gebhart/patrepeval huggingface dataset:
Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes (2002)

Besides cytotoxicity, taxanes induce other biological effects, especially in the immune system. Taxanes have demonstrated immunostimulatory effects against neoplasms, supporting the idea that these agents suppress cancer through several mechanisms and not solely through inhibiting cell division. The purpose of the present study was to evaluate the effect of taxanes (paclitaxel and docetaxel) and investigate their ability in alterating important immunological parameters in breast cancer patients. Thirty women with advanced breast cancer undergoing chemotherapy were randomly assigned into two groups treated with either single agent Paclitaxel or Docetaxel. Sera from patients before the first and after the last treatment cycle and from normal donors were assayed by ELISA for IL-2, IL-1beta, IFN-gamma, GM-CSF, IL-6, TNF-alpha, and PGE2 levels. In these same blood samples, NK and LAK cell activity was tested in the total PBMC population against NK-sensitive K562 tumour targets, respectively, and autologous mixed lymphocyte reaction was tested by (3)H-thymidine proliferation assays. All patients in both groups responded to therapy. Significant differences were observed in the following immune parameters between the control group of healthy blood donors and the pretreatment values of both taxane groups; IL-2, GM-CSF, IFN-gamma levels and NK and LAK cell cytotoxicity were depressed, whereas TNF-alpha and IL-6 levels were raised in breast cancer patients before treatment compared to controls. There were no significant differences between the two treatment groups regarding any of the parameters studied. Both drugs led to increases in MLR values, NK and LAK cell cytotoxicity, and IL-6, GM-CSF, IFN-gamma levels, and decreases for IL-1, TNF, and PGE2 levels. The percentage of these differences was greater for docetaxel in comparison to paclitaxel (P<0.0001). More specifically, docetaxel demonstrated a more pronounced effect on enhancing MLR, NK, LAK activity and IFN-gamma, IL-2, IL-6, and GM-CSF levels, as well as caused more potent reduction in IL-1 and TNF-alpha levels when compared to paclitaxel. The present study indicates that patients responded to treatment of advanced breast cancer with single-agent paclitaxel or docetaxel leads to an increase in serum IFN-gamma, IL-2, IL-6, GM-CSF cytokine levels and enhancement of PBMC NK and LAK cell activity, while they both lead to a decrease of acute phase serum cytokine levels of IL-1 and TNF-alpha. Moreover, the effects of docetaxel are in all the above parameters more pronounced than those of paclitaxel.
Assembly and Regulation of the CD40 Receptor Complex in Human B Cells (1997)

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. Studies with human B cells show that the binding of CD154 (gp39, CD40L) to CD40 recruits TNF receptor- associated factor 2 (TRAF2) and TRAF3 to the receptor complex, induces the downregulation of the nonreceptor-associated TRAFs in the cell and induces an increased expression of Fas on the cell surface. Combined signaling through the interluekin 4 receptor and CD40 induces an increased expression of Fas with a commensurate increase in the level of TRAF2, but not TRAF3, that is recruited to the receptor complex. In contrast, engagement of the membrane immunoglobulin and CD40 limits Fas upregulation and reduces the recruitment of TRAF2, relative to TRAF3, to the CD40 receptor complex. These studies show that the TRAF composition of the CD40 receptor complex can be altered by signals that influence B cell differentiation.
Studies on Soil Acrasieae: 1. Distribution of species of Dictyostelium in soils of Great Britain and the effect of bacteria on their development (1947)

SUMMARY: A method of isolating species of Dictyosteliaceae from soil and other substrates is described. Of ninety-three different strains of bacteria tested as food for Dictyostelium giganteum and D. mucoroides, some were readily or slowly but completely eaten, others were partly eaten and the rest were inedible. No correlation between the edibility of the bacteria and the formation of normal fruiting bodies could be found. More Gram-negative than Gram-positive strains were edible, and non-pigmented bacteria proved more suitable than pigmented bacteria for the normal development of Dictyostelium spp. Values of pH between 4·1 and 8·9 had no effect on the abundance or on the types of fruiting bodies produced in either D. giganteum or D. mucoroides when suitable strains of bacteria were supplied as food to the myxamoebae on non-nutrient agar. The maximum dimensions and the form of sorocarps and occasionally the colour of the sori were influenced by the type of bacteria used as food supplies. The influence of the bacterial food supply on the classification of Acrasieae is discussed and one new species (D. giganteum) is described. Species of Dictyostelium are frequently present in arable soils in Great Britain. The common occurrence of Dictyostelium spp. in soils, which have been unmanured or treated with artificial fertilizers only for 100 years or more, disproves the belief that Dictyostelium spp. are dung organisms.
Electrogenerated Chemiluminescence of trans‐Stilbene Derivatives (1981)

Fluorescence maxima, fluorescence quantum yields, electrode potentials, and electrogenerated chemiluminescence (ecl) of 16 t‐stilbene derivatives such as substituted indenes and dihydronaphthalenes (DHNP) are reported. Both indenes and DHNP's were found to have greatly enhanced fluorescence quantum yields in comparison to t‐stilbene. Twelve single systems of 16 compounds gave ecl mostly attributed to the singlet excited state. With tri‐p‐tolylamine (TPTA) added as a source of cation radical, most of the systems produced ecl having shorter wavelength emission corresponding to the singlet excited state of the t‐stilbene derivatives and longer wavelength emission attributed to the exciplex. The ecl intensities with respect to the possible applications are discussed.
Nonlinear acoustical response of coated microbubbles in diagnostic ultrasound (1994)

Microbubbles coated with a thin biodegradable polymer shell are used in SHU 563 A, a new kind of ultrasound contrast medium. These particles are durable linear scatterers for prolonged times at low acoustic pressure amplitudes. They will immediately rupture at higher amplitudes within the range of diagnostic ultrasound causing a transient nonlinear response termed “Acoustically Stimulated Acoustic Emission”. Characteristics of this effect and some potential applications in novel and extraordinary sensitive conventional and Harmonic Imaging modes are discussed
Dry HCl in Parallel Synthesis of Fused Pyrimidin-4-ones (2008)

The parallel solution-phase synthesis of substituted thieno[2,3- d]pyrimidin-6-carboxylic acids has been accomplished. This strategy relies on a cyclization of 2-aminothiophen-3,5-dicarboxylates with a set of nitriles, followed by hydrolysis to construct the library of corresponding acids. The convenient procedure for use and dosage of dry HCl for the reaction was elaborated and adapted for semiautomated solution-phase parallel synthesis. With the use of another (hetero)aromatic ortho-aminocarboxylate, mini-libraries of diverse fused pyrimidin-4-ones were synthesized. The scope and limitations of the approach are discussed.
Interpolating subroutine for high power system design (1980)

The Aero Propulsion Laboratory is currently developing a computer-aided design program for high power airborne systems. An important part of this design program will be the feasibility study which was to be based on summary algorithms. These algorithms were to relate the weight and volume of each system component to the contributing operating parameters. This study first centers on the requirements for an interpolation scheme to form the summary algorithms. The scheme will need to work in at least four dimensions and produce accurate results over wide ranges. The advantages of the two possible interpolation approaches (algorithm development and direct interpolation) are described. The results of this comparison show clear advantages in the direct interpolation approach using stored data. The remainder of this study is a description and evaluation of the subroutine which was developed, INTERP. It has the flexibility to interpolate a data array with two or more independent variables and will output the values of any number of dependent variables. The routine also compensates for missing values in the known data array and issues an error message to the user when a test point beyond the data range is input. (Author)
Isolation and properties of 7.BETA.-(4-carboxybutanamido)cephalosporanic acid acylase-producing bacteria. (1981)

A search was undertaken for microorganisms that produce an enzyme capable of deacylating 7β-(4-carboxybutanamido)cephalosporanic acid (glutaryl 7-ACA, GL-7-ACA) to 7-aminocephalosporanic acid. Pseudomonas putida ATCC 950 was selected from our stock cultures, and Pseudomonas SY-77-1 was isolated from soil. Adding glutaric acid to the growth media enhanced the production of GL-7-ACA acylase by Pseudomonas SY-77-1. A β-lactamase-deficient mutant, Pseudomonas NS-2, was derived from Pseudomonas SY-77-1 treated with a mutagen. The cell suspension of Pseudomonas NS-2 specifically hydrolyzed cephalosporin compounds having aliphatic dicarboxylic acid in the acyl side chain.
Mannosylated and Histidylated LPR Technology for Vaccination with Tumor Antigen mRNA (2012)

mRNA-based vaccines are currently being developed for treating various diseases including cancers. For this purpose, synthetic or in vitro transcribed (IVT) mRNA encoding tumor antigen offers several advantages over plasmid DNA encoding tumor antigen including better delivery and security. In this chapter, we report the preparation of mannosylated mRNA nanoparticles termed mannosylated lipopolyplexes or Man-LPR loaded with mRNA encoding a melanoma antigen. This formulation enhances the transfection of dendritic cells (DCs) in vivo and the anti-B16F10 melanoma vaccination in mice. The mRNA is formulated with histidylated liposomes and a histidylated polymer. Those pH-sensitive vectors promote membrane destabilization in endosomes upon the protonation of their histidine groups, allowing nucleic acid delivery in the cytosol. To favor DCs targeting via the mannose receptor, a mannose lipid is incorporated in the liposomes. Here, we provide protocols for the preparation of mannosylated liposomes, the synthesis of mRNA, mice immunization based on systemic injection, measurement of the cellular immune response and determination of the number of transfected splenic DC.
A Novel Member of the Leukocyte Receptor Complex Regulates Osteoclast Differentiation (2002)

Osteoclasts (OCs) are multinucleated cells that resorb bone and are essential for bone homeostasis. They develop from hematopoietic cells of the myelomonocytic lineage. OC formation requires cell-to-cell interactions with osteoblasts and can be achieved by coculturing bone marrow precursor cells with osteoblasts/stromal cells. Two of the key factors mediating the osteoblast-induced osteoclastogenesis are macrophage-colony stimulating factor (M-CSF) and the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE) that are produced by osteoblasts/stromal cells in response to various bone resorbing hormones. In addition, other factors produced by osteoblasts/stromal cells further influence osteoclastogenesis. Here we report the identification and characterization of OC-associated receptor (OSCAR), a novel member of the leukocyte receptor complex (LRC)-encoded family expressed specifically in OCs. Genes in the LRC produce immunoglobulin (Ig)-like surface receptors and play critical roles in the regulation of both innate and adaptive immune responses. Different from the previously characterized members of the LRC complex, OSCAR expression is detected specifically in preosteoclasts or mature OCs. Its putative-ligand (OSCAR-L) is expressed primarily in osteoblasts/stromal cells. Moreover, addition of a soluble form of OSCAR in coculture with osteoblasts inhibits the formation of OCs from bone marrow precursor cells in the presence of bone-resorbing factors, indicating that OSCAR may be an important bone-specific regulator of OC differentiation. In addition, this study suggests that LRC-encoded genes may have evolved to regulate the physiology of cells beyond those of the immune system.
Cloning the vaccinia virus genome as a bacterial artificial chromosome in Escherichia coli and recovery of infectious virus in mammalian cells (2002)

The ability to manipulate the vaccinia virus (VAC) genome, as a plasmid in bacteria, would greatly facilitate genetic studies and provide a powerful alternative method of making recombinant viruses. VAC, like other poxviruses, has a linear, double-stranded DNA genome with covalently closed hairpin ends that are resolved from transient head-to-head and tail-to-tail concatemers during replication in the cytoplasm of infected cells. Our strategy to construct a nearly 200,000-bp VAC-bacterial artificial chromosome (BAC) was based on circularization of head-to-tail concatemers of VAC DNA. Cells were infected with a recombinant VAC containing inserted sequences for plasmid replication and maintenance in Escherichia coli; DNA concatemer resolution was inhibited leading to formation and accumulation of head-to-tail concatemers, in addition to the usual head-to-head and tail-to-tail forms; the concatemers were circularized by homologous or Cre-loxP-mediated recombination; and E. coli were transformed with DNA from the infected cell lysates. Stable plasmids containing the entire VAC genome, with an intact concatemer junction sequence, were identified. Rescue of infectious VAC was consistently achieved by transfecting the VAC-BAC plasmids into mammalian cells that were infected with a helper nonreplicating fowlpox virus.
Dissociation of the Complex between the Neuroendocrine Chaperone 7B2 and Prohormone Convertase PC2 is not Associated with proPC2 Maturation (1996)

7B2 is a highly conserved neuroendocrine protein that is associated with the proform of the prohormone convertase PC2 in the early stages of the secretory pathway in intermediate pituitary cells of Xenopus laevis. Subsequent processing of 7B2 and dissociation of the 7B2/proPC2 complex is thought to be associated with the conversion of proPC2 to the mature enzyme. Here, we report that, in both Xenopus and mouse intermediate cells, proPC2 maturation does not take place when the proenzyme is associated with the 7B2 precursor and that, in contrast to the previous notion, dissociation of the complex between proPC2 and the N-terminal 7B2 fragment precedes, and is thus not directly linked to, proPC2 maturation. In vitro, conversion of newly synthesized proPC2 was efficiently blocked by recombinant 7B2 and studies with truncation mutants indicated that a short segment in the C-terminal region of 7B2 is necessary and sufficient for this inhibitory effect. Our results indicate that, after 7B2 precursor processing and dissociation of the N-terminal fragment, the C-terminal fragment of 7B2 may remain associated with proPC2, thereby preventing autocatalytic conversion of the proenzyme until the appropriate site for activation in the secretory pathway is reached.
Biochemical Evidence That a D-Loop Is Part of a Four-Stranded PNA−DNA Bundle. Nickel-Mediated Cleavage of Duplex DNA by a Gly-Gly-His Bis-PNA (1996)

A peptide nucleic acid (PNA) with improved strand-displacement capability and a site-specific DNA cleavage function is a novel reagent for probing the structure of PNA-DNA complexes in solution. By linking two PNAs in tandem with an aliphatic linker, the bis-PNA forms a bis-PNA-DNA triple-stranded complex having a higher stability to thermal denaturation than conventional monomeric PNAs. When a Gly-Gly-His tripeptide is placed on either the Watson-Crick or Hoogsteen bis-PNA strand, nickel-mediated cleavage is detected at specific sites on the displaced and hybridized DNA strands. Because the displaced strand is cleaved when GGH is placed on either PNA strand, the D-loop must be close to the backbone of the bis-PNA-DNA triplex. Furthermore, the pattern of cleavage on the displaced strand suggests the nickel-tripeptide complex lies in a groove formed by the displaced DNA strand and both PNA strands. These observations suggest that the D-loop is a part of a four-stranded bis-PNA-DNA2 bundle.
Pattern and Kinetics of Cytokine Production Following Administration of Phosphorothioate Oligonucleotides in Mice (1997)

Phosphorothioate oligonucleotides with certain sequences or structure motifs can stimulate the immune system. We administered to mice a 27-mer phosphorothioate oligonucleotide (sequence 5'-TCG TCG CTG TCT CCG CTT CTT CTT GCC-3'), which has previously been shown to cause splenomegaly and hypergamma-globulinemia on in vivo administration in mice, and studied the pattern and kinetics of cytokine production at both the splenic mRNA and serum protein levels. Following i.p. administration of 50 mg/kg of oligonucleotide, significant increases in the splenic mRNA levels of IL-6, IL-12p40, IL-1 beta, and IL-1Ra and serum levels of IL-6, IL-12, MIP-1 beta, and MCP-1 were observed. In contrast, no significant differences in splenic mRNA levels of IL-2, IL-4, IL-5, IL-9, IL-13, IL-15, IFN-gamma, or MIF or serum levels of IL-2, IL-4, IL-5, IL-10, IFN-gamma, or GM-CSF were detected. The induction of IL-12 secretion was dependent on the sequence and dose of the oligonucleotides. One oligonucleotide (sequence 5'-GAG AAC GCT CGA CCT TCG AT-3') induced a high level of IL-12 secretion even at 5 mg/kg, whereas another oligonucleotide (sequence 5'-CTC TGC CAC CCA TCT CTC TCC TTC T-3') did not induce significant IL-12 secretion even at 50 mg/kg. IL-12 secretion induced by various doses of oligonucleotide has the same kinetics but differs in magnitude. These studies show a distinct pattern and kinetics of cytokine production following oligonucleotide administration and further demonstrate that cytokine induction is not a general property of phosphorothioate oligonucleotides but is dependent on the sequence and dose of the oligonucleotides.
The status of platinum anticancer drugs in the clinic and in clinical trials (2010)

Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin and ProLindac). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade.
Detection of an equilibrium intermediate in the folding of a monomeric insulin analog (1992)

To determine the conformational properties of the C-terminal region of the insulin B-chain relative to the helical core of the molecule, we have investigated the fluorescence properties of an insulin analog in which amino acids B28 and B29 have been substituted with a tryptophan and proline residue respectively, ([WB28,PB29]insulin). The biological properties and far-UV circular dichroism (CD) spectrum of the molecule indicate that the conformation is similar to that of native human insulin. Guanidine hydrochloride (GdnHCl)-induced equilibrium denaturation of the analog as monitored by CD intensity at 224 nm indicates a single cooperative transition with a midpoint of 4.9 M GdnHCl. In contrast, when the equilibrium denaturation is observed by steady-state fluorescence emission intensity at 350 nm, two distinct transitions are observed. The first transition accounts for 60% of the observed signal and has a midpoint of 1.5 M GdnHCl. The second transition roughly parallels that observed by CD measurements with an approximate midpoint of 4.5 M GdnHCl. The near-UV CD spectrum, size-exclusion, and ultracentrifugation properties of [WB28,PB29]insulin indicate that this analog does not self-associate in a concentration-dependent manner as does human insulin. Thus, the observed fluorescence changes must be due to specific conformational transitions which occur upon unfolding of the insulin monomer with the product of the first transition representing a stable folding intermediate of this molecule.
Functional Coupling between Sulfonylurea Receptor Type 1 and a Nonselective Cation Channel in Reactive Astrocytes from Adult Rat Brain (2003)

We previously identified a novel, nonselective cation channel in native reactive (type R1) astrocytes (NR1As) from injured rat brain that is regulated by cytoplasmic Ca2+ and ATP (NC(Ca-ATP)) and exhibits sensitivity to block by adenine nucleotides similar to that of sulfonylurea receptor type 1 (SUR1). Here we show that SUR1 is involved in regulation of this channel. NR1As within the site of injury and after isolation exhibited specific binding of FITC-tagged glibenclamide and were immunolabeled with anti-SUR1 antibody, but not with anti-SUR2, anti-Kir6.1 or anti-Kir6.2 antibodies, indicating absence of ATP-sensitive K+ (KATP) channels. RT-PCR confirmed transcription of mRNA for SUR1 but not SUR2. Several properties previously associated exclusively with SUR1-regulated KATP channels were observed in patch-clamp experiments using Cs+ as the charge carrier: (1) the sulfonylureas, glibenclamide and tolbutamide, inhibited NCCa-ATP channels with EC50 values of 48 nm and 16.1 microm, respectively; (2) inhibition by sulfonylureas was lost after exposure of the intracellular face to trypsin or anti-SUR1 antibody; (3) channel inhibition was caused by a change in kinetics of channel closing, with no change in channel amplitude or open-channel dwell times; and (4) the SUR activator ("KATP channel opener"), diazoxide, activated the NCCa-ATP channel, whereas pinacidil and cromakalin did not. Also, glibenclamide prevented cell blebbing after ATP depletion, whereas blebbing was produced by exposure to diazoxide. Our data indicate that SUR1 is functionally coupled to the pore-forming portion of the NC(Ca-ATP) channel, providing the first demonstration of promiscuity of SUR1 outside of the K+ inward rectifier family of channels.
Increased Circulating Levels of Interleukin-1 Receptor Antagonist in Patients with Inflammatory Bowel Disease. (1998)

Plasma levels of interleukin-1 receptor antagonist (IL-1ra), a potent inhibitor of IL-1, were measured in patients with inflammatory bowel disease. Plasma IL-1 ra levels in patients with active ulcerative colitis and Crohn's disease were higher than in normal controls. No significant difference was noted in plasma IL-1 ra concentrations between active ulcerative colitis and Crohn's disease patients. The levels in patients with inactive disease were lower than in active patients, but were higher than in normal controls. Plasma IL-1ra levels correlated significantly with clinical disease activity and laboratory parameters such as C-reactive protein or leukocyte count. In conclusion, circulating IL-1ra in patients with inflammatory bowel disease may be a useful marker of disease activity.