Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Origin Recognition Complex”

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 1,081 records · Page 60Linked to original sources
PubMed1982

Self recognition in allogeneic thymic chimeras. Self recognition by T helper cells from thymus-engrafted nude mice is restricted to the thymic H-2 haplotype.

To examine the possibility that the thymus determines the I region-restricted self-recognition repertoire expressed by T helper (TH) cells, thymic chimeras were constructed by transplanting allogeneic neonatal thymic lobes into congenitally athymic nude mice. Spleen TH cells from the thymic chimeras were themselves of nude host origin but only cooperated with B+ accessory cells of the thymic haplotype for primary in vitro responses to sheep erythrocytes and trinitrophenyl conjugate of keyhole limpet hemocyanin. Thus, these experiments demonstrate that the self-recognition repertoire expressed by TH cells is determined by the H-2 phenotype of the intrathymic environment in which the TH cells had differentiated.

Animals↗
PubMed2003

Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome.

Monosomy 1p36 is the most common terminal deletion syndrome. This contiguous gene deletion syndrome is presumably caused by haploinsufficiency of a number of genes. We have constructed a contig of overlapping large-insert clones for the most distal 10.5 Mb of 1p36, evaluated the deletion sizes in 61 subjects with monosomy 1p36 from 60 families, and created a natural deletion panel. We found pure terminal deletions, interstitial deletions, derivative chromosomes, and more complex rearrangements. Breakpoints were "binned" into 0.5-Mb regions. Analyses revealed some clustering of breakpoints but no single common breakpoint. Determination of the parental origin showed that 60% of de novo 1p36 terminal deletions arose from the maternally inherited chromosome. Of the 61 subjects, 30 were examined systematically through a protocol at the Texas Children's Hospital General Clinical Research Center. Specifically, we report hearing evaluations, palatal and ophthalmological examinations, echocardiograms, neurological assessments, and thyroid function tests. To our knowledge, this systematic molecular and clinical characterization of monosomy 1p36 is the largest and most comprehensive study of this deletion syndrome to date. Many cytogenetically visible, apparent terminal deletions are more complex than anticipated by cytogenetics, as revealed at the molecular level by our study. Our clinical findings allow for the more accurate recognition of the syndrome and for proper medical evaluation.

Abnormalities, Multiple↗
PubMed2000

Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding.

Human O(6)-alkylguanine-DNA alkyltransferase (AGT), which directly reverses endogenous alkylation at the O(6)-position of guanine, confers resistance to alkylation chemotherapies and is therefore an active anticancer drug target. Crystal structures of active human AGT and its biologically and therapeutically relevant methylated and benzylated product complexes reveal an unexpected zinc-stabilized helical bridge joining a two-domain alpha/beta structure. An asparagine hinge couples the active site motif to a helix-turn-helix (HTH) motif implicated in DNA binding. The reactive cysteine environment, its position within a groove adjacent to the alkyl-binding cavity and mutational analyses characterize DNA-damage recognition and inhibitor specificity, support a structure-based dealkylation mechanism and suggest a molecular basis for destabilization of the alkylated protein. These results support damaged nucleotide flipping facilitated by an arginine finger within the HTH motif to stabilize the extrahelical O(6)-alkylguanine without the protein conformational change originally proposed from the empty Ada structure. Cysteine alkylation sterically shifts the HTH recognition helix to evidently mechanistically couple release of repaired DNA to an opening of the protein fold to promote the biological turnover of the alkylated protein.

Alkylation↗
PubMed1976

Amylase polymorphism: studies of sera and duodenal aspirates in normal individuals and in cystic fibrosis.

Prior genetic studies of the human pancreatic amylase (Amy2) locus have been directed principally to the electrophoretic analysis of serum and urine, on the assumption that these fluids receive negligible contributions from the salivary (Amy 1) locus. In support of that assumption was the observation that the isozyme bands were lacking in patients with cystic fibrosis and in a postpancreatectomy patient. We have examined the sera of 97 patients having cystic fibrosis and find normal levels of serum amylase. On electrophoresis, three-quarters of the cystic fibrosis patients have a pattern (F-pattern) not observed in normal sera. The pattern is characterized by the absence of Pa 1. Comparative electrophoresis and mixing experiments indicate that the F-pattern is of salivary origin and is unmasked in cystic fibrosis by the absence of a pancreatic contribution. The normal serum pattern is considered to be an admixture of salivary and pancreatic amylase. On the assumption that duodenal fluids might more closely reflect the pancreatic (Amy 2) locus, electrophoretic studies were performed on 148 normal individuals and 37 individuals with cystic fibrosis. Electrophoretic phenotypes in duodenal aspirates are more complex than previously reported in studies of urine and serum; presumably because of the higher concentrations of amylase in the aspirates. Comparative electrophoresis and mixing experiments indicate that the phenotypes observed in duodenal aspirates also reflect admixture of pancreatic and salivary amylase. This recognition of pancreatic and salivary admixture in sera fortunately does not alter our prior understanding of the genetics of the Amy 2 polymorphism. The extensive studies which led to the delineation of the Amy 2 polymorphism were essentially based on the presence or absence of a variant band which proves now to be outside the zone of admixture.

Amylases↗
PubMed1997

The self-incompatibility (S) haplotypes of Brassica contain highly divergent and rearranged sequences of ancient origin.

In Brassica, the recognition of self-related pollen by the stigma is controlled by the highly polymorphic S locus that encodes several linked and coadapted genes and can span several hundred kilobases. We used pulsed-field gel electrophoresis to analyze the structure of different S haplotypes. We show that the S2 and S13 haplotypes of Brassica oleracea contain extensive sequence divergence and rearrangement relative to each other. In contrast, haplotypic configuration is more conserved between B. oleracea S13 and B. campestris S8, two haplotypes that have been proposed to be derived from a common ancestral haplotype based on sequence comparisons. These results support the view that extensive restructuring of the S locus preceded speciation in Brassica. This structural heteromorphism, together with haplotype-specific sequences, may suppress recombination within the S locus complex, potentially providing a mechanism for maintaining the linkage of coadapted allelic combinations of genes over time.

Brassica↗
PubMed1995

A functional role for corpora amylacea based on evidence from complement studies.

Few theories have been advanced for the production of corpora amylacea (CA) by the normal ageing brain and by the CNS under various neurological conditions. Proteins derived from neurons and oligodendrocytes are found in CA and to understand their origins brain tissue from patients with Alzheimer's disease (AD), multiple sclerosis (MS) and Pick's disease (PD) were tested for complement activity. All CA were immunopositive for antisera to classical pathway-specific components, the activation products C3d and the terminal complement complex (TCC), the C3 convertase regulator membrane cofactor protein (MCP) and the fluid phase regulators S-protein and clusterin. CA were immunonegative for the alternative complement pathway proteins and the complement regulators, decay accelerating factor (DAF) and CD59. Western immunoblotting of isolated solubilized CA from the same tissues demonstrated a weak band for MCP but TCC was more easily shown by immunoprecipitation. A filamentous fringe around CA, probably of astrocytic origin, was also immunopositive for complement factors. CA consist of an inert mucopolysaccharide matrix encasing ubiquitinated proteins, resulting from death of and damage to neurons, myelin and oligodendrocytes. A function of CA, therefore, could be to prevent the recognition of these immunogenic proteins by lymphocytes and microglia and thus protect the CNS from further injury.

Aging↗
PubMed1981

[The application of a numerical method to the taxonomy of the genus Leishmania Ross, 1903,--The recognition of 146 original lines in the Old World. Use of allozymic characters. Epidemiological and phyletic significance (author's transl)].

Using enzyme characters determined by starch gel electrophoresis, the authors have applied the method of Numerical Taxonomy to the genus Leishmania Ross, 1903. Eight isoenzymes (PGI, ME, PGM, GOT, G-6-PDH, 6-PGDH, MDH and IDH) of 146 Old World strains are examined. 35 electromorphs, corresponding to equivalent number of isoenzymes, are identified by this method, and then grouped into 14 zymodemes. These zymodemes were used as Operational Taxonomy Units (OTU) and pairs were compared, using Jaccard's index of similarity. A matrix of association was constructed using these indices and it forms the basis for the taxonomic scheme elaborated. The final relationships are exhibited in the agglomerative dendrogram, constructed using complete linkage. The separation into phylons is confirmed by correspondence analysis. It is concluded that the original lines fall into five groups corresponding to the complexes Leishmania donovani, Leishmania tropica, Leishmania major, Leishmania aethiopica and cf. Leishmania tarentolae. The phylons as recognised by Numerical Taxonomy, can be equated with the taxa of traditional systematics. The phyletic significance of the individualized phylons is then provided by a genetic approach. Thus, it is possible to compute the genetic distances of Nei with allozyme frequency values of 0,0.5 and 1. The new dendrogram is similar to the previous one: Leishmania major constitutes an homogeneous taxon, long isolated from the others. Leishmania donovani and Leishmania tropica have retained a nonnegligible amount of genetic similarity, attesting both a common origin and a more recent evolutionary divergence.

Animals↗
PubMed2005

Possibilities and limitations in the rational design of modified peptides for T cell mediated immunotherapy.

Therapeutic intervention in experimental autoimmune diseases by modulation of the T cell mediated autoimmune response has been accomplished in the past using altered peptide ligands (APLs). These peptides are usually created by applying alterations to the T cell epitope recognized by the autoaggressive T cells. In this study, we investigated whether it was possible to design APLs in a rational way, using knowledge of molecular interaction in the MHC-peptide-T cell receptor (TCR) complex, for the therapeutic intervention in experimental autoimmune encephalomyelitis (EAE). Additionally, the value of peptidomimetic modification and alterations based on posttranslational modifications for the design of APLs was examined. Based on a molecular model of the MHC-peptide complex, the T cell receptor contact residues were identified and selected alterations were applied. The designed APLs were tested for MHC binding capacity, T cell recognition, blocking of the autoreactive T cell response, immunogenicity, encephalitogenicity, and therapeutic activity. Based on the results of the in vitro assays, it was expected that some of our APLs would be able to modulate EAE. Nevertheless, none of these APLs displayed clear therapeutic activity in vivo. Thus, rational design of modified peptides for immunotherapy has to await further insights into the relationships between structure and peptide/peptidomimetic induced T cell activation, and until that, there is no possibility to take advantage of the tailor made origin of peptidomimetics.

Amino Acid Sequence↗
PubMed1996

Complementary mutations in an antigenic peptide allow for crossreactivity of autoreactive T-cell clones.

T cells recognize antigen by formation of a trimolecular complex in which the T-cell receptor (TCR) recognizes a specific peptide antigen within the groove of a major histocompatibility complex (MHC) molecule. It has generally been assumed that T-cell recognition of two distinct MHC-antigen complexes is due to similarities in the three-dimensional structure of the complexes. Here we report results of experiments examining the crossreactivity of TCRs recognizing the myelin basic protein peptide MBPp85-99 and several of its analogs in the context of MHC. We demonstrate that single conservative amino acid substitutions of the antigenic peptide at the predominant TCR contact residues at positions 91 and 93 totally abrogate reactivity of specific T-cell clones. Yet, when a conservative substitution is made at position 91 concomitant with a substitution at position 93, the T-cell clones regain reactivity equivalent with that of the original stimulating peptide. Thus, the exact nature of the amino acid side chains engaging one TCR functional pocket may change the apparent selectivity of the other predominant TCR functional pocket, thus suggesting a remarkable degree of receptor plasticity. This ability of the TCR-MHC-peptide complex to undergo conformational changes provides a conceptual framework for reconciling the apparent paradox of the extreme selectivity of the TCR and its remarkable crossreactivity with different MHC-peptide complexes.

Amino Acid Sequence↗
PubMed1988

An immunohistochemical study of primary ovarian sarcoma. An evaluation of nine tumors.

Nine cases of primary ovarian sarcoma were studied with a panel of 10 antibodies by using the avidin-biotin-complex immunoperoxidase technique. Original diagnoses included five mixed müllerian tumors (MMT) homologous type, two MMT heterologous type, and two pure sarcomas (PS). Cytokeratin immunoreactivity was observed in epithelial components of all MMTs, but was not observed in PS. Two tumors originally classified as MMT also showed cytokeratin positivity in spindle-cell components. All the PSs and the spindle-cell components in six of seven MMTs showed positive staining for vimentin. Positive staining for desmin and myoglobin was found in one MMT in which cells with cytoplasmic cross-striations were identified on hematoxylin and eosin sections. However, less differentiated rhabdomyoblastic cells also stained for desmin and myoglobin, facilitating their recognition. Immunoreactivity for epithelial membrane antigen was noted in well-differentiated epithelial components of six MMT cases. One case stained with antibodies to carcinoembryonic antigen, four with S-100 protein, five with alpha-1-antitrypsin, and four with muramidase. No staining of stromal hyaline droplets was observed with any antibodies. Because of the immunohistochemical staining pattern, two of the original diagnoses were changed. Application of immunohistochemistry to spindle tumors of ovary is discussed.

Female↗
PubMed2006

S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules.

Damage-associated molecular pattern (DAMP) molecules have been introduced as important proinflammatory factors of innate immunity. One example known for many years to be expressed in cells of myeloid origin are phagocytic S100 proteins, which mediate inflammatory responses and recruit inflammatory cells to sites of tissue damage. An emerging concept of pattern recognition involves the multiligand receptor for advanced glycation end products (RAGE) and Toll-like receptors (TLRs) in sensing not only pathogen-associated molecular patterns (PAMPs) but also endogenous DAMPs, including S100 proteins. S100A8, S100A9, and S100A12 are found at high concentrations in inflamed tissue, where neutrophils and monocytes belong to the most abundant cell types. They exhibit proinflammatory effects in vitro at concentrations found at sites of inflammation in vivo. Although S100A12 binds to RAGE, at least part of the proinflammatory effects of the S100A8/S100A9 complex depend upon interaction with other receptors. Because of the divergent expression patterns, the absence of S100A12 in rodents, the different interaction partners described, and the specific intracellular and extracellular effects reported for these proteins, it is important to differentiate between distinct S100 proteins rather than subsuming them with the term "S100/calgranulins." Analyzing the molecular basis of the specific effects exhibited by these proteins in greater detail bears the potential to elucidate important mechanisms of innate immunity, to establish valid biomarkers of phagocytic inflammation, and eventually to reveal novel targets for innovative anti-inflammatory therapies.

Animals↗
PubMed2004

Wide complex tachycardia: recognition and management in the emergency room.

Cardiac arrhythmias often present as urgent medical conditions requiring immediate care. Patient presenting with a tachyarrhythmia is a common finding in the emergency room. They also occur commonly in patients undergoing non-cardiovascular procedures including surgeries. It is thus pertinent that the physician handling such cases must be appropriately trained to diagnose and provide emergency management till the case is referred to a specialist. Most cases present as a narrow or a wide complex tachycardia. The differential diagnosis is arrived at by deciding on the ECG morphology alongwith relevant history and physical examination where feasible. This article describes the bedside approach to diagnose and treat an arrhythmia presenting as a wide complex. Wide complex tachycardia can result from rhythms originating both from the atrium and the ventricle. Appropriate deduction of the source of the arrhythmia is essential to decide on drug therapy as wrong diagnosis with inappropriate therapy can result in fatalities.

Diagnosis, Differential↗
PubMed1998

Elucidation of a common structure of selective fibrinogen receptor antagonists.

In this paper, we investigate the common structural and electrostatic parameters of a series of specific inhibitors of the alpha IIb beta 3 integrin. Molecular dynamics simulations with an explicit aqueous environment led to an original theoretical pattern. Our results may suggest that the studied non-peptide alpha IIb beta 3 antagonists developed upon the Arg-Gly-Asp ubiquitous recognition sequence, in fact, should mimic the C-terminus part of the fibrinogen gamma chain. This assumption could, therefore, explain their specificity with respect to other Arg-Gly-Asp-dependent integrins.

Amino Acid Sequence↗
PubMed1983

Temporal correlates of discrimination learning.

The relationship between human temporal behavior and learning was investigated by means of an experimental design which measured temporal behavior using the methods of reproduction and production as possible correlates for a complex-form of discrimination-reversal learning. The results indicated that the method of reproduction is a temporal correlate of original learning and that the method of production is a temporal correlate of reversal learning. The theoretical explanations proposed for these results employed the mechanisms of conditioning, extinction, and stimulus generalization, the intervening variables of excitation and inhibition and the Pavlovian levels of behavioral organization of the first and second signalling systems.

Adult↗
PubMed2004

Structural and functional complexity of the humoral response against the Trypanosoma cruzi ribosomal P2 beta protein in patients with chronic Chagas' heart disease.

High levels of antibodies against the C-terminus of the Trypanosoma cruzi TcP2 beta ribosomal protein, defined by the peptide EEEDDDMGFGLFD, named R13, have been measured in sera from patients with chronic Chagas' Heart Disease (cChHD). These antibodies also recognize an epitope on the second extracellular loop of the beta 1-adrenergic receptor, inducing a functional response on cardiomyocytes. The aim of this study was to gain novel insights into the structural basis of this cross-reactivity as well as to evaluate the origin of anti-M2- cholinergic receptor antibodies, which are also commonly found in cChHD patients. To address these questions we immunopurified anti-R13 antibodies and studied the structural requirements of epitope recognition. Results showed that the immunopurified antibodies recognized a conformation of R13 in which the third Glu residue was essential for binding, explaining their low affinity for the mammalian homologue (peptide H13: EESDDDMGFGLFD). Alanine mutation scanning showed individual variations in epitope recognition in each of the studied patients. The importance of a negatively charged residue at position 3 for the recognition of anti-R13 antibodies was further confirmed by competition experiments using a Ser3-phosphorylated H13 analogue, which had 10 times more affinity for the anti-R13 antibody than the native H13 peptide. Moreover, anti-R13 antibodies stimulated either the beta 1-adrenergic or the M2-cholinergic receptor, in strict agreement with the functional properties of the IgG fractions from which they derived, demonstrating that the same parasite antigen may generate antibody specificities with different functional properties. This may be a clue to explain the high variability of electrophysiological disturbances found in cChHD.

Animals↗
PubMed1976

The retrograde His bundle deflection: its recognition and value in the analysis of tachyarrhythmias induced by stimulation on the T wave.

Interpretation of deflections presumably retrograde His bundle in origin has to be performed in context considering the coexisting changes in simultaneously recorded intracardiac and surface leads. His bundle electrocardiography thus conceived is helpful in the analysis of the runs of ectopic beats elicited by premature ventricular stimulation during the antecedent T wave in patients without coronary artery or primary myocardial disease. Identification of AV nodal echoes within the paroxysms as well as the subsequent runs of reciprocating tachycardias, was possible in patients with and without preexcitation, although a thorough study of these cases also requires recording of coronary sinus and low lateral right atrial electrograms. The behavior of the retrograde H deflection in respect to the first extra beat following the premature QRS complex helped in excluding bundle branch reentry. The latter is improbable in patients with 'complete' bundle branch block pattern, if extra beats show a contralateral bundle branch morphology. However, in absence of bundle branch block, retrograde H deflections were not helpful in elucidating the mechanisms of pacemaker-induced intraventricular (bundle branch, fasicular or vulnerability-related) reentry.

Atrioventricular Node↗
PubMed1981

Autologous mixed lymphocyte reactions in NZB mice: analysis in recombinant inbred lines shows a T cell defect unrelated to autoantibody production.

The autologous mixed lymphocyte reaction (AMLR) has been examined in the AMLR-deficient strain, NZB, in C58 mice, which have normal AMLR responses, and in the (NZB x C58) recombinant inbred (NX8 RI) lines. Half of the NX8 RI lines had deficient AMLR and half were comparable in reactivity to the C58 parent strain. AMLR unresponsiveness did not correlate in the NX8 RI lines with H-2 or any other marker known to affect immune recognition. Non-T cells from H-2k NX8 RI lines which had deficient AMLR were able to stimulate an MLR when cultured with T cells of C58 origin. AMLR-positive H-2d lines responded to NZB stimulators, whereas NZB T cells did not respond to any of the H-2d NX8 RI lines but did exhibit strong alloreactivity. Thus, the AMLR defect in NZB mice is due to a T cell lesion. Furthermore, since AMLR deficiency in the NX8 RI lines did not correlate with a positive Coombs test or the production of naturally occurring thymocytotoxic antibody, we conclude that autoimmunity in NZB mice is a complex disease resulting from the inheritance of multiple independently segregating genes.

Animals↗
PubMed1995

Glycosyltransferase mutants: key to new insights in glycobiology.

Glycosyltransferases (Glyc-T's) catalyze the synthesis of the carbohydrate portions of glycoproteins, glycolipids, and proteoglycans. Most Glyc-T's transfer one sugar in one linkage and are encoded by a unique gene. Thus, synthesis of a branched carbohydrate may require expression of at least 30 Glyc-T genes. Mutations that alter Glyc-T activity therefore provide an approach to identifying functions for carbohydrates. These fall into two general categories: 1) intramolecular functions pertaining to the physical and biochemical properties of a glycoconjugate; and 2) intermolecular functions that involve recognition of sugar (or sugars) by another molecule, such as the selectins that bind to specific sugar sequences at the cell surface. In this review, the origin, nature, and uses of Glyc-T mutants that have been used to study both types of carbohydrate function will be summarized. Many Glyc-T genes are now cloned, so transgenic and gene disruption techniques are the latest strategies for identifying new functions for carbohydrates. It is already apparent that the consequences of altering the spectrum of carbohydrates expressed by a cell or an organism range from "none" to "death." A key challenge for the future is to identify molecular bases for the complex phenotypes created by glycosylation engineering. Equally important will be to understand factors that regulate Glyc-T genes, a new class of genes whose study may reveal novel mechanisms of biological regulation.

Animals↗