SEARCH · Search PubMed

Results for “Variant interpretation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

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

At least 1,441 records · Page 80Linked to original sources

PubMed2004

Laboratory assessment of oxygenation in methemoglobinemia.

BACKGROUND: This case conference reviews laboratory methods for assessing oxygenation status: arterial blood gases, pulse oximetry, and CO-oximetry. Caveats of these measurements are discussed in the context of two methemoglobinemia cases. CASES: Case 1 is a woman who presented with increased shortness of breath, productive cough, chest pain, nausea, fever, and cyanosis. CO-oximetry indicated a carboxyhemoglobin (COHb) fraction of 24.9%. She was unresponsive to O(2) therapy, and no source of carbon monoxide could be noted. Case 2 is a man who presented with syncope, chest tightness, and signs of cyanosis. His arterial blood was dark brown, and CO-oximetry showed a methemoglobin (MetHb) fraction of 23%. ISSUES: Oxygen saturation (So(2)) can be measured by three approaches that are often used interchangeably, although the measured systems are quite different. Pulse oximetry is a noninvasive, spectrophotometric method to determine arterial oxygen saturation (S(a)O(2)). CO-oximetry is a more complex and reliable method that measures the concentration of hemoglobin derivatives in the blood from which various quantities such as hemoglobin derivative fractions, total hemoglobin, and saturation are calculated. Blood gas instruments calculate the estimated O(2) saturation from empirical equations using pH and Po(2) values. In most patients, the results from these methods will be virtually identical, but in cases of increased dyshemoglobin fractions, including methemoglobinemia, it is crucial that the distinctions and limitations of these methods be understood. CONCLUSIONS: So(2) calculated from pH and Po(2) should be interpreted with caution as the algorithms used assume normal O(2) affinity, normal 2,3-diphosphoglycerate concentrations, and no dyshemoglobins or hemoglobinopathies. CO-oximeter reports should include the dyshemoglobin fractions in addition to the oxyhemoglobin fraction. In cases of increased MetHb fraction, pulse oximeter values trend toward 85%, underestimating the actual oxygen saturation. Hemoglobin M variants may yield normal MetHb and increased COHb or sulfhemoglobin fractions measured by CO-oximetry.

Adult↗

PubMed2003

Peripheral macrohemodynamics in patients with lower limb arteriosclerosis obliterans and type II diabetes mellitus.

The paper presents characteristic features of lower limb atherosclerotic lesions in patients with diabetes mellitus: more prominent calcification of vascular wall (involving media), frequent involvement of distal vascular segments and a symmetry of lesions. Typical variants are shown in images obtained with duplex angioscanning. The authors conclude that there are no principal differences in the course of lower limb arteriosclerosis obliterans between diabetics and non-diabetics. Nevertheless some special features were mentioned, particularly in clinical manifestation of intermittent claudication that can be attributed to concurrent diabetic neuropathy. Difficulties in clinical interpretation of lower limb arterial insufficiency for patients with diabetes mellitus determine the necessity of obligatory examination of peripheral vasculature. The authors advocate the discrete subclinical stage of the disease with increased rate of vascular accidents. The data may be interesting for angiologists, vascular surgeons, endocrine legists and other medical professions.

Aged↗

PubMed1988

Identification of an apoC-II variant (apoC-IIBethesda) in a kindred with apoC-II deficiency and type I hyperlipoproteinemia.

Apolipoprotein (apo) C-II deficiency is characterized by elevated plasma triglycerides, chylomicrons, and very low density lipoproteins, as well as reduced levels of low density and high density lipoproteins. A subject with apoC-II deficiency has been identified with an apoC-II plasma level of less than 0.05 mg/dl. The plasma apoC-II in the proband was immunochemically similar to apoC-II in normal subjects when analyzed by Ouchterlony immunodiffusion, however the apoC-II had an apparently lower molecular weight and higher pI when analyzed by two-dimensional gel electrophoresis. This apoC-II variant, designated apoC-IIBethesda, was not affected by neuraminidase treatment or reduction. Two-dimensional gel electrophoresis of the plasma of the mother of the proband revealed both normal apoC-II and apoC-IIBethesda, whereas analysis of the father and two siblings revealed apoC-II of normal electrophoretic mobility. These results were interpreted as indicating that the proband was a compound heterozygote with one allele for apoC-IIBethesda inherited from the mother and an allele coding for an abnormality which results in the virtual or complete absence of plasma apoC-II from the father. This proband represents the first example of a compound heterozygote for an apolipoprotein defect associated with a dyslipoproteinemia.

Apolipoprotein C-II↗

PubMed2000

Risk of venous thrombosis in carriers of the prothrombin G20210A variant and factor V Leiden and their interaction with oral contraceptives.

BACKGROUND AND OBJECTIVES: The prothrombin G20210A mutation and factor V Leiden have been found to be associated with an increased risk of venous thrombosis, but the reported prevalences of the prothrombin gene variant both in the normal population and in patients with deep venous thrombosis (DVT) vary greatly in the literature. Moreover, the influence of oral contraceptives (OC) on thrombotic events in patients with the prothrombin G20210A variant has not been well established. In this study we evaluate both circumstances. DESIGN AND METHODS: A case-control study was run on 229 patients with DVT and 246 healthy controls. The patients' history of thrombosis and acquired thrombotic risk factors, especially OC, were recorded. Prothrombin G20210A mutation, factor V Leiden, antithrombin, heparin II cofactor, plasminogen and proteins C and S were evaluated. RESULTS: Seven and a half percent of the patients and 2.9% of the controls were carriers of the prothrombin mutation, while 12.2% of the patients and 1.6% of the controls had factor V Leiden. Among the 229 DVT patients there were 130 patients with clinically suspected thrombophilia (first thrombotic event occurring before the age of 45 years or positive family history of thrombosis or recurrent venous thrombosis). Ten percent of these 130 patients were carriers of the prothrombin G20210A mutation and 18.5% had the factor V Leiden mutation. The odds ratios (OR) for DVT risk were: 2.4 (95% CI, 1.0-6.3) for the total DVT patients and 5.2 (95% CI, 1.4-19.5) for the patients with clinically suspected thrombophilia with the prothrombin mutation. The risk of thrombosis was 6.9 (95% CI, 2.3-20.6) for the DVT patients and 14.3 (95% CI, 3.3-64.6) for the patients with clinically suspected thrombophilia with factor V Leiden. Fifty-five percent of the patients with combined congenital defects (prothrombin mutation G20210A plus another congenital defect) had recurrent thrombosis. In women receiving OC the risk of DVT was 3.5 (95% CI, 1.5-8.2) that of the patients not receiving OC. When women with combined defects were also taking OC, the risk of thrombosis increased significantly. INTERPRETATION AND CONCLUSIONS: The prevalence of the prothrombin G20210A mutation in the healthy population in our study is similar to that observed in other southern European countries. The prothrombin G20210A mutation does not by itself seem to be a high thrombotic risk factor. However, when it is present together with other thrombotic risk factors, the predicted risk of thrombotic events increases. The use of OC by women with the prothrombin G20210A variant or FV Leiden, either alone or combined with other thrombotic risk factors, was associated with a significant increase in the risk of venous thrombosis.

Adult↗

PubMed1982

Superficial ulcerating necrobiosis in rheumatoid arthritis. A variant of the necrobiosis lipoidica-rheumatoid nodule spectrum?

Although necrobiosis is not a precise term, it primarily refers to collagen changes found in association with the palisading granulomas seen in granuloma annulare, necrobiosis lipoidica diabeticorum (NLD), and rheumatoid nodules. While the pathogenesis of each of these conditions remains unknown, immune complex vasculitis and delayed hypersensitivity mechanisms have been postulated. Two patients are described, having "classic" rheumatoid arthritis with chronic, superficial, ulcerating, discrete lesions on their lower legs that histologically were interpreted as NLD. While the argument for a chance association of NLD and rheumatoid arthritis could be advanced, the occurrence of identical lesions in two patients with high-titer rheumatoid factor, rheumatoid nodules, and some clinical and microscopic evidence of a low-grade rheumatoid vasculitis suggests a new subset of patients with necrobiotic palisading granulomas.

Aged↗

PubMed1980

Ossifying tumor of infantile kidney: report of two cases.

Two patients, both male infants, presented with hematuria and were found to have small calcified intrarenal masses interpreted as calculi radiographically. These were found at surgery to be firmly adherent to parenchyma. Dense, stone-like cores, after decalcification, were found to be composed of bone, while the periphery was composed of uniform, undifferentiated cells. We believe these tumors were derived from urothelium rather than the metanephros, and that they represent yet another benign variant of pediatric renal tumors.

Diagnosis, Differential↗

PubMed1975

Biochemical and cytogenetic studies on the nucleolus organizing regions (NOR) of man. II. A family with the 15/21 translocation.

The amount of ribosomal DNA (rDNA) was determined quantitatively by RNA-DNA hybridization in the genomes of a mother and her daughter, both with the karyotype 45,XX,t(15q21q). The saturation values found were 0.030% (mother), 0.023% (daughter), and 0.022% for the husband and father of the daughter. A detailed cytogenetic analysis of the short arms of the acrocentric chromosomes of these probands allowed the biochemical results to be interpreted in terms of the size of the individual set of nucleolus organizing regions (NORs) present in each proband. The correlation existing between the biochemical and the cytogenetic findings shows that the amount of rDNA in the human genome is not primarily a function of the number of acrocentric chromosomes, but depends on the individual combination of variant NORs occurring in the human genome.

Cell Nucleolus↗

PubMed1996

MRI of anatomical variants of the wrist in women.

In the analysis of magnetic resonance (MR) images of the wrist joint, some structural variations may lead to misinterpretation. Our aim was to search for different anatomical variants and their MR characteristics on axial images. Two groups of patients with rheumatoid arthritis (thirty one) and carpal tunnel syndrome (sixty two), and a group of asymptomatic controls (fifty four) underwent bilateral MR axial wrist imaging from the metacarpal bases to the distal radiocarpal joint. The imaging techniques included spin echo (SE), turbo spin echo (TSE) and fast field echo (FFE) sequences, using 3 mm-slice thickness. Different anatomical variants including hypoplasia of the hamulus or hook of the hamate bone (4 cases), anomalous muscles (lumbricals) inside the carpal tunnel (2 cases), unusual location (5 cases) and double branching of the median nerve (14 cases), and aberrant median artery (one case) were detected. These variants, if unfamiliar to MR readers, may be misinterpreted as pathological features.

Adolescent↗

PubMed2003

Iterative reconstruction with correction of the spatially variant fan-beam collimator response in neurotransmission SPET imaging.

The dopamine transporter (DAT) has been shown to be a sensitive indicator of nigrostriatal dopamine function. Although visual inspection is often sufficient to assess DAT imaging, quantification could improve the diagnostic accuracy of single-photon emission tomography (SPET) studies of the dopaminergic system. The aim of this study was to assess the accuracy of quantification of the striatal/background uptake ratio when correction for attenuation, scatter and spatially variant fan-beam collimator response is performed in technetium-99m and iodine-123 SPET imaging. A numerical striatal phantom was implemented, and simulated projections of low-energy photons were obtained by using the SimSET Monte Carlo code. High-energy contamination in 123I studies was modelled from experimental measurements with 99mTc and 123I. The ordered subsets expectation maximisation (OSEM) algorithm was employed in reconstruction. Mean improvements of 8% and 16% were obtained in the calculated striatal/background uptake ratio in the putamen and the caudate, respectively, when the spatially variant point spread function was included in the transition matrix. Ideal scatter correction resulted in improvements in the putamen and caudate of 9% for 99mTc agents and 19% for 123I agents. Improvements averaged 31% in the putamen and 43% in the caudate when correction for attenuation, scatter and spatially variant collimator response was included in the reconstruction.

Algorithms↗

PubMed1988

Bloodstain characterization in the EAP, Hp, Hb, AK and Glo I typing systems using minigels and the PhastSystem.

Application of minigels and the PhastSystem to obtain phenotyping results from bloodstains in the EAP, Hp, AK, and Glo I typing systems was investigated. Nonequilibrium isoelectric focusing with 4-6.5 PhastGel produced readily interpretable phenotypes in the EAP typing system. Both 4-6.5 and 5-8 PhastGel produced AK typing system phenotypes using nonequilibrium isoelectric focusing conditions. The 8-25% PAG PhastGel developed by two staining techniques allowed discrimination of phenotypes for the Hp typing system. Phenotypes from the Glo I typing system were also obtained with this gel type. Variant haemoglobins could be detected on pH 5-8 PhastGel using isoelectric focusing conditions. Much potential for standardized, rapid phenotyping of bloodstains was found to exist utilizing the PhastSystem.

Acid Phosphatase↗

PubMed1985

Effects of hemoglobin variants on Hb A1c determinations using Bio-Rad columns.

In the column chromatographic determination of Hb A1c, hemoglobin variants affect Hb A1c results and column patterns. Samples from several patients with hemoglobin variants were run on Bio-Rad Hb A1c columns to demonstrate these patterns. Columns should be examined during the run to detect the presence of Hb F which migrates very rapidly, and after the run to detect abnormal column patterns. Hb A1c levels in patients heterozygous for Hb S or C are low but may be interpreted in relation to the patient's level of Hb A. On the other hand, Hb A1c results on patients with homozygous Hb S, Hb C, or high levels of Hb F cannot be interpreted.

Chromatography↗

PubMed2002

Probing the effect of side chains on the conformation and stability of helical peptides via isotope-edited infrared spectroscopy.

The mechanism of helix stabilization or destabilization by different amino acids has been the subject of several experimental and theoretical studies; these studies suggest that large or bulky side chains may modulate helix stability by altering the hydration of the helix backbone. In this paper, we report a spectroscopic study to determine the effect of alanine to leucine substitutions on the conformation and solvation of specific segments of a model helical peptide. A 25-residue, alanine-rich, helical peptide [Ac-(AAAAK)(4)-AAAAY-NH(2) (AKA)] and its two leucine variants [Ac-LLLLK-(AAAAK)(3)-AAAAY-NH(2) (LKA) and Ac-(AAAAK)(4)-LLLLY-NH(2) (AKL)] were characterized by infrared (IR) and electronic circular dichroism (ECD) spectroscopies. Introduction of (13)C isotopes into specific, consecutive, backbone carbonyls for certain blocks of each of the peptides mentioned above allows the IR spectra to be interpreted in terms of the conformation and solvation of specific residues within the helix. These isotope-edited IR spectra of the leucine peptides do not show evidence of a decrease in the degree of backbone solvation compared to the alanines, but suggest that the peptide may adopt a distorted conformation to accommodate the larger leucine side chains at the N-terminus. These experiments demonstrate the power of isotope-edited IR in dissecting subtle changes in helix conformation at the residue level.

Alanine↗

PubMed2005

Cross sections of the O+ + H2 --> OH+ + H ion-molecule reaction and isotopic variants (D2, HD): quasiclassical trajectory study and comparison with experiments.

A dynamics study [cross section and microscopic mechanism versus collision energy (E(T))] of the reaction O+ + H2 --> OH+ + H, which plays an important role in Earth's ionosphere and interstellar chemistry, was conducted using the quasiclassical trajectory method, employing an analytical potential energy surface (PES) recently derived by our group [R. Martinez et al., J. Chem. Phys. 120, 4705 (2004)]. Experimental excitation functions for the title reaction, as well as its isotopic variants with D2 and HD, were near-quantitatively reproduced in the calculations in the very broad collision energy range explored (E(T) = 0.01-6.0 eV). Intramolecular and intermolecular isotopic effects were also examined, yielding data in good agreement with experimental results. The reaction occurs via two microscopic mechanisms (direct and nondirect abstraction). The results were satisfactorily interpreted based on the reaction probability and the maximum impact parameter dependences with E(T), and considering the influence of the collinear [OHH]+ absolute minimum of the PES on the evolution from reactants to products. The agreement between theory and experiment suggests that the reaction mainly occurs through the lowest energy PES and nonadiabatic processes are not very important in the wide collision energy range analyzed. Hence, the PES used to describe this reaction is suitable for both kinetics and dynamics studies.

Journal Article↗

PubMed1987

Frequencies of independent and simultaneous selection of Chinese hamster cells for methotrexate and doxorubicin (adriamycin) resistance.

We have determined the frequency with which Chinese hamster cells become resistant to either methotrexate or doxorubicin (former generic name, adriamycin) alone or to the two drugs simultaneously. We find that the frequency of acquisition of simultaneous resistance is 10-100 times higher than that predicted from the frequency of each resistance selected independently. In approximately 50% of cloned resistant variants, resistance is the result of amplification of the dihydrofolate reductase gene (methotrexate) and/or of the multiple-drug-resistance P-glycoprotein gene (doxorubicin). Prior exposure of cells to hypoxia markedly enhances these resistance frequencies. Our results indicate that the simultaneous emergence of resistance to these two cancer chemotherapeutic agents are not independent events, and we interpret them to constitute two consequences of the same basic process occurring at a high frequency.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Genomic DNA fingerprinting of clinical Haemophilus influenzae isolates by polymerase chain reaction amplification: comparison with major outer-membrane protein and restriction fragment length polymorphism analysis.

Non-capsulate strains of Haemophilus influenzae were genotyped by analysis of variable DNA segments obtained by amplification of genomic DNA with the polymerase chain reaction (PCR fingerprinting). Discrete fragments of 100-2000 bp were obtained. The reproducibility of the procedure was assessed by comparing: (i) the fingerprints of 16 colonies of a single H. influenzae strain; (ii) isolates obtained from individual sputum samples (a total of 57 H. influenzae isolates from three cystic fibrosis patients); and (iii) 17 isolates collected during an outbreak of H. influenzae infection in a local pulmonary rehabilitation centre. The discriminatory power of the method was demonstrated by showing that the PCR fingerprints of eight unrelated H. influenzae strains from sputum samples of patients with chronic obstructive pulmonary disease (COPD) and 32 strains from cystic fibrosis patients were all different. These 40 isolates also differed with respect to their restriction fragment length polymorphisms (RFLP) and major outer-membrane protein (MOMP) composition. Twelve MOMP antigenic strain variants from sputum samples of five COPD patients had identical PCR fingerprints and RFLPs. It was concluded that PCR fingerprinting is a reliable and reproducible method for genotyping non-capsulate strains of H. influenzae. The discriminatory power of PCR fingerprinting was similar to that of RFLP analysis, but the results of PCR fingerprinting were easier to interpret.

Bacterial Outer Membrane Proteins↗

PubMed2003

Non-Markovian stochastic Liouville equation and its Markovian representation.

The non-Markovian variant of the stochastic Liouville equation (SLE) is studied within the continuous time random walk approach (CTRWA). The CTRWA-based non-Markovian SLE is shown to be equivalently represented by the corresponding conventional Markovian SLE. This Markovian representation provides a rigorous method for deriving the non-Markovian SLE and allows for a physically clear interpretation of the specific features of this SLE. It also enables one to develop convenient non-Markovian models useful for applications, some of which are discussed in detail. Special attention is given to the discussion of anomalous long-tailed CTRW processes and non-Markovian SLE. The obtained results are applied to the analysis of the effect of rate fluctuations on chemical reaction kinetics. It is shown, in particular, that the anomalous fluctuations not only influence the reaction rate but also change the reaction kinetics itself.

Journal Article↗

PubMed2005

Role of the microbiology laboratory in infectious disease surveillance, alert and response.

Surveillance is usually defined as the ongoing and systematic collection, analysis and interpretation of health data essential to the planning, implementation and evaluation of public health practice. During recent years, most of these programmes have been developed in the field of antimicrobial resistance and nosocomial infections, but efforts have also been made in other areas. Recent experiences of emerging microbial threats, including severe acute respiratory syndrome and new influenza variants affecting humans, the re-emergence of infectious disease problems and the possibility of bioterrorism have evidenced the need for implementation of infectious disease surveillance programmes. clinical microbiology laboratories play a pivotal role in these programmes. They have the first opportunity to detect these problems and should participate in the design of reporting strategies and dissemination of this information. Policies for the flow of data to national and international authorities should be established using passive surveillance strategies. However, active surveillance programmes taking advantage of new methodologies, including virtual tools and mathematical programs, should be the goal for early detection of unusual patterns of microbial pathogens, outbreaks and healthcare-associated infections. In addition, early implementation of response strategies should be designed and performed with the cooperation of microbiology laboratories, and intervention and response protocols should be defined with the participation of clinical microbiologists.

Communicable Disease Control↗

PubMed2006

Cytogenetic heteromorphisms: survey results and reporting practices of giemsa-band regions that we have pondered for years.

CONTEXT: Cytogenetic heteromorphisms (normal variants) pose diagnostic dilemmas. Common Giemsa-band heteromorphisms are not described in the literature, although Giemsa-banding is the method most frequently used in cytogenetic laboratories. OBJECTIVE: To summarize the responses from more than 200 cytogeneticists concerning the definition and reporting of cytogenetic heteromorphisms, to offer these responses as a reference for use in clinical interpretations, and to provide guidance for interpretation of newly defined molecular cytogenetic heteromorphisms. DESIGN: The Cytogenetics Resource Committee of the College of American Pathologists and the American College of Medical Genetics administered a proficiency testing survey in 1997 to 226 participant cytogenetic laboratories. Supplemental questions asked whether participants considered particular Giemsa-banded chromosomal features to be heteromorphisms and if these would be described in a cytogenetic clinical report. RESULTS: Responses were obtained from 99% of participants; 61% stated they would include selected heteromorphism data in a clinical report. More than 90% considered prominent short arms, large or double satellites, or increased stalk length on acrocentric chromosomes to be heteromorphisms; 24% to 36% stated that they would include these in a clinical report. Heterochromatic regions on chromosomes 1, 9, 16, and Y were considered heteromorphisms by 97% of participants, and 24% indicated they would report these findings. Pericentric inversions of chromosomes 1, 2, 3, 5, 9, 10, 16, and Y were considered heteromorphisms with more than 75% of respondents indicating they would report these findings. CONCLUSIONS: Responses were not unanimous, but a clear consensus is presented describing which Giemsa-band regions were considered heteromorphisms and which would be reported.

Azure Stains↗