consecutive patients with surgically resected NRSTS treated at their institution between February 1978 and September 1999. Ninety-four (81.0%) patients had undergone unplanned resections before referral to their institution for further therapy. Demographic data, tumor characteristics, treatment administered, and outcomes were recorded. RESULTS: Sixty-nine patients (73.4%) underwent PRE at a median interval after the initial unplanned resection of 29 days. Twenty-five patients were thought unsuitable for PRE because of the proximity to vital neurovascular bundles. Tumors deemed not feasible for PRE were more likely to be greater than 5 cm (P =.0094) and high grade (P =.0200). Tumor was found in 33 (47.8%) of the PRE specimens, and 24 of these patients (72.7%) were deemed disease free after achieving negative surgical margins. Residual tumor was more likely to be found after PRE in head and neck primary tumors than in trunk wall or extremity primary tumors (P =.0128). There were no local failures in the 60 PRE patients who achieved clear margins. The estimated 5-year event-free and 5-year overall survival rates in these 60 patients were 98.3% +/- 2.0% and 98.2% +/- 2.1%, respectively. CONCLUSIONS: Pretreatment reexcision should be performed whenever feasible in pediatric patients with NRSTS who had an initial unplanned resection. The proportion of patients with residual tumor in the PRE specimen is high, and negative microscopic margins can be achieved after PRE in most patients with residual tumor. Despite delay in obtaining a complete surgical resection, no local recurrences were seen. The possibility of NRSTS should be considered when resecting a soft tissue mass in children, and diagnostic incisional biopsy followed by wide local excision with negative microscopic margins should be the surgical goal.

Adolescent↗

PubMed2002

3D dosimetry study of 188Re liquid balloon for intravascular brachytherapy using bang polymer gel dosemeters.

It has been suggested that the combination of intravascular brachytherapy and coronary stent implantation may result in further reduction of restenosis after percutaneous balloon angioplasty. The use of an angioplasty balloon filled with a 188Re liquid beta source for intravascular brachytherapy provides the advantages of accurate source positioning and uniform dose distribution to the coronary vessel wall. The effect of source edge and stent on the dose distribution of the target tissue may be clinically important. In BANG gels, the absorbed radiation produces free-radical chain polymerisation of acrylic monomers that are initially dissolved in the gel. The number of polymer particles is proportional to the absorbed dose. In this study, 3D dose distributions are presented for 188Re balloons, with and without stents, using a prototype He-Ne laser CT scanner and the proprietary BANG polymer gel dosemeters.

Brachytherapy↗

PubMed2002

Antibody-based approach to high-volume genotyping for MIC-1 polymorphism.

Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the TGF-beta superfamily. There are at least two known alleles of MIC-1 that are due to a G-->C point substitution at position 6 of the mature protein, which alters a histidine to an aspartic acid (MIC-1 H and MIC-1 D). We have determined the phenotype of MIC-1 circulating in serum by exploiting the differences in the affinity of the two monoclonal antibodies to the H and D alleles of MIC-1. A PCR-RFLP-based method for genotyping MIC-1 is also described. We validate these two assays using DNA sequencing of 19 subjects as the standard. We then used the validated assay to determine the frequency of the two MIC-1 alleles in a population of 261 adult blood donors. Inter-assay and sequencing concordance was 100%. The frequency of the three common MIC-1 genotypes was homozygous (HH), 54%; heterozygous (HD), 39%; and homozygous (DD), 7%. This novel antibody-based assay confidently determines the genotype of MIC-1. It offers the advantages of an ELISA-ease of automation, high-volume throughput of samples, and ease of use in a routine, clinical laboratory.

Adolescent↗

PubMed2002

Ammonia inhibition on thermophilic aceticlastic methanogens.

The inhibition effects of total ammonia nitrogen (TAN) on aceticlastic methanogenic activity using biomass from thermophilic anaerobic reactors were investigated in this study. Anaerobic Toxicity Assays (ATA) were conducted after the biomass was acclimated to different levels of TAN. The TAN background concentrations in the reactors were 400, 1,200, and 3,050 mg/L. The results from ATA showed: 1) high TAN concentrations could cause inhibition of aceticlastic methanogens; 2) biomass acclimated to higher TAN concentrations could alleviate the inhibition effect due to the increase of TAN concentration; 3) the lethal TAN concentration for methanogens was approximately 10,000 mg/L regardless of the background TAN concentration; 4) ATA results also revealed the role played by pH. At a given TAN concentration, methanogenic activity varied with the pH values. The highest methanogenic activity was always observed at a pH of 7.0-7.5. 5) It was also observed that acclimation could increase the pH tolerance range, which made methanogens less sensitive to pH changes.

Adaptation, Physiological↗

PubMed2001

Capillary electrophoresis-electrospray mass spectrometry for the characterization of high-mannose-type N-glycosylation and differential oxidation in glycoproteins by charge reversal and protease/glycosidase digestion.

The characterization of high-mannose-type N-glycosylation by capillary electrophoresis-electrospray mass spectrometry (CE-ESI MS) was described. In addition to the use of a cationic noncovalent capillary coating, strong acidic buffer, and charge reversal to increase the glycoform resolving power, N-glycosidase F (PNGase F) combined with a basic protease and alpha-mannosidase combined with an acidic protease were used to analyze the high-mannose-type N-glycosylation in ribonuclease B (RNase B) and in a novel C-type lectin from the venom of Trimeresurus stejnegeri (TSL). The structures of oligosaccharide, glycosylation sites, and glycoform distributions were determined simultaneously, and the differential oxidation of Met residues in glycopeptides obtained from TSL protease digestion was also characterized successfully by CE-MS/MS. The results showed that the oligosaccharide attached to RNase B has a structure of GlcNAc2Man5 approximately 9, and that attached to TSL has a structure of GlcNAc2Min5 approximately 8. The glycoform distributions in these glycoproteins are quite different, with the GlcNAc2Man5 type predominant in RNase B, and the GlcNAc2Man8 type, in TSL This method may be useful not only for the characterization of glycosylation sites and glycan structures, but also for the determination of the relative abundance of individual glycoforms.

Alkylation↗

PubMed2001

FeMo cofactor of nitrogenase: a density functional study of states M(N), M(OX), M(R), and M(I).

The M(N) S = (3)/(2) resting state of the FeMo cofactor of nitrogenase has been proposed to have metal-ion valencies of either Mo(4+)6Fe(2+)Fe(3+) (derived from metal hyperfine interactions) or Mo(4+)4Fe(2+)3Fe(3+) (from Mössbauer isomer shifts). Spin-polarized broken-symmetry (BS) density functional theory (DFT) calculations have been undertaken to determine which oxidation level best represents the M(N) state and to provide a framework for understanding its energetics and spectroscopy. For the Mo(4+)6Fe(2+)Fe(3+) oxidation state, the spin coupling pattern for several spin state alignments compatible with S = (3)/(2) were generated and assessed by energy and geometric criteria. The most likely BS spin state is composed of a Mo3Fe cluster with spin S(a) = 2 antiferromagnetically coupled to a 4Fe' cluster with spin S(b) = (7)/(2). This state has a low DFT energy for the isolated FeMoco cluster and the lowest energy when the interaction with the protein and solvent environment is included. This spin state also displays calculated metal hyperfine and Mössbauer isomer shifts compatible with experiment, and optimized geometries that are in excellent agreement with the protein X-ray data. Our best model for the actual spin-coupled state within FeMoco alters this BS state by a slight canting of spins and is analogous in several respects to that found in the 8Fe P-cluster in the same protein. The spin-up and spin-down components of the LUMO contain atomic contributions from Mo(4+) and the homocitrate and from the central prismane Fe sites and muS(2) atoms, respectively. This qualitative picture of the accepting orbitals for M(N) is consistent with observations from Mössbauer spectra of the one-electron reduced states. Similar calculations for the Mo(4+)4Fe(2+)3Fe(3+) oxidation state yield results that are in poorer agreement with experiment. Using the Mo(4+)6Fe(2+)Fe(3+) oxidation level as the most plausible resting state, the geometric, electronic and energetic properties of the one-electron redox transition to the oxidized state, M(OX), catalytically observed M(R) and radiolytically reduced M(I) states have also been explored.

Binding Sites↗

PubMed2001

Search for the decay B0-->gammagamma.

We present a limit on the branching fraction for the decay B0-->gammagamma using data collected at the Upsilon(4S) resonance with the BABAR detector at the PEP-II asymmetric energy e+e- collider. Based on the observation of one event in the signal region, out of a sample of 21.3x10(6) e+e--->Upsilon(4S)-->BB decays, we establish an upper limit on the branching fraction of B(B0-->gammagamma)<1.7x10(-6) at the 90% confidence level. This result substantially improves upon existing limits.

Journal Article↗

PubMed2001

Measurement of the B--> J/psiK*(892) decay amplitudes.

We present a measurement of the decay amplitudes in B-->J/psiK*(892) channels using 20.7 fb(-1) of data collected at the Upsilon(4S) resonance with the BABAR detector at PEP-II. We measure a P-wave fraction R(perpendicular) = (16.0 +/- 3.2 +/- 1.4)% and a longitudinal polarization fraction (59.7 +/- 2.8 +/- 2.4)%. The measurement of a relative phase that is neither 0 nor pi, phi = 2.50 +/- 0.20 +/-0.08 radians, favors a departure from the factorization hypothesis. Although the decay B-->/psiK(pi) proceeds mainly via K*(892), there is also evidence for K2*(1430) and K(pi) S-wave contributions.

Journal Article↗

PubMed2001

Measurements of the branching fractions of exclusive charmless B meson decays with eta(') or omega mesons.

We present the results of searches for B decays to charmless two-body final states containing eta(') or omega mesons, based on 20.7 fb(-1) of data collected with the BABAR detector. We find the branching fractions Beta(B(+)-->eta(')K(+)) = (70+/-8+/-5) x 10(-6), Beta(B(0)-->eta(')K(0)) = (42(+13)(-11) +/- 4) x 10(-6), and Beta(B(+)-->omega pi(+)) = (6.6(+2.1)(-1.8) +/- 0.7) x 10(-6), where the first error quoted is statistical and the second is systematic. We give measurements of four additional modes for which the 90% confidence level upper limits are Beta(B(+)-->eta(')pi(+)) < 12 x 10(-6), Beta(B(+)-->omega K(+)) < 4 x 10(-6), Beta(B(0)-->omega K(0)) < 13 x 10(-6), and Beta(B(0)-->omega pi(0)) < 3 x 10(-6).

Journal Article↗

PubMed2001

Polymer-assisted formation of giant polyoxomolybdate structures.

A highly ordered, porous nanoscale network structure of polyoxomolybdate was prepared from the slow decomposition of an unstable precursor compound MoO(2)(OH)(OOH) in the presence of PEO-containing triblock copolymer gels or semidilute/concentrated poly(ethylene oxide) (PEO) homopolymer solutions. Small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) measurements of the 1-microm size crystals revealed an extremely ordered primitive cubic (pc) structure made of polyoxomolybdates. Scanning electron microscopy (SEM) measurements showed that the overall size of these single crystals was close to 1 microm, in agreement with estimates from the scattering peak widths. Evidence from both scattering measurements and transmission electron microscope (TEM) measurements suggested that the system formed a highly porous primitive cubic network similar to that of certain zeolite structures. However, the observed lattice constant of 5 nm was much larger. The function of the PEO-containing polymer network was found to be very subtle and complex. Presumably, PEO acted simultaneously as a weak reducing agent and as a viscous matrix to ensure sufficient time for the formation of long-range ordered structures, resulting in the growth of extremely uniform but probably hollow "nanospheres". We suggest that this new material may find unique applications as a high-efficiency absorbent or catalyst. Furthermore, the current synthetic method may open up new pathways to prepare similar functional nanomaterials.

Journal Article↗

PubMed2001

The role of hPMS1 and hPMS2 in predisposing to colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is attributable to a deficiency of mismatch repair. Inactivation of DNA mismatch repair underlies the genesis of microsatellite instability in colorectal cancer. Germline mutations in three DNA mismatch repair genes, hMSH2, hMLH1, and hMSH6, have been found to segregate in HNPCC and HNPCC-like families. The two DNA mismatch repair genes hPMS1 and hPMS2 have also been suggested to predispose to HNPCC. In this study, 84 HNPCC and HNPCC-like kindreds without known mutations in the other three known DNA mismatch repair genes were screened for germline mutations in the hPMS1 or hPMS2 gene. No clear-cut pathogenic mutations were identified. Conversion technology was used to detect a large hMSH2 deletion in two affected members of the kindred in which the hPMS1 mutation was originally reported, whereas the hPMS1 mutation was only present in one of these two individuals. Since the hPMS1 and hPMS2 genes were first reported, germline mutations in hPMS2 have been demonstrated primarily in patients with Turcot's syndrome. However, no mutation in any of the two genes has been found to segregate in HNPCC families. Until there is better evidence for an increased colorectal cancer risk associated with germline mutations in these genes, a conservative interpretation of the role of mutations in these genes is advised.

Adenosine Triphosphatases↗