gebhart/patrepeval huggingface dataset:
Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With Polyethylated Castor Oil–Based Paclitaxel in Women With Breast Cancer (2005)

ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.
Successful treatment of collagen‐induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity (2003)

Counteracting extracellular HMGB-1 with either neutralizing antibodies or a specific HMGB-1 antagonist may offer a new method for the successful treatment of arthritis. Inflammation and tissue destruction were suppressed in CIA after HMGB-1 blockade.
Spatial and temporal control of RNA stability (2001)

Maternally encoded RNAs and proteins program the early development of all animals. A subset of the maternal transcripts is eliminated from the embryo before the midblastula transition. In certain cases, transcripts are protected from degradation in a subregion of the embryonic cytoplasm, thus resulting in transcript localization. Maternal factors are sufficient for both the degradation and protection components of transcript localization. Cis-acting elements in the RNAs convert transcripts progressively (i) from inherently stable to unstable and (ii) from uniformly degraded to locally protected. Similar mechanisms are likely to act later in development to restrict certain classes of transcripts to particular cell types within somatic cell lineages. Functions of transcript degradation and protection are discussed.
Proteome-wide detection ofphospholipid–protein interactions in mitochondria by photocrosslinking and click chemistry (2010)

Photoactivatable lipid analogues are uniquely suited for the detection of lipid-protein interactions in biological membranes. Based on photocrosslinking, new methodology has been developed for the proteome-wide detection of lipid-protein interactions. Bifunctional lipid analogues containing a tag for click chemistry in addition to the photoactivatable moiety enable the enrichment of the crosslinked proteins that is required for subsequent identification by mass spectrometry. In principle the phospholipid interaction-based membrane protein proteomics approach is applicable to any biomembrane and any lipid. Here, we review the background and the development of the new methodology. Results obtained with photocrosslinking in purified mitochondrial membranes from the yeast Saccharomyces cerevisiae are summarized and future perspectives discussed.
Nitric oxide and the respiratory system (2003)

Nitric oxide (NO) is a significant biologically active molecule; its role in controlling cellular and organ functions, especially the respiratory, cardiovascular, nervous and immune system, has been well established. In the respiratory system, this molecule is responsible for maintaining pulmonary vascular integrity. It improves arterial oxygenation, which may be associated with its action on the distribution of blood flow in the lungs. This property is the basis for i nhaled nitric oxide (INO) being employed in the treatment of high altitude pulmonary edema (HAPE), acute respiratory distress syndrome and persistent pulmonary hypertension of the newborn. The combined use of NO and oxygen has cumulative effect on the pulmonary haemodynamics and gas exchange. Soldiers of the Indian army deployed at high altitude are prone to develop acute mountain sickness and HAPE. Inhalation of NO is preferred for the treatment of these patients. Clinical application of INO has been fr equently tempered by difficulties in sa fe and accurate INO delivery. NO inhalation has a number of short -term and long-term conflicting effects, and is still at the experimental stage. The fundamental outline of a delivery system should be able to provide for safe gas delivery and accurate gas analysis or mon itoring. Clinical interest in the identification of exhaled nitric oxide (ENO) as a marker of diseases is mounting, notably with reference to inflammatory airway diseases. Further studies and standardization of ENO testing are needed to tu rn these findings into a rel iable diagnostic tool.
Identification of the transcriptional regulatory sequences of human kallikrein 2 and their use in the construction of calydon virus 764, an attenuated replication competent adenovirus for prostate cancer therapy. (1999)

Human glandular kallikrein (hK2) and prostate-specific antigen (PSA) are related members of the human kallikrein gene family. The genes for hK2 and PSA are expressed predominately in the prostate, are transcriptionally up-regulated by androgens, and share 78% homology. Previously, one functional androgen response element was identified within the proximal promoter (-324 to +33 relative to the cap site) of the hK2 gene. To detect additional upstream regulatory elements, the 12.3 kbp between the PSA gene and 5' to the hK2 gene were amplified by PCR and linked to a promoterless firefly luciferase reporter gene. Transient transfection experiments showed an androgen-dependent enhancer, located between -3.4 and -5.2 kb upstream of the transcription start site of the hK2 gene. This hK2 enhancer increased luciferase expression 100-fold in the presence of the testosterone analogue R1881. The hK2 enhancer contains an androgen response element that lost activity when mutated. The hK2 enhancer/promoter demonstrated activity in PSA(+) LNCaP cells whereas the enhancer/promoter was inactive in PSA(-) 293, A549, HBL100, HUH-7, LoVo, MCF-7, OVCAR-3, and PC-3 cells. Insertion of the hK2 enhancer/promoter into adenovirus to drive the E1A genes of adenovirus type 5 (Ad5) created an attenuated replication competent adenovirus variant Calydon virus (CV) 763, which replicates similarly to wild-type adenovirus in prostate tumor cells but is attenuated in nonprostate tumor cells. In addition, CV764, an adenovirus variant containing the previously cloned prostate-specific enhancer (to drive the Ad5 E1A genes) and the hK2 enhancer/promoter (to drive the Ad5 E1B genes) was constructed. CV764 is significantly attenuated and has a high therapeutic index with a cell specificity of 10,000:1 for PSA(+) LNCaP cells, compared to ovarian cancer OVCAR-3 cells and SK-OV-3 cells and PA-1 cells. CV764 is also highly attenuated in primary human microvascular endothelial cells.
An unattended device for sleep-related breathing disorders: validation study in suspected obstructive sleep apnoea syndrome (1996)

Portable devices for the diagnosis of obstructive sleep apnoea (OSA) are considered to be an acceptable alternative to polysomnography (PSG), but their validation is essential. The aim of our study was to validate a device specifically designed for OSA diagnosis. Twenty nine suspected OSA patients were studied with simultaneous nocturnal PSG and an unattended recording device (MicroDigitrapper-S) (M-S). The device measured body position, snoring sound, oronasal flow, thoracic and abdominal effort, heart rate and percentage arterial oxygen saturation (Sa,O2%). We compared the apnoea plus hypopnoea index (AHI) and Sa,O2% results of PSG with that of the system's automatic analysis (M-SA). We also performed a semiautomatic analysis (M-SS) with visual editing of the raw data. Results at different AHI cut-off levels were analysed to obtain an indication of accuracy in diagnosis and severity. Both M-SA and M-SS showed a sensitivity and specificity of 100% at the cut-off level of AHI > 10. When increasing the cut-off levels, M-SA sensitivity decreased (55% for AHI > 40), while specificity remained high (95%). This was improved to a clinically acceptable level of agreement by M-SS analysis (sensitivity 91% and specificity 94%). In conclusion, the MicroDigitrapper-S device showed a good sensitivity and specificity for the diagnosis of OSA. However, the device could not predict the severity of OSA precisely enough. In severe cases (apnoea plus hypopnoea index > 40), semi-automatic scoring was necessary to obtain a more accurate detection of the severity of the disease.
A physiologic function for p-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels (1998)

P-glycoprotein (MDR-1) is a well-known transporter that mediates efflux of chemotherapeutic agents from the intracellular milieu and thereby contributes to drug resistance. MDR-1 also is expressed by nonmalignant cells, including leukocytes, but physiologic functions for MDR-1 are poorly defined. Using an initial screening assay that included >100 mAbs, we observed that neutralizing mAbs MRK16, UIC2, and 4E3 against MDR-1 specifically and potently blocked basal-to-apical transendothelial migration of mononuclear phagocytes, a process that may mimic their migration into lymphatic vessels. Antagonists of MDR-1 then were used in a model of authentic lymphatic clearance. In this model, antigen-presenting dendritic cells (DC) migrate out of explants of cultured human skin and into the culture medium via dermal lymphatic vessels. DC and T cells derived from skin expressed MDR-1 on their surfaces. Addition of anti-MDR-1 mAbs MRK16, UIC2, or the MDR-1 antagonist verapamil to skin explants at the onset of culture inhibited the appearance of DC, and accompanying T cells, in the culture medium by approximately 70%. Isotype-matched control mAbs against other DC molecules including CD18, CD31, and major histocompatibility complex I did not block. In the presence of MDR-1 antagonists, epidermal DC were retained in the epidermis, in contrast to control conditions. In summary, this work identifies a physiologic function for MDR-1 during the mobilization of DC and begins to elucidate how these critical antigen-presenting cells migrate from the periphery to lymph nodes to initiate T lymphocyte-mediated immunity.
Inhibition of Tumor Growth by Ribozyme-Mediated Suppression of Aberrant Epidermal Growth Factor Receptor Gene Expression (1998)

Ribozymes targeted to aberrant EGFR mRNA can inhibit the growth of tumors formed by cells that express this mRNA.
Core‐shell type dually fluorescent polymer nanoparticles for ratiometric pH‐sensing (2008)

Abstract The synthesis and pH‐sensing properties of fluorescent polymer nanoparticles (NPs) in the 20 nm diameter range with a sensitive dye covalently attached to the particle surface and a reference dye entrapped within the particle core are presented. Fluorescein‐functionalized NPs were readily obtained by conjugation of fluorescein isothiocyanate (FITC) to amine‐coated crosslinked polystyrene‐based nanoparticles prepared by microemulsion polymerization followed by postfunctionalization. This all water‐based method gave access to stable aqueous suspensions of pH‐sensing fluorescent NPs. The encapsulation of the insensitive reference fluorescent dye (1,9‐diphenylanthracene, DPA) was then conveniently achieved by soaking leading to dual fluorescent NPs containing about 20 DPA and 55 fluorescein, as deduced from spectroscopic analyses. This core‐shell type architecture maximizes the interactions of the sensing dye with the medium while protecting the reference dye. The variations of the ratio of the fluorescence emission intensities of the sensitive dye (fluorescein) to the reference dye (DPA) with pH show that the dual fluorescent NPs act as a ratiometric pH sensor with a measuring range between pH 4 and pH 8. This pH nanosensor was found to be fast, fully reversible, and robust without any leaching of dye over a long period of time. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6206–6213, 2008
Nuclease P1 Digestion Combined with Tandem Mass Spectrometry for the Structure Determination of DNA Photoproducts (1999)

UV irradiation of oligodeoxynucleotides at 254 nm generates several different types of DNA photoproducts, such as cis-syn cyclobutane pyrimidine dimers, pyrimidine[6-4]pyrimidone photoproducts and their Dewar valence isomers, and thymine-adenine photoproducts (TA). Nuclease P1 degrades the oligodeoxynucleotide photoproducts to small photoproduct-containing trinucleotides which are more amenable to tandem mass spectrometry (MS/MS) and HPLC. Product-ion mass spectra of these digestion products give characteristic fragmentations, allowing us to identify quickly the types of photomodifications. The results also show that mass spectrometry will be a tool for studying enzyme reaction mechanisms because it can determine rapidly and with high sensitivity the structures of the products that are generated.
Tissue-Specific Cadherin CDH17 Is a Useful Marker of Gastrointestinal Adenocarcinomas With Higher Sensitivity Than CDX2 (2012)

Cadherin 17 (CDH17) is a cell adhesion molecule expressed in intestinal epithelium and transcriptionally regulated by CDX2. We compared the usefulness of CDH17 as an immunohistochemical intestinal marker to that of CDX2 in gastrointestinal and extragastrointestinal carcinomas and nonneoplastic tissues. Nonneoplastic intestinal and pancreatic duct epithelia were CDH17-positive. Most esophageal (79%), gastric (86%), and colonic (99%) adenocarcinomas were CDH17-positive/CDX2-positive, whereas 1% of colonic, 18% of esophageal, and 10% of gastric adenocarcinomas were CDH17-negative/CDX2-negative. Rare colonic, esophageal, and gastric adenocarcinomas were CDH17-positive/CDX2-negative (1%, 3%, and 4%, respectively), and none were CDH17-negative/CDX2-positive. Diffuse CDH17 was also observed in all metastatic colon carcinomas, 20% of which were only focally CDX2-positive. Of intestinal low-grade neuroendocrine tumors, 74% coexpressed CDX2 and CDH17. CDH17 was also positive in 12% of pancreatic and 24% of bronchial neuroendocrine tumors, all of which were CDX2-negative. Pancreatic adenocarcinomas and cholangiocarcinomas were more frequently CDH17-positive than CDX2-positive (50% vs 27%, 53% vs 27%). One (2%) hepatocellular carcinoma was CDH17-positive/CDX2-negative. Nine percent of non-small cell lung cancers and 7% of endometrial carcinomas were CDH17-positive, whereas 3% of lung, 5% of endometrial, 3% of ovarian, and 2% of breast carcinomas were CDX2-positive. Thus, CDH17 is slightly more sensitive than CDX2 when detecting gastrointestinal adenocarcinomas.
Interaction of the bHLH-zip domain of c-Myc with H1-type peptides. Characterization of helicity in the H1 peptides by NMR. (1994)

The carboxyl-terminal 92 residues of c-Myc-92 display site-specific DNA binding specificity for the consensus sequence 5'-CACCACGTGGTG-3' (Blackwell, T. K., Kretzner, L., Blackwood, E. M., Eisenman, R. N., and Weintraub, H. (1990) Science 250, 1149-1151). Size exclusion high pressure liquid chromatography analysis of the purified fusion protein, glutathione S-transferase-c-Myc-92, indicates that c-Myc-92 is tetrameric with a dissociation constant of < 60 nM. Helix-1 (H1) and leucine zipper peptides from the basic-helix-loop-helix-zipper domain of c-Myc and Max were assayed as potential inhibitors of c-Myc-92 DNA binding. H1 peptides with substitutions that confer greater helicity are found to inhibit c-Myc-92 DNA binding. The mechanism of inhibition involves the cooperative binding of H1 peptides with tetrameric c-Myc-92 as determined by a spectrophotometric assay employing 2,4-dinitrophenyl-H1-F8A. NMR structural characterization reveals a correlation between helicity and inhibition. In a partially hydrophobic environment, H1-Mx (from Max) is a random coil, while H1-WT, H1-F8A, and H1-F8A,S6A (from c-Myc) display differing degrees of helicity. Structure determination on the basis of nuclear Overhauser effect data indicates that the H1-F8A helix is significantly more ordered than H1-WT. Analysis on the basis of the Max x-ray structure (Ferré-D'Amaré, R., Prendergast, G. C., Ziff, E. B., and Burley, S. K. (1993) Nature 363, 38-45) suggests that H1 peptide binding to c-Myc-92 may occur through an alteration in the packing of helix-1 in c-Myc-92 or through an interaction with an exposed hydrophobic cluster of residues at each H1-H2 interface. This binding site for H1 peptides may be of significance in the interaction of c-Myc with proteins involved in transcriptional regulation.
Structure and Spectroscopy of Copper−Dioxygen Complexes (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure and Spectroscopy of Copper−Dioxygen ComplexesLiviu M. Mirica, Xavier Ottenwaelder, and T. Daniel P. StackView Author Information Department of Chemistry, Stanford University, Stanford, California 94305 Cite this: Chem. Rev. 2004, 104, 2, 1013–1046Publication Date (Web):January 29, 2004Publication History Received15 August 2003Published online29 January 2004Published inissue 1 February 2004https://pubs.acs.org/doi/10.1021/cr020632zhttps://doi.org/10.1021/cr020632zresearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views12998Altmetric-Citations1226LEARN 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 SUBJECTS:Ions,Ligands,Oxides,Peptides and proteins,Spectroscopy Get e-Alerts
Decreased Metallation and Activity in Subsets of Mutant Superoxide Dismutases Associated with Familial Amyotrophic Lateral Sclerosis (2002)

Over 90 different mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause approximately 2% of amyotrophic lateral sclerosis (ALS) cases by an unknown mechanism. We engineered 14 different human ALS-related SOD1 mutants and obtained high yields of biologically metallated proteins from an Sf21 insect cell expression system. Both the wild type and mutant "as isolated" SOD1 variants were deficient in copper and were heterogeneous by native gel electrophoresis. By contrast, although three mutant SOD1s with substitutions near the metal binding sites (H46R, G85R, and D124V) were severely deficient in both copper and zinc ions, zinc deficiency was not a consistent feature shared by the as isolated mutants. Eight mutants (A4V, L38V, G41S, G72S, D76Y, D90A, G93A, and E133 Delta) exhibited normal SOD activity over pH 5.5-10.5, per equivalent of copper, consistent with the presumption that bound copper was in the proper metal-binding site and was fully active. The H48Q variant contained a high copper content yet was 100-fold less active than the wild type enzyme and exhibited a blue shift in the visible absorbance peak of bound Cu(II), indicating rearrangement of the Cu(II) coordination geometry. Further characterization of these as-isolated SOD1 proteins may provide new insights regarding mutant SOD1 enzyme toxicity in ALS.
Effects of new antioxidant compounds PNU‐104067F and PNU‐74389G on antioxidant defense in normal and diabetic rats (2000)

Diabetes mellitus and its complications are associated with elevated oxidative stress, leading to much interest in antioxidant compounds as possible therapeutic agents. Two new classes of antioxidant compounds, the pyrrolopyrimidines and the 21-aminosteroids, are known to inhibit lipid peroxidation and other biomolecular oxidation. We hypothesized that in the presence of excess oxidants or the impaired antioxidant defense seen in diabetes mellitus, administration of antioxidants such as these may reverse the effects of diabetes on antioxidant parameters. This study measured the effects of subchronic (14 day) treatment with a pyrrolopyrimidine (PNU-104067F) or a 21-aminosteroid (PNU-74389G) in normal and diabetic Sprague-Dawley rats. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, concentrations of oxidized and reduced glutathione, and lipid peroxidation were used as measures of antioxidant defense in liver, kidney, heart, and brain tissue. In normal rats, the only effect was a 43% increase in cardiac lipid peroxidation after treatment with PNU-104067F. In diabetic rats, the only reversals of the effects of diabetes were a 30% decrease in hepatic glutathione peroxidase activity after PNU-74389G treatment and a 33% increase in cardiac glutathione disulfide concentration after PNU-104067F treatment. In contrast to these effects, increased cardiac glutathione peroxidase and catalase activities, increased brain glutathione peroxidase activity, increased hepatic lipid peroxidation, decreased hepatic glutathione content, and decreased hepatic catalase activity were seen in diabetic rats, reflecting an exacerbation of the effects of diabetes. © 2000 John Wiley & Sons, Inc. J Biochem Toxicol 14:189–194, 2000
ARP Is a Plasma Membrane-associated Ras-related GTPase with Remote Similarity to the Family of ADP-ribosylation Factors (1995)

The human and rat homologues of a novel Ras-related GTPase with unique structural features were cloned by polymerase chain reaction amplification and cDNA library screening. Their deduced amino acid sequences are highly homologous (97% identical amino acids; 88.3% identical nucleotides within the coding region) and comprise all six of the conserved motifs presumably involved in GTP binding. Because the sequences exhibit some similarity with members of the ADP-ribosylation factor (ARF) family (33% identity with ADP-ribosylation factor 1 (ARF1), 39% identity with ARF-like 3), the protein was designated ARP (ARF-related protein). In contrast to all other members of the ARF family, ARP lacks the myristoylation site at position 2 and comprises an insertion of 8 amino acids in the region between PM1 and PM2. mRNA was found in most rat tissues examined (skeletal muscle, fat, liver, kidney, spleen, testis, adrenals, ovary, thymus, intestine, and lung). Western blot analysis with antiserum against recombinant ARP showed a 25-kDa protein in membranes from rat liver, testis, and kidney. Thus, the protein appears to be post-translationally modified for membrane anchoring. Unlike ARF, the ARP immunoreactivity was detected in plasma membranes but not in cytosol of fractionated 3T3-L1 cells. Recombinant ARP exhibited specific and saturable GTP gamma S (guanosine 5'-3-O-(thio)triphosphate) binding and, unlike ARF isotypes, GTPase activity in the absence of tissue extracts or phospholipids. Thus, the structural and functional characteristics of ARP indicate that it represents a novel subtype of GTPases, presumably exerting a unique function and possibly involved in plasma membrane-related signaling events.
Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior (2006)

A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.