gebhart/patrepeval huggingface dataset:
Impairment of concanavalin A-inducible suppressor activity following administration of cyclophosphamide to patients with advanced cancer. (1984)

We have shown that cyclophosphamide (CY) can augment the development of delayed-type hypersensitivity to a primary antigen in patients with advanced cancer. In the present study, we administered CY (1000 mg/sq m) to 19 patients with advanced, metastatic cancer and monitored the compositional and functional changes in their peripheral blood mononuclear cells. Within 2 days of administration of CY, the lymphocyte count fell significantly (mean decrease = 26.0%) and remained significantly depressed through Day 14 with recovery beginning by Day 21. T- and B-lymphocytes were depleted to about the same degree at each time point. Moreover, there was no selective depletion of the Leu 2(+) (suppressor-cytotoxic) or Leu 3(+) (helper-inducer) subsets of T-lymphocytes. Proliferative responses to mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen) and to allogeneic cells fell significantly within 1 day of administration of CY and continued to be diminished on Day 2. However, these responses recovered to pretreatment levels by Day 3, and, in some cases, exceeded pretreatment levels on Day 7. Concanavalin A-inducible suppressor activity was also diminished on Day 1 (mean decrease, 23.4%) and Day 2 (mean decrease, 39.2%). However, in contrast to the proliferative responses, suppressor activity continued to be significantly impaired on Day 3 (mean decrease, 31.6%) and only partially recovered by Day 7 (mean decrease, 22.1%). Both concanavalin A-inducible suppression and proliferative responses declined again on Days 14 and 21. Thus, between 3 and 7 days after administration of CY, there appeared to be impairment of nonspecific T-cell-mediated suppressor activity of peripheral blood lymphocytes that was not merely a reflection of impaired lymphocyte function in general. This could account for the augmented delayed-type hypersensitivity responses of CY-treated patients.
Dicamba resistance in kochia (2001)

Kochia plants resistant (R) to field rates of dicamba were characterized for their frequency of occurrence and levels of resistance and for the physiological fate of applied 14C-dicamba. Of 167 randomly sampled fields and seven fields identified by producers to contain R kochia, 19 contained plants that produced 1% or more R progeny. The maximum percentage of R progeny produced by parental plants from any field was 13%. An inbred R line derived from a field collection was 4.6-fold more resistant to dicamba than an inbred susceptible (S) line. Rates of 14C-dicamba uptake and translocation were similar in R and susceptible (S) plants up to 168 h after treatment (HAT). Concentrations of the primary metabolite, 5-hydroxy dicamba, were similar in R and S tissues up to 60 HAT, although amounts were significantly greater in R treated leaves by 96 and 168 HAT. However, because there were negligible levels of dicamba metabolites in R shoots and because the rate of metabolism was relatively slow, the observed changes were inadequate to account for observed resistance levels. Thus, dicamba resistance in kochia cannot be attributed to differential herbicide absorption, translocation, or metabolism. These findings, together with our field observations on the unusually slow spread of resistance within and among fields may indicate that dicamba resistance is a quantitative trait.
Antibody–Drug Conjugates: An Emerging Concept in Cancer Therapy (2014)

Traditional cancer chemotherapy is often accompanied by systemic toxicity to the patient. Monoclonal antibodies against antigens on cancer cells offer an alternative tumor-selective treatment approach. However, most monoclonal antibodies are not sufficiently potent to be therapeutically active on their own. Antibody-drug conjugates (ADCs) use antibodies to deliver a potent cytotoxic compound selectively to tumor cells, thus improving the therapeutic index of chemotherapeutic agents. The recent approval of two ADCs, brentuximab vedotin and ado-trastuzumab emtansine, for cancer treatment has spurred tremendous research interest in this field. This Review touches upon the early efforts in the field, and describes how the lessons learned from the first-generation ADCs have led to improvements in every aspect of this technology, i.e., the antibody, the cytotoxic compound, and the linker connecting them, leading to the current successes. The design of ADCs currently in clinical development, and results from mechanistic studies and preclinical and clinical evaluation are discussed. Emerging technologies that seek to further advance this exciting area of research are also discussed.
Yersinia pestis--etiologic agent of plague (1997)

Plague is a widespread zoonotic disease that is caused by Yersinia pestis and has had devastating effects on the human population throughout history. Disappearance of the disease is unlikely due to the wide range of mammalian hosts and their attendant fleas. The flea/rodent life cycle of Y. pestis, a gram-negative obligate pathogen, exposes it to very different environmental conditions and has resulted in some novel traits facilitating transmission and infection. Studies characterizing virulence determinants of Y. pestis have identified novel mechanisms for overcoming host defenses. Regulatory systems controlling the expression of some of these virulence factors have proven quite complex. These areas of research have provide new insights into the host-parasite relationship. This review will update our present understanding of the history, etiology, epidemiology, clinical aspects, and public health issues of plague.
Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates (2000)

We evaluated the effects of the lipophilic nonpeptide corticotropin-releasing hormone (CRH) type 1 receptor antagonist antalarmin on the behavioral, neuroendocrine, and autonomic components of the stress response in adult male rhesus macaques. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid by a mass spectrometry-gas chromatography assay developed specifically for this purpose. Pharmacokinetic and dose-response studies suggested that an oral dose of 20 mg/kg was optimal for behavioral and endocrine effects. We then administered this dose in a double-blind, placebo-controlled fashion to monkeys exposed to an intense social stressor: namely, placement of two unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. We conclude that CRH plays a broad role in the physiological responses to psychological stress in primates and that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity.
Carbon Nanotube Tips:  High-Resolution Probes for Imaging Biological Systems (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCarbon Nanotube Tips: High-Resolution Probes for Imaging Biological SystemsStanislaus S. Wong, James D. Harper, Peter T. Lansbury,, and Charles M. LieberView Author Information Department of Chemistry and Chemical Biology Harvard University, 12 Oxford Street Cambridge, Massachusetts 02138 Center for Neurologic Disease, Brigham and Women's Hospital and Harvard Medical School 77 Avenue Louis Pasteur, Boston, Massachusetts 02115 Cite this: J. Am. Chem. Soc. 1998, 120, 3, 603–604Publication Date (Web):January 8, 1998Publication History Received3 November 1997Revised10 December 1997Published online8 January 1998Published inissue 1 January 1998https://pubs.acs.org/doi/10.1021/ja9737735https://doi.org/10.1021/ja9737735rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1107Altmetric-Citations270LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Carbon nanotubes,Nanofibers,Nanotubes,Probes,Silicon Get e-Alerts
E‐selectin expression induced by pancreas‐carcinoma‐derived interleukin‐1α results in enhanced adhesion of pancreas‐carcinoma cells to endothelial cells (1995)

Cellular adhesion of sialyl-Lewis-a(SLea)-positive pancreas carcinoma to endothelial cells (EC) is augmented by activation of EC via up-regulated E-selectin expression on EC. Co-cultivation of pancreas-carcinoma cells, PCI-24, with human umbilical-vein endothelial cells (HUVEC) for 5 hr at the PCI-to-HUVEC ratio of 1:10 induced E-selectin expression on the endothelial-cell surface, augmenting SLea-positive pancreas-carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested pancreas-carcinoma cell lines contained soluble, E-selectin-inducing factor(s). The E-selectin-inducing effect by the supernatants was blocked by the protein-kinase-C inhibitor, H7. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased pancreas-carcinoma-to-endothelial attachment. Paraformaldehyde(PFA)-fixed PCI-24 cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane-bound form. The 6 pancreas-carcinoma lines all produced IL-1 alpha mRNA and protein but not IL-1 beta or TNF-alpha protein and/or mRNA. Absorption of IL-1 alpha from the supernatants by IL-1 alpha-specific antibody almost completely abolished E-selectin-inducing activity. Anti-IL-1 alpha antibody also abolished the E-selectin-inducing activity of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulated by TNF-alpha. These observations suggest that substance(s) produced by pancreas-carcinoma cells, in this case, IL-1 alpha, may contribute to pancreas-carcinoma-cell colonization in non-inflamed, distant locations in vivo, by activating vascular endothelial cells.
Involvement of matrix metalloproteinase type‐3 in hepatocyte growth factor‐induced invasion of human hepatocellular carcinoma cells (2001)

Intra-hepatic invasion is a key feature of hepatocellular carcinoma (HCC) progression. We have shown that human liver myofibroblasts induce invasion of HCC cells through Matrigel, via the secretion of hepatocyte growth factor (HGF). In our study, we investigated the role of matrix metalloproteinases (MMP) in HGF-induced HCC cells invasion. Marimastat, a synthetic MMP inhibitor, dose-dependently decreased HGF-induced invasion of HepG2 cells with a maximum of 82.7 +/- 13.3% at 20 microM. TIMP-2, a natural inhibitor, decreased invasion up to 51.2 +/- 11.2% at 200 ng/ml. To determine the target for these inhibitors, we examined MMP expression using RT-PCR. MMPs 1, 7-9 and 10 were not expressed in HepG2 cells either in the absence or in the presence of HGF. MMP-2 and MMP-13 transcripts were detected in unstimulated cells but their expression was unchanged after exposition to HGF. MMP-3 transcripts were undetectable in unstimulated HepG2 cells. They became clearly expressed in HGF-stimulated cells, however, and this was confirmed by Northern blot. By Western blot, HGF dose-dependently stimulated the secretion of pro-MMP-3 in the culture medium. The role of MMP-3 in HGF-induced invasion was directly confirmed by using an antibody to MMP-3, that blocked invasion. Finally, RT-PCR demonstrated MMP-3 expression in 10/16 human HCCs tested, but not in normal liver. In conclusion, our data demonstrate that MMPs, most likely MMP-3, mediate HGF-induced invasion of HCC cells. The in vivo expression of MMP-3 in HCC suggests a role for this protease in HCC progression.
Inhaled Nitric Oxide Selectively Reverses Human Hypoxic Pulmonary Vasoconstriction without Causing Systemic Vasodilation (1993)

Inhalation of 40 ppm NO selectively induced pulmonary vasodilation and reversed hypoxic pulmonary vasoconstriction in healthy humans without causing systemic vasodilation.
Tracking of Proinflammatory Collagen-Specific T Cells in Early and Late Collagen-Induced Arthritis in Humanized Mice (2004)

Rheumatoid arthritis is a chronic inflammatory disease associated with certain HLA-DR4 subtypes. The target autoantigen(s) is unknown, but type II collagen (CII) is a candidate, with a single immunodominant DR4-restricted 261-273 T cell epitope (CII(261-273)). In the present study, we have prepared HLA-DR4:CII(261-273) tetramers and analyzed peripheral blood, lymph node, and synovial fluid cells from DR4-transgenic mice with early and late collagen-induced arthritis to draw a fuller picture of the role of CII-reactive Th cells in disease development. Their frequencies increased approximately 20-fold in blood 1-2 wk postimmunization, and even more in acutely arthritic joints. Our data strongly suggest that CII-specific Th cells are necessary, but not sufficient for collagen-induced arthritis. The CII-specific Th cells displayed an activated proinflammatory Th1 phenotype, and their expansion correlated with onset and severity of arthritis and also with anti-CII Ab levels. Surprisingly, shortly after the first clinical signs of arthritis, activated HLA-DR4:CII tetramer(+) cells became undetectable in the synovial fluid and rare in the blood, but persisted in lymph nodes. Consequently, future human studies should focus on patients with early arthritis, and on their synovial cells, to re-evaluate the occurrence and pathogenic importance of CII-specific or other Th cells in rheumatoid arthritis.
N-Heterocyclic Carbenes in Late Transition Metal Catalysis (2009)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTN-Heterocyclic Carbenes in Late Transition Metal CatalysisSilvia Díez-González†, Nicolas Marion‡†, and Steven P. Nolan*†§View Author Information Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain, and School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K.*[email protected]†Institute of Chemical Research of Catalonia.‡Present address: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.§University of St Andrews.Cite this: Chem. Rev. 2009, 109, 8, 3612–3676Publication Date (Web):July 9, 2009Publication History Received24 February 2009Published online9 July 2009Published inissue 12 August 2009https://pubs.acs.org/doi/10.1021/cr900074mhttps://doi.org/10.1021/cr900074mreview-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views36042Altmetric-Citations2763LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Addition reactions,Catalysts,Chemical reactions,Hydrocarbons,Ligands Get e-Alerts
Synthesis of some possible metabolites of thyroxine and triiodothyronine (1956)

Research Article| August 01 1956 Synthesis of some possible metabolites of thyroxine and triiodothyronine J. H. Wilkinson J. H. Wilkinson 1The Vincent Square Laboratories of Westminster Hospital, 124 Vauxhall Bridge Road, London, S.W. 1 Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd © 1956 CAMBRIDGE UNIVERSITY PRESS1956 Biochem J (1956) 63 (4): 601–605. https://doi.org/10.1042/bj0630601 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 J. H. Wilkinson; Synthesis of some possible metabolites of thyroxine and triiodothyronine. Biochem J 1 August 1956; 63 (4): 601–605. doi: https://doi.org/10.1042/bj0630601 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 Journal Search Advanced Search This content is only available as a PDF. © 1956 CAMBRIDGE UNIVERSITY PRESS1956 Article PDF first page preview Close Modal You do not currently have access to this content.
Monocrotaline pyrrole-induced endothelial cell megalocytosis involves a Golgi blockade mechanism (2004)

Pyrrolizidine alkaloids initiate disease in the lung (pulmonary hypertension), liver (veno-occlusive disease and cirrhosis), and kidneys (afferent arteriolar block and mesangiolysis) by inducing a megalocytotic phenotype in target endothelial and parenchymal cells. A "hit-and-run" type of exposure to the bioactive pyrrolizidine results, within 2-3 days, in enlarged cells with large nuclei and enlarged Golgi and endoplasmic reticulum, while the cells remain in G2/M block. In the present study, we recapitulated monocrotaline pyrrole (MCTP)-induced megalocytosis in cultures of bovine pulmonary arterial endothelial cells (PAEC), human Hep3B hepatocytes, human type II-like alveolar epithelial cells (A549), and human pulmonary arterial smooth muscle cells (PASMC) and investigated the subcellular mechanism involved. There was an inverse relationship between reduction in caveolin (Cav)-1 levels and stimulation of promitogenic STAT3 and ERK1/2 cell signaling. In megalocytotic PAEC, the Golgi scaffolding protein GM130 was shifted from membranes with heavy density to those with a lighter density. This lighter Golgi fraction was enriched for hypo-oligomeric Cav-1, indicating dysfunctional trafficking of cargo. Immunofluorescence imaging studies confirmed the trapping of Cav-1 in a GM130-positive Golgi compartment. There was an increase in Ser25 phosphorylation of GM130 (typically a prelude to Golgi fragmentation and mitosis) and increased association between pGM130, cdc2 kinase, and Cav-1. Nevertheless, megalocytotic MCTP-treated cells showed reduced entry into mitosis upon stimulation with 2-methoxyestradiol (2-ME), reduced 2-ME-induced Golgi fragmentation, and a slowing of Golgi reassembly after nocodazole-induced fragmentation. These data suggest that a disruption of the trafficking and mitosis sensor functions of the Golgi may represent the subcellular mechanism leading to MCTP-induced megalocytosis ("the Golgi blockade hypothesis").
Immunotherapy of cancer using heat shock proteins (2002)

Tumor derived heat shock protein (hsp)-peptide complexes (particularly hsp70 and grp94/gp96) have been demonstrated to serve as effective vaccines, producing anti-tumor immune responses in animals and in man. This approach utilizes the peptide binding properties of stress proteins which are responsible for their functions as molecular chaperones in numerous cellular processes. The present review briefly introduces the reader to the basic stress protein families, i.e. heat shock and glucose regulated proteins, their regulation, compartmentalization and family members. It then introduces the reader to aspects of hsps/grp function and interactions with the host's immune system. An overview of the conventional uses of hsp/grp vaccines as autologous vaccines derived from cancers is presented. We then discuss other stress protein related vaccination approaches. This includes the use of recombinant antigens, both proteins and peptides, naturally complexed to hsp/grps; hsp/grp DNA vaccines, hsp/grp fusion proteins and cell based hsp/grp vaccines. The advantages and disadvantages of each vaccination approach are discussed. Lastly, means of further enhancing the already potent activity of stress protein vaccines are presented, specifically the use of hyperthermia or CTLA-4 blockade as adjuvants.
Stereo-controlled synthesis of dl-prostaglandins F2.alpha. and E2 (1969)

A new approach to the synthesis of prostaglandins, designed with the following objectives in mind, is reported. The objectives were: 1) control of stereochemistry; 2) the synthesis of all of the primary prostaglandins and a variety of analogs from a single precursor; and 3) optical resolution at an early stage. The fifteenth synthesis step yielded dl-prostaglandin F2 alpha identical to the natural hormone. Step by step routes of synthesis and stereochemistry are depicted in the text.
Reduction of Selenite and Detoxification of Elemental Selenium by the Phototrophic Bacterium Rhodospirillum rubrum (1999)

The effect of selenite on growth kinetics, the ability of cultures to reduce selenite, and the mechanism of detoxification of selenium were investigated by using Rhodospirillum rubrum. Anoxic photosynthetic cultures were able to completely reduce as much as 1. 5 mM selenite, whereas in aerobic cultures a 0.5 mM selenite concentration was only reduced to about 0.375 mM. The presence of selenite in the culture medium strongly affected cell division. In the presence of a selenite concentration of 1.5 mM cultures reached final cell densities that were only about 15% of the control final cell density. The cell density remained nearly constant during the stationary phase for all of the selenite concentrations tested, showing that the cells were not severely damaged by the presence of selenite or elemental selenium. Particles containing elemental selenium were observed in the cytoplasm, which led to an increase in the buoyant density of the cells. Interestingly, the change in the buoyant density was reversed after selenite reduction was complete; the buoyant density of the cells returned to the buoyant density of the control cells. This demonstrated that R. rubrum expels elemental selenium across the plasma membrane and the cell wall. Accordingly, electron-dense particles were more numerous in the cells during the reduction phase than after the reduction phase.
Effects of Transdermal Testosterone on Bone and Muscle in Older Men With Low Bioavailable Testosterone Levels (2001)

Background. A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men. The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation.