gebhart/patrepeval huggingface dataset:
Biological Activity and Ferric Ion Binding of Fragments of Glycine-Extended Gastrin (2004)

Nonamidated gastrins such as progastrin and glycine-extended gastrin17 (Ggly) induce cell proliferation and migration in vitro and colonic mucosal proliferation in vivo. Our earlier NMR study defined the structure of Ggly and showed that ferric ions are essential to its biological activity, with the first binding to Glu7 and the second to Glu8 and Glu9 (Pannequin, J. et al. (2002) J. Biol. Chem. 277, 48602-48609). The aims of this study were to define the minimum biologically active fragment of Ggly and to determine whether ferric ions were also required for its activity. Cell-proliferation studies with Ggly fragments containing the five glutamate residues showed that the nonapeptide LE(5)AYG, the octapeptide LE(5)AY, and the heptapeptides E(5)AY and LE(5)A were fully active and that their activity was dependent on the presence of ferric ions. The activity of the hexapeptides LE(5) and E(5)A and the pentapeptide E(5) was reduced and independent of the presence of iron. The stoichiometry of ferric ion binding to LE(5)AYG, LE(5)AY, and E(5)AY, determined by absorption spectroscopy, was 2 mol/mol. NMR spectroscopy showed that the nonapeptide LE(5)AYG and shorter fragments had no defined structure and that the iron-binding sites differed from those in Ggly. We conclude that, in contrast to amidated gastrins where the C-terminal tetrapeptide is the minimum bioactive fragment, the shortest fully active fragments of Ggly are the heptapeptides LE(5)A and E(5)AY. These observations indicate that extensive proteolytic processing may not completely inactivate Ggly and that bioactive forms that are not detected by current radioimmunoassays may be present in tissues and/or plasma.
Association of BoLA class II haplotypes with subclinical progression of bovine leukaemia virus infection in Holstein-Friesian cattle. (1996)

The influence of bovine lymphocyte antigen (BoLA) complex polymorphism on subclinical progression of bovine leukaemia virus (BLV) infection was investigated in 41 Holstein-Friesian cows from two herds in Italy. All cows were seropositive for BLV and 22 had persistent lymphocytosis (PL). BoLA-A specificities were defined by serology, and class II haplotypes were defined based on restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR)-RFLP analysis of DQ and DR genes. Chi-square analysis revealed a significant and absolute association of haplotype DQA*3A-DQB*3A-DRB2*2A-DRB3.2*11 with resistance to PL (P chi 2 = 0.028, relative risk (RR) = 0.061). Consistent with this observation, multiple regression analysis revealed that animals carrying this haplotype had lower lymphocyte counts (P = 0.0057). By contrast, haplotype DQA*12-DQB*12-DRB2*3A-DRB3.2*8 was associated with susceptibility to PL (P chi 2 = 0.043, RR = 9.625) and increased lymphocyte counts (P = 0.0537). These results confirm the association of haplotype DQA*3A-DQB*3A-DRB2*2A-DRB3.2*11 with resistance to PL, and substantiate earlier findings of haplotype DQA*12-DQB*12-DRB2*3A-DRB3.2*8 as a risk factor for subclinical progression to PL in BLV-infected Holstein-Friesian cattle.
Actual Targets in Cytodifferentiation Cancer Therapy (2004)

Transformation of a normal cell into a tumor cell results from six essential alterations in cell physiology. There is a complex relationship that exists between growth, differentiation, neoplastic transformation, and the expression of genes and tumor suppressor genes. The knowledge of these mechanisms demonstrates that it is possible to pharmacologically modulate the growth and differentiation of tumor cells. The differentiation therapy focuses on demonstrating that cancer is a reversible state with altered maturation in which the transformed phenotype may be suppressed by cytostatic agents and by the pharmacological differentiation towards benign forms with no proliferative potential. One of the mechanisms determining the activity of target genes is the post-translational modification of the N-terminal tails of core histones. Inappropriate repression of genes required for cell differentiation has been linked to several forms of cancer. Histone deacetylase inhibitors modulate transcription, and are endowed with cytodifferentiating, antiproliferative and apoptogenic properties. Retinoids modulate cell differentiation, proliferation, apoptosis and morphogenesis in vertebrates, and have proved to be clinically useful. Their biological effects are mediated by the activation of retinoic acid receptors, which are ligand-dependent gene transcription factors. Checkpoints during cell cycle allow the cell to respond to proliferation signals or decide between the alternate pathways leading to cytokinesis, differentiation, quiescence, and cell death. Abrogation of normal cell cycle controls in tumor cells contributes to their inability to differentiate and the restoration of such controls in G1 can lead to the resumption of differentiation and terminal cell division. Chemical inhibitors of cyclin-dependent kinases have been reported to stimulate differentiation of tumor-cell lines.
Pretreatment serum markers and lymphocyte response to interleukin-2 therapy (1999)

Lymphocytosis is a marker of subcutaneous interleukin (IL)-2 therapy efficacy, whereas baseline elevated inflammatory indices were noticed in IL-2-resistant disease. The aim of this study was to analyse the relationship between pretreatment circulating values of IL-6, neopterin, sIL-2R, ESR and the changes in lymphocyte number in response to IL-2 administration. Twenty metastatic renal cell cancer patients were treated with subcutaneous IL-2 immunotherapy (6 000 000 IU day–1 for 6 days per week for 4 weeks); tumour response consisted of partial response (PR) in four patients, stable disease (SD) in eight patients and progressive disease (PD) in eight patients. Abnormally high pretreatment values of each marker were found as follows: IL-6 in seven patients, neopterin in nine patients, sIL-2R in 13 patients. In response to IL-2 immunotherapy, a significantly higher mean increase in lymphocyte number and a higher percentage of patients with tumour response or stable disease were observed when pretreatment values of IL-6, neopterin and sIL-2R were within the normal range, in comparison to patients with high values for these markers. The pretreatment excess of these serum inflammatory markers seems to negatively influence both the host and tumour response to IL-2 administration, by preventing the IL-2-induced lymphocytosis and resulting in tumour progression. Further studies are requested to verify if overall survival and quality of life may depend on pretreatment host immune status and/or lymphocyte response after IL-2 administration.
AllMusic. http://www.allmusic.com/. (2013)

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Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats (2014)

The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions.
Purification and characterisation of the protein encoded by the activated human N-ras gene and its membrane localisation. (1987)

Using a transformed human embryo retinal cell line (Ad 2 E1A + N-ras HER 313A), which expresses activated N-ras p21 at a high level, we have examined various properties of the protein. Immunoprecipitated p21 has covalently bound lipid attached to it through an alkali-labile thioester bond. This incorporation of fatty acid into the protein proceeds in vitro and probably in vivo via a palmitoyl-CoA intermediate and is catalysed by a crude microsomal preparation. A novel purification procedure has been developed for the protein based on its solubility in high concentrations of ethanol. Residual protein impurities were removed by gel filtration in the presence of detergent. Using a membrane preparation from Ad 2 E1A + N-ras HER 313A cells, we have shown that N-ras p21 is firmly anchored in the cell membrane and is not removed by extraction with salts, chelating agents or reducing agents, but is only solubilised by detergents at high concentrations. Exposure of cell membrane preparations and purified N-ras p21 to proteolytic enzymes gives rise to similar degradation patterns. Based on these observations and the known amino acid sequence of p21, it is concluded that attachment to the cell membrane is through the lipid at the C-terminus and not through the incorporation of the polypeptide chain into the lipid bilayer. These results are discussed in relation to the hypothesis that the mode of action of p21 is analogous to that of G proteins.
RNAi-based drug discovery and its application to therapeutics. (2008)

The discovery of RNA interference (RNAi) for target-specific gene silencing via short interfering RNA (siRNA) has rapidly created a powerful tool for the exploration of pathogenesis of disease. The identification of this remarkable molecular pathway has manifested in the new field of RNAi therapy. In efforts to establish the therapeutic application of RNAi therapy, a major focus has been on target gene-specific siRNA-delivery technology in vivo. In particular, creating a pinpoint delivery system for siRNAs is a priority because such a system would be a key technology for the development of the next generation of drugs, including anticancer therapies. Drug discovery studies and novel treatments based on RNAi are currently targeting a wide range of diseases, including viral infections and cancer. This feature review focuses on recent progress in the nonviral systemic delivery of siRNA in animal models and in clinical trials, as well as on the application of microRNAs in RNAi therapy.
Graphite Thin Films Consisting of Nanograins of Multilayer Graphene on Sapphire Substrates Directly Grown by Alcohol Chemical Vapor Deposition (2011)

Graphene has been attracting a strong interest as a transparent electrode as well as a THz nanoelectronic device owing to its unique properties. To date, large-area graphene growth has been realized by chemical vapor deposition (CVD) with a catalyst metal. To avoid the transfer of segregated graphene, we have examined directly graphite thin film growth on nonpolar a -sapphire substrates without any catalyst metal by alcohol CVD. Graphite thin films consisting of nanograins of multilayer graphene on a -sapphire substrates were verified by a combination of transmission electron spectroscopy (TEM), and Raman analyses, and optical transparent and sheet resistance measurements.
Novel anti‐idiotype antibody therapy for lipooligosaccharide‐induced experimental autoimmune neuritis: Use relevant to Guillain‐Barré syndrome (2010)

Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C.jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies.
Cloning of terminal transferase cDNA by antibody screening. (1984)

A cDNA library was prepared from a terminal deoxynucleotidyltransferase-containing thymoma in the lambda phage vector lambda gt11. By screening plaques with anti-terminal transferase antibody, positive clones were identified of which some had beta-galactosidase-cDNA fusion proteins identifiable after electrophoretic fractionation by immunoblotting with anti-terminal transferase antibody. The predominant class of cross-hybridizing clones was determined to represent cDNA for terminal transferase by showing that one representative clone hybridized to a 2200-nucleotide mRNA in close-matched enzyme-positive but not to enzyme-negative cells and that the cDNA selected a mRNA that translated to give a protein of the size and antigenic characteristics of terminal transferase. Only a small amount of genomic DNA hybridized to the longest available clone, indicating that the sequence is virtually unique in the mouse genome.
Interleukin 6 perfusion stimulates reconstitution of the immune and hematopoietic systems after 5-fluorouracil treatment. (1990)

Effects of interleukin 6 (IL-6) on the functional capacity of the immune and hematopoietic systems in 5-fluorouracil (5-FU)-treated mice were determined. IL-6 (5 x 10(4) units/mouse/day) was administered s.c. for 7 days by implantation of an osmotic pump, since it was demonstrated that a much higher increase in the primary response to sheep RBC was observed by administration of slowly released rather than daily s.c. injection of IL-6. IL-6 perfusion significantly augmented anti-sheep RBC antibody responses depressed by 5-FU (150 mg/kg) treatment. IL-6 also was shown to stimulate hematological recovery in mice treated with 5-FU. Namely, IL-6 perfusion accelerated the recovery of the number of hematopoietic stem cells, granulocyte-macrophage progenitors, and mature neutrophils in the spleen, although IL-6 did not stimulate the recovery of the neutrophil count in blood. Recovery of the platelet count in blood was stimulated by IL-6. Furthermore, it was found that the endogenous IL-6 level in serum increased after 5-FU treatment, which suggests that IL-6 may play some role in the recovery of the immune and hematopoietic systems. Finally, we examined the effect of IL-6 on the survival of mice treated with a higher dosage of 5-FU (300 mg/kg). IL-6 perfusion produced a distinct increase in survival rate at Day 30 (74% versus 28%). It is of note that the number of bacteria (identified as Escherichia coli) cultured from the spleen and the liver decreased in IL-6-perfused mice. This IL-6-induced effect was accompanied by enhancement of an oxidative burst response. Moreover, the anti-E. coli antibody titer in serum was higher in IL-6-perfused mice than in control mice. These results suggest the possible use of IL-6 for stimulating the reconstitution of the immune and hematopoietic systems after chemotherapy treatment.
The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience (2015)

This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.
Expression cloning of a human corticotropin-releasing-factor receptor. (1993)

Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. We report here the cloning of a cDNA coding for a CRF receptor from a human corticotropic tumor library. The cloned cDNA encodes a 415-amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G protein-coupled receptors. The receptor expressed in COS cells binds rat/human CRF with high affinity (Kd = 3.3 +/- 0.45 nM) and specificity and is functionally coupled to adenylate cyclase. The CRF antagonist alpha-helCRF-(9-41) inhibits the CRF-stimulated increase in intracellular cAMP. Northern blot analysis reveals that the CRF receptor is expressed in the rat pituitary and brain as well as in the mouse AtT20 corticotropic cells. We also describe an alternatively spliced form of the receptor which includes an insert of 29 amino acids in the first intracellular loop.
Studies on Nicotinoids as an Insecticide (1963)

3-Pyridylmethylamines, such as 3-pyridylmethyl-N-diethylamine, N-(3-pyridylmethyl)-piperidine and 3-pyridylmethyl-N-dimethylamine provided with the essential moiety of nicotinoids molecule, show comparable toxicity to nicotine against house flies.3-Pyridylmethylamine without substituent on amino-nitrogen, N-(3-pyridylmethyl)-morpholine having low basic nitrogen, 4-pyridylmethyl-N-diethylamine not provided with proper N-N distance and some nicotine-methiodides having quaternary nitrogen show low or no toxicity.These data support our proposition that the essential moiety of nicotinoids molecule responsible for high toxicity is 3-pyridylmethylamine grouping.
Human dendritic cells genetically engineered to express high levels of the human epithelial tumor antigen mucin (MUC-1). (1996)

We have achieved stable high-level expression of a human tumor antigen, epithelial cell mucin (MUC-1), on human dendritic cells (DCs) by retroviral transduction of CD34+ progenitor cells and their subsequent cytokine-induced differentiation into DCs. The process of retroviral transduction did not alter the growth or differentiation of DCs from CD34+ progenitor cells. Immunofluorescence and electron microscopy studies revealed that the expression of mucin was limited to the body of the DCs and was excluded from the cytoplasmic veils of the DCs. Furthermore, the expression of mucin on DCs was similar, if not identical, to the nonpolarized expression of mucin found on carcinoma cells. In functional studies, the MUC-1(+)-transduced DCs were potent stimulators of allogeneic CD4+ T cells and, in fact, were superior to MUC-1- DCs. Thus, MUC-1+ DCs are expected to be a valuable tool in the immunotherapeutic treatment of patients with tumors that express MUC-1.
Embryos with high implantation potential after intracytoplasmic sperm injection can be recognized by a simple, non-invasive examination of pronuclear morphology (2000)

Embryos are conventionally selected for transfer based on the evaluation of the cleavage speed and extent of blastomere fragmentation. Here we examined whether the predictive value of these criteria, as indicators of the chance of embryo implantation, can be further potentiated by adding previously described criteria reflecting the regularity of pronuclear development. In a group of embryos selected for transfer in 380 fresh embryo transfer cycles according to the conventional criteria, the transfer of only those embryos that developed from zygotes judged normal at the pronuclear stage (pattern 0) gave significantly higher pregnancy (44.8%) and implantation (30.2%) rates compared with the pregnancy (22.1%; P < 0. 05) and implantation rates (11.2%; P < 0.001) for the transfers of only those embryos that developed from zygotes judged abnormal (non-pattern 0). The transfer of only one pattern 0 embryo was sufficient for the optimal chance of pregnancy (no differences in pregnancy rates after transfer of one, two or three pattern 0 embryos), whereas the transfer of two pattern 0 embryos mostly resulted in a twin pregnancy. The inclusion of the criteria based on pronuclear morphology can thus lead to the application of a single embryo transfer policy and optimize the selection of embryos for transfer and cryopreservation.
Computed Tomography and Positron Emission Transaxial Tomography Evaluations of Normal Aging and Alzheimer's Disease (1983)

Young normal subjects, old normal subjects, and patients with senile dementia of the Alzheimer's type (SDAT) were studied with both computed tomography (CT) and positron emission transaxial tomography (PETT). Increases in ventricular size with both aging and disease were measured. Regional glucose metabolic rate was not affected by age, but was markedly reduced in SDAT patients. These data indicate that in normal aging, structural brain changes may be more salient than biochemical changes. Although both structural and biochemical changes occur in SDAT, the biochemical changes are more marked. The results suggest that PETT is potentially more useful than CT in the in vivo diagnosis of SDAT.
Hydrogen−Deuterium (H/D) Exchange Mapping of Aβ1-40 Amyloid Fibril Secondary Structure Using Nuclear Magnetic Resonance Spectroscopy (2005)

We describe here details of the hydrogen-deuterium (H/D) exchange behavior of the Alzheimer's peptide Abeta(1)(-)(40), while it is a resident in the amyloid fibril, as determined by high-resolution solution NMR. Kinetics of H/D exchange in Abeta(1)(-)(40) fibrils show that about half the backbone amide protons exchange during the first 25 h, while the other half remain unexchanged because of solvent inaccessibility and/or hydrogen-bonded structure. After such a treatment for 25 h with D(2)O, fibrils of (15)N-enriched Abeta were dissolved in a mixture of 95% dimethyl sulfoxide (DMSO) and 5% dichloroacetic acid (DCA) and successive heteronuclear (1)H-(15)N HSQC spectra were collected to identify the backbone amides that did not exchange in the fibril. These studies showed that the N and C termini of the peptide are accessible to the solvent in the fibril state and the backbone amides of these residues are readily exchanged with bulk deuterium. In contrast, the residues in the middle of the peptide (residues 16-36) are mostly protected, suggesting that that many of the residues in this segment of the peptide are involved in a beta structure in the fibril. Two residues, G25 and S26, exhibit readily exchangeable backbone amide protons and therefore may be located on a turn or a flexible part of the peptide. Overall, the data substantially supports current models for how the Abeta peptide folds when it engages in the amyloid fibril structure, while also addressing some discrepancies between models.