gebhart/patrepeval huggingface dataset:
The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands (1998)

Dietary n-6 polyunsaturated fatty acids (PUFAs) promote rat mammary cancer while n-3 PUFAs are inhibitory. The purpose of this study was to determine whether the fats exert their effects by altering the expression of genes that affect cancer development. Therefore, we have examined the effect of PUFAs on the expression of the cyclooxygenase (COX) 1 and 2 genes that are involved in prostaglandin biosynthesis. We also investigated the effect of dietary PUFAs on the expression of the p21ras protein and Ha-ras mRNA. Rats were fed either low- (7%; LF) or high- (21%; HF) fat diets that were rich in either n-6 PUFAs (safflower oil, S) or n-3 PUFAs (menhaden oil, M) for 3 weeks. COX-1 mRNA levels were approximately the same in groups fed diets containing either level of menhaden oil, but were increased by approximately 30% in the LFS and HFS groups (P < 0.05). Transcripts of the inducible COX-2 gene were not detectable in the menhaden oil groups, but this gene was expressed in animals fed either level of safflower oil and in the HFS group was associated with increased levels of COX enzymatic activity and production of PGE2. Animals fed safflower oil had elevated levels of p21ras protein compared to animals fed menhaden oil. Ha-ras mRNA was increased by approximately 35% in animals fed HFS compared to the group fed HFM (P < 0.05). These results demonstrate that dietary n-6 PUFAs upregulate COX-2 and, to some extent, COX-1 expression. There was a concomitant increase in COX enzyme activity and PG synthesis in the mammary glands of rats fed high levels of n-6 PUFAs. Together with associated changes in p21ras expression, these results may explain, at least in part, the promoting effects of dietary n-6 PUFAs on mammary carcinogenesis.
Site-specific cleavage of a DNA hairpin by topoisomerase II. DNA secondary structure as a determinant of enzyme recognition/cleavage. (1994)

To further define the nucleic acid determinants that govern the recognition of DNA by topoisomerase 11, the ability of the enzyme to cleave a 51-base oligonucleotide that contained a centrally located 19-base hairpin was characterized.Topoisomerase I1 cleaved the 51-mer in a site-specific fashion, within the hairpin, one nucleotide from the 3'-base of the stem.Protein denaturants were not required to trap cleavage products.Although the sequence of the oligonucleotide influenced levels of enzyme-mediated DNA scission, it did not affect the spatial location of cleavage.DNA scission required a doublestrandedkingle-stranded junction at the 3'-base of the hairpin and a tail (either singleor double-stranded) at least 8 bases in length on the 5'-side.Cleavage was not observed when base-pairing within the oligonucleotide was eliminated or when the hairpin was extended to produce a completely double-stranded substrate.Finally, the enzyme displayed a size constraint for both the stem and loop structures of the hairpin.These results indicate that topoisomerase 11 is capable of recognizing secondary structure within nucleic acids and identifies the first secondary structure-specific DNA recognition/ cleavage site for the type I1 enzyme. ~~ ~ ~~~Topoisomerase I1 is a highly conserved enzyme (1, 2) that plays critical roles in chromosome structure (3-7) and function (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).The enzyme modulates the topological state of DNA in eukaryotic cells by passing an intact nucleic acid helix through a transient double-stranded break made in a second helix (21)(22)(23).During its scission reaction, topoisomerase I1 maintains the topological integrity of its nucleic acid substrate by forming covalent phosphotyrosine bonds with both newly generated 5'- DNA termini (24-28).Type I1 topoisomerases share the ability to cleave and religate DNA with a number of enzymes that mediate site-specific recombination such as A Int (29-311, P1 Cre (29,32), and yeast Flp (29, 33, 34).Consequently, in addition to its physiological roles in regulating homologous DNA recombination and resolving recombination products (13,35,36), topoisomerase I1 also is believed to mediate nonhomologous (illegitimate) recombination events in the cell (37).Several lines of evidence support this hypothesis.First, introduction of exogenous topoisomerase
Update on cytokines in rheumatoid arthritis (2007)

It is unclear whether the novel cytokines described in the present review will influence clinical practise. The involvement of IL-17 in murine arthritis may not translate as effectively to human arthritis - the ultimate test is a clinical trial in humans. The lack of efficacy of a recent anti-MCP-1/CCL-2 trial in rheumatoid arthritis highlights this dilemma. Finally, while technological advances including microarray analysis have broadened the scope for cytokine detection in rheumatoid arthritis, these methods have yet to translate to therapy in the clinic.
Falla cardíaca crónica etapa C (2016)

"Introducción: los estadios de falla cardíaca de la ACCF/AHA enfatizan el desarrollo y progresión de la enfermedad mientras que la clasificación funcional NYHA se enfoca en la capacidad de ejercicio y el estado sintomático de la enfermedad. El estadio C señala los pacientes con enfermedad cardíaca estructural con síntomas actuales o previos de falla cardíaca. Metodología: para la creación de la guía de práctica clínica (GPC) basada en la evidencia se siguieron los pasos definidos en la Guía Metodológica para la Elaboración de Guías de Práctica Clínica con Evaluación Económica en el Sistema General de Seguridad Social en Salud Colombiano del Ministerio de Salud y Protección Social. Resultados: se establecen las recomendaciones de tratamiento para la falla cardiaca etapa C. Conclusión: el tratamiento farmacológico actual ha logrado modificar en forma significativa el pronóstico de los pacientes en falla cardíaca disminuyendo la mortalidad y los reingresos por exacerbación de la falla y mejorando la calidad de vida."
ARGININE POLYMERS INHIBIT GRAFT CORONARY ARTERY DISEASE FOLLOWING CARDIAC TRANSPLANTATION. (2000)

Kown, Murray H.1; Steenhoven, Tim van der1,2; Jahncke, Christina L.1; Hoyt, Grant E.1; Rothbard, Jonathan B.3; Robbins, Robert C.1 Author Information
Pharmacodynamic monitoring of BAY 43‐9006 (Sorafenib) in phase I clinical trials involving solid tumor and AML/MDS patients, using flow cytometry to monitor activation of the ERK pathway in peripheral blood cells (2006)

These findings support the further development of flow cytometry applications to monitor signal transduction inhibitors during early phase clinical trials.
Survival and Axonal Elongation of Adult Rat Retinal Ganglion Cells (1989)

A peripheral nerve exudate, collected in situ from the proximal end of a severed rat sciatic nerve, can induce substantial axonal elongation from ganglion cells when tested on explanted adult rat retinae. The responsive cells are identified on the basis of their Thy 1.1 immunostaining properties. Similar outgrowth can be obtained from explants when the culture medium is supplemented with brain-derived neurotrophic factor (BDNF). In addition, both BDNF and the sciatic nerve exudate can prevent ganglion cell degeneration as shown by the retrograde transport of a fluorescent dye that had been applied to the superior colliculus prior to explantation. The results demonstrate that soluble components, released by lesioned peripheral nerves, can effect adult retinal ganglion cells in a way that is reminiscent of that which has been described in vivo using sciatic nerve grafts after sectioning of the optic nerve. The molecular nature of these components is discussed.
Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis (2013)

PROSPERO (CRD42013004385).
Monoclonal antibody 806 inhibits the growth of tumor xenografts expressing either the de2-7 or amplified epidermal growth factor receptor (EGFR) but not wild-type EGFR. (2001)

The monoclonal antibody (mAb) 806 was raised against the delta2-7 epidermal growth factor receptor (de2-7 EGFR or EGFRvIII), a truncated version of the EGFR commonly expressed in glioma. Unexpectedly, mAb 806 also bound the EGFR expressed by cells exhibiting amplification of the EGFR gene but not to cells or normal tissue expressing the wild-type receptor in the absence of gene amplification. The unique specificity of mAb 806 offers an advantage over current EGFR antibodies, which all display significant binding to the liver and skin in humans. Therefore, we examined the antitumor activity of mAb 806 against human tumor xenografts grown in nude mice. The growth of U87 MG xenografts, a glioma cell line that endogenously expresses approximately 10(5) EGFRs in the absence of gene amplification, was not inhibited by mAb 806. In contrast, mAb 806 significantly inhibited the growth of U87 MG xenografts transfected with the de2-7 EGFR in a dose-dependent manner using both preventative and established tumor models. Significantly, U87 MG cells transfected with the wild-type EGFR, which increased expression to approximately 10(6) EGFRs/cell and mimics the situation of gene amplification, were also inhibited by mAb 806 when grown as xenografts in nude mice. Xenografts treated with mAb 806 all displayed large areas of necrosis that were absent in control tumors. This reduced xenograft viability was not mediated by receptor down-regulation or clonal selection because levels of antigen expression were similar in control and treated groups. The antitumor effect of mAb 806 was not restricted to U87 MG cells because the antibody inhibited the growth of new and established A431 xenografts, a cell line expressing >10(6) EGFRs/cell. This study demonstrates that mAb 806 possesses significant antitumor activity.
Enhancement effect of water activity on enzymatic synthesis of cephalexin (1993)

The effect of water activity (a(w)) of the reaction medium on the enzymatic synthesis of cephalexin (CEX) from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and D-alpha-phenylglycine methyl ester (PGM) was investigated using the alpha-amino acid ester hydrolase enzyme from Xanthomonas citri. It was found that the synthetic activity of the enzyme and the conversion yield were markedly improved when the a(w) of the reaction medium was lowered to about 0.97. The water activity depressing agents evaluated were glycerol, sucrose, and sorbitol, and the conversion yields were improved up to 170% with 15% glycerol, 230% with 30% sucrose, and 270% with 20% sorbitol, respectively. The extent of favorable effect of a(w) on the conversion yield was not the same among the a(w) depressors, probably due to other unknown interactions between the enzyme and depressors. However, optimal a(w) values corresponding to the maximum conversion yield coincided for all a(w) depressors used. The conversion yield of CEX showed an increasing trend with increasing a(w) up to the optimal a(w) value (0.96-0.97) which corresponds to the maximum conversion yield and a decreasing trend beyond the optimal a(w). There appears to be a delicate balance between the hydrolytic reaction of PGM and synthetic reaction of CEX. The increasing a(w)-[E . PGM] complex and the branched reaction pathway fluxes from [E . PGM] to PG (D-alpha-phenyl glycine) and CEX are balanced in such a way that the maximum CEX conversion yield is obtained at a(w) value of 0.96-0.97. The a(w) depressors stabilized the enzyme somewhat, but this positive effect was considered to be only a minor contribution to the substantial yield enhancement. The a(w) depressor effect on viscosity and in turn the mass transfer rate limitation was ruled out since the change in conversion due to the viscosity change was found to be insignificant.
CD86 and CD80 Differentially Modulate the Suppressive Function of Human Regulatory T Cells (2004)

Regulatory T cells (Treg) are important in maintaining tolerance to self tissues. As both CD28 and CTLA-4 molecules are implicated in the function of Treg, we investigated the ability of their two natural ligands, CD80 and CD86, to influence the Treg-suppressive capacity. During T cell responses to alloantigens expressed on dendritic cells, we observed that Abs against CD86 potently enhanced suppression by CD4(+)CD25(+) Treg. In contrast, blocking CD80 enhanced proliferative responses by impairing Treg suppression. Intriguingly, the relative expression levels of CD80 and CD86 on dendritic cells are modulated during progression from an immature to a mature state, and this correlates with the ability of Treg to suppress responses. Our data show that CD80 and CD86 have opposing functions through CD28 and CTLA-4 on Treg, an observation that has significant implications for manipulation of immune responses and tolerance in vivo.
Application of High-Density Array-Based Signature-Tagged Mutagenesis To Discover Novel Yersinia Virulence-Associated Genes (2001)

Yersinia pestis, the causative agent of plague, and the enteropathogen Yersinia pseudotuberculosis have nearly identical nucleotide similarity yet cause markedly different diseases. To investigate this conundrum and to study Yersinia pathogenicity, we developed a high-density oligonucleotide array-based modification of signature-tagged mutagenesis (STM). Y. pseudotuberculosis YPIII mutants constructed with the tagged transposons were evaluated in the murine yersiniosis infection model. The DNA tags were amplified using biotinylated primers and hybridized to high-density oligonucleotide arrays containing DNA complementary to the tags. Comparison of the hybridization signals from input pools and output pools identified a mutant whose relative abundance was significantly reduced in the output pool. Sequence data from 31 transposon insertion regions was compared to the complete Y. pestis CO92 genome sequence. The 26 genes present in both species were found to be almost identical, but five Y. pseudotuberculosis genes identified through STM did not have counterparts in the Y. pestis genome and may contribute to the different tropisms in these closely related pathogens. Potential virulence genes identified include those involved in lipopolysaccharide biosynthesis, adhesion, phospholipase activity, iron assimilation, and gene regulation. The phospholipase A (PldA) mutant exhibited reduced phospholipase activity compared to the wild-type strain and in vivo attenuation of the mutant was confirmed. The combination of optimized double tag sequences and high-density array hybridization technology offers improved performance, efficiency, and reliability over classical STM and permits quantitative analysis of data.
The Cambridge Dictionary of Statistics (1999)

The Cambridge dictionary of statistics , The Cambridge dictionary of statistics , کتابخانه دیجیتال جندی شاپور اهواز
Stabilization of a reaction intermediate as a catalytic device: definition of the functional role of the flexible loop in triosephosphate isomerase (1990)

The function of the mobile loop of triosephosphate isomerase has been investigated by deleting four contiguous residues from the part of this loop that interacts directly with the bound substrate. From the crystal structure of the wild-type enzyme, it appears that this excision will not significantly alter the conformation of the rest of the main chain of the protein. The specific catalytic activity of the purified mutant enzyme is nearly 10(5)-fold lower than that of the wild type. Kinetic measurements and isotopic partitioning studies show that the decrease in activity is due to much higher activation barriers for the enolization of enzyme-bound substrate. Although the substrates bind somewhat more weakly to the mutant enzyme than to the wild type, the intermediate analogue phosphoglycolohydroxamate binds much less well (by 200-fold) to the mutant. It seems that the deleted residues of the loop contribute critically to the stabilization of the enediol phosphate intermediate. Consistent with this view, the mutant enzyme can no longer prevent the loss of the enediol phosphate from the active site and its rapid decomposition to methylglyoxal and inorganic phosphate. Indeed, when glyceraldehyde 3-phosphate is the substrate, the enediol phosphate intermediate is lost (and decomposes) 5.5 times faster than it reprotonates to form the product dihydroxyacetone phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
A 44 kilodalton cell surface homodimer regulates interleukin 2 production by activated human T lymphocytes. (1986)

We previously described a cell surface antigen, termed Tp44, detected by monoclonal antibody 9.3 on approximately 80% of mature human T lymphocytes. Analysis by SDS-polyacrylamide gel electrophoresis and isoelectric focusing demonstrated that this antigen consists of two identical 44 kilodalton glycopeptides that form a disulfide-linked homodimer. Competitive binding experiments showed that antibody 9.3 and an anti-CD3 antibody (64.1) recognize distinct antigenic determinants; furthermore, the binding of antibody 9.3 was unaffected by prior modulation of CD3. Thus, Tp44 has no detectable cell surface association with CD3. By itself, antibody 9.3 had no detectable effect on either IL 2 receptor expression or IL 2 release, and did not cause T cell proliferation even when monocytes were present and exogenous IL 2 was provided, indicating that binding of antibody 9.3 does not provide a primary signal for T cell activation. However, the proliferative responses of T lymphocytes activated by phytohemagglutinin, concanavalin A, or an anti-CD3 monoclonal antibody were strikingly enhanced in the presence of antibody 9.3, an effect associated with increased IL 2 receptor expression and increased IL 2 secretion. Antibody 9.3 enabled anti-CD3-Sepharose-activated T cells and anti-CD3 antibody-activated Jurkat cells to release IL 2 in the absence of monocytes. Fab fragments of antibody 9.3 had no effect on anti-CD3-induced IL 2 release by Jurkat cells, whereas F(ab')2 fragments had activity comparable to that of unmodified antibody, indicating that bivalent binding of Tp44 molecules is required for IL 2 secretion. Together, these results suggest that TP44 may function as a receptor for accessory signals in the activation of T cells.
A single polypeptide acts both as the beta subunit of prolyl 4-hydroxylase and as a protein disulfide-isomerase. (1987)

A single polypeptide is shown to act both as the beta subunit of the proline hydroxylase (EC 1.14.11.2) and as a protein disulfide-isomerase (EC 5.3.4.1). When isolated from chick embryos or rat liver, the beta subunit of prolyl 4-hydroxylase and the enzyme protein disulfide-isomerase have identical molecular weights and peptide maps as produced by digestion with Staphylococcus aureus V8 protease. The apparent molecular weights of both proteins isolated from human placental tissue are slightly higher, and the human beta subunit and one of its peptides have molecular weights about Mr 500 higher than the protein disulfide-isomerase and its corresponding peptide. Experiments with polyclonal and monoclonal antibodies also suggest a structural identity between the two proteins. The beta subunit isolated from the prolyl 4-hydroxylase tetramer has protein disulfide-isomerase activity similar to protein disulfide-isomerase itself, and even the beta subunit when present in the prolyl 4-hydroxylase tetramer has one-half of this activity.
CDP571, a humanised monoclonal antibody to tumour necrosis factor α, for moderate to severe Crohn’s disease: a randomised, double blind, placebo controlled trial (2004)

CDP571 is modestly effective for short but not long term treatment of unselected patients with moderate to severe Crohn's disease. The clinical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (> or =10 mg/l). CDP571 is well tolerated.
Characterization of Escherichia coli strains with gapA and gapB genes deleted (1997)

We obtained a series of Escherichia coli strains in which gapA, gapB, or both had been deleted. Delta gapA strains do not revert on glucose, while delta gapB strains grow on glycerol or glucose. We showed that gapB-encoded protein is expressed but at a very low level. Together, these results confirm the essential role for gapA in glycolysis and show that gapB is dispensable for both glycolysis and the pyridoxal biosynthesis pathway.
Doppler echocardiographic predictors of outcome in newborns with persistent pulmonary hypertension (2004)

Detailed Doppler echocardiographic screening of patients with suspected persistent pulmonary hypertension of the newborn may refine the selection of groups for specific treatment, and identify risk factors.
Dissociation kinetics of 19 base paired oligonucleotide-DNA duplexes containing different single mismatched base pairs (1987)

The dissociation kinetics of 19 base paired oligonucleotide-DNA duplex containing a various single mismatched base pair are studied on dried agarose gels. The kinetics of the dissociation are first order under our experimental conditions. The incorporation of a single mismatched base pair destabilizes the DNA duplexes to some extent, the amount depending on the nature of the mismatched base pair. G-T and G-A mismatches slightly destabilize a duplex, while A-A, T-T, C-T and C-A mismatches significantly destabilize it. The activation energy for the overall dissociation processes for these oligonucleotide-DNA duplexes containing 19 base pairs is 52 +/- 2 Kcal mol-1 as determined from the slope of Arrhenius plot.
Remyelination Induced by a DNA Aptamer in a Mouse Model of Multiple Sclerosis (2012)

Multiple sclerosis (MS) is a debilitating inflammatory disease of the central nervous system (CNS) characterized by local destruction of the insulating myelin surrounding neuronal axons. With more than 200 million MS patients worldwide, the absence of treatments that prevent progression or induce repair poses a major challenge. Anti-inflammatory therapies have met with limited success only in preventing relapses. Previous screening of human serum samples revealed natural IgM antibodies that bind oligodendrocytes and promote both cell signaling and remyelination of CNS lesions in an MS model involving chronic infection of susceptible mice by Theiler's encephalomyelitis virus and in the lysolecithin model of focal demyelination. This intriguing result raises the possibility that molecules with binding specificity for oligodendrocytes or myelin components may promote therapeutic remyelination in MS. Because of the size and complexity of IgM antibodies, it is of interest to identify smaller myelin-specific molecules with the ability to promote remyelination in vivo. Here we show that a 40-nucleotide single-stranded DNA aptamer selected for affinity to murine myelin shows this property. This aptamer binds multiple myelin components in vitro. Peritoneal injection of this aptamer results in distribution to CNS tissues and promotes remyelination of CNS lesions in mice infected by Theiler's virus. Interestingly, the selected DNA aptamer contains guanosine-rich sequences predicted to induce folding involving guanosine quartet structures. Relative to monoclonal antibodies, DNA aptamers are small, stable, and non-immunogenic, suggesting new possibilities for MS treatment.