gebhart/patrepeval huggingface dataset:
IgE antibodies to Staphylococcus aureus and Candida albicans in patients with the syndrome of hyperimmunoglobulin E and recurrent infections. (1980)

Abstract Staphylococcal abscesses and chronic mucocutaneous candidiasis are the primary infectious problems in patients with the hyper-immunoglobulin E (hyper-IgE) syndrome. In order to better understand the pathogenesis of these infections, we investigated the antimicrobial specificity of the IgE antibodies in 17 patients with this syndrome. Radioiodinated anti-IgE was used to detect IgE that bound to microorganisms serving as a solid phase. Thirteen of 17 patients had IgE that bound to Staphylococcus aureus, and 12 of 17 had IgE that bound to Candida albicans. In contrast, none had IgE that bound to Escherichia coli, and only 4 had IgE that bound to Streptococcus pneumoniae. Four of the hyper-IgE syndrome patients’ sera did not contain IgE antibodies to either Staphylococcus or Candida. IgE binding to Staphylococcus or Candida was not detected in the sera of patients with parasitic infections and high IgE, of patients with primary neutrophil defects and recurrent Staphylococcus infections, or from normal subjects. Adsorption of sera from patients with the hyper-IgE syndrome with Candida resulted in an 85% reduction in binding of IgE to Candida (p &amp;lt; 0.001) and a 5% reduction in binding to Staphylococcus (p &amp;gt; 0.05). Adsorption with Staphylococcus resulted in a 76% reduction in binding of IgE to Staphylococcus (p &amp;lt; 0.001) and a 28% reduction in binding of IgE to Candida (p &amp;lt; 0.001). The total IgE concentrations in the sera were not reduced by these adsorptions, indicating that nonspecific binding did not occur. The concordance in production of IgE against both Staphylococcus and Candida and the finding of cross-reactivity may indicate partial antigenic similarity between these 2 organisms. We speculate that the production of IgE antibodies against Staphylococcus and Candida but not other common pathogens may contribute to the increased susceptibility of patients with the hyper-IgE syndrome to infections with these particular organisms.
Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients (2015)

The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent acute liver failure, and also to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome.
Some substrate properties of analogues of oligothymidylates with p-s-C5′bonds (1981)

The action of T4 polynucleotide kinase, T4 DNA polymerase, E. coli DNA polymerase I, snake venom phosphodiesterase (VPDE) and S1 nuclease on analogues of oligothymidilates with p-s-C5' bonds and the ability of these analogues to prime the replication of poly (dA) by T4 DNA polymerase were studied. These analogues were shown to be substrates for all these enzymes. Substitution of these analogues for corresponding oligothymidilates in the reaction mixtures resulted in drop in rates of enzymic reactions. This drop in reactions rates was not significant when these oligonucleotides were phosphorylated with T4 polynucleotide kinase or used as a primers, however in comparison with oligothymidilates these analogues were found to be considerably more resistant to nucleolytic hydrolysis. Some possible applications of these analogues are discussed.
Where is the evidence? (2007)

The place of qualified nurses within the community care workforce continues to be contested across the country because the evidence base demonstrating the effect of nursing interventions is weak. The separation of the provider-commissioning functions is also providing the opportunity for a major reassessment of the cost of different configurations of the nursing workforce.
Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15–18 Months of Age in Mexico (2017)

Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.
Clinical Experience Using Adjunctive Gabapentin in Treatment-Resistant Bipolar Mixed States (1999)

These results show that gabapentin appears to be potentially useful in the adjunctive treatment of drug-resistant bipolar mixed states, and that it was particularly effective in relation to depressive symptomatology.
Evaluation of a PCR Assay for Quantitation of Rickettsia rickettsii and Closely Related Spotted Fever Group Rickettsiae (2003)

A spotted fever rickettsia quantitative PCR assay (SQ-PCR) was developed for the detection and enumeration of Rickettsia rickettsii and other closely related spotted fever group rickettsiae. The assay is based on fluorescence detection of SYBR Green dye intercalation in a 154-bp fragment of the rOmpA gene during amplification by PCR. As few as 5 copies of the rOmpA gene of R. rickettsii can be detected. SQ-PCR is suitable for quantitation of R. rickettsii and 10 other genotypes of spotted fever group rickettsiae but not for R. akari, R. australis, R. bellii, or typhus group rickettsiae. The sensitivity of SQ-PCR was comparable to that of a plaque assay using centrifugation for inoculation. The SQ-PCR assay was applied successfully to the characterization of rickettsial stock cultures, the replication of rickettsiae in cell culture, the recovery of rickettsial DNA following different methods of extraction, and the quantitation of rickettsial loads in infected animal tissues, clinical samples, and ticks.
Biodistribution properties of (111)indium-labeled C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid humanized 3S193 diabody and F(ab')(2) constructs in a breast carcinoma xenograft model. (2001)

The humanized complementarity determining region-grafted anti-Lewis Y (Le(y)) monoclonal antibody [humanized 3S193 (hu3S193)] was developed for targeting Le(y)-expressing epithelial tumors such as breast, colon, lung, prostate, and ovarian carcinoma. We are exploring the potential use of smaller molecular size, bivalent analogues of hu3S193, because the faster blood clearance of M(r) approximately 54,000 diabody and M(r) approximately 110,000 F(ab')(2) molecules may be advantageous in achieving optimal and rapid tumor uptake for diagnostic and potential therapeutic applications. The single-chain variable fragment-5 residue linker construct (diabody) was expressed using the bacterial secretion vector pPOW3, and soluble product was purified without refolding processes. The F(ab')(2) fragment was obtained by pepsin digest of parental hu3S193. To facilitate evaluations, the radiometal (111)In was used to label C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid chelated diabody and F(ab')(2). The immunoreactivity of the radiolabeled constructs was 41.3 and 58.6%, and the K(a) was 1.68 x 10(6) M(-1) and 5.33 x 10(6) M(-1) for the diabody and F(ab')(2), respectively. Radioconjugates were injected into mice bearing Le(y)-positive MCF-7 tumors, and biodistribution properties were determined at various time points after injection. The uptake of radiolabeled diabody in xenografts was maximal at 1 h after injection (4.7 +/- 0.6% injected dose/g), whereas the F(ab')(2) peaked at 8 h after injection (14.2 +/- 2.4% injected dose/g). The tumor:blood ratio at 4 h for the diabody and F(ab')(2) was 5:1 and 2:1, which increased to 20:1 and 5:1, respectively, at 8 h and increased further to 40:1 and 130:1, respectively, at 48 h. These results demonstrate that the diabody construct may have applications as a diagnostic imaging reagent, whereas F(ab')(2) displayed effective tumor targeting and may have potential as a therapeutic molecule in patients with Le(y)-expressing tumors.
Regulation of glutamine production by skeletal muscle cells in culture (1985)

Cells of the L6 rat myogenic line consume glutamine in contrast to skeletal muscle in vivo, which produces glutamine. The basis of glutamine consumption in the cultured cells and the conditions under which net glutamine production occurs were investigated. After treating cultures with cytosine-1-beta-D-arabinofuranoside to eliminate replicating myoblasts remaining after differentiation, the L6 cells continued to consume glutamine from medium containing normal plasma levels (650 microM). Consumption declined when cells were incubated with 325 microM glutamine, and, at 0 microM, net production occurred. In addition to the tendency to consume glutamine, the cells rapidly consumed glutamic acid. When medium glutamic acid was increased from 70 to 150, 500, and 1,000 microM, glutamine production increased. Alterations in levels of NH3, the other substrate for glutamine synthesis, did not have this effect. The L6 cells were found to have glutamine synthetase activity similar to normal rat skeletal muscle but markedly increased glutaminase activity. In spite of the imbalance in synthetic and degradative activities, however, inhibitor studies with L-methionine sulfoximine and 6-diazo-5-oxo-L-norleucine showed that flux through both pathways influenced net glutamine production.
Long-Term Results From a Randomized Phase II Trial of Standard- Versus Higher-Dose Imatinib Mesylate for Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing KIT (2008)

Nearly 50% of patients with advanced GIST who were treated with imatinib mesylate survived for more than 5 years, regardless of a 400 or 600 mg/d starting dose.
Preparative and Stereoselective Synthesis of the Versatile Intermediate for Carbocyclic Nucleosides:  Effects of the Bulky Protecting Groups to Enforce Facial Selectivity (2004)

The preparative and stereoselective synthesis (45-50% overall yields) of the target compound 17 has been accomplished from D-ribose. The bulky protecting groups such as TBDPS and Trityl enforced the facial selectivity during Grignard reaction to give the tertiary beta-allylic alcohol 16 as the sole product, which was oxidatively rearranged to the key molecule 17 in excellent yield.
Serotonergic and non‐serotonergic targets in the pharmacotherapy of visceral hypersensitivity (2007)

Visceral hypersensitivity is considered a key mechanism in the pathogenesis of functional gastrointestinal (GI) disorders. Targeting visceral hypersensitivity seems an attractive approach to the development of drugs for functional GI disorders. This review summarizes current knowledge on targets for the treatment of visceral hypersensitivity, and the status of current and future drug and probiotic treatment development, and the role of pharmacogenomic factors.
Triple Immune Suppression Increases Short-Term Survival of Porcine Fetal Retinal Pigment Epithelium Xenografts (2003)

Systemic immune suppression increased the 4-week survival of porcine RPE xenografts in the albino rabbit subretinal space, but there was poor survival in immune-suppressed and -competent animals 12 weeks after surgery. Many pigment-containing cells 4 or more weeks after surgery were PRE negative, indicating that they are of host origin.
A photochemically based synthesis of the benzannelated analog of the CC-1065 A-unit (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA photochemically based synthesis of the benzannelated analog of the CC-1065 A-unitKevin J. Drost and Michael P. CavaCite this: J. Org. Chem. 1991, 56, 6, 2240–2244Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/jo00006a052https://doi.org/10.1021/jo00006a052research-articleACS PublicationsRequest reuse permissionsArticle Views441Altmetric-Citations30LEARN 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
DISTANCE-BASED REDUNDANCY ANALYSIS: TESTING MULTISPECIES RESPONSES IN MULTIFACTORIAL ECOLOGICAL EXPERIMENTS (1999)

We present a new multivariate technique for testing the significance of individual terms in a multifactorial analysis-of-variance model for multispecies response variables. The technique will allow researchers to base analyses on measures of association (distance measures) that are ecologically relevant. In addition, unlike other distance-based hypothesis-testing techniques, this method allows tests of significance of interaction terms in a linear model. The technique uses the existing method of redundancy analysis (RDA) but allows the analysis to be based on Bray-Curtis or other ecologically meaningful measures through the use of principal coordinate analysis (PCoA). Steps in the procedure include: (1) calculating a matrix of distances among replicates using a distance measure of choice (e.g., Bray-Curtis); (2) determining the principal coordinates (including a correction for negative eigenvalues, if necessary), which preserve these distances; (3) creating a matrix of dummy variables corresponding to the design of the experiment (i.e., individual terms in a linear model); (4) analyzing the relationship between the principal coordinates (species data) and the dummy variables (model) using RDA; and (5) implementing a test by permutation for particular statistics corresponding to the particular terms in the model. This method has certain advantages not shared by other multivariate testing procedures. We demonstrate the use of this technique with experimental ecological data from intertidal assemblages and show how the presence of significant multivariate interactions can be interpreted. It is our view that distance-based RDA will be extremely useful to ecologists measuring multispecies responses to structured multifactorial experimental designs.
A Novel Chimeric Protein Composed of Interleukin 13 and Pseudomonas Exotoxin Is Highly Cytotoxic to Human Carcinoma Cells Expressing Receptors for Interleukin 13 and Interleukin 4 (1995)

Chimeric proteins provide a unique opportunity to target therapeutic bacterial toxins to a subset of specific cells. We have generated a new recombinant chimeric toxin composed of human interleukin 13 (hIL13) and a Pseudomonas exotoxin A (PE) mutant, PE38QQR. The hIL13-PE38QQR chimera is highly cytotoxic to cell lines derived from several human epithelial carcinomas such as adenocarcinoma of stomach, colon, and skin. The cytotoxic action of hIL13-PE38QQR, which can only occur upon internalization of ligand-receptor complex, is blocked by an excess of hIL13 but not of hIL2. This action is not solely hIL13-specific because an excess of hIL4 also blocks the cytotoxicity of hIL13-toxin. Conversely, hIL13 blocks the cytotoxicity of a hIL4-PE38QQR chimera. Binding studies showed that hIL13 displaces competitively 125I-labeled hIL4-PE38QQR on carcinoma cells. These results indicate that IL4 and IL13 compete for a common binding site on the studied human cell lines. Despite this competition, hIL4 but not hIL13 decreased protein synthesis in malignant cells susceptible to the cytotoxicity of both hIL13- and hIL4-PE38QQR. Our results suggest that a spectrum of human carcinomas express binding sites for IL13. Furthermore, hIL13 and hIL4 compete reciprocally for a form of the receptor that is internalized upon binding a ligand. Thus, cancer cells represent an interesting model for studying receptors for these two growth factors. Finally, hIL13-PE38QQR may be a useful agent in the treatment of several malignancies.
Purification and partial characterization of lactacin F, a bacteriocin produced by Lactobacillus acidophilus 11088 (1991)

Lactacin F, a bacteriocin produced by Lactobacillus acidophilus 11088 (NCK88), was purified and characterized. Lactacin F is heat stable, proteinaceous, and inhibitory to other lactobacilli as well as Enterococcus faecalis. The bacteriocin was isolated as a floating pellet from culture supernatants brought to 35 to 40% saturation with ammonium sulfate. Native lactacin F was sized at approximately 180 kDa by gel filtration. Column fractions having lactacin F activity were examined by electron microscopy and contained micelle-like globular particles. Purification by ammonium sulfate precipitation, gel filtration, and high-performance liquid chromatography resulted in a 474-fold increase in specific activity of lactacin F. The purified bacteriocin was identified as a 2.5-kDa peptide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The lactacin F peptide retained activity after extraction from SDS-PAGE gel slices, confirming the identity of the 2.5-kDa peptide. Variants of NCK88 that failed to exhibit lactacin F activity did not produce the 2.5-kDa band. Sequence analysis of purified lactacin F identified 25 N-terminal amino acids containing an arginine residue at the N terminus. Composition analysis indicates that lactacin F may contain as many as 56 amino acid residues.
The combination of stabilized plasmid lipid particles and lipid nanoparticle encapsulated CpG containing oligodeoxynucleotides as a systemic genetic vaccine (2008)

Abstract Background DNA vaccines offer unique potential for generating protective and therapeutic immunity against infectious and malignant diseases. Unfortunately, rapid degradation and poor cellular uptake has significantly limited the efficacy of ‘naked’ plasmid DNA vaccines. We have previously described stabilized plasmid lipid particles (SPLP) as effective nonviral gene delivery vehicles for the transfection of tumours at distal sites following intravenous administration. Based on their low toxicity and favourable transfection profile following systemic administration, we investigate SPLP as gene delivery vehicles for the generation of a systemically administered genetic vaccine. Methods The uptake of SPLP and their ability to transfect splenic antigen presenting cells (APC) following systemic administration is assessed through fluorescently‐labelled SPLP in combination with phenotype markers and a very sensitive flow cytometry‐based assay for the detection of the transgene, beta‐galactosidase. The priming of antigen‐specific adaptive and humoural immune responses following vaccination with SPLP alone or in combination with liposomal nanoparticle encapsulated CpG‐ODN containing oligodeoxynucleotides (LN CpG‐ODN) is characterized through the use of antigen‐specific cytotoxicity assays, interferon‐γ secretion assays and enzyme‐linked immunosorbant assay. Results We demonstrate that SPLP are taken up by and transfect APC in the spleen following intravenous administration and that, in the presence of a strong immunostimulatory signal provided by LN CpG‐ODN, are able to prime transgene‐specific humoural and cellular immune responses. Conclusions SPLP represent an effective candidate for the nonviral delivery of a systemic genetic vaccine when combined with additional immune stimulation provided by LN CpG‐ODN. Copyright © 2008 John Wiley &amp; Sons, Ltd.
Evidence that flavivirus NS1-NS2A cleavage is mediated by a membrane-bound host protease in the endoplasmic reticulum (1995)

Previous deletion mutagenesis studies have shown that the flavivirus NS1-NS2A clevage requires the eight C-terminal residues of NS1, constituting the cleavage recognition sequence, and sequences in NS2A far downstream of the cleavage site. We now demonstrate that replacement of all of NS1 upstream of the cleavage recognition sequence with prM sequences still allows cleavage in vivo. Thus, other than the eight C-terminal residues, NS1 is dispensable for NS1-NS2A cleavage. However, deletion of the N-terminal signal sequence abrogated cleavage, suggesting that entry into the exocytic pathway is required. Cleavage in vivo was not blocked by brefeldin A, and cleavage could occur in vitro in the presence of dog pancreas microsomes, indicating that NS1-NS2A cleavage occurs in the endoplasmic reticulum. Four in-frame deletions in NS2A were cleavage defective in vitro, as were two mutants in which NS4A-NS4B sequences were substituted for NS2A, suggesting that most of NS2A is required. A series of substitution mutants were constructed in which all Asp, Cys, Glu, His, and Ser residues in NS2A were collectively replaced; all standard proteases require at least one of these residues in their active sites. No single mutant was cleavage defective, suggesting that NS2A is not a protease. Fractionation of the microsomes indicated that the lumenal contents were not required for NS1-NS2A cleavage. It seems most likely that NS1-NS2A cleavage is effected by a host membrane-bound endoplasmic reticulum-resident protease, quite possibly signalase, and that NS2A is required to present the cleavage recognition sequence in the correct conformation to the host enzyme for cleavage.
Comparing the immunosuppressive potency of naïve marrow stromal cells and Notch-transfected marrow stromal cells (2011)

The results demonstrated that the immunosuppressive activity of the expanded NICD-transfected MSCs is comparable to the parental MSCs, in spite of the appearance of a small number of senescent-like cells.
Mapping translocation breakpoints by next-generation sequencing (2008)

Balanced chromosome rearrangements (BCRs) can cause genetic diseases by disrupting or inactivating specific genes, and the characterization of breakpoints in disease-associated BCRs has been instrumental in the molecular elucidation of a wide variety of genetic disorders. However, mapping chromosome breakpoints using traditional methods, such as in situ hybridization with fluorescent dye-labeled bacterial artificial chromosome clones (BAC-FISH), is rather laborious and time-consuming. In addition, the resolution of BAC-FISH is often insufficient to unequivocally identify the disrupted gene. To overcome these limitations, we have performed shotgun sequencing of flow-sorted derivative chromosomes using "next-generation" (Illumina/Solexa) multiplex sequencing-by-synthesis technology. As shown here for three different disease-associated BCRs, the coverage attained by this platform is sufficient to bridge the breakpoints by PCR amplification, and this procedure allows the determination of their exact nucleotide positions within a few weeks. Its implementation will greatly facilitate large-scale breakpoint mapping and gene finding in patients with disease-associated balanced translocations.
A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes (2000)

A growing number of medical research teams have begun to explore the experimental advantages of using a genetic animal model, the nematode worm Caenorhabditis elegans, with a view to enhancing our understanding of genes underlying human congenital disorders. In this study, we have compared sequences of positionally cloned human disease genes with the C.elegans database of predicted genes. Drawing on examples from spinal muscular atrophy, polycystic kidney disease, muscular dystrophy and Alzheimer's disease, we illustrate how data from C.elegans can yield new insights into the function and interactions of human disease genes.