gebhart/patrepeval huggingface dataset:
Fibroblast growth factor-1 interacts with the glucose-regulated protein GRP75/mortalin (1999)

Fibroblast growth factor-1 (FGF-1), which lacks a signal peptide and is intracellularly localized as a result of endogenous expression or endocytosis, is thought to be involved in regulating cell growth and differentiation. In the study reported here, we purified proteins that bind intracellular FGF-1. Affinity adsorption was used to purify FGF-1-binding proteins from rat L6 cells expressing FGF-1. One of the isolated proteins was identified as the glucose-regulated protein GRP75/mortalin/PBP-74/mthsp70, a member of the hsp70 family of heat-shock proteins known to be involved in regulating glucose responses, antigen processing and cell mortality. The interaction of FGF-1 and GRP75/mortalin in vivo was confirmed by co-immunoprecipitation, immunohistochemical co-localization in Rat-1 fibroblasts and by using the yeast two-hybrid system. Moreover, a binding assay in vitro with the use of recombinant FGF-1 and mortalin demonstrated a direct physical interaction between the two proteins. These results reveal that GRP75/mortalin is an intracellular FGF-1-binding protein in cells and suggest that GRP75/mortalin is involved in the trafficking of and/or signalling by FGF-1.
Human acid beta-glucosidase. N-glycosylation site occupancy and the effect of glycosylation on enzymatic activity (1993)

The five potential N-glycosylation sites (sequons) of human acid beta-glucosidase were individually mutated to determine site occupancy and the effect of site occupancy on selected catalytic and stability properties of this enzyme. Each N-glycosylation consensus sequence [Asn-Xaa-(Ser/Thr)] was obliterated by individually substituting glutamine (Q) for asparagine (N). By expression of the normal and mutated cDNAs in insect (Sf9) and COS-1 cells and subsequent immunoblotting with anti-human acid beta-glucosidase antibodies, the four sequons at Asn-19, Asn-59, Asn-146, and Asn-270 were shown to be glycosylated in either source. The sequon at Asn-462 was never occupied. The mutant enzymes N59Q, N146Q, and N270Q were catalytically active and had normal interactions with active site-directed inhibitors as well as with the activators, phosphatidylserine and saposin C. Of the occupied sequons, N-glycosylation of the first was critical to the synthesis of a catalytically active enzyme. Alteration of this sequon, Asn-19-Ala-20-Thr-21, by the substitutions N19Q, N19D, N19E, or T21G led to a lack of glycosylation at this site. Enzymes containing N19Q, N19E, or T21G had significant decreases (3- to 60-fold) in intrinsic enzyme activity. The N19D enzyme had nearly normal catalytic activity and had enhanced activation by phosphatidylserine. These results show that sequon occupancy as well as steric effects at residue 19 are important for the development of an active conformer of this enzyme. This is the first example of a lysosomal hydrolase that requires sequon occupancy for the synthesis of a catalytically active enzyme.
An Essential Role of Cytosolic Phospholipase A2α in Prostaglandin E2–mediated Bone Resorption Associated with Inflammation (2003)

Prostaglandin E (PGE)2 produced by osteoblasts acts as a potent stimulator of bone resorption. Inflammatory bone loss is accompanied by osteoclast formation induced by bone-resorbing cytokines, but the mechanism of PGE2 production and bone resorption in vivo is not fully understood. Using cytosolic phospholipase A2alpha (cPLA2alpha)-null mice, we examined the role of cPLA2alpha in PGE2 synthesis and bone resorption. In bone marrow cultures, interleukin (IL)-1 markedly stimulated PGE2 production and osteoclast formation in wild-type mice, but not in cPLA2alpha-null mice. Osteoblastic bone marrow stromal cells induced the expression of cyclooxygenase (COX)-2 and membrane-bound PGE2 synthase (mPGES) in response to IL-1 and lipopolysaccharide (LPS) to produce PGE2. Osteoblastic stromal cells collected from cPLA2alpha-null mice also induced the expression of COX-2 and mPGES by IL-1 and LPS, but could not produce PGE2 due to the lack of arachidonic acid release. LPS administration to wild-type mice reduced femoral bone mineral density by increased bone resorption. In cPLA2alpha-null mice, however, LPS-induced bone loss could not be observed at all. Here, we show that cPLA2alpha plays a key role in PGE production by osteoblasts and in osteoclastic bone resorption, and suggest a new approach to inflammatory bone disease by inhibiting cPLA2alpha.
Lymphoid tissue- and inflammation-specific endothelial cell differentiation defined by monoclonal antibodies. (1987)

Abstract Endothelial cells play an essential role in immune responses by regulating the entry of leukocytes into lymphoid tissues and sites of inflammation. As an initial approach to analyzing endothelial cell specialization in relation to such immune function, we have produced monoclonal antibodies (MAB) against mouse lymph node endothelium. Three antibodies were selected: MECA-20, recognizing the endothelium of all blood vessels in lymphoid as well as non-lymphoid organs; MECA-217, which stains the endothelium lining large elastic arteries, but among small vessels is specific for post-capillary venules within lymphoid organs and tissues exposed to exogenous antigen, such as skin and uterus; and MECA-325, an antibody that demonstrates specificity for the specialized high endothelial venules (HEV) that control lymphocyte homing into lymph nodes and Peyer's patches. MECA-325 failed to stain vessels in any non-lymphoid organs tested. Immunoperoxidase studies of HEV in lymph node frozen sections, and of isolated high endothelial cells in suspensions, demonstrated that the antigens recognized by all three antibodies are expressed at the cell surface; those defined by MECA-20 and MECA-325 are also present in the cytoplasm. To study the regulation of the antigens defined by these MAB in relation to extra-lymphoid immune reactions, we assessed their expression in induced s.c. granulomas as a model for chronic inflammation. Small vessels in the granulomas were already stained by MECA-217 in the first days of development. In contrast MECA-325 detected postcapillary venules (which frequently displayed the morphologic characteristics of HEV) only from approximately 1 wk, in parallel with the development of a persistent mononuclear cell infiltrate including numerous lymphocytes. The selective appearance of the MECA-325 antigen on vascular endothelium supporting lymphocyte traffic in both lymphoid and extra-lymphoid sites suggests that this antigen may play an important role in the process of lymphocyte extravasation. The demonstration of lymphoid organ- and inflammation-specific microvascular antigens offers direct evidence for a complex specialization of endothelium in relation to immune stimuli, and supports the concept that microvascular differentiation may play an important role in local immune responses.
Tables As a Paradigm for Querying and Restructuring (1996)

) Marc Gyssens y University of Limburg Laks V.S. Lakshmanan z Concordia University Iyer N. Subramanian z Concordia University Abstract Tables are one of the most natural representations of real-life data. Previous table-based data models (such as relational, nested relational, and complex objects models) capture only a limited variety of real-life tables. In this paper, we study the foundations of tabular representations of data. We propose the tabular database model for handling a broad class of natural data representations and develop tabular algebra as a language for querying and restructuring tabular data. We show that the tabular algebra is complete for a very general class of transformations and show that several languages designed for very different purposes can naturally be embedded into the tabular model. We also demonstrate the applicability of our model as a theoretical foundation for on-line analytical processing (OLAP), an emerging technology for complementing the r...
Levetiracetam in Autistic Children: An Open-Label Study (2002)

The objectives of this study were to determine whether autistic children taking levetiracetam (1) showed improvement in the areas of aggression, impulsivity, hyperkinesis, and mood instability, and (2) showed a nootropic response. Ten white autistic boys ranging from 4 to 10 years were compared pretreatment and while taking levetiracetam for an average of 4.1 weeks. Inattention, hyperkinesis, and impulsivity were evaluated using the Achenbach Attention Problems scale, Conners DSM-IV Total scale, and the Conners Attention-Deficit Hyperactivity Disorder Index scale, all of which showed statistically significant improvements. Mood instability was measured with the Conners Global Index (CGI) Emotional Lability and CGI Total scales, both of which showed statistically significant improvements. Aggressive behavior, as measured with the Achenbach Aggression scale, showed statistically significant improvement only for subjects who were not recently weaned from medications that reduce aggression (e.g., risperidone, carbamazepine, desipramine). Levetiracetam may reduce hyperactivity, impulsivity, mood instability, and aggression in autistic children with these problems. No nootropic effect was observed.
Extensive diversity in the recognition of influenza virus hemagglutinin by murine T helper clones. (1986)

A panel of H-2k class II-restricted Th clones were established from individual CBA mice primed by infection with X31 influenza virus. 27 clones, which showed specific recognition of the HA surface glycoprotein, were all H3N2 subtype specific, in contrast to a T cell line which was crossreactive and which may have other specificities. 20 distinct HA-specific clones recognized a tryptic cleavage fragment of X31 consisting of residue 28-328 of HA1 (tops) which includes all the Ab-combining regions of the HA molecule. Seven other HA-specific clones failed to respond to either tops or to aggregate (the remainder of the virus after tryptic cleavage of tops). The specificity of these clones has been mapped, tentatively, to a conformational determinant in the interface antibody-binding region of the HA trimer. Analysis of the fine specificity of the HA-specific clones against a panel of H3N2 natural variant viruses isolated from major virus epidemics from 1968 to 1984 revealed a hitherto unrecognized diversity in T cell recognition of a HA. A total of 12 specificity groupings were evident, and varied from groups of clones that recognized all natural variants to one clone that responded only to isolates from 1968 to 1972. Six out of eight clones from a major specificity group, which failed to recognize variants TX/77, BK/79, or CN/84, responded to two overlapping peptides (48-68 and 53-87), corresponding to a region of HA1 that includes part of two antibody combining sites. An examination of the amino acid sequences of natural variant viruses from this region of HA revealed that residues Asn53 and Asn54 and/or Ile62 were critical for recognition by these clones. We conclude that recognition of HA by Th cells is not restricted to a limited number of epitopes in the conserved regions of the molecule, but is extremely diverse and includes specificities that map to variable antibody-combining regions of the molecule. In addition, the sensitivity of the T cell clones to the amino acid substitutions occurring in HA1 of natural variant viruses suggests that Th may play a role in the immune pressure for antigenic variation in the HA molecule.
Mass fragmentographic assay for 25‐hydroxyvitamin D in plasma without derivatization: Enhanced sensitivity for metabolites of vitamins D2 and D3 after pre‐column dehydration (1995)

Abstract A mass fragmentographic method for the measurement in plasma of underivatized, dehydrated 25‐hydroxyvitamin D 2 and 25‐hydroxyvitamin D 3 was developed. Quantitative dehydration of vitamin D metabolites was achieved prior to gas chromatography using a new high‐temperature injection system and a small precolumn packed with aluminium powder in the injection port, followed by mass fragmentography on an inexpensive bench‐top mass spectrometer. Plasma (2 ml) was incubated with hexadeuteriated 25‐hydroxyvitamin D 3 prior to acetonitrile extraction and purification using cartridges pre‐packed with microparticulate silica using reversed‐ and normal‐phase solvent systems. After purification, capillary gas chromatography mass spectrometry was carried out following dehydration of the secosteroids on the aluminium power pre‐column at 400°C. High‐intensity dehydrated molecular ions were produced which were used for selected ion monitoring. The assay sensitivity for 25‐hydroxyvitamin D was approximately 1 ng ml −1 . The intra‐assay variation was less than 7% and the recovery of added standard was quantitative. It is suggested that this method may be used to provide target values for much needed quality control schemes to monitor assays routinely used in the estimation of 25‐hydroxyvitamin D. The behaviour of a number of other hydroxylated vitamin D metabolites, when injected without derivatization on to a gas chromatographic column, was also investigated.
Ethnic Differences in Arterial Wave Reflections and Normative Equations for Augmentation Index (2011)

Data regarding ethnic differences in wave reflections, which markedly affect the central pressure profile, are very limited. Furthermore, because age, heart rate, and body height are strong determinants of augmentation index, relating single measurements to normative data (in which augmentation index values correspond with average population values of its determinants) is challenging. We studied subject-level data from 10 550 adults enrolled in large population-based studies. In a healthy reference sample (n=3497), we assessed ethnic differences in augmentation index (ratio of second/first systolic peaks) and generated equations for adjusted z scores, allowing for a standardized comparison between individual augmentation index measurements and the normative population mean from subjects of the same age, sex, ethnic population, body height, and heart rate. After adjustment for age, body height, heart rate, and mean arterial pressure, African blacks (women: 154%; men: 138%) and Andean Hispanics (women: 152%; men: 133%) demonstrated higher central (aortic) augmentation index values than British whites (women: 140%; men: 128%), whereas American Indians (women: 133%; men: 122%) demonstrated lower augmentation index (all P<0.0001), without significant differences between Chinese and British whites. Similar results were found for radial augmentation index. Nonlinear ethnic/sex-specific equations for z scores were successfully generated to adjust individual augmentation index values for age, body height, and heart rate. Marked ethnic differences in augmentation index exist, which may contribute to ethnic differences in hypertensive organ damage. Our study provides normative data that can be used to complement the interpretation of individual hemodynamic assessments among men and women of various ethnic populations, after removing the effect of various physiological determinants.
Characterization of human colon cancer antigens recognized by autologous antibodies (1998)

The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) has proven to be a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. In the present study, 48 distinct antigens (NY-CO-1-NY-CO-48) reactive with autologous IgG were identified by SEREX analysis in 4 patients with colon cancer. Sequencing analysis showed that 17 of the cDNA clones were previously uncharacterized molecules and 31 represented known gene products. The individual cDNA clones were analyzed in the following manner: a search for mutations or other structural changes; an analysis of mRNA expression in a panel of normal tissues; and a frequency analysis of the antibody response to the expressed product in the sera of colon cancer patients and normal individuals. The initial analysis showed NY-CO-13 to be a mutated version of the p53 tumor suppressor gene. Three of the 48 antigens showed a differential pattern of mRNA expression, with NY-CO-27 (galectin-4) expressed primarily in gastrointestinal tract, and NY-CO-37 and -38 showing a pattern of tissue-specific isoforms. With regard to immunogenicity, 20 of the 48 antigens were detected by allogeneic sera; 14 of these were reactive with sera from both normal donors and cancer patients, and 6 other clones (NY-CO-8, -9, -13, -16, -20 and -38) reacted exclusively with sera from colon cancer patients (ranging from 14% to 27%). Our results on colon cancer illustrate both the complexity and the potential of the SEREX approach for analysis of the humoral immune response against human cancer.
The Chemistry of Isatin. (1944)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of Isatin.Ward C. SumpterCite this: Chem. Rev. 1944, 34, 3, 393–434Publication Date (Print):June 1, 1944Publication History Published online1 May 2002Published inissue 1 June 1944https://pubs.acs.org/doi/10.1021/cr60109a003https://doi.org/10.1021/cr60109a003research-articleACS PublicationsRequest reuse permissionsArticle Views5117Altmetric-Citations141LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A novel bite force recorder and maximal isometric bite force values for healthy young adults (1993)

Human bite forces have been studied with several types of equipment, and the maximal values reported have varied greatly. In the present study, a new bite force recorder was developed to measure human bite forces. When measuring maximal bite force, the mandible is, laterally and sagittally, almost in the intercuspal position, while the vertical opening of the jaws in the molar region is about 14 mm. Several teeth bite upon the housing. A quartz force transducer serves as a sensory unit. A microprocessor produces a numeric result, shown on a liquid crystal display (LCD). In order to adapt the sensor to be a part of a bite force recorder, we designed a unilateral housing of nonhardened tool steel. In laboratory calibration tests, a series of loads from 112.8 to 1691.5 N was used. The maximal bite forces of healthy undergraduate dental students, 15 men and 15 women, were investigated. The results for both genders remarkably exceeded the values previously reported for unilateral housings. The mean maximal bite force value in the molar region was 847 N for men and 597 N for women. The finding that pain or lack of muscular strength most often limited the clenching suggests that the actual masticatory potential was registered.
Heat Shock Protein and Gliadin Peptide Promote Development of Peptidase Antibodies in Children with Autism and Patients with Autoimmune Disease (2004)

Searching for a mechanism underlying autoimmunity in autism, we postulated that gliadin peptides, heat shock protein 60 (HSP-60), and streptokinase (SK) bind to different peptidases resulting in autoantibody production against these components. We assessed this hypothesis in patients with autism and in those with mixed connective tissue diseases. Associated with antigliadin and anti-HSP antibodies, children with autism and patients with autoimmune disease developed anti-dipeptidylpeptidase I (DPP I), anti-dipeptidylpeptidase IV (DPP IV [or CD26]) and anti-aminopeptidase N (CD13) autoantibodies. A significant percentage of autoimmune and autistic sera were associated with elevated immunoglobulin G (IgG), IgM, or IgA antibodies against three peptidases, gliadin, and HSP-60. These antibodies are specific, since immune absorption demonstrated that only specific antigens (e.g., DPP IV absorption of anti-DPP IV), significantly reduced IgG, IgM, and IgA antibody levels. For direct demonstration of SK, HSP-60, and gliadin peptide binding to DPP IV, microtiter wells coated with DPP IV were reacted with SK, HSP-60, and gliadin. They were then reacted with anti-DPP IV or anti-SK, anti-HSP, and antigliadin antibodies. Adding SK, HSP-60, and gliadin peptides to DPP IV resulted in 27 to 43% inhibition of the DPP IV-anti-DPP IV reaction, but DPP IV-positive peptides caused 18 to 20% enhancement of antigen-antibody reactions. We propose that (i) superantigens (e.g., SK and HSP-60) and dietary proteins (e.g., gliadin peptides) in individuals with predisposing HLA molecules bind to aminopeptidases and (ii) they induce autoantibodies to peptides and tissue antigens. Dysfunctional membrane peptidases and autoantibody production may result in neuroimmune dysregulation and autoimmunity.
Properties of Kaurene Synthetase from Marah macrocarpus Endosperm: Evidence for the Participation of Separate but Interacting Enzymes (1981)

Ent-kaurene is synthesized from geranylgeranyl pyrophosphate in a two step sequence catalyzed by kaurene synthetase; the first step (A activity) involves the conversion of geranylgeranyl pyrophosphate into the intermediate ent-trans labda-8(17), 13-dien-15-yl pyrophosphate (copalyl pyrophosphate) which is further cyclized to ent-kaurene in the second step (B activity). The resolution of enzyme fractions which catalyze each step independent of the other has been accomplished for the first time by means of QAE Sephadex A-50 chromatography and polyacrylamide gel electrophoresis of kaurene synthetase preparations from endosperm tissue of immature seed of Marah macrocarpus. Molecular weights for the A and B enzymes were each estimated as approximately 82,000 by means of gel filtration chromatography and sedimentation velocity determinations.Experiments in which [(14)C]geranylgeranyl pyrophosphate and [(3)H]copalyl pyrophosphate were incubated simultaneously with kaurene synthetase preparations demonstrated that copalyl pyrophosphate derived from [(14)C]geranylgeranyl pyrophosphate is more readily converted to kaurene than is exogenously added [(3)H]copalyl pyrophosphate. This implies that copalyl pyrophosphate derived from the catalytic site of the A enzyme is preferentially channelled to the B enzyme catalytic site for conversion to ent-kaurene, rather than freely equilibrating with a pool of copalyl pyrophosphate in the medium. Experiments in which the rates of the overall AB and independent B activities of kaurene synthetase preparations were measured as a function of total protein concentration further suggest that overall AB activity is catalyzed by an AB enzyme complex which is in equilibrium with free A and B enzymes. A model is proposed for M. macrocarpus kaurene synthetase in which separate but interacting A and B enzymes must associate for the efficient production of ent-kaurene from geranylgeranyl pyrophosphate.