Biomedical subjects

Dajun Qian

Publications and source records attributed to Dajun Qian.

11 recordsLinked to original sources

PubMed2007

Single nucleotide polymorphisms of tumor necrosis factor-alpha and the susceptibility to bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy. A "New" BPD has been characterized in preterm infants that may begin in utero, and then progress post-natally, resulting in arrested lung development and alveolar hypoplasia. Foundations for this "New" BPD may be derived from pro-inflammatory genes including tumor necrosis factor-alpha (TNFalpha). The hypothesis of the current study is that single nucleotide polymorphisms (SNPs) of the pro-inflammatory TNFalpha gene place preterm infants at increased risk for BPD. Preterm infants (105 in number) with birthweights <or=1 kg, who survived to at least 36 weeks postmenstrual age (PMA) or discharge were enrolled into this study. They were stratified for BPD according to their need for supplemental oxygen at 28 days and at 36 weeks PMA (non-, mild-, moderate-, or severe-BPD). DNA was extracted from these infants and subjected to analyses for the TNFalpha SNPs: -1,031, -863, -857, -308, and -238. The PHASE software (version 2.1) was used to reconstruct haplotypes and estimate their frequencies within the study population. Differences in birth weight (P < 0.001) and gestational age (P < 0.001), but not in racial distribution between the groups were found. Haplotype-specific analysis revealed no significant association between BPD severity and any of the 5-marker common haplotypes with 10 or more copies in this study population. Additionally, no significant association was observed in any three SNP haplotypes at -1,031, -863, and -857, and two SNP haplotypes at -308 and -238. We observed no association between BPD severity and the five TNFalpha SNPs investigated.

Bronchopulmonary Dysplasia↗

PubMed2006

The genetic basis for bronchopulmonary dysplasia.

While the 'original' bronchopulmonary dysplasia (BPD) was attributed to the iatrogenic effects of oxygen and barotrauma on the preterm lung, analyses of the 'new' BPD suggests that these environmental effects may contribute to arrested pulmonary development, and that there may also be genetic foundations for the susceptibility to BPD. Twinning, family and population studies implicate heritable factors in the evolution of BPD. The candidate genes examined for their potential role in BPD include surfactant apoprotein and inflammatory genes. With the identification and mapping of single nucleotide polymorphisms (SNPs), an explosion of testing for these genetic components that may contribute to a number of complex, multigenic disease conditions-including BPD-have been initiated. Sophisticated multiplex analyses are now available to link candidate SNPs to conditions such as BPD. However, there continues to be wide variation in the expression of BPD throughout neonatal units. Differentiating the effects caused by environmental and environmental-genetic interactions from isolated genetic etiologies is still problematic and will require carefully designed genetic analyses of preterm infant groups and their families.

Alleles↗

PubMed2005

Haplotype sharing correlation of alcohol dependence on chromosomes 1-6 in 93 nuclear families.

Haplotype data contain signatures of ancestral alleles and increased information for mapping genes associated with complex traits. The motivation of this paper is to test the feasibility of a recently developed haplotype reconstruction algorithm and to perform haplotype-sharing correlation (HSC) analysis in nuclear families using data provided by the Genetic Analysis Workshop 14 and the Collaborative Study of the Genetics of Alcoholism. As an exemplary analysis, haplotype data on chromosomes 1-6 were reconstructed from genotype data in 93 nuclear families by minimizing both the recombinants in within-family haplotypes and the tree distance in between-family haplotypes. HSC analysis was performed using the best set of reconstructed haplotypes, and chromosome-wide significance was evaluated using a permutation procedure. Three markers were found to have significant haplotype associations with DSM-IV alcohol dependence that exceeded the 0.05 level of chromosome-wide significance: marker rs895941 at 36.7 cM on chromosome 3 (p = 0.03), marker rs1631833 at 109.1 cM on chromosome 4 (p = 0.008), and marker rs953887 at 74.2 cM on chromosome 6 (p = 0.02). These results indicated the usefulness of HSC analysis and provided further evidence on chromosome regions associated with alcohol dependence.

Alcoholism↗

PubMed2005

A quantitative high-throughput chemotaxis assay using bioluminescent reporter cells.

Here we report on a novel biophotonic assay system for the detection and quantitation of chemotaxis, the directed movement of cells in response to chemokine concentration gradients. Our assay employs a firefly luciferase (ffLuc)-generated biophotonic signal to quantify cellular migration in 96-well microplate chemotaxis instruments. When compared to direct cell enumeration, the biophotonic reporter method is superior in accuracy, reproducibility, and sensitivity. As a proof-of-concept, we demonstrate the utility of this assay for quantifying the chemotactic response of ex vivo expanded ffLuc(+) primary human T-cells to recombinant human chemokines MCP-1, RANTES, and IP-10. The 96-well microplate format and in situ biophotonic detection of cells are amenable to high-throughput screening of peptides and small molecule libraries to identify agonists and antagonists of cellular chemotaxis, to analyze biological fluids for chemotactic activity, and to study chemotaxis in a variety of cell types.

Animals↗

PubMed2005

Metaplastic breast cancer: clinical features and outcomes.

Metaplastic carcinoma of the breast, a neoplasm with both epithelial and mesenchymal elements, represents less than 1 per cent of all breast cancer. We reviewed the records of all patients diagnosed with localized metaplastic breast cancer from 1991 to 2003 at our institution. We identified 21 patients. Mean primary tumor size was 4.62 cm. Eight patients (38%) had axillary node involvement at presentation. All the tumors were high grade. Only two (10%) of the tumors were hormone receptor positive. Seventeen (81%) of the patients received adjuvant chemotherapy, and 12 (57%) of the patients received radiation. Ten (29%) patients suffered a local recurrence. With a mean follow-up of 46 months, the 5-year disease-free and overall survival was 42 per cent (95% CI: 20% to 65%) and 71 per cent (95% CI: 46% to 96%), respectively. Stage-specific overall survival was 100 per cent, 83 per cent, and 53 per cent for stages I, II, and III, respectively. By multivariate analysis, there was no impact on recurrence or survival with regard to size, age, menopausal status, nodal status, histologic subtype, adjuvant therapy, or extent of surgery. Metaplastic breast cancer is a unique neoplasm that tends to present at an advanced stage and has a propensity for local recurrence. When stratified by stage, however, survival appears similar to that of adenocarcinoma of the breast, and these tumors should be treated as such.

Adult↗

PubMed2004

Haplotype sharing correlation analysis using family data: a comparison with family-based association test in the presence of allelic heterogeneity.

The haplotype-sharing correlation (HSC) method for association analysis using family data is revisited by introducing a permutation procedure for estimating region-wise significance at each marker on a study segment. In simulation studies, the HSC method has a correct type 1 error rate in both unstructured and structured populations. The HSC signals on disease segments occur in the vicinity of a true disease locus on a restricted region without recombination hotspots. However, the peak signal may not pinpoint the true disease location in a small region with dense markers. The HSC method is shown to have higher power than single- and multilocus family-based association test (FBAT) methods when the true disease locus is unobserved among the study markers, and especially under conditions of weak linkage disequilibrium and multiple ancestral disease alleles. These simulation results suggest that the HSC method has the capacity to identify true disease-associated segments under allelic heterogeneity that go undetected by the FBAT method that compares allelic or haplotypic frequencies.

Alleles↗

PubMed2004

Axillary recurrence in DCIs: is axillary lymphadenectomy warranted?

Widespread use of screening mammography has resulted in a remarkable increase in the incidence (or detection rate) of ductal carcinoma in situ (DCIS). Axillary lymph node involvement in DCIS is reported to occur at a frequency of 1-12 per cent. Over the past few years, however, there has been increasing emphasis on axillary sampling, limited axillary dissection, and the potential role of sentinel lymph node biopsy. The clinical relevance of axillary lymph node biopsy or dissection remains unanswered. This retrospective analysis was performed on 171 patients who underwent treatment for DCIS at a tertiary care center over a period of 14 years. Clinical and tumor factors were evaluated, and the local, axillary, and systemic recurrence rates were noted. No axillary recurrences from the primary DCIS diagnosis were noted in the entire group of 171 patients. During a mean follow-up of 70 months, 10 patients (6%) developed recurrence in the ipsilateral breast. Six of these recurrences were in the form of DCIS, whereas, four recurred as invasive cancers. Nine patients developed a new primary (seven DCIS and two invasive) in the same breast but in a different quadrant. Two patients with ipsilateral invasive disease also developed systemic disease and eventually died of disease. During the same period, 10 patients (6%) developed DCIS, and seven patients (4%) developed invasive cancer in the contralateral breast. The data show that the risk of axillary recurrence in pure DCIS is, at most, extremely low and support the position that nodal sampling or dissection is unwarranted.

Adult↗

PubMed2003

Treatment with oxandrolone and the durability of effects in older men.

We investigated the effects of the anabolic androgen, oxandrolone, on lean body mass (LBM), muscle size, fat, and maximum voluntary muscle strength, and we determined the durability of effects after treatment was stopped. Thirty-two healthy 60- to 87-yr-old men were randomized to receive 20 mg oxandrolone/day (n = 20) or placebo (n = 12) for 12 wk. Body composition [dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging, and (2)H(2)O dilution] and muscle strength [1 repetition maximum (1 RM)] were evaluated at baseline and after 12 wk of treatment; body composition (DEXA) and 1-RM strength were then assessed 12 wk after treatment was discontinued (week 24). At week 12, oxandrolone increased LBM by 3.0 +/- 1.5 kg (P < 0.001), total body water by 2.9 +/- 3.7 kg (P = 0.002), and proximal thigh muscle area by 12.4 +/- 8.4 cm(2) (P < 0.001); these increases were greater (P < 0.003) than in the placebo group. Oxandrolone increased 1-RM strength for leg press by 6.7 +/- 6.4% (P < 0.001), leg flexion by 7.0 +/- 7.8% (P < 0.001), chest press by 9.3 +/- 6.7% (P < 0.001), and latissimus pull-down exercises by 5.1 +/- 9.1% (P = 0.02); these increases were greater than placebo. Oxandrolone reduced total (-1.9 +/- 1.0 kg) and trunk fat (-1.3 +/- 0.6 kg; P < 0.001), and these decreases were greater (P < 0.001) than placebo. Twelve weeks after oxandrolone was discontinued (week 24), the increments in LBM and muscle strength were no longer different from baseline (P > 0.15). However, the decreases in total and trunk fat were sustained (-1.5 +/- 1.8, P = 0.001 and -1.0 +/- 1.1 kg, P < 0.001, respectively). Thus oxandrolone induced short-term improvements in LBM, muscle area, and strength, while reducing whole body and trunk adiposity. Anabolic improvements were lost 12 wk after discontinuing oxandrolone, whereas improvements in fat mass were largely sustained.

Aged↗

PubMed2002

Prospective, intensive study of metabolic changes associated with 48 weeks of amprenavir-based antiretroviral therapy.

To determine whether a 48-week course of amprenavir-based antiretroviral therapy is associated with metabolic alterations, 14 clinically stable human immunodeficiency virus (HIV)-infected, protease inhibitor-naive adults initiated amprenavir-based triple therapy. Twelve subjects (86%) achieved HIV RNA levels of <400 copies/mL at week 24. Fasting glucose and insulin levels did not change. Insulin sensitivity did not decrease in the first 24 weeks, but a trend toward a decrease appeared at week 48. Six subjects experienced onset or worsening of glucose tolerance by week 24. Levels of fasting triglycerides and low-density lipoprotein, high-density lipoprotein, and total cholesterol increased. Bone mineral content, lean tissue, total fat, trunk fat, limb fat, and the ratio of trunk to limb fat increased at week 48. Amprenavir-based therapy was associated with increases in serum lipid levels but no short-term decrease in insulin sensitivity. A trend toward insulin resistance appeared late in the study following weight gain, particularly of trunk fat, but without loss of limb fat.

Adult↗

PubMed2002

Minimum-recombinant haplotyping in pedigrees.

This article presents a six-rule algorithm for the reconstruction of multiple minimum-recombinant haplotype configurations in pedigrees. The algorithm has three major features: First, it allows exhaustive search of all possible haplotype configurations under the criterion that there are minimum recombinants between markers. Second, its computational requirement is on the order of O(J(2)L(3)) in current implementation, where J is the family size and L is the number of marker loci under analysis. Third, it applies to various pedigree structures, with and without consanguinity relationship, and allows missing alleles to be imputed, during the haplotyping process, from their identical-by-descent copies. Haplotyping examples are provided using both published and simulated data sets.

Algorithms↗

PubMed2002

Lifestyle and other risk factors for thyroid cancer in Los Angeles County females.

PURPOSE AND METHODS: We conducted a population-based case-control study of thyroid cancer. Cases were 292 women, aged 15-54 when diagnosed between the years 1980 and 1983 (145 diagnosed in 1980-81 and 147 diagnosed in 1982-83). Female neighborhood controls (n = 292) were matched to each case on birth-year and race. RESULTS: Among women < 35 years, thyroid disease in first-degree relatives increased thyroid cancer risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1-3.7]. Risk was not associated with fish consumption, although high childhood consumption of shellfish decreased thyroid cancer risk (OR = 0.2, 95% CI = 0.05-0.7 for consumption at least a few times weekly). Among papillary thyroid cancers (82% of cases), frequent adult consumption of saltwater fish decreased risk. Cancer risk was reduced with consumption of certain vegetables, wine, and tea. Other dietary variables, including milk, beer and hard liquor, and coffee were not related to thyroid cancer risk. Among the papillary sample, risk increased with longer use of multivitamins (OR = 2.9, 95% CI = 1.2-7.4 for > 10 years of use). Smoking and body mass were not associated with thyroid cancer risk. CONCLUSIONS: These results suggest a role of family history of thyroid disease and certain dietary variables in the etiology of thyroid cancer in adult females.

Adolescent↗