Biomedical subjects

Q Lan

Publications and source records attributed to Q Lan.

At least 19 recordsLinked to original sources

PubMed2024

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Humans↗

PubMed2007

Two-sample comparison based on prediction error, with applications to candidate gene association studies.

To take advantage of the increasingly available high-density SNP maps across the genome, various tests that compare multilocus genotypes or estimated haplotypes between cases and controls have been developed for candidate gene association studies. Here we view this two-sample testing problem from the perspective of supervised machine learning and propose a new association test. The approach adopts the flexible and easy-to-understand classification tree model as the learning machine, and uses the estimated prediction error of the resulting prediction rule as the test statistic. This procedure not only provides an association test but also generates a prediction rule that can be useful in understanding the mechanisms underlying complex disease. Under the set-up of a haplotype-based transmission/disequilibrium test (TDT) type of analysis, we find through simulation studies that the proposed procedure has the correct type I error rates and is robust to population stratification. The power of the proposed procedure is sensitive to the chosen prediction error estimator. Among commonly used prediction error estimators, the .632+ estimator results in a test that has the best overall performance. We also find that the test using the .632+ estimator is more powerful than the standard single-point TDT analysis, the Pearson's goodness-of-fit test based on estimated haplotype frequencies, and two haplotype-based global tests implemented in the genetic analysis package FBAT. To illustrate the application of the proposed method in population-based association studies, we use the procedure to study the association between non-Hodgkin lymphoma and the IL10 gene.

Adult↗

PubMed2006

Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

Asian People↗

PubMed2006

Design and microsurgical anatomy of the retrosigmoid-retrocondylar keyhole approach without occipital condyle removal.

OBJECTIVE: The goal of this study was to design a new retrosigmoid-retrocondylar keyhole approach based on the minimally invasive keyhole idea and to explore its feasibility and indications, which can be regarded as the base of this keyhole approach in clinical use. METHODS: 8 adult cadaveric heads fixed in formalin and with intracranial vessels perfused by colored latex were used in this study. To search for the most suitable length and shape of the skin incision, we examined two kinds of incision (a longitudinal "S" shape and a straight one) and two lengths (5 cm and 7 cm, respectively). Due to the complexity and thickness of the suboccipital muscles, two ways of muscle dissection were compared: 1) the muscles were incised perpendicularly in layers; 2) the muscles were detached and reflected in layers. A 3-cm diameter retrosigmoid-retrocondylar bone flap was made with a craniotome. Many anatomic structures could be observed under the microscope when the cerebellar hemisphere was retracted. After comparing and balancing the above steps in all specimens, a feasible, duplicable retrosigmoid-retrocondylar keyhole approach was devised. RESULTS: The proper incision of the retrosigmoid-retrocondylar keyhole approach was a longitudinal "S" shaped skin incision about 7 cm in length with its superior border 2 cm behind the middle point of mastoid and inferior margin at the level of C-2. The method of detachment and reflection of occipital muscles was superior to the method of cutting them perpendicularly. By means of adjusting the head position and the angle of microscope, the ipsilateral vertebral artery, posterior inferior cerebellar artery, anterior inferior cerebellar artery, VII, VIII, IX, X, XI, XII cranial nerves and the ventral lateral aspect of medulla oblongata were exposed via this keyhole approach. CONCLUSIONS: The novel retrosigmoid-retrocondylar keyhole approach has practical value for clinical applications. With the techniques of modern microsurgery, several diseases such as an aneurysm situated at the vertebral artery or the posterior inferior cerebellar artery, a small hypoglossal neurinoma and tumor located at the ventral lateral aspect of the medulla oblongata, may be operated via this retrosigmoid-retrocondylar keyhole approach without drilling the occipital condyle.

Adult↗

PubMed2005

Functional analysis of AeSCP-2 using gene expression knockdown in the yellow fever mosquito, Aedes aegypti.

The effect of gene expression knockdown was used to study the function of the sterol carrier protein-2 (AeSCP-2) in the yellow fever mosquito, Aedes aegypti. Injection of small double stranded AeSCP-2 RNAs into mosquito larvae resulted in the knockdown of gene products. The lack of AeSCP-2 in larvae coincided with a reduction in accumulated cholesterol in pupae, supporting the hypothesis that AeSCP-2 may be involved in cholesterol uptake in mosquito larvae. Knockdown of AeSCP-2 caused a high mortality rate in developing adult and reduced egg viability. Results from this study indicate that AeSCP-2 is important for adult development and for the viability of the eggs.

Aedes↗

PubMed2005

Aedes aegypti phosphohexomutases and uridine diphosphate-hexose pyrophosphorylases: comparison of primary sequences, substrate specificities and temporal transcription.

Phosphohexomutases reversibly catalyse the transfer of the phosphate group of a glycosyl phosphate between the C6 and C1 positions, and uridine diphosphate (UDP)-hexose pyrophosphorylases catalyse the synthesis of UDP-hexose from uridine triphosphate (UTP) and hexose-1-phosphate. Both enzyme families are essential for nucleoside diphosphate hexose biosynthesis and are therefore critical for various physiological functions in the midgut of mosquitoes after a blood meal. We cloned and sequenced three phosphohexomutase and two UDP-hexose pyrophosphorylase cDNAs from Aedes aegypti. The products of the cDNAs were expressed and substrate specificities were examined. Herein we describe Ae. aegypti phosphoglucomutase 1, phosphoglucomutase 2, phosphoacetylglucosamine mutase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase. Transcripts of the genes expressing the enzymes are constitutively present in all life stages and blood-feeding does not seem to influence transcript abundance.

Aedes↗

PubMed2004

Stage-specific expression of two actin genes in the yellow fever mosquito, Aedes aegypti.

Abstract The expression patterns of two muscle-specific actin genes were studied in the yellow fever mosquito, Aedes aegypti. The coding sequence of AeAct-2 exhibits between 82 and 85% similarity with coding sequences of the Drosophila melanogaster and predicted Anopheles gambiae actin genes. The transcription of the AeAct-2 gene was differentially regulated during developmental stages with higher levels of expression in larvae and lower levels in pupae and adults. The AeAct-2 gene is mainly expressed in the head and body wall tissues. Transcripts of the AeAct-3 gene are not detectable in larvae until late 4th instar and the level increased in male pupae and early male adults. The main site of expression of the AeAct-3 gene was the thoracic tissue. Thus, AeAct-3 is the first reported male-specific actin gene in mosquitoes.

Actins↗

PubMed2004

Expression of a sterol carrier protein-x gene in the yellow fever mosquito, Aedes aegypti.

The sterol carrier protein-x (SCP-x), a peroxisomal thiolase/nonspecific lipid binding protein, was characterized in the yellow fever mosquito, Aedes aegypti. The Aedes aegypti SCP-x (AeSCP-x) has 83% and 75% similarities to Drosophila and mammalian SCP-x, respectively. However, the AeSCP-x gene did not produce multiple transcripts, which is characteristic of the vertebrate SCP-x gene. Levels of AeSCP-x transcription were higher in larvae and pupae. Gut tissue showed the highest level of AeSCP-x mRNA in larvae. In adults, low levels of AeSCP-x transcription were detected in both sexes. Polyclonal antibodies against the sterol carrier protein-2 (SCP-2) domain of AeSCP-x detected two proteins of 62 kDa and 13 kDa. The results indicate that AeSCP-x is proteolytically cleaved after translation to produce a smaller protein that contains only the SCP-2 domain, which is similar to post-translational modification of the vertebrate's SCP-x to produce multiple products.

Aedes↗

PubMed2003

Isolation and expression of a sterol carrier protein-2 gene from the yellow fever mosquito, Aedes aegypti.

Trafficking of cholesterol in insects is a very important process due to the fact that insects depend on dietary cholesterol to fulfil their physiological needs. We identified a putative mosquito sterol carrier protein-2 (SCP-2) cDNA from fourth instar subtracted cDNA library. The AeSCP-2 protein has high degree homology in the sterol transfer domain to both rat and human SCP-2. Transcripts of AeSCP-2 in fourth instars were detected strongly in the midgut, and weakly in the head and hindgut. In the early pupae, AeSCP-2 transcription was observed in the thorax, head and body wall of abdomen, but not in the gut. The interaction of mosquito sterol carrier protein-2 (AeSCP-2) with cholesterol was examined. The Kd of purified recombinant AeSCP-2 to cholesterol was 5.6 +/- 0.6 x 10-9 m using radiolabelled cholesterol-binding assay. The results suggest that AeSCP-2 has high affinity to cholesterol and may function as a carrier protein in mosquitoes.

Aedes↗

PubMed2001

Isolation and developmental expression of two nuclear receptors, MHR4 and betaFTZ-F1, in the tobacco hornworm, Manduca sexta.

The cDNAs for two members of the nuclear receptor superfamily were isolated from the tobacco hornworm, Manduca sexta. The deduced amino acid sequence of MHR4 shows 93-95% identity in the DNA-binding domain and the first portion of the hinge (D) region with the germ cell nuclear factor (GCNF)-related factors (GRFs) of the silkworm, Bombyx mori, and the mealworm, Tenebrio molitor, and with a genomic sequence from the fruit fly, Drosophila melanogaster. Northern blot hybridization showed that a 7.5 kb MHR4 mRNA appeared in Manduca abdominal epidermis just as the ecdysteroid titer began to decline during the larval molt, disappeared about 12 h later, then transiently reappeared shortly before larval ecdysis. During the pupal and adult molts, a similar pattern of expression was seen (the very end of the adult molt was not studied). At peak times of expression in the epidermis, MHR4 mRNA was also present in fat body and the central nervous system (CNS). The deduced amino acid sequence of Manduca FTZ-F1 is 100% and 96% identical to that of B. mori and Drosophila betaFTZ-F1, respectively, in the DNA-binding domain and the adjacent hinge region including the FTZ-F1 box. Northern blot analysis showed that the >9.5 kb betaFTZ-F1 mRNA appeared in Manduca epidermis during the decline of the ecdysteroid titer in the larval, pupal and adult molts as the first peak of MHR4 mRNA declined, then it disappeared in the larval and pupal molts before the second peak of MHR4 appeared. betaFTZ-F1 mRNA was also found in fat body and the CNS at the time of peak expression in the epidermis during the larval and pupal molts. Both MHR4 and betaFTZ-F1 mRNAs were found in the testis during the onset of spermatogenesis in the prepupal period.

Amino Acid Sequence↗

PubMed2001

Glutathione S-transferase genotypes and stomach cancer in a population-based case-control study in Warsaw, Poland.

Glutathione S-transferases are important in the detoxification of a wide range of human carcinogens. Previous studies have shown inconsistent associations between the GSTT1 and GSTM1 null genotypes and stomach cancer risk. We investigated the relationship between these and related genotypes and stomach cancer risk in a population-based case-control study in Warsaw, Poland, where stomach cancer incidence and mortality rates are among the highest in Europe. DNA from blood samples was available for 304 stomach cancer patients and 427 control subjects. We observed a 1.48-fold increased risk for stomach cancer (95% confidence interval 0.97-2.25) in patients with the GSTT1 null genotype but no evidence of increased risk associated with the GSTM1, GSTM3 or GSTP1 genotypes. Furthermore, the stomach cancer risk associated with the GSTT1 null genotype varied by age at diagnosis, with odds ratios of 3.85, 1.91, 1.78 and 0.59 for those diagnosed at ages less than 50, 50-59, 60-69 and 70 years or older, respectively (P trend = 0.01). This was due to a shift in the GSTT1 genotype distribution across age groups among stomach cancer patients only. These results suggest that the GSTT1 null genotype may be associated with increased risk of stomach cancer.

Adult↗

PubMed2001

p53 gene expression in relation to indoor exposure to unvented coal smoke in Xuan Wei, China.

Lung cancer mortality rates in Xuan Wei County, which are among the highest in China, have previously been associated with exposure to indoor emissions from burning smoky coal. To determine if this association is stronger among lung cancer patients with abnormal expression of p53, we performed a population-based case-control study. Ninety-seven newly diagnosed lung cancer patients and 97 controls, individually matched by age, sex, and home fuel type, were enrolled. We used immunocytochemical methods to assess p53 protein accumulation in exfoliated tumor cells isolated from sputum samples. As expected, the amount of lifetime smoky coal use was associated with an overall increase in lung cancer risk. Compared with subjects who used less than 130 tons of smoky coal during their lifetime, the odds ratios (OR) for lung cancer were 1.48 (95% confidence interval [CI], 0.73 to 3.02) for subjects exposed to 130 to 240 tons, and 3.21 (95% CI, 1.23 to 9.03) for subjects who used more than 240 tons of smoky coal (P for trend 0.01). The effect was due almost exclusively to the pattern in women, almost all of whom were nonsmokers. Further, among highly exposed women, the association was substantially larger and achieved statistical significance only among patients with sputum samples that were positive for p53 overexpression (OR, 18.72; 95% CI, 1.77 to 383.38 vs OR, 4.80; 95% CI, 0.66 to 43.87 for p53-negative cases). This study suggests that exposure to the combustion products of smoky coal in Xuan Wei is more strongly associated with women who have lung cancer accompanied by p53 protein overexpression in exfoliated tumor cells.

Air Pollution, Indoor↗

PubMed2000

Considerations on surgical treatment for elderly patients with intracranial aneurysms.

BACKGROUND: The purpose of this study was to investigate why elderly patients have poorer outcomes and to determine indications for surgery in elderly patients. METHODS: One hundred fifty-four patients with intracranial aneurysms admitted to the Department of Neurosurgery, Showa University School of Medicine, from 1990 through 1996 were reviewed. The patients were classified by age into three groups (young group, middle-aged group, elderly group). RESULTS: Forty-four patients (28.6%) were in the elderly group (mean age, 73 years). No difference in outcome was found between middle-aged and elderly patients if patients were stratified according to clinical grade. In addition, the main factors related to unfavorable outcomes in elderly patients were infection, organ failure, aneurysm rerupture before operation, and delayed ischemic deterioration. Elderly patients were more likely to experience rebleeding and have poor outcomes. CONCLUSIONS: Our results suggest that elderly patients should have early surgery. Furthermore, we found that the presence of hypertension or atherosclerosis had no significant effect on outcome. We conclude that early surgical treatment of aneurysms is indicated for elderly patients with good clinical grades in the absence of organ failure.

Adult↗

PubMed2000

Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk: a case-control study in Xuan Wei, China.

The lung cancer mortality rate in Xuan Wei County, China is among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons. This risk may be modified by variation in metabolism genes, including GSTM1, which encodes an enzyme known to detoxify polycyclic aromatic hydrocarbons. To investigate the relationship between GST genotypes and lung cancer risk in Xuan Wei County, we analyzed GSTM1 and GSTT1 genotypes in a population-based case-control study. A total of 122 lung cancer patients and 122 controls, individually matched by age, sex, and home fuel type, were studied. Compared to subjects who used less than 130 tons of smoky coal during their lifetime, heavier users (> or =130 tons) had a 2.4-fold (95% confidence interval, 1.3-4.4) increased risk of lung cancer. The GSTM1-null genotype was associated with a 2.3-fold (95% confidence interval, 1.3-4.2) increased risk of lung cancer. Furthermore, there was some evidence that smoky coal use was more strongly associated with lung cancer risk among GSTM1-null versus GSTM1-positive individuals. In contrast, the GSTT1 genotype was not significantly associated with lung cancer risk. Our data suggest that the GSTM1-null genotype may enhance susceptibility to air pollution from indoor coal combustion emissions.

Air Pollution, Indoor↗

PubMed1999

A new kinetic model of protein adsorption on suspended anion-exchange resin particles.

The kinetics of adsorption of bovine serum albumin on an anion-exchange resin were measured in a batch system using a flow cell and ultraviolet absorbance, as a function of initial liquid-phase protein concentration and solid-to-liquid phase ratio. A new mathematical model for adsorption kinetics is presented that fits the experimental data to give a highly linear relationship with time, following a short transient period. Numerical integration of the differential form of the new composite nonlinear (CNL) kinetic model, containing three independent parameters, is shown to describe the dynamics of batch adsorption much better than alternative lumped parameter models. Although the new model is phenomenological rather than mechanistic, its principal parameter is shown to be a direct linear function of a physically measurable quantity. This study demonstrates that the model can accurately simulate protein concentration-time profiles using parameter estimates derived from correlations over a wide range of initial protein concentrations and phase ratios. The new CNL model is shown to be considerably superior to the Langmuir and solid-film linear kinetic models in this regard, having the additional advantage that an equilibrium isotherm for the system is not required.

Adsorption↗

PubMed1999

Ligand regulation of juvenile hormone binding protein mRNA in mutant Manduca sexta.

Insect hemolymph juvenile hormone binding protein (hJHBP) regulates peripheral titers of its ligands, the juvenile hormones. In larvae of the black (bl) strain of the tobacco hornworm, Manduca sexta, treatment with small doses of juvenile hormone I (JH I) can also regulate titers of hJHBP. To further investigate this regulation, responsiveness of hJHBP mRNA expression to JH I was characterized in vivo. RNA analyzes revealed that transcript levels in fat body, the site of hJHBP synthesis, increased fivefold within several hours of treatment with physiological doses of hormone and remained elevated for approximately 16 h. Sensitivity to JH treatment was found to vary temporally. To ensure transcript identity, a wild-type cDNA clone and a bl RT-PCR fragment were sequenced and found to be 99% homologous. Together, these results suggest that JH participates in regulating expression of its transport protein in bl larvae by modifying the in vivo abundance of hJHBP's mRNA transcript.

Amino Acid Sequence↗

PubMed1999

[Glutathione S-transferase GSTM1 and GSTT1 genotypes and susceptibility to lung cancer].

A 1:1 matched population-based case-control study was conducted in Xuanwei City, Yunnan Province, where the lung cancer mortality is among China's highest. In this study there were 86 newly diagnosed lung cancer cases and 86 matched control subjects with the same sex, fuel type used, and age(+/- 2 years). Buccal cells were collected from each subject to determine the genotypes of GSTM1 and GSTT1. It was found that the rate of GSTM1 null genotype was higher in the case group than in the control group, and its odds ratio was 2.39(95% CI: 1.25-4.56). The odds ratio became 2.62(95% CI: 1.33-5.15) when other possible confounding factors such as smoking, COPD, and the lifetime exposure to unvented fuel combustion (tons) were adjusted. No association was found between GSTT1 null genotype and lung cancer. The rate of GSTM1 null genotype in Xuanwei City was found to be similar to those of other Chinese populations.

Case-Control Studies↗

PubMed1999

Activation of a delayed-early gene encoding MHR3 by the ecdysone receptor heterodimer EcR-B1-USP-1 but not by EcR-B1-USP-2.

MHR3, a homolog of the retinoid orphan receptor (ROR), is a transcription factor in the nuclear hormone receptor family that is induced by 20-hydroxyecdysone (20E) in the epidermis of the tobacco hornworm, Manduca sexta. Its 2.7-kb 5' flanking region was found to contain four putative ecdysone receptor response elements (EcREs) and a monomeric (GGGTCA) nuclear receptor binding site. Activation of this promoter fused to a chloramphenicol acetyltransferase (CAT) reporter by 2 micrograms of 20E per ml in Manduca GV1 cells was similar to that of endogenous MHR3, with detectable CAT by 3 h. When the ecdysone receptor B1 (EcR-B1) and Ultraspiracle 1 (USP-1) were expressed at high levels under the control of a constitutive promoter, CAT levels after a 3-h exposure to 20E increased two- to sixfold. In contrast, high expression of EcR-B1 and USP-2 caused little increase in CAT levels in response to 20E. Moreover, expression of USP-2 prevented activation by EcR-B1-USP-1. Deletion experiments showed that the upstream region, including the three most proximal putative EcREs, was responsible for most of the 20E activation, with the EcRE3 at -671 and the adjacent GGGTCA being most critical. The EcRE1 at -342 was necessary but not sufficient for the activational response but was the only one of the three putative EcREs to bind the EcR-B1-USP-1 complex in gel mobility shift assays and was responsible for the silencing action of EcR-B1-USP-1 in the absence of hormone. EcRE2 and EcRE3 each specifically bound other protein(s) in the cell extract, but not EcR and USP, and so are not EcREs in this cellular context. When cell extracts were used, the EcR-B1-USP-2 heterodimer showed no binding to EcRE1, and the presence of excess USP-2 prevented the binding of EcR-B1-USP-1 to this element. In contrast, in vitro-transcribed-translated USP-1 and USP-2 both formed heterodimeric complexes with EcR-B1 that bound ponasterone A with the same Kd (7 x 10(-10) M) and bound to both EcRE1 and heat shock protein 27 EcRE. Thus, factors present in the cell extract appear to modulate the differential actions of the two USP isoforms.

Animals↗