SEARCH · PubMed Health

Results for “Reference panel”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

PubMed1998

Structural analysis and evaluation of the aldosterone synthase gene in hypertension.

Anomalies in either of the tightly linked genes encoding the enzymes CYP11B1 (11beta-hydroxylase) or CYP11B2 (aldosterone synthase) can lead to important changes in arterial pressure and are responsible for several monogenically inherited forms of hypertension. Mutations in these genes or their regulatory regions could thus contribute to genetic variation in susceptibility to essential hypertension. To test this hypothesis, we performed 2 complementary studies of the CYP11B1/CYP11B2 locus in essential hypertension. After characterizing a DNA contig containing the CYP11B1 gene and mapping the gene in the Centre d'Etudes du Polymorphisme Humain reference panel of families, we performed a linkage study with 292 hypertensive sibling pairs and a highly informative microsatellite marker near CYP11B1. We also analyzed the association of 2 frequent biallelic polymorphisms of the CYP11B2 gene, 1 in the promoter at position -344 (-344C/T) and the other, a common gene conversion in intron 2, with hypertension in 380 hypertensive patients and 293 normotensive individuals. Statistical analyses did not show significant linkage of the CYP11B1 microsatellite marker to hypertension. No positive association with hypertension was found with the gene conversion in intron 2, but a positive association with hypertension was found with the -344T allele. The hypertensive and normotensive samples differed significantly in both genotype (P=0.023) and allele frequencies (P=0.010). Our data suggest a modest contribution of the CYP11B2 gene to essential hypertension.

Adult↗

PubMed1989

Comparison of single breath carbon monoxide diffusing capacity and pressure-volume curves in detecting emphysema.

To evaluate the sensitivity of diffusing capacity (DLCO) and pressure-volume (P-V) curves in the detection of emphysema, these tests were compared with pathologic assessment of emphysema in patients undergoing lung resection for a localized tumor, and with the overall extent of emphysema as assessed by computed tomography (CT). The resected lung specimens were fixed in the inflated state and cut at 1-cm intervals in the horizontal plane. The pathologic extent of emphysema was quantitated by comparison with a standard reference panel of emphysema grading. The overall extent of emphysema on CT was assessed by a visual scoring system in a total of 55 patients, 19 undergoing lung resection and 36 not undergoing lung resection. Analysis of 37 patients by pathology scores revealed 18 with no or trivial emphysema (emphysema grades less than or equal to 5; mean grade, 2.2 +/- SD 2.6) and 19 with emphysema (grades greater than or equal to 10; mean grade, 33.2 +/- SD 24.2). Diffusing capacity, the ratio of DLCO to alveolar volume (DLCO/VA), maximal lung elastic recoil (PLmax), and lung elastic recoil at 90% of total lung capacity (PL90) were significantly different between the two groups, whereas K (the exponential constant describing the shape of the P-V curve) was not. The pathology grade of emphysema showed a significant correlation with (DLCO) (r = -0.53) and DLCO/VA (r = -0.55), which was greater than the correlation with PLmax (r = -0.42) and PL90 (r = -0.43).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Pulmonary capillary blood volume in emphysema.

We determined single breath diffusing capacity (DLCO) and pulmonary capillary blood volume (Vc) in a total of 110 patients, who were being evaluated for resectional lung surgery for a localized tumor or lesion. Pathologic assessment of emphysema was obtained in 55 cases who had resection of a lung or an upper lobe, based on a standard reference panel for emphysema grading. In 86 cases, the extent of emphysema was quantitated by computed tomography (CT) of the chest. There was a significant negative correlation between Vc and emphysema assessed by either pathology or CT (r = about -0.5, p less than 0.001) similar to the correlation between DLCO and the extent of emphysema. Results of Vc were significantly lower in cases with moderate emphysema (pathologic grade greater than or equal to 30) than those with no emphysema (grade less than or equal to 5) (p less than 0.001) or mild emphysema (grade 10 to 25) (p less than 0.05), and they were significantly lower (p less than 0.05) in the group with mild emphysema compared with the group with no emphysema on pathologic assessment similar to DLCO results. Although Vc was reduced in emphysema, determination of Vc did not result in improved discrimination in separating cases with emphysema from those without emphysema when compared with DLCO.

Adult↗

PubMed2004

Burkholderia cenocepacia lipopolysaccharide, lipid A, and proinflammatory activity.

Organisms from the Burkholderia cepacia complex are important pathogens in cystic fibrosis and are associated with increased rates of sepsis and death. These organisms comprise nine closely related species known as genomovars. B. cenocepacia (genomovar III) is the most prevalent and appears the most virulent. We investigated the biological activity of a reference panel of strains using whole-cell lysates to induce septic-shock related cytokines from differentiated human monocytic cells. We found varying biological activity within and between genomovars, with B. cenocepacia strains possessing the greatest cytokine induction activity. This activity was CD-14 dependent, suggesting that LPS was responsible for the cytokine induction. Cytokine induction was not simply related to the expression of rough or smooth LPS. We purified LPS from two strains, B. cenocepacia LMG 12614 and B. multivorans LMG 14273, each possessing rough LPS. Divergence in biological activity of the two genomovars was preserved when human monocytic cells were stimulated with purified LPS. Lipid A purified from LMG 14273 and LMG 12614 were analyzed by matrix-assisted laser desorption ionization/time of flight mass spectrometry. Lipid A from the less effective cytokine inducer LMG 14273 was found to be missing a beta-hydroxymyristate (3-OH C14:0) relative to the lipid A of B. cenocepacia LMG 12614.

Burkholderia cepacia complex↗

PubMed2004

Microsatellite instability and MLH1 promoter methylation in human retinoblastoma.

PURPOSE: To investigate the link between microsatellite instability and epigenetic silencing of the MLH1 gene in the human retinoblastoma genome. METHODS: Methylation at the 5' region of MLH1 was studied, along with its protein expression level by using immunohistochemical staining in 51 retinoblastoma tumors and 2 retinoblastoma cell lines. Also assessed was the genomic stability of 26 retinoblastoma DNAs from microdissected tumor tissue and matched normal retina tissue obtained from the same patient by microsatellite instability (MSI) analysis. The National Cancer Institute-designed reference panel, and 85 markers on chromosomes 1, 6, 9, and 13 were used. RESULTS: Hypermethylation of the MLH1 promoter was detected in the WERI-Rb1 cell line and in 34 (67%) of the 51 tumors, but not in cell line Y79 and the other 17 tumors. MLH1 hypermethylation was associated with null MLH1 protein expression (P < 0.0005) and with well-differentiated histology (P < 0.05). MSI at three markers (D2S123, D6S470, and D13S265) was frequently identified among 26 retinoblastoma specimens with matched normal DNA. Among these 26 retinoblastomas, high-frequency MSI (MSI-H) tumors were detected in 19% (5/26) and low-frequency MSI (MSI-L) in another 19% (5/26). The remaining 62% (15/26) were genetically stable (MSS). MSI status (MSS, MSI-L, and MSI-H) was not associated with MLH1 promoter hypermethylation (P = 0.088; Kruskal-Wallis test). CONCLUSIONS: Epigenetic silencing of the DNA repair gene MLH1 by promoter hypermethylation is a frequent event in retinoblastoma. The results showed that somatic genetic changes involving MSI occur in a subset of retinoblastoma and implicated the presence of a defective DNA mismatch repair pathway resulting in MSI in retinoblastoma.

Adaptor Proteins, Signal Transducing↗

PubMed2003

InterRett and RettBASE: International Rett Syndrome Association databases for Rett syndrome.

In 2001, the International Rett Syndrome Association funded the establishment of a World Wide Web-based database to collect and display the genetic data of children and adults with Rett syndrome from around the world. RettBASE ( ) encompasses both published and unpublished data; includes pathogenic mutations, benign polymorphisms, and sequence variations of uncertain significance; and has a range of query capabilities, allowing for simple or complex interrogation of the database. To undertake genotype-phenotype correlations and to identify the likely subtle differences in phenotype, detailed phenotype data on large samples will be provided by the International Rett Syndrome Association International Phenotype database InterRett. InterRett is under development by the Australian Rett syndrome study group at the Telethon Institute for Child Health Research in Perth, Western Australia. It will collect data from clinicians and families and provide deidentified, collated data on the Internet ( ). Data records will be linked with RettBASE through a common unique identifier. An international reference panel is advising on the development of the database. Data collection procedures from families and clinicians are currently being piloted. Full data collection from both groups began in the second half of 2003. Concurrently, the output database will be developed to provide deidentified individual records and collated data for clinicians and researchers and collated data for families and the general public. This Web-based database will be an invaluable resource for understanding the nature of the disorder and managing children and adults with Rett syndrome.

Data Collection↗

PubMed2026

Quantitative trait loci mapping of gene expression and chromatin accessibility in primary fibroblasts reveals shared allelic effects between Latin American and European ancestries.

BACKGROUND: Quantitative Trait Locus (QTL) analysis of molecular data has identified genetic variants associated with traits such as gene expression, and colocalization of these functional QTL with GWAS risk loci has offered insights into the genetic basis of human disease. We employed gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) obtained from human primary fibroblasts to investigate quantitative trait loci (QTLs) in cohorts ascertained for bipolar disorder of European (n = 150) and Latin American (n = 96) ancestries. RESULTS: Leveraging data from three countries of origin (The Netherlands, Colombia, Costa Rica) within our cohort, we characterized differences among individuals at the SNP, gene, and accessible-chromatin levels to compute ancestry-specific expression (e)QTLs and chromatin-accessibility (ca)QTLs. Across ancestries, we observed R2 ≥ 0.93 for eQTL effect sizes and R2 ≥ 0.95 for caQTLs, indicating a high degree of concordance. Integrating chromatin data with expression and genotype information enabled precise fine-mapping of eQTLs, yielding 203 genes with high-confidence (posterior probability > 90%) candidate regulatory pathways. In downstream analyses, transcriptome-wide (TWAS) and chromatin-wide (CWAS) association studies with brain- and skin-related GWAS identified 36 TWAS-significant genes and 77 CWAS-significant open chromatin regions. CONCLUSIONS: These findings underscore the shared genetic regulatory mechanisms across European and Latin American ancestries, while demonstrating that ancestry-specific reference panels enhance the accuracy of TWAS and CWAS in diverse populations. More broadly, this study highlights the value of paired multi-omic datasets from diverse cohorts for interpreting disease-associated genetic variation.

Humans↗

PubMed1980

Mesothelioma in man and experimental animals.

Asbestos has been established as the cause of most cases of diffuse malignant mesothelioma occurring in the industrialized world. The morphology of mesothelioma may be complex, and the employment of chemical, histochemical and ultrastructural studies are often helpful in identification. Diagnostic difficulties may to some degree blur the extent of its prevalence and reliance on exposure history may not reveal its association with asbestos. Reference panels can be useful in assessing the former and analysis of lung tissue asbestos content may help to clarify the latter, especially in the low dose range. Electron microscopy may prove to be of assistance in this respect, possibly with particular attention to the peripheral areas of the lung. Animal experimentation has supported epidemiologic conclusions and revealed the phenomenon of fiber carcinogenesis. The morphology of mesothelioma in experimental animals is very similar to that in humans, including ultrastructural and biochemical features.

Animals↗

PubMed2024

Larval density can be used to predict genetic modifiers of glucagon signaling in Drosophila melanogaster.

Obesity is a growing concern. 42.3% of people in the U.S were considered obese between 2017-2018. Much is still unknown about the genetic components that contribute to weight gain. In humans, the hormone glucagon is a major contributor to the body's energy regulation as it signals for the breakdown of lipids. Treatments targeting the glucagon pathway have helped patients with both weight loss and appetite suppression. Understanding the genetic modifiers of glucagon signaling and its downstream pathways could enable the development of a wider variety of effective therapeutics. In this study, we blocked the glucagon pathway in Drosophila melanogaster by reducing the expression of the fly ortholog of the glucagon receptor (AKHR). We then crossed our model to the Drosophila Genetic Reference Panel (DGRP) and looked for natural variation in fat content. We used variation in larval density to identify candidate modifier genes through a genome-wide association study. We then tested these modifier genes by increasing or decreasing their expression in the AKHR model. We screened these candidates initially with the same density assay used in the original study to narrow down to four candidate genes that substantially impacted the density of the larvae: THADA, AmyD, GluRIIC, and CG9826. We further characterized these candidates using biochemical assays to analyze stored metabolites such as triglycerides, glucose, glycogen, and protein under control, high sugar, and high fat conditions to see if the larvae are resistant to environmental changes. Our results indicate consistency between the results of the density assay and direct measurement of metabolite levels. In particular, THADA and AmyD are highlighted as interesting genes for additional study. We hope to improve our understanding of the glucagon signaling pathway, obesity, and lipid metabolism. We also aim to provide candidate genes that can be regarded as future therapeutic targets.

Animals↗

PubMed2006

Ultrasensitive monitoring of HIV-1 viral load by a low-cost real-time reverse transcription-PCR assay with internal control for the 5' long terminal repeat domain.

BACKGROUND: Current HIV-1 viral-load assays are too expensive for resource-limited settings. In some countries, monitoring of antiretroviral therapy is now more expensive than treatment itself. In addition, some commercial assays have shown shortcomings in quantifying rare genotypes. METHODS: We evaluated real-time reverse transcription-PCR with internal control targeting the conserved long terminal repeat (LTR) domain of HIV-1 on reference panels and patient samples from Brazil (n = 1186), South Africa (n = 130), India (n = 44), and Germany (n = 127). RESULTS: The detection limit was 31.9 IU of HIV-1 RNA/mL of plasma (> 95% probability of detection, Probit analysis). The internal control showed inhibition in 3.7% of samples (95% confidence interval, 2.32%-5.9%; n = 454; 40 different runs). Comparative qualitative testing yielded the following: Roche Amplicor vs LTR assay (n = 431 samples), 51.7% vs 65% positives; Amplicor Ultrasensitive vs LTR (n = 133), 81.2% vs 82.7%; BioMerieux NucliSens HIV-1 QT (n = 453), 60.5% vs 65.1%; Bayer Versant 3.0 (n = 433), 57.7% vs 55.4%; total (n = 1450), 59.0% vs 63.8% positives. Intra-/interassay variability at medium and near-negative concentrations was 18%-51%. The quantification range was 50-10,000,000 IU/mL. Viral loads for subtypes A-D, F-J, AE, and AG yielded mean differences of 0.31 log(10) compared with Amplicor in the 10(3)-10(4) IU/mL range. HIV-1 N and O were not detected by Amplicor, but yielded up to 180 180.00 IU/mL in the LTR assay. Viral loads in stored samples from all countries, compared with Amplicor, NucliSens, or Versant, yielded regression line slopes (SD) of 0.9 (0.13) (P < 0.001 for all). CONCLUSIONS: This method offers all features of commercial assays and covers all relevant genotypes. It could allow general monitoring of antiretroviral therapy in resource-limited settings.

Brazil↗

PubMed1975

The detection of hepatitis B surface antigen by radioimmunoassay.

A comparative study was performed to assess the sensitivity and specificity of counterimmunoelectrophoresis (CIEP) and radioimmunoassay (RIA) for the detection of hepatitis B surface antigen. The 8,823 sera examined included selected reference panels and sera collected from populations with low, moderate and high rates of chronic antigen carriage. Overall, hepatitis B surface antigen was detected in 265 sera by CIEP and in 376 by RIA. As well as detecting 46.4% additional positives, the RIA test detected all CIEP-positive sera; i.e., there were no false negative results. However, 150 sera (1.8% of the total tested) gave a positive result by RIA which was not repeatable on retesting. The explanation for this phenomenon appeared to lie in inadequate washing of the antibody-coated tubes.

Blood Donors↗

PubMed2023

The genetic basis of adaptation to copper pollution in Drosophila melanogaster.

Introduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations. Methods: We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organism Drosophila melanogaster. Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance. Results and Discussion: Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations near CG11825, a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in the Drosophila Synthetic Population Resource (DSPR) and the Drosophila Genetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition to CG11825, which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance.

Drosophila↗

PubMed2005

Differential diagnosis of benign and malignant mesothelial proliferations on pleural biopsies.

CONTEXT: Although much of the pathology literature focuses on differential diagnosis of diffuse malignant mesothelioma from other types of cancer, the primary diagnostic challenge facing the pathologist is often whether a mesothelial proliferation on a pleural biopsy represents a malignancy or a benign reactive hyperplasia. DESIGN: Based on previous medical publications, extensive personal consultations, and experience on the United States-Canadian Mesothelioma Reference Panel and the International Mesothelioma Panel, salient information was determined about interpretation of benign versus malignant mesothelial proliferations on pleural biopsies. RESULTS: Differentiation of benign reactive mesothelial hyperplasia from diffuse malignant mesothelioma is often difficult. Benign reactive mesothelial hyperplasia may mimic many features ordinarily associated with malignancy, and diffuse malignant mesothelioma may be cytologically bland. Entrapment of benign reactive mesothelial cells within organizing pleuritis may mimic tissue invasion. CONCLUSIONS: Various histologic clues favor a benign over a malignant mesothelial proliferation and vice versa. Invasion is the most reliable criterion for determining that a mesothelial proliferation is malignant. When there is any doubt that a pleural biopsy represents a malignancy, we recommend a diagnosis of atypical mesothelial proliferation.

Biopsy↗

PubMed2026

FM-GPT: Bayesian fine mapping for phenome-wide transcriptome-wide association studies.

Transcriptome-wide association studies (TWAS) integrate genome wide association studies with expression quantitative trait locus reference panels to identify genes associated with traits of interest. However, linkage disequilibrium and correlated gene expression can induce spurious TWAS signals, motivating fine mapping methods to prioritize putatively causal genes within associated loci. The rapid growth of large-scale phenomic resources (e.g. electronic health records (EHRs)) has shifted genetic studies from single-trait analyses to phenome-wide investigations that jointly evaluate many closely related phenotypes. We introduce FM-GPT (Fine-mapping of causal Genes for Phenome-wide Transcriptome-wide association studies), a novel Bayesian fine mapping method for prioritizing causal genes across multiple correlated phenotypes with potentially mixed outcome types (e.g., binary, count or continuous) in phenome-wide TWAS. FM-GPT performs gene-guided dimension reduction of the phenotypes and reveals pleiotropic or phenotype-specific effects of the identified genes. In simulations, FM-GPT identified true causal genes more accurately than other fine mapping methods while controlling false positives. We applied FM-GPT to two applications using data from UK Biobank: a brain-wide genetic analysis of MRI data derived regional cortical thickness measures and a phenome-wide genetic analysis of clinical phenotypes derived from EHR data. FM-GPT greatly narrowed down the set size of putatively causal genes and identified: 1. genes with pleiotropic effects on regional cortical thickness across the cerebral cortex, including five genes BCAS3, LRRC37A, NOS2P3, ARL17B and UBB on chromosome 17 regulating neuronal morphology and cortical organization; and 2. genes that influence multiple medical conditions across the circulatory, metabolic, digestive, respiratory and genitourinary systems, revealing two major axes of variation among these conditions that point to a potential trade-off in gene regulation between immune and metabolic functions. These results highlight FM-GPT's power to disentangle complex gene-phenotype relationships in large-scale phenome-wide studies, uncovering shared biological mechanisms across diverse human traits and advancing translational and comorbidity research.

Bayesian fine mapping↗

PubMed1998

Leptospira interrogans antibodies in feral pigs from New South Wales.

The sera of 195 hunter-killed feral pigs (Sus scrofa), collected in New South Wales (Australia) from April to November 1995, were screened against a reference panel of 14 Leptospira interrogans serovars using a microscopic agglutination test (MAT). The panel represented those serovars previously isolated from wild and domestic mammals in mainland Australia. Antileptospiral agglutinins were detected in 20% of the sera tested and included nine L. interrogans serovars. The majority of serological reactors (63%) were to L. interrogans serovar pomona. Sera from 26% of immunoreactors cross reacted with antigens from one or more serovars. No differences were noted in the prevalence of L. interrogans antibodies between the sexes, or between pigs from areas of low and high rainfall. The implications of leptospirosis in feral pigs on the transmission of leptospires to wildlife, livestock, and humans are discussed.

Agglutination Tests↗

PubMed2002

Leptospiral antibodies in flying foxes in Australia.

The sera of 271 pteropid bats (or flying foxes) collected from Queensland, New South Wales, Western Australia, and the Northern Territory were screened against a reference panel of 21 Leptospira spp. using the microscopic agglutination test (MAT). Sera were collected from December 1997 through August 1999. The MAT panel represented those serovars previously isolated in Australia, as well as exotic serovars found in neighboring countries. Leptospiral antibodies were detected in 75 (28%) of the sera and represented seven serovars, one of which, L. interrogans serovar cynopteri has been regarded as exotic to Australia. Sixty sera were reactive to one serovar, 12 sera were reactive to two serovars, and three sera were reactive to three serovars. The L. kirschneri serovar australis was most frequently identified (60.2%). The findings suggest a previously unrecognized role of pteropid bats in the natural history of leptospirosis. The potential exists for establishment of infection in new host species, the transmission of new serovars to known host species, and for changes in virulence of leptospires as a result of passage through these species.

Agglutination Tests↗

PubMed1998

[Studies on multiple infection with hepatitis B, C and G viruses].

OBJECTIVE: To study if there exists superinfection and multiple infection in the patients with hepatitis G virus (HCV) infection. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) technique in non-structural gene 3 (NS3) region of HGV was used to detect HGV RNA in serially diluted quality control sera and HGV-C reference panel of samples provided by Abbott Co. Ltd, in 90 cases with positive hepatitis C virus (HCV) RNA, and 12 blood donors with super-infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). RESULTS: Serially diluted quality control sera showed positive for HGV RNA at dilutions of 10(-1) to 10(-5), but negative at dilutions of 10(-6) to 10(-8). HGV RNA was positive in two samples of HGV-C serum provided by Abbott Co. HGV RNA was positive in eight of the 90 cases with positive HCV RNA and in four of the 12 cases with super-infection with HCV and HBV. CONCLUSION: There are not only super-infection of HBV and HCV, but also multiple infection.

Flaviviridae↗

PubMed2000

Membership by Assessment of Performance: developing a method for assessing established general practitioners.

Over 200 general practitioners (GPs) and others have contributed to the development of Membership by Assessment of Performance (MAP): a new scheme for assessing established GPs. By means of a Delphi consultation with a broad cross-section of the profession, a working conference, piloting with potential candidates, and repeated checking with reference panels, the assessment was developed within two years. We report the development of MAP, including the results of the Delphi consultation, which asked 'Which aspects of a general practitioners performance are important to assess?'.

Delphi Technique↗