gebhart/patrepeval huggingface dataset:
Ceftazidime-avibactam (CTZ-AVI) as a treatment for hospitalized adult patients with complicated intra-abdominal infections (2016)

Avibactam, a novel β-lactamase inhibitor, has recently been co-formulated with ceftazidime and approved for use in patients with complicated intra-abdominal and urinary tract infections, where no better treatment alternative exists. The basis for its FDA approval has been the extensive clinical experience with ceftazidime and the demonstration in vitro and in animal models that the addition of avibactam reverses resistance to ceftazidime in extended-spectrum β-lactamase and some carbapenemase-producing Enterobacteriaceae. Early clinical data are promising, with efficacy demonstrated in patients with complicated intra-abdominal and urinary tract infections. This review will summarize the in vitro, animal and clinical data available on this agent to date.
Synapse formation and establishment of neuronal polarity by P19 embryonic carcinoma cells and embryonic stem cells (1996)

A number of different cell lines that exhibit a partial neuronal phenotype have been identified, but in many cases the full extent of their neuronal differentiation has not been directly addressed by functional studies. We have used electrophysiology and immunofluorescence to examine the formation of synapses and the development of neuronal polarity by murine embryonic stem (ES) cells and the mouse P19 embryonic carcinoma cell line. Within 2-3 weeks after induction by retinoic acid, subsets of P19 and ES cells formed excitatory synapses, mediated by glutamate receptors, or inhibitory synapses, mediated by receptors for GABA or glycine. In ES-cell cultures, both NMDA and non-NMDA receptors contributed to the excitatory postsynaptic response. Staining with antibodies to growth-associated protein-43 and microtubule-associated protein-2 revealed segregation of immunoreactivity into separate axonal and somato-dendritic compartments, respectively. Consistent with our physiological evidence for synapse formation, intense punctate staining was observed with antibodies to the synaptic vesicle proteins synapsin, SV2, and synaptophysin. These results demonstrate the in vitro acquisition by pluri-potent cell lines of neuronal polarity and functional synaptic transmission that is characteristic of CNS neurons.
Serum levels of interleukin-6 as a prognostic factor in advanced non-small cell lung cancer. (1998)

Serum levels of interleukin-6 (IL-6) were evaluated in a group of advanced non-small cell lung cancer (NSCLC) patients using an enzyme-linked immunosorbent assay. The data were related to clinical status and to cisplatin-based chemotherapy response. The mean IL-6 concentrations were higher than the controls (p<0.0001); patients with metastatic tumor had higher levels than those with undisseminated disease (p<0.006). Tumor progression was associated with an increase of IL-6 levels. Patients who responded to chemotherapy had lower serum IL-6 levels compared with unresponsive patients (p<0.0001). These data suggest that NSCLC patients with high levels of IL-6 have a worse clinical outcome and may manifest resistance to cisplatin chemotherapy.
Making Antibodies in Bacteria (2006)

Phage-Displayed Library .................................................. 169 8.3.2.4 Preparation of Electrocompetent E. coli SS320 .............. 170 8.3.2.5 E. coli Electroporation and Phage Propagation ............... 1718.3.3 Selection of Antigen-Specific Antibodies ....................................... 172 8.3.3.1 Selection against Immobilized Antigen ........................... 172 8.3.3.2 Selection against Biotinylated Antigen ............................ 173 8.3.3.3 Analysis of Binding Clones by Phage ELISA................. 1738.3.3.3.1 Direct-Binding Phage ELISA ........................ 174 8.3.3.3.2 Single-Point Competitive Phage ELISA........ 175 8.3.3.3.3 Multipoint Competitive Phage ELISA........... 1758.3.3.4 DNA Sequencing .............................................................. 176 8.3.3.5 Protein Purification........................................................... 176References.............................................................................................................. 177The bacterium Escherichia coli is a well-characterized and extremely robust host for recombinant protein expression. Among other advantages, expression in E. coli permits efficient mutagenesis and DNA manipulation, rapid establishment andFIGURE 8.1 (Caption on facing page)FabFvFcgrowth of expression cultures, and in ideal cases, high yields of purified proteins. Thus, the ability to express and purify antibody fragments from E. coli has been of great utility for both basic research into antibody structure and function and for the development of antibody reagents and therapeutics. However, because of the complex nature of the immunoglobulin molecule, the development of efficient expression protocols in bacteria faced significant challenges, which have nonetheless been gradually surmounted through the efforts of many researchers.
Currently Marketed Oral Lipid-Based Dosage Forms: Drug Products and Excipients (2007)

This chapter focuses on the commercially available lipid-based formulations for oral delivery, along with the lipid excipients in the formulations. The geographical focus is the United States, the United Kingdom, and Japan since formulation information of commercial pharmaceutical products is available for these countries (1-3), but not so readily with other locations (4). The lipid excipients employed in lipid-based oral formulations have been reviewed (5) and include oils composed of medium-chain triglycerides or long-chain triglycerides, lipid soluble solvents, and surfactants. The published information on oral formulations usually includes only the qualitative list of most excipients (1-5); thus determining the exact amounts of excipients in a particular formulation is not possible. In certain cases, more quantitative formulation information is provided, thus allowing for estimates of the amount administered of a specific excipient.
Asymmetric Synthesis Catalyzed by Chiral Ferrocenylphosphine–Transition Metal Complexes. I. Preparation of Chiral Ferrocenylphosphines (1980)

Abstract As chiral ligands for transition metal complex catalyzed asymmetric reactions, various kinds of chiral ferrocenylphosphines, which have planar chirality due to 1,2-unsymmetrically substituted ferrocene structure and also have a functional group on the side chain of the ferrocene nucleus, were prepared. (S)-N,N-dimethyl-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethylamine [(S)-(R)-PPFA], (S)-N,N-dimethyl-1-[(R)-1′,2-bis(diphenylphosphino)ferrocenyl]ethylamine [(S)-(R)-BPPFA], and their dimethylphosphino derivatives were prepared by way of lithiation of optically resolved N,N-dimethyl-1-ferrocenylethylamine. The 1-(dimethylamino)ethyl group on the ferrocenylphosphines was converted stereospecifically by nucleophilic substitution reactions into 1-methoxy-, 1-hydroxy-, 1-diphenylphosphino-, and several 1-(dialkylamino)ethyl groups. 1-Diphenylphosphino-2-(dimethylaminomethyl)ferrocene (FcPN) was optically resolved via its phosphine sulfide dibenzoyltartaric acid salt. The relationship between CD spectra of the chrial ferrocenylphosphines and the configuration of their planar chirality is discussed.
Insect silk contains both a Kunitz‐type and a unique Kazal‐type proteinase inhibitor (2001)

Insect silk is made up of structural fibrous (fibroins) and sticky (sericins) proteins, and contains a few small peptides of hitherto unknown functions. We demonstrate that two of these peptides inhibit bacterial and fungal proteinases (subtilisin, proteinase K and pronase). These 'silk proteinase inhibitors' 1 and 2 (SPI 1 and 2) are produced in the middle section of the silk-secreting glands prior to cocoon spinning and their production is controlled at transcription level. The full length cDNA of pre-SPI 1 contains 443 nucleotides and encodes a peptide of 76 amino-acid residues, of which 20 make up a signal sequence. The mature SPI 1 (6056.7 Da, 56 residues) is a typical thermostable Kunitz-type proteinase inhibitor with Arg in P1 position. The cDNA of pre-SPI 2 consists of 260 nucleotides and yields a putative secretory peptide of 58 amino-acid residues. The functional SPI 2 (3993 Da, 36 residues) is a single-domain Kazal-type proteinase inhibitor with unique structural features: free segment of the N-terminus is reduced to a single amino-acid residue, lack of CysI and CysV precludes formation of the A-ring and provides increased flexibility to the C-ring, and absence of several residues around the normal position of CysV shortens and changes the alpha helix segment of the protein. The structure reveals that the length and arrangement of the B-ring, including exposure of the P1 residue, and the position of the C-terminus relative to the B-loop, are essential for the activity of the Kazal-type inhibitors.
Characterization of clone-specific rearrangement T-cell receptor gamma- chain genes in lymphomas and leukemias by the polymerase chain reaction and DNA sequencing (1994)

The structures of rearranged gamma-chain T-cell antigen receptor (TCR) genes were analyzed in 5 cases of T-cell acute lymphoblastic leukemia (T-ALL), in 15 cases of peripheral T-cell non-Hodgkin's lymphoma (T-NHL), in 1 case with large granular CD8 lymphocytosis, 1 case with CD8 lymphocytosis after autologous bone marrow transplantation for Hodgkin's disease, and in 2 cases with nonneoplastic diseases. Rearranged V-J TCR gamma-gene segments were amplified by the polymerase chain reaction (PCR). Because most of the biopsy tissue or bone marrow samples contained significant amounts of admixed nonmalignant T-cells, direct DNA sequencing of the PCR products yielded mixed sequence data because of coamplification of clonal together with polyclonal TCR gamma V-N-J junctions. Reliable data could only be obtained by cloning the V gamma-J gamma PCR products and sequencing several (4 to 10) randomly chosen clones. In the polyclonal samples, all PCR-derived clones differed in their specific V-N-J junctions, as expected. In the two T-cell lines and in most of the T-cell malignancies, monoclonal PCR products could be identified by the demonstration of clonally restricted V-N-J junctions. In most cases, this information yielded the desired clone-specific sequence and showed a background population of polyclonal TCR gamma cells in each specimen, except for those that were obtained from the T-ALL samples, the cell lines, or the NHL samples with high tumor cell fraction. The results obtained by PCR-directed sequencing were confirmed by temperature-gradient gel electrophoresis (TGGE) that showed distinct DNA bands only with the PCR products containing predominant (ie, monoclonal) TCR gamma V-N-J junctions. By combined sequence and TGGE analysis, it was found that PCR/TGGE is able to distinguish between monoclonal and polyclonal TCR gamma-PCR products. This finding prompted us to complete the analysis of the TCR gamma locus in the samples by PCR/TGGE using primer mixes which covered all possible V gamma and J gamma recombinations. Monoclonality was shown with all mixes by PCR/TGGE in 21 of 24 (87%) of the lymphoproliferations. In summary, the present study shows that the combination of amplifying TCR gamma V-N-J junctions by PCR with the identification of clonal PCR products by TGGE and DNA sequencing is a reliable method for the characterization of clonal TCR gamma sequences.
Purification and properties of the alpha-interferon receptor of human lymphoblastoid (Namalva) cells. (1984)

The interferon receptor was solubilized from human lymphoblastoid (Namalva) cell membranes with Triton X-100. It was purified by chromatography on wheat-germ lectin-Sepharose and hydroxyapatite and by affinity chromatography on interferon-hexanoyl-Sepharose. The partially purified receptor was analyzed by gel filtration on Sepharose 6B and by sucrose gradient sedimentation in the presence of 0.1% Triton X-100. Gel filtration analysis yielded a Stokes radius of 74 A for the receptor-Triton X-100 complex. Sedimentation in sucrose gradients revealed an heterogeneous pattern of distribution with a plateau of activity between 4 and 10 S. Removal of suspected lipid material and Triton X-100 by extraction with isoamyl alcohol resulted in an accelerated rate of receptor sedimentation in a sodium dodecyl sulfate-containing sucrose gradient. Under these conditions it manifested an apparent sedimentation coefficient of 13.6 S. The dissociation constants Kd derived from Scatchard analysis of binding data with the purified receptor were in the range of 0.2-0.5 nM.
Internalization, Intracellular Trafficking, Biodistribution of Monoclonal Antibody 806: A Novel Anti-Epidermal Growth Factor Receptor Antibody (2007)

Overexpression of the epidermal growth factor receptor (EGFR) in epithelial tumors is associated with poor prognosis and is the target for a number of cancer therapeutics. Monoclonal antibody (mAb) 806 is a novel anti-EGFR antibody with significant therapeutic efficacy in tumor models when used as a single agent, and displays synergistic antitumor activity in combination with other EGFR therapeutics. Unlike other EGFR antibodies, mAb 806 is selective for tumor cells and does not bind to normal tissue, making it an ideal candidate for generation of radioisotope or toxin conjugates. Ideally, antibodies suited to these therapeutic applications must bind to and actively internalize their cognate receptor. We investigated the intracellular trafficking of fluorescently tagged mAb 806 in live cells and analyzed its biodistribution in a tumor xenografted nude mouse model. Following binding to EGFR, mAb 806 was internalized through dynamin-dependent, clathrin-mediated endocytosis. Internalized mAb 806 localized to early endosomes and subsequently trafficked to and accumulation in lysosomal compartments. Furthermore, biodistribution analysis in nude mice showed specific uptake and retention of radiolabeled mAb 806 to human tumor xenografts. These results highlight the potential use of mAb 806 for generation of conjugates suitable for diagnostic and therapeutic use in patients with EGFR-positive malignancies.
Buspirone in Levodopa-Induced Dyskinesias (1994)

We made a double-blind, crossover comparison of buspirone (10 mg orally, twice a day) and placebo in 10 patients with Parkinson's disease and levodopa-induced dyskinesias. The duration of the study was 3 weeks, for both buspirone and for placebo treatment. Chronic therapies remained unchanged. The extrapyramidal symptoms, dyskinesias, and anxious/depressive symptoms were evaluated at the beginning of the study and after the buspirone and placebo treatments. Seven patients concluded the trial. The extrapyramidal symptoms, evaluated in both the "off" and "on" states during an oral L-Dopa test, did not show any worsening during the trial. Buspirone significantly lessened the severity of levodopa-induced dyskinesias in five of the seven patients, whereas it proved ineffective in the two patients with the mildest dyskinesias. There were no changes in the mild anxious and depressive symptoms at any time during the study. The activities of buspirone on the serotonin and dopamine systems might have led to the antidyskinetic effect we observed. At daily dosages of 20 mg, buspirone might prove effective in reducing levodopa-induced dyskinesias without worsening of parkinsonism.
Parametric array in air: Distortion reduction by preprocessing (1998)

In a parametric array, highly directional low-frequency sound is generated by the self-demodulation of an intense, amplitude-modulated high-frequency sound beam as a result of nonlinear propagation effects. The term ‘‘audio spotlight’’ was introduced by Yoneyama et al. [J. Acoust. Soc. Am. 73, 1532 (1983)] for a parametric array in air used to generate directional audio frequency sound with an ultrasonic primary beam. Berktay’s far-field solution [Berktay, J. Sound Vib. 2, 435 (1965)] predicts a demodulated secondary waveform along the axis of the beam that is proportional to the second time derivative of the square of the modulation envelope. The secondary wave is therefore generated with high levels of harmonic distortion, even at moderate modulation indexes [Blackstock, J. Acoust. Soc. Am. 102, 3106(A) (1997)]. Integrating the modulation signal twice and taking the square root removes this distortion; however, the resulting reduction in distortion due to taking the square root is severely limited by the bandwidth of the primary beam transducer. Here, the characteristics of the transducer are taken into account in developing an appropriate predistortion scheme to achieve high quality reproduction. Relationships between distortion, modulation index, secondary bandwidth, and secondary sound-pressure level are also discussed, and results of simulations are presented. [Work supported in part by ARL:UT IR&amp;D.]
The HSP90 inhibitor ganetespib has chemosensitizer and radiosensitizer activity in colorectal cancer (2014)

The integration of targeted agents to standard cytotoxic regimens has improved outcomes for patients with colorectal cancer (CRC) over recent years; however this malignancy remains the second leading cause of cancer mortality in industrialized countries. Small molecule inhibitors of heat shock protein 90 (HSP90) are one of the most actively pursued classes of compounds for the development of new cancer therapies. Here we evaluated the activity of ganetespib, a second-generation HSP90 inhibitor, in models of CRC. Ganetespib reduced cell viability in a panel of CRC cell lines in vitro with low nanomolar potency. Mechanistically, drug treatment exerted concomitant effects on multiple oncogenic signaling pathways, cell cycle regulation, and DNA damage repair capacity to promote apoptosis. Combinations of ganetespib and low-dose ionizing radiation enhanced the radiosensitivity of HCT 116 cells and resulted in superior cytotoxic activity over either treatment alone. In vivo, the single-agent activity of ganetespib was relatively modest, suppressing HCT 116 xenograft tumor growth by approximately half. However, ganetespib significantly potentiated the antitumor efficacy of the 5-Fluorouracil (5-FU) prodrug capecitabine in HCT 116 xenografts, causing tumor regressions in a model that is intrinsically resistant to fluoropyrimidine therapy. This demonstration of combinatorial benefit afforded by an HSP90 inhibitor to a standard CRC adjuvant regimen provides an attractive new framework for the potential application of ganetespib as an investigational agent in this disease.
Circulating microRNAs in breast cancer and healthy subjects (2009)

1) RNA species can be detected in archived serum; 2) miR-155 may be differentially expressed in the serum of women with hormone sensitive compared to women with hormone insensitive breast cancer. Screening serum for miRNAs that predict the presence of breast cancer is feasible, and may be useful for breast cancer detection.
Imatinib in Pulmonary Arterial Hypertension Patients with Inadequate Response to Established Therapy (2010)

These data from a Phase II study are consistent with imatinib being well tolerated in patients with PAH, and provide proof of concept for further studies evaluating its safety, tolerability, and efficacy in PAH. Clinical trial registered with www.clinicaltrials.gov (NCT00477269).
Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda (2003)

Mal de Meleda is an autosomal recessive inflammatory and keratotic palmoplantar skin disorder due to mutations in the ARS B gene, encoding for SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1). SLURP-1 belongs to the Ly-6/uPAR superfamily of receptor and secreted proteins, which participate in signal transduction, immune cell activation or cellular adhesion. The high degree of structural similarity between SLURP-1 and the three fingers motif of snake neurotoxins and Lynx1 suggests that this protein interacts with the neuronal acetylcholine receptors. We found that SLURP-1 potentiates the human alpha 7 nicotinic acetylcholine receptors that are present in keratinocytes. These results identify SLURP-1 as a secreted epidermal neuromodulator which is likely to be essential for both epidermal homeostasis and inhibition of TNF-alpha release by macrophages during wound healing. This explains both the hyperproliferative as well as the inflammatory clinical phenotype of Mal de Meleda.
cDNA sequence of a new chicken embryonic rho-globin. (1981)

In order to use specific DNA probes for the study of developmentally regulated gene expression, we have prepared cDNA clones corresponding to chicken embryonic globins by inserting cDNA.mRNA hybrids into the Pst I site of the plasmid pBR322 by using poly(dG) and poly(dC) linkers. The nucleotide sequence of the insert of one clone, representing a nearly full-length copy of an embryonic beta-like globin cDNA, has been determined. The amino acid sequence of the globin encoded by this insert is identical to the sequence of embryonic rho-globin, except for four amino acid residues near the carboxy terminus. Comparison of mRNA sequences of the embryonic and adult chicken beta-globins indicates the presence of extensive deletions in the 3' untranslated region of the embryonic gene.
Molecular Cloning of a Novel Human CC Chemokine Secondary Lymphoid-Tissue Chemokine That Is a Potent Chemoattractant for Lymphocytes and Mapped to Chromosome 9p13 (1997)

By searching the Expressed Sequence Tag (EST) data base, we identified partial cDNA sequences potentially encoding a novel human CC chemokine. We determined the entire cDNA sequence which encodes a highly basic polypeptide of 134 amino acids total with a putative signal peptide of 23 amino acids. The predicted mature protein of 111 amino acids has the four canonical cysteine residues and shows 21-33% identity to other human CC chemokines, but has a unique carboxyl-terminal extension of about 30 amino acids which contains two extra cysteine residues. The mRNA was expressed strongly in tissues such as the lymph nodes, Appendix, and spleen. The recombinant protein, which was produced by the baculovirus system and purified to homogeneity, was a highly efficient chemoattractant for certain human T cell lines and a highly potent one for freshly isolated peripheral blood lymphocytes and cultured normal T cells expanded by phytohemagglutinin and interleukin 2. Unlike most other CC chemokines, however, this novel chemokine was not chemotactic for monocytes or neutrophils, suggesting that it is specific for lymphocytes. From these results, we designated this novel CC chemokine as SLC from secondary lymphoid-tissue chemokine. SLC fused with the secreted form of alkaline phosphatase (SLC-SEAP) was used to characterize the SLC receptor. Binding of SLC-SEAP to freshly isolated lymphocytes was blocked by SLC (IC50, 0.12 nM) but not by any other CC chemokine so far tested, suggesting that resting lymphocytes express a class of receptors highly specific for SLC. By using somatic cell hybrids, radiation hybrids, and selected yeast and bacterial artificial chromosome clones, we mapped the SLC gene (SCYA21) at chromosome 9p13 and between chromosomal markers, D9S1978(WI-8765) and AFM326vd1, where the gene for another novel CC chemokine termed ELC from EBI1-ligand chemokine (SCYA19) also exists. Collectively, SLC is a novel CC chemokine specific for lymphocytes and, together with ELC, constitutes a new group of chemokines localized at chromosome 9p13.