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Biomedical subjects

Lu Tian

Publications and source records attributed to Lu Tian.

At least 19 recordsLinked to original sources
PubMed2006

Syntheses and structures of [M{In(SC{O}Ph)4}2] (M = Mg and Ca): single molecular precursors to MIn2S4 materials.

The compounds [Mg{In(SC{O}Ph)4}2] (1) and [Ca(H2O)x{In(SC{O}Ph)4}2].yH2O (x = 0, y = 1, 2 major product; x = 1, y = 0, 2a minor product; x = 2, y = 2, 2b minor product) have been synthesized by reacting InCl3 and M(SC{O}Ph)2 (M = Mg and Ca) prepared in situ in the molar ratio 1:2. The structures of 1, 2a, and 2b have been determined by X-ray crystallography. The structure of 1 consists of two tetrahedral [In(SC{O}Ph)4]- anions sandwiching the Mg(II) metal ions through six carbonyl O atoms. The coordination geometry at the Mg(II) metal atom is distorted octahedral with an O(6) donor set. The structures of 2a and 2b consist of two [In(SC{O}Ph)4]- anions sandwiching the Ca(II) metal ion through five and four carbonyl O atoms, and the octahedral coordination at the Ca(II) centers is completed by one and two aqua ligands, respectively. Two aqua ligands and two lattice water molecules form a H-bonded water chain in the channel created by [Ca{In(SC{O}Ph)4}2] molecules in the crystal structure of 2b. The thermal decomposition of 1 and 2 indicated the formation of the corresponding MIn2S4 materials, and this was confirmed by X-ray powder diffraction patterns.

Journal Article↗
PubMed2006

Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease.

Some experts propose C-reactive protein (CRP) as a screening tool for prediction of cardiovascular disease (CVD). Many epidemiologic studies show positive associations between elevated CRP levels and incident CVD. Assessment of the value of new prognostic tests, however, must rely on understanding of test characteristics rather than on associations measured by relative risks. In the case of CRP, test characteristics must be judged in the context of currently available CVD risk prediction algorithms. In this review of literature published before January 2006, the authors describe what is known about the additional utility of CRP in risk prediction. They find no definitive evidence that, for most individuals, CRP adds substantial predictive value above that provided by risk estimation using traditional risk factors for CVD. Use of CRP may add to risk estimation in a limited subset of individuals who are at intermediate predicted risk according to the Framingham risk score. The authors propose that many questions still must be addressed before CRP is incorporated into risk prediction algorithms and before universal screening with CRP can be recommended.

Algorithms↗
PubMed2006

Physical activity during daily life and mortality in patients with peripheral arterial disease.

BACKGROUND: We determined whether patients with lower-extremity peripheral arterial disease (PAD) who are more physically active during daily life have lower mortality rates than PAD patients who are less active. METHODS AND RESULTS: Participants were 460 men and women with PAD (mean age 71.9+/-8.4 years) followed up for 57 months (interquartile range 36.6 to 61.9 months). At baseline, participants were interviewed about their physical activity. Vertical accelerometers measured physical activity continuously over 7 days in 225 participants. Analyses were adjusted for age, sex, race, body mass index, hypertension, smoking, comorbidities, total cholesterol, HDL cholesterol, leg symptoms, and ankle-brachial index. At 57-month follow-up, 134 participants (29%) had died, including 75 participants (33%) who wore accelerometers. Higher baseline physical activity levels measured by vertical accelerometer were associated with lower all-cause mortality (P(trend)=0.003). Relative to PAD participants in the highest quartile of accelerometer-measured physical activity, those in the lowest quartile had higher total mortality (hazard ratio 3.48, 95% confidence interval 1.23 to 9.87, P=0.019). Similar results were observed for the combined outcome of cardiovascular events or cardiovascular mortality (P(trend)=0.005). Higher numbers of stair flights climbed during 1 week were associated with lower total mortality (P(trend)=0.035). CONCLUSIONS: PAD patients with higher physical activity during daily life have reduced mortality and cardiovascular events compared with PAD patients with the lowest physical activity, independent of confounders. Further study is needed to determine whether interventions that increase physical activity during daily life are associated with improved survival in patients with PAD.

Activities of Daily Living↗
PubMed2006

Nonadditive regulation of FRI and FLC loci mediates flowering-time variation in Arabidopsis allopolyploids.

Allopolyploidy is formed by combining two or more divergent genomes and occurs throughout the evolutionary history of many plants and some animals. Transcriptome analysis indicates that many genes in various biological pathways, including flowering time, are expressed nonadditively (different from the midparent value). However, the mechanisms for nonadditive gene regulation in a biological pathway are unknown. Natural variation of flowering time is largely controlled by two epistatically acting loci, namely FRIGIDA (FRI) and FLOWERING LOCUS C (FLC). FRI upregulates FLC expression that represses flowering in Arabidopsis. Synthetic Arabidopsis allotetraploids contain two sets of FLC and FRI genes originating from Arabidopsis thaliana and A. arenosa, respectively, and flower late. Inhibition of early flowering is caused by upregulation of A. thaliana FLC (AtFLC) that is trans-activated by A. arenosa FRI (AaFRI). Two duplicate FLCs (AaFLC1 and AaFLC2) originating from A. arenosa are expressed in some allotetraploids but silenced in other lines. The expression variation in the allotetraploids is associated with deletions in the promoter regions and first introns of A. arenosa FLCs. The strong AtFLC and AaFLC loci are maintained in natural Arabidopsis allotetraploids, leading to extremely late flowering. Furthermore, FLC expression correlates positively with histone H3-Lys4 methylation and H3-Lys9 acetylation and negatively with H3-Lys9 methylation, epigenetic marks for gene activation and silencing. We provide evidence for interactive roles of regulatory sequence changes, chromatin modification, and trans-acting effects in natural selection of orthologous FLC loci, which determines the fate of duplicate genes and adaptation of allopolyploids during evolution.

Acetylation↗
PubMed2006

Statin use and functional decline in patients with and without peripheral arterial disease.

OBJECTIVES: We determined whether statin use (vs. non-use) is associated with less annual decline in lower-extremity functioning in patients with and without lower-extremity peripheral arterial disease (PAD) over three-year follow-up. BACKGROUND: It is unclear whether statin use is associated with less functional decline in patients with PAD. METHODS: Participants included 332 men and women with an ankle brachial index (ABI) <0.90 and 212 with ABI 0.90 to 1.50. Functional outcomes included 6-min walk distance and usual and rapid-pace 4-m walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for five repeated chair rises into an ordinal score ranging from 0 to 12 (12 = best). RESULTS: Adjusting for age, race, gender, comorbidities, education, health insurance, total cholesterol/high-density lipoprotein level, body mass index, pack-years of smoking, leg symptoms, immediately previous year functioning, statin use/non-use, ABI, and change in ABI, the PAD participants using statins had less annual decline in usual-pace walking velocity (0.002 vs. -0.024 m/s/year, p = 0.013), rapid-pace walking velocity (-0.006 vs. -0.042 m/s/year, p = 0.006), 6-min walk performance (-34.5 vs. -57.9 feet/year, p = 0.088), and the summary performance score (-0.152 vs. -0.376, p = 0.067) compared with non-users. These associations were attenuated slightly by additional adjustment for high-sensitivity C-reactive protein levels. Among non-PAD participants, there were no significant associations between statin use and functional decline. CONCLUSIONS: The PAD patients on statins have less annual decline in lower-extremity performance than PAD patients who are not taking statins.

Aged↗
PubMed2006

Physical performance in peripheral arterial disease: a slower rate of decline in patients who walk more.

BACKGROUND: Exercise rehabilitation programs increase treadmill walking performance in patients with peripheral arterial disease (PAD) and intermittent claudication. However, it is unknown whether patients with PAD who walk for exercise regularly have less functional decline than those with less walking activity. OBJECTIVE: To determine whether patients with PAD who report that they walk for exercise 3 or more times per week have less annual functional decline than those who walk for exercise less frequently. DESIGN: Prospective cohort study with a median follow-up of 36 months (interquartile range, 24 to 36 months). SETTING: Academic medical center. PARTICIPANTS: 417 men and women with PAD. MEASUREMENTS: Participants were classified at baseline and annually according to the number of times they reportedly walked for exercise each week. Functional assessments (6-minute walk distance, 4-meter walking speed, summary performance score) were measured at baseline and annually. Results were adjusted for age, sex, ethnicity, comorbid conditions, body mass index, ankle-brachial index, education, leg symptoms, cigarette use, geriatric depression score, previous year's level of functioning, and patterns of missing data. RESULTS: Compared with those who exercised less frequently, patients who walked for exercise 3 or more times per week had a significantly smaller average annual decline in 6-minute walking distance (-48.0 feet per year compared with -56.6 feet per year for those who walked 1 to 2 times per week and -79.4 feet per year for nonexercisers; P for trend = 0.037). Patients who walked for exercise at least 3 times per week experienced a smaller average annual decline in the usual-paced 4-meter walking velocity (-0.014 m/s per year compared with -0.022 m/s per year for those who walked 1 to 2 times per week and -0.045 m/s per year for nonexercisers; P = 0.005). Similar findings were observed for the fast-paced 4-meter walk. The subset of asymptomatic patients who walked for exercise 3 or more times per week had annual declines in 6-minute walking performance (P = 0.107), normal-paced walking velocity (P = 0.065), and the summary performance score (P = 0.115); however, these declines were smaller than those observed in asymptomatic participants who walked fewer than 3 times per week. LIMITATIONS: Because this was an observational study, associations reported here cannot be construed as causal relationships. Sample sizes for subgroup analyses were small, which limited statistical power. CONCLUSION: Among patients with PAD, self-directed walking exercise performed at least 3 times weekly is associated with significantly less functional decline during the subsequent year. Similar trends were observed in the subset of asymptomatic patients with PAD. These findings may be particularly important for the numerous patients with PAD who do not have access to supervised walking exercise programs.

Disability Evaluation↗
PubMed2006

Obesity, weight change, and functional decline in peripheral arterial disease.

BACKGROUND: Our objectives were to determine whether obesity is associated with a greater functional decline compared with the ideal body mass index (BMI) among persons with peripheral arterial disease (PAD) and to determine the associations between weight gain and loss and functional declines in PAD. We hypothesized that baseline obesity and weight gain during follow-up would each be associated with functional declines in persons with PAD. METHODS: The design was a prospective cohort study. The subjects were 389 men and women with PAD (mean ankle-brachial index, 0.65 +/- 0.14) who were followed up prospectively for a median of 48 months. The main outcome measures were functional assessments (6-minute walk, usual- and rapid-paced 4-m walking speed, and summary performance score). Weight and height were measured at baseline and annually. Results were adjusted for age, sex, race, comorbidities, ankle-brachial index, education, leg symptoms, exercise status, depressive symptoms, pack-years of cigarette smoking, prior-year functioning, and patterns of missing data. RESULTS: Compared with those with a baseline BMI between 20 and 25 kg/m2, PAD participants with baseline BMI greater than 30 kg/m2 had a significantly greater average annual decline in 6-minute walk performance (-13.1 vs -26.5 m/y; P = .004), usual-paced 4-m walking velocity (-0.028 vs -0.055 m/s per year; P = .024), and fast-paced 4-m walking velocity (-0.053 vs -0.086 m/s per year; P = .012). Persons with weight gain between 5 and 10 pounds after baseline who walked for exercise regularly had significantly less decline in the 6-minute walk than persons without significant weight change who did not walk for exercise (P = .04). CONCLUSIONS: Obesity is associated with functional decline in persons with PAD. Walking exercise may protect against functional decline in PAD persons with modest weight gain.

Aged↗
PubMed2006

Arabidopsis thaliana histone deacetylase 1 (AtHD1) is localized in euchromatic regions and demonstrates histone deacetylase activity in vitro.

Arabidopsis thaliana histone deacetylase 1 (AtHD1 or AtHDA19), a homolog of yeast RPD3, is a global regulator of many physiological and developmental processes in plants. In spite of the genetic evidence for a role of AtHD1 in plant gene regulation and development, the biochemical and cellular properties of AtHD1 are poorly understood. Here we report cellular localization patterns of AtHD1 in vivo and histone deacetylase activity in vitro. The transient and stable expression of a green fluorescent protein (GFP)-tagged AtHD1 in onion cells and in roots, seeds and leaves of the transgenic Arabidopsis, respectively, revealed that AtHD1 is localized in the nucleus presumably in the euchromatic regions and excluded from the nucleolus. The localization patterns of AtHD1 are different from those of AtHD2 and AtHDA6 that are involved in nucleolus formation and silencing of transgenes and repeated DNA elements, respectively. In addition, a histone deacetylase activity assay showed that the recombinant AtHD1 produced in bacteria demonstrated a specific histone deacetylase activity in vitro. The data suggest that AtHD1 is a nuclear protein and possesses histone deacetylase activities responsible for global transcriptional regulation important to plant growth and development.

Acetylation↗
PubMed2006

Functional decline in patients with and without peripheral arterial disease: predictive value of annual changes in levels of C-reactive protein and D-dimer.

BACKGROUND: Inflammation may be a potential mechanism of aging-related functional decline. We determined whether greater annual increases in levels of high sensitivity C-reactive protein (hsCRP) and D-dimer predicted greater decline in functioning among persons with and without lower extremity peripheral arterial disease (PAD). METHODS: We prospectively studied 296 men and women with PAD and 191 without PAD. Objective measures of functioning, hsCRP, and D-dimer were obtained at baseline and annually for 3 years (mean follow-up = 36.3 +/- 6.4 months). RESULTS: Among PAD participants, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk performance (-2.63 ft/mg/L, p =.039) but not in other functional outcomes. Higher prior year absolute hsCRP levels were associated with greater declines in 6-minute walk (-2.93 ft/mg/L, p =.022), summary performance score (-0.038/mg/L, p =.017), and rapid paced 4-meter walk (-0.29 cm/s/mg/L, p =.026) during the subsequent year. Among participants without PAD, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk (-7.47 ft/mg/L, p =.002), usual-pace 4-meter walk (-0.33 cm/s/mg/L, p <.001), fast paced 4-meter walk (-0.56 cm/s/mg/L, p =.003), and the summary performance score (-0.029 mg/L, p <.001). There were no consistent associations between D-dimer levels and functional decline. CONCLUSION: These findings suggest that inflammation may play a role in functional decline in persons with and without PAD.

Aged↗
PubMed2006

Analysis of a partially observed binary covariate process and a censored failure time in the presence of truncation and competing risks.

We develop methods for assessing the association between a binary time-dependent covariate process and a failure time endpoint when the former is observed only at a single time point and the latter is right censored, and when the observations are subject to truncation and competing causes of failure. Using a proportional hazards model for the effect of the covariate process on the failure time of interest, we develop an approach utilizing EM algorithm and profile likelihood for estimating the relative risk parameter and cause-specific hazards for failure. The methods are extended to account for other covariates that can influence the time-dependent covariate process and cause-specific risks of failure. We illustrate the methods with data from a recent study on the association between loss of hepatitis B e antigen and the development of hepatocellular carcinoma in a population of chronic carriers of hepatitis B.

Algorithms↗
PubMed2006

Development of an emergency department work score to predict ambulance diversion.

OBJECTIVES: The authors sought to develop and validate an emergency department (ED) work score that could be used in real time to quantify crowding and staff workload in an ED. This work score could be used by public health officials to direct ambulance traffic based on an objective measure of ED status and to track ED conditions over time. In addition, the authors sought to determine which portion of ED care was most responsible for crowding. METHODS: The setting was a tertiary teaching hospital with an emergency medicine residency. A number of ED parameters were measured throughout 2003 and then matched to times that an ED was on diversion status. Odd months of the year were used to develop the standard and even months to validate the standard. A marginal logistic regression analysis was used to develop the standard. The decision to divert ambulances was used as the criterion for ED crowding. RESULTS: The logistic regression demonstrated excellent correlation between the work score and diversion status. At the point of maximum inflection of the receiver operating characteristic curve, the work score predicted diversion status with 86% sensitivity and 80% specificity. CONCLUSIONS: An ED work score was successfully developed and internally validated. External validation should be performed before widespread use.

Ambulances↗
PubMed2005

One- and two-sample nonparametric inference procedures in the presence of a mixture of independent and dependent censoring.

In survival analysis, the event time T is often subject to dependent censorship. Without assuming a parametric model between the failure and censoring times, the parameter Theta of interest, for example, the survival function of T, is generally not identifiable. On the other hand, the collection Omega of all attainable values for Theta may be well defined. In this article, we present nonparametric inference procedures for Omega in the presence of a mixture of dependent and independent censoring variables. By varying the criteria of classifying censoring to the dependent or independent category, our proposals can be quite useful for the so-called sensitivity analysis of censored failure times. The case that the failure time is subject to possibly dependent interval censorship is also discussed in this article. The new proposals are illustrated with data from two clinical studies on HIV-related diseases.

Anti-HIV Agents↗
PubMed2005

Genomewide nonadditive gene regulation in Arabidopsis allotetraploids.

Polyploidy has occurred throughout the evolutionary history of all eukaryotes and is extremely common in plants. Reunification of the evolutionarily divergent genomes in allopolyploids creates regulatory incompatibilities that must be reconciled. Here we report genomewide gene expression analysis of Arabidopsis synthetic allotetraploids, using spotted 70-mer oligo-gene microarrays. We detected >15% transcriptome divergence between the progenitors, and 2105 and 1818 genes were highly expressed in Arabidopsis thaliana and A. arenosa, respectively. Approximately 5.2% (1362) and 5.6% (1469) genes displayed expression divergence from the midparent value (MPV) in two independently derived synthetic allotetraploids, suggesting nonadditive gene regulation following interspecific hybridization. Remarkably, the majority of nonadditively expressed genes in the allotetraploids also display expression changes between the parents, indicating that transcriptome divergence is reconciled during allopolyploid formation. Moreover, >65% of the nonadditively expressed genes in the allotetraploids are repressed, and >94% of the repressed genes in the allotetraploids match the genes that are expressed at higher levels in A. thaliana than in A. arenosa, consistent with the silencing of A. thaliana rRNA genes subjected to nucleolar dominance and with overall suppression of the A. thaliana phenotype in the synthetic allotetraploids and natural A. suecica. The nonadditive gene regulation is involved in various biological pathways, and the changes in gene expression are developmentally regulated. In contrast to the small effects of genome doubling on gene regulation in autotetraploids, the combination of two divergent genomes in allotetraploids by interspecific hybridization induces genomewide nonadditive gene regulation, providing a molecular basis for de novo variation and allopolyploid evolution.

Arabidopsis↗
PubMed2005

Discovering statistically significant pathways in expression profiling studies.

Accurate and rapid identification of perturbed pathways through the analysis of genome-wide expression profiles facilitates the generation of biological hypotheses. We propose a statistical framework for determining whether a specified group of genes for a pathway has a coordinated association with a phenotype of interest. Several issues on proper hypothesis-testing procedures are clarified. In particular, it is shown that the differences in the correlation structure of each set of genes can lead to a biased comparison among gene sets unless a normalization procedure is applied. We propose statistical tests for two important but different aspects of association for each group of genes. This approach has more statistical power than currently available methods and can result in the discovery of statistically significant pathways that are not detected by other methods. This method is applied to data sets involving diabetes, inflammatory myopathies, and Alzheimer's disease, using gene sets we compiled from various public databases. In the case of inflammatory myopathies, we have correctly identified the known cytotoxic T lymphocyte-mediated autoimmunity in inclusion body myositis. Furthermore, we predicted the presence of dendritic cells in inclusion body myositis and of an IFN-alpha/beta response in dermatomyositis, neither of which was previously described. These predictions have been subsequently corroborated by immunohistochemistry.

Algorithms↗
PubMed2005

Nanoscale anionic macromolecules for selective retention of low-density lipoproteins.

Synthetically designed anionic nanocarriers that mimic the charge properties of glycosaminoglycans can potentially sequester low-density lipoproteins (LDL) during the treatment of atherosclerosis. In this study, we explore the LDL retentivity of 15-20 nm anionic micelles formed from amphiphilic scorpion-like macromolecules (AScMs) as building blocks. The macromolecules comprise four aliphatic chains attached to mucic acid and a linear polyethylene glycol (PEG) segment to form micellar nanocarriers with a hydrophobic core and hydrophilic corona. Dynamic light scattering and transmission electron microscopy studies indicate that the carboxylate-terminated nanocarriers (20 nm) sequester LDL (22 nm), resulting in complexes with a diameter of 60-90 nm, but neutral ethoxy-terminated nanocarriers do not retain LDL. Further, carboxylate-terminated nanocarriers consistently bound to unoxidized LDL (Relative Electrophoretic Mobility, REM=1.0) and mildly oxidized LDL (REM=1.5), but not highly oxidized LDL (REM=3.6), whereas the neutral nanocarriers displayed no preference/affinity at all, indicating that the nanocarrier-LDL binding is charge-dependent. The binding affinity of unoxidized LDL for differentially charged nanocarriers, formed from varying ratios of carboxylate- and ethoxy-terminated macromolecules, was quantified. The 100% carboxylated nanocarriers elicited the highest binding affinity (K(d)=567 nm), whereas mixed micelles elicited significantly lower levels of binding affinity. Our results highlight the promise of synthetically designed nanomaterials in lipoprotein retention, a key step in managing the escalation of atherosclerosis.

Anions↗