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  • 1
    Online Resource
    Online Resource
    An Imbalance Between CD36 and ABCA1 Protein Expression Favors Lipid Accumulation in Stroke-Prone Ulcerated Carotid Plaques
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Stroke Vol. 41, No. 2 ( 2010-02), p. 389-393
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 2 ( 2010-02), p. 389-393
    Abstract: Background— CD36 is a macrophage scavenger receptor mediating the uptake of modified lipoproteins, whereas the ABCA1 transporter counteracts this effect by mediating cellular lipid efflux. Based on a DNA microarray, we previously found that the CD36 and ABCA1 genes were overexpressed in symptom-causing carotid plaques (CP) compared with nonsymptom-causing CP. To evaluate their role in CP destabilization, we conducted detailed immunohistochemical studies on the localization of lipids, CD36 and ABCA1 proteins, extravasated red blood cells, and atheromatous/necrotic tissue. Methods— Ninety-two high-grade ( 〉 70%) stenosing CP obtained from carotid endarterectomy were Oil-red-O–stained for evaluation of neutral lipids. Subgroups of nonsymptom-causing and symptom-causing CP (n=42) were further analyzed by immunostaining adjacent histological sections against CD36 and ABCA1 and examining them microscopically. Results— When compared with nonsymptom-causing CP, the amount of extracellular lipid and the expression of CD36 protein were elevated in symptom-causing CP, but no difference was found in ABCA1 expression. These observations were also confirmed when ulcerated and nonulcerated CP were compared. In ulcerated CP, CD36 protein expression was higher than that of ABCA1, and the opposite was true in nonulcerated CP. CD36 colocalized with extravasated red blood cells and atheromatous or necrotic areas in the various types of CP. Conclusions— Our results suggest that an imbalance between lipid influx (CD36) and efflux (ABCA1) favors lipid accumulation in macrophages of ulcerated CP, thus contributing to plaque destabilization. Furthermore, colocalization of CD36 protein with red blood cells suggests that intraplaque hemorrhages may contribute to the lipid load and thus the stability of CP.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.109.567636
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 1467823-8
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  • 2
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    Online Resource
    Predisposition to Atopic Symptoms to Inhaled Antigens May Protect From Childhood Type 1 Diabetes
    American Diabetes Association ; 2002
    In:  Diabetes Care Vol. 25, No. 5 ( 2002-05-01), p. 865-868
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 25, No. 5 ( 2002-05-01), p. 865-868
    Abstract: OBJECTIVE—To assess the inverse association between type 1 diabetes and asthma to establish whether environmental and/or genetic factors predisposing to asthma or to atopic symptoms to inhaled antigens protect from diabetes. RESEACH DESIGN AND METHODS—Questionnaires were returned by 306 probands with childhood type 1 diabetes, their 506 nonaffected siblings, and 406 age- and sex-matched unaffected population control subjects. The main outcome measures were self-reported physician-diagnosed asthma and atopic symptoms to animal dust and pollen. RESULTS—Risk of diabetes was inversely associated with asthma (odds ratio 0.49 [95% CI 0.24–1.00]), allergy to animal dust (0.67 [0.45–0.99] ), and to a lesser degree to pollen (0.74 [0.51–1.07]) when the probands were compared with the population control subjects. Among the children of the families of an affected proband, the risk of diabetes appeared to be inversely associated with asthma (0.54 [0.27–1.09] ) but not with allergy to animal dust (0.99 [0.66–1.47]) nor allergy to pollen (0.88 [0.62–1.27] ). CONCLUSIONS—The frequency of asthma and atopic symptoms to some inhaled antigens is decreased in individuals with childhood type 1 diabetes. Factors predisposing to atopic symptoms to inhaled antigens may protect from childhood type 1 diabetes.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/diacare.25.5.865
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2002
    detail.hit.zdb_id: 1490520-6
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  • 3
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    Online Resource
    Importance of risk factor clustering in coronary heart disease mortality and incidence in eastern Finland
    Ovid Technologies (Wolters Kluwer Health) ; 1995
    In:  Journal of Cardiovascular Risk Vol. 2, No. 1 ( 1995-02), p. 63-70
    Details
    In: Journal of Cardiovascular Risk, Ovid Technologies (Wolters Kluwer Health), Vol. 2, No. 1 ( 1995-02), p. 63-70
    Type of Medium: Online Resource
    ISSN: 1350-6277
    URL: Article
    DOI: 10.1097/00043798-199502000-00010
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1995
    detail.hit.zdb_id: 2030671-4
    detail.hit.zdb_id: 2646239-4
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  • 4
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    Genome-wide landscape establishes novel association signals for metabolic traits in the Arab population
    Springer Science and Business Media LLC ; 2021
    In:  Human Genetics Vol. 140, No. 3 ( 2021-03), p. 505-528
    Details
    In: Human Genetics, Springer Science and Business Media LLC, Vol. 140, No. 3 ( 2021-03), p. 505-528
    Abstract: While the Arabian population has a high prevalence of metabolic disorders, it has not been included in global studies that identify genetic risk loci for metabolic traits. Determining the transferability of such largely Euro-centric established risk loci is essential to transfer the research tools/resources, and drug targets generated by global studies to a broad range of ethnic populations. Further, consideration of populations such as Arabs, that are characterized by consanguinity and a high level of inbreeding, can lead to identification of novel risk loci. We imputed published GWAS data from two Kuwaiti Arab cohorts ( n  = 1434 and 1298) to the 1000 Genomes Project haplotypes and performed meta-analysis for associations with 13 metabolic traits. We compared the observed association signals with those established for metabolic traits. Our study highlighted 70 variants from 9 different genes, some of which have established links to metabolic disorders. By relaxing the genome-wide significance threshold, we identified ‘novel’ risk variants from 11 genes for metabolic traits. Many novel risk variant association signals were observed at or borderline to genome-wide significance. Furthermore, 349 previously established variants from 187 genes were validated in our study. Pleiotropic effect of risk variants on multiple metabolic traits were observed. Fine-mapping illuminated rs7838666/ CSMD1 rs1864163/ CETP and rs112861901/[ INTS10,LPL ] as candidate causal variants influencing fasting plasma glucose and high-density lipoprotein levels. Computational functional analysis identified a variety of gene regulatory signals around several variants. This study enlarges the population ancestry diversity of available GWAS and elucidates new variants in an ethnic group burdened with metabolic disorders.
    Type of Medium: Online Resource
    ISSN: 0340-6717 , 1432-1203
    URL: Article
    DOI: 10.1007/s00439-020-02222-7
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1459188-1
    SSG: 12
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  • 5
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    Online Resource
    Off-Label Thrombolysis Is Not Associated With Poor Outcome in Patients With Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Stroke Vol. 41, No. 7 ( 2010-07), p. 1450-1458
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 7 ( 2010-07), p. 1450-1458
    Abstract: Background and Purpose— Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. Methods— All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (n=1104). After excluding basilar artery occlusions (n=119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. Results— One or more license contraindications to thrombolysis was present in 51% of our patients (n=499). The most common of these were age 〉 80 years (n=159), mild stroke National Institutes of Health Stroke Scale score 〈 5 (n=129), use of intravenous antihypertensives prior to treatment (n=112), symptom-to-needle time 〉 3 hours (n=95), blood pressure 〉 185/110 mm Hg (n=47), and oral anticoagulation (n=39). Age 〉 80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. Conclusions— Off-license thrombolysis was not associated with poorer clinical outcome, except for age 〉 80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.109.576140
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 1467823-8
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  • 6
    Online Resource
    Online Resource
    Adipophilin Expression Is Increased in Symptomatic Carotid Atherosclerosis : Correlation With Red Blood Cells and Cholesterol Crystals
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Stroke Vol. 38, No. 6 ( 2007-06), p. 1791-1798
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. 6 ( 2007-06), p. 1791-1798
    Abstract: Background and Purpose— Adipophilin is an adipose differentiation–related protein expressed in lipid-containing cells. Using DNA microarray analysis, we previously found the adipophilin gene ( ADFP ) to be overexpressed in symptomatic carotid plaques (CP). This led us to further examine the role of adipophilin in carotid atherosclerosis relative to symptom status. Methods— Ninety-eight high-grade ( 〉 70%) CPs were obtained in carotid endarterectomy. The relative expression of ADFP mRNA was measured by quantitative real-time RT-PCR, and the relative amount of adipophilin protein was quantified with Western blotting. Detailed topographical correlations with extravasated red blood cells and extracellular cholesterol crystals were obtained by means of immunohistochemistry. Results— The relative expression of ADFP mRNA was increased in symptomatic compared with asymptomatic CPs at both the mRNA level (1.82±0.19[SE] versus 1.25±0.15, P =0.012) and the protein level (1.04±0.23 versus 0.46±0.14, P =0.043). Adipophilin colocalized with macrophage foam cells, extravasated red blood cells ( P 〈 0.0001), and cholesterol crystals ( P 〈 0.0001), and its expression associated with macroscopic ulceration of CP ( P 〈 0.0001). Conclusions— Intraplaque hemorrhages may contribute to intracellular lipid accumulation and consequent adipophilin expression. Because adipophilin blocks cholesterol efflux from lipid-laden cells, they may die and develop a necrotic lipid core, thereby destabilizing the plaque.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.106.478867
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1467823-8
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  • 7
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    Online Resource
    Genome-wide association study identifies novel risk variants from RPS6KA1, CADPS, VARS, and DHX58 for fasting plasma glucose in Arab population
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-01-13)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-01-13)
    Abstract: Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 ( RPS6KA1 ) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; β-discovery = 8.315; β-replication = 3.442; β-combined = 6.551). Further, three suggestive associations (p-values  〈  8.2E-06) with high FPG were observed at rs487321 ( CADPS ), rs707927 ( VARS and 2Kb upstream of VWA7 ), and rs12600570 ( DHX58 ); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-019-57072-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 8
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    Online Resource
    Maternal First-Trimester Enterovirus Infection and Future Risk of Type 1 Diabetes in the Exposed Fetus
    American Diabetes Association ; 2002
    In:  Diabetes Vol. 51, No. 8 ( 2002-08-01), p. 2568-2571
    Details
    In: Diabetes, American Diabetes Association, Vol. 51, No. 8 ( 2002-08-01), p. 2568-2571
    Abstract: Previous studies have suggested that enterovirus infections during pregnancy may increase the risk of type 1 diabetes in the offspring. Our aim was to evaluate the role of first trimester enterovirus infections in a larger cohort of pregnant women. Two series of pregnant women were analyzed as follows: 948 women (series 1) and 680 women (series 2) whose child developed clinical diabetes before the ages of 15 or 7 years, respectively. An equal number of control women with a nondiabetic child was selected. Acute enterovirus infections were diagnosed by measuring IgM class antibodies against coxsackievirus B5 (series 1) and a mixture of coxsackievirus B3, coxsackievirus A16, and echovirus 11 antigens (series 2). In series 2, all sera were also analyzed for IgG class antibodies against an enterovirus peptide antigen. In addition, 152 randomly selected case-control pairs and all IgM-positive mothers’ sera were tested for enterovirus RNA (series 2). In series 1, 3.1% of case women had IgM antibodies against coxsackievirus B5 antigen compared with 4.1% of control women (NS). In series 2, 7.1% of case and 5.3% of control women had IgM against the mixture of enterovirus antigens (NS). IgG class enterovirus antibodies did not differ between the groups. Enterovirus RNA was found only in one case woman (0.3%) of the subgroup of samples and in 5.7% of 70 IgM-positive women. The results suggest that enterovirus infection during the first trimester of pregnancy is not associated with increased risk for type 1 diabetes in the child.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/diabetes.51.8.2568
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2002
    detail.hit.zdb_id: 1501252-9
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  • 9
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    Online Resource
    Global comparative transcriptomes uncover novel and population-specific gene expression in esophageal squamous cell carcinoma
    Springer Science and Business Media LLC ; 2023
    In:  Infectious Agents and Cancer Vol. 18, No. 1 ( 2023-08-28)
    Details
    In: Infectious Agents and Cancer, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2023-08-28)
    Abstract: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and is one of the deadliest gastrointestinal malignancies. Despite numerous transcriptomics studies to understand its molecular basis, the impact of population-specific differences on this disease remains unexplored. Aims This study aimed to investigate the population-specific differences in gene expression patterns among ESCC samples obtained from six distinct global populations, identify differentially expressed genes (DEGs) and their associated pathways, and identify potential biomarkers for ESCC diagnosis and prognosis. In addition, this study deciphers population specific microbial and chemical risk factors in ESCC. Methods We compared the gene expression patterns of ESCC samples from six different global populations by analyzing microarray datasets. To identify DEGs, we conducted stringent quality control and employed linear modeling. We cross-compared the resulting DEG lists of each populations along with ESCC ATLAS to identify known and novel DEGs. We performed a survival analysis using The Cancer Genome Atlas Program (TCGA) data to identify potential biomarkers for ESCC diagnosis and prognosis among the novel DEGs. Finally, we performed comparative functional enrichment and toxicogenomic analysis. Results Here we report 19 genes with distinct expression patterns among populations, indicating population-specific variations in ESCC. Additionally, we discovered 166 novel DEGs, such as ENDOU, SLCO1B3, KCNS3, IFI35, among others. The survival analysis identified three novel genes (CHRM3, CREG2, H2AC6) critical for ESCC survival. Notably, our findings showed that ECM-related gene ontology terms and pathways were significantly enriched among the DEGs in ESCC. We also found population-specific variations in immune response and microbial infection-related pathways which included genes enriched for HPV, Ameobiosis, Leishmaniosis, and Human Cytomegaloviruses. Our toxicogenomic analysis identified tobacco smoking as the primary risk factor and cisplatin as the main drug chemical interacting with the maximum number of DEGs across populations. Conclusion This study provides new insights into population-specific differences in gene expression patterns and their associated pathways in ESCC. Our findings suggest that changes in extracellular matrix (ECM) organization may be crucial to the development and progression of this cancer, and that environmental and genetic factors play important roles in the disease. The novel DEGs identified may serve as potential biomarkers for diagnosis, prognosis and treatment.
    Type of Medium: Online Resource
    ISSN: 1750-9378
    URL: Article
    DOI: 10.1186/s13027-023-00525-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2251117-9
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