gebhart/patrepeval huggingface dataset:
Combined Ventricular Systolic and Arterial Stiffening in Patients With Heart Failure and Preserved Ejection Fraction (2003)

Patients with HF-lnEF have systolic-ventricular and arterial stiffening beyond that associated with aging and/or hypertension. This may play an important pathophysiological role by exacerbating systemic load interaction with diastolic function, augmenting blood pressure lability, and elevating cardiac metabolic demand under stress.
Nonnucleoside Reverse Transcriptase Inhibitor Resistance and the Role of the Second-Generation Agents (2009)

NNRTI resistance is an increasing problem that may impair the chances for therapeutic success in HIV-infected patients. Novel agents such as etravirine and rilpivirine provide new, sensitive options for patients and significantly improve the rate of virologic suppression when appropriately applied.
Cytotoxic Steroidal Saponins from Polygonatum zanlanscianense (2004)

Four new steroidal saponins, polygonatosides A-D (1-4), were isolated from the rhizomes of Polygonatum zanlanscianense, together with six known spirostanols (5-10) and a known megastigmane glycoside (11). Their structures were elucidated on the basis of spectroscopic analysis and the results of acidic and enzymatic hydrolysis. The cytotoxic activities of 1-11 against HeLa cells are described.
Effects of anti-nuclear factor kappa B reagents in blocking adhesion of human cancer cells to vascular endothelial cells. (1995)

Transcription factor nuclear factor kappa B (NF kappa B) controls gene expression of a number of genes including cell adhesion molecules such as E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 1. These cell adhesion molecules are known to play important roles in a critical step of tumor metastasis, arrest of tumor cells onto the venous or capillary bed of the target organ. NF kappa B is activated by extracellular signals such as those elicited by proinflammatory cytokines, tumor necrosis factor and interleukin 1 (IL-1). Here we demonstrate that IL-1 beta induces nuclear translocation of NF kappa B in human umbilical vein endothelial cells, followed by induction of cell surface expression of E-selectin, intercellular adhesion molecule-1, and vascular adhesion molecule 1, and subsequently augments adhesion of those cancer cells expressing sialyl Lewis X antigen, a ligand to E-selectin. We have also demonstrated that the adhesion of tumor cells to IL-1 beta-treated human umbilical vein endothelial cells can be inhibited by anti-NF kappa B reagents such as N-acetyl L-cysteine, aspirin, or pentoxifylline. These observations indicate the involvement of NF kappa B in cancer metastasis and the feasibility of using anti-NF kappa B reagents in preventing metastasis.
Coherent beam combining and phase noise measurements of ytterbium fiber amplifiers (2004)

Phase noise characterization of a 10-W Yb fiber amplifier is presented, and we demonstrate phase locking of two fiber amplifiers with near-perfect fringe contrast at power levels of as much as 10 W per fiber. Coherent beam combining is maintained during the turn-on transient as well as in thermal steady-state operation.
Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis (1994)

Abstract The EDI monoclonal antibody recognizes an antigen in lysosomal membranes of phagocytes. The expression of this antigen in cells increases during phagocytic activity. Here we describe the expression of ED1‐immunoreactivity during the various stages of both acute (monophasic) and chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. During the first attack of acute and chronic relapsing EAE, ED1‐immunoreactivity was present in macrophages and in cells which displayed morphologic features of activated microglial cells (i.e., cells with thick short processes). At the ultrastructural level these cells were seen to contain phagocytosed myelin structures in lysosomes. ED1‐immunoreactivity in these cells was present in the cytoplasm near lysosomes. During the remission phase of acute EAE and the relapse phase of chronic relapsing EAE, ED1‐positive cells with dendritic morphology not only were present in or nearby lesions, but were also found at sites distant from lesions throughout large parts of the brain. These cells had a morphology comparable to microglial cells in normal brain. A major difference between animals which were in remission and animals which on day 25 were suffering from a relapse, was that the latter showed the presence of lesions with darkly stained round ED1‐positive macrophages and activated microglial cells. These results indicate that during a relapse, newly recruited bloodborne macrophages infiltrate the brain and, together with activated lymphocytes and microglial cells, recommence a new demyelination process. © 1994 Wiley‐Liss, Inc.
TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. (1994)

The Saccharomyces cerevisiae genes TOR1 and TOR2 were originally identified by mutations that confer resistance to the immunosuppressant rapamycin. TOR2 was previously shown to encode an essential 282-kDa phosphatidylinositol kinase (PI kinase) homologue. The TOR1 gene product is also a large (281 kDa) PI kinase homologue, with 67% identity to TOR2. TOR1 is not essential, but a TOR1 TOR2 double disruption uniquely confers a cell cycle (G1) arrest as does exposure to rapamycin; disruption of TOR2 alone is lethal but does not cause a cell cycle arrest. TOR1-TOR2 and TOR2-TOR1 hybrids indicate that carboxy-terminal domains of TOR1 and TOR2 containing a lipid kinase sequence motif are interchangeable and therefore functionally equivalent; the other portions of TOR1 and TOR2 are not interchangeable. The TOR1-1 and TOR2-1 mutations, which confer rapamycin resistance, alter the same potential protein kinase C site in the respective protein's lipid kinase domain. Thus, TOR1 and TOR2 are likely similar but not identical, rapamycin-sensitive PI kinases possibly regulated by phosphorylation. TOR1 and TOR2 may be components of a novel signal transduction pathway controlling progression through G1.
THE RECEPTOR FOR EGF AND ITS LIGANDS - EXPRESSION, PROGNOSTIC VALUE AND TARGET FOR THERAPY IN CANCER (REVIEW) (1994)

The results of recent studies suggest that overexpression of the EGF receptor accompanied by production of its ligands is an important characteristic of human squamous cell carcinomas. The EGF receptor which transmits the growth promoting or inhibitory effects of epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) and amphiregulin is a member of the type I family of growth factor receptors which possess tyrosine kinase activity. In this review we a) discuss the role played by this receptor and its ligands in the transformation of normal cells, b) analyze the evidence for expression of the receptor and its ligands as prognostic markers in cancer patients and c) indicate ways that the overexpressed EGF-receptor system on human malignant cells can be targeted for therapeutic application.
DGD1-independent biosynthesis of extraplastidic galactolipids after phosphate deprivation in Arabidopsis (2000)

The galactolipids, mono- and digalactosyldiacylglycerol (DGDG), are the most common nonphosphorous lipids in the biosphere and account for 80% of the membrane lipids found in green plant tissues. These lipids are major constituents of photosynthetic membranes (thylakoids), and a large body of evidence suggests that galactolipids are associated primarily with plastid membranes in seed plants. A null-mutant of Arabidopsis (dgd1), which lacks the DGDG synthase (DGD1) resulting in a 90% reduction in the amount of DGDG under normal growth conditions, accumulated DGDG after phosphate deprivation up to 60% of the amount present in the wild type. This observation suggests the existence of a DGD1-independent pathway of galactolipid biosynthesis. The fatty acid composition of the newly formed DGDG was distinct, showing an enrichment of 16-carbon fatty acids in the C-1 position of the glycerol backbone of DGDG. Roots with their rudimentary plastids accumulated large amounts of DGDG after phosphate deprivation, suggesting that this galactolipid may be located in extraplastidic membranes. Corroborating evidence for this hypothesis was obtained directly by fractionation of subcellular membranes from leaf tissue and indirectly by lipid analysis of the phosphate-deprived fad3 mutant primarily deficient in extraplastidic fatty acid desaturation. The discovery of extraplastidic DGDG biosynthesis induced by phosphate deprivation has revealed a biochemical mechanism for plants to conserve phosphate. Apparently, plants replace phospholipids with nonphosphorous galactolipids if environmental conditions such as phosphate deprivation require this for survival.
Novel heterocycles. I. Synthesis and reactions of 6,7‐dihydro‐1H,3H,5H‐pyrido[3,2,l‐ij] [3,1]benzoxazine‐1,3‐dione (1978)

Abstract 6,7‐Dihydro‐1 H ,3 H ,5 H ‐pyrido[3,2,l‐ ij ][3,1 ]benzoxazine‐1,3‐dione ( 1b ) was synthesized by a new route and its reactions with various nueleophiles are described.
Lead toxicity and chelation therapy (2006)

Lead toxicity remains a significant public health concern. Elimination of elevated blood lead levels in children can be accomplished by educating appropriate health care providers and caregivers, recognizing potential lead sources, and adopting aggressive prevention and case management measures.
Dipole moment, nuclear magnetic resonance, and infrared studies of phosphorus configurations and equilibriums in 2-R-2-oxo-1,3,2-dioxaphosphorinanes (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDipole moment, nuclear magnetic resonance, and infrared studies of phosphorus configurations and equilibriums in 2-R-2-oxo-1,3,2-dioxaphosphorinanesJohn A. Mosbo and John G. VerkadeCite this: J. Org. Chem. 1977, 42, 9, 1549–1555Publication Date (Print):April 1, 1977Publication History Published online1 May 2002Published inissue 1 April 1977https://pubs.acs.org/doi/10.1021/jo00429a015https://doi.org/10.1021/jo00429a015research-articleACS PublicationsRequest reuse permissionsArticle Views147Altmetric-Citations51LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Increased Copy Number of the Interleukin-6 Receptor Gene Is Associated with Adverse Survival in Multiple Myeloma Patients Treated with Autologous Stem Cell Transplantation (2011)

Interleukin-6 (IL-6) is a potent pleiotropic cytokine that regulates plasma cell (PC) growth via the IL-6 receptor (IL-6R). We hypothesized that up-regulation of IL-6R in myeloma cells might confer the growth privilege to myeloma cells over bone marrow (BM) hematopoietic cells. We investigated the frequency and prognostic implication of increased copy number of the IL-6R gene by fluorescence in situ hybridization (FISH) in patients with newly diagnosed multiple myeloma (MM). One hundred two patients with newly diagnosed MM were enrolled. The FISH study for IL-6R was performed using a homemade bacterial artificial chromosome (BAC) probe for IL6R at chromosome 1q21. FISH signals were counted among BM plasma cells sorted by cytoplasmic immunoglobulin light chain staining (cIg FISH). The amplification of IL-6R was detected in 53/102 patients (52.0%). The 5-year overall survival (OS) rate of patients with IL-6R gene amplification was 41.3% versus 44.8% for those with a normal IL-6R (P = .425). In 44 patients treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT), patients with ≥3.1 copy numbers of IL-6R per PC showed adverse 5-year OS compared to those with <2.1 copies of IL-6R gene (44.4% versus 78.0%, P = .024). In multivariate analysis, the increase of IL-6R copy numbers (mean copy/PC ≥3.1) could be considered as an independent prognostic factor for MM patients who underwent ASCT. The gain of the IL-6R gene was frequent in myeloma, showing an association with adverse prognosis in myeloma patients treated with ASCT. These findings suggest the potential role of IL-6R in myeloma cell growth and therapeutic implications of the IL-6R blocker in the future.
Anti-AIDS Agents 49. Synthesis, Anti-HIV, and Anti-Fusion Activities of IC9564 Analogues Based on Betulinic Acid (2002)

The betulinic acid derivative IC9564 inhibits human immunodeficiency virus (HIV)-1 entry. Among a series of IC9564 derivatives, 5 and 20 were the most promising compounds against HIV infection with EC(50) values of 0.33 and 0.46 microM, respectively. Both compounds inhibited syncytium formation with EC(50) values of 0.40 and 0.33 microM, respectively. The comparable EC(50) values in the two assays suggested that these compounds are fusion inhibitors. The structure-activity relationship data also indicated that a double bond in IC9564 can be eliminated and the statine moiety can be replaced with L-leucine while retaining anti-HIV activity.
Protection of chimpanzees from type B hepatitis by immunization with woodchuck hepatitis virus surface antigen (1986)

Two chimpanzees immunized with woodchuck hepatitis virus (WHV) surface antigen (WHsAg) developed antibodies cross-reactive with hepatitis B virus (HBV) surface antigen (HBsAg). After challenge with HBV, one animal was completely protected and the other experienced a subclinical infection, without evidence of liver disease. Three woodchucks immunized with HBsAg developed antibodies to HBsAg which did not cross-react with WHsAg. After challenge with WHV, all three woodchucks developed typical acute infections with associated hepatic lesions. Serological studies with the cross-reactive antibodies raised in chimpanzees suggested that the protective epitopes of WHsAg were related to the group a specificity of HBsAg. These studies indicated that cross-protective epitopes are shared by HBV and WHV; however, the humoral response to these epitopes can vary among species.
Inactivation of 14-3-3σ Influences Telomere Behavior and Ionizing Radiation-Induced Chromosomal Instability (2000)

Telomeres are complexes of repetitive DNA sequences and proteins constituting the ends of linear eukaryotic chromosomes. While these structures are thought to be associated with the nuclear matrix, they appear to be released from this matrix at the time when the cells exit from G(2) and enter M phase. Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. The 14-3-3sigma gene has been reported to be a checkpoint control gene, since it promotes G(2) arrest following DNA damage. Here we demonstrate that inactivation of this gene influences genome integrity and cell survival. Analyses of chromosomes at metaphase showed frequent losses of telomeric repeat sequences, enhanced frequencies of chromosome end-to-end associations, and terminal nonreciprocal translocations in 14-3-3sigma(-/-) cells. These phenotypes correlated with a reduction in the amount of G-strand overhangs at the telomeres and an altered nuclear matrix association of telomeres in these cells. Since the p53-mediated G(1) checkpoint is operative in these cells, the chromosomal aberrations observed occurred preferentially in G(2) after irradiation with gamma rays, corroborating the role of the 14-3-3sigma protein in G(2)/M progression. The results also indicate that even in untreated cycling cells, occasional chromosomal breaks or telomere-telomere fusions trigger a G(2) checkpoint arrest followed by repair of these aberrant chromosome structures before entering M phase. Since 14-3-3sigma(-/-) cells are defective in maintaining G(2) arrest, they enter M phase without repair of the aberrant chromosome structures and undergo cell death during mitosis. Thus, our studies provide evidence for the correlation among a dysfunctional G(2)/M checkpoint control, genomic instability, and loss of telomeres in mammalian cells.
Immunochemical Properties of Alpha-Fetoprotein (AFP) and Antibodies to Autologous AFP (1978)

Alpha-fetoprotein (AFP) is a strong immunogen when injected into another species, but does not elicit an immune response in the species of origin of the AFP. AFPs from different mammalian species are crossreactive. AFP and albumin show sequence homology. They do not crossreact in their native state, but their unfolded (reduced and carboxamidomethylated) forms are immunologically crossreactive. Antibodies to autologous AFP can be induced in animals by immunization with heterologous or modified homologous AFP. These antibodies eliminate the AFP normally measurable in the serum and delay the elevation of serum AFP caused by hepatomas, but do not protect against such tumors.
Discovery of (2S)-8-[(3R)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: A Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors (2014)

Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives. Starting with hit compound 1a, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.
Cellular Trafficking of G Protein-coupled Receptor/β-Arrestin Endocytic Complexes (1999)

beta-Arrestins are multifunctional proteins identified on the basis of their ability to bind and uncouple G protein-coupled receptors (GPCR) from heterotrimeric G proteins. In addition, beta-arrestins play a central role in mediating GPCR endocytosis, a key regulatory step in receptor resensitization. In this study, we visualize the intracellular trafficking of beta-arrestin2 in response to activation of several distinct GPCRs including the beta2-adrenergic receptor (beta2AR), angiotensin II type 1A receptor (AT1AR), dopamine D1A receptor (D1AR), endothelin type A receptor (ETAR), and neurotensin receptor (NTR). Our results reveal that in response to beta2AR activation, beta-arrestin2 translocation to the plasma membrane shares the same pharmacological profile as described for receptor activation and sequestration, consistent with a role for beta-arrestin as the agonist-driven switch initiating receptor endocytosis. Whereas redistributed beta-arrestins are confined to the periphery of cells and do not traffic along with activated beta2AR, D1AR, and ETAR in endocytic vesicles, activation of AT1AR and NTR triggers a clear time-dependent redistribution of beta-arrestins to intracellular vesicular compartments where they colocalize with internalized receptors. Activation of a chimeric AT1AR with the beta2AR carboxyl-terminal tail results in a beta-arrestin membrane localization pattern similar to that observed in response to beta2AR activation. In contrast, the corresponding chimeric beta2AR with the AT1AR carboxyl-terminal tail gains the ability to translocate beta-arrestin to intracellular vesicles. These results demonstrate that the cellular trafficking of beta-arrestin proteins is differentially regulated by the activation of distinct GPCRs. Furthermore, they suggest that the carboxyl-tail of the receptors might be involved in determining the stability of receptor/betaarrestin complexes and cellular distribution of beta-arrestins.
Yolk Degradation in Tick Eggs: III. Developmentally Regulated Acidification of the Yolk Spheres (1991)

Yolk spheres in tick eggs contain a latent procathepsin L, which is activated in vivo, in parallel with yolk degradation, and in vitro by acid treatment (Fagotto, F., Arch. Insect Biochem. Physiol., 1990b in press). Mature cathepsin L hydrolyzes vitellin at acidic pH (Fagotto, F., Arch. Insect Biochem. Physiol., 1990a in press). Here, yolk spheres' pH has been estimated using acridine orange. In the early development, all yolk spheres are neutral, then an increasing number acidify, until hatching, where general acidification seems to occur. This fits well with vitellin utilized slowly during embryogenesis, more intensely at hatching (Chinzei, Y. and I. Yano, Experientia 41, 948, 1985), and can be related to sequential degradation of individual spheres observed during embryonic development, then extensive yolk liquefaction in the larva. Different yolk spheres populations have been separaded on Percoll density gradients. In freshly laid eggs, yolk spheres are dense, neutral, undegrated and contain exclusively the precursor of cathepsin L. In later stages, yolk spheres are progressively recovered in lower density fractions, displaying acidic interior and cytological signs of degradation. They cosediment with mature cathepsin L. It is concluded that acidification initiates yolk degradation through procathepsin L activation.
The production of DNA strand breaks in human leukocytes by superoxide anion may involve a metabolic process. (1985)

H2O2 is known to be capable of inducing strand-break damage in intracellular DNA, but whether O2- also can do so in the absence of H2O2 is uncertain. The difficulty in distinguishing the effects of the two is that, under physiological conditions, dismutation of O2- to H2O2 can readily occur. When human leukocytes are stimulated with phorbol 12-myristate 13-acetate (PMA), they release O2-, and within a few minutes strand breakage in intracellular DNA can be observed. We have attempted to determine whether the O2- produced is itself capable of causing DNA damage or whether H2O2 alone, or in combination with O2-, is responsible for the observed damage. Addition of catalase (up to 250 micrograms/ml) to remove H2O2 prevented no more than about 50% of the DNA damage. The majority of the remaining damage could be blocked, in a dose-dependent manner, by superoxide dismutase (SOD) or a SOD-mimetic copper complex, identifying a fraction of damage to intracellular DNA dependent upon extracellular O2-. We studied this O2(-)-specific fraction through the use of three metabolic poisons (fluoride, 2-deoxyglucose, and A23187). These agents largely blocked DNA damage, while affecting extracellular O2- levels only slightly. For comparison, H2O2-induced DNA damage was studied with glucose oxidase to generate a flux of H2O2. The first two metabolic poisons had little effect, whereas A23187 did inhibit H2O2-induced DNA damage. We conclude that O2(-)-induced damage occurs through a mechanism that differs, at least in part, from the H2O2 damage pathway and that the former may involve one or more metabolic steps.