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 505 records · Page 28Linked to original sources
PubMed1990

Hyperacute T-wave criteria using computer ECG analysis.

Hyperacute T waves (HATWs) have been described as tall-amplitude, primary T-wave abnormalities sometimes seen in the early phases of transmural myocardial infarction. Despite numerous human and animal studies addressing the presence and significance of HATWs, there are no widely held, reliable ECG criteria for their accurate identification. Using a specially designed computer program on a Hewlett-Packard Realm ECG analysis system, we screened 13,393 adult ECGs to identify those having T-wave amplitudes greater than accepted standards (limb leads, greater than 0.5 mV; precordial leads, greater than 1.0 mV). Patients with other known causes of primary and secondary tall T waves were excluded from the study sample. Patients with tall-amplitude T-waves who then developed clinically verifiable myocardial infarction were labeled the HATW group. The HATW group (21) represented 4.1% of the tall T wave group (513) and 0.16% of the entire sample. The remaining patients, who did not meet HATW criteria, were called the early repolarization variant (ERV) group (51). Both groups underwent comparative computer morphology analysis. Nine parameters were statistically significant in discriminating HATWs from early repolarization variants. A combination of J-point position/T-wave amplitude of more than 25%, T-wave amplitude/QRS amplitude of more than 75%, J-point position of more than 0.30 mV, and age of more than 45 years predicted HATWs from a control group with a specificity of 98.0% and a sensitivity of 61.9% and with positive and negative predictive values of 92.9% and 86.2%, respectively. We conclude that HATWs have characterizable discriminating ECG morphology as determined by computer ECG analysis compared with a control group.

Electrocardiography↗
PubMed1997

Neuronal ceroid lipofuscinosis in the Czech Republic: analysis of 57 cases. Report of the 'Prague NCL group'.

A series of 57 patients (from 51 families) with neuronal ceroid lipofuscinosis (NCL) has been diagnosed during the last 25 years. Using clinical and electrophysiological criteria together with results of ultrastructural, histochemical, immunohistochemical and neuropathological analyses it has been possible to classify the following NCL types. Two cases were of the infantile type (CLN1), one case of the juvenile (CLN3) type and one case of the adult (CLN4) type. The bulk of the series was represented by 26 cases of the late infantile (CLN2) type and by 27 cases of the early juvenile (CLN6) type (also called non-Finnish variant late infantile, or Lake-Cavanagh). Besides the infantile form, microcephaly was a relatively frequent finding (nine cases) in the late infantile and early juvenile NCLs. In more than half of the late infantile and early juvenile cases there was a significant reduction of the nerve conduction velocity. The early juvenile CLN6 type was found to have a relatively high incidence in the Romany population (12 cases in nine families). Incidence of NCL in the Czech republic is estimated to be 1.3:100,000.

Adolescent↗
PubMed2002

Persistent human papillomavirus infection and cervical neoplasia.

The development of cervical cancer is preceded by precursor lesions (cervical intraepithelial neoplasia). Evidence-based epidemiological and molecular data suggest that persistent infections with human papillomavirus (HPV) types that carry ahigh oncogenic risk are the intermediate endpoints, leading to both intraepithelial and invasive cervical neoplasia. Integration of highly oncogenic HPVs into host-cell chromosomes is followed by binding of HPV E6 and E7 oncoproteins to tumour-suppressor genes p53 and RB, respectively. This process results in impaired tumour-suppressor-gene function, involving DNA repair, decreased apoptosis, and eventual cell immortalisation. Mutations causing chromosomal alterations, loss of heterozygosity, and proto-oncogene and telomerase activation in immunopermissive individuals have important roles in virus-induced cervical carcinogenesis. The so-called non-European variants of HPV 16 and 18 may increase the degradation potential of p53. HPV 16 is polymorphic and, although the evidence is controversial, the Arg/Arg genotype of p53 could have greater susceptibility to HPV-E6 degradation than the other genotypes. The coincident interplay between the non-European genomic variants of HPV 16/18 and p53 Arg/Arg may explain, at least in part, the persistence of HPV infection and tumour progression in women with cervical neoplasia. Further epidemiological and molecular research is needed, to gain insight into HPV-mediated cervical carcinogenesis. The evidence highlights the need to develop appropriate prophylactic HPV vaccines and diagnostic and screening tests.

Biopsy, Needle↗
PubMed1982

A possible genetic pattern of taurine urinary excretion in Friedreich's Ataxia.

The taurine urinary excretion pattern, before and after an oral load of 250 mg taurine, was studied in normal control subjects and in patients with typical Friedreich's ataxia. It was demonstrated that in both situations the ataxic patients fell within the sub-types of "intermediate" and "high taurine excretors" while non were "low taurine excretors". It was also demonstrated that the excretion of taurine after a load in the obligate heterozygotes parents of the ataxic patients was intermediate between normal controls and patients. It is postulated that patients with Friedreich's Ataxia lack normal regulation of the high affinity-low capacity uptake system for taurine (the TH system) in the brush border of kidney tubules. The low affinity-high capacity uptake system in the same membranes (the TL system) appears to be normal in Friedreich's patients. The normal allele could be called THN and the variant THF and this trait would be inherited in an autosomal recessive fashion if it is linked to the Friedreich phenotype. Whether this finding is or is not the basic genetic defect in Friedreich's Ataxia will require more studies to clarify, but it is of interest to note that a similar pattern appears to be present in the fibroblasts of these patients.

Adult↗
PubMed2005

[Anti IgE antibodies for the treatment of difficult asthma].

INTRODUCTION: Immunoglobulin E (IgE) is a key factor of allergic reaction and is known to be involved in the immunopathology of asthma. In this review, we discuss the results of trials of a monoclonal antibody (omalizumab) against IgE in patients with allergic asthma. STATE OF THE ART: Omalizumab is a humanised murine IgG1 kappa monoclonal antibody which is administered subcutaneously every 2 to 4weeks at a dose calculated according to the patient's body weight and total plasma IgE concentrations. It binds free circulating IgE thus preventing it from binding to high affinity receptors. Omalizumab therapy significantly reduces asthma exacerbations, improves quality of life and has a steroid-sparing effect. It has a good safety profile. This treatment appears to be more effective in the patients with the most severe disease and the worst lung function. CONCLUSION AND PERSPECTIVES: Omalizumab therapy is an important novel treatment for difficult-to-control allergic asthma. Because of its systemic mechanism of action, it may be of particular use in patients displaying multiple allergic pathologies. It remains unknown whether the beneficial effects of omalizumab could be extended to patients with severe non allergic (so-called "intrinsic") asthma, a variant of the disease which is often difficult to control.

Administration, Oral↗
PubMed2001

Removal of the pro-domain does not affect the conformation of the procaspase-3 dimer.

We have investigated the oligomeric properties of procaspase-3 and a mutant that lacks the pro-domain (called pro-less variant). In addition, we have examined the interactions of the 28 amino acid pro-peptide when added in trans to the pro-less variant. By sedimentation equilibrium studies, we have found that procapase-3 is a stable dimer in solution at 25 degrees C and pH 7.2, and we estimate an upper limit for the equilibrium dissociation constant of approximately 50 nM. Considering the expression levels of caspase-3 in Jurkat cells, we predict that procaspase-3 exists as a dimer in vivo. The pro-less variant is also a dimer, with little apparent change in the equilibrium dissociation constant. Thus, in contrast with the long pro-domain caspases, the pro-peptide of caspase-3 does not appear to be involved in dimerization. Results from circular dichroism, fluorescence anisotropy, and FTIR studies demonstrate that the pro-domain interacts weakly with the pro-less variant. The data suggest that the pro-peptide adopts a beta-structure when in contact with the protein, but it is a random coil when free in solution. In addition, when added in trans, the pro-peptide does not inhibit the activity of the mature caspase-3 heterotetramer. On the other hand, the active caspase-3 does not efficiently hydrolyze the pro-domain at the NSVD(9) sequence as occurs when the pro-peptide is in cis to the protease domain. Based on these results, we propose a model for maturation of the procaspase-3 dimer.

Caspase 3↗
PubMed1997

Speed and sequential effects in reaching.

To investigate the impact of future task demands on reaching, participants performed repetitive sagittal-plane reaches at low and high speeds. In a control condition, they reached from a start location to a target and back. In the experimental conditions, they reached from the start to the target, then to a second target (the location of which varied between trials), then back to the first target, and finally back to the start. Contributions of the hip, shoulder, and elbow to reaches made to the first target depended on the second target's location, on movement speed, and on repetition. Participants combined sustained and transient postural adjustments to minimize effort. The results support the knowledge model of movement selection (D. A. Rosenbaum, L. D. Loukopoulos, R. G. M. Meulenbroek, J. Vaughan, & S. E. Engelbrecht, 1995) but also call for its elaboration. Variants of the model are explored through simulations of the above study.

Adult↗
PubMed1998

Differentiation-associated surface antigen variation in the ancient eukaryote Giardia lamblia.

Encystation of Giardia lamblia is required for survival outside the host, whereas excystation initiates infection. The dormant cyst was considered an adaptation to external survival and passage through the stomach. However, we found previously that trophozoites which had recovered after completion of the life cycle had switched their major variant surface protein (VSP), called TSA 417, but neither the timing nor the molecular mechanism of switching had been elucidated. Here we demonstrate that TSA 417 predominates in cysts, but is downregulated during the stage of excystation that models cyst arrival in the small intestine. Transcripts of new VSPs appear late in encystation, and during and after excystation. Trophozoites appear to prepare for switching during encystation, when the major VSP on the cell surface diminishes and is internalized in lysosome-like vacuoles. As short-range DNA rearrangements were not detected, giardial VSP switching during differentiation appears to resemble the in situ switching of surface glycoproteins in African trypanosomes. We also report a unique extended 15 nucleotide polyadenylation signal in all VSP transcripts, but not in other known giardial genes. Antigenic variation during encystation-excystation may be a novel form of immune evasion that could help explain the common occurrence of reinfection by Giardia and other parasites with similar life cycles.

Animals↗
PubMed2005

[Cluster of meningococcal diseases in Allgaeu -- strategies for intervention].

In spring 2004 an accumulation of cases of invasive meningococcal disease was observed in the Allgaeu/Bavaria. Investigations of the isolates showed, that four cases in neighbouring municipalities of the district Oberallgaeu were caused by an identical strain of serogroup C. The particular strain was a rare variant of the so called ET-15 clone, which had caused several outbreaks of severe meningococcal disease among young people in the past, for example in Rottal/Inn (1998), Karlsruhe (1999 - 2000) and Schwerte (2003). The involved health authorities had to decide, which intervention strategies were reasonable and appropriate to the given situation. An epidemiological assessment of the situation was made by the Bavarian Health and Food Safety Authority (LGL) using the recommendations of the permanent immunization committee at the Robert Koch-Institute and of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) . The LGL together with the Robert Koch-Institute and the national meningococcal reference centre concluded that the situation fulfilled the criteria for a vaccination indication in accordance with section sign 20 Abs. 5 of the infectious disease control act (Infektionsschutzgesetz, IfSG). On the basis of this assessment the responsible regional health authority issued a public recommendation for vaccination and the district health authority of the Oberallgaeu was assigned to implement a vaccination campaign. The Oberallgaeu health authority offered vaccination sessions to the public in the concerned communities. The target group comprised babies, children, young people and adults up to twenty years, who lived in the concerned communities in the northern part of Oberallgaeu, as well as close contacts of cases and members of the above age group, who had visited communal facilities in the communities concerned. Our report describes the implementation of the vaccination campaign.

Bacterial Vaccines↗
PubMed2006

Primary sclerosing cholangitis: epidemiology, natural history, and prognosis.

Primary sclerosing cholangitis is a progressive disease associated with significant morbidity and mortality that continues to draw attention from investigators worldwide. Epidemiologic studies indicate that its annual incidence remains stable, although more asymptomatic cases are being diagnosed. Nevertheless, even asymptomatic cases can progress to end-stage liver disease, albeit at a highly variable rate. Moreover, patients are predisposed to several malignancies, especially cholangiocarcinoma, which contributes to their decreased survival. On the other hand, a subgroup of patients with the so-called small-duct variant may have a better prognosis, and those with overlap syndromes with autoimmune hepatitis may respond well to immunosuppressants. Otherwise, efficient treatment is not available for patients with primary sclerosing cholangitis. Thus, even though it occurs rarely, this disease is commonly an indication for liver transplantation. Fortunately, transplantation outcomes are excellent, with overall 5-year survival rates of approximately 80%.

Cholangitis, Sclerosing↗
PubMed1998

Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment.

The PML/SP100 nuclear bodies (NBs) were first described as discrete subnuclear structures containing the SP100 protein. Subsequently, they were shown to contain the PML protein which is part of the oncogenic PML-RARalpha hybrid produced by the t(15;17) chromosomal translocation characteristic of acute promyelocytic leukemia. Yet, the physiological role of these nuclear bodies remains unknown. Here, we show that SP100 binds to members of the heterochromatin protein 1 (HP1) families of non-histone chromosomal proteins. Further, we demonstrate that a naturally occurring splice variant of SP100, here called SP100-HMG, is a member of the high mobility group-1 (HMG-1) protein family and may thus possess DNA-binding potential. Both HP1 and SP100-HMG concentrate in the PML/SP100 NBs, and overexpression of SP100 leads to enhanced accumulation of endogenous HP1 in these structures. When bound to a promoter, SP100, SP100-HMG and HP1 behave as transcriptional repressors in transfected mammalian cells. These observations present molecular evidence for an association between the PML/SP100 NBs and the chromatin nuclear compartment. They support a model in which the NBs may play a role in certain aspects of chromatin dynamics.

Amino Acid Sequence↗
PubMed1989

Amyloid proteins and amyloidoses: complexity updated.

Amyloid is a beta-pleated fibrillar protein principally constituted of light chains of immunoglobulins (kappa or lambda) in primary or myeloma-associated amyloidosis, of AA proteins in secondary amyloidosis and familial. Mediterranean fever, and of variants of prealbumin - now called transthyretin - in senile amyloidosis and in familial polyneuropathies. Other identified amyloidogenic proteins involve APUD protein derivatives (calcitonin), beta 2 microglobulin in chronic hemodialysis-related amyloidosis and beta protein in Alzheimer disease. After a short review of experimental findings and theories concerning the pathogenesis of amyloid deposition, the clinical aspects of amyloidosis are discussed stressing their great diversity. The diagnostic approach is also examined, with particular emphasis on rectal and kidney biopsy and subcutaneous adipose tissue aspirates. Finally, some comments on the treatment of amyloidosis (role of colchicine and DMSO) are made.

Amyloid↗
PubMed1997

Antibiotic resistance in Streptococcus pneumoniae.

Pneumococci were once among the most highly penicillin-susceptible bacteria. However, reports of multidrug-resistant strains have been published since the late 1970s. The rapid spread of resistant clones and the emergence of new variants of resistance mechanisms call for effective surveillance systems and collaboration among clinicians, scientists, the pharmaceutical industry, and regulatory and public health agencies.

Drug Resistance, Microbial↗
PubMed2005

Production of viral vectors using recombinase-mediated cassette exchange.

DNA viruses are often used as vectors for foreign gene expression, but large DNA region from cloned or authentic viral genomes must usually be handled to generate viral vectors. Here, we present a unique system for generating adenoviral vectors by directly substituting a gene of interest in a small transfected plasmid with a replaced gene in a replicating viral genome in Cre-expressing 293 cells using the recombinase-mediated cassette exchange (RMCE) reaction. In combination with a positive selection of the viral cis-acting packaging signal connected with the gene of interest, the purpose vector was enriched to 97.5 and 99.8% after three and four cycles of infection, respectively. Our results also showed that the mutant loxP V (previously called loxP 2272), a variant target of Cre used in the RMCE reaction, was useful as a non-compatible mutant to wild-type loxP. This method could be useful for generating not only a large number of adenovirus vectors simultaneously, but also other DNA virus vectors including helper-dependent adenovirus vector.

Adenoviridae↗
PubMed2001

Development of an advanced polysome display system dependent on a specific protein-RNA motif interaction.

The ribosome display system is a very powerful too for in vitro screening of mRNAs that encode proteins (or peptides) with specific (known and unknown) functions. The ribosome display system depends on the stability of ribosome-mRNA complexes that have been achieved by the removal of a stop codon. An additional interaction we employed was between tandem fused MS2 coat protein (MSp) dimer and the RNA of its specific motif called a "C-variant" (or "Cv"). The MSp dimer and the Cv were placed at the N-terminal end of a nascent protein translated in vitro and the 5'-end of its mRNA, that might circularize the polysome complex and, as a result, further stabilize the ribosome-mRNA complex. The selectivity of mRNAs after selection was increased 2-fold by the introduction of the interaction between the MSp dimer and Cv.

Base Sequence↗
PubMed2000

Use of green fluorescent protein color variants expressed on stable broad-host-range vectors to visualize rhizobia interacting with plants.

We developed two sets of broad-host-range vectors that drive expression of the green fluorescent protein (GFP) or color variants thereof (henceforth collectively called autofluorescent proteins [AFPs]) from the lac promoter. These two sets are based on different replicons that are maintained in a stable fashion in Escherichia coli and rhizobia. Using specific filter sets or a dedicated confocal laser scanning microscope setup in which emitted light is split into its color components through a prism, we were able to unambiguously identify bacteria expressing enhanced cyan fluorescent protein (ECFP) or enhanced yellow fluorescent protein (EYFP) in mixtures of the two. Clearly, these vectors will be valuable tools for competition, cohabitation, and rescue studies and will also allow the visualization of interactions between genetically marked bacteria in vivo. Here, we used these vectors to visualize the interaction between rhizobia and plants. Specifically, we found that progeny from different rhizobia can be found in the same nodule or even in the same infection thread. We also visualized movements of bacteroids within plant nodule cells.

Bacteriological Techniques↗
PubMed1987

Steakhouse spasm.

Sudden esophageal obstruction after eating poorly chewed meat has been called the Steakhouse syndrome. Some cases have demonstrable esophageal narrowing above which food impacts, but in many patients with identical symptoms no underlying obstruction is demonstrated. We report four patients with acute dysphagia who were unable to swallow liquids or solids for as long as 72-96 h. Onset occurred after eating meat in three patients and after taking psyllium in one. All had a structurally normal esophagus demonstrated by x-ray and endoscopy, but motor disorders were defined by manometry in three. We hypothesize that an underlying motor abnormality led to food impaction and call this presumed spastic variant "Steakhouse spasm." We suspect that this is a common but frequently unrecognized manifestation of esophageal dysmotility.

Adult↗
PubMed2004

Natural selection and the organ-specific differentiation of HIV-1 V3 hypervariable region.

The existence of organ-specific HIV-1 populations within infected hosts has been studied for many years; nonetheless results reported by different authors are somewhat discrepant. To tackle this problem, we used a population genetics approach to analyze previously published data from the V3 hypervariable region of the envelope env gene. Our results are compatible with a population subdivision by organs in 95% of individuals analyzed at autopsy. In addition, populations infecting the nervous system and testicles clearly appear as differentiated subsets of the so-called macrophage-tropic variants. Liver and kidney may harbor differentiated populations as well. Although it is widely accepted that organ compartmentalization arises as a consequence of different selective pressures imposed by different organs, a definitive demonstration has not yet been provided. Our analysis of the pattern of synonymous and nonsynonymous nucleotide substitutions provides evidence supporting this hypothesis, without discarding the role of other evolutionary processes. In contrast, positive selection does not seem to be the mechanism responsible for the evolution of patient-specific sequences.

Analysis of Variance↗