gebhart/patrepeval huggingface dataset:
Neuroendocrine Regulation of mucosal Immunity (1989)

In view of the extensive innervation of the gastrointestinal tract, including the mucosa, and the high number of immune effector cells present in this tissue, we have studied the effects of certain neurotransmitters on immune responses. We have concentrated on the effects of the neuropeptides substance P (SP), somatostatin (SOM) and vasoactive intestinal peptide (VIP). We have found that SP causes an increase in the proliferation of Peyer's patch lymphocytes as well as immunoglobulin (especially IgA) synthesis, when compared to splenic cells; and that there is a greater expression of SP receptors on lymphocytes derived from Peyer's patches compared to the spleen, without a significant difference in the expression between subsets of T and B cells. Furthermore, we have shown that intraepithelial leukocytes (IEL) show significantly increased cytotoxic activity following incubation with SP; whereas splenic lymphocytes were not stimulated in the same system. The effects of SOM where bi-directional depending upon the concentration employed but in general, SOM was inhibitory, in terms of proliferation, as was VIP. Although many more experiments are required to prove a physiological significance for the results that we have obtained, and to examine the whole gamut of neurotransmitters, we suggest that neuroendocrine regulation may play an important part in mucosal immunity.
Early magnetic resonance imaging findings in patients receiving tissue plasminogen activator predict outcome: Insights into the pathophysiology of acute stroke in the thrombolysis era (2003)

We measured ischemic brain changes with diffusion and perfusion MRI in 42 ischemic stroke patients before and 2 hours (range approximately 1.5 to 4.5 hours) after standard intravenous tissue plasminogen activator (tPA) therapy. The median time from stroke onset to tPA was 131 minutes. Clinical and MRI variables (change in perfusion and/or diffusion weighted lesion volume) were compared between those with excellent outcome defined as 3-month modified Rankin score (mRS) of 0 to 1 and those with incomplete recovery (mRS >1). In multivariate logististic regression analysis, the most powerful independent predictor for excellent outcome was improved brain perfusion: hypoperfusion volume on mean transit time (MTT) map decrease >30% from baseline to 2-hour post tPA scan (p=0.009; odds ratio [95% confidence interval], 20.7 [2.1-203.9]). Except for age < 70 years, no other baseline clinical or imaging variable was an independent predictor of outcome. We propose MTT lesion volume decrease more than 30% 2 hours after tPA as an early marker of long-term clinical benefit of thrombolytic therapy.
Melanoma cell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis (2005)

Melanoma is the most aggressive of skin cancers because of its high resistance to currently available therapy. Although melanoma cells often retain wild-type p53 tumour suppressor protein and express it at high levels, the p53 mediated apoptosis pathway is suppressed. Histone deacetylase (HDAC) inhibitors are a promising group of compounds inducing differentiation, growth arrest and apoptosis in tumour cells in preclinical studies. We have studied the cellular effects of trichostatin A (TSA), a HDAC inhibitor, in a panel of melanoma cell lines and its mechanism of action in relation to p53. TSA stabilized wild-type p53, but p53 protein accumulation was overridden by simultaneous downregulation of p53 mRNA leading to a decrease in p53 protein. While growth arrest was induced in all cell lines studied and apoptosis in most (6/7), these cellular effects were independent of the p53 status of the cells. Inhibiting p53 function by a dominant negative p53 (p53(175His)) confirmed that the HDAC inhibitor induced apoptosis was independent of wild-type p53, even though TSA slightly activated p53 in a reporter assay. The results indicate that while the action of TSA is independent of p53, the activation of the apoptosis pathway by the HDAC inhibitors may provide therapeutic approaches for melanoma treatment.
Triple light chain antibodies: Factors that influence its formation in cell culture (2009)

THIOMABs are recombinant antibodies engineered with reactive cysteines, which can be covalently conjugated to drugs of interest to generate targeted therapeutics. During the analysis of THIOMABs secreted by stably transfected Chinese Hamster Ovary (CHO) cells, we discovered the existence of a new species--Triple Light Chain Antibody (3LC). This 3LC species is the product of a disulfide bond formed between an extra light chain and one of the engineered cysteines on the THIOMAB. We characterized the 3LC by size exclusion chromatography, mass spectrometry, and microchip electrophoresis. We also investigated the potential causes of 3LC formation during cell culture, focusing on the effects of free light chain (LC) polypeptide concentration, THIOMAB amino acid sequence, and glutathione (GSH) production. In studies covering 12 THIOMABs produced by 66 stable cell lines, increased free LC polypeptide expression--evaluated as the ratio of mRNA encoding for LC to the mRNA encoding for heavy chain (HC)--correlated with increased 3LC levels. The amino acid sequence of the THIOMAB molecule also impacted its susceptibility to 3LC formation: hydrophilic LC polypeptides showed elevated 3LC levels. Finally, increased GSH production--evaluated as the ratio of the cell-specific production rate of GSH (q(GSH)) to the cell-specific production rate of THIOMAB (q(p))--corresponded to decreased 3LC levels. In time-lapse studies, changes in extracellular 3LC levels during cell culture corresponded to changes in mRNA LC/HC ratio and q(GSH)/q(p) ratio. In summary, we found that cell lines with low mRNA LC/HC ratio and high q(GSH)/q(p) ratio yielded the lowest levels of 3LC. These findings provide us with factors to consider in selecting a cell line to produce THIOMABs with minimal levels of the 3LC impurity.
Restriction Fragment Mapping of Nontypable Hoemophilus Influenzae: A New Tool to Study This Middle Ear Pathogen (1989)

Isolates of nontypable haemophilus influenzae (NTHI) recovered from paired nasopharyngeal (NP) and middle ear (ME) fluid cultures performed simultaneously on seven children with otitis media with effusion (OME) were studied by analysis of the restriction fragment patterns produced from total genomic DNA. This method provides a sensitive measure of the genetic similarities between strains. In the seven pairs examined, the NP and ME strains were indistinguishable from one another, whereas each pair was distinct from the other, except for two siblings in whom all four strains were identical. This information provides evidence that the pathogenesis of OME caused by NTHI involves spread of the bacteria from NP to the ME. Analysis of paired NP and ME isolates from three children with recurrent OME caused by NTHI indicated that the second episode was caused by the reinfection with a different strain rather than persistence and reemergence of the first strain. Finally, DNA analysis of strains from two siblings with concurrent OME suggested that person-to-person transmission of NTHI can occur among children. These findings suggest that at any one time the NTHI population in the NP is relatively homogenous, at least at the time of acute upper respiratory disease. Our observation that the strains present at the second episode of otitis media were different than the strains present in the first episode is consistent with strain replacement in the NP. Restriction fragment mapping analysis of genomic DNA of NTHI could provide a powerful tool for investigating the rate of turnover of the NTHI population in the NP.
Phase III Study of R-CVP Compared With Cyclophosphamide, Vincristine, and Prednisone Alone in Patients With Previously Untreated Advanced Follicular Lymphoma (2008)

Analysis of all outcome measures, including OS, confirm the benefit of adding R to CVP in the front-line treatment of FL.
Manipulation of organoactinide coordinative unsaturation and stereochemistry. Properties of chelating bis(polymethylcyclopentadienyl) hydrocarbyls and hydrides (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTManipulation of organoactinide coordinative unsaturation and stereochemistry. Properties of chelating bis(polymethylcyclopentadienyl) hydrocarbyls and hydridesCarol M. Fendrick, Eric A. Mintz, Larry D. Schertz, and Tobin J. MarksCite this: Organometallics 1984, 3, 5, 819–821Publication Date (Print):May 1, 1984Publication History Published online1 May 2002Published inissue 1 May 1984https://pubs.acs.org/doi/10.1021/om00083a036https://doi.org/10.1021/om00083a036research-articleACS PublicationsRequest reuse permissionsArticle Views459Altmetric-Citations80LEARN 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
Tle4 Regulates Epigenetic Silencing of Gamma Interferon Expression during Effector T Helper Cell Tolerance (2013)

In response to suboptimal activation, T cells become hyporesponsive, with a severely reduced capacity to proliferate and produce cytokines upon reencounter with antigen. Chromatin analysis of T cells made tolerant by use of different in vitro and in vivo approaches reveals that the expression of gamma interferon (IFN-γ) is epigenetically silenced in anergic effector TH1 cells. In those T cells, calcium signaling triggers the expression of Tle4, a member of the Groucho family of corepressors, which is then recruited to a distal regulatory element in the Ifng locus and causes the establishment of repressive epigenetic marks at the Ifng gene regulatory elements. Consequently, impaired Tle4 activity results in a markedly reduced capacity to inhibit IFN-γ production in tolerized T cells. We propose that Blimp1-dependent recruitment of Tle4 to the Ifng locus causes epigenetic silencing of the expression of the Ifng gene in anergic TH1 cells. These results define a novel function of Groucho family corepressors in peripheral T cells and demonstrate that specific mechanisms are activated in tolerant T helper cells to directly repress expression of effector cytokines, supporting the hypothesis that stable epigenetic imprinting contributes to the maintenance of the tolerance-associated hyporesponsive phenotype in T cells.
[The experimental study of bone marrow mesenchymal stem cells on the repair of skin wound combined with local radiation injury]. (2002)

Local transplanted MSC promoted the repair of skin wounds combined with irradiation injury. The promotion effects were achieved by the interaction between MSC and wound microenviroment.
In vivo Knockdown of the Androgen Receptor Results in Growth Inhibition and Regression of Well-Established, Castration-Resistant Prostate Tumors (2008)

Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.
MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4 (2011)

MicroRNA-21 (miR-21) is a key regulator of oncogenic processes. It is significantly elevated in the majority of human tumors and functionally linked to cellular proliferation, survival and migration. In this study, we used two experimental-based strategies to search for novel miR-21 targets. On the one hand, we performed a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE) to identify proteins suppressed upon enhanced miR-21 expression in LNCaP human prostate carcinoma cells. The tumor suppressor acidic nuclear phosphoprotein 32 family, member A (ANP32A) (alias pp32 or LANP) emerged as the most strongly downregulated protein. On the other hand, we applied a mathematical approach to select correlated gene sets that are negatively correlated with primary-miR-21 (pri-miR-21) expression in published transcriptome data from 114 B-cell lymphoma cases. Among these candidates, we found tumor suppressor SMARCA4 (alias BRG1) together with the already validated miR-21 target, PDCD4. ANP32A and SMARCA4, which are both involved in chromatin remodeling processes, were confirmed as direct miR-21 targets by immunoblot analysis and reporter gene assays. Furthermore, knock down of ANP32A mimicked the effect of enforced miR-21 expression by enhancing LNCaP cell viability, whereas overexpression of ANP32A in the presence of high miR-21 levels abrogated the miR-21-mediated effect. In A172 glioblastoma cells, enhanced ANP32A expression compensated for the effects of anti-miR-21 treatment on cell viability and apoptosis. In addition, miR-21 expression clearly increased the invasiveness of LNCaP cells, an effect also seen in part upon downregulation of ANP32A. In conclusion, these results suggest that downregulation of ANP32A contributes to the oncogenic function of miR-21.
Follicular Dendritic Cell Regulation of CXCR4-Mediated Germinal Center CD4 T Cell Migration (2004)

Follicular dendritic cells (FDCs) up-regulate the chemokine receptor CXCR4 on CD4 T cells, and a major subpopulation of germinal center (GC) T cells (CD4(+)CD57(+)), which are adjacent to FDCs in vivo, expresses high levels of CXCR4. We therefore reasoned that GC T cells would actively migrate to stromal cell-derived factor-1 (CXCL12), the CXCR4 ligand, and tested this using Transwell migration assays with GC T cells and other CD4 T cells (CD57(-)) that expressed much lower levels of CXCR4. Unexpectedly, GC T cells were virtually nonresponsive to CXCL12, whereas CD57(-)CD4 T cells migrated efficiently despite reduced CXCR4 expression. In contrast, GC T cells efficiently migrated to B cell chemoattractant-1/CXCL13 and FDC supernatant, which contained CXCL13 produced by FDCs. Importantly, GC T cell nonresponsiveness to CXCL12 correlated with high ex vivo expression of regulator of G protein signaling (RGS), RGS13 and RGS16, mRNA and expression of protein in vivo. Furthermore, FDCs up-regulated both RGS13 and RGS16 mRNA expression in non-GC T cells, resulting in their impaired migration to CXCL12. Finally, GC T cells down-regulated RGS13 and RGS16 expression in the absence of FDCs and regained migratory competence to CXCL12. Although GC T cells express high levels of CXCR4, signaling through this receptor appears to be specifically inhibited by FDC-mediated expression of RGS13 and RGS16. Thus, FDCs appear to directly affect GC T cell migration within lymphoid follicles.
A Unified Framework for Opinion Retrieval (2008)

The popularity of Web 2.0 has promoted the web to be a valuable source for accessing opinions. Unfortunately, due to the large number of user generated content, it is difficult to access and utilize the opinion resource efficiently. Developing an opinion retrieval system is a promising way to overcome the problem of overloaded opinion information. In this paper, we propose a unified framework for opinion retrieval, which is based on generative model and opinion mining technologies. Within this framework, relevance, quality and temporal dimension information of user generated content are incorporated in a unified language model, and on the top of which an opinion summary is proposed. We have developed an Opinion Retrieval System, (ORS), to retrieve opinions in customer review domain. Our evaluation on a real-world data set shows that ORS can effectively retrieve, summarize and visualize customer opinions.
Can PPAR&#947; Ligands Be Used in Cancer Therapy? (2004)

The role of peroxisome-proliferator activated receptor (PPAR)gamma in tumor growth inhibition has been extensively studied during last seven years but still remains debated. Many in vitro and xenograft studies have demonstrated that PPARgamma ligands are anti-tumorigenic due to anti-proliferative, pro-differentiation and anti-angiogenic effects. In animal models, PPARgamma ligands have shown preventive effects against chemical carcinogenesis. On the other hand, evidences are accumulating against the possible use of this ligand activated nuclear receptor in molecular targeting for cancer therapy. The growth inhibitory effects of certain PPARgamma ligands have recently been shown to be independent of PPARgamma-activation. Studies have also come up with results indicating the growth promoting effects of PPARgamma-activation, particularly in certain animal models genetically predisposed to cancer development. Loss-of-function mutations of PPARgamma in tumors and increased susceptibility of PPARgamma heterozygote knockout mice to carcinogenesis suggested a tumor-suppressing role of PPARgamma. However, recent findings do not support PPARgamma as a tumor suppressor gene. Although initial clinical trials with PPARgamma ligand troglitazone reported promising results in liposarcoma and prostate cancers, recent studies failed to show the expected therapeutic values in advanced colorectal and breast cancers. In this review, we have addressed these controversies on potential use of PPARgamma ligands in cancer therapy.
Permeable Layers with Large Windows in [(CH3CH2CH2)2NH2] 5In5Sb6S19 ×1.45H2O: High Ion‐Exchange Capacity, Size Discrimination, and Selectivity for Cs Ions. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Mitochondrial Apoptosis Induced by the HIV‐1 Envelope (2003)

The envelope glycoprotein complex (Env), encoded by the human immunodeficiency virus (HIV-1), kills uninfected cells expressing CD4 and/or the chemokine receptor CXCR4 or CCR5, via at least three independent mechanisms. First, the soluble Env product gp120 can induce the apoptotic cell death of lymphocytes, neurons, and myocardiocytes, via interaction with surface receptors. Second, Env present on the surface of HIV-1 infected cells can transiently interact with cells expressing CD4 and CXCR4/CCR5, thereby provoking a hemifusion event that results in the death of the uninfected cell. Third, the interaction between Env on infected cells and its receptors on uninfected cells can result in syncytium formation. Such syncytia undergo apoptosis after a phase of latency. In several models of Env-induced apoptosis, early signs of mitochondrial membrane permeabilization (MMP) become manifest. Such signs include a loss of the mitochondrial transmembrane potential and the release of cytochrome c and AIF. The mechanisms of Env-triggered apoptotic MMP may involve an elevation of cytosolic Ca(2+), reactive oxygen species and/or the transcriptional activation of p53, with the consequent expression of pro-apoptotic proteins such as Bax, which permeabilizes mitochondrial membranes. The implications of these findings for the pathophysiology of HIV-1 infection is discussed.
Cloning and characterization of a novel mouse immunoglobulin superfamily gene expressed in early spermatogenic cells (2001)

We cloned and characterized a novel immunoglobulin superfamily gene from the cDNA library of adult mouse testis. This gene was expressed in the spermatogenic cells and hence termed SgIGSF. The predicted SgIGSF protein was composed of 445 amino-acid residues and contained a signal peptide, three extracellular immunoglobulin (Ig)-like domains, a transmembranous domain, and a cytoplasmic domain. SgIGSF mRNA consisted of two size species, 2.1- and 4.5-kb in length. Besides testis, SgIGSF mRNA was also expressed in a variety of organs, including the cerebrum, liver, kidney, and epididymis. The testis and liver expressed both the 2.1- and 4.5-kb transcripts, whereas the cerebrum and epididymis predominantly expressed the 4.5-kb one. In situ hybridization analysis in testis revealed that SgIGSF mRNA signal was localized to the spermatogenic cells from spermatogonia to zygotene spermatocytes. These results suggested that SgIGSF occurs in the plasma membrane of spermatogenic cells during the earlier stages of spermatogenesis.
A digital microfluidic electrochemical immunoassay (2013)

Digital microfluidics (DMF) has emerged as a popular format for implementing quantitative immunoassays for diagnostic biomarkers. All previous reports of such assays have relied on optical detection; here, we introduce the first digital microfluidic immunoassay relying on electrochemical detection. In this system, an indium tin oxide (ITO) based DMF top plate was modified to include gold sensing electrodes and silver counter/pseudoreference electrodes suitable for in-line amperometric measurements. A thyroid stimulating hormone (TSH) immunoassay procedure was developed relying on magnetic microparticles conjugated with primary antibody (Ab1). Antigen molecules are captured followed by capture of a secondary antibody (Ab2) conjugated with horseradish peroxidase enzyme (HRP). HRP catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) which can be detected amperometrically. The limit of detection of the technique (2.4 μIU mL(-1)) is compatible with clinical applications; moreover, the simplicity and the small size of the detector suggest utility in the future for portable analysis.
Ocular Pharmacokinetics of Fluocinolone Acetonide After Retisert™ Intravitreal Implantation in Rabbits Over a 1-Year Period (2004)

In this rabbit study, the Retisert provides relatively constant levels of FA in the posterior pole, which is consistent with previous reports of its clinical utility.