gebhart/patrepeval huggingface dataset:
Asymmetrische reduktive Aminierung von Cycloalkanonen, 7. Mitt. Die asymmetrische Synthese von cis‐1R,2R‐ und cis‐1S,2S‐2‐Arylcyclohexanaminen (1989)

Abstract Die asymmetrische Synthese von optisch aktiven cis‐2‐Arylcyclohexanaminen 4 wird in einem dreistufigen Verfahren beschrieben: Durch Kondensation der razemischen 2‐Arylcyclohexanone 1 mit den chiralen Hilfsaminen R‐(+)‐ bzw. S‐(−)‐1‐Phenylethylamin werden Imin‐Isomerengemische 2 erhalten, die nach Hydrierung über Raney‐Nickel ein einziges cis‐konfiguriertes sekundäres Amin 3 liefern. Hydrogenolyse über Pd/C führt zu den optisch aktiven primären cis‐2‐Arylcyclohexanaminen 4 . Die relative Konfiguration sowie die Konformation wurde durch 1 H‐NMR‐Spektroskopie, die absolute Konfiguration der hochgradig enantiomerenreinen Verbindungen 4 mil Hilfe der CD‐Spektroskopie bestimmt.
Comprehensive glyco‐proteomic analysis of human α1‐antitrypsin and its charge isoforms (2006)

Human alpha1-antitrypsin (A1PI) is a well-known glycoprotein in human plasma important for the protection of tissues from proteolytic enzymes. The three N-glycosylation sites of A1PI contain diantennary N-glycans but also triantennary and even traces of tetraantennary structures leading to the typical IEF pattern observed for A1PI. Here we present an approach to characterize A1PI isoforms from human plasma and its PTMs by LC-ESI-MS and LC-ESI-MS/MS of peptides obtained by proteolytic digestion. The single cysteine residue of A1PI formed a disulfide bridge with free cysteine. The variability of the number of antennae and hence sialic acids on glycosylation site N107, which even contained minute amounts of tetraantennary structures, emerged as a major cause for the IEF pattern of A1PI. Only negligible amounts of triantennary structures were identified attached to N70, and exclusively diantennary structures were present on site N271 in each of the isoforms analyzed. Exoglycosidase digests revealed alpha2,6-linked neuraminic acids on diantennary N-glycans, and triantennary contained additionally one single alpha2,3-neuraminic acid per N-glycan, which, together with a fucose, formed a sialyl Lewis X determinant on the beta1,4-linked N-acetylglucosamine, as shown by 2-D-HPLC of pyridylaminated asialoglycans. Fucosylation of diantennary structures was marginal and of the core alpha1,6 type.
Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells (2006)

Embryonic stem (ES) cells are self-renewing cells that maintain pluripotency to differentiate into all types of cells. Because of their potential to provide a variety of tissues for use in regenerative medicine, there is great interest in the identification of growth factors that govern these unique properties of ES cells. However, the signaling pathways controlling ES cell proliferation remain largely unknown. Since transforming growth factor beta (TGFbeta) superfamily members have been implicated in the processes of early embryogenesis, we investigated their roles in ES cell self-renewal. Inhibition of activin-Nodal-TGFbeta signaling by Smad7 or SB-431542 dramatically decreased ES cell proliferation without decreasing ES pluripotency. By contrast, inhibition of bone morphogenetic protein (BMP) signaling by Smad6 did not exhibit such effects, suggesting that activin-Nodal-TGFbeta signaling, but not BMP signaling, is indispensable for ES cell propagation. In serum-free culture, supplementation of recombinant activin or Nodal, but not TGFbeta or BMP, significantly enhanced ES cell propagation without affecting pluripotency. We also found that activin-Nodal signaling was constitutively activated in an autocrine fashion in serum-free cultured ES cells, and that inhibition of such endogenous signaling by SB-431542 decreased ES cell propagation in serum-free conditions. These findings suggest that endogenously activated autocrine loops of activin-Nodal signaling promote ES cell self-renewal.
The use of anti-idiotypic antibodies as a strategy for studying glutamate receptors (1991)

Conference Article| February 01 1991 The use of anti-idiotypic antibodies as a strategy for studying glutamate receptors Ian R. Duce; Ian R. Duce *Department of Zoology, University of Nottingham, University Park, Nottingham NG7 2RD, U.K. Search for other works by this author on: This Site PubMed Google Scholar Timothy C. Budd; Timothy C. Budd ‡ *Department of Zoology, University of Nottingham, University Park, Nottingham NG7 2RD, U.K. Search for other works by this author on: This Site PubMed Google Scholar Peter J. Richardson Peter J. Richardson †Department of Pharmacology, University of Cambridge, Hills Road, Cambridge, U.K. Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Received: September 27 1990 Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1991 Biochemical Society1991 Biochem Soc Trans (1991) 19 (1): 143–146. https://doi.org/10.1042/bst0190143 Article history Received: September 27 1990 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation Ian R. Duce, Timothy C. Budd, Peter J. Richardson; The use of anti-idiotypic antibodies as a strategy for studying glutamate receptors. Biochem Soc Trans 1 February 1991; 19 (1): 143–146. doi: https://doi.org/10.1042/bst0190143 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: NMDA, N-methyl-D-aspartate, AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid, BSA, bovine serum albumin, IC50, concentration required to inhibit by 50% This content is only available as a PDF. © 1991 Biochemical Society1991 Article PDF first page preview Close Modal You do not currently have access to this content.
Accelerating cardiac cine 3D imaging using k‐t BLAST (2004)

By exploiting spatiotemporal correlations in cardiac acquisitions using k-t BLAST, gated cine 3D acquisitions of the heart were accelerated by a net factor of 4.3, making single breathhold acquisitions possible. Sparse sampling of k-t space along a sheared grid pattern was implemented into a cine 3D SSFP sequence. The acquisition of low-resolution training data, which was required to resolve aliasing in the k-t BLAST method, was either interleaved into the sampling process or obtained in a separate prescan to allow for shorter breathhold durations in patients with heart disease. Volumetric datasets covering the heart with 20 slices at a spatial resolution of 2 x 2 x 5 mm3 were recorded with 20 cardiac phases in a total breathhold duration of 25-27 sec, or 18 sec if partial Fourier sampling was additionally employed. The feasibility of the method was demonstrated on healthy volunteers and on patients. The comparison of endocardial area derived from single slices of the 3D dataset with values extracted from separate single-slice acquisitions showed no significant differences. By shortening the acquisition substantially, k-t BLAST may greatly facilitate volumetric imaging of the heart for evaluation of regional wall motion and the assessment of ventricular volume and ejection fraction.
Structural requirements for the cytoprotective actions of mono‐unsaturated fatty acids in the pancreatic β‐cell line, BRIN‐BD11 (2008)

The data reveal the structural requirements that dictate the cytoprotective actions of mono-unsaturated fatty acids in pancreatic beta-cells. Metabolic activation is not required and the data point at the potential involvement of a fatty acid receptor in mediating cytoprotection.
Macrophage inflammatory protein‐1α influences eosinophil recruitment in antigen‐specific airway inflammation (1995)

Abstract Allergic airway inflammation is characterized by peribronchial eosinophil accumulation within the submucosa of the airway of the lung. In the present study we have utilized a model of airway inflammation induced by intratracheal challenge with parasite ( Schistosoma mansoni ) egg antigen (SEA) in presensitized mice. The recruitment of neutrophils and eosinophils into the airway was found to be maximal at 8 and 48 h post challenge, respectively. Since macrophage inflammatory protein‐1α (MIP‐1α) has previously been found to be chemotactic for eosinophils, in vitro , we postulated that MIP‐1α was involved in the airway inflammation and more specifically in eosinophil recruitment into the airway. Initial studies demonstrated an increase in MIP‐1α mRNA expression at 8 h post‐SEA challenge, as compared to vehicle‐treated control mice. We next demonstrated a significant increase in MIP‐1α protein in the lungs of SEA‐challenged mice at 8 h compared to control challenged mice, correlating to the mRNA data. Immunohistochemical staining of lungs from SEA‐challenged mice demonstrated MIP‐1α protein expression in airway epithelial cells, alveolar macrophages and in recruited mononuclear cell populations. Immunolocalization of MIP‐1α to cells within the bronchoalveolar lavage fluid demonstrated that macrophages and eosinophils stained positive for the protein. To determine the contribution of MIP‐1α expression to eosinophil accumulation, SEA‐challenged mice were passively immunized with either neutralizing MIP‐1α antibodies or normal rabbit IgG, 3–4 h prior to the intratracheal SEA challenge. These studies demonstrated a &gt; 50% decrease in eosinophil recruitment to the lungs and airway in animals receiving neutralizing MIP‐1α antibodies with no effect on early neutrophil recruitment. These results suggest that the production of MIP‐1α, induced by an antigen‐specific response, plays an important role in recruitment of eosinophils in this airway model of inflammation.
Different Binding Properties and Affinities for ATP and ADP among Sulfonylurea Receptor Subtypes, SUR1, SUR2A, and SUR2B (2000)

ATP-sensitive potassium (K(ATP)) channels, composed of sulfonylurea receptor (SURx) and Kir6.x, play important roles by linking cellular metabolic state to membrane potential in various tissues. Pancreatic, cardiac, and vascular smooth muscle K(ATP) channels, which consist of different subtypes of SURx, differ in their responses to cellular metabolic state. To explore the possibility that different interactions of SURx with nucleotides cause differential regulation of K(ATP) channels, we analyzed the properties of nucleotide-binding folds (NBFs) of SUR1, SUR2A, and SUR2B. SURx in crude membrane fractions was incubated with 8-azido-[alpha-(32)P]ATP or 8-azido-[gamma-(32)P]ATP under various conditions and was photoaffinity-labeled. Then, SURx was digested mildly with trypsin, and partial tryptic fragments were immunoprecipitated with antibodies against NBF1 and NBF2. Some nucleotide-binding properties were different among SUR subtypes as follows. 1) Mg(2+) dependence of nucleotide binding of NBF2 of SUR1 was high, whereas those of SUR2A and SUR2B were low. 2) The affinities of NBF1 of SUR1 for ATP and ADP, especially for ATP, were significantly higher than those of SUR2A and SUR2B. 3) The affinities of NBF2 of SUR2B for ATP and ADP were significantly higher than those of SUR2A. This is the first biochemical study to analyze and compare the nucleotide-binding properties of NBFs of three SUR subtypes, and our results suggest that their different properties may explain, in part, the differential regulation of K(ATP) channel subtypes. The high nucleotide-binding affinities of SUR1 may explain the high ability of SUR1 to stimulate pancreatic K(ATP) channels. It is also suggested that the C-terminal 42 amino acids affect the physiological roles of SUR2A and SUR2B by changing the nucleotide-binding properties of their NBFs.
The ets sequence from the transforming gene of avian erythroblastosis virus, E26, has unique domains on human chromosomes 11 and 21: both loci are transcriptionally active. (1985)

Human DNA segments homologous to the ets region from the transforming gene of avian erythroblastosis virus, E26, were molecularly cloned and shown to be closely related to the viral equivalent by hybridization and partial sequence analysis. The transforming gene of E26 has a tripartite origin with the structure delta gag [1.2 kilobases (kb) from the viral gag gene]-myb(0.9 kb from the chicken myb gene)-ets (1.6 kb from the chicken ets gene). Human ets DNA is located on two distinct human chromosomes. The human ets-1 locus on chromosome 11 encodes a single mRNA of 6.8 kb; the second locus, ets-2 on chromosome 21, encodes three mRNAs of 4.7, 3.2, and 2.7 kb. The ets-related sequences of human DNA on chromosomes 11 and 21 are discontiguous, except for a small overlap region encoding 14 amino acids, where 12 are conserved between these two loci. By contrast, the chicken homolog has contiguous ets-1 and ets-2 sequences and is primarily expressed in normal chicken cells as a single 7.5-kb mRNA. We conclude that the ets sequence shared by the virus, the chicken, and humans is likely to contain at least two dissociable functional domains, ets-1 and ets-2. Thus, the tripartite transforming gene of E26 includes four distinct domains that may be functionally relevant for the transforming function of the virus (delta gag, myb, ets-1, and ets-2).
Particle enrichment employing grooved microfluidic channels (2008)

The well-studied chaotic micromixer has found its application on the enrichment of microparticles. Here, we report the use of such patterning flows produced by a grooved surface integrated into a microfluidic device to continuously concentrate the flowing particles of comparable sizes to the depth of the channel. The particle distributions after passing through the grooves illustrate the enrichment profiles and the size-dependent patterns. We expect that the alignment of the concentrated particles can facilitate the visualization of sizing and counting in cell-based devices.
Expression of pro form of prostate-specific antigen by mammalian cells and its conversion to mature, active form by human kallikrein 2. (1997)

To study the expression, biosynthesis, and processing of prostate-specific antigen (PSA) in mammalian cells, recombinant PSA was expressed in Syrian hamster tumor cell line AV12-664 (AV12-PSA). Expression of PSA was monitored by the Tandem-MP PSA assay. PSA was secreted into the medium during the logarithmic phase of cell growth at >9 microg/ml and was stable. The PSA purified from spent medium of AV12-PSA cells did not exhibit any enzymatic activity and did not complex with the protease inhibitor, alpha-1-antichymotrypsin. These findings indicated that an inactive form of PSA was expressed by AV12-PSA cells. NH2-terminal sequencing confirmed the identity of the PSA purified from the spent medium of AV12-PSA cells to be pro-PSA. This demonstrates that PSA is expressed as pro-PSA by mammalian cells and suggests that pro-PSA may be present in biological fluids. Human kallikrein 2 (hK2), another member of the hK family, is also expressed predominantly in prostate epithelium. Although hK2 has been shown to exhibit trypsin-like activity, little is known about its natural substrates. Using purified proteins, we show that hK2 can convert pro-PSA to mature, enzymatically active PSA, thus establishing a physiological connection between hK2 and PSA. These findings imply that hK2 may be regulating PSA activity in vivo.
Role of hydrogen sulfide in acute pancreatitis and associated lung injury (2005)

Hydrogen sulfide (H2S) is a naturally occurring gas with potent vasodilator activity. Cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) utilize L-cysteine as substrate to form H2S. Of these two enzymes, cystathionine-gamma-lyase (CSE) is believed to be the key enzyme that forms H2S in the cardiovascular system. Whilst H2S has been reported to relax precontracted rat arteries in vitro and to lower blood pressure in the rat, its effect in an inflammatory condition such as acute pancreatitis has not previously been reported. In this paper, we report the presence of H2S synthesizing enzyme activity and CSE (as determined by mRNA signal) in the pancreas. Also, prophylactic, as well as therapeutic, treatment with the CSE inhibitor, DL-propargylglycine (PAG), significantly reduced the severity of caerulein-induced pancreatitis and associated lung injury, as determined by 1) hyperamylasemia [plasma amylase (U/L) (control, 1204+/-59); prophylactic treatment: placebo, 10635+/-305; PAG, 7904+/-495; therapeutic treatment: placebo, 10427+/-470; PAG, 7811+/-428; P<0.05 PAG c.f. placebo; n=24 animals in each group]; 2) neutrophil sequestration in the pancreas [pancreatic myeloperoxidase oxidase (MPO) activity (fold increase over control) (prophylactic treatment: placebo, 5.78+/-0.63; PAG, 2.97+/-0.39; therapeutic treatment: placebo, 5.48+/-0.52; PAG, 3.03+/-0.47; P<0.05 PAG c.f. placebo; n=24 animals in each group)]; 3) pancreatic acinar cell injury/necrosis; 4) lung MPO activity (fold increase over control) [prophylactic treatment: placebo, 1.99+/-0.16; PAG, 1.34+/-0.14; therapeutic treatment: placebo, 2.03+/-0.12; PAG, 1.41+/-0.97; P<0.05 PAG c.f. placebo; n=24 animals in each group]; and 5) histological evidence of lung injury. These effects of CSE blockade suggest an important proinflammatory role of H2S in regulating the severity of pancreatitis and associated lung injury and raise the possibility that H2S may exert similar activity in other forms of inflammation.
Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin. (1997)

E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonami de), an orally active sulfonamide antitumor agent that is currently in a Phase I clinical trial, showed rather consistent growth-inhibitory activities against a panel of 26 human tumor cell lines (IC50 = 0.06-0.8 microg/ml), in contrast to vincristine (VCR; IC50 = 0.0002-0.04 microg/ml), 5-fluorouracil (IC50 = 0.2-30 microg/ml), Adriamycin (IC50 = 0.002-0.7 microg/ml), mitomycin C (IC50 = 0.007-3 microg/ml), 1-beta-D-arabinofuranoxylcytosine (IC50 = 0.005 to >30 microg/ml), camptothecin (IC50 = 0.002-0.4 microg/ml), and cisplatin (IC50 = 0.5-20 microg/ml). It caused a dose-dependent increase in the percentage of mitotic cells in parallel with a decrease in cell proliferation, like VCR. It also showed a dose-dependent inhibition of tubulin polymerization, which correlated well with the cell growth-inhibitory activity. 14C-labeled E7010 bound to purified tubulin, and this binding was inhibited by colchicine but not by VCR. However, its binding properties were different from those of colchicine, as well as those of VCR. E7010 was active against two kinds of VCR-resistant P388 cell lines, one of which showed multidrug resistance due to the overexpression of P-glycoprotein (resistant to Taxol), and the other did not show multidrug resistance (sensitive to Taxol). Furthermore, four E7010-resistant P388 cell lines showed no cross-resistance to VCR, a different pattern of resistance to podophyllotoxin, and collateral sensitivity to Taxol. Therefore, E7010 is a novel tubulin-binding agent that has a wider antitumor spectrum than VCR and has different properties from those of VCR or Taxol.
What Price Support? Ventricular Assist Device Induced Systemic Response (2003)

Use of ventricular support systems has been associated with myriad systemic complications. Engendered by the blood-biomaterial interface of a unique host/device relationship, these complications include diverse humoral dyscrasias that frequently culminate in episodes of bleeding, hemolysis and thrombogenicity, heightened susceptibility to inflammation and infection, and transient immunal compromise. Recent endeavor in biocompatibility research has served to illustrate the critical role played by cellular, humoral, and neurohormonal components in regulating cytokine expression and has provided insight into the complexities involved in such biomechanical juxtapositions. The following is intended as a review of current literature attempting to address the many aspects of this host/device interaction and their consequences for the supported patient.
Identification of a Novel Family of Nonclassic Yeast Phosphatidylinositol Transfer Proteins Whose Function Modulates Phospholipase D Activity and Sec14p-independent Cell Growth (2000)

Yeast phosphatidylinositol transfer protein (Sec14p) is essential for Golgi function and cell viability. We now report a characterization of five yeast SFH (Sec Fourteen Homologue) proteins that share 24-65% primary sequence identity with Sec14p. We show that Sfh1p, which shares 64% primary sequence identity with Sec14p, is nonfunctional as a Sec14p in vivo or in vitro. Yet, SFH proteins sharing low primary sequence similarity with Sec14p (i.e., Sfh2p, Sfh3p, Sfh4p, and Sfh5p) represent novel phosphatidylinositol transfer proteins (PITPs) that exhibit phosphatidylinositol- but not phosphatidylcholine-transfer activity in vitro. Moreover, increased expression of Sfh2p, Sfh4p, or Sfh5p rescues sec14-associated growth and secretory defects in a phospholipase D (PLD)-sensitive manner. Several independent lines of evidence further demonstrate that SFH PITPs are collectively required for efficient activation of PLD in vegetative cells. These include a collective requirement for SFH proteins in Sec14p-independent cell growth and in optimal activation of PLD in Sec14p-deficient cells. Consistent with these findings, Sfh2p colocalizes with PLD in endosomal compartments. The data indicate that SFH gene products cooperate with "bypass-Sec14p" mutations and PLD in a complex interaction through which yeast can adapt to loss of the essential function of Sec14p. These findings expand the physiological repertoire of PITP function in yeast and provide the first in vivo demonstration of a role for specific PITPs in stimulating activation of PLD.
Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway (2007)

Ghrelin is expressed in normal human adrenocortical cells and induces their proliferation through growth hormone secretagogue receptor 1a (GHS-R1a). Consequently, it was of interest to us to determine whether acylated ghrelin and its predominant serum isoform, unacylated ghrelin, also act as factors for adrenocortical carcinoma cell growth. To examine a potential ghrelin-regulated system in adrenocortical tumors, we measured proliferative effects of acylated and unacylated ghrelin in the adrenocortical carcinoma cell lines SW-13 and NCI-H295R. We also examined the expression of ghrelin, GHS-R1a, and corticotrophin-releasing factor receptor 2 (CRF-R2). Acylated and unacylated ghrelin in the nanomolar range dose-dependently induced adrenocortical cell growth up to 200% of untreated controls, as measured by thymidine uptake and WST1 assay. The proliferative effects of acylated and unacylated ghrelin in SW-13 cells was blocked by [D-Lys(3)]growth hormone-releasing peptide 6 (GHRP6), but a CRF-R2 antagonist had no effect on unacylated ghrelin growth stimulation. Cell cycle analysis suggests that acylated and unacylated ghrelin suppress the sub-G(0)/apoptotic fraction by up to 50%. Measurement of DNA fragmentation and caspase-3 and -7 activity in SW-13 cells confirmed that acylated and unacylated ghrelin suppress apoptotic rate. SW-13 cells express preproghrelin mRNA and secrete ghrelin, and [D-Lys(3)]GHRP6 suppresses their basal proliferation rate, strongly suggesting that ghrelin could act as an auto/paracrine growth factor. Acylated and unacylated ghrelin are potential auto/paracrine factors acting through an antiapoptotic pathway to stimulate adrenocortical tumor cell growth. Unacylated ghrelin-stimulated growth is suppressed by an antagonist of GHS-R1a, suggesting either that unacylated ghrelin is acylated before its action or that ghrelin, unacylated ghrelin, and [D-Lys(3)]GHRP-6 bind to a novel receptor in these cells.