SEARCH · PubMed Health

Results for “Variant interpretation”

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 487 records · Page 27Linked to original sources

PubMed1999

Preferential associations of alleles of three distinct genes argue for the existence of two prototype variants of human herpesvirus 7.

We had previously described six distinct alleles of the glycoprotein B (gB) gene of human herpesvirus 7 (HHV-7). The genetic changes corresponding to these alleles did not affect gB gene transcription or translation in in vitro assays. The study of distinct HHV-7-positive human samples showed preferential associations of some gB alleles with some alleles of two other genes, distantly located on the HHV-7 genome, coding for the phosphoprotein p100 (p100) and the major capsid protein (MCP). Two allele combinations, corresponding to 44 and 31% of the samples studied, respectively, were interpreted as the genetic signatures of two major prototype HHV-7 variants.

Alleles↗

PubMedDate not supplied

Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants.

A rapidly emerging clinical application of positron emission tomography (PET) is the detection and staging of cancer with the glucose analogue tracer 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). Proper interpretation of FDG PET images requires knowledge of the normal physiologic distribution of the tracer, frequently encountered physiologic variants, and benign pathologic causes of FDG uptake that can be confused with a malignant neoplasm. One hour after intravenous administration, high FDG activity is present in the brain, the myocardium, and--due to the excretory route--the urinary tract. Elsewhere, tracer activity is typically low, a fact that allows sensitive demonstration of tracer accumulation in many malignant neoplasms. Interpretive pitfalls commonly encountered on FDG PET images of the body obtained 1 hour after tracer administration can be mistaken for cancer. Such pitfalls include variable physiologic FDG uptake in the digestive tract, thyroid gland, skeletal muscle, myocardium, bone marrow, and genitourinary tract and benign pathologic FDG uptake in healing bone, lymph nodes, joints, sites of infection, and cases of regional response to infection and aseptic inflammatory response. In many instances, these physiologic variants and benign pathologic causes of FDG uptake can be specifically recognized and properly categorized; in other instances, such as the lymph node response to inflammation or infection, focal FDG uptake is nonspecific.

Diagnosis, Differential↗

PubMedDate not supplied

A novel three-dimensional variant of the watershed transform for segmentation of electron density maps.

Electron density maps at moderate resolution are often difficult to interpret due to the lack of recognizable features. This is especially true for electron tomograms that suffer in addition to the resolution limitation from low signal-to-noise ratios. Reliable segmentation of such maps into smaller, manageable units can greatly facilitate interpretation. Here, we present a segmentation approach targeting three-dimensional electron density maps derived by electron microscopy. The approach consists of a novel three-dimensional variant of the immersion-based watershed algorithm. We tested the algorithm on calculated data and applied it to a wide variety of electron density maps ranging from reconstructions of single macromolecules to tomograms of subcellular structures. The results indicate that the algorithm is reliable, efficient, accurate, and applicable to a wide variety of biological problems.

Actin Cytoskeleton↗

PubMed2002

Detection & differentiation of Coxsackie A 24 variant isolated from an epidemic of acute haemorrhagic conjunctivitis in north India by RT-PCR using a novel primer pair.

BACKGROUND & OBJECTIVES: An epidemic of acute haemorrhagic conjunctivitis (AHC) occurred in north India during July to September 1994. We report a reverse transcription-polymerase chain reaction (RT-PCR) using known and novel primers to differentiate and identify the CA 24 virus isolated from the epidemic of AHC. METHODS: Conjunctival swabs were collected from 46 patients (in 12 patients from both the eyes) yielding 58 swabs. The swabs were inoculated in RD 19S and HeLa-199 cell monolayers and observed for cytopathic effect. Serum neutralizing antibodies were tested in 17 acute and 10 convalescent phase serum samples. RT-PCR was done on 9 isolates (7 Coxsackie A 24 and 2 ECHO-1 as identified by neutralization test) using known and a novel primer. Fourteen virus isolates (9 CA 24, 3 ECHO-1 and 2 untyped) were inoculated in suckling mice and these mice were observed daily for 10 days for flaccid paralysis of hind limb or death. RESULTS: Cytopathic virus was isolated from conjunctival swabs in 21 of 46 (45.6%) patients subjected to virus isolation. Sixteen of 21 (76.2%) isolates were neutralized by CA 24 specific antisera, 3 isolates were identified as ECHO-1 with Schmidt enteroviruses antiserum pools while 2 remained untypable. Of these 21 isolates, 9 representative isolates (7 CA 24 and 2 ECHO-1) tested by RT-PCR had enterovirus common region DNA but did not show any amplification in RT-PCR with EV-70 specific primers (VP-1 and VP-3). Using CA 24 specific novel (VP 3-1) primers amplification was seen in 6 of 7 CA 24 isolates while 2 ECHO-1 remained unamplified. In contrast with 3C-proteinase region primers, only 2 of 7 CA 24 were amplified along with false amplification of both ECHO-1. Serum neutralizing antibodies were seen in 2 of 17 (11.7%) acute phase sera and 6 of the 10 (60%) convalescent phase sera while in paired sera (available in two patients) a four-fold rise in titres were observed. Hind-limb paralysis and/or death occurred in all suckling mice inoculated with CA 24 isolates while mice remained healthy after inoculation with 3 isolates of ECHO-1 and 2 untypable isolates. INTERPRETATION & CONCLUSION: The epidemic of AHC was caused by a variant of CA 24. Molecular typing can detect and differentiate between CA 24 and EV-70 viruses. Novel primer pair was found useful in the identification and confirmation of CA 24 isolates.

Adolescent↗

PubMed2026

Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages.

Genetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers' genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology.

Humans↗

PubMedDate not supplied

Pitfalls in 16-detector row CT of the coronary arteries.

Recently developed 16-detector row computed tomography (CT) has been introduced as a reliable noninvasive imaging modality for evaluating the coronary arteries. In most cases, with appropriate premedication that includes beta-blockers and nitroglycerin, ideal data sets can be acquired from which to obtain excellent-quality coronary CT angiograms, most often with multiplanar reformation, thin-slab maximum intensity projection, and volume rendering. However, various artifacts associated with data creation and reformation, postprocessing methods, and image interpretation can hamper accurate diagnosis. These artifacts can be related to pulsation (nonassessable segments, pseudostenosis) as well as rhythm disorders, respiratory issues, partial volume averaging effect, high-attenuation entities, inappropriate scan pitch, contrast material enhancement, and patient body habitus. Some artifacts have already been resolved with technical advances, whereas others represent partially inherent limitations of coronary CT angiography. Familiarity with the pitfalls of coronary angiography with 16-detector row CT, coupled with the knowledge of both the normal anatomy and anatomic variants of the coronary arteries, can almost always help radiologists avoid interpretive errors in the diagnosis of coronary artery stenosis.

Adult↗

PubMed2004

Toxicological considerations in the application and interpretation of susceptibility biomarkers in epidemiological studies.

With major advances in genotyping technology, it has become practical and affordable to screen biological samples for multiple polymorphisms for which there is more or less knowledge about their functional relevance in relation to toxicological agents or disease. This situation creates some unique epidemiological challenges in which careful consideration of the mechanisms underlying genotype-disease and genotype-exposure-disease relationships, or the lack of knowledge thereof, may help to prevent false-positive results or misinterpretation of data that could mislead future research. Coordination and linkage of data resources on toxicological exposures, genes and disease would be useful as an integrated source of information to devise study design, analysis and interpretation. Such a database could be useful in collating information from which to determine relevant exposures for the disease and to guide the selection of susceptibility markers for study. Further information on toxicological mechanisms and functional relevance of gene variants in relation to disease could be accounted for in statistical analyses and interpretation. Statistical methods that can incorporate this prior information on mechanism, such as hierarchical regression modelling, may help to mitigate some of the problems inherent to these studies by adjusting estimates and confidence limits according to this prior information. Even in the situation where little information on etiological mechanisms is available, application of a less informed prior can be beneficial in improving the accuracy and precision for an ensemble of estimates. The changing paradigm of epidemiological research with regard to increasing detail of underlying mechanisms and the sheer amount of data being evaluated necessitates access to sources of information and analytic methods that can integrate this complexity.

Biomarkers↗

PubMed1994

Pleomorphic fibrohistiocytoma of the breast: a potential pitfall in breast biopsy interpretation.

We describe a benign mammary mesenchymal tumour with atypical stromal giant cells in the contralateral breast of a 66-year-old woman with infiltrating ductal carcinoma. The clinical, morphological and immunohistochemical features of this tumour suggest a pleomorphic variant of fibrous histiocytoma. This benign lesion represents a possible pitfall in breast pathology when interpreting a frozen section or fine needle aspiration biopsy.

Aged↗

PubMed1997

Combined mass spectrometric methods for the characterization of human hemoglobin variants localized within alpha T9 peptide: identification of Hb Villeurbanne alpha 89 (FG1) His-->Tyr.

Mutation-induced amino acid exchanges occurring on the large T9 peptide of the alpha-chain of human hemoglobin (residues 62-90) are difficult to identify. Despite their high m/z value (around m/z 3000), collision-induced dissociation spectra of liquid secondary ion mass spectrometrically generated protonated alpha T9 peptides were performed successfully. In parallel electrospray mass spectrometry (MS) was used both to measure the molecular mass of the intact proteins and to determine the number of protonatable sites in the alpha T9 peptides. Peptide ladder sequencing using carboxypeptidase digestions and analysis of the truncated peptides by matrix-assisted laser desorption ionization time-of-flight MS confirmed the interpretation. This set of methods allowed the characterization of three hemoglobin variants, with amino acid exchanges located in the alpha T9 part of the sequence. Two of them, Hb Aztec [alpha 76(EF5) Met-->Thr] and Hb M-Iwate [alpha 87(F8) His-->Tyr] were already known. The third [alpha 89(FG1) His-->Tyr] was novel and named Hb Villeurbanne.

Amino Acid Sequence↗

PubMed2004

Cortical scintigraphy in the evaluation of renal defects in children with vesico-ureteral reflux--optimization of the procedure and study interpretation.

BACKGROUND: The objective of this study was to analyse the performance of several variants of kidney scintigraphy in children from the standpoint of: scar detection, an assessment of the rating of the pathology and an investigation of interobserver variability involved in the diagnostic procedure. MATERIAL AND METHODS: The analysis is based on results of a planar kidney scintigraphy and of a tomographic (SPECT) procedure. The latter was performed in two variants: 1) in which slices were obtained with axis of reconstruction identical with longitudinal axis of the body (SPECT I) and 2) in which axes were fitted to the long axis of each kidney separately (SPECT II). The rating of the diagnosed pathology was made using two scales, according to Goldraich and Howard. Evaluation of the images involved on the one hand, 150 individual kidneys and 75 patients on the other. The assessment was made by three independent observers, differing in experience in nuclear medicine and employed in three independent departments. In the statistical analysis, as a measure of observer agreement, a proportion of agreeing readings (%) was accepted; in addition, the kappa index of agreement was calculated. RESULTS: Better agreement among three observers was attained when planar images were read in contrast to SPECT (I and II) results. The reading of SPECT II images yielded a higher frequency of diagnosed pathology (scars) in kidneys and is characterized by better overall agreement in detection by individual observers than a similar evaluation of SPECT I images. The Goldraich scale secures better interobserver agreement of renal scar detection than is seen when the Howard scale was applied to acquire the rating. CONCLUSIONS: The conclusion may be drawn that kidney scintigraphy is a method still burdened with a substantial subjectivism. Planar scintigraphy should be treated as a basic option for imaging post-inflammatory changes in kidneys.

Child↗

PubMed1979

Variant angina pectoris: investigation of indexes of sympathetic nervous system function.

One thousand forty-five spontaneous episodes of S-T segment elevation were observed in three patients over a total of 72 days of continuous electrocardiographic monitoring. Eighty-nine percent of episodes were asymptomatic; chest pain tended to occur with episodes longer than 3 minutes, and ventricular ectopy occurred almost exclusively with symptomatic episodes. Nitroglycerin regularly relieved angina or S-T elevation, or both. Plasma and urinary catecholamines and their metabolites were normal. Episodes of variant angina were not associated with a generalized increase in sympathetic outflow because serum catecholamine levels at the onset and termination of the S-T abnormalities were not elevated. Controlled trials of propranolol showed no significant beneficial effect. Propranolol significantly increased the length of episodes of S-T elevation in one patient, increasing ventricular irritability. The overall course of variant angina was quite variable, with spontaneous and long-lasting remissions, necessitating cautions interpretation of clinical trials.

Angina Pectoris↗

PubMed1996

Eruptive vellus hair cysts and steatocystoma multiplex. variants of one entity?

Eruptive vellus hair cysts and steatocystoma multiplex are two clinically similar conditions which show multiple papules and nodules, mainly located over the anterior chest wall. Most cases can be differentiated on histological examination, but in some patients overlapping histological features have been described. We present a patient who showed features of both entities and interpret this as suggesting that eruptive vellus hair cysts and steatocystoma multiplex are variants of one disorder which originates in the pilosebaceous duct.

Adult↗

PubMed1996

Malignant plexiform tumor of the uterus: an unusual variant of epithelioid leiomyosarcoma.

A 46-year-old woman with the complaint of hypermenorrhea underwent hysterectomy for a presumed uterine myoma. The solid tumor in the myometrium was gray in color, was 4 cm in diameter, and showed hemorrhage and necrosis. Histologically, the tumor consisted of round or polygonal cells arranged in cords and nests, and its histological features closely resembled those of plexiform tumor which has been reported as a benign, epithelioid smooth muscle tumor of the uterus. In the tumor in our patient, however, mild nuclear atypia and two to three mitoses/10 high-power fields were present. Two months after the hysterectomy, the patient was found to have metastatic foci in the lumbar vertebrae and iliac bone, which contained tumor cells with the same histological features. Accordingly, the present tumor might be interpreted as a malignant plexiform tumor of the uterus, an unusual variant of epithelioid leiomyosarcoma.

Biomarkers, Tumor↗

PubMed1999

Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications.

BACKGROUND: The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case. The allelic variants are associated with impaired hydroxylation of S-warfarin in in-vitro expression systems. We have studied the effect of CYP2C9 polymorphism on the in-vivo warfarin dose requirement. METHODS: Patients with a daily warfarin dose requirement of 1.5 mg or less (low-dose group, n=36), randomly selected patients with a wide range of dose requirements from an anticoagulant clinic in north-east England (clinic control group, n=52), and 100 healthy controls from the community in the same region were studied. Genotyping for the CYP2C9*2 and CYP2C9*3 alleles was done by PCR analysis. Case notes were reviewed to assess the difficulties encountered during the induction of warfarin therapy and bleeding complications in the low-dose and clinic control groups. FINDINGS: The odds ratio for individuals with a low warfarin dose requirement having one or more CYP2C9 variant alleles compared with the normal population was 6.21 (95% CI 2.48-15.6). Patients in the low-dose group were more likely to have difficulties at the time of induction of warfarin therapy (5.97 [2.26-15.82]) and have increased risk of major bleeding complications (rate ratio 3.68 [1.43-9.50]) when compared with randomly selected clinic controls. INTERPRETATION: We have shown that there is a strong association between CYP2C9 variant alleles and low warfarin dose requirement. CYP2C9 genotyping may identify a subgroup of patients who have difficulty at induction of warfarin therapy and are potentially at a higher risk of bleeding complications.

Aged↗

PubMed2003

The influence of hinge region residue Glu-381 on antithrombin allostery and metastability.

Antithrombin becomes an efficient inhibitor of factor Xa and thrombin by binding a specific pentasaccharide sequence found on a small fraction of the heparan sulfate proteoglycans lining the microvaculature. In the structure of native antithrombin, the reactive center loop is restrained due to the insertion of its hinge region into the main beta-sheet A, whereas in the heparin-activated state the reactive center loop is freed from beta-sheet A. In both structures, hinge region residue Glu-381 makes several stabilizing contacts. To determine the role of these contacts in the allosteric mechanism of antithrombin activation, we replaced Glu-381 with an alanine. This variant is less active toward its target proteases than control antithrombin, due to a perturbation of the equilibrium between the two forms, and to an increase in stoichiometry of inhibition. Pentasaccharide binding affinity is reduced 4-fold due to an increase in the off-rate. These data suggest that the main role of Glu-381 is to stabilize the activated conformation. Stability studies also showed that the E381A variant is resistant to continued insertion of its reactive center loop upon incubation at 50 degrees C, suggesting new stabilizing interactions in the native structure. To test this hypothesis, and to aid in the interpretation of the kinetic data we solved to 2.6 A the structure of the variant. We conclude that wild-type Glu-381 interactions stabilize the activated state and decreases the energy barrier to full loop insertion.

Allosteric Regulation↗

PubMed1991

Experience-dependent modifications of hippocampal place cell firing.

Understanding the empirical rules that regulate alterations of hippocampal firing fields will enhance our understanding of hippocampal function. The current study sought to extend previous research in this area by examining the effect of substituting a new stimulus for a familiar stimulus in a familiar environment. Hippocampal place cells were recorded while rats chased food pellets scattered onto the floor of a cylindrical apparatus with a white cue card affixed to the apparatus wall. Once a place cell had been recorded in the presence of the white card, the white card was replaced by a black card of the same size and shape. The place cell was then recorded in the presence of the black card. Thirty-six cells were recorded using this procedure. All cells had stable firing fields in the presence of the white card. Both the white and black cards had stimulus control over place cell firing; generally, rotation of either card caused an equal rotation of the firing fields present. When the black card was substituted for the white card, place cells showed time-variant changes in their spatial firing patterns. The change was such that the spatial firing patterns of the majority of place cells were similar in the presence of the white and black cards during initial black card exposures. During subsequent presentations of the black card, the spatial firing patterns associated with the 2 cards became distinct from each other. Once the differentiation of firing patterns had occurred in a given rat, all place cells subsequently recorded from that rat had different firing patterns in the presence of the white and black cards. The findings are discussed relative to sensory-, motor-, attentional-, and learning-related interpretations of hippocampal function. It is argued that the time-variant alteration of place cell firing fields observed following exposure to a novel stimulus in this study reflects an experience-dependent modification of place cell firing patterns.

Animals↗

PubMed2005

Routine HLA-B genotyping with PCR-sequence-specific oligonucleotides detects a B52 variant (B5206).

A new human leukocyte antigen (HLA)-B allele was found during routine typing of samples for a German unrelated bone marrow donor registry, the "Aktion Knochenmarkspende Bayern". After first interpretation of data of two independent low-resolution sequence-specific oligonucleotide typing tests, a B*51 variant was suggested. Further analysis via sequence-based typing identified the sequence as new B*52 allele. This new allele officially assigned as B*5206 differs from HLA-B*520102 by one nucleotide exchange in exon 2. The mutation is located at nucleotide position 274, at which a cytosine is substituted by a thymine leading to an amino acid change at protein position 67 from serine (TCC) to phenylalanine (TTC).

Alleles↗

PubMed1993

Molecular evolution of the staphylococcal and streptococcal pyrogenic toxin gene family.

The pyrogenic toxin (PT) family is composed of the staphylococcal enterotoxins (SE), the toxic shock syndrome toxin, and the streptococcal pyrogenic exotoxins (SPE). Whereas considerable effort has focused on characterization of PTs due to their unique biological properties, our understanding of the evolution of this gene family is incomplete. Phylogenetic relationships for members of the PT family were estimated by examining the previously reported nucleotide sequences of the genes encoding SPEA, SPEC, SEA, SEB, SEC1, SEC2, SEC3, SED, and SEE. Additionally, we present and analyze sequence data on seven previously unreported sec genes. Within the PT family, sequence divergence was partitioned in a hierarchical fashion such that mean sequence divergence ranged from 1.179 among all 16 toxin genes, 0.443 among those restricted to Staphylococcus, and 0.028 among the genes encoding 10 variants of Type C SE. Results of this study are interpreted as suggesting that the PT family consists of two large clades. One clade consists of the staphylococcal toxins SEA, SEE, and SED, being closely related to the streptococcal toxin SPEC, whereas the other clade depicts close relationships of the staphylococcal toxins SEC and SEB with the streptococcal toxin SPEA.

Amino Acid Sequence↗