gebhart/patrepeval huggingface dataset:
Reciprocal inhibition of binding between interleukin 3 and granulocyte-macrophage colony-stimulating factor to human eosinophils. (1989)

125I-labeled recombinant human interleukin 3 (IL-3) bound, at 4 degrees C, to a single class of high-affinity receptors on human eosinophils with an apparent dissociation constant (Kd) of 470 pM, but it did not bind to human neutrophils. 125I-labeled recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) also bound to a single class of high-affinity receptors on eosinophils with an apparent Kd of 44 pM and on neutrophils with an apparent Kd of 70 pM. These binding characteristics were consistent with the biological activities of IL-3 and GM-CSF on eosinophils and with the lack of stimulation of neutrophil function by IL-3. Specificity studies under conditions shown to prevent receptor internalization showed that the binding of 125I-labeled IL-3 to eosinophils was partially inhibited by GM-CSF but not by other cytokines. Reciprocal experiments with 125I-labeled GM-CSF showed that IL-3 but not other cytokines partially inhibited binding to eosinophils. In contrast, the binding of 125I-labeled GM-CSF to neutrophils was not inhibited by IL-3 or other cytokines tested. Quantitative inhibition binding experiments on eosinophils showed that the reciprocal inhibition between IL-3 and GM-CSF was not complete up to a concentration of heterologous ligand of 100 nM. These results show that (i) IL-3 binds to eosinophils but not neutrophils and (ii) IL-3 and GM-CSF specifically interact on the surface of eosinophils, providing a possible mechanism for the overlapping activities of IL-3 and GM-CSF on these cells.
A PCR-mediated gene synthesis strategy involving the assembly of oligonucleotides representing only one of the strands. (1992)

A modification of PCR-mediated gene synthesis strategy is introduced. This modification enables the synthesis of a gene from oligonucleotides comprising only one of the two strands. Bridging oligonucleotides (approximately 20-mers in length) complementary to the junctions of template strand oligonucleotides and two outer primers are also needed for PCR. A two-step PCR containing a first step of 10 cycles, followed by a second step of 20 cycles, differing only in the annealing conditions was used. A single-step PCR combining the two different cycle conditions could also be used successfully. Optimal conditions for gene synthesis (and amplification) are described. Human and porcine colipase genes (297 and 309 bp, respectively) have been successfully synthesized, cloned into the Invitrogen TA cloning vector and sequenced. There was absolutely no error in the clones that were sequenced.
High levels of transglutaminase expression in doxorubicin‐resistant human breast carcinoma cells (1994)

Tissue type II transglutaminase (TGase) is a member of the TGase family that catalyzes Ca(2+)-dependent covalent cross-linking of several amines to the gamma-carboxamide group of protein-bound glutamine residues. The degree of therapeutic efficacy or toxicity of drugs may be related to their ability to serve as a substrate for TGase and their covalent linkage to glutamine residues of regulatory proteins through the catalytic action of this enzyme. Here, doxorubicin (adriamycin)-resistant human breast carcinoma MCF-7ADR cells exhibited 40- to 6C-fold higher TGase activity than control drug-sensitive MCF-7WT cells. The same was observed in vivo: a small proportion of tumor cells became positive for TGase after administration of adriamycin-based chemotherapy to patients with breast carcinoma. Similarly, continuous culture of MCF-7WT cells in the presence of adriamycin led to the appearance of the drug-resistant phenotype that was in turn associated with increased expression of TGase. This increase in TGase was specific for adriamycin resistance. Like most known TGase, MCF-7ADR TGase was completely dependent on the presence of Ca2+ for its catalytic activity. Based on its immunoreactivity, the TGase in MCF-7ADR cells was identified as an 85-kDa tissue-type TGase and was present only in the soluble form. Immunoblot analysis revealed that the increase in TGase activity was due to accumulation of the protein. Two cytosolic proteins of approximately 20 and 30 kDa in MCF-7 cells served as suitable acyl donor substrates in TGase-catalyzed reactions.
Stereoregularity of polystyrene and mechanism of polymerization (1975)

Abstract The Stereoregularity of polystyrenes prepared with radical, anionic, and cationic initiators was determined by means of 13 C‐NMR spectroscopy. Aromatic C 1 carbon spectra measured on o ‐dichlorobenzene solutions consisted of about six peaks and the peak at the highest magnetic field (at 146,3 ppm) was assigned to an rrrr pentad. The proportion of racemic dyads P r , was directly calculated from the proportion of the rrrr pentad peak assuming that the Bernoullian statistics holds for the polymerization of styrene. The P r values of polystyrenes prepared with radical initiators at temperatures from 80° to 0°C were 0,72–0,73, while the cationic polymerizations gave P r values ranging from 0,54 to 0,68. The P r values of the same polystyrenes were also calculated by use of a p ‐xylene/chloroform mixture as solvent for the 13 C‐NMR measurements. For anionically obtained polystyrenes, considerably different P r values were found using both solvent systems. From this, it was considered that the anionic polymerization of styrene with butyllithium as catalyst does not obey the Bernoullian statistics.
Neurite growth-inhibitory properties of amyloid β-peptidesin vitro: Aβ25-35, but not Aβ1-40, is inhibitory (1997)

The effects of freshly-solubilized synthetic amyloid β-peptides on the growth of neurites from high density cultures of embryonic chick dorsal root ganglia and retinal pieces over periods of 24 to 48 hours were examined. The undecapeptide β25–35, the presumed neurotoxic moiety of β1–40, was found to inhibit neurite outgrowth, whereas β1–40 and β1–28 were without effect. The growth-inhibitory effect of β25–35 was apparent at a concentration of 10 ng/ml and showed concentration dependence. The inhibitory effect was reversible, since dorsal root ganglia grown initially in β25–35-supplemented medium showed more extensive neurite outgrowth when transferred to normal growth medium after 24 hours than dorsal root ganglia maintained in freshly-made β25–35-supplemented medium throughout. It is concluded that β25–35 has neurite growth-inhibitory properties in vitro not shared by β1–40 or β1–28. The differences in peptide behaviour may be related to aggregation state. These findings may have implications for understanding plaque morphology in normal ageing and Alzheimer's disease, since N-terminally truncated amyloid β-peptides are preferentially localized in the diffuse plaques which lack a surrounding neuritic reaction; this may also indicate a physiological neurite growth-inhibitory activity for N-terminally truncated amyloid β-peptides. © 1997 John Wiley & Sons, Ltd.
Insertion and deletion mutagenesis of the human cytomegalovirus genome. (1987)

Studies on human cytomegalovirus (CMV) have been limited by a paucity of molecular genetic techniques available for manipulating the viral genome. We have developed methods for site-specific insertion and deletion mutagenesis of CMV utilizing a modified Escherichia coli lacZ gene as a genetic marker. The lacZ gene was placed under the control of the major beta gene regulatory signals and inserted into the viral genome by homologous recombination, disrupting one of two copies of this beta gene within the L-component repeats of CMV DNA. We observed high-level expression of beta-galactosidase by the recombinant in a temporally authentic manner, with levels of this enzyme approaching 1% of total protein in infected cells. Thus, CMV is an efficient vector for high-level expression of foreign gene products in human cells. Using back selection of lacZ-deficient virus in the presence of the chromogenic substrate 5-bromo-4-chloro-3-indolyl beta-D-galactoside, we generated random endpoint deletion mutants. Analysis of these mutants revealed that CMV DNA sequences flanking the insert had been removed, thereby establishing this approach as a means of determining whether sequences flanking a lacZ insertion are dispensable for viral growth. In an initial test of the methods, we have shown that 7800 base pairs of one copy of L-component repeat sequences can be deleted without affecting viral growth in human fibroblasts.
Alteration of Glial Fibrillary Acidic Proteins Immunoreactivity in Astrocytes of the Spinal Cord Diabetic Rats (2008)

Diabetes affects retinal and nervous glial cells, especially the astrocytes. A key indicator of this response is the alteration in the level of intermediate filament glial fibrillary acidic protein (GFAP) and number of GFAP-immunoreactive astrocytes. To date, no study has investigated the effect of diabetes on the distribution of GFAP-immunoreactive astrocytes in the spinal cord. Therefore, the present study investigated the effect of diabetes on the number of GFAP-immunoreactive astrocytes in the gray matter of the spinal cord of streptozotocin-induced diabetic Wistar rats. Animals were divided into six groups (n = 7); 6 weeks and 12 weeks diabetic duration groups and their respective age-matched normal control and sham control groups. Our results demonstrated a significant (P < 0.001) decrease in the number of GFAP-immunoreactive astrocytes in different areas of the spinal cord sections of the 6 weeks and 12 weeks long diabetic rats when compared with the spinal cord of normal and sham control groups of comparable age. The mean percentage in total number of GFAP-immunoreactive astrocytes in the whole gray matter areas of the spinal cord of the 6 and 12 weeks diabetic groups were approximately 28% and 41% less than control groups. Furthermore, the 12 weeks diabetic group showed a significant (P < 0.001) reduction in the number of GFAP-immunoreactive astrocytes when compared with the 6 weeks diabetic animals. These results suggest that the induction of diabetes is associated with a reduction in GFAP-positive astrocytes in the spinal cord, which may affect the functional support and role of astrocytic cells in the nervous tissue. This in turn may contribute to the pathological changes associated with diabetic state in the central nervous system.
[Progress on OECD Chemicals Programme (13)--SIAM 22 in Paris, 2006]. (2007)

The 22nd Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 22) was held at the Organisation for Economic Co-operation and Development (OECD) headquarters in Paris, France. The initial assessment documents of five substances (CAS numbers: 75-59-2, 80-51-3, 101-83-7, 103-24-2, 27813-02-1) sponsored by Japan were all agreed at the meeting. In this report, the documents of these substances are introduced.
Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs (2002)

Cytochrome P450 CYP2D6 is the most extensively characterized polymorphic drug-metabolizing enzyme. A deficiency of the CYP2D6 enzyme is inherited as an autosomal recessive trait; these subjects (7% of Caucasians, about 1% of Orientals) are classified as poor metabolizers. Among the rest (extensive metabolizers), enzyme activity is highly variable, from extremely high in ultrarapid metabolizers, to markedly reduced in intermediate metabolizers. The CYP2D6 gene is highly polymorphic, with more than 70 allelic variants described so far. Of these, more than 15 encode an inactive or no enzyme at all. Others encode enzyme with reduced, "normal" or increased enzyme activity. The CYP2D6 gene shows marked interethnic variability, with interpopulation differences in allele frequency and existence of "population-specific" allelic variants, for instance among Orientals and Black Africans. The CYP2D6 enzyme catalyses the metabolism of a large number of clinically important drugs including antidepressants, neuroleptics, some antiarrhythmics, lipophilic beta-adrenoceptor blockers and opioids. The present-day knowledge on the influence of the genetic variability in CYP2D6 on the clinical pharmacokinetics and therapeutic effects/adverse effects of psychotropic drugs is reviewed.
Tumor Necrosis Factor Death Receptor Signaling Cascade Is Required for Amyloid-β Protein-Induced Neuron Death (2004)

Tumor necrosis factor type I receptor (TNFRI), a death receptor, mediates apoptosis and plays a crucial role in the interaction between the nervous and immune systems. A direct link between death receptor activation and signal cascade-mediated neuron death in brains with neurodegenerative disorders remains inconclusive. Here, we show that amyloid-β protein (Aβ), a major component of plaques in the Alzheimer's diseased brain, induces neuronal apoptosis through TNFRI by using primary neurons overexpressing TNFRI by viral infection or neurons from TNFRI knock-out mice. This was mediated via alteration of apoptotic protease-activating factor (Apaf-1) expression that in turn induced activation of nuclear factor κB (NF-κB). Aβ-induced neuronal apoptosis was reduced with lower Apaf-1 expression, and little NF-κB activation was found in the neurons with mutated Apaf-1 or a deletion of TNFRI compared with the cells from wild-type (WT) mice. Our studies suggest a novel neuronal response of Aβ, which occurs through a TNF receptor signaling cascade and a caspase-dependent death pathway.
Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization (2004)

Pretreatment with a combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) has been reported to attenuate left ventricular (LV) remodeling after acute myocardial infarction (MI). We here examined whether the cytokine treatment started after MI has also beneficial effects. Anterior MI was created in the recipient mice whose bone marrow had been replaced with that of transgenic mice expressing enhanced green fluorescent protein (GFP). We categorized mice into five groups according to the following treatment: 1) saline; 2) administration of G-CSF and SCF from 5 days before MI through 3 days after; 3) administration of G-CSF and SCF for 5 days after MI; 4) administration of G-CSF alone for 5 days after MI; 5) administration of SCF alone for 5 days after MI. All the three treatment groups with G-CSF showed less LV remodeling and improved cardiac function and survival rate after MI. The number of capillaries, which express GFP, was increased and the number of apoptotic cells was decreased in the border area of all the treatment groups with G-CSF. Even if the cytokine treatment is started after MI, it could prevent LV remodeling and dysfunction after MI--at least in part--through an increase in neovascularization and a decrease in apoptosis in the border area.
The Nithsdale Schizophrenia Surveys. XI: Relatives' Expressed Emotion (1993)

The level of expressed emotion (EE) in 32 relationships between relatives and schizophrenic patients was assessed on three separate occasions over five years. EE was high on all three occasions in 25% of relatives, low on all three in 38%, and fluctuating in 38%; that is, in the majority of relatives (63%) the level of EE was stable over time. Three relatives who had previously shown high EE had evidence of dementia at the time of the third assessment, and showed low EE. Fourteen patients relapsed at least once over five years; patients who relapsed were evenly spread throughout those living in a home in which EE was consistently high, consistently low, or fluctuating. However, patients living in low-EE homes who did relapse did so significantly less often than those who relapsed and were living in homes in which EE was high or fluctuating. At the time of relapse, EE was not consistently high, and some patients in consistently high-EE homes did not relapse at all over five years.
Subunit interactions in hemoglobin probed by fluorescence and high-pressure techniques (1990)

The dissociation of the subunits of human adult oxyhemoglobin has been investigated by using steady-state fluorescence anisotropy, multifrequency phase fluorometry, and high hydrostatic pressure. Human hemoglobin obtained by using two purification procedures (bulk preparation by centrifugation or further fractionation using anion-exchange chromatography) was labeled with an extrinsic fluorescent probe, 5-(dimethylamino)naphthalene-1-sulfonyl chloride (DNS-Cl). The long fluorescence lifetime of this probe allows for the observation of the macromolecular tumbling, and thus provides a method for observing changes in the size of the complex upon subunit dissociation under differing solution conditions of proton and organic phosphate concentration. At pH 7, the dansylated preparations of bulk and fractionated hemoglobin showed a concentration-dependent decrease in the anisotropy which though not identical can only arise from the tetramer to dimer dissociation. We observed primarily the dimer at pH 9 and a small destabilization of the tetramer in the presence of saturating inositol hexaphosphate (IHP). High-pressure experiments allowed for the observation of the dissociation of the hemoglobin dimer into monomers. From these measurements, we estimate the dimer dissociation constant to be between 0.1 and 1 nM. We compare the present results on the subunit affinities in hemoglobin obtained from steady-state and time-resolved fluorescence data with those obtained previously by using gel filtration, sedimentation, and kinetic techniques. These comparisons are indicative of a certain degree of conformational heterogeneity in the hemoglobin preparations.
Statistical handbook on infectious diseases (2003)

This statistical handbook is designed to offer students, researchers, practitioners, and the general adult population a comprehensive statistical overview of the status of infectious disease worldwide. The availability of this information has increased dramatically on the Internet, yet the data are often too extensive, hard to find, or difficult to interpret. A carefully selected array of tables and charts present authoritative statistical information, placing valuable statistics into context with introductory text. Detailed source information in each table, figure, and chart allows the user to pursue further information and uncover the stories behind the numbers. The book concludes with a glossary of key terms, bibliography, guide to information sources available on the Internet, and a detailed index.
Use of Epstein-Barr virus-transformed B cell lines for the generation of immunoglobulin-producing human B cell hybridomas. (1982)

HGPRTase-deficient EBV-transformed B cell lines were shown to be effective fusion partners with mitogen-activated human B cells for the construction of Ig-producing human B cell hybridomas. In a series of experiments using these lines and B cells from several tissue sources, approximatley 20% of the cultures plated were consistently positive for growth after hypoxanthine-aminopterin-thymidine selection and approximatley 30% of these synthesized significant new Ig. A marked increase in Ig secretion was observed after hybridization, which was due to new Ig; Ig from the parental lime was shown to disappear in several instances. Special analyses were carried out on a human hybridoma secreting antibody specific for tetanus toxoid and tetanus toxin and stable subclones were derived. These studies suggest that EBV-transformed lines will prove useful in human hybridization studies, thus making a large library of B cell lines available for the generation of human monoclonal antibodies.
A Review of the Effect of Engine Operating Conditions on Borderline Knock (1996)

&lt;div class="htmlview paragraph"&gt;The effects of engine operating conditions on the octane requirement and the resulting knock-limited output were studied on a single cylinder engine using production cylinder heads. A 4-valve cylinder head with port deactivation was used to study the effect of fuel octane, inlet air temperature, coolant temperature, air/fuel ratio, compression ratio and exhaust back pressure. The effect of the thermal environment was studied in more detail using separate cooling systems for the cylinder head and engine block on a 2-valve cylinder head.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The results of this study compared closely with results found in the literature even though the engine and/or operating conditions were quite different in many cases. Guidelines on the effect of various parameters on the octane requirement of an engine can be summarized as follows:&lt;/div&gt; &lt;div class="htmlview paragraph"&gt; &lt;ul class="list disc"&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Spark Advance: 1 ON/1° SA&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Intake Air Temperature: 1 ON/7 K&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Air/Fuel Ratio: peaks at 5% rich of stoichiometric, decreases by around 2 ON / air/fule ratio around peak&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Intake Pressure: 3-4 ON/10 kPa&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Compression Ratio: 5 ON/CR&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Exhaust Back Pressure: 1 ON/30 kPa&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Coolant Temperature: 1 ON/10 K (Similar effect of head and block temperature., Larger effect at low speed.)&lt;/div&gt;&lt;/li&gt; &lt;/ul&gt; &lt;/div&gt;
Identification and molecular characterization of shrunken-2 cDNA clones of maize. (1990)

Mutation at the shrunken-2 (Sh2) locus of maize, a gene described more than 40 years ago, greatly reduces starch levels in the endosperm through its effect on the starch synthetic enzyme ADP-glucose pyrophosphorylase, an enzyme thought to be regulatory in this biosynthetic pathway. Although our previous work has suggested that Sh2 is a structural gene for this enzyme, we have also reported data compatible with Sh2 acting post-transcriptionally. In this study, we took advantage of a transposable element-induced Sh2 allele, its progenitor, and revertants to identify a clone for this locus. Although the cloning and identification were done independently of any knowledge concerning the product of this gene, examination of the deduced amino acid sequence revealed much similarity to known ADP-glucose pyrophosphorylase subunits of plants and bacteria, including regions involved in substrate binding and activator binding. Little sequence similarity, however, was found at the DNA level. These observations provide direct evidence that Sh2 encodes a subunit for endosperm ADP-glucose pyrophosphorylase. Analysis of several phenotypically wild-type alleles arising from a mutable sh2-Ds allele revealed one unexpected case in which DNA sequences of Sh2 were rearranged in comparison with the progenitor Sh2. In contrast to wild type, the Ds-induced sh2 allele conditions at least two transcripts in the endosperm.