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C S Rose

Publications and source records attributed to C S Rose.

At least 19 recordsLinked to original sources
PubMed2006

Genetic analysis of the estrogen-related receptor alpha and studies of association with obesity and type 2 diabetes.

BACKGROUND: The estrogen-related receptor alpha (ERRalpha or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRalpha (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction with the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), ERRalpha regulates key enzymes involved in the beta-oxidation of fatty acids. RESULTS: By screening 48 overweight or obese subjects for variants in the exons, exon-intron boundaries and 1000 base pairs (bp) of the promoter region of ESRRA using bi-directional nucleotide sequencing, we identified seven variants. Four rare variants had minor allele frequencies (MAF) below 1%: Pro369Pro, Gly406Asp, 3'UTR+418G>A, 3'UTR+505C>A. Two single-nucleotide polymorphisms, Pro116Pro and IVS6+65C>T (MAF 15%), were in complete linkage disequilibrium (LD) (r (2)=1). We also confirmed the presence of a reported 23 bp microsatellite repeat (ESRRA23). The Pro116Pro and ESRRA23 variants were not associated with obesity, type 2 diabetes or related phenotypes in a large population-based study of 6365 Danish whites. The two variants were examined for interactions with variants in the peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -beta; however, no evidence of epistatic effects between the variants was demonstrated. CONCLUSION: The ESRRA23 and Pro116Pro variants of the gene encoding ERRalpha are not associated with obesity, type 2 diabetes or related quantitative traits in the examined Danish whites.

Aged↗
PubMed2005

Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population.

AIMS/HYPOTHESIS: The hepatocyte nuclear factor (HNF)-4alpha is an orphan nuclear receptor, which plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion. The gene encoding HNF-4alpha (HNF4A) is located on chromosome 20q12-q13 in a region that in several studies has shown linkage with type 2 diabetes. Recently, two independent studies identified single nucleotide polymorphisms (SNPs) in a 90-kb region spanning HNF4A, which showed strong association with type 2 diabetes in the Finnish and Ashkenazi Jewish populations. In an attempt to replicate and extend these findings, we selected four SNPs in the same HNF4A region, which in the Finnish and Ashkenazi Jewish populations were associated with type 2 diabetes, and examined their relationships with type 2 diabetes and prediabetic phenotypes in the Danish Caucasian population. METHODS: The rs1884614, rs2425637, rs1885088 and rs3818247 were analysed in case-control studies of 1387, 1429, 1417 and 1371 type 2 diabetic patients and 4766, 4727, 4665 and 4748 glucose-tolerant subjects respectively. Genotype-quantitative trait analyses comprised 4430, 4394, 4336 and 4413 middle-aged glucose-tolerant subjects from the population-based Inter99 cohort for the rs1884614, rs2425637, rs1885088 and rs3818247 respectively. RESULTS: The risk allele of the rs1884614, which is located 4 kb upstream of the HNF4A P2 promoter, was associated with type 2 diabetes (odds ratio [OR]=1.14, p=0.02) and with a subtle increase in post-OGTT plasma glucose levels in glucose-tolerant subjects (additive model, p=0.05). CONCLUSIONS/INTERPRETATION: Consistent with results from studies of Finnish and Ashkenazi Jewish subjects, variation near the P2 region of HNF4A is associated with type 2 diabetes in the Danish population.

Cohort Studies↗
PubMed2005

Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes.

AIMS/HYPOTHESIS: The cytokine interleukin 6 (IL-6) is an essential regulator of the acute phase response associated with insulin-resistant states including type 2 diabetes and obesity. Three polymorphisms at positions -597, -572, and -174 of the IL6 promoter have been reported to influence IL6 transcription. The aim of this study was to investigate whether the IL6 promoter polymorphisms were associated with features of the WHO-defined metabolic syndrome and related quantitative traits in 7,553 Caucasian Danes. METHODS: Using analysis of PCR-generated primer extension products by mass spectrometry we examined -597 G/A, -572 G/C, and -174 G/C IL6 variants in the population-based Inter99 study cohort of middle-aged people (n=6,164) and in a group of type 2 diabetic patients (n=1,389). RESULTS: The -174 G/C and -597 G/A polymorphisms were in strong linkage disequilibrium (R(2)=0.95). In the Inter99 cohort the -174 G-allele was associated with insulin resistance (p<0.02) and dyslipidaemia (p<0.007) whereas the C-allele of the -572 polymorphism was associated with increased serum insulin release during an OGTT (p<0.0005). Composite genotype or haplotype analyses of all 3 IL6 promoter variants showed associations with type 2 diabetes (p<0.002), obesity (p<0.02), and the metabolic syndrome (p<0.01). CONCLUSIONS: The present studies suggest that single-nucleotide polymorphisms and composite genotypes or haplotypes of the IL6 promoter may be associated with several features of the metabolic syndrome in Caucasians.

Base Sequence↗
PubMed2005

Genome-wide search for sarcoidosis susceptibility genes in African Americans.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

Black or African American↗
PubMed2005

Studies of relationships between the GLUT10 Ala206Thr polymorphism and impaired insulin secretion.

AIMS: This study aimed to investigate if the previously observed association between the GLUT10 Ala206Thr polymorphism and variation in fasting and oral glucose-induced serum insulin concentrations could be replicated in a large-scale population-based cohort of Danish whites. METHODS: The GLUT10 Ala206Thr polymorphism was genotyped in a case-control study of 880 Type 2 diabetic patients and 4372 glucose-tolerant control subjects. The latter group was also enrolled in an assessment of fasting and post-OGTT circulating levels of plasma glucose and serum insulin in relation to genotype. The variant was genotyped by analysis of PCR-generated primer extension by matrix-assisted laser desorption/ionization time-of-flight analysis. RESULTS: The Ala206Thr variant was equally frequent among Type 2 diabetic patients and glucose-tolerant subjects (P = 0.9) and there was no difference in the distribution of genotype groups (P = 1.0). In the 4372 glucose-tolerant subjects there was no statistically significant association between the polymorphism and levels of fasting and post-oral glucose tolerance test plasma glucose and serum insulin along with the insulinogenic index and the homeostasis model of assessment for insulin resistance and insulin secretion. Likewise, in an age-stratified subgroup comprising 1264 subjects, we observed no relationships between the GLUT10 polymorphism and the selected metabolic features. CONCLUSIONS: The GLUT10 Ala206Thr polymorphism is not associated with Type 2 diabetes in the Danish population. Furthermore, in the present large-scale cohort, the polymorphism does not associate with phenotypes such as fasting and oral glucose-induced levels of plasma glucose and serum insulin.

Adult↗
PubMed2005

Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity.

BACKGROUND: Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) is a recently identified homologue of the tissue specific coactivator PGC-1alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1alpha is involved in adipogenesis, mitochondrial biogenesis, fatty acid beta oxidation, and hepatic gluconeogenesis. METHODS: We studied variation in the coding region of human PPARGC1B in Danish whites and related these variations to the prevalence of obesity and type 2 diabetes in population based samples. RESULTS: Twenty nucleotide variants were identified. In a study of 525 glucose tolerant subjects, the Ala203Pro and Val279Ile variants were in almost complete linkage disequilibrium (R2 = 0.958). In a case-control study of obesity involving a total of 7790 subjects, the 203Pro allele was significantly less frequent among obese participants (p = 0.004; minor allele frequencies: normal weight subjects 8.1% (95% confidence interval: 7.5 to 8.8), overweight subjects 7.6% (7.0 to 8.3), obese subjects 6.5% (5.6 to 7.3)). In a case-control study involving 1433 patients with type 2 diabetes and 4935 glucose tolerant control subjects, none of the examined variants were associated with type 2 diabetes. CONCLUSIONS: Variation of PGC-1beta may contribute to the pathogenesis of obesity, with a widespread Ala203 allele being a risk factor for the development of this common disorder.

Aged↗
PubMed2004

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release.

AIMS/HYPOTHESIS: The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals. METHODS: We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middle-aged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes. RESULTS: There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middle-aged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels. CONCLUSIONS/INTERPRETATION: The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.

Adult↗
PubMed2001

High beryllium-stimulated TNF-alpha is associated with the -308 TNF-alpha promoter polymorphism and with clinical severity in chronic beryllium disease.

Beryllium (Be)-antigen stimulates tumor necrosis factor-alpha (TNF-alpha) from bronchoalveolar lavage (BAL) cells in chronic beryllium disease (CBD). This study tested the hypothesis that high concentrations of Be-stimulated TNF-alpha are related to polymorphisms in the TNF-alpha promoter and clinical markers of disease severity in CBD. Demographic and clinical information was obtained from patients with CBD (n = 20). TNF-alpha concentrations were measured in BAL cell culture supernatant by ELISA. A priori, we categorized CBD subjects as either high or low TNF-alpha producers using a cutoff of 1,500 pg/ml. The TNF-alpha promoter sequence, +64 to -1045, was determined by direct sequencing. Human leukocyte-associated antigen (HLA)-DPB1 and -DRB1 genotyping was determined by polymerase chain reaction (PCR). High Be-stimulated TNF-alpha was associated with TNF2 alleles, Hispanic ethnicity, presence of HLA-DPB1 Glu69, and absence of HLA-DR4. Be-stimulated TNF-alpha concentrations correlated with markers of disease severity, including chest radiograph, beryllium lymphocyte proliferation, and spirometry. We found no novel TNF-alpha promoter polymorphisms. These data suggest that the TNF2 A allele at -308 in the TNF-alpha promoter region is a functional polymorphism, associated with a high level of Be-antigen-stimulated TNF-alpha and that these high TNF-alpha levels indicate disease severity in CBD.

Antigens↗
PubMed2001

Indirect and direct gas exchange at maximum exercise in beryllium sensitization and disease.

STUDY OBJECTIVES: To determine whether pulse oximetry accurately estimates arterial blood gas measurements during exercise in the assessment of chronic beryllium disease (CBD) and beryllium sensitization (BeS). DESIGN: Participants underwent maximal exercise physiology testing in a clinical-practice setting. Oxygen saturation in the blood was measured through an indwelling arterial line and by pulse oximetry. SETTING: All exercise physiology tests were performed in the pulmonary physiology unit of the National Jewish Medical and Research Center (NJMRC) between December 1985 and November 1998. PATIENTS: We analyzed the exercise physiology data for 168 individuals who were referred to NJMRC for evaluation of possible CBD and underwent exercise testing. On evaluation, they subsequently received diagnoses of either CBD or BeS. RESULTS: In BeS subjects, the percentage of oxygen saturation as measured by pulse oximetry (SpO(2)) often underestimated the percentage of arterial oxygen saturation (SaO(2)) (mean [+/- SD] underestimation, 0.88 +/- 4.6%) at maximum exercise and showed no significant correlation (r = -0.13; p = 0.3). The use of SpO(2) misclassified 14.9% of BeS subjects as having abnormal gas exchange levels (< 90%) that were normal by arterial blood gas measurement. In contrast, SpO(2) and SaO(2) values correlated at maximum exercise in CBD subjects (r = 0.55 [corrected]; p = 0.0001) without exhibiting SpO(2) underestimation of SaO(2), and misclassification occurred in only 5.9%. CONCLUSIONS: These data suggest that pulse oximetry cannot be used reliably to distinguish between CBD and BeS and, thus, is not an adequate substitute for arterial blood gas analysis with exercise.

Adult↗
PubMed2000

Bronchoalveolar lavage macrophage-lymphocyte clusters in granulomatous disease are linked to lymphocytosis.

BACKGROUND AND AIM OF THE WORK: Clusters of macrophages associated with lymphocytes (ML clusters) have been observed among the bronchoalveolar lavage (BAL) cells of patients with pulmonary disease. We tested the hypothesis that ML clusters might be found among the BAL cells from patients with granulomatous disease. METHODS: We measured the number of ML clusters among the BAL cells from normal controls (n = 13), sarcoidosis patients (n = 18), beryllium-sensitized (BeS) patients (n = 21) and chronic beryllium disease (CBD) patients (n = 15). RESULTS: ML clusters were observed in the BAL cells of all groups, but at different frequencies: normal 8.5% (median, range 2-15%); BeS 7% (range 2-31%); sarcoidosis 14% (range 4-50%); and CBD 17% (range 6-73%). This data suggested that ML clusters were increased in granulomatous lung disease. However, the percentage of ML clusters strongly correlated with the BAL lymphocyte percentage (rho = 0.79). Cohort analysis showed that increases in macrophages having 2, 3 or > 3 associated lymphocytes correlated with an increase in lymphocyte percentage. CONCLUSIONS: An increase in ML clusters in BAL cells is not specific for granulomatous disease and is associated with the increase in BAL lymphocytes.

Adult↗
PubMed1998

The expression pattern of thyroid hormone response genes in remodeling tadpole tissues defines distinct growth and resorption gene expression programs.

Thyroid hormone (TH) induces dramatic skeletal and tissue remodeling of the anuran head and body at metamorphosis. The expression pattern of TH up-regulated genes has been correlated with tissues that either grow or resorb at metamorphosis. Whereas the expression of the thyroid hormone receptors in Xenopus laevis tadpoles is ubiquitous, the locations where many of the TH up-regulated genes are activated fall into distinct classes. Genes in the early response class are expressed predominantly in cartilage and brain regions undergoing cell proliferation and at a higher level in the remodeling and growing body than in the resorbing tail. In contrast, expression of genes in the delayed response class is highest in resorbing tissues and higher in the tail than in the body within the subepidermal fibroblast layer, further indicating that this single cell layer is involved in tissue resorption. The expression boundary of delayed response class genes in the subepidermal fibroblasts in the body correlates with epidermal lamella invasion and subsequent adult skin differentiation. Differences in the expression patterns of stromelysin-3 and the delayed response proteinases in the head delineate separate programs of tissue resorption, one for the loss of epithelial structures, and one for the loss of cartilages. Expression of the type III deiodinase is up-regulated in growing tissues nearing completion of their metamorphic changes, suggesting a role for the deiodinase in modulating the influence of TH on these tissues.

Animals↗
PubMed1998

"Lifeguard lung": endemic granulomatous pneumonitis in an indoor swimming pool.

OBJECTIVES: Two sequential outbreaks of respiratory disease among lifeguards at an indoor swimming pool with water spray features were investigated. METHODS: Questionnaires were administered to recreation center employees following each outbreak. Respondents reporting 2 or more pool-related symptoms were offered clinical evaluation, including bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Pool air and water were sampled for fungi, bacteria, amoebae, endotoxin, and respirable particulates. RESULTS: Thirty-three lifeguards had noncaseating granulomas on biopsy and/or bronchoalveolar lavage lymphocytosis. Attack rates for the outbreaks were 27% and 65%. Case patients had higher cumulative hours of work and tended to work more hours per week. Analyses indicated increased levels of endotoxin in pool air and water (relative to control pools) and gram-negative bacterial colonization of water sprays. Use of water spray features generated a 5.2-fold increase in the number of respirable particles and up to an 8-fold increase in air endotoxin levels. CONCLUSIONS: Lifeguards in this indoor swimming pool developed granulomatous lung disease associated with endotoxin-containing respirable bioaerosols from water spray features, which ventilation system improvements did not prevent.

Adolescent↗
PubMed1997

Sarcoidosis.

Explore the source record for details and available documents.

Adrenal Cortex Hormones↗
PubMed1997

The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases.

The TWIST gene maps to 7p21 and mutations in the gene have been reported in the Saethre-Chotzen form of craniosynostosis. The position of the Saethre-Chotzen gene has previously been refined by FISH analysis of four patients carrying balanced translocations involving 7p21 which suggested that it was located between D7S488 and D7S503. We report here that the breakpoints in four translocation patients do not interrupt the coding sequence of the TWIST gene and thus most likely act through a positional effect. Twelve Saethre-Chotzen cases were found to have TWIST mutations. Four of these families had been used as part of the linkage study of the Saethre-Chotzen locus. The mutations detected included missense and nonsense mutations and three cases of a 21 bp duplication. Although phenotypically diagnosed as having Saethre-Chotzen syndrome, three families were found to have a pro250arg mutation of FGFR3.

Acrocephalosyndactylia↗
PubMed1995

Endemic work-related febrile respiratory illness among construction workers.

Construction workers building Denver International Airport (DIA) reported work-related respiratory and flulike symptoms of several months duration. We performed a cross-sectional interview study of 495 randomly selected DIA workers from six contractors in comparison with preplacement workers. We defined cases as workers with two work-attributed lower respiratory symptoms and one work-attributed systemic symptom. Case rates were significantly higher among DIA workers (34%) compared with those who had never worked at DIA (2%). Risk factors for illness included exposure to fireproofing (OR, 4.21; 95% CI, 1.95-9.08), work in tunnels and adjoining areas (OR, 3.07; 95% CI, 1.84-5.12), length of DIA employment (OR, 0.65; 95% CI, 0.46-0.92), and preexisting bronchitis (OR, 2.43; 95% CI, 1.17-5.05). Our industrial hygiene investigation revealed alkaline dust (pH 11) present at a worksite associated with elevated risk of illness, and we identified airborne Penicillium mold widely distributed indoors at DIA. Clinical evaluation of 26 self-identified symptomatic DIA employees, including bronchoalveolar lavage and biopsy in 10, revealed work-related asthma in three workers and histologic evidence of chronic bronchitis in four who had never smoked. We concluded that future investigations of endemic work-related febrile respiratory illness among construction workers should evaluate its association with indoor exposure to dusts from alkaline fireproofing, Penicillium mold, mycotoxins, and bacterial bioaerosols.

Adult↗
PubMed1994

Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.

Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539-540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre-Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p.

Acrocephalosyndactylia↗
PubMed1994

Evidence for locus heterogeneity in acrocephalosyndactyly: a refined localization for the Saethre-Chotzen syndrome locus on distal chromosome 7p--and exclusion of Jackson-Weiss syndrome from craniosynostosis loci on 7p and 5q.

Craniosynostosis (premature fusion of the skull sutures) occurs as a clinically heterogeneous group of disorders, frequently involving digital abnormalities. We have previously provisionally assigned the gene for one such condition, Saethre-Chotzen syndrome (ACS III), to chromosome 7p. Linkage analysis is now reported between ACS III and dinucleotide repeat loci on distal 7p. The maximum lod scores, Zmax, were 5.57 at a recombination fraction of .05, with D7S488, and 4.74 at a recombination fraction of .05, with D7S493. Only weak linkage, not reaching significance, was found with distal markers (D7S513 and afm281vc9) and a proximal marker (D7S516). Multipoint analysis shows that the disease locus lies between D7S513 and D7S516. Analysis of individual recombinants shows that the most likely position is between D7S493 and D7S516. Linkage data in regard of Jackson-Weiss syndrome demonstrate that this autosomal dominant form of acrocephalosyndactyly does not map to the ACS III region on 7p or to the acrocephalosyndactyly locus on 5q (Boston type). These findings underline the genetic heterogeneity among the different clinical conditions manifesting with acrocephalosyndactyly.

Acrocephalosyndactylia↗