Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Variant calling”

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.

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

At least 1,189 records · Page 66Linked to original sources
PubMed1987

Reduction of the observed prevalence of so-called non-A non-B hepatitis using sensitive markers of HBV and herpes viruses infections.

In the absence of a specific marker, the observed prevalence of so called non-A non-B hepatitis depends on the sensitivity of the markers of the other viral infections known to induce hepatitis. We have reevaluated this prevalence after using sensitive markers of HBV (HBs monoclonal radioimmunoassay M-RIA and IgM anti-HBc), EBV (IgM anti-VCA), CMV (IgM anti-CMV) and HSV (IgM anti-HSV) in a group of 53 subjects usually considered as having acute or chronic hepatitis. Detection of IgM against HBc, CMV and HSV used immunocapture tests. Among the 37 patients with acute hepatitis, 11 (30 p. 100) were positive for at least one sensitive marker, including 10 markers of HBV (7 M-RIA and 3 IgM anti-HBc) and one IgM anti-CMV. Among the 16 patients with chronic hepatitis, one was positive for HBV by M-RIA; five patients had a false positive reaction to EBV (IgM anti-VCA) disappearing when rheumatoid factor was eliminated. This study shows that many cases of the so-called non-A non-B hepatitis are in fact due to HBV or to a variant of HBV. Definition of non-A non-B hepatitis must include subjects negative for HBV by M-RIA and IgM anti-HBc and negative for CMV by IgM anti-CMV.

Acute Disease↗
PubMed1986

Pseudotumor of the pterygomaxillary space presenting as anesthesia of the mandibular nerve.

Pseudotumor is a term used to describe a space occupying inflammatory lesion which mimics a true neoplastic process in its clinical presentation. In this paper, we report a pseudotumor of the pterygomaxillary space that presented with anesthesia and paralysis of the mandibular nerve. The importance of this case is to call attention to pseudotumors as a clinical entity and to document a case of an extraordinarily aggressive variant that required a surgical approach usually reserved for malignant tumors.

Cranial Nerve Diseases↗
PubMedDate not supplied

[Comparison of the changes in bioelectric activity recorded simultaneously from the amygdaloid body and the hippocampus and from the cranial surface during the stereoelectroencephalographic examination in epilepsy].

The authors analysed 95 SEEG records in epileptics with prevalent temporal-lobe changes comparing the bioelectric activity of the brain recorded simultaneously in the amygdala, hippocampus, temporal cortex and cranial surface during these investigations and relating them to EEG records obtained before the operation. In these records pathological elements typical of epilepsy were found occurring in different variants synchronously or asynchronously in leads at three above mentioned levels. In the findings reported attention is called to occurrence of seizure discharges in the amygdala and hippocampus which had no equivalent in cortical or cranial bioactivity records. In the light of these SEEG observations and a survey of the literature the authors stress the diagnostic importance of SEEG investigations in epilepsy.

Action Potentials↗
PubMed1977

The Kell blood group, Kx antigen, and chronic granulomatous disease.

The Kell blood group has 18 associated red cell antigens. One, named KX, is the product of an X-linked gene and appears to be a precursor in the Kell biosynthetic pathway. Lack of KX on red cells, caused by inheritance of a variant allele at the X-linked locus, results in gross changes in Kell antigenicity, an effect called the McLeod phenotype. Such cells also show striking morphologic changes. Normal phagocytic leukocytes lack Kell antigens but have strong KX. The leukocytes of boys with X-linked chronic granulomatous disease lack KX antigen and have defective bactericidal function. The fundamental defect in chronic granulomatous disease appears to be failure to inherit the X-linked gene that determines KX synthesis. The enzymatic and functional disorders of the leukocytes, and the structural changes in the red cells, are consequences that follow.

Antibodies↗
PubMed1998

Cryptorchidism as a caudal developmental field defect. A new description of cryptorchidism associated with malformations and dysplasias of the kidneys, the ureters and the spine from T10 to S5.

Cryptorchidism is a feature of abnormalities in the hypothalamo-pituitary-testicular axis, and almost all disorders of sexual differentiation in which a testis is present. We found cryptorchidism to be associated with malformations and dysplasias of the kidneys, the ureters and the spine from T10 to S5. The description of this association is new. The association was seen in 18% of cryptorchid boys younger than 3 years of age in a department of paediatric surgery, in 34% of cryptorchid foetuses who died in the third trimester, in 65% of cryptorchid patients with imperforate anus, and in all individuals with tritonmelia, the male variant of sirenomelia. Sirenomelia/tritonmelia is an extreme degree of abnormal differentiation of the caudal developmental field, also called caudal dysplasia, the caudal regression syndrome and the caudal regression malformation sequence. Caudal developmental field defects were also the predominant abnormalities in the other groups of patients. Thus, cryptorchidism may be a feature of abnormal differentiation of the caudal developmental field. Position and histology of the undescended testes of the patients included in the association were similar to in cryptorchidism in general. In the literature the association was reported in 5-10% of boys considered to suffer from cryptorchidism only. Furthermore, our observations are concordant with recent theories about cryptorchidism. Consequently, we propose that cryptorchidism in general may be a caudal developmental field defect. Study of cryptorchid patients exhibiting malformations or dysplasias of the kidneys, the ureters or the spine from T10 to S5 is essential in order to isolate new genetic disorders and to spot environmental factors causing cryptorchidism.

Animals↗
PubMed1997

P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1.

The factors determining disease severity in malaria are complex and include host polymorphisms, acquired immunity and parasite virulence. Studies in Africa have shown that severe malaria is associated with the ability of erythrocytes infected with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form rosettes. The molecular basis of resetting is not well understood, although a group of low-molecular-mass proteins called rosettins have been described as potential parasite ligands. Infected erythrocytes also bind to endothelial cells, and this interaction is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP1, which is encoded by the var gene family. Here we report that the parasite ligand for rosetting in a P. falciparum clone is PfEMP1, encoded by a specific var gene. We also report that complement-receptor 1 (CR1) on erythrocytes plays a role in the formation of rosettes and that erythrocytes with a common African CR1 polymorphism (S1(a-)) have reduced adhesion to the domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans that influence the interaction between erythrocytes and PfEMP1 may protect against severe malaria.

Africa↗
PubMedDate not supplied

Unusual variant of holoprosencephaly in monosomy 13q.

The clinical phenotype related to the terminal deletion of the long arm of the chromosome 13 (the so-called 13q- syndrome) includes a considerable number of malformations, especially of the brain. This report describes five cases of a cerebral midline anomaly that leads to a particular clover-shaped type of holoprosencephaly in 13q- fetuses at different stages of the second and third trimesters of gestation. Our cases are compared to those in literature reviews. This malformation has only been described by computer tomography and magnetic resonance imaging in eight children of various ages and has been called "middle interhemispheric fusion" or syntelencephaly. Recently, the human gene ZIC2, the mutation of which leads to holoprosencephaly, has been mapped to the long arm of chromosome 13. on band q32. These findings suggest that this particular type of holoprosencephaly may be related to ZIC2 gene loss of function.

Adult↗
PubMed1975

[Dense deposit nephropathy: a peculiar variant of glomerulonephritis or a distinct disease entity (author's transl)].

In four renal biopsies of two patients with chronic glomerulonephritis (GN), the so-called dense deposit nephropathy (NDD) was diagnosed by means of light, electron, and immunofluorescence microscopy. In routine paraffin sections the picture approached that of the membrano-proliferative GN. In semithin sections (toluidine blue, periodic acid-Ag-methenamine) and especially in the ultrastructure there appeared extensive confluent deposits of a very dense substance, infiltrating the lamina densa of glomerular capillaries, basal membranes of both Bowman's capsules and tubules, and arteriolar walls. In this localization, a non-diffuse "psdudolinear" deposition of beta1c was detected, whereas antisera to main Ig-fractions and fibrin(ogen) were not fixed. In a biopsy performed six years later, a concentration of dense depositis towards the mesangial area and a partial regeneration of basal membranes were observed. In a part of dense deposits there appeared vacuolization, primarily in tubular and arteriolar basal membranes. In glomeruli, focal IgM deposits were apparent at an advanced stage. NDD apparently is a sequel of a particular metabolic (immune?) process, afflicting solely the renal membranous system and distinctly dns known at present. The noncharacteristic clinical presentation resembles chronic. GN, is very protracted, lengthy, and relatively benigh, with a chance of functional and possible even morphological remission.

Adult↗
PubMed1991

Disease progression and viral genome variants in experimental feline leukemia virus-induced immunodeficiency syndrome.

A fatal immunodeficiency syndrome with clinical and pathologic features similar to human AIDS is inducible in cats by experimental inoculation with a specific strain of feline leukemia virus (FeLV) called FeLV-FAIDS. The course of the feline disease is characterized by an age-dependent prodromal period during which a non-disease-specific, common form of proviral DNA is detected in bone marrow. Preceding clinical onset of immunodeficiency is production of high levels of specific, pathogenic variant genomes, primarily as unintegrated viral DNA, in bone marrow. Acute immunodeficiency syndrome (survival period approximately 3 months) is associated with a short prodromal period and appearance of a characteristic variant genome (variant A) that persists at high copy number as integrated and full-length unintegrated viral DNA in bone marrow. Chronic immunodeficiency syndrome (survival greater than 1 year) is marked by a longer prodromal period, a more gradual onset of severe clinical immunosuppression, and a predominance of other variant genomes that often contain substantial internal deletions. In both forms of the disease, tissue-specific replication of certain variant viruses is noted in the bone marrow, intestine, and lymph nodes. Evidence from in vitro and in vivo virus transmission studies indicates that the appearance of FeLV-FAIDS variant viruses reflects differential replication of viral genomes pre-existing in the inoculum rather than rapid de novo evolution of new variants within each animal. These results demonstrate that retrovirus-induced immunodeficiency disease in cats can be associated with and prefigured by the amplified replication of specific viral variants in target tissues.

Animals↗
PubMed1985

[Erosive pustular dermatosis of the scalp. A new entity or a variant of pyoderma vegetans].

We report on a 69-year-old woman suffering from an erosive pustular and crusted lesion of the scalp having persisted over years. There could not be found any external cause, and a large number of different physical and medicamental therapies failed. Prompt healing was achieved, however, after a low serum zinc level was corrected by a zinc preparation administered orally.-The dermatosis described closely resembles the so-called "erosive pustular dermatosis of the scalp". A search of the earlier dermatological literature supported our view that this is not a new disease, but rather a variant of pyoderma vegetans, a disease showing extremely variable clinical and histopathological features.

Aged↗
PubMed2006

Known pitfalls of the thyroid neoplasm diagnostics in the view of the new (2004) WHO Classification.

The new (2004) WHO Classification of Tumours of the Thyroid and Parathyroid Gland exhibits both formal and contentual changes compared to the previous one from the year 1988. Comparing both texts we have tried to apply the new norm to some recent diagnostic tasks. The classification of poorly differentiated and undifferentiated neoplasms has been successfully solved by employing the immunohistochemical procedures into the daily routine. Nevertheless, some diagnostic problems persist and can not be solved this way. This is true especially for the borderline neoplasm in the FVPTC category and even more for its oncocytic variant. There appeared shift in the criteria for the diagnosis of oncocytic variant of papillary carcinoma. Newly, the obligatory presence of the nuclei with the characteristics of the conventional papillary neoplasms is required. Thorough elaboration of the TNM system has solved the problem of multifocal lesion staging. Moreover, a web consultation source is recommended. The new Classification includes descriptions of the basic cytodiagnostic features. The post aspiration capsular damage consideration in relation to the diagnosis of the minimally invasive follicular carcinoma is one practical profit thereof. In terms of formal logic a criticisable feature of the new classification is the introduction of the so called "Synonyms". These listings include in fact partly real synonyms by definition, but together in one table quite often also subunits or variants of the nosologic units described. In general, the new Classification represents a successful consensus reached. As there are newly also references with varying opinions included, it is presented more like a point of gravity in this field than an undoubted truth. This also makes it a valuable and useful normative text.

Humans↗
PubMed1999

Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5'-upstream regulatory region.

Cytochrome P450 3A4, the most abundant P450 form in human liver, exhibits a very broad substrate specificity and is of great importance for drug metabolism. The interindividual difference in the hepatic expression of CYP3A4 is considerable. In order to investigate possible genetic factor(s) causing this variation, the rate of 6beta-hydroxylation of testosterone in human liver microsomes prepared from 46 different human liver samples was determined and the 5'upstream region (+10 to -490 bp) was sequenced from genomic DNA isolated from 39 of these livers. We found a 31-fold variation of the testosterone hydroxylase activity between the samples. However, a very high sequence homology between the CYP3A4 5'-upstream regions sequenced from the 78 different alleles was found. In fact, only three variant nucleotide exchanges were identified, all causing a -290 A-->G mutation (CYP3A4-V) in a so called nifedipine specific element (NFSE). The importance of this element and the polymorphism was evaluated by gel shift analysis. Competition experiments revealed that the binding of nuclear proteins, although having lower affinity to the CYP3A4-V form of the element, was unspecific in nature. In accordance, no influence of this polymorphism was seen on the microsomal testosterone hydroxylase activity in vitro. It is concluded that the promoter region of CYP3A4 is highly conserved, the only polymorphism being in the NFSE, which however does not influence the enzyme expression in liver to a significant degree. This casts doubt of a previously described relationship between the CYP3A4-V allele and cancer in the prostate and leukaemia.

Adolescent↗
PubMed2000

The Caenorhabditis elegans Ldb/NLI/Clim orthologue ldb-1 is required for neuronal function.

LIM homeodomain (LIM-HD) and nuclear LIM-only proteins play important roles in a variety of developmental processes in animals. In some cases their activities are modulated by a nuclear LIM binding protein family called Ldb/NLI/Clim. Here we characterize the Ldb/NLI/Clim orthologue ldb-1 of the nematode Caenorhabditis elegans. Two alternatively spliced variants exist, which differ in their amino-termini. The ldb-1 orthologue of Caenorhabditis briggsae has the same structure as that of C. elegans and is highly conserved throughout the open reading frame, while conservation to fly and vertebrate proteins is restricted to specific domains: the dimerization domain, the nuclear localization sequence, and the LIM interaction domain. C. elegans ldb-1 is expressed in neurogenic tissues in embryos, in all neurons in larval and adult stages, and in vulval cells, gonadal sheath cells, and some body muscle cells. C. elegans LDB-1 is able to specifically bind LIM domains in yeast two-hybrid assays. RNA inactivation studies suggest that C. elegans ldb-1 is not required for the differentiation of neurons that express the respective LIM-HD genes or for LIM-HD gene autoregulation. In contrast, ldb-1 is necessary for several neuronal functions mediated by LIM-HD proteins, including the transcriptional activation of mec-2, the mechanosensory neuron-specific stomatin.

Amino Acid Sequence↗
PubMed2004

Special indications in gamma knife surgery.

Pilocytic astrocytoma (PA) represent a rare indication for Gamma Knife Surgery. Mostly small remnants after surgical debulking are treated. The prognosis depends on specific variants of biological and clinical criteria. In this regard we differentiated two groups of tumors; the so-called 'typical' tumors with a histological grading of WHO Grade I, no prior fractionated radiotherapy and no cystic component and the so called 'atypical' tumors with either a malignant transformation, previous fractionated radiotherapy and/or cystic components. The outcome after GKS was much more favourable for typical PA than for atypical. In typical cases a high tumor control with a very low risk of side effects can be achieved.

Adolescent↗
PubMed1981

Spectrum of lymphoid hyperplasia: colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease.

The radiographic pattern of nodular lymphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases.

Adult↗
PubMed2003

Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry.

Of about one dozen human P450 s that catalyze biotransformations of xenobiotics, CYP2D6 is one of the more important ones based on the number of its drug substrates. It shows a very high degree of interindividual variability, which is primarily due to the extensive genetic polymorphism that influences expression and function. This so-called debrisoquine/sparteine oxidation polymorphism has been extensively studied in many different populations and over 80 alleles and allele variants have been described. CYP2D6 protein and enzymatic activity is completely absent in less than 1% of Asian people and in up to 10% of Caucasians with two null alleles, which do not encode a functional P450 protein product. The resulting "poor metabolizer" (PM) phenotype is characterized by the inability to use CYP2D6-dependent metabolic pathways for drug elimination, which affect up to 20% of all clinically used drugs. The consequences are increased risk of adverse drug reactions or lack of therapeutic response. Today, genetic testing predicts the PM phenotype with over 99% certainty. At the other extreme, the "Ultrarapid Metabolizer" (UM) phenotype can be caused by alleles carrying multiple gene copies. "Intermediate Metabolizers" (IM) are severely deficient in their metabolism capacity compared to normal "Extensive Metabolizers" (EM), but in contrast to PMs they express a low amount of residual activity due to the presence of at least one partially deficient allele. Whereas the intricate genetics of the CYP2D6 polymorphism is becoming apparent at ever greater detail, applications in clinical practice are still rare. More clinical studies are needed to show where patients benefit from drug dose adjustment based on their genotype. Computational approaches are used to predict and rationalize substrate specificity and enzymatic properties of CYP2D6. Pharmacophore modeling of ligands and protein homology modeling are two complementary approaches that have been applied with some success. CYP2D6 is not only expressed in liver but also in the gut and in brain neurons, where endogenous substrates with high-turnover have been found. Whether and how brain functions may be influenced by polymorphic expression are interesting questions for the future.

Alleles↗
PubMed2006

Detecting fluorescent protein expression and co-localisation on single secretory vesicles with linear spectral unmixing.

Many questions in cell biology and biophysics involve the quantitation of co-localisation and the interaction of proteins tagged with different fluorophores. However, the incomplete separation of the different colour channels due to the presence of autofluorescence, along with cross-excitation and emission "bleed-through" of one colour channel into the other, all combine to render the interpretation of multi-band images ambiguous. Here we introduce a new live-cell epifluorescence spectral imaging and linear unmixing technique for classifying resolution-limited point objects containing multiple fluorophores. We demonstrate the performance of our technique by detecting, at the single-vesicle level, the co-expression of the vesicle-associated membrane protein, VAMP-2 (also called synaptobrevin-2), linked to either enhanced green fluorescent protein (EGFP) or citrine [a less pH-sensitive variant of enhanced yellow fluorescent protein (EYFP)], in mouse cortical astrocytes. In contrast, the co-expression of VAMP-2-citrine and the lysosomal transporter sialine fused to EGFP resulted in little overlap. Spectral imaging and linear unmixing permit us to fingerprint the expression of spectrally overlapping fluorescent proteins on single secretory organelles in the presence of a spectrally broad autofluorescence. Our technique provides a robust alternative to error-prone dual- or triple colour co-localisation studies.

Animals↗
PubMed1991

Chick laminin: isolation by monoclonal antibodies and differential distribution of variants in the embryo.

In order to study the expression and function of laminin variants during chick embryonic development, we have generated monoclonal antibodies against chick heart laminin. One monoclonal antibody (mAb), called 9/F-10, could be used to purify chick laminin to homogeneity. By rotary shadowing, cross-shaped and T-shaped laminin particles as well as aggregates of two laminin molecules crosslinked via their short arms could be observed in this preparation. Purified chick laminin was very potent in mediating neurite growth by chick embryonic neurons. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced chick heart laminin revealed a complex pattern of polypeptides which are immunologically related to several mammalian laminin chains. The two mAbs, 9/F-10 and 3/E-8, recognize two different types of chick laminin subunits. By immunofluorescence, antibody 3/E-8 labels basement membranes, aortic smooth muscle, and mesenchyme of 6-day-old chick embryos. In contrast, staining by mAb 9/F-10 is confined to basement membranes. Therefore, the two antibodies seem to distinguish between two different chick laminin isoforms.

Animals↗