gebhart/patrepeval huggingface dataset:
Human mesenchymal stromal cells : biological characterization and clinical application (2010)

This thesis focuses on the characterization of the biological and functional properties of human mesenchymal stromal cells (MSCs), isolated from different tissue sources. The differentiation capacity of MSCs from fetal and adult tissues has been tested and compared. Umbilical cord blood (UCB) has been investigated as a potential novel source of MSCs for clinical application and the immunomodulatory properties of UCB-derived MSCs have been characterized in comparison with those of MSCs of bone marrow (BM) origin. Moreover, it has been attempted to optimize the experimental conditions for MSC ex vivo expansion. Alternative culture methods, devoid of animal proteins, have been applied by introducing expansion procedures based on platelet-derived growth factors. The potential susceptibility of MSCs to undergo malignant transformation after long-term in vitro culture has been investigated and discussed in view of their clinical application, especially in immunocompromised hosts. The role of MSC therapy in the context of hematopoietic stem cell transplantation (HSCT) has been explored, focusing in particular on the co-transplantation of MSCs to promote engraftment of hematopoietic progenitors, and on the administration of MSCs for the treatment of steroid-resistant, severe acute graft-versus-host disease (GvHD). The role of MSCs in the treatment of inflammatory bowel diseases refractory to conventional therapies, as well as the concept for treating refractory autoimmune diseases has been discussed.
Cystatin F Is a Glycosylated Human Low Molecular Weight Cysteine Proteinase Inhibitor (1998)

A previously undescribed human member of the cystatin superfamily called cystatin F has been identified by expressed sequence tag sequencing in human cDNA libraries. A full-length cDNA clone was obtained from a library made from mRNA of CD34-depleted cord blood cells. The sequence of the cDNA contained an open reading frame encoding a putative 19-residue signal peptide and a mature protein of 126 amino acids with two disulfide bridges and enzyme-binding motifs homologous to those of Family 2 cystatins. Unlike other human cystatins, cystatin F has 2 additional Cys residues, indicating the presence of an extra disulfide bridge stabilizing the N-terminal region of the molecule. Recombinant cystatin F was produced in a baculovirus expression system and characterized. The mature recombinant protein processed by insect cells had an N-terminal segment 7 residues longer than that of cystatin C and displayed reversible inhibition of papain and cathepsin L (Ki = 1.1 and 0.31 nM, respectively), but not cathepsin B. Like cystatin E/M, cystatin F is a glycoprotein, carrying two N-linked carbohydrate chains at positions 36 and 88. An immunoassay for quantification of cystatin F showed that blood contains low levels of the inhibitor (0.9 ng/ml). Six B cell lines in culture secreted barely detectable amounts of cystatin F, but several T cell lines and especially one myeloid cell line secreted significant amounts of the inhibitor. Northern blot analysis revealed that the cystatin F gene is primarily expressed in peripheral blood cells and spleen. Tissue expression clearly different from that of the ubiquitous inhibitor, cystatin C, was also indicated by a high incidence of cystatin F clones in cDNA libraries from dendritic and T cells, but no clones identified by expressed sequence tag sequencing in several B cell libraries and in >600 libraries from other human tissues and cells.
Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin's lymphoma (1996)

Patients with non-Hodgkin's B-cell lymphoma who received an antitumor vaccine of idiotypic ig protein showed humoral and proliferative immune responses. Because immunity to some antigens, including tumor antigens and human pathogenic viruses, may be better correlated with the cytolytic cellular immune response, we evaluated 16 non-Hodgkin's lymphoma patients immunized with autologous idiotypic ig molecules for changes in tumor-specific cytotoxic T-lymphocyte precursor (CTLp) frequency using limiting dilution analysis. Eleven patients had a significant increase in tumor-specific CTLp. Eight of these 11 patients remain without evidence of disease or with stable minimal disease. In contrast, all five patients who did not have a significant change in tumor-specific CTLp have developed progressive disease. Patient vaccination with tumor associated protein antigens can increase tumor-specific CTLp frequencies. The correlation of increased tumor specific CTLp with freedom from progression is significant at P = .002. This study indicates that measurement of CTLp frequencies are relevant to the clinical evaluation of human tumor vaccines and suggests that cell-mediated cytolytic immune responses may be an important determinant of vaccine efficacy.
Identification of a Novel Proline-directed Serine/Threonine Protein Kinase in Rat Pheochromocytoma (1989)

During investigations of the regulation of tyrosine hydroxylase (TH) by protein phosphorylation, a novel protein kinase activity has been discovered in rat pheochromocytoma. Originally detected as a trace contaminant in preparations of highly purified TH, this novel kinase activity phosphorylated TH at serine 8 in the proline-rich amino-terminal region of the enzyme. This particular site is not phosphorylated by, nor is the amino acid sequence surrounding this site selective for, any of the classical (i.e. well characterized) protein kinases. In this report, we describe the identification, characterization, and partial purification of this novel protein kinase. By utilizing a synthetic peptide corresponding to the amino-terminal region of TH, a selective assay for this protein kinase was developed. The kinase activity utilized ATP and magnesium, although GTP could also be utilized as a phosphate donor. The kinase activity was found to co-purify with TH activity through ammonium sulfate precipitation and DEAE-cellulose chromatography and could be only partially resolved from TH by heparin-agarose affinity chromatography. Substantial kinase activity could be resolved from TH by phosphocellulose chromatography. The novel kinase migrates as a protein with a molecular mass of approximately 45 kDa on gel permeation chromatography as well as sucrose density gradient centrifugation. Studies of site specificity indicate that this Ser/Thr kinase activity appears to be directed by an adjacent (carboxyl-terminal) proline residue, exhibiting a minimal recognition sequence of -X-Ser/Thr-Pro-X-. In addition to TH, this proline-directed protein kinase will also phosphorylate synapsin I, histone H1, and glycogen synthase, suggesting that this kinase may have multiple substrates in vivo. Additional findings indicate that the activity of proline-directed protein kinase is increased transiently in PC12 pheochromocytoma cells following treatment with nerve growth factor. Distinctions between this novel kinase and other well characterized protein kinases can be made on the basis of phosphorylation site specificity, chromatographic behavior, and physical characteristics.
Case study : Ningbo, China - cultural heritage conservation in urban upgrading (1999)

This case study is related to the Ningbo Basic Urban Services Upgrading Component of the Zhejiang Multicities Development Project (Credit 2475). The historic city of Ningbo in the coastal province of Zhejiang is an example of a city working to resolve the inherent conflicts between upgrading older urban areas and conserving cultural heritage. The Zhejiang Multicities Development Project included funding the widening of major traffic arteries and upgrading of basic services in the heart of old Ningbo. The Zhejiang Multicities Development Project was designed to improve water supply, land development, environmental management, institutional coordination, and traffic management in three of Zhejiang metropolitan areas. Through this component, the city's political leaders, preservationists, and planners cooperated to implement important development activities which improved people's lives and also conserved valuable cultural heritage.
SWADDLING, A CHILD CARE PRACTICE: HISTORICAL, CULTURAL, AND EXPERIMENTAL OBSERVATIONS (1965)

INFANT care practices are deeply rooted in culture and represent the end results of generations of experience and conviction. It is understandable that few systematic studies of specific aspects of infant care have been undertaken; for each practice (whether feeding, fondling, toileting, etc.) is characterized by a complex process of interaction and methods of evaluation are difficult to define. Yet with progress in the study of physiologic, psychologic, and socio-cultural processes, it should become possible to study the physiologic and developmental consequences of specific infant care practices. The objective of this report is to present the results of our efforts to study one infant care practice—that of swaddling. Interest in this practice grew out of our long-term studies of the development of autonomic nervous system function in infancy. These studies of swaddling and early neurophysiologic capacity complement each other in many ways, as will be shown later. An earlier study of motor restraint by means of swaddling was designed primarily to observe the relationships between autonomic and musculo-skeletal reactivity to stimulation. As the experiment progressed, however, it appeared clear that the process of restraining the infant, per se, often produced a tranquil, "co-operative" state which greatly facilitated the studies of physiologic reactivity. As it became increasingly apparent that pacification was produced in most newborn infants, we considered with heightened curiosity what implications these findings held for clinical pediatrics and, more broadly, for evaluating the cultural practice of infant bundling or swaddling. We began to wonder whether there was not some more pervasive reason for this previously ubiquitous infant care practice, apart from the common anthropologic interpretations which will be described later in this paper.
Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery (2015)

The atomic coordinates and structure factors for tubulin complexed with lexibulin, nocodazole, plinabulin and tivantinib have been deposited in the Protein Data Bank under accession codes 5CA0, 5CA1, 5C8Y and 5CB4, respectively.
Cloning and Nucleotide Sequence of senN, a Novel 'Bacillus natto' (B. subtilis) Gene That Regulates Expression of Extracellular Protein Genes (1988)

A new ‘Bacillus natto’ gene, senN, that regulates the expression of several extracellular proteins in B. subtilis has been cloned and sequenced. senN codes for a small, highly basic protein with an amino acid sequence different from the products coded by the regulatory genes sacQ, sacV, prtR and hpr. SenN stimulates gene expression at the transcriptional level. A putative homologous locus has been detected in the B. subtilis chromosome by Southern blotting.
Type XXVI Collagen, a New Member of the Collagen Family, Is Specifically Expressed in the Testis and Ovary (2002)

HSP47 is a collagen-specific molecular chaperone that specifically recognizes and binds to the triple helical domain of various types of collagens. Here we report the cloning of the entire coding region of a novel collagen-like protein by yeast two-hybrid screening of a 17.5-day whole mouse embryo cDNA library using HSP47 as a bait. The cDNA of this protein and its deduced amino acid sequence are 2,690 bp and 438 amino acids long, respectively. The protein contains two clusters of Gly-X-Y collagenous repeats and three noncollagenous domains. Northern blot analysis showed that its mRNA is specifically expressed in the testis and ovary in adult tissues and that expression in these tissues is highest in the neonate. Biochemical characterization of this protein revealed that its proline residues are hydroxylated, it undergoes N-linked glycosylation, it forms trimers, and it is secreted in vitro. Immunohistochemical studies showed that the myoid cells and the pre-theca cells synthesized it in the testis and ovary, respectively, resulting in the accumulation of this protein in the extracellular spaces of these organs. These observations suggest that this protein is a new member of the collagen protein family. We thus designated this protein as type XXVI collagen.
Structure of theRhizomucor mieheiaspartic proteinase complexed with the inhibitor pepstatin A at 2.7 Å resolution (1999)

Crystals of Rhizomucor miehei aspartic proteinase (RMP) complexed with pepstatin A grew in the orthorhombic space group P212121 and were isomorphous to native RMP crystals. The unit-cell dimensions are a = 41.52, b = 50.82, c = 172.71 A. There is one RMP-pepstatin A complex per asymmetric unit. The structure of the RMP-pepstatin A complex has been refined to a crystallographic R value of 19.3% and an Rfree value of 28.0% at 2.7 A resolution. A pepstatin A molecule fits into the large substrate-binding cleft between the two domains of RMP in an extended conformation up to the alanine residue at the P2' position. The dipeptide analogue statine residue at the P3'-P4' position forms an inverse gamma-turn (P3'-P1') with the statine residue at the P1-P1' position and its leucyl side chain binds back into the S1' subsite. The inhibitor interacts with the residues of the substrate-binding pocket by both hydrogen bonds and hydrophobic interactions. The hydroxyl group of the statine residue at the P1-P1' position forms hydrogen bonds with both catalytic aspartate residues (Asp38 and Asp237). This conformation mimics the expected transition state of the enzyme-substrate interaction. The binding of the inhibitor to the enzyme does not produce large distortions of the active site. No domain movement was observed compared with the native enzyme structure. However, the surface-flap region (residues 82-88) undergoes a conformational change, moving toward the inhibitor and becoming rigid owing to the formation of hydrogen bonds with the inhibitor. B-factor calculations of the two domains suggest that the C-terminal domain becomes more rigid in the complex than in the native structure.
Intrinsic Constraint on Plasmablast Growth and Extrinsic Limits of Plasma Cell Survival (2000)

B cells recruited into splenic antibody responses grow exponentially, either in extrafollicular foci as plasmablasts, or in follicles where they form germinal centers. Both responses yield plasma cells. Although many splenic plasma cells survive <3 d, some live much longer. This study shows that early plasma cell death relates to a finite capacity of the spleen to sustain plasma cells rather than a life span endowed by the cell's origin or the quality of antibody it produces. Antibody responses were compared where the peak numbers of plasma cells in spleen sections varied between 100 and 5,000 cells/mm(2). In each response, plasmablast clones divided some five times, with the peak numbers of plasma cells produced relating directly to the number of B cells recruited into the response. The spleen seems to have the capacity to sustain between 20 and 100 plasma cells/mm(2). When this number is exceeded, there is a loss of excess cells. Immunoglobulin variable region gene sequencing, and 5-bromo-2'-deoxyuridine pulse-chase studies indicate that long-lived splenic plasma cells are a mixture of cells derived from the extrafollicular and germinal center responses and cells derived from virgin and memory B cells. Only a proportion has switched immunoglobulin class.
Development and characterization of surface chemistries for microfabricated biosensors (1999)

The high cost and harsh processing conditions associated with microfabricated biosensors demand a new approach to receptor immobilization. We have grafted biotin labeled, 3400 molecular weight poly(ethylene glycol) (PEG) to silicon surfaces to produce a dense PEG monolayer with functionally active biotin. These surfaces have been activated with antibodies through the strong streptavidin-biotin interaction by simply incubating the surfaces with antibody-streptavidin conjugates. The stability of the biotinylated PEG monolayers produces a sensing element that can be regenerated by removal of the streptavidin conjugate and stored in a dry state for extended periods of time.
Diagnostic Skin Test Reactions with Varicella Virus Antigen and Clinical Application of the Test (1977)

Varicella virus antigen was prepared and used in skin testing of 75 children one to 17 years old. Results of skin tests were analyzed in relation to history of varicella, presence of absence of neutralizing antibody, and susceptibility to clinical varicella. All 22 children with no history of varicella and no neutralizing antibody were negative in the skin test when an erythematous change of greater than or equal to 5 mm in diameter was taken as a positive result. Of the 53 children with neutralizing antibody, only three were negative in the skin test. The skin test was applied clinically in an institution for mentally retarded children immediately after varicella infection occurred in a patient. A total of 65 patients were examined by the skin test, and 24 children with negative results were given live varicella virus vaccine. As a result, no spread of varicella was observed except for three cases, which developed two weeks after onset of illness in the index case. Thus the skin test seems clinically useful in the determination of susceptibility of individuals to clinical varicella.
Bioactive angiotensin peptides: focus on angiotensin IV (2001)

JRAAS 2001;2:205-10 Introduction The renin-angiotensin system (RAS) was initially identified as a circulating humoral system with the effector peptide,angiotensin II (Ang II),generated by an enzymatic cascade. Angiotensinogen, which is synthesised in the liver, is cleaved by renin,a product of the juxtaglomerular cells of the kidney, to form angiotensin I (Ang I), which in turn is cleaved by angiotensin-converting enzyme (ACE) to form Ang II. ACE is membrane-bound and predominates on the endothelial cells of all vascular beds.Apart from the production of Ang II in plasma,Ang II, renin and ACE have all been described in tissues such as the brain, kidney, adrenal, vasculature, heart and ovaries. This suggests a separate and distinct RAS in these tissues and implies endocrine,paracrine and autocrine roles for Ang II. A variety of other angiotensin peptides are also produced,although their activities have only recently received attention.
Mouse FcγRII is a negative regulator of FcγRIII in IgG immune complex-triggered inflammation but not in autoantibody-induced hemolysis (2000)

Murine low-affinity receptors for IgG, FcgammaRII and FcgammaRIII, differ by their distinct capacities in mediating down-regulation or activation of cellular effector functions, respectively. In this study, antibodies detecting the mouse Ly-17.1 / 2 alloantigen system are demonstrated to be specific for FcgammaRII with no cross-reactivities to other FcgammaR, including FcgammaRIII. Using these FcgammaRII-specific monoclonal antibodies (mAb), the significance of FcgammaRII inhibition of FcgammaRIII was examined in two models of autoantibody [autoimmune hemolytic anemia (AIHA)]- and IgG immune complex-induced (Arthus reaction) inflammation in C57BL / 6 mice in comparison with FcgammaRII(- / -) and FcgammaRIII(- / -) mice. Our results demonstrate that both FcgammaRIII and FcgammaRII contributed to the binding of erythrocytes opsonized with the pathogenic IgG1 autoreactive anti-murine red blood cell antibody 105-2H. However, the functional blocking with anti-FcgammaRII mAb in C57BL / 6 mice and the lack of FcgammaRII expression in FcgammaRII(- / -) mice, which both lowered the threshold level of FcgammaRIII-triggered phagocytosis in vitro, did not results in enhanced disease development of 105-2H mAb-induced AIHA in vivo. This was in sharp contrast to cutaneous Arthus reaction, where FcgammaRIII-mediated activation was inhibited by FcgammaRII. Together these results show that murine AIHA is markedly different from other FcgammaR-dependent inflammatory diseases where FcgammaRIII is normally counterregulated by FcgammaRII.
Direct activation of PDE5 by cGMP (2003)

In platelets, the nitric oxide (NO)-induced cGMP response is indicative of a highly regulated interplay of cGMP formation and cGMP degradation. Recently, we showed that within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred. Here, we identify cyclic GMP-dependent protein kinase I as the kinase responsible for the NO-induced PDE5 phosphorylation. However, we demonstrate that cGMP can directly activate PDE5 without phosphorylation in platelet cytosol, most likely via binding to the regulatory GAF domains. The reversal of activation was slow, and was not completed after 60 min. Phosphorylation enhanced the cGMP-induced activation, allowing it to occur at lower cGMP concentrations. Also, in intact platelets, a sustained NO-induced activation of PDE5 for as long as 60 min was detected. Finally, the long-term desensitization of the cGMP response induced by a low NO concentration reveals the physiological relevance of the PDE5 activation within NO/cGMP signaling. In sum, we suggest NO-induced activation and phosphorylation of PDE5 as the mechanism for a long-lasting negative feedback loop shaping the cGMP response in human platelets in order to adapt to the amount of NO available.
Discussion (1996)

An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Synthesis and Biophysical and Biological Properties of Oligonucleotides Containing 2-Aza-2'-Deoxyinosine (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and Biophysical and Biological Properties of Oligonucleotides Containing 2-Aza-2'-DeoxyinosineMontse Acedo, Erik De Clercq, and Ramon EritjaCite this: J. Org. Chem. 1995, 60, 20, 6262–6269Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October 1995https://pubs.acs.org/doi/10.1021/jo00125a009https://doi.org/10.1021/jo00125a009research-articleACS PublicationsRequest reuse permissionsArticle Views143Altmetric-Citations14LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts