Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Structural variants”

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 829 records · Page 46Linked to original sources
PubMed1983

Cytogenetic findings in 311 couples with infertility and reproductive disorders.

Chromosome studies in married couples were performed in order to elucidate their infertility, spontaneous abortions and foetal wastage. Peripheral blood lymphocyte metaphases of 311 persons revealed chromosomal abnormalities in 26 married people. Chromosome aberrations found here were distributed among sex chromosome aneuploidy (complete and mosaic form), structural anomalies of the Y chromosome, autosomal chromosome aneuploidy (mosaic form), and balanced autosomal translocations (complete and mosaic forms). Chromosomal structural variants were observed in chromosome A-1 (1qh +) in one person and in acrocentric chromosomes in 21 persons. They consisted mainly in elongated secondary constriction (NOR) and in large or very large satellites. The acrocentric association frequencies per metaphase were strongly increased in a group of probands carrying acrocentric variants. Their significance awaits further study.

Abortion, Spontaneous↗
PubMed1981

DNA-dependent RNA polymerase I from hepatomas: comparison of activity levels and properties.

Activity levels of DNA-dependent RNA polymerase I (Pol I; ribonucleoside triphosphate: RNA ribonucleotidyl transferase, E.C. 2.7.7.6, eucaryotic type I) have been compared in five transplantable murine hepatomas and livers of three inbred mouse host strains. Three tumors (H6, H4 and H134) contained about 350-450 units of Pol I activity/g of tissue. Two hepatomas (H129 and BW7756) contained about 120-150 units of activity/g of tissue. Livers contained about 100-150 units/g of tissue. Chromatographic comparisons revealed that hepatoma Pol I is slightly less anionic than the liver enzyme. Thermal denaturation studies were carried out using Pol I partially purified from a high-activity line hepatoma (H6), a low-activity line hepatoma (H129) and livers of the appropriate host strains. Pol I from H6 tumors was denatured at 40 degrees C with a half-time of 2 min. The enzyme from H129 tumors and host livers was denaturated with a half-time of 7 min. These data indicate that hepatoma H6 expressed a structural variant of Pol I. This is the first Pol I variant ever reported.

Animals↗
PubMed1994

The FAR domain defines a new Xenopus laevis zinc finger protein subfamily with specific RNA homopolymer binding activity.

The zinc finger motif defines a large superfamily of nucleic acid binding proteins. Conserved amino acid sequence elements associated with structurally variant zinc finger clusters define subfamilies of zinc finger proteins (ZFPs). The FAR domain (Finger Associated Repeats) is a novel type of repeat element found at the amino-terminus in a subfamily of Xenopus laevis ZFPs. Northern blot analyses of three different members of the FAR subfamily (XFO 6, XFO 9-3 and XFG 68) revealed that each of these genes is transcribed during oogenesis, embryogenesis and in all investigated tissues of adult animals thereby indicating a ubiquitous distribution of transcripts. All FAR-ZFPs tested so far have specific RNA homopolymer binding activity; they associate preferentially with poly(U). The FAR repeats possess limited primary sequence homology with a sequence in the nucleolar shuttling protein NO38, within a region that contains a casein kinase II phosphorylation site.

Amino Acid Sequence↗
PubMed1994

Identification of a novel type of alternative splicing of a tyrosine kinase receptor. Juxtamembrane deletion of the c-met protein kinase C serine phosphorylation regulatory site.

We have detected a novel type of structural variant of the tyrosine kinase receptor for c-met, also known as the hepatocyte growth factor receptor, in mouse tissues. The cDNA of the variant transcript of c-met lacks 141 base pairs, which predicts an in-frame deletion of 47 amino acids in the juxtamembrane region of the cytoplasmic domain. Sequence analysis of genomic DNA containing the c-met locus revealed that the absence of a discrete exon is responsible for this 141-base pair deletion and that alternative splicing leads to production of two forms of transcript. These two forms of transcript are designated as c-metsm (for small) and c-metlg (for large) to distinguish the absence or presence of the 141-base pair segment, respectively. The c-metsm variant is present in adult mouse tissues including kidney, liver, and brain as well as in 9-10-day-old embryos. In all cases, expression of c-metsm was lower than that of the normal transcript, c-metlg. An antiserum against mouse c-Met protein immunoprecipitated corresponding protein forms of approximately 152 and approximately 145 kDa from whole kidney lysate under reducing conditions. The size difference of approximately 7 kDa between these isoforms corresponds to the predicted difference of 47 amino acids. The presence of this shorter variant transcript and its corresponding protein isoform in a variety of normal tissues suggests a physiological role. The deleted region in the cytoplasmic domain of c-metsm contains a sequence motif (S985ARS) for protein kinase C phosphorylation that has recently been shown to play a key role in the down-regulation of hepatocyte growth factor receptor kinase activity. The identification of this novel isoform, c-metsm, demonstrates that a tyrosine kinase receptor can achieve additional diversity by alternative splicing at a key regulatory site in its cytoplasmic domain.

Alternative Splicing↗
PubMed1995

Regulation of alpha 6 beta 1 integrin-mediated migration in macrophages.

Several integrin alpha subunits have structural variants that are identical in their extracellular and transmembrane domains but that differ in their cytoplasmic domains. In the present study, we examined the possibility that the A and B variants of the alpha 6 beta 1 integrin laminin receptor differ in function. P388D1 macrophages that had been transfected with the alpha A integrin subunit were 3-4 fold more migratory than P388D1 macrophages that had been transfected with the alpha 6 B integrin subunit. Deletion of the alpha 6 cytoplasmic domain markedly inhibited the ability of the alpha 6 beta 1 receptor to promote migration.

Calcium↗
PubMed1994

Signal transduction in host cells mediated by glycosylphosphatidylinositols of the parasitic protozoa, or why do the parasitic protozoa have so many GPI molecules?

Considerable circumstantial evidence indicates that glycosylphosphatidylinositol (GPI) molecules of mammalian origin are able to mediate signal transduction in lymphoid cells. For example, perturbation of GPI-anchored surface proteins, but not transmembrane forms of these molecules, can lead to the activation of T lymphocytes. GPIs appear also to be precursors of pharmacologically active phosphoinositol-glycans which mediate responses to hormones such as insulin, nerve growth factor and IL-2. Nonetheless, the biochemical mechanisms of signal transduction by GPIs remain obscure. We have shown that structurally defined GPIs of protozoal parasite origin are able to mediate signal transduction in host macrophages and lymphocytes, by substituting for the putative endogenous GPI-based signalling mechanisms of the host. Signalling by parasite GPIs appears to involve the activation of protein tyrosine kinase and protein kinase C. Evidence from other sources indicates that structurally variant GPIs may provide anergic signals to down-regulate host cell function. These phenomena may represent mechanisms by which eukaryotic parasites regulate host cell function, and can explain a variety of pathological and immunological features of protozoal infections. Furthermore, protozoal GPIs may prove to be an informative model system for the analysis of GPI-mediated signal transduction in lymphocytes and macrophages.

Animals↗
PubMed1993

[The karyotypic characteristics of a skin fibroblast line from the Indian muntjac cultured with different sera].

The karyotypic structure of the Indian muntjak skin fibroblast cell line, with 7 chromosomes in modal class, was compared in the cells cultures, with 10 and 3% of fetal calf serum of two different lots. In addition, the effect of the same serum lot on chromosome variability in the two different Indian muntjac skin fibroblast sublines differing in the modal class stability was investigated. In both the cases, the serum affects the cell distribution for the chromosome number. The analysis of correlations between the main and other structure variants of the karyotype (MSVK and SVK) showed that the karyotypic variants are selected for the balanced genotype rather than for particular chromosomes. The changed cultural conditions resulted primary in the selection of the preexisting SVK to convert into MSVK. The lowering in the serum content to 3% induced the increase in chromosome aberrations. The frequency of chromosome aberrations depends on both the serum lot and the chromosomal composition of sublines. Chromosomal breaks and dicentrics are the predominant types of chromosomal disturbances. Dicentrics are produced mainly by chromosomes 1 and 2. The data obtained may suggest that sera could affect karyological characteristics of cultured cells. This indicates that the cytogenetical monitoring is necessary during a long-term cultivation of cell lines.

Animals↗
PubMedDate not supplied

[Endocrine-cell stomach tumors].

Screening of the endocrine cell participation in the stomach carcinoma has been performed. Endocrine cells are found in all stomach tumors and those in which these cells occupy more than 75% of the surface are distinguished as endocrine cell carcinomas (ECC). They are subdivided into well (WD), moderately (MD) and poorly differentiated (PD). ECC are more frequently observed in males, their predominant location is cardia and fundus. The growth in the deep parts of mucosa and submucosa (this determines late clinical symptoms) is characteristic for these tumors. Alveolar, trabecular and glandular structural variants are observed in WD ECC and MD ECC, while PD ECC corresponded to small cell carcinoma (iat cell and intermediate types). Prognosis is unfavorable in MD ECC and PD ECC. Apart from this amacrine and combined tumors with an endocrine component are described. The authors emphasize the necessity to single out ECC from whole group of stomach carcinoma.

Apudoma↗
PubMedDate not supplied

[Carcinoid lung tumors: clinico-morphologic characteristics, diagnosis].

Review of the literature on carcinoid lung tumors covers classification, macro- and microscopical structure, prognosis of typical and atypical carcinoids, role of special staining methods and electron microscopy in their diagnosis. The role of electron microscopy in the diagnosis of a rare structural variant, oncocytic carcinoid, is emphasized.

Carcinoid Tumor↗
PubMed1996

[The effect of the Mycoplasma contamination of 2 kidney cell sublines from the kangaroo rat on their karyotypic structure].

The karyotypic variability has been investigated for two cell sublines of Rat kangaroo kidney cultured for 40-160 days after contamination with Acholeplasma laidlawii, strain PG-8. The contaminated cultures did not differ from non-contaminated ones in cell distribution for chromosome number. The majority of cells of subline NBL-3-11 with modal number of chromosomes displayed the main structural variant of the karyotype (SVK)--2+2+2+2+2+1; in subline NBL-3-17 the main SVK being 3+3+3+3+3+2. A comparison of intact cultures of these sublines in cell distribution for chromosome number show just the opposite direction of aneuploidy processes: cell heterogeneity for chromosome number decreased in NBL-3-11 and increased in NBL-3-17. The quantity of chromosomal aberrations, primarily chromosomal breaks, increases within 40-160 days of cultivation of contaminated cells of subline NBL-3-11. The number of chromosomal aberrations, mainly at the expense of dicentrics due to telomeric associations, increases after 40 days of cultivation of subline NBL-3-17 contaminated cells. During a long-term cultivation (110 days) of subline NBL-3-17 intact cells, there is an increase in the number of chromosomal aberrations, mainly dicentrics, whereas the extent of chromosomal breaks appears much less. The present results and other additional experimental data make it possible to suppose that the increase in chromosomal instability seen in subline NBL-3-17 at a long-term cultivation may be characteristic of this culture, in distinction to subline NBL-3-11. The most frequent breaks were seen in chromosomes 1, 2 and X of intact and contaminated cells in both the sublines. Chromosomes 1, 2 and 4 are mainly involved in dicentric formations by q (long) arms. The role of dicentrics in cell adaptation to in vitro conditions is discussed.

Acholeplasma laidlawii↗
PubMed1996

[Multicenter evaluation of thr Abbott glycosylated hemoglobin assay on IMx].

The Abbott IMx glycated hemoglobin assay was evaluated in a multicentre study. This method utilizes boronate affinity chromatography, and ion-capture technology. This assay determines both total glycohemoglobin (% GHb) and percentage of hemoglobin Alc (% HbAlc). The precision of the assay was evaluated: the intra-assay and interassay coefficients of variation were judged to be satisfactory (< 6.5%). We determined the accuracy of the assay by comparison with a reference HPLC assay for 603 specimens; coefficients of correlation were between 0.88 and 0.96. We studied the interference of bilirubin and glucose and found no interference at usual concentrations. The presence of abnormal hemoglobins (HbF and some Hb structural variants HbS, HbC) was not detected with the Abbott IMx assay; however, this assay showed no significant interference from the hemoglobin variants tested for heterozygous hemoglobinopathies (percentage of abnormal hemoglobin < 60%). We also determined normal values for HbAlc with this technology (164 specimens): 4.1 to 6.1%.

Chromatography, Affinity↗
PubMed1997

Allopeptide-specific T cell reactivity altered by peptide analogs.

Recent evidence indicates that indirect allorecognition plays a key role in initiating and sustaining graft rejection. This self-restricted T cell response is generally limited to a restricted set of dominant immunogenic peptides derived from allogeneic HLA molecules. Here, we have examined whether peptide analogues of the dominant determinant of HLA-DRbeta1*0101 molecule (peptide DR1/22-35), recognized in the context of HLA-DRbeta1*1101 protein, are able to modulate the T cell response against the wild-type peptide Ag. The peptide analogues were generated by introducing single amino acid substitutions at putative MHC and TCR contact positions. Two analogues, 25R/A and 28E/Q, which bound to soluble DR11 protein, but did not stimulate an anti-DR1-specific T cell clone, inhibited the response of the clone to the wild-type peptide by TCR antagonism. Analogs 25R/A and 28E/Q were also able to inhibit the differentiation of Th precursors specific for peptide DR1/22-35. Two other peptides, 26L/I and 27L/V, acted as powerful TCR agonists, inducing a higher proliferative response of the DR1-specific T cell clone, compared with the wild-type peptide. At high concentrations, these peptides induced hyporesponsiveness of TCC-ZL36 in a manner similar to the wild-type peptide. Taken together, the results of this study indicate that specific suppression of indirect allorecognition can be achieved by using structural variants of the dominant allodeterminant.

Amino Acids↗
PubMed1997

Intracellular IL-1 receptor antagonist promoter: cell type-specific and inducible regulatory regions.

The objective of these studies was to examine the molecular mechanisms involved in transcriptional regulation of the gene for the intracellular structural variant of the IL-1 receptor antagonist (icIL-1Ra) molecule. By reverse transcription-PCR analysis, constitutive expression of endogenous icIL-1Ra mRNA was observed in the epithelial cell lines A431 and HT-29, but not in the macrophage cell lines RAW 264.7 and U937, or in the lymphocyte cell lines Raji and Jurkat. However, icIL-1Ra mRNA expression was observed in response to stimulation with LPS in RAW 264.7 cells and to PMA and LPS in U937 cells. To examine the mechanisms of transcriptional regulation, 4.5 kb of the 5' flanking sequence was isolated from the human icIL-1Ra gene, sequenced, cloned into a luciferase expression vector (pIC4525.Luc), and examined in transfection studies. The pIC4525.Luc construct exhibited a pattern of expression in epithelial and macrophage cell lines similar to that of the endogenous icIL-1Ra gene. To obtain a generalized map of cell type-specific and inducible cis-acting DNA elements, nested 5' deletional mutants of the icIL-1Ra promoter were constructed. Results from transfection studies with these icIL-1Ra promoter/luciferase fusion constructs indicated that constitutive expression in epithelial cells was under the control of three positively acting regions located between bases -4525 to -1438, -288 to -156, and -156 to -49. In contrast, basal expression of pIC4525.Luc in transfected but unstimulated RAW 264.7 cells was under the control of a weak inhibitory region located between bases -4525 to -1438 and a strong positive element between -156 and -49. LPS induction of icIL-1Ra transcription in RAW 264.7 cells was regulated by strong positively acting DNA regions between bases -1438 to -909 and -156 to -49. In summary, the proximal region of the icIL-1Ra promoter, between bases -156 to -49, contains positive cis-acting elements that are needed for expression in both epithelial and monocyte cell lines. However, our results indicate that the ability of this proximal promoter region to control expression is strongly influenced, both positively and negatively, by other upstream cis-acting elements in a cell type-specific manner.

Amino Acid Sequence↗
PubMed1997

The human ALL-1/MLL/HRX antigen is predominantly localized in the nucleus of resting and proliferating peripheral blood mononuclear cells.

The ALL-1 gene is an important regulator of embryonal and hematopoietic development, and structural variants of the human gene generated by chromosomal translocations and other genomic alterations presumably act as oncogenes in the pathogenesis of acute leukemias and other hematological malignancies. Antisera against two different epitopes of the human ALL-1 protein (anti-ALL1-N and anti-ALL1-C) were produced. Both sera revealed indistinguishable patterns of antigen localization in human peripheral blood mononuclear cells (PBMCs). In resting PBMCs, the antigen was distributed in a speckled pattern across the nuclei, with an increased density at the nuclear envelope and the nuclear indentation. In mitotically stimulated PBMCs, the antigen surrounded the condensing chromosomes but did not colocalize with chromatin or the nuclear scaffold. The antigen is considered a marker for a novel nuclear subcompartment, a perichromosomal area termed the "chromosomal envelope." In Western blot experiments, the anti-ALL1-N serum reacted with a polypeptide corresponding to the expected full-length 430-kDa ALL-1 protein. Recombinant proteins representing the AT-hook and zinc binding subdomains of the ALL-1 protein interacted in vitro with a degenerate mixture of double-stranded oligodeoxynucleotides. Thus, the ALL-1 protein probably is a DNA-binding protein with both a sequence-unspecific (AT-hook) and a sequence-specific (zinc binding subdomains) double-stranded DNA binding mode.

Animals↗
PubMed1997

Quantitation and histochemical localization of galectin-1 and galectin-1-reactive glycoconjugates in fetal development of bovine organs.

The display of cellular oligosaccharide chains is known to undergo marked developmental changes, as monitored histochemically with plant lectins. In conjunction with endogenous lectins respective ligand structures may have a functional role during fetal development. The assumption of a recognitive, functionally productive interplay prompts the study of the expression of a tissue lectin and of lectin-reactive glycoconjugates concomitantly. Focusing on common beta-galactosides as constituents of oligosaccharide chains and the predominant member of the family of galectins in mammals, namely galectin-1, the question therefore is addressed as to whether expression of lectin and lectin-reactive glycoconjugates exhibits alterations, assessed in three morphologically defined fetal stages and in adult bovine organs. Using a sandwich ELISA, the level of the rather ubiquitous galectin-1 is mostly increased in adult organs relative to respective fetal stages, except for the case of kidney. This developmental course is seen rather seldom, when the amounts of lectin-reactive glycoproteins or glycolipids are quantitated in solid-phase assays after tissue homogenization. Western blotting, combined with probing by labeled galectin-1, discloses primarily quantitative changes in the reactivity of individual glycoproteins. Performing the same assays on extract aliquots with a plant agglutinin, namely the galactoside-binding mistletoe lectin, whose fine specificity is different from galectin-1, its reduced extent of binding in solid-phase assays and the disparate profile of lectin-reactive glycoproteins reveal a non-uniform developmental alteration within the group of structural variants of beta-galactosides. Although sample preparation can affect ligand preservation and/or presentation and thus restricts the comparability of biochemical and histochemical results, especially for soluble reactants, the histochemical studies on frozen and paraffin-embedded sections of bovine heart, kidney and liver demonstrate that the localization of the galectin and of lectin-reactive epitopes can show a similar distribution, as seen in liver and heart, with organ-typical quantitative changes of a rather similar staining profile (heart, kidney) or notable changes in the spatial distribution (liver) in the course of development. This report emphasizes the potential value of combined monitoring of the lectin and its potential in vivo ligands to contribute to eventually unravel organ-related function(s) of a tissue lectin.

Animals↗
PubMedDate not supplied

Hst7: a male sterility mutation perturbing sperm motility, flagellar assembly, and mitochondrial sheath differentiation.

Hst7, a mouse hybrid sterility locus, has been mapped in close linkage to four other hybrid sterility loci, on proximal chromosome 17 within the t complex. When an allele (s) of Hst7 from the species Mus spretus is crossed into the Mus musculus domesticus (laboratory mouse) background, all male offspring are sterile. This occurs regardless of whether the Hst7 allele on the other chromosome 17 homolog is wild-type (+) or an allele (t) derived from the structurally variant homolog known as a t haplotype. Males of the Hst7 genotype s/+ produce sperm that, after release from the cauda epididymis, display moderate asthenospermia (straight line velocity = 49 +/- 4 microm/second, significantly lower than 102 +/- 7 microm/second for congenic wild-type controls) and normal morphology. However, males of the Hst7 genotype s/t produce sperm whose forward movement is below the detectable limit of the sperm motion analysis system. In addition, these sperm exhibit a variety of flagellar abnormalities, with about one third having normal heads attached to sacklike caudal regions. These sacks consist of membrane-delimited cytoplasm containing disorganized and/or misshapen axonemal elements. The remainder of the sperm from s/t mice have flagella with seemingly normal axonemes, although many exhibit enlarged areas of cytoplasm in their midpieces with extra layers of misaligned mitochondria. The s/t sperm mitochondria also display diffuse and vacuolated matrices reminiscent of meiotic germ cell and spermatid mitochondria. Observations of developing spermatids in the s/t testis reveal an unusual phenotype in which gaps of varying length occur in the mitochondrial wrapping of the midpiece. These data suggest that both the s and t alleles of Hst7 are defective alleles that contribute differentially to the severe asthenospermia phenotype and interact genetically to perturb flagellar development.

Alleles↗
PubMed1976

[Pathophysiological and anatomical prerequisites of hemodynamic disorders in the system of small saphenous vein].

112 patients with varicose small sephenous vein were operated upon. The operation was preceded by a careful clinical investigation, including phlebography. The observed changes were correlated with operative findings. It is shown that varicosity may be conditioned by an obstruction of blood outflow in the popliteal vein or small saphenous vein ostium. A relationship between some structural variants of the small saphenous vein and hemodynamic disturbances was noted.

Adolescent↗
PubMedDate not supplied

[Immunohistochemical and ultrastructural characteristics of papillary carcinoma of the thyroid in people living in regions contaminated with radionuclides].

Papillary thyroid carcinoma was studied in 12 patients who lived in the radionuclide polluted and nonpolluted areas. Neither immunohistochemical nor EM differences in the structure of the carcinoma between the contaminated and non-contaminated regions were found. Three structural variants were identified: classical, follicular and mixed, immunohistochemically having follicular-cell differentiation. Three EM types of cell were observed: dark, clear and intermediate.

Adolescent↗