gebhart/patrepeval huggingface dataset:
Erythropoietin-associated hypertensive posterior leukoencephalopathy (1997)

Human recombinant erythropoietin is used to treat chronic anemia in patients with end-stage renal failure. Erythropoietin causes hypertension, and hypertensive encephalopathy has been associated with its use. We describe six dialysis-dependent, chronic renal failure patients who developed hypertension, headache, and seizures while on erythropoietin. Four of the six patients had posterior white matter changes on neuroimaging. The encephalopathy was managed by prompt antihypertensive and anticonvulsant treatment and by discontinuation of erythropoietin. Hypertensive posterior leukoencephalopathy is associated with erythropoietin use.
The Regulatory Role of MRP8 (S100A8) and MRP14 (S100A9) in the Transendothelial Migration of Human Leukocytes (1999)

The hallmark of developing inflammatory lesions is the excess migration of recruited phagocytes together with the enhanced cell surface expression of adhesion molecules. Recent investigations give evidence that the two myeloid-related proteins MRP8 (S100A8) and MRP14 (S100A9), which are abundant in activated or recruited phagocytes, may have a modulatory role in inflammatory responses. S100A9 displays a regulatory role in the transendothelial migration of human monocytes, and the secreted S100A8/A9 complex may serve as a transport protein to move arachidonic acid to its target cells.
FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration. (2005)

FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, (S)-enantiomer of FTY720-phosphate [(S)-FTY720-P] on experimental autoimmune encephalomyelitis (EAE) in rats and mice. Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE, and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4(+) T cells into spinal cord was decreased by prophylactic treatment with FTY720 and (S)-FTY720-P. When FTY720 or (S)-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-beta, and the area of demyelination and the infiltration of CD4(+) T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4(+) T cells into the inflammation site.
Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses (2003)

Poor immune reconstitution after haploidentical stem cell transplantation results in a high mortality from viral infections and relapse. One approach to overcome this problem is to selectively deplete the graft of alloreactive cells using an immunotoxin directed against the activation marker CD25. However, the degree of depletion of alloreactive cells is variable following stimulation with recipient peripheral blood mononuclear cells (PBMCs), and this can result in graft versus host disease (GVHD). We have refined this approach using recipient Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) as stimulators to activate donor alloreactive T cells. Our studies demonstrate that allodepletion with an anti-CD25 immunotoxin following stimulation with HLA-mismatched host LCLs more consistently depleted in vitro alloreactivity than stimulation with host PBMCs, as assessed in primary mixed lymphocyte reactions (MLRs). Allodepletion using this approach specifically abrogates cytotoxic T-cell responses against host LCLs. In interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assays, antiviral responses to adenovirus and cytomegalovirus (CMV) were preserved following allodepletion. Likewise, using HLA-A2-pp65 tetramers, we have shown that the frequency of CMV-specific T cells is unaffected by allodepletion. Moreover, the donor anti-EBV response is partially retained by recognition of EBV antigens through the nonshared haplotype. Finally, we studied whether allodepletion affects the response to candidate tumor antigens in myeloid malignancies. Using HLA-A2-PR1 tetramer analysis, we found that the frequency of T cells recognizing the PR1 epitope of proteinase 3 was not significantly different in allodepleted and unmanipulated PBMCs from patients with chronic myeloid leukemia (CML) undergoing transplantation. Based on these data, we have embarked on a phase 1 clinical trial of addback of allo-LCL-depleted donor T cells in the haplo-identical setting.
Progressive Neurodegeneration of Retina in Alzheimer’s Disease — Are β-Amyloid Peptide and Tau New Pathological Factors in Glaucoma? (2013)

Progressive Neurodegeneration of Retina in Alzheimer’s Disease — Are β-Amyloid Peptide and Tau New Pathological Factors in Glaucoma?
Highly Reactive β‐Dicalcium Silicate: IV, Ball‐Milling and Static Hydration at Room Temperature (1992)

The ball‐milling hydration of highly reactive β‐Ca 2 SiO 4 synthesized from hillebrandite, Ca 2 (SiO 3 )(OH) 2 , was investigated and compared with its static hydration under a water/solid ratio of 10. In static hydration, the hydration is completed in 8 d to yield C‐S‐H with a Ca/Si ratio of 1.81 and Ca(OH) 2 . There is no major change after this period. In the case of ball milling, the hydration is completed in 2 d to yield C‐S‐H with Ca/Si = 1.81 and Ca(OH) 2 . After this, the two products react to form a C‐S‐H(II)‐like monophase hydrate having a Ca/Si ratio of 1.98. The morphology and structure of this hydrate are different from those of the earlier hydrate, and afwillite is not formed. 29 Si MAS NMR measurements indicated the C‐S‐H to be a mixture of dimers and single‐chain structures. Dimeric species are the main species up to completion of the reaction, but polymerization progresses very rapidly after the completion.
Synthesis of Novel Peptidomimetics, Cyclic Hexamers of Unnatural Amino Acids, 2,5-Disubstituted 3-Aminobenzoic Acids (1999)

Coupling of 3-aminobenwic acids and cyclizalion of their peptides have been accomplished, for the first time, using methanesulfonyl chloride.Cylindrical conformations for the 30-membered cyclic hexapeptides, with trans configuration at the amide bonds, are suggested by ROESY study as well as MM calculations.Biochemical activity of peptides is due primarily to the spacial disposition of certain amino acid residues, while the peptide backbone is, in many cases, merely for holding such structural requiremenL2 This report describes a novel design and synthesis of such cyclic peptides, as those having various functional groups on a rigid peptide framework, from appropriately substituted 3-aminobenwic acids.The building blocks, 5-alkyl-3-amino-2-methoxyethylbenzoic acids (la), were selected for this purpose, and were synthesized from 4-isopropylbenzaldehyde or cinnamic acid.)The substituent at 2-position could be modified to such functional groups as those of natural amino acid residues4 The other substituent at 5-position endows the amino acids and the peptides with lipophilic or hydrophilic characters, as well as to restrict conformational mobility.
Lanadelumab for the treatment of hereditary angioedema (2019)

<b>Introduction</b>: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare yet still probably underdiagnosed clinical condition. Recurrent episodes of subcutaneous and sub-mucosal swelling may involve the skin, the gastrointestinal tract or even the upper airways, exposing the patients to the risk of death. With the aim of improving patients' quality of life, the therapeutic scenario has expanded over the years.<b>Areas covered</b>: The focus of the present review is lanadelumab, a fully human, κ-light-chain, monoclonal immunoglobulin G1 against plasma kallikrein, currently approved for long-term prophylaxis of C1-INH-HAE attacks in the USA and Canada and designated as an orphan drug by the European Medicines Agency.<b>Expert opinion</b>: Lanadelumab is able to inhibit plasma kallikrein with high selectivity and affinity. The subsequent phases of drug development and the ongoing open-label trial have proven its safety and efficacy. It overcomes some of the limitations of other drugs available for long-term prophylaxis, given the easy route of administration, the simple administration schedule and the possibility to tailor the treatment to each patient. Further studies are needed to test its efficacy also in other types of angioedema for which a central role of plasma kallikrein is envisaged.
Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells. (1990)

Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location of amplified c-myc oncogene sequences in HL-60 promyelocytic leukemia cells. In passages 46-62 of the cells, the cells contain amplified c-myc sequences on submicroscopic circular extrachromosomal DNA (episomes). With increased passages in culture (passages 63-72) the cells lose the episome c-myc sequences with a shift of those sequences to double minutes. With additional passage in culture, the c-myc shifts from the double minutes to a chromosomal site der(5)t(5;17)(q11.2;q?11.2). Concomitant with the shift of the c-myc sequences into the chromosomal compartment is a phenotypic change of a shortened cell-doubling time. These studies provide the first molecular evidence of a progression from a submicroscopic location for amplified oncogene sequences to a chromosomal location for the amplified sequences. This molecularly documented model can now be used to test various strategies to prevent incorporation of extrachromosomally located oncogene sequences into chromosomal sites. Prevention of integration of the oncogene sequences into chromosomal sites could modulate progression of patients' tumors.
Comparison of the action of BD 40 A and some other beta-adrenoceptor stimulants on the isolated trachea and atria of the guinea pig. (1976)

<P>Abstract copyright UK Data Service and data collection copyright owner.</P>
Macromolecular intravenous contrast agent for MR lymphography: characterization and efficacy studies. (1996)

When labeled with Gd-DTPA, the PGM-based graft copolymer significantly increases signal intensity at MR imaging of normal but not metastatic lymph nodes without causing distortion artifacts.
Colonial Opacity Variations among the Choleragenic Vibrios (1997)

Cultures of Vibrio cholerae 01, biotype El Tor, from the current epidemic of cholera in the Western Hemisphere, and of the new V. cholerae serogroup O139, from the current outbreak in India and Bangladesh, revealed marked colonial heterogeneity when received by the authors. By comparison with reference colony types, using a stereoscope and transmitted oblique illumination, colonies of approximately 10 different degrees of opacity could be distinguished. In contrast, strains freshly isolated from patients and rapidly and carefully preserved were more homogeneous although still differentiable by this technique. These (and older) observations prompted the questions: (1) why is a V. cholerae colony opaque or translucent? and (2) what benefit is it to the vibrios to vary their colonial appearance? The observed changes in colonial opacity, which are reversible, are sometimes (rarely) accompanied by changes in virulence for infant rabbits and, more frequently, by other phenotypic variations including the ability to produce poly-beta-hydroxybutyrate inclusion bodies on glycerol-containing medium, the degree of encapsulation in 0139, changes in outer-membrane proteins, alteration in lipopolysaccharide structure, changes in expression of glycolytic pathways, and differences in ability to survive under adverse conditions. Colonial variations in choleragenic vibrios are phenotypically multifactorial. The genetic mechanisms(s) underlying the observed phenotypic changes remain to be defined.
Quantitative paper spray mass spectrometry analysis of drugs of abuse (2013)

An ambient method for rapid monitoring and quantitation of drugs of abuse in dried blood spots was developed using paper spray tandem mass spectrometry (PS-MS).
Effects of local infusion of TGF? on bone ingrowth in rabbit chambers (2000)

The local delivery of exogenous growth factors may help achieve a stable, long-lasting prosthetic interface around primary and revision joint replacements. This study examines the effects of local infusion of transforming growth factor beta (TGFbeta) in an in vivo model of tissue differentiation within bone. The Drug Test Chamber was implanted in the proximal medial tibial metaphysis of 8 mature rabbits unilaterally. The chamber contained a 1 x 1 x 5 mm canal for tissue ingrowth. The chamber was connected to an osmotic diffusion pump via polyvinyl tubing. 3.5 microg of recombinant TGFbeta1 was infused for 1 day or 1 week with subsequent harvesting of the ingrown tissue after 3 weeks. Each TGFbeta treatment was followed by two, 3-week infusions of carrier alone and harvesting of the ingrown tissue. TGFbeta for 1 day increased, and TGFbeta for 1 week decreased the percentage of bone in the chamber, compared to the initial control harvest after carrier alone. These changes, however, did not reach statistical significance. The number of vitronectin receptor positive cells in total, adjacent to bone and away from bone was higher after treatment with TGFbeta for 1 day, compared to 1 week. In an "unperturbed" bone ingrowth system (i.e., if bone ingrowth is not initially suppressed by other stimuli), this dose of TGFbeta did not enhance bone ingrowth using the DTC model.
Oligomerization domain-directed reassembly of active dihydrofolate reductase from rationally designed fragments (1998)

Reassembly of enzymes from peptide fragments has been used as a strategy for understanding the evolution, folding, and role of individual subdomains in catalysis and regulation of activity. We demonstrate an oligomerization-assisted enzyme reassembly strategy whereby fragments are covalently linked to independently folding and interacting domains whose interactions serve to promote efficient refolding and complementation of fragments, forming active enzyme. We show that active murine dihydrofolate reductase (E.C. 1.5.1.3) can be reassembled from complementary N- and C-terminal fragments when fused to homodimerizing GCN4 leucine zipper-forming sequences as well as heterodimerizing protein partners. Reassembly is detected by an in vivo selection assay in Escherichia coli and in vitro. The effects of mutations that disrupt fragment affinity or enzyme activity were assessed. The steady-state kinetic parameters for the reassembled mutant (Phe-31 --> Ser) were determined; they are not significantly different from the full-length mutant. The strategy described here provides a general approach for protein dissection and domain swapping studies, with the capacity both for rapid in vivo screening as well as in vitro characterization. Further, the strategy suggests a simple in vivo enzyme-based detection system for protein-protein interactions, which we illustrate with two examples: ras-GTPase and raf-ras-binding domain and FK506-binding protein-rapamycin complexed with the target of rapamycin TOR2.
Functional and structural features of γ‐zeathionins, a new class of sodium channel blockers (1998)

Gamma1- and gamma2-zeathionins (gamma1-Z and gamma2-Z) are members of a family of small and basic peptides involved in plant protection. These plant defensins exhibit remarkable structural similarity to scorpion neurotoxins and insect defensins. In the present report, we used the whole-cell patch clamp technique to investigate the inhibition of the sodium current (I(Na)) by gamma1-Z and gamma2-Z in the GH3 cell line. Both gamma1-Z and gamma2-Z rapidly and reversibly inhibited I(Na) without changing the kinetics or voltage dependence of activation or inactivation. To our knowledge, this is the first example of a plant protein that inhibits the sodium channel. From structural comparisons with the mu-conotoxins, a family of peptides that block the sodium channel, we detected some similar features that could provide the basis of inhibition of sodium channels by gamma-zeathionins.
Microdroplets: A sea of applications? (2008)

The exploitation of microdroplets produced within microfluidic environments has recently emerged as a new and exciting technological platform for applications within the chemical and biological sciences. Interest in microfluidic systems has been stimulated by a range of fundamental features that accompany system miniaturization. Such features include the ability to process and handle small volumes of fluid, improved analytical performance when compared to macroscale analogues, reduced instrumental footprints, low unit cost, facile integration of functional components and the exploitation of atypical fluid dynamics to control molecules in both time and space. Moreover, microfluidic systems that generate and utilize a stream of sub-nanolitre droplets dispersed within an immiscible continuous phase have the added advantage of allowing ultra-high throughput experimentation and being able to mimic conditions similar to that of a single cell (in terms of volume, pH, and salt concentration) thereby compartmentalizing biological and chemical reactions. This review provides an overview of methods for generating, controlling and manipulating droplets. Furthermore, we discuss key fields of use in which such systems may make a significant impact, with particular emphasis on novel applications in the biological and physical sciences.
Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity. (1980)

In a previous study we demonstrated that antiviral response against the coliphage MS-2 can be elicited by immunization with a synthetic antigen consisting of a conjugate (P2-A -- L) of a synthetic fragment (P2) of the virus coat protein attached to a synthetic polymeric carrier. The antiviral response was induced when the antigen was administered in complete Freund's adjuvant or when it was administered in incomplete adjuvant, provided that a peptidoglycan was covalently attached to it. In the present study we demonstrate the adjuvant effect of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in this system. Immunization with a mixture of MDP and P2-A -- L brought about only slight enhancement in the titer of neutralizing antibodies, as compared to the immunization with P2-A -- L in saline. The best results were achieved when the MDP was chemically conjugated to P2-A -- L. This completely synthetic material, when administered in aqueous solution, yielded highly inactivating antiserum with a titer similar to that obtained with complete Freund's adjuvant in the absence of MDP. MDP-P2-A -- L elicited also a humoral immune response to MDP, but with much lower titer than that induced by complete Freund's adjuvant containing P2-A -- L only. It was also observed that the capacity of MDP-P2-A -- L to increase resistance against infection was more than a 100-fold greater than that of unconjugated MDP.
A review of SSRIs and SNRIs in neuropathic pain (2010)

SSRIs and SNRIs may be considered in the treatment of neuropathic pain if treatment with tricyclic antidepressants and anticonvulsants fails, or if there are contraindications to these drugs. There is also sufficient evidence to indicate that SNRIs are effective in the treatment of fibromyalgia and may be considered early in the treatment of fibromyalgia.
In Vivo Structure−Activity Relationship Study of Dorsomorphin Analogues Identifies Selective VEGF and BMP Inhibitors (2009)

The therapeutic potential of small molecule signaling inhibitors is often limited by off-target effects. Recently, in a screen for compounds that perturb the zebrafish embryonic dorsoventral axis, we identified dorsomorphin, the first selective inhibitor of bone morphogenetic protein (BMP) signaling. Here we show that dorsomorphin has significant "off-target" effects against the VEGF (vascular endothelial growth factor) type-2 receptor (Flk1/KDR) and disrupts zebrafish angiogenesis. Since both BMP and VEGF signals are known to be involved in vascular development, we sought to determine whether dorsomorphin's antiangiogenic effects are due to its impact on the BMP or VEGF signals through the development of analogues that target BMP but not VEGF signaling and vice versa. In a structure-activity relationship (SAR) study of dorsomorphin analogues based primarily on their effects on live zebrafish embryos, we identified highly selective and potent BMP inhibitors as well as selective VEGF inhibitors. One of the BMP inhibitors, DMH1, which exclusively targets the BMP but not the VEGF pathway, dorsalized the embryonic axis without disrupting the angiogenic process, demonstrating that BMP signaling was not involved in the angiogenic process. This is one of the first full-scale SAR studies performed in vertebrates and demonstrates the potential of zebrafish as an attractive complementary platform for drug development that incorporates an assessment of in vivo bioactivity and selectivity in the context of a living organism.
Total Synthesis of (−)-Ascochlorin via a Cyclobutenone-Based Benzannulation Strategy (2000)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTTotal Synthesis of (−)-Ascochlorin via a Cyclobutenone-Based Benzannulation StrategyGregory B. Dudley, Katherine S. Takaki, Don D. Cha, and Rick L. DanheiserView Author Information Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Cite this: Org. Lett. 2000, 2, 21, 3407–3410Publication Date (Web):September 23, 2000Publication History Received7 September 2000Published online23 September 2000Published inissue 1 October 2000https://pubs.acs.org/doi/10.1021/ol006561chttps://doi.org/10.1021/ol006561crapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views3818Altmetric-Citations58LEARN 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 SUBJECTS:Alcohols,Aromatic compounds,Hydrocarbons,Molecular structure,Reaction products Get e-Alerts