gebhart/patrepeval huggingface dataset:
Susceptibility locus for inflammatory bowel disease on chromosome 16 has a role in Crohn's disease, but not in ulcerative colitis (1996)

In the Western world, chronic inflammatory bowel disease (IBD) presents as two major clinical forms, Crohn's disease (CD) and ulcerative colitis (UC) [Targan, S.R. and Shanahan, F. (1994). In Retford, D.C (ed.), Inflammatory Bowel Disease: From Bench to Bedside. Williams and Wilkins, Baltimore]. Genetic epidemiological studies, the occurrence of rare syndromes associated with IBD, and animal models suggest that inherited factors play significant roles in the susceptibility to both forms of IBD [Yang, H.-Y. and Rotter, J.I. (1995) In Kirsner, J.B. and Shorter, R.G. (eds). Genetic Aspects of Idiopathic Inflammatory Bowel Disease. Williams and Wilkins, Baltimore, pp.301-331]. Recently, a genome-wide search on European families with multiple affected members with CD identified a putative susceptibility locus in the centromeric region of chromosome 16 [Hugot, J.-P. et al. (1996) Nature, 379, 821-823]. We have now tested this region in an independent set of US families, confirmed that this region is likely to contain a gene predisposing to CD, and further refined the chromosomal location of this gene. Most importantly with respect to this locus, our data also seem to indicate that there is heterogeneity both within the CD group, and between the CD and UC groups with respect to this locus. The susceptibility locus appears to be involved only in non-Jewish CD sibpairs and not in our Ashkenazi Jewish CD sibpairs. Additionally, we have tested sibpairs having either only UC or both UC and CD for involvement of this locus, and have found no evidence that this region predisposes to IBD in these patients.
Inhibition of human ornithine decarboxylase activity by enantiomers of difluoromethylornithine (2003)

Racemic difluoromethylornithine (D/L-DFMO) is an inhibitor of ODC (ornithine decarboxylase), the first enzyme in eukaryotic polyamine biosynthesis. D/L-DFMO is an effective anti-parasitic agent and inhibitor of mammalian cell growth and development. Purified human ODC-catalysed ornithine decarboxylation is highly stereospecific. However, both DFMO enantiomers suppressed ODC activity in a time- and concentration-dependent manner. ODC activity failed to recover after treatment with either L- or D-DFMO and dialysis to remove free inhibitor. The inhibitor dissociation constant (K(D)) values for the formation of enzyme-inhibitor complexes were 28.3+/-3.4, 1.3+/-0.3 and 2.2+/-0.4 microM respectively for D-, L- and D/L-DFMO. The differences in these K(D) values were statistically significant ( P <0.05). The inhibitor inactivation constants (K(inact)) for the irreversible step were 0.25+/-0.03, 0.15+/-0.03 and 0.15+/-0.03 min(-1) respectively for D-, L- and D/L-DFMO. These latter values were not statistically significantly different ( P >0.1). D-DFMO was a more potent inhibitor (IC50 approximately 7.5 microM) when compared with D-ornithine (IC50 approximately 1.5 mM) of ODC-catalysed L-ornithine decarboxylation. Treatment of human colon tumour-derived HCT116 cells with either L- or D-DFMO decreased the cellular polyamine contents in a concentration-dependent manner. These results show that both enantiomers of DFMO irreversibly inactivate ODC and suggest that this inactivation occurs by a common mechanism. Both enantiomers form enzyme-inhibitor complexes with ODC, but the probability of formation of these complexes is 20 times greater for L-DFMO when compared with D-DFMO. The rate of the irreversible reaction in ODC inactivation is similar for the L- and D-enantiomer. This unexpected similarity between DFMO enantiomers, in contrast with the high degree of stereospecificity of the substrate ornithine, appears to be due to the alpha-substituent of the inhibitor. The D-enantiomer may have advantages, such as decreased normal tissue toxicity, over L- or D/L-DFMO in some clinical applications.
Basic manual lensometry: a guide for measuring distance and near glasses. (2001)

Manual lensometry is a basic component of ophthalmic clinical care. You will find it necessary to check lens prescriptions manually when the written prescription does not match the results of an automated lensometer or when automated lensometry is not available.
UGT pharmacogenomics: implications for cancer risk and cancer therapeutics. (2003)

UDP-glucuronosyltransferases (UGTs) belong to a superfamily of microsomal enzymes responsible for glucuronidation of numerous endogenous and exogenous compounds including bilirubin, hormones, various drugs as well as environmental carcinogens. Glucuronidation predominantly serves as a pathway for elimination of the different glucuronidated compounds. Seventeen human UGT transcripts have been identified thus far, and the UGT proteins are differentially expressed in a wide-range of human tissues. Genetic variants have been identified in coding and non-coding sequences of several UGT genes, and similar observations should be anticipated for all UGTs. As glucuronidation plays a critical part in the inactivation or elimination of countless substrates, genetic variants in this enzyme family that lead to altered expression or activity of UGTs are likely to have some physiologic and pharmacological consequences. This article focuses on the potential impact of various UGTs or their variants on cancer risk and cancer therapeutics.
Curcumin Synergizes With Resveratrol to Inhibit Colon Cancer (2009)

Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.
A Genomic Score Prognostic of Outcome in Trauma Patients (2009)

Traumatic injuries frequently lead to infection, organ failure, and death. Health care providers rely on several injury scoring systems to quantify the extent of injury and to help predict clinical outcome. Physiological, anatomical, and clinical laboratory analytic scoring systems (Acute Physiology and Chronic Health Evaluation [APACHE], Injury Severity Score [ISS]) are utilized, with limited success, to predict outcome following injury. The recent development of techniques for measuring the expression level of all of a person's genes simultaneously may make it possible to develop an injury scoring system based on the degree of gene activation. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. To test such a scoring system, we measured gene expression of peripheral blood leukocytes from patients within 12 h of traumatic injury. cRNA derived from whole blood leukocytes obtained within 12 h of injury provided gene expression data for the entire genome that were used to create a composite gene expression score for each patient. Total blood leukocytes were chosen because they are active during inflammation, which is reflective of poor outcome. The gene expression score combines the activation levels of all the genes into a single number which compares the patient's gene expression to the average gene expression in uninjured volunteers. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 h following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE, and ISS scores with outcome. We hypothesized that patients with a total gene response more different from uninjured volunteers would tend to have poorer outcome than those more similar. Our data show that for measures of poor outcome, such as infections, organ failures, and length of hospital stay, this is correct. DFR scores were associated significantly with adverse outcome, including multiple organ failure, duration of ventilation, length of hospital stay, and infection rate. The association remained significant after adjustment for injury severity as measured by APACHE or ISS. A single score representing changes in gene expression in peripheral blood leukocytes within hours of severe blunt injury is associated with adverse clinical outcomes that develop later in the hospital course. Assessment of genome-wide gene expression provides useful clinical information that is different from that provided by currently utilized anatomic or physiologic scores.
Biomarkers of HIV replication (2010)

In patients with untreated HIV-1 infection, the level of viremia is a direct indication of the level of viral replication and a predictor of the rate of CD4 depletion. However, when viral replication is suppressed by HAART, the level of residual viremia is to a large extent an indication of virus release from stable viral reservoirs.
Antigen Concentration and Precursor Frequency Determine the Rate of CD8+ T Cell Tolerance to Peripherally Expressed Antigens (1999)

Expression of transgene-encoded proteins in the pancreatic islets can cause peripheral deletion of T cells. However, tolerance has not been observed in all transgenic models. It has been proposed that the determining factor for successful peripheral tolerance is the amount of Ag cross-presented by quiescent APCs. Using InsHA mice, which demonstrate peripheral tolerance to the influenza virus hemagglutinin (HA) expressed in the pancreatic islet beta cells, we have investigated the consequences when different amounts of HA are expressed. As compared with InsHA mice that are heterozygous for the InsHA transgene, homozygous InsHA mice demonstrated enhanced activation and proliferation of Kd-restricted HA-specific CD8+ T cells in the pancreatic lymph nodes. However, despite such activation, insulitis was not observed, and the T cells were gradually functionally deleted. Deletion of these activated cells occurred much more rapidly in homozygous than in heterozygous InsHA mice. These data demonstrate that there is a direct correlation between the amount of HA expressed in the periphery, and both the degree of T cell proliferation in the pancreatic lymph nodes and the rate of tolerance of HA-specific CD8+ T cells. This strongly supports the hypothesis that activation of T cells through cross-presentation of peripheral Ags in a noninflammatory environment is an important part of the normal mechanism of tolerance to Ags expressed in the pancreatic islets.
The active form of tumor necrosis factor is a trimer. (1987)

Natural human and recombinant human and murine tumor necrosis factors (TNF) were fractionated by gel filtration chromatography on Sephadex G-75. The active form of TNF was identified by its inhibitory activity in receptor binding assays with HeLa cells and was eluted as a protein of Mr approximately 55,000. Radioiodinated human and murine TNF were fractionated by gel filtration into a major peak of Mr approximately 55,000, corresponding to a trimer, and a minor peak of Mr approximately 17,000, corresponding to a monomer. Binding assays showed that the timer was at least 8-fold more active than the monomer. The human TNF partially dissociated into monomers upon addition of the nonionic detergent Triton X-100. Isolated monomers showed low binding affinity (KD = 70 nM) and reduced cytotoxicity, whereas trimers showed high binding affinity (KD = 90 pM) and cytotoxicity. When 125I-TNF was bound to cells, no release of monomer was detectable, suggesting that the trimer could directly bind to cellular receptors without dissociating into subunits. Further evidence for such binding was obtained by cross-linking 125I-TNF trimers with bis[2-(succinimidooxycarbonyloxy)ethyl]sulfone. These trimers were bound to HeLa cells, could be dissociated from cellular receptors, and elicited a cytotoxic response. These results show that trimers, whether native or cross-linked, bind to receptors and are the biologically active form of TNF.
Advances in Bioconjugation (2009)

Bioconjugation is a burgeoning field of research. Novel methods for the mild and site-specific derivatization of proteins, DNA, RNA, and carbohydrates have been developed for applications such as ligand discovery, disease diagnosis, and high-throughput screening. These powerful methods owe their existence to the discovery of chemoselective reactions that enable bioconjugation under physiological conditions-a tremendous achievement of modern organic chemistry. Here, we review recent advances in bioconjugation chemistry. Additionally, we discuss the stability of bioconjugation linkages-an important but often overlooked aspect of the field. We anticipate that this information will help investigators choose optimal linkages for their applications. Moreover, we hope that the noted limitations of existing bioconjugation methods will provide inspiration to modern organic chemists.
Significance of Extracellular Enveloped Virus in the in vitro and in vivo Dissemination of Vaccinia (1980)

The significance of extracellular enveloped vaccinia (EEV) for the in vitro and in vivo dissemination of vaccinia virus was investigated. The quantity of in vitro released extracellular virus correlated very closely with the ability of 13 vaccinia strains to cause long-range spread of infection (comet formation) in cell cultures infected at low m.o.i. but was not correlated with plaque size. The kinetics of virus spread after low m.o.i. was related to the amount of virus released from primary infected cells but not to their content of intracellular naked vaccinia (INV). Most extracellular vaccinia virus from IHD-J-infected RK-13 cells banded in CsCl density gradients as EEV (88%) while very little banded as INV (2%). Antisera to the enveloped prevented comet formation while antisera to INV did not. CsCl centrifugation of blood-borne extracellular virus from rabbits infected intravenously with vaccinia virus after cyclophosphamide treatment revealed that 64% of the virus banded as EEV but only 11% as INV. High in vitro EEV-yielding vaccinia strains were able to spread from the respiratory tract to the brains of mice and cause death. Low in vitro EEV-yielding vaccinia strains were generally not able to disseminate in vivo or cause mouse mortality. The notable exception to this trend was strain WR, which, although releasing small amounts of virus in vitro, could nevertheless very effectively disseminate in vivo, causing a high rate of mouse mortality. Treatment with anti-envelope serum protected mice from a lethal vaccinia infection whereas antiserum to inactivated INV did not. These results indicate that the in vitro dissemination of vaccinia infection is mediated by EEV and implicate EEV as having a role in the in vivo dissemination.
Alkylation of isobutane with C4 olefins. 2. Production and characterization of conjunct polymers (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkylation of isobutane with C4 olefins. 2. Production and characterization of conjunct polymersLyle F. Albright, Mark A. Spalding, Christopher G. Kopser, and Roger E. EckertCite this: Ind. Eng. Chem. Res. 1988, 27, 3, 386–391Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/ie00075a004https://doi.org/10.1021/ie00075a004research-articleACS PublicationsRequest reuse permissionsArticle Views618Altmetric-Citations49LEARN 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 Get e-Alerts
Comparison of a rational vs. high throughput approach for rapid salt screening and selection (2012)

In recent years, high throughput (HT) screening has become the most widely used approach for early phase salt screening and selection in a drug discovery/development setting. The purpose of this study was to compare a rational approach for salt screening and selection to those results previously generated using a HT approach. The rational approach involved a much smaller number of initial trials (one salt synthesis attempt per counterion) that were selected based on a few strategic solubility determinations of the free form combined with a theoretical analysis of the ideal solvent solubility conditions for salt formation. Salt screening results for sertraline, tamoxifen, and trazodone using the rational approach were compared to those previously generated by HT screening. The rational approach produced similar results to HT screening, including identification of the commercially chosen salt forms, but with a fraction of the crystallization attempts. Moreover, the rational approach provided enough solid from the very initial crystallization of a salt for more thorough and reliable solid-state characterization and thus rapid decision-making. The crystallization techniques used in the rational approach mimic larger-scale process crystallization, allowing smoother technical transfer of the selected salt to the process chemist.
Analysis of Green Fluorescent Protein Expression in Transgenic Rats for Tracking Transplanted Neural Stem/Progenitor Cells (2005)

Green fluorescent protein (GFP) expression was evaluated in tissues of different transgenic rodents--Sprague-Dawley (SD) rat strain [SD-Tg(GFP)Bal], W rat strain [Wistar-TgN(CAG-GFP)184ys], and M mouse strain [Tg(GFPU)5Nagy/J]--by direct fluorescence of native GFP expression and by immunohistochemistry. The constitutively expressing GFP transgenic strains showed tissue-specific differences in GFP expression, and GFP immunohistochemistry amplified the fluorescent signal. The fluorescence of stem/progenitor cells cultured as neurospheres from the ependymal region of the adult spinal cord from the GFP SD and W rat strains was assessed in vitro. After transplantation of the cells into wild-type spinal cord, the ability to track the grafted cells was evaluated in vivo. Cultured stem/progenitor cells from the SD strain required GFP immunostaining to be visualized. Likewise, after transplantation of SD cells into the spinal cord, immunohistochemical amplification of the GFP signal was required for detection. In contrast, GFP expression of stem/progenitor cells generated from the W strain was readily detected by direct fluorescence both in vitro and in vivo without the need for immunohistochemical amplification. The cultured stem/progenitor cells transplanted into the spinal cord survived for at least 49 days after transplantation, and continued to express GFP, demonstrating stable expression of the GFP transgene in vivo.
Anti–G Protein Antibody Responses to Respiratory Syncytial Virus Infection or Vaccination Are Associated with Inhibition of G Protein CX3C‐CX3CR1 Binding and Leukocyte Chemotaxis (2004)

Respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract illness in infants and the elderly. Presently, no safe and efficacious RSV vaccine exists; however, advances in our understanding of immunity and the pathogenesis of disease associated with RSV infection may lead to new vaccine strategies. RSV G protein contains a CX3C chemokine motif that interacts with the CX3CR1 chemokine receptor and modifies the activities of fractalkine. In the present study, we show that anti-RSV G protein antibody responses after recent RSV infection or vaccination are associated with inhibition of RSV G protein CX3C-CX3CR1 interaction and RSV G protein-mediated leukocyte chemotaxis.
Animal models for the study of tendinopathy (2006)

Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.
Evaluation of Spinach Germplasm for Resistance to a New Race (Race 4) of Peronospora farinosa f. sp. spinaciae (1992)

Spinach germplasm (707 accessions) from collections from six countries were screened for resistance to race 4 of the downy mildew pathogen Peronospora farinosa f. sp. spinaciae; these collections contained germplasm that originated from 41 countries. The predominant species examined was Spinacia oleracea L., however, eight accessions of S. turkestanica Iljin and two accessions of S. tetrandra Stev. were also tested. About 40 seedlings of each accession were inoculated. The cultivar St. Helens was included as a susceptible control in each test. The majority of accessions tested (&gt;98%) were susceptible to race 4. Nine accessions exhibited some resistance to race 4 (9% to 38% of the seedlings within an accession were resistant), and two accessions, CGNO 9546 and SPI 82/87, exhibited a high level of resistance (60% and 80% resistant, respectively). Resistance identified in several of the accessions in this study may be useful for breeding for race 4 resistance.