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 613 records · Page 34Linked to original sources

PubMed2004

Lipomas, lipoma variants, and well-differentiated liposarcomas (atypical lipomas): results of MRI evaluations of 126 consecutive fatty masses.

OBJECTIVE: Our objectives were to evaluate the reliability of MRI in distinguishing simple lipomas, lipoma variants, and well-differentiated liposarcomas (atypical lipomas) and to identify various imaging mimics of well-differentiated liposarcoma. MATERIALS AND METHODS: One hundred twenty-six consecutively imaged grossly fatty masses were retrospectively reviewed. MRI examinations, their prospective interpretations, and their corresponding pathology reports were compared to determine the reliability of MRI in distinguishing simple lipomas, lipoma variants, and well-differentiated liposarcomas. RESULTS: The success of MRI in identifying well-differentiated liposarcomas among other fatty masses was as follows: sensitivity, 100%; specificity, 83%; accuracy, 84%; positive predictive value, 38%; and negative predictive value, 100%. MRI was 100% specific in the diagnosis of simple lipoma. Sixty-three percent of lesions considered suspicious for well-differentiated liposarcoma were actually simple lipomas (13%) and benign lipoma variants (50%), including chondroid lipoma (13%), osteolipoma (6%), hibernoma (6%), lipoleiomyoma (6%), angiolipoma (6%), and infarcted lipoma (13%). CONCLUSION: Because of differences in treatment, prognosis, and long-term follow-up, it is important to preoperatively distinguish simple lipomas from well-differentiated liposarcomas. MRI is highly sensitive in the detection of well-differentiated liposarcomas and highly specific in the diagnosis of simple lipomas. However, when an extremity or body wall lesion is considered suspicious for well-differentiated liposarcoma, it is more likely (64%) to represent one of many benign lipoma variants.

Adult↗

PubMed1984

Interpretation of measured red cell mass and plasma volume in males with elevated venous PCV values.

A method of interpretation of red cell mass (RCM) and plasma volume (PV) data is described. The results in 188 males with PCV's over 0.50 places the patients in 4 groups: true (absolute) polycythemias, relative (low plasma volume) polycythemias, high normal red cell mass (HNRCM) and 'physiological variant'. Absolute polycythemias were increasingly frequent at higher PCV levels but only reached 100% at a PCV of 0.60. They showed an 18% incidence in the lower PCV range of 0.500-0.519. Relative (low PV) polycythaemia was found in 18% of the patients with PCV values in the range 0.500 to 0.599. Although the HNRCM and 'physiological variant' types found mainly in the lower PCV ranges they occurred at the 0.54 level. While this method of interpretation of RCM and PV data is perhaps arbitrary, it does provide a basis for the proper study of the common group of patients with raised PCV levels in which classification, course and treatment are uncertain. In addition the findings suggest that both RCM and PV should be measured at all levels of PCV over 0.50; that relative (low PV) polycythaemia is a real entity but less common than sometimes believed; that diuretics do not have a notable part in its causation and that the common HNRCM, 'physiological variant' groups are incompletely understood and require further study.

Diuretics↗

PubMedDate not supplied

The pediatric cervical spine: developmental anatomy and clinical aspects.

The radiographic interpretation of the pediatric cervical spine can be a perplexing problem for the emergency physician. Given the wide range of variances in the ossification centers, the unfused synchondroses, and the relative hypermobility of the pediatric cervical spine, radiographs may be easily misread if one is not thoroughly familiar with the developmental anatomy and variants. This paper discusses those developmental aspects of the pediatric cervical spine that impact on emergency radiographic interpretation. Frequently encountered pediatric cervical spine fracture/dislocations are reviewed with an analysis of age-related distributions. Finally, the syndrome of Spinal Cord Injury Without Radiographic Abnormality (SCIWORA) is discussed.

Adolescent↗

PubMed1997

Effect of preformed correct tertiary interactions on rapid two-state tendamistat folding: evidence for hairpins as initiation sites for beta-sheet formation.

The role of preformed correct side chain interactions, such as disulfide bonds, on protein folding kinetics is still not well understood. We investigated the effect of disulfide bond replacements on folding and stability of the small beta-sheet protein tendamistat. Tendamistat folds very fast (tau = 10 ms at pH 7 in water) and without detectable intermediates, which facilitates molecular interpretation of the kinetic data. Tendamistat contains two disulfide bonds, one between cysteines 11 and 27, which connects the ends of a beta-hairpin, and a second one between cysteines 45 and 73, which brings together the two outer strands of a three-stranded beta-sheet. Two single-disulfide variants of the protein were prepared by site-directed mutagenesis (tendamistat C11A/C27S and tendamistat C45A/C73A), and the effects on stability and on folding were monitored. Replacement of either disulfide bond leads to a large decrease in protein stability (DeltaDeltaG0 = 6.0 kcal/mol for the C11A/C27S variant and 5.1 kcal/mol for the C45A/C73A variant). This effect is caused both by entropic stabilization of the unfolded state and by enthalpic destabilization of the native structure. Kinetic experiments show that the main effect of fixed side chain contacts is on the unfolding rate. For both single-disulfide variants, unfolding is strongly accelerated (4250 times in the C11A/C27S variant and 250 times in the C45A/C73A variant) whereas the refolding rate constants are only slightly decreased. The activation parameters show that the observed small effect on the refolding reaction in the C11A/C27S variant is a consequence of large and compensating changes in the entropy and enthalpy of activation. Structural interpretation of the kinetic data suggests that formation of the beta-hairpin stabilized by the C11-C27 disulfide bond forms in the rate-limiting step of the refolding process. The interactions between the outer strands of the beta-sheet connected by the C45-C73 disulfide bond, in contrast, are made late in refolding. These results support the idea that beta-hairpins are initiation sites for beta-sheet formation and that additional strands are added late in the folding process.

Disulfides↗

PubMed2026

Evaluating the pathogenic significance of unique chromosomal variants in craniosynostosis using patient-derived induced pluripotent stem cells and mouse modelling.

PURPOSE: Unravelling causal links between unique structural/copy-number variants (SV/CNV) and associated phenotypes is essential for correct genetic counselling. We investigated two families in which patients with craniosynostosis had SV/CNV potentially dysregulating a fibroblast growth factor (FGF)-encoding gene; a 730 kb dup(4)(q21.21) including FGF5; and a complex 568 kb interspersed 13q12.11 duplication, located 841 kb from FGF9. METHODS: We combined bioinformatic predictions of altered topologically-associating domain (TAD) structure, with experimental analysis (RNA- and ATAC- [assay for transposase-accessible chromatin] sequencing) of patient induced pluripotent stem cell lines (iPSCs) differentiated to neural crest (NCC) and osteoprogenitor (OPC) identities. For the dup(4)(q21.21) we generated a mouse bearing an equivalent rearrangement using CRISPR-Cas9 targeting. RESULTS: TAD analysis suggested potential dysregulation of the FGF5/FGF9 gene by bringing it into a novel genomic milieu. The RNA- and ATAC-seq assays demonstrated FGF5/FGF9 upregulation (2.7-18x) and local opening of chromatin, in 3/4 cell lines. For the dup(4)(q21.21), a causal role was supported by the mouse model, whereas interpretation of the 13q12.11 SV is confounded by a co-existing FOXP2 pathogenic variant. CONCLUSION: Patient iPSC-differentiated NCC and OPC lines, combined with TAD-based modelling to generate testable functional hypotheses, provide valuable functional evidence when evaluating causation of unique SV/CNV in craniosynostosis.

copy-number variant↗

PubMed1982

ECG poor R-wave progression: review and synthesis.

Poor R-wave progression is a common ECG finding that is often inconclusively interpreted as suggestive, but not diagnostic, of anterior myocardial infarction (AMI). Recent studies have shown that poor R-wave progression has the following four distinct major causes: AMI, left ventricular hypertrophy, right ventricular hypertrophy, and a variant of normal with diminished anterior forces. Standard ECG criteria that identify and distinguish these causes have been developed. An interpretive approach to the ECG with poor R-wave progression is presented that has clinical relevance in the daily treatment of patients.

Angiography↗

PubMed1990

Polynesian face and dentition: functional perspective.

Widely dispersed throughout the Pacific, Polynesians are a biologically distinctive people in form and size of both body and head. Large-bodied and well-muscled, their body phenotype is suited to life in a thermolabile oceanic environment. Their craniofacial skeleton is large and robust, with mandibular size and form (the "rocker" mandible) being especially characteristic. In this paper the Polynesian variants of body form, and of facial size (including dentition) and form, are interpreted from a functional perspective.

Anthropometry↗

PubMed2001

Palilalia and repetitive speech: two case studies.

Palilalia, a disorder of speech characterized by compulsive repetitions of utterances has been found in various neurological and psychiatric disorders. It has commonly been interpreted as a defect of motor speech. This article describes palilalia and other variants of verbal repetitive behavior, such as monosyllabic iterations and conduite d'approche. The clinical features of palilalia, its prevalence in different language tasks, and the individual patterns of verbal repetitive behavior are illustrated in two patients with a long-standing cerebrovascular disease. An attempt is made to locate the origin of different forms of verbal repetitions in a standard model of speech production (Butterworth, 1980a; Garrett, 1980; Levelt, 1989) by analysis of their morphology and correlation with impairments of lexical or phonological processes. From these observations it is suggested that palilalia results from control malfunctions at the level of the Articulator, whereas other variants of pathological verbal iterations result from an impairment of the Formulator or from malfunctions of both the Articulator and the Formulator.

Aged↗

PubMed2003

Skeletal scintigraphic appearance of an auto-transplanted osteoarticular plug: epiphyseal transplant.

Nuclear medicine bone scan is an essential diagnostic imaging tool both for the diagnosis and staging of bone tumors and in the follow-up of these patients. It is very important that we be able to discriminate between normal variants, changes related to altered physical stress, and recurrent disease in order to interpret the bone scan meaningfully. We wish to report the appearance of the isotope bone scan, technetium 99m-labeled methylene diphosphonate ((99m)Tc-MDP), associated with an auto-transplanted osteoarticular plug (epiphyseal transplant) performed following limb amputation. This reconstructive surgery can give a potentially misleading appearance on the nuclear medicine bone scan if one is unfamiliar with this surgical technique.

Adolescent↗

PubMed2025

Vaccine efficacy of NVX-CoV2373 against SARS-CoV-2 infection in adolescents in the USA: an ancillary study to a phase 3, observer-blinded, randomised, placebo-controlled trial.

BACKGROUND: Although existing COVID-19 vaccines are known to be highly effective against severe disease and death, data are needed to assess their ability to reduce SARS-CoV-2 infection. We aimed to estimate the efficacy of the NVX-CoV2373 protein subunit vaccine against SARS-CoV-2 infection, regardless of symptoms, among adolescents. METHODS: We performed an ancillary observational study (SNIFF) to the phase 3, observer-blinded, randomised, placebo-controlled PREVENT-19 trial that assessed vaccine efficacy against symptomatic COVID-19 in the USA. Participants in the PREVENT-19 trial included healthy adolescents aged 12-17 years and with no history of laboratory-confirmed SARS-CoV-2 infection. They were randomly assigned (2:1) to receive either the NVX-CoV2373 (Novavax, Gaithersburg, MD, USA) vaccine (immediate NVX-CoV2373 group) or placebo (delayed NVX-CoV2373 group) on days 0 and 21 (initial series). After 2 months, in a crossover series, participants received two doses, 21 days apart, of the intervention that they did not receive in their initial series. Participants at 47 of the PREVENT-19 sites were invited to participate in the SNIFF study and self-collect nasal swabs at home twice weekly for SARS-CoV-2 testing to assess vaccine efficacy against SARS-CoV-2 infection. This primary outcome was defined as the first identification of SARS-CoV-2 detected by RT-PCR, regardless of symptoms, with onset within 4 weeks after the second dose of the initial vaccination series until the second dose of the crossover series. Secondary outcomes were vaccine efficacy against asymptomatic and minimally symptomatic SARS-CoV-2 infection, durability of vaccine efficacy against SARS-CoV-2 infection, and durability of vaccine efficacy against asymptomatic and minimally symptomatic infections. Outcomes were analysed in the modified intention-to-treat population, which included all participants without previous SARS-CoV-2 infection and was restricted to participants enrolled within 4 weeks of the second dose of the primary (primary analysis population) or crossover (post-crossover analysis population) series. This study is registered with ClinicalTrials.gov (NCT04611802). FINDINGS: Between June 1 and Dec 17, 2021, 1196 (53·2%) of the 2247 adolescent participants recruited in the PREVENT-19 trial enrolled in the SNIFF study. The primary analysis population included 471 participants in the immediate NVX-CoV2373 group and 220 in the delayed NVX-CoV2373 group. Incidence of SARS-CoV-2 infection was 14·9 cases per 100 person-years (95% CI 7·9-25·5) in the immediate group and 54·2 cases per 100 person-years (33·6-82·9) in the delayed group; vaccine efficacy was 73·5% (95% CI 47·1-86·7; p=0·0002). Incidence of minimally symptomatic or asymptomatic SARS-CoV-2 infection was 10·3 cases per 100 person-years (95% CI 4·7-19·6) in the immediate group and 36·1 cases per 100 person-years (19·8-60·7) in the delayed group; vaccine efficacy was 72·8% (95% CI 37·1-88·2; p=0·0023). After the second crossover dose, incidence of SARS-CoV-2 was 14·6 cases per 100 person-years (95% CI 8·6-23·0) in the immediate group (receiving placebo at crossover) and 9·1 cases per 100 person-years (3·0-21·3) in the delayed group, with a durability ratio of 160·3 (95% CI 59·5-431·6; p=0·35). Almost all infections after crossover were minimally symptomatic or asymptomatic, with a durability ratio of 151·4 (55·9-410·4; p=0·41). INTERPRETATION: Among adolescents participating in the PREVENT-19 trial during the delta (B.1.617.2) variant wave of the COVID-19 pandemic, the NVX-CoV2373 vaccine was highly efficacious against SARS-CoV-2 infection regardless of symptoms, indicating its potential to reduce the reservoir of infections that contribute to community transmission. FUNDING: US Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.

Adolescent↗

PubMed2004

Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice.

At approximately 6300 amino acids, very large G-protein-coupled receptor-1 (VLGR1, also termed Mass1) is the largest known cell surface protein. It is expressed at high levels within the embryonic nervous system, especially the ventricular zone. A naturally occurring nonsense mutation in VLGR1, V2250X, is linked with susceptibility to audiogenic seizures in mice. Interpretation of this finding is complicated by the existence of splice and transcriptional variants. We targeted the transmembrane and cytoplasmic domains of VLGR1, yielding a gene encoding the complete ectodomain of VLGR1 fused to antigenic tags (VLGR/del7TM). Homozygous mutant mice are susceptible to audiogenic seizures. Western blots detect a single very high molecular weight protein in brain extracts from VLGR/del7TM mice. These findings suggest that loss of VLGR1 transmembrane and cytoplasmic domains underlies the seizure phenotype in both mutant mouse strains, perhaps by disrupting signals regulating neural development.

Alternative Splicing↗

PubMed1996

Sonography of the placenta with emphasis on pathological correlation.

The placenta is a most interesting but unfortunately often ignored and misunderstood organ. Included in its many functions are fetal oxygenation and nutrition as well as a myriad of endocrinological contributions and protein synthesis. The sonologist is strongly encouraged to study this amazing structure with ultrasound because significant pathology afflicts the placenta, often before affecting the fetus. Placental abnormalities, therefore, can be an "early warning system" for fetal problems. Recognition of clinically important lesions (abruption, accreta) as well as important anatomical variants (intervillous thrombosis, septal cyst) is crucial for the physician who performs and interprets prenatal ultrasound. This article discusses the common abnormalities of the placenta and highlights some correlative pathological processes, which will serve to enhance the reader's understanding of sonographic findings. A practical approach is presented with respect to assessment of the hypoechoic lesion, placental infarction, thick placenta, placenta previa, abruption, placenta accreta, and placental tumors.

Female↗

PubMed1982

A molecular explanation of frequency-dependent selection in Drosophila.

Frequency-dependent selection provides a means for maintaining genetic variability within populations, without incurring a large genetic load. There is a wealth of experimental evidence for the existence of frequency-dependent changes in genotypic fitness among a wide variety of organisms. Examples of traits which have been shown to be subject to frequency-dependent selection include the self-incompatibility alleles of plants, chromosomal rearrangements in Drosophila, visible mutations, enzyme variants and rare-male mating advantage in Drosophila. These experiments have been interpreted in a number of different ways. Principally, frequency dependence of genotype fitness may result from intergenotype facilitation due to the production of biotic residues, or from the differential use of resources by the competing genotypes. However, it has proved extremely difficult to isolate and identify any biotic residue of importance or, alternatively, to understand the manner in which genotypes partition the environment. Thus, the difficulty in the interpretation of experiments which show frequency-dependent selective effects stems largely from our lack of understanding of the exact physiological mechanisms which produce these frequency-dependent effects. The principal aim of this study was to investigate the mechanisms associated with frequency-dependent selection at the amylase locus in Drosophila melanogaster. The excretion of catalytically active amylase enzyme and its effect on food medium composition were correlated with the outcome of intraspecific competition between amylase-deficient and amylase-producing genotypes. Amylase-producing genotypes were shown to excrete enzymatically active amylase protein into the food medium. The excreted amylase causes the external digestion of dietary starch; this accounts for the frequency-dependent increase in the viability of the amylase-deficient mutants in mixed cultures, maintained on a starch-rich diet.

Amylases↗

PubMed2002

Giant ancient schwannoma of the posterior mediastinum cytologically misdiagnosed as a malignant tumour. A case report.

We report a case of a 45-year old woman who was found to have a giant mediastinal tumour with radiological degenerative changes. She underwent thoracotomy to remove the mass, which was eventually diagnosed histologically as an ancient schwannoma, whereas cytological interpretation of the accompanying pleural fluid was malignant. Ancient schwannoma is a rare variant of schwannoma, histologically showing atypical features that may result in erroneous diagnosis of a malignant tumour. Clinical and radiological findings are important aids for further consideration of surgical removal of these potentially resectable tumours.

Female↗

PubMed1989

Cell-wall-defective variants of Fusobacterium.

The activity of antimicrobial agents against Fusobacterium species has been reported as variable in the literature. For some strains, the inconsistency arises from difficulty in determining the endpoint of growth in agar dilution susceptibility tests. Certain strains persist as a subtle haze beyond the levels of antibiotic that permit conventional colonial growth. We have determined by light and electron microscopy that this haze represents the colonial growth of cell-wall-defective (CWD) variants of the parent Fusobacterium. The CWD forms could be propagated indefinitely in hypertonic medium containing the antibiotic inducing agent. However, when the antibiotic was eliminated, the organisms would revert to their native morphology. Formation of CWD variants was observed in the presence of cell-wall-active drugs (e.g., beta-lactam agents) but not with drugs that work by a different mechanism (e.g., clindamycin or chloramphenicol). Fourteen of 22 F. varium strains, 8 of 11 F. mortiferum strains, 2 of 10 F. gonidiaformans strains, and 1 of 4 of F. necrophorum strains could be induced to a CWD form in vitro in the usual agar dilution susceptibility test. Although the clinical significance of CWD variants of Fusobacterium is unknown, they may be a source of confusion in interpreting agar dilution susceptibility tests.

Anti-Bacterial Agents↗

PubMed1985

The cerebellopontine angle and internal auditory canal: neurovascular anatomy on gas CT cisternograms.

We reviewed 103 normal gas CT cisternograms to delineate the appearance of normal neurovascular structures in the cerebellopontine angle (CPA) and internal auditory canal (IAC). Cranial nerves VII and VIII were identified in the CPA in 97% of cases, either separately (53%) or as a bundle (44%). Intracanalicular branches of the VIIIth cranial nerve were identified in 20% of cases, and cranial nerve V was visualized in the CPA in 14%. The characteristic vascular loop, usually the anterior inferior cerebellar artery, was visible in 35% of cases, and, in 22% of visualized cases, was in an intracanalicular location. The internal auditory artery was questionably visualized in one case. In 10% of cases, greater than 66% of the IAC was occupied by the neurovascular bundle. Familiarity with the normal anatomy and variants seen on gas CT cisternograms is necessary to prevent false-positive interpretations.

Cerebellopontine Angle↗

PubMed2006

CTL epitope distribution patterns in the Gag and Nef proteins of HIV-1 from subtype A infected subjects in Kenya: use of multiple peptide sets increases the detectable breadth of the CTL response.

BACKGROUND: Subtype A is a major strain in the HIV-1 pandemic in eastern Europe, central Asia and in certain regions of east Africa, notably in rural Kenya. While considerable effort has been focused upon mapping and defining immunodominant CTL epitopes in HIV-1 subtype B and subtype C infections, few epitope mapping studies have focused upon subtype A. RESULTS: We have used the IFN-gamma ELIspot assay and overlapping peptide pools to show that the pattern of CTL recognition of the Gag and Nef proteins in subtype A infection is similar to that seen in subtypes B and C. The p17 and p24 proteins of Gag and the central conserved region of Nef were targeted by CTL from HIV-1-infected Kenyans. Several epitope/HLA associations commonly seen in subtype B and C infection were also observed in subtype A infections. Notably, an immunodominant HLA-C restricted epitope (Gag 296-304; YL9) was observed, with 8/9 HLA-CW0304 subjects responding to this epitope. Screening the cohort with peptide sets representing subtypes A, C and D (the three most prevalent HIV-1 subtypes in east Africa), revealed that peptide sets based upon an homologous subtype (either isolate or consensus) only marginally improved the capacity to detect CTL responses. While the different peptide sets detected a similar number of responses (particularly in the Gag protein), each set was capable of detecting unique responses not identified with the other peptide sets. CONCLUSION: Hence, screening with multiple peptide sets representing different sequences, and by extension different epitope variants, can increase the detectable breadth of the HIV-1-specific CTL response. Interpreting the true extent of cross-reactivity may be hampered by the use of 15-mer peptides at a single concentration and a lack of knowledge of the sequence that primed any given CTL response. Therefore, reagent choice and knowledge of the exact sequences that prime CTL responses will be important factors in experimentally defining cross-reactive CTL responses and their role in HIV-1 disease pathogenesis and validating vaccines aimed at generating broadly cross-reactive CTL responses.

Base Sequence↗

PubMed2004

Determination of kinetic parameters for hammerhead and hairpin ribozymes.

The application of conventional enzymological methods to the study of hairpin and hammerhead ribozymes has led to valuable insights into the mechanisms by which these small RNAs catalyze phosphodiester cleavage and ligation reactions. Here, protocols are presented for measuring rate constants for simple cleavage and ligation reactions mediated by minimal hammerhead and hairpin ribozymes under standard experimental conditions. Information is also provided to help researchers recognize and interpret more complex reaction kinetics that can be observed for ribozyme-sequence variants under a variety of reaction conditions.

Catalysis↗