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Results for “Association and function analysis”

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PubMed2002

Peptide-specific CD8+ T-cell evolution in vivo: response to peptide vaccination with Melan-A/MART-1.

Monitoring of CD8+ T-cell responses in cancer patients during peptide vaccination is essential to provide useful surrogate markers and to demonstrate vaccine efficacy. We have longitudinally followed CD8+ T-cell responses in 3 melanoma patients who were immunized with peptides derived from Melan-A/MART-1. Recombinant HLA-A2 tetramers loaded with the naturally presented Melan-A/MART-1 nonamer peptide (AAGIGILTV) and the Melan-A/MART-1 analog (ELAGIGILTV) were used in combination with phenotypical analysis for different T-cell subsets including naive T cells, effector T cells, "true memory" T cells and "memory effector" T cells, based on CD45RA/RO and CCR7-expression. At least in a single patient, T cells binding to the AAGIGILTV epitope were detected in naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding to the analog ELAGIGILTV peptide were identified in the terminally differentiated (CD45RA+/CCR7-) T-cell subset. Molecular and functional analysis of tetramer-binding T cells revealed that the T-cell receptor (TCR) repertoire was oligo/polyclonal in AAGIGILTV-reactive T cells, but different and restricted to a few TCR clonotypes in ELAGIGILTV-reactive T cells prior to vaccination. The TCR repertoire reactive with Melan-A/MART-1 peptide epitopes was broadened during vaccination and exhibited a different profile of cytokine release after specific stimulation: tetramer-binding T cells from 2/3 patients secreted granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma but not interleukin-2 (IL-2) in response to Melan-A/MART-1 peptides. In the third patient, tetramer-binding T cells secreted IL-2 exclusively. Our results show that T-cell responses to peptide vaccination consist of different T-cell subsets associated with different effector functions. Complementary analysis for TCR CDR3 and cytokine profiles may be useful to define the most effective CD8+ T-cell population induced by peptide vaccination.

ATP-Binding Cassette Transporters↗

PubMed1994

Epstein-Barr virus nuclear protein 2A forms oligomers in vitro and in vivo through a region required for B-cell transformation.

Epstein-Barr virus nuclear antigen 2 (EBNA-2) has been shown to be indispensable for immortalization of latently infected B lymphocytes, and it has been shown that EBNA-2 exists in a high-molecular-weight complex in these cells. In order to study the components of this protein machinery, we have purified baculovirus-expressed EBNA-2 from insect cells to greater than 95% homogeneity. We have shown by both gel filtration and sucrose gradient analysis that the purified material corresponds to a multimer containing eight EBNA-2 subunits. This multimeric complex is stable in 1.0 M NaCl, suggesting that the self-association is quite strong in vitro. By expressing portions of the EBNA-2 open reading frame to generate fusion proteins in yeast cells, we have used the two-hybrid system to demonstrate that this self-association occurs in vivo and is mediated at least in part by a domain of EBNA-2 encompassing amino acids 122 to 344. Mutational analysis of the self-association function suggests that two subdomains that flank amino acid 232 may each play a role in EBNA-2 protein-protein interaction.

Amino Acid Sequence↗

PubMed2003

Selective breeding, quantitative trait locus analysis, and gene arrays identify candidate genes for complex drug-related behaviors.

Acute functional tolerance to ethanol develops during a single exposure to ethanol; it has been suggested to be a predisposing factor for the development of ethanol dependence. Genetic determinants of acute functional tolerance, as well as of ethanol dependence, have been clearly demonstrated. We describe a novel approach that uses a combination of selective breeding (to segregate genes contributing to the phenotype of interest, i.e., acute functional tolerance to the incoordinating effect of ethanol), quantitative trait locus analysis (to define chromosomal regions associated with acute functional tolerance), and DNA microarray technology (to identify differentially expressed genes in the brains of the selected lines of mice) to identify candidate genes for the complex phenotype of ethanol tolerance. The results indicate the importance of a signal transduction cascade that involves the glutamate receptor delta2 protein, the Ephrin B3 ligand, and the NMDA receptor, as well as a transcriptional regulatory protein that may be induced by activation of the NMDA receptor (zinc finger protein 179) and a protein that can modulate downstream responses to NMDA receptor activation (peroxiredoxin), in mediating acute tolerance to the incoordinating effect of ethanol.

Alcohol-Induced Disorders↗

PubMed2003

Genome-wide array analysis of normal and malformed human hearts.

BACKGROUND: We present the first genome-wide cDNA array analysis of human congenitally malformed hearts and attempted to partially elucidate these complex phenotypes. Most congenital heart defects, which account for the largest number of birth defects in humans, represent complex genetic disorders. As a consequence of the malformation, abnormal hemodynamic features occur and cause an adaptation process of the heart. METHODS AND RESULTS: The statistical analysis of our data suggests distinct gene expression profiles associated with tetralogy of Fallot, ventricular septal defect, and right ventricular hypertrophy. Applying correspondence analysis, we could associate specific gene functions to specific phenotypes. Furthermore, our study design allows the suggestion that alterations associated with primary genetic abnormalities can be distinguished from those associated with the adaptive response of the heart to the malformation (right ventricular pressure overload hypertrophy). We provide evidence for the molecular transition of the hypertrophic right ventricle to normal left ventricular characteristics. Furthermore, we present data on chamber-specific gene expression. CONCLUSIONS: Our findings propose that array analysis of malformed human hearts opens a new window to understand the complex genetic network of cardiac development and adaptation. For detailed access, see the online-only Data Supplement.

Adaptation, Physiological↗

PubMed2003

Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) open reading frame 4 protein (kaposica) is a functional homolog of complement control proteins.

The genome analysis of Kaposi's sarcoma-associated herpesvirus (KSHV) has revealed the presence of an open reading frame (ORF 4) with sequence homology to complement control proteins. To assign a function to this protein, we have now expressed this ORF using the Pichia expression system and shown that the purified protein inhibited human complement-mediated lysis of erythrocytes, blocked cell surface deposition of C3b (the proteolytically activated form of C3), and served as a cofactor for factor I-mediated inactivation of complement proteins C3b and C4b (the subunits of C3 convertases). Thus, our data indicate that this KSHV inhibitor of complement activation (kaposica) provides a mechanism by which KSHV can subvert complement attack by the host.

Cloning, Molecular↗

PubMed1991

Acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIb-IIIa complex--1. Glycoprotein analysis.

A patient with idiopathic thrombocytopenic purpura developed after splenectomy a thrombasthenia-like severe haemorrhagic diathesis characterized by a normal or subnormal platelet count, prolonged bleeding time, strongly reduced platelet adhesion to glass and defective platelet aggregation in response to ADP and collagen. In contrast to hereditary thrombasthenia membrane glycoproteins (GP) IIb and IIIa were normally present in the patient's platelets. Immunoelectrophoretic analysis revealed an abnormal behaviour of the patient's GP IIb-IIIa complex. Autoantibodies against GP IIb-IIIa were detected in Triton-extracted washed platelets. Incubation of normal platelets with plasma from the patient resulted in a similar immunoelectrophoretic abnormality of the GP IIb-IIIa complex indicating that bound autoantibodies (IgG) are responsible for the abnormal immunoelectrophoretic behaviour of the patient's GP IIb-IIIa complex. Platelet fibrinogen was severely reduced similar to classical thrombasthenia suggesting that the GP IIb-IIIa complex is involved in platelet fibrinogen storage.

Autoantibodies↗

PubMed2004

Long-term functional results after sphincter-saving resection for rectal cancer.

INTRODUCTION: A number of patients suffer from gastrointestinal side effects following sphincter-saving resection of the rectum. The aim of this study was to assess frequency and risk factors of long-term gastrointestinal side effects after sphincter-saving resection for rectal cancer. PATIENTS AND METHODS: Between 1980 and 1997, among 209 patients treated for rectal cancer by rectal resection and sphincter conservation, 145 who were alive without recurrence or colostomy, responded to a questionnaire. There were 85 males and 60 females with a mean age of 64 Years; the follow-up was 5.4 Years. The functional result was considered good if the number of stools per 24h was three or less with normal continence and poor if the number of stools was four or more or if fecal incontinence was present. Influence of age, gender, anastomotic height, type of sutured colon, colonic pouch, defunctioning stoma, leakage, stenosis, radiotherapy, history of irritable bowel syndrome and follow-up were analyzed. RESULTS: The mean anastomotic height was 5 cm from the anal margin. Functional results were good in 56% of patients and poor in 44%. Univariate analysis showed three variables to be significantly associated with the functional results: anastomotic height (P=0.001), radiotherapy (P=0.03) and follow-up > 24 Months (P=0.009). Multivariate analysis showed that only anastomotic height independently influenced functional results. They were good in 76%, 53% and 35% of patients for anastomoses located above 6 cm, between 6 and 3 cm, and below 3 cm from the anal margin, respectively. CONCLUSION: After sphincter-saving resection for rectal cancer, about half of patients have poor long-term functional results, the latter being related only to the anastomotic height. This suggests the need to preserve a small part of the rectum when oncologically feasible.

Adult↗

PubMed2001

Null missense ABCR (ABCA4) mutations in a family with stargardt disease and retinitis pigmentosa.

PURPOSE: To determine the type of ABCR mutations that segregate in a family that manifests both Stargardt disease (STGD) and retinitis pigmentosa (RP), and the functional consequences of the underlying mutations. METHODS: Direct sequencing of all 50 exons and flanking intronic regions of ABCR was performed for the STGD- and RP-affected relatives. RNA hybridization, Western blot analysis, and azido-adenosine triphosphate (ATP) labeling was used to determine the effect of disease-associated ABCR mutations in an in vitro assay system. RESULTS: Compound heterozygous missense mutations were identified in patients with STGD and RP. STGD-affected individual AR682-03 was compound heterozygous for the mutation 2588G-->C and a complex allele, [W1408R; R1640W]. RP-affected individuals AR682-04 and-05 were compound heterozygous for the complex allele [W1408R; R1640W] and the missense mutation V767D. Functional analysis of the mutation V767D by Western blot and ATP binding revealed a severe reduction in protein expression. In vitro analysis of ABCR protein with the mutations W1408R and R1640W showed a moderate effect of these individual mutations on expression and ATP-binding; the complex allele [W1408R; R1640W] caused a severe reduction in protein expression. CONCLUSIONS: These data reveal that missense ABCR mutations may be associated with RP. Functional analysis reveals that the RP-associated missense ABCR mutations are likely to be functionally null. These studies of the complex allele W1408R; R1640W suggest a synergistic effect of the individual mutations. These data are congruent with a model in which RP is associated with homozygous null mutations and with the notion that severity of retinal disease is inversely related to residual ABCR activity.

ATP-Binding Cassette Transporters↗

PubMedDate not supplied

Functional analysis of the cooled rat testis.

Direct cooling of the testis results in the depletion of most germ cells in vivo. Germ cell-depleted testes are now commonly used to investigate spermatogenic regeneration and can serve as recipients for germ cell transplantation. The present study explored the effects of cooling rat testes on the depletion of endogenous germ cells, spermatogenic regeneration, and Sertoli cell function. Adult rat testes were cooled with iced Ringer's solution for 60 minutes, which results in the initiation of apoptotic germ cell loss within 8 hours. Pachytene spermatocytes at stages XII-I were the cells most sensitive to cooling. In 46%-67% of seminiferous tubule cross-sections, only Sertoli cells remained in the cooled testes 3-10 weeks after treatment. Germ cell loss was accompanied by a significant decrease in circulating inhibin B and an increase in follicle-stimulating hormone concentrations, which indicated a change in Sertoli cell function. Quantitative analysis of mRNA expression associated with apoptotic signals showed no significant uniform changes among the cooled testes, although some individuals had a distinct up-regulation of FAS mRNA at 24 hours. Attempts to use the cooled testes as recipient testes for mouse-to-rat germ cell transplantation were undertaken, but none of the mouse germ cells transplanted into the testes 15-34 days after cooling appeared to have undergone spermatogenesis 64-92 days after transplantation. These data suggest that modifications to Sertoli cell function resulting from testicular cooling create an environment that is unable to support spermatogenesis by donor germ cells.

Animals↗

PubMed2005

Structural and functional analysis of 5S rRNA in Saccharomyces cerevisiae.

5S rRNA extends from the central protuberance of the large ribosomal subunit, through the A-site finger, and down to the GTPase-associated center. Here, we present a structure-function analysis of seven 5S rRNA alleles which are sufficient for viability in the yeast Saccharomyces cerevisiae when expressed in the absence of wild-type 5S rRNAs, and extend this analysis using a large bank of mutant alleles that show semi-dominant phenotypes in the presence of wild-type 5S rRNA. This analysis supports the hypothesis that 5S rRNA serves to link together several different functional centers of the ribosome. Data are also presented which suggest that in eukaryotic genomes selection has favored the maintenance of multiple alleles of 5S rRNA, and that these may provide cells with a mechanism to post-transcriptionally regulate gene expression.

Alleles↗

PubMed2004

Landscape character and fish assemblage structure and function in western Lake Superior streams: general relationships and identification of thresholds.

As part of a comparative watershed project investigating land-cover/land-use disturbance gradients for streams in the western Lake Superior Basin, we examined general relationships between landscape character and fish assemblage structure and function. We also examined the shape of those relationships to identify discontinuity thresholds where small changes in landscape character were associated with marked shifts in the fish assemblages. After completing a geographic analysis of second- and third-order watersheds in the western Lake Superior drainage, we randomly selected 48 streams along mature forest and watershed storage gradients in 2 hydrogeomorphic regions as our study sites. During the summers of 1997 and 1998, we used electrofishing to sample fish assemblages from each stream. Each of the landscape factors was significantly associated with fish assemblage structure and function based on analysis of covariance. Watershed storage was related to the greatest number of fish assemblage characteristics, but hydrogeopmorphic region and mature forest cover were strongly associated as well. The hydrogeomorphic region also mediated relationships between watershed character and fish assemblages. Discontinuity thresholds for our fish assemblages averaged 11% for watershed storage and 50% for watershed mature forest cover based on piecewise regression analysis. Although many of the landscape-fish relationships might have been manifest through effects on in-stream habitat, our results highlight the importance of management and land-use planning decisions at the watershed and landscape scales.

Animals↗

PubMed2006

Factors associated with decreased cerebral blood flow in congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Cerebral blood flow (CBF) is decreased and cognitive dysfunction develops in the advanced stages of heart failure. However, few data are available regarding the factors associated with decreased CBF. Fifty-two patients with advanced congestive heart failure (CHF) secondary to idiopathic dilated cardiomyopathy (ejection fraction <or=35%) and 10 healthy volunteers were included in this study. Echocardiography and symptom-limited bicycle exercise testing were performed. Global CBF was measured by radionuclide angiography. Global CBF was 19% less in patients with CHF than in controls (p <0.01). Such reduced CBF became normalized in 4 patients with CHF who underwent cardiac transplantation. In a univariate linear regression analysis, global CBF was significantly associated with New York Heart Association functional class, disease duration, atrial fibrillation, serum B-type natriuretic peptide level, the early mitral velocity/early diastolic annular velocity ratio, and pulmonary artery systolic pressure. Global CBF was not found to be associated with the ejection fraction, peak oxygen consumption, or anaerobic threshold. In a stepwise multivariate linear regression analysis, serum B-type natriuretic peptide level (p = 0.047) and New York Heart Association functional class (p = 0.003) were significantly related to global CBF (global CBF = 48.373 - 0.05 x serum B-type natriuretic peptide level - 3.283 x New York Heart Association functional class; r(2) = 0.401). In conclusion, CBF is decreased in patients with CHF, which may be used to predict disease severity and chronicity.

Adult↗

PubMed2003

Contribution of variants in the small heterodimer partner gene to birthweight, adiposity, and insulin levels: mutational analysis and association studies in multiple populations.

Loss of function mutations in the small heterodimer partner (SHP) gene have been reported to cause obesity and increased birth weight. We examined the relation between genetic variation in SHP and birth weight, adiposity, and insulin levels in three independent populations. The coding regions and 562 bases of the SHP promoter were screened for mutations in 329 subjects with severe early-onset obesity. Two novel missense mutations, R34G and R36C, were identified; these were not found in control subjects and did not cosegregate with obesity in family studies. Two common polymorphisms, G171A and -195CTGAdel, were found in 12 and 16% of subjects, respectively. Within the obese cohort, G171A and -195CTGAdel carriers had higher and lower birth weights, respectively, than wild-type subjects, the rare homozygotes for G171A being particularly large at birth. In a U.K. population-based cohort of 1,079 children, the 171A allele was associated with higher BMI (P < 0.05) and waist circumference (P = 0.001). Children carrying the G171A variant had higher 30-min insulin responses to a glucose load (P = 0.03). In conclusion, although mutations in SHP are not a common cause of severe human obesity, genetic variation in the SHP locus may influence birth weight and have effects on BMI, possibly through effects on insulin secretion.

Adipose Tissue↗

PubMed2026

Characterisation of whole-blood extrachromosomal circular DNAs in Kawasaki disease complicated by coronary artery aneurysm.

BACKGROUND: Extrachromosomal circular DNAs are critical regulators of stress responses, immunity, and inflammation pathways. However, their role and underlying mechanisms in Kawasaki disease complicated by coronary artery aneurysm remain poorly understood. METHODS: Whole blood samples from six children with Kawasaki disease, including three with coronary artery aneurysm group and three without coronary artery aneurysm (control group), were subjected to extrachromosomal circular DNA sequencing. Putative extrachromosomal circular DNAs were identified using Circle-Map. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on genes associated with upregulated extrachromosomal circular DNAs, and an exploratory immune-signature profiling was performed using the single-sample gene set enrichment analysis algorithm. RESULTS: We identified 4,790 differential extrachromosomal circular DNAs between the coronary artery aneurysm and control groups, of which 4,789 were upregulated in the CAA group. The extrachromosomal circular DNAs in the coronary artery aneurysm group were more concentrated and shorter in length than those in the control group. Upregulated extrachromosomal circular DNAs were mainly derived from autosomes, particularly chromosomes 3, 4, and 7. Functional enrichment analysis indicated that genes associated with upregulated extrachromosomal circular DNAs were mainly involved in response to stimulus-related terms and pathways, including chemokine signalling, cGMP-PKG signalling, and calcium signalling. Immune-signature analysis suggested that the coronary artery aneurysm group exhibited more specific immune responses, whereas the control group tended towards broader immune regulatory processes. CONCLUSIONS: Coronary artery aneurysm and control groups exhibited distinct extrachromosomal circular DNA profiles. These findings suggest that extrachromosomal circular DNA alterations are associated with coronary artery aneurysm in Kawasaki disease and may provide new insights into the molecular features underlying this condition.

Coronary artery aneurysm↗

PubMed2026

RECQL correlates with immune infiltration and serves as a prognostic biomarker and therapeutic predictor in gastric cancer.

BACKGROUND: RecQ-like helicase (RECQL), a member of the RecQ-like DNA helicase family, plays a crucial role in maintaining genomic stability. However, its relevance in gastric cancer (GC) has not been fully investigated. This study aimed to explore the clinical significance, biological functions, and potential role of RECQL in the tumor immune microenvironment of GC through comprehensive bioinformatics analyses and in vitro experiments. METHODS: Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and least absolute shrinkage and selection operator (LASSO) regression were performed using public datasets [The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE150290] to identify key genes associated with GC progression. Subsequently, key pathways were identified through functional enrichment analysis, while immune infiltration and spatial transcriptomic analyses were conducted to characterize RECQL expression and its association with the tumor immune microenvironment. Finally, the effects of RECQL knockdown on the biological function of GC cells were assessed through Cell Counting Kit-8 (CCK-8), colony formation, scratch, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: RECQL was significantly upregulated in GC tissues and correlated with advanced clinical stage and poor prognosis. Gene set enrichment analysis (GSEA) revealed a strong association between high RECQL expression and DNA repair pathway. Immune infiltration analysis indicated significant enrichment of M2 macrophages in the high-RECQL group, along with upregulation of immune checkpoint molecules including PDCD1, CTLA4, and CD274. Spatial transcriptomics further demonstrated co-localization of RECQL with myeloid cell-enriched regions in tumor parenchymal areas. Furthermore, in vitro experimental results indicated that RECQL was highly expressed in GC cell lines, and its knockdown effectively inhibited the viability, proliferation, and migration capabilities of HGC-27 cells, while enhancing their apoptosis. CONCLUSIONS: RECQL serves as a promising biomarker and potential therapeutic target in GC.

DNA repair↗

PubMed2025

Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.

BACKGROUND: Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel disease (IBD) are closely associated and becoming global health burdens. However, the causal relationships and common pathogeneses between them are uncertain. Furthermore, they are uncurable. Thus, we aimed to identify the causal relationships and novel therapeutic targets shared between them based on their common pathophysiological mechanisms in gut-brain-axis (GBA). METHODS: A meta-analysis on bidirectional Mendelian randomization (MR) utilizing various datasets was performed to estimate their causal relationship. Then, pleiotropic analysis under the composite null hypothesis (PLACO) with functional mapping combined with annotation of genetic associations (FUMA) analysis were conducted to identify pleiotropic genes. Next, blood, brain and intestine expression quantitative trait locus (eQTL) were taken to perform drug-target MR finding common causal genes in two diseases. Colocalization analysis ensured the eQTLs of corresponding gene colocalized with disease. Enrichment analysis and protein‒protein interaction (PPI) network were done to explore common pathogenesis pathways. Genes passed all analysis were regarded as drug targets. RESULTS: Our MR meta-analysis revealed the bidirectional causal relationship between diseases, with combined ORs for PD on IBD, CD, UC (1.050 [95% CI 1.014-1.086], 1.044 [95% CI 0.995-1.095], 1.063 [95% CI 1.016-1.120]); for IBD, CD, UC on PD (1.003 [95% CI 0.973-1.034], 1.035 [95% CI 1.004-1.067], 1.008 [95% CI 0.977-1.040]). Overall, 277, 216 and 201 genes were identified as pleiotropic genes between PD and IBD, CD, UC. Total of 733 genes were classified as tier 3 (found in only one tissue) druggable targets, 57 as tier 2 (found in two tissues, 51 protein-coding genes) and 9 as tier 3 (found in three tissues). Among 60 protein-coding druggable targets over tier 2, 18 overlapped with pleiotropic genes and enriched in mitochondria, antigen presentation, processing and immune cell regulation pathways. Three druggable genes (LRRK2, RAB29 and HLA-DQA2) passed colocalization analysis. LRRK2 and RAB29 were reported to be pleiotropic genes, and RAB29 and HLA-DQA2 were reported for the first time as potential drug targets. CONCLUSIONS: This study established a reliable causal relationship, possible shared drug targets and common pathogenesis pathways of two diseases, which had important implications for intervention and treatment of two diseases simultaneously.

Humans↗

PubMed2005

Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas.

Gene expression profiling has proven useful in subclassification and outcome prognostication for human glial brain tumors. The analysis of biological significance of the hundreds or thousands of alterations in gene expression found in genomic profiling remains a major challenge. Moreover, it is increasingly evident that genes do not act as individual units but collaborate in overlapping networks, the deregulation of which is a hallmark of cancer. Thus, we have here applied refined network knowledge to the analysis of key functions and pathways associated with gliomagenesis in a set of 50 human gliomas of various histogenesis, using cDNA microarrays, inferential and descriptive statistics, and dynamic mapping of gene expression data into a functional annotation database. Highest-significance networks were assembled around the myc oncogene in gliomagenesis and around the integrin signaling pathway in the glioblastoma subtype, which is paradigmatic for its strong migratory and invasive behavior. Three novel MYC-interacting genes (UBE2C, EMP1, and FBXW7) with cancer-related functions were identified as network constituents differentially expressed in gliomas, as was CD151 as a new component of a network that mediates glioblastoma cell invasion. Complementary, unsupervised relevance network analysis showed a conserved self-organization of modules of interconnected genes with functions in cell cycle regulation in human gliomas. This approach has extended existing knowledge about the organizational pattern of gene expression in human gliomas and identified potential novel targets for future therapeutic development.

Adult↗

PubMed2003

Lung function and incident coronary heart disease: the Atherosclerosis Risk in Communities Study.

The authors examined the association between lung function, as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity, and the 10-year incidence of coronary heart disease among 14,480 participants in the Atherosclerosis Risk in Communities Study (1987-1998). Separate proportional hazards models were used for FEV1 and forced vital capacity, with gender-specific lung function quartiles and lung function x gender interaction terms. An association between lung function and coronary heart disease was observed in both genders and was stronger among women. After adjustment for age, race, study center, height, height squared, smoking, and cardiovascular disease risk factors, the hazard ratios for the first (lowest), second, and third quartiles of FEV1 were 3.70 (95% confidence interval (CI): 2.19, 6.24), 2.54 (95% CI: 1.49, 4.32), and 2.25 (95% CI: 1.31, 3.87) for women and 1.51 (95% CI: 1.07, 2.13), 1.59 (95% CI: 1.15, 2.20), and 1.52 (95% CI: 1.10, 2.09) for men. After stratification by smoking status, associations were observed in each smoking group for women, while those in men were weaker and less consistent. Similar results were obtained for forced vital capacity. This analysis indicates an association between lung function and incident coronary heart disease that may be stronger in women than in men.

Black or African American↗