New Variants (new + variants)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Water Deprivation Headache: "New" Variants of Phenomenology

HEADACHE, Issue 10 2004
Vinod Kumar Gupta MD
No abstract is available for this article. [source]

R6TT,2, New Variants of the Fe2P Structure Type.

CHEMINFORM, Issue 15 2004
Lu6MoSb, Sc6TTe2 (T: Ru, the anti-Typic Sc6Te0.80Bi1.68.
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

New variants of polar glycopeptidolipids detected in Mycobacterium simiae, including ,habana' strains, as evidenced by electrospray ionization-ion trap-mass spectrometry

L. Mederos
Abstract Aims:, To determine the composition of polar glycopeptidolipids (pGPLs) of Mycobacterium simiae and, particularly, those of ,habana' strains, in a search for specific markers given the immunogenic potential of ,habana' TMC 5135 in experimental tuberculosis. Methods and Results:, pGPLs were determined in free lipid extracts using electrospray ionization-ion trap-mass spectrometry (ESI-IT-MS), working in both negative- and positive-ion mode. In the case of TMC 5135, the presence of the previously characterized GPL-II (containing 2,4-di-O-CH3 glucuronic acid as distal sugar in the oligosaccharide antigenic moiety) and GPL-III (containing 4-O-CH3 glucuronic acid as distal sugar) was confirmed using MS/MS and MS/MS/MS approaches. Interestingly, some ,habana' strains presented variants of GPL-II, designated GPL-II,-A and GPL-II,-B. A di-O-CH3 -deoxy-hexose (tentatively, 2,3-di-O-CH3 -fucose) was identified as the penultimate sugar in the oligosaccharide moiety of GPL-II,-A, whereas in GPL-II,-B the penultimate sugar was fucose (tentative identification). On the contrary, the distal sugar of the oligosaccharide chain of pGPLs of Myco. simiae ATCC 25275T was identified as tri-O-CH3 -glucuronic acid (designated GPL-simT -I, with two variants: GPL-simT -I-A and GPL-simT -I-B), O-CH3 -glucuronic acid (designated GPL-simT -II) and di-O-CH3 -glucuronic acid (GPL-II,-A and GPL-II,-B). The penultimate sugar of the oligosaccharide chain of GPL-simT -I-A and GPL-simT -II was identified as di-O-CH3 -deoxy-hexose (tentatively, 2,3-di-O-CH3 fucose), and that of GPL-simT -I-B as deoxy-hexose (tentatively, fucose). In all strains studied, each [M-H], and [M+Na]+ ion was revealed as a mixture of homologous compounds varying in the number of ,O-CH3 groups present in the oligosaccharide moiety and in the length of the fatty acyl linked to the peptide. Conclusions:, The present work indicates that, within a similar general pattern of pGPLs, different strains of Myco. simiae present some variations, so that new compounds (GPL-II,-A, GPL-II,-B, GPL-simT -I-A, GPL-simT -I-B and GPL-simT -II) were defined. Noteworthy was the fact that the ,habana' strains clearly differed from the type strain of Myco. simiae. Significance and Impact of the Study:, The data obtained can be used in the delineation of the ,habana' group of Myco. simiae, including the quality control of the immunogenic strain ,habana' TMC 5135. [source]

Genetic variations associated with psoriasis and psoriatic arthritis found by genome-wide association

Kristina Callis Duffin
ABSTRACT Psoriasis and psoriatic arthritis are immune disorders with a complex polygenic basis. HLA-Cw6, which lies in the major histocompatibility region on chromosome 6, is considered the major genetic determinant of psoriasis. Recent genome-wide association studies have identified new variants outside of the MHC with relevance to the immunology of psoriasis. Variants in or near genes that encode subunits of cytokines (IL12B, IL23A) or cytokine receptors (IL23R) are interesting given that the gene product of IL12B, p40, is the target of a recently approved monoclonal antibody therapy for psoriasis (ustekinumab). Association with psoriasis and psoriatic arthritis has been found in TNFAIP3 and TNFIP1, ubiquitin ligases in the NF-,B pathway, and IL13, a Th2 cytokine. Copy number variation of human beta-defensin and late cornified envelope genes also associate with psoriasis. Many of these genetic variations also associate with immune disorders considered psoriatic co-morbidities, including Crohn's disease and diabetes. [source]

Development of recombinant inhibitors specific to human kallikrein 2 using phage-display selected substrates

FEBS JOURNAL, Issue 3 2004
Sylvain M. Cloutier
The reactive site loop of serpins undoubtedly defines in part their ability to inhibit a particular enzyme. Exchanges in the reactive loop of serpins might reassign the targets and modify the serpin,protease interaction kinetics. Based on this concept, we have developed a procedure to change the specificity of known serpins. First, reactive loops are very good substrates for the target enzymes. Therefore, we have used the phage-display technology to select from a pentapeptide phage library the best substrates for the human prostate kallikrein hK2 [Cloutier, S.M., Chagas, J.R., Mach, J.P., Gygi, C.M., Leisinger, H.J. & Deperthes, D. (2002) Eur. J. Biochem. 269, 2747,2754]. Selected substrates were then transplanted into the reactive site loop of ,1-antichymotrypsin to generate new variants of this serpin, able to inhibit the serine protease. Thus, we have developed some highly specific ,1-antichymotrypsin variants toward human kallikrein 2 which also show high reactivity. These inhibitors might be useful to help elucidate the importance of hK2 in prostate cancer progression. [source]

Lep d 2 polymorphisms in wild and cultured Lepidoglyphus destructor mites

FEBS JOURNAL, Issue 4 2003
Liselotte Kaiser
We have previously cloned, expressed and characterized two variants of the major allergen Lep d 2 from cultured Lepidoglyphus destructor mites. These variants, Lep d 2.0101 and Lep d 2.0201, differ at 13 amino acid positions. In this study we investigated Lep d 2 sequence diversity between wild and cultured mites. PCR, Southern blot and DNA sequence analysis revealed the presence of two different Lep d 2 genes, one with and one without an intron. In addition, two new variants of Lep d 2, Lep d 2.0102 and Lep d 2.0202, were found at different frequencies in wild and cultured mites. When we expressed the Lep d 2 variants and compared their IgE binding properties by ELISA inhibition, we found that Lep d 2.0102 was a more potent inhibitor than Lep d 2.0101, and to a lesser extent Lep d 2.0202 was more potent than Lep d 2.0201. Long-term cultures of peripheral blood mononuclear cells were used to assess the ability of the expressed Lep d 2 variants to induce cytokine release. Although cells from different individuals released different amounts of interferon-, and interleukin-5, no consistent cytokine release pattern could be linked to any specific Lep d 2 variant. In conclusion, we show that both cultured and wild Lepidoglyphus destructor mites contain the same pattern of polymorphism. Furthermore, this Lep d 2 sequence diversity seems not to have any significant impact on the allergens IgE binding or its ability to induce T cell cytokine release. [source]

Six novel alleles identified in Italian hereditary fructose intolerance patients enlarge the mutation spectrum of the aldolase B gene,,

HUMAN MUTATION, Issue 6 2004
Gabriella Esposito
Abstract Hereditary fructose intolerance (HFI) is a recessively inherited disorder of carbohydrate metabolism caused by impaired functioning of human liver aldolase (B isoform; ALDOB). To-date, 29 enzyme-impairing mutations have been identified in the aldolase B gene. Here we report six novel HFI single nucleotide changes identified by sequence analysis in the aldolase B gene. Three of these are missense mutations (g.6846T>C, g.10236G>T, g.10258T>C), one is a nonsense mutation (g.8187C>T) and two affect splicing sites (g.8180G>C and g.10196A>G). We have expressed in bacterial cells the recombinant proteins corresponding to the g.6846T>C (p.I74T), g.10236G>T (p.V222F), and g.10258T>C (p.L229P) natural mutants to study their effect on aldolase B function and structure. All the new variants were insoluble; molecular graphics data suggest this is due to impaired folding. © 2004 Wiley-Liss, Inc. [source]

Novel variants within the coding regions of the Slc11A1 gene identified in Bos taurus and Bos indicus breeds

R. Martínez
Summary Although in the cow the genetic resistance to brucellosis has been previously attributed to the Slc11A1 gene encoding Nramp1 protein, none of the mutations described to date seems to be the cause. To be able to associate another polymorphism of the gene to brucellosis resistance, we characterized the gene and identified in different breeds of Bos taurus and Bos indicus, six new variants among a total of 11 single nucleotide mutations, of which five occurred in the coding sequence (three are missense mutations), one in the promoter region and five in introns. The allelic and genotypic frequencies calculated revealed differences (p < 0.05) among the breeds studied. [source]

Two novel fibrinogen variants found in patients with pulmonary embolism and their families

M. M. L. Hanss
Summary.,Background:,The occurrence of dysfibrinogen is quite rare in comparison with other hemostatic defects, specially in cases of venous thrombosis. Objectives:,Fibrinogen is known to have multiple functions, which are not evaluated by simple coagulation testing. We have used gel electrophoresis to search for new mutations. Patients and methods:,Specimens of purified fibrinogen from 217 consecutive patients with familial or recurrent or early thrombosis and from 490 control subjects were evaluated by electrophoresis. Plasma fibrinogen levels and coagulation-dependent tests (electromechanical and optical coagulometric determinations, immunological measurement, thrombin and Reptilase® times) were normal. Results:,Two novel familial variants were detected. For a 42-year-old patient, an in-frame 117 base pair insertion in the A,-chain gene caused a 5-kDa mobility shift of the A, chain. This corresponds to a 39 amino acid duplication in the connector domain (fibrinogen Champagne au Mont d'Or). This pattern was also found in the patient's mother and child. A second 31-year-old patient presented an extra band under non-reducing conditions, 30 kDa larger than HMW fibrinogen and reacting with antifibrinogen antibodies (fibrinogen Lozanne). A heterozygous 5909A,G mutation was found on the B,-chain gene leading to heterozygous B, Tyr236, stop codon. The predicted truncated B, chain could participate in chain assembly. Two family members were also affected, one of whom had suffered early venous thrombosis. Conclusions:,Electrophoretic testing of apparently normal fibrinogens can reveal new variants which may be clinically relevant. [source]

Distance-two interpolation for parallel algebraic multigrid

Hans De Sterck
Abstract Algebraic multigrid (AMG) is one of the most efficient and scalable parallel algorithms for solving sparse linear systems on unstructured grids. However, for large 3D problems, the coarse grids that are normally used in AMG often lead to growing complexity in terms of memory use and execution time per AMG V-cycle. Sparser coarse grids, such as those obtained by the parallel modified independent set (PMIS) coarsening algorithm, remedy this complexity growth but lead to nonscalable AMG convergence factors when traditional distance-one interpolation methods are used. In this paper, we study the scalability of AMG methods that combine PMIS coarse grids with long-distance interpolation methods. AMG performance and scalability are compared for previously introduced interpolation methods as well as new variants of them for a variety of relevant test problems on parallel computers. It is shown that the increased interpolation accuracy largely restores the scalability of AMG convergence factors for PMIS-coarsened grids, and in combination with complexity reducing methods, such as interpolation truncation, one obtains a class of parallel AMG methods that enjoy excellent scalability properties on large parallel computers. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Linkage and quantitative trait locus mapping of foliage late blight resistance in the wild species Solanum vernei

PLANT BREEDING, Issue 3 2006
K. K. Sřrensen
Abstract The global cultivation of potato (Solanum tuberosum) is threatened by epidemics caused by new variants of the late blight pathogen, Phytophthora infestans. New sources of durable late blight resistance are urgently needed and these may be found in wild Solanum species. The diploid wild species, S. vernei, has not previously been subjected to mapping of quantitative trait loci (QTLs) for late blight resistance. Two populations designated HGIHJS and HGG, originating from a cross between a clone of S. vernei and two different S. tuberosum clones were evaluated in field trials for late blight infestation. The relative area under the disease progress curve (RAUDPC) was estimated and used for QTL mapping. A linkage map of S. vernei, comprising 11 linkage groups, nine of which could be assigned to chromosomes, was constructed. Results indicated that the resistance in S. vernei was quantitatively inherited. Significant QTLs for late blight resistance were identified on chromosomes VIII (HGG), VI and IX (HGIHJS). In addition, potential QTLs were detected on chromosomes VII (HGIHJS) and IX (HGG). A putative and a significant QTL for tuber yield were found on chromosomes VI and VII in HGG, but no linkage between yield and resistance was indicated. The QTL for late blight resistance, which mapped to chromosome IX, could be useful for late blight resistance breeding as it was located close to the microsatellite marker STM1051 in both populations. [source]

Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity

Jorge S Reis-Filho
Abstract Immunohistochemical analysis of E-cadherin has changed the way lobular neoplasia is perceived. It has helped to classify difficult cases of carcinoma in situ with indeterminate features and led to the identification of new variants of lobular carcinoma. Pleomorphic lobular carcinoma (PLC) and pleomorphic lobular carcinoma in situ (PLCIS), recently described variants of invasive and in situ classic lobular carcinoma, are reported to be associated with more aggressive clinical behaviour. Although PLC/PLCIS show morphological features of classic lobular neoplasia and lack E-cadherin expression, it is still unclear whether these lesions evolve through the same genetic pathway as lobular carcinomas or are high-grade ductal neoplasms that have lost E-cadherin. Here we have analysed a case of extensive PLCIS and invasive PLC associated with areas of E-cadherin-negative carcinoma in situ with indeterminate features, using immunohistochemistry, chromogenic in situ hybridization, high-resolution comparative genomic hybridization (CGH) and array-based CGH. We observed that all lesions lacked E-cadherin and ,-catenin and showed gain of 1q and loss of 16q, features that are typical of lobular carcinomas but are not seen in high-grade ductal lesions. In addition, amplifications of c-myc and HER2 were detected in the pleomorphic components, which may account for the high-grade features in this case and the reported aggressive clinical behaviour of these lesions. Taken together, these data suggest that at least some PLCs may evolve from the same precursor or through the same genetic pathway as classic lobular carcinomas. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: First adult-onset patients of a childhood disease

Otto P. Van Diggelen PhD
The fluorogenic enzyme assay for palmitoyl-protein thioesterase (PPT) has greatly facilitated the diagnosis of infantile neuronal ceroid lipofuscinosis (Santavuori-Haltia disease) and the search for possible new variants with atypical clinical presentation. Here, we present the first cases of adult neuronal ceroid lipofuscinosis with onset in the fourth decade of life due to a profound deficiency of PPT. The causative mutations in the CLN1 gene were the known, deleterious mutation R151X and the novel missense mutation G108R. Patients presented at onset (31 and 38 years), with psychiatric symptoms only. At present (ages 56 and 54 years), visual, verbal, and cognitive losses have progressed and both patients have cerebellar ataxia and cannot walk without support. [source]

Changes of the Swedish Bordetella pertussis population in incidence peaks during an acellular pertussis vaccine period between 1997 and 2004,

APMIS, Issue 4 2007
In a surveillance programme undertaken from 1997 through 2004, Bordetella pertussis isolates and clinical information were collected after introduction of acellular pertussis vaccines (Pa) in 1996. Changes in the B. pertussis population were studied in three incidence peaks: 1999,2000, 2002 and 2004. Available isolates from 158 fully vaccinated children representing all of Sweden, plus 37 from the Gothenburg area 2003,2004, were analysed by pulsed-field gel electrophoresis (PFGE), serotyping and sequencing of the virulence factor genes pertussis toxin subunits 1 and 3 (ptxA, ptxC), pertactin (prn), tracheal colonisation factor (tcfA) and fimbria3 (fim3). Allele ptxA1 was found in all isolates. There was a statistically significant increasing trend in three out of five studied genes, ptxC, prn and tcfA, and for a fourth, Fim3, if Gothenburg strains were included. The PFGE profile BpSR11 appearing in the 1999,2000 peak dominated by ,23% during the entire period, bringing with it the allele combination 1/2/2/2/B (ptxA1/ptxC2/prn2/tcfA2/fim3B). Other BpSR11-related profiles with the same allele combination and more than 82% similarity,BpSR5 in the 2002 peak and BpSR12 in the 2004 peak,appeared with an increasing trend. Although vaccination with Pa has reduced disease, new variants have emerged representing clones surviving in the immunized population. [source]

Comparison of multivariate methods for robust parameter design in sheet metal spinning

Corinna Auer
Abstract Sheet metal spinning is a very complex forming process with a large number of quality characteristics. Within the scope of a joint project of the Department of Statistics and the Chair of Forming Technology the impact of process parameters (design factors) on important quality characteristics has been investigated both theoretically and experimentally. In the past, every response has been treated individually and uncontrollable disturbances (noise factors) have been neglected. Now this approach has been extended to robust multiresponse parameter design. For this, a review of common multivariate approaches for robust parameter design has been carried out, which also leads to the proposal of some new variants. In addition to the theoretical comparison, the methods were applied to data gained in the sheet metal spinning process. The obtained results were evaluated in terms of applicability, limitations and quality accuracy. Practical experiments confirmed the high degree of efficiency that the finally proposed method based on desirabilities promises. Copyright © 2004 John Wiley & Sons, Ltd. [source]

A novel missense mutation in the COL7A1 gene causes epidermolysis bullosa pruriginosa

B.-J. Shi
Summary Epidermolysis bullosa (EB) pruriginosa, characterized by severe itching and the presence of nodular prurigo-like or lichenoid lesions, is a rare clinical type of dystrophic EB. Mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils, have been implicated in the pathogenesis of the disorder. In the present study, we screened a Chinese family with EB pruriginosa for COL7A1 mutations by PCR amplification of genomic sequences and direct nucleotide sequencing. The mutation consists of a G,T substitution at nucleotide 6724 in exon 85, which leads to the substitution of glycine by tryptophan at codon 2242. This report adds new variants to the known COL7A1 mutations underlying EB pruriginosa, and provides the basis for genetic counselling and prenatal diagnosis for affected families. [source]