gebhart/patrepeval huggingface dataset:
Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury (2008)

Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)
Development of Novel Yeast Cell Surface Display System for Homo-oligomeric Protein by Coexpression of Native and Anchored Subunits (2006)

Streptavidin derived from Streptomyces avidinii was displayed on the cell surface of the yeast Saccharomyces cerevisiae by cell-surface engineering using two types of plasmid for the expression of a native subunit and an anchored subunit fused with the C-terminus of 318 amino acids of Flo1p containing a glycosylphosphatidylinositol anchor attachment signal. The displayed streptavidin had the binding ability for biotinylated compounds. This was confirmed by fluorescence microscopy after the adsorption of yeast cells displaying streptavidin and biotinylated fluorescein isothiocyanate. On the other hand, streptavidin produced by cells harboring only the plasmid for the expression of the anchored subunit showed a very low binding activity for biotinylated compounds. Cells displaying streptavidin may constitute novel whole-cell affinity adsorbents widely used for immunoassay and biosensing. This coexpression method will ensure that proteins, such as homo- and hetero-oligomeric proteins, are displayed on the cell surface in an active form.
Prevention of graft-versus-host disease by anti–IL-7Rα antibody (2007)

Graft-versus-host disease (GVHD) continues to be a serious complication that limits the success of allogeneic bone marrow transplantation (BMT). Using IL-7-deficient murine models, we have previously shown that IL-7 is necessary for the pathogenesis of GVHD. In the present study, we determined whether GVHD could be prevented by antibody-mediated blockade of IL-7 receptor alpha (IL-7Ralpha) signaling. C57/BL6 (H2K(b)) recipient mice were lethally irradiated and underwent cotransplantation with T-cell-depleted (TCD) BM and lymph node (LN) cells from allogeneic BALB/c (H2K(d)) donor mice. Following transplantation, the allogeneic BMT recipients were injected weekly with either anti-IL-7Ralpha antibody (100 mug per mouse per week) or PBS for 4 weeks. Anti-IL-7Ralpha antibody treatment significantly decreased GVHD-related morbidity and mortality compared with placebo (30% to 80%). IL-7Ralpha blockade resulted in the reduction of donor CD4(+) or CD8(+) T cells in the periphery by day 30 after transplantation. Paradoxically, the inhibition of GVHD by anti-IL-7Ralpha antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti-IL-7Ralpha antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T-cell reconstitution.
Efficacy of a recombinant equine influenza vaccine against challenge with an American lineage H3N8 influenza virus responsible for the 2003 outbreak in the United Kingdom (2005)

Fifteen influenza-naive Welsh mountain ponies were randomly assigned to three groups of five. A single dose of a recombinant ALVAC vaccine was administered intramuscularly to five of the ponies, two doses, administered five weeks apart, were administered to five, and the other five served as unvaccinated, challenge controls. Two weeks after the completion of the vaccination programme, the ponies were all challenged by exposure to an aerosol of influenza virus A/eq/Newmarket/5/03. Their clinical signs were scored daily for 14 days according to a standardised scoring protocol, and nasal swabs were taken daily for 10 days to monitor the excretion of virus. The challenge produced severe clinical signs of influenza (fever, coughing, nasal discharge and dyspnoea) in all five control ponies, but the vaccinated ponies developed only mild disease, consisting of a serous nasal discharge lasting for only one day. The excretion of virus was almost completely suppressed in the vaccinated ponies, but the control ponies shed the virus for up to seven days after the challenge.
Reflex Pharyngeal Dilator Muscle Activation by Stimuli of Negative Airway Pressure in Awake Man (1993)

This paper summarizes evidence for reflex genioglossus muscle activation by stimuli of negative airway pressure in normal, awake human subjects. Stimuli of negative airway pressure (range -5 to -35 cm H2O) caused activation of the genioglossus muscle. The larger values of negative pressure gave larger responses. Response latencies (median = 34 milliseconds) were much faster than the time for voluntary muscle activation (median = 184 milliseconds), suggesting that the responses were reflex in origin. The reflex nature of the responses was confirmed by studies with local anesthetics. The trigeminal, superior laryngeal and the glossopharyngeal nerves all mediated a component of the responses observed from the upper airway.
Tetracycline Repressor, tetR, rather than the tetR–Mammalian Cell Transcription Factor Fusion Derivatives, Regulates Inducible Gene Expression in Mammalian Cells (1998)

This article describes the first (to our knowledge) tetracycline-inducible regulatory system that demonstrates that the tetracycline repressor (tetR) alone, rather than tetR-mammalian cell transcription factor fusion derivatives, can function as a potent trans-modulator to regulate gene expression in mammalian cells. With proper positioning of tetracycline operators downstream of the TATA element and of human epidermal growth factor (hEGF) as a reporter, we show that gene expression from the tetracycline operator-bearing hCMV major immediate-early enhancer-promoter (pcmvtetO) can be regulated by tetR over three orders of magnitude in response to tetracycline when (1) the reporter was cotransfected with tetR-expressing plasmid in transient expression assays, and (2) the reporter unit was stably integrated into the chromosome of a tetR-expressing cell line. This level of tetR-mediated inducible gene regulation is significantly higher than that of other repression-based mammalian cell transcription switch systems. In an in vivo porcine wound model, close to 60-fold tetR-mediated regulatory effects were detected and it was reversed when tetracycline was administered. Collectively, this study provides a direct implementation of this tetracycline-inducible regulatory switch for controlling gene expression in vitro, in vivo, and in gene therapy.
Activation of Human Platelets by Misfolded Proteins (2007)

Protein misfolding resulting in the appearance of amyloid induces platelet aggregation. Amyloid activates platelets through 2 pathways: one is through CD36, p38(MAPK), thromboxane A2-mediated induction of aggregation; the other is through glycoprotein Ib alpha-mediated aggregation and agglutination. The platelet stimulating properties of amyloid might explain the enhanced platelet activation observed in many diseases accompanied by the appearance of misfolded proteins with amyloid.
Purification, Properties, and Feedback Control of l-Threonine Dehydratase from Spinach (1970)

Abstract Biosynthetic l-threonine dehydratase (l-threonine hydrolyase, deaminating, EC 4.2.1.16) has been purified about 2500-fold from extracts of spinach leaves by ammonium sulfate fractionation, controlled heat treatment, and chromatography on triethylaminoethyl cellulose and hydroxylapatite. The feedback control and other properties of the purified enzyme are essentially the same as that of the native enzyme. Although the enzyme is active on both l-threonine and l-serine, the former is the preferred substrate. The ratio of the two activities remains about the same throughout purification. The activity of the purified enzyme is not stimulated by added pyridoxal phosphate which suggests that the coenzyme is rather tightly bound. Monovalent cations such as K+, NH4+, and Li+ stimulate the enzyme activity about 4- to 5-fold. The feedback inhibitor, l-isoleucine, protects the enzyme against inactivation at low temperatures. Analyses of Lineweaver-Burk plots show that the enzyme obeys Michaelis-Menten laws in the absence of l-isoleucine. However, in the presence of relatively low concentrations of the inhibitor the kinetics becomes sigmoidal. The kinetics is normalized by addition of l-valine. At low substrate concentrations (below 5 mm), l-valine activates the enzyme in the presence of l-isoleucine. The stimulatory effect of l-valine is, however, not observed at high substrate concentration. l-Valine reverses the l-isoleucine inhibition partially, the extent of reversion being dependent upon the concentration of l-isoleucine. Kinetic data suggest that the enzyme may have more than one binding site for l-isoleucine. Exposure of the purified enzyme to HgCl2 causes desensitization; i.e. the treated enzyme is less sensitive to feedback inhibition.
Induction of Both Thymidine and Deoxycytidine Kinase Activity by Herpes Viruses (1974)

SUMMARY Genetical and biochemical evidence indicates that herpes simplex virus (types 1 and 2) specifies a unique kinase activity which is able to phosphorylate both thymidine and deoxycytidine. Pseudorabies virus specifies an enzyme which has only thymidine kinase activity and so does vaccinia virus, while equine abortion virus does not induce either activity. It is shown that the HSV specified deoxypyrimidine kinase is indispensable for virus growth in serum starved cells but not important for virus replication in actively growing culture cells.
Comparison of methods for instantaneous angiographic blood flow measurement (1999)

Several different algorithms have been reported for measurement of blood flow rates and velocities from digital x-ray angiograms. We compare four videodensitometric methods: (1) distance-density curve matching (DDCM), (2) distance-density curve matching with curve-fitting (DDCM-F), (3) bolus mass tracking with curve-fitting (BMT-F) and (4) fluid continuity method (FCM). We tested the flow algorithms with simulated angiograms and with images obtained from a programmable flow phantom under clinically realistic flow and contrast injection conditions including imperfect mixing. All methods perform well for simulated angiograms. On phantom angiograms with constant flow, all methods tended to underestimate flow velocities by at least 7% and demonstrate high variability between consecutive measurements. The FCM demonstrated relatively low variability, but a large negative bias. The DDCM method was moderately biased and had the highest variability. The BMT-F method demonstrated the lowest bias (-7.1%) and the lowest variability both within (27%) and between (27%) studies. No method yields reliable measurements near the peak contrast opacification, when little or no gradient of contrast is present. The extrapolating version of the BMT-F method was also the most robust for estimation of interframe displacements longer than the field of view.
Inhibitory effect of antibody against basic fibroblast growth factor on androgen- or glucocorticoid-induced growth of Shionogi carcinoma 115 cells in serum-free culture. (1989)

Shionogi carcinoma 115 (SC115) has been accepted for 20 years as an androgen-responsive mouse mammary tumor. However, we and others recently found that the growth of SC115 cells is also stimulated by high doses of glucocorticoids. We already reported the following findings. In a serum-free medium [Ham's F-12: Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin], greater than or equal to 10(-9) M testosterone and greater than or equal to 10(-8) M dexamethasone significantly stimulated the growth of SC-3 cells (a cloned cell line from a SC115 tumor) through androgen and glucocorticoid receptors, respectively. In the present study, we have demonstrated that higher concentrations (10(-7)-10(-6) M) of weak androgens such as 4-androstene-3,17-dione or weak glucocorticoids such as corticosterone also significantly stimulate the growth of SC-3 cells and that their relative potency is found to be in parallel with their binding affinity for their receptors, respectively. Furthermore, DNA synthesis of SC-3 cells induced by 0.1 ng/ml basic fibroblast growth factor (FGF), 10(-8) M testosterone, 10(-6) M 4-androstene-3,17-dione, 10(-7) M dexamethasone, or 10(-6) M corticosterone was found to be similarly and significantly inhibited by the addition of basic FGF neutralizing antibody IgG in the present study; approximately 70% inhibition of the basic FGF, androgen, or glucocorticoid effects was attained. We already reported findings which suggest that SC-3 cells produce FGF-like peptide for their testosterone-induced growth. Therefore, the present study presents new additive information to demonstrate that the growth-stimulatory activity of various androgens or possibly glucocorticoids on SC-3 cells is mediated through a FGF-like peptide in an autocrine mechanism.
Feasibility of US-guided High-Intensity Focused Ultrasound Treatment in Patients with Advanced Pancreatic Cancer: Initial Experience (2005)

The study was approved by the university ethics committee, and informed consent was obtained from all patients. The purpose of this study was to prospectively evaluate ultrasonographically guided high-intensity focused ultrasound in the treatment of patients with advanced-stage pancreatic cancer. Eight patients underwent high-intensity focused ultrasound ablation, and laboratory and radiologic examinations were performed after intervention. Changes in symptoms and survival time were noted at follow-up. No complications were observed, and preexisting severe back pain disappeared after intervention. Follow-up images revealed an absence of tumor blood supply and shrinkage of the ablated tumor. Four patients died, and four patients were alive at the time of this writing, with a median survival time of 11.25 months. The authors conclude that high-intensity focused ultrasound ablation is safe and feasible in the treatment of advanced pancreatic cancer.
Preparation, biodistribution and dosimetry of copper-64-labeled anti-colorectal carcinoma monoclonal antibody fragments 1A3-F(ab')2. (1995)

The improved dosimetry of 64Cu-labeled FPLC purified BAT-2IT-1A3-F(ab')2 should more readily allow this agent to be investigated clinically to image colorectal cancer using PET.
Expression of transfected mutant beta-actin genes: transitions toward the stable tumorigenic state. (1987)

Mutant human beta-actin genes were introduced into normal human (KD) fibroblasts and the derivative cell line HuT-12, which is immortalized but nontumorigenic, to test their ability to promote conversion to the tumorigenic state. Transfected substrains of HuT-12 fibroblasts that expressed abundant levels of mutant beta-actin (Gly-244----Asp-244) produced subcutaneous tumors in athymic mice after long latent periods (1.5 to 3 months). However, transfected substrains of KD fibroblasts retained their normal finite life span in culture and consequently were incapable of producing tumors. Substrains of HuT-12 cells transfected with the wild-type beta-actin gene and some transfected strains that expressed low or undetectable levels of mutant beta-actin did not produce tumors. Cell lines derived from transfectant cell tumors always exhibited elevated synthesis of the mutant beta-actin, ranging from 145 to 476% of the level expressed by the transfected cells that were inoculated to form the tumor. In general, primary transfectant cells that expressed the highest levels of mutant beta-actin were more tumorigenic than strains that expressed lower levels. The tumor-derived strains were stable in tumorigenicity and produced tumors with shortened latent periods of only 2 to 4 weeks. These findings imply that the primary transfectant strains develop subpopulations of cells that are selected to form tumors because of their elevated rate of exogenous mutant beta-actin synthesis. Actin synthesis and accumulation of gamma-actin mRNA from the endogenous beta- and gamma-actin genes were diminished in tumor-derived strains, apparently to compensate for elevated mutant beta-actin synthesis and maintain the normal cellular concentration of actin. Synthesis of the transformation-sensitive tropomyosin isoforms was decreased along with mutant beta-actin expression. Such modulations in tropomyosin synthesis are characteristically seen in transformation of avian, rodent, and human fibroblasts. Our results suggest that this mutant beta-actin contributes to the neoplastic phenotype of immortalized human fibroblasts by imposing a cytoarchitectural defect and inducing abnormal expression of cytoskeletal tropomyosins.
Oxidation of thiols with methyltriphenylphosphonium dichromate (MTPPD) in dichloromethane at room temperature (2006)

A chemoselective, straight-forward and rapid method for oxidation coupling of thiols to the corresponding disulfides using methyltriphenylphosphonium dichromate (MTPPD) in dichloromethane at room temperature. The reaction has been carried out in excellent yield and short reaction time.
Experimental examination of a targeted hyperthermia system using inductively heated ferromagnetic microspheres in rabbit kidney (2001)

It is known that significant heating can be generated by magnetic hysteresis effects in small ferromagnetic particles exposed to a rapidly alternating magnetic field. If such particles can be made to infiltrate the vascular bed surrounding a tumour by intravascular infusion then it may be possible to generate sufficient heating to destroy the tumour by hyperthermia. One of the constraints on such a technique is the limited amount of magnetic material that can be delivered to a tumour via the intravascular route and the consequent heating that can be induced by this material. Here, we report on a series of experiments in which doses of microspheres containing different amounts of ferromagnetic material were infused into rabbit kidneys via the renal artery with the aim of testing whether adequate tissue heating could be achieved using realistic concentrations of the embolised material. Heating rates were measured for each infused quantity under similar conditions with the animal alive and dead to examine the role of blood flow in the heating process. The results show that tissue temperatures above the therapeutic threshold of 42 degrees C can be readily achieved using this method with clinically relevant concentrations of microspheres in living tissue.
Induction by Soluble Factors of Organized Axial Structures in Chick Epiblasts (1990)

Inductive action of soluble factors was tested on isolated chick epiblasts. An assay was developed wherein conditioned medium derived from the Xenopus XTC cell line induced the formation of a full-length notochord and rows of bilaterally symmetric somites. Basic fibroblast growth factor, epidermal growth factor, retinoic acid, and transforming growth factor type B1 and B2 were not capable of inducing axial structures. Thus, soluble factors can elicit the development of polarity stored in the epiblast and behave as true morphogens since they can induce the formation of the organized complex structures that constitute the embryonic axis.
Sensitivity to Poly(ADP-ribose) Polymerase (PARP) Inhibition Identifies Ubiquitin-specific Peptidase 11 (USP11) as a Regulator of DNA Double-strand Break Repair (2010)

DNA damage repair and checkpoint responses prevent genome instability and provide a barrier to the development of cancer. Inherited mutations in DNA damage response (DDR) genes such as those that encode the homologous recombination (HR) proteins BRCA1 and BRCA2 cause cancer predisposition syndromes. PARP inhibitors are an exciting new class of targeted therapy for treating patients with HR repair-defective tumors. In this study, we use an RNAi screen to identify genes that when silenced cause synthetic lethality with the PARP inhibitor AZD2281. This screen identified the deubiquitylating enzyme USP11 as a participant in HR repair of DNA double-strand breaks. Silencing USP11 with siRNA leads to spontaneous DDR activation in otherwise undamaged cells and hypersensitivity to PARP inhibition, ionizing radiation, and other genotoxic stress agents. Moreover, we demonstrate that HR repair is defective in USP11-silenced cells. Finally, the recruitment of a subset of double-strand break repair proteins including RAD51 and 53BP1 to repair foci is misregulated in the absence of USP11 catalytic activity. Thus, our synthetic lethal approach identified USP11 as a component of the HR double-strand break repair pathway.
Dopamine release is severely compromised in the R6/2 mouse model of Huntington's disease (2006)

Abstract Recently, alterations in dopamine signaling have been implicated in Huntington's disease. In this work, dopamine release and uptake was measured in striatal slices from the R6/2 transgenic mouse model of Huntington's disease using fast‐scan cyclic voltammetry at carbon‐fiber microelectrodes. Dopamine release in brain slices from 6‐week‐old R6/2 mice is substantially reduced (53% of wild type), while dopamine uptake is unaffected. In agreement with this, R6/2 mice injected with the dopamine uptake inhibitor cocaine exhibited a blunted motor activity response (54% of wild type). At 10 weeks of age, an even more dramatic motor activity decrease in response to cocaine injection (21% of wild type) was observed. Moreover, the pre‐drug activity of 10‐week‐old R6/2 mice was significantly reduced (by 37%) compared with 6‐week‐old R6/2 mice. Striatal dopamine release decreased with age, indicating that progressive alterations in dopaminergic pathways may affect motor activity. The inhibition constants of cocaine and methamphetamine (METH) determined in brain slices differed little between genotype or age group, suggesting that the decreased responses to cocaine and METH arise from compromised dopamine release rather than differences in uptake or drug action. Collectively, these data demonstrate (i) a reduction in the ability of dopamine terminals to release dopamine and (ii) the importance of this attenuation of release on the motor symptoms of Huntington's disease.
The diverse functions of Krüppel‐like factors 4 and 5 in epithelial biology and pathobiology (2007)

The Krüppel-like factors (KLFs) comprise a family of evolutionarily conserved zinc finger transcription factors that regulate numerous biological processes including proliferation, differentiation, development and apoptosis. KLF4 and KLF5 are two closely related members of this family and are both highly expressed in epithelial tissues. In the intestinal epithelium, KLF4 is expressed in terminally differentiated epithelial cells at the villus borders of the mucosa and inhibits cell growth, while KLF5 is expressed in proliferating epithelial cells at the base of the intestinal crypts and promotes cell growth. KLF4 and KLF5 respond to a myriad of external stress stimuli and are likely involved in restoring cellular homeostasis following exposure to stressors. Confirming their importance in maintaining tissue integrity, KLF4 and KLF5 are both dysregulated in various types of cancer. Here we review the recent advances in defining the physiological and pathobiological roles of KLF4 and KLF5, focusing on their functions in the intestinal epithelium.