gebhart/patrepeval huggingface dataset:
Therapy of leukemia by nonimmune syngeneic spleen cells. (1980)

In previous studies mice bearing an established transplanted syngeneic leukemia were cured by the adoptive transfer of immune lymphoid cells inoculated as an adjunct to chemotherapy, whereas nonimmune cells had no effect. By employing a smaller initial tumor inoculum to enhance the sensitivity of the chemoimmunotherapy model, the current study demonstrated that cells from normal nonimmune donors can also eradicate tumor. Thus, adult BALB/c mice given a lethal dose (1 x 10(4)) of LSTRA on day 0 were treated on day 5 with cyclophosphamide (CY) alone or CY plus nonimmune cells. Untreated mice all died by day 10. Cy alone prolonged median survival time (MST) to day 20, but all mice died. Treatment with CY plus 1 x 10(7) nonimmune cells prolonged the MST to day 26 and cured 16 of 48 mice. The effector cells, present in the spleens of normal and nude mice, were nonadherent lymphocytes resistant to anti Thy + C. These results are consistent with this effector cell in adoptive chemoimmunotherapy being an NK cell. However, they are distinct from classical NK cells since they are not directly cytotoxic in vitro in a short term CRA and do not neutralize tumor in vivo in a Winn assay.
Analytical Investigation of the Interactions between SC3 Hydrophobin and Lipid Layers:  Elaborating of Nanostructured Matrixes for Immobilizing Redox Systems (2006)

Hydrophobins are highly tensioactive fungal proteins with a pronounced affinity for interfaces and a propensity for self-assembly. Recently, these proteins were shown to be useful in retaining different molecules on solid surfaces. This finding offers a possibility for developing new functional materials, while creating the necessity of further research at a deeper mechanistic level. In this work, the mechanisms governing the surface phenomena were studied using native Schizophyllum commune hydrophobin (SC3) and lipid mono- and bilayers; the soft matter systems were used to get a handle on the interactive protein/interface effects at a molecular level. The results obtained indicated that the SC3/lipid membrane interactions were adjusted by protein conformational adaptation, allowing its incorporation into lipid matrixes; the incorporation of a chelating SC3 hydrophobin (PFA-SC3) in a monoolein cubic phase yielded a biomimetic, cell-like system of Cu(II) cation immobilization. This system, which is suitable for modifying electrode surface and monitoring the Cu(II)/Cu(0) redox process, may be of practical interest in switching and sensing.
Probiotics in the Mechanism of Protection Against Gut Inflammation and Therapy of Gastrointestinal Disorders (2014)

A growing body of experimental and clinical evidence supports the hypothesis that the intestinal microbiota markedly influences function and the structure of the mucosal lining. Intestinal microbiota can potentially cause damage to the mucosa either directly by releasing toxins or indirectly by causing a detrimental immune response. Probiotic bacteria have been defined as live microorganisms, which when consumed in adequate amounts, confer a health benefit for the host. In recent years, the therapeutic and preventive application of probiotics for several gastrointestinal and liver disorders has received increasing attention. Probiotics appear to be beneficial for premature infants who suffer necrotizing enterocolitis. The effectiveness of certain probiotics as treatment for infectious and antibioticassociated diarrhea in adults and for allergic disorders in children has been supported by clinical studies; however, the potential mechanism( s) remains to be studied. Experimental studies and clinical trials for probiotic treatment of inflammatory bowel diseases (IBD) have yielded conflicting results. Daily intake of selected probiotics was effective in the prevention of ulcerative colitis and the attenuation of the active onset of Crohn's disease or ulcerative colitis but others failed to show a beneficial effect. The combination of Lactobacillus, Bifidobacterium, Saccharomyces boulardi and the treatment with Escherichia coli Nissle were found beneficial in inducing and maintaining remission of disease activity of gut inflammation and moderately severe ulcerative colitis. Probiotic bacteria were considered in some studies as a safe adjuvant when added to triple eradication therapy against the symptoms induced by the major gastric pathogen, Helicobacter pylori. This review attempted to overview these new exciting advances in the role of these microbes in the pathogenesis, management and treatment of gastrointestinal disorders.
High-resolution three-dimensional magnetic resonance imaging for the investigation of knee joint damage during the time course of antigen-induced arthritis in rabbits (1999)

Qualitative information derived from MR images correlated extremely well with histologic findings. These results indicate the great potential of MRI for noninvasive investigation of drug effects in this model of arthritis.
Stiripentol for the treatment of Dravet syndrome (2014)

Stiripentol for the treatment of Dravet syndrome Catherine Chiron1&ndash;31INSERM U1129, Paris, France; 2Paris Descartes University, Paris, France; 3CEA, Gif-sur-Yvette, FranceAbstract: Stiripentol (marketed by Biocodex as Diacomit&reg;) is an anticonvulsant drug, structurally unrelated to any other compound, which has recently been approved as adjunctive therapy with clobazam and valproate for Dravet syndrome in Europe, Canada, and Japan. This rare form of early childhood epilepsy is associated with subsequent cognitive impairment, significant risk of death, and high pharmacoresistance. Based on an efficacy signal of stiripentol added to clobazam and valproate in an observational, prospectively conducted, exploratory study including 10% of children with Dravet syndrome, a randomized placebo-controlled trial was specifically dedicated to patients with Dravet syndrome inadequately controlled by clobazam and valproate. Results showed significantly higher responder rates (71% versus 5%; P&lt;0.0001) and decrease in seizure frequency (-69% versus +7%; P&lt;0.002) on stiripentol than on placebo. A second, independently performed, randomized controlled trial confirmed these results 2 years later, and both trials were plotted in a meta-analysis. Efficacy was supported by three subsequent observational studies, with, respectively, 46 (France), 23 (Japan), and 82 (USA) children with Dravet syndrome treated with stiripentol for up to 5 years. Based on the experiences of more than 2,000 patients with Dravet syndrome who were exposed to stiripentol, drowsiness, loss of appetite, and weight loss are the most frequent adverse events and may be reduced by decreasing the dosage of co-medication. The inhibition of stiripentol by the cytochrome P450 complex (CYP2C19, and CYP3A4) leads to clinically significant interactions. Experimental data, both in vitro and in vivo, have definitively established that stiripentol is a GABAergic anticonvulsant and acts on different sites than benzodiazepines. The pharmacodynamic interactions also enhance the anticonvulsant effect of the stiripentol&ndash;clobazam combination in patients with Dravet syndrome, irrespective of the GABAergic effect. Stiripentol is currently the only drug specifically indicated in Dravet syndrome.Keywords: childhood epilepsy, antiepileptic drug trials, orphan drugs, clobazam, GABAergic drugs, CYP450
Golden v. Planning Bd. of Ramapo Revisited: Old Lessons for New Problems (1992)

However, a balance must be struck between the local interest in maintaining authority over land use decisions and the state interest in regulating these decisions to minimize the impact on the region or the state.In a 1972 decision, the New York Court of Appeals addressed the proper scope of local governmental authority over the development of its land.In Golden v. Planning Bd. of Ramapo," the court upheld the municipality's right to regulate development.The municipality could effectively prevent subdivision on a given plat 5 for as long as eighteen years through special permits for subdivision approval. 6 Ramapo's effort to control the growth of its town is not unique. 7Through a variety of techniques," many towns attempt to maintain their character or status quo 9 and to avoid the problems related to increased development and urbanization. 10 This Comment will examine whether the ability to regulate land use decisions" is properly vested in local government, or whether it should be shifted to regionalor even stategovernment to consider broader issues and impacts not currently examined by municipalities.Part II of this Comment Will examine Golden v. Planning Bd. of Ramapo 2 and the court's reasoning in upholding the local measure.Part II will also examine the current trends in New York Court of Appeals' decisions to illustrate the dichotomy among these decisions.Fur-4.30 N.Y.2d 359, 285 N.
Outer membrane protein F preparation of Pseudomonas aeruginosa as a vaccine against chronic pulmonary infection with heterologous immunotype strains in a rat model (1988)

Outer membrane protein F (porin) was purified by extraction from polyacrylamide gels of cell envelope proteins of the Pseudomonas aeruginosa PAO1 strain. Rats were immunized intramuscularly with 25 micrograms of protein F on days 1 and 14 and then challenged on day 28 via intratracheal inoculation of bacterium-containing agar beads. On day 35 the lungs were either fixed for histological examination or submitted for quantitation of the bacteria present. protein F immunization afforded significant protection against challenge with six of six heterologous lipopolysaccharide immunotype strains of P. aeruginosa. By an enzyme-linked immunosorbent assay, the protein F-immunized rats had both immunoglobulin G and M antibody responses to cell envelopes of all six of the heterologous immunotype strains. Protein F immunization greatly enhanced the ability of the rats to clear the inoculated P. aeruginosa from the lungs and significantly reduced the incidence and severity of pulmonary lesions as compared with those in bovine serum albumin-immunized control rats. These data show the efficacy of outer membrane protein F as a protective vaccine in a rat model of chronic pulmonary infection.
A genetic variant near olfactory receptor genes influences cilantro preference (2012)

The leaves of the Coriandrum sativum plant, known as cilantro or coriander, are widely used in many cuisines around the world. However, far from being a benign culinary herb, cilantro can be polarizing---many people love it while others claim that it tastes or smells foul, often like soap or dirt. This soapy or pungent aroma is largely attributed to several aldehydes present in cilantro. Cilantro preference is suspected to have a genetic component, yet to date nothing is known about specific mechanisms. Here we present the results of a genome-wide association study among 14,604 participants of European ancestry who reported whether cilantro tasted soapy, with replication in a distinct set of 11,851 participants who declared whether they liked cilantro. We find a single nucleotide polymorphism (SNP) significantly associated with soapy-taste detection that is confirmed in the cilantro preference group. This SNP, rs72921001, (p=6.4e-9, odds ratio 0.81 per A allele) lies within a cluster of olfactory receptor genes on chromosome 11. Among these olfactory receptor genes is OR6A2, which has a high binding specificity for several of the aldehydes that give cilantro its characteristic odor. We also estimate the heritability of cilantro soapy-taste detection in our cohort, showing that the heritability tagged by common SNPs is low, about 0.087. These results confirm that there is a genetic component to cilantro taste perception and suggest that cilantro dislike may stem from genetic variants in olfactory receptors. We propose that OR6A2 may be the olfactory receptor that contributes to the detection of a soapy smell from cilantro in European populations.
Regulation of Development, Survival and Neoplastic Growth of Mast Cells through the c-<i>kit</i> Receptor (1995)

Signaling through the c-kit receptor tyrosine kinase (Kit) is essential for development and survival of mast cells but not of basophils. Moreover, we recently found an activation mutation of Kit in several tumor mast cell lines.
The effect of promoter strength in adenoviral vectors containing herpes simplex virus thymidine kinase on cancer gene therapy in vitro and in vivo. (1997)

The use of adenoviral vectors to deliver the herpes simplex virus thymidine kinase (HSVtk) gene followed by treatment with the prodrug ganciclovir (GCV) has promise for a variety of applications where excess cell proliferation is detrimental such as treatment of tumors and vascular restenosis. Optimizing this system is thus an important goal. The purpose of this study was to determine if the induction of higher levels of HSVtk expression would augment the sensitivity to GCV. This was accomplished by generating adenoviral vectors that expressed HSVtk from promoters of different efficiencies (the CMV versus RSV promoters). Despite higher levels of HSVtk expression per cell with the CMV promoter, there was no significant enhancement of antitumor effects between RSV- and CMV-driven adenovirus vectors in in vitro and in vivo studies indicating that simply increasing HSVtk enzyme levels per cell above a minimal threshold level will not be effective in augmenting the HSVtk/GCV system. These results suggest that other strategies, e.g., the use of higher doses of GCV, augmentation of the "bystander effect," the generation of mutant HSVtk genes with higher substrate affinities, the discovery of improved vectors with increased transduction efficiencies, or the development of new prodrugs with higher affinities for HSVtk will therefore be needed to enhance therapeutic responses.
Enhanced Functional Maturation of Fetal Porcine Hepatocytes in Three-Dimensional Poly-L-lactic Acid Scaffolds: A Culture Condition Suitable for Engineered Liver Tissues in Large-Scale Animal Studies (2006)

To engineer liver tissues with a clinically significant size, in vivo evaluation of performance using large-scale animal studies are necessary before proceeding to human clinical trials. As pigs are the most suitable candidates, the development of culture conditions suitable for porcine hepatocyte progenitors is very important to engineer pig liver tissue equivalents. We therefore investigated the efficacy of poly-L-lactic acid (PLLA) three-dimensional (3D) scaffolds on the functional maturation of fetal porcine hepatocytes in the presence of various combinations of biofactors. Cells were isolated from pig fetuses obtained from a local slaughterhouse, and cultured for 15 days both in monolayer and PLLA scaffolds. Although 15 days of culture resulted in almost the same ratio of proliferation (about fivefold) in both monolayer and 3D PLLA culture, the PLLA culture with hepatocyte growth factor (HGF, 10 ng/ml) and sodium butylate (Sb, 1 mM) remarkably enhanced various liver-specific functions of fetal porcine hepatocytes. The final attained functions based on the numbers of immobilized cells on day 1 compared with those of day 1 monolayers; 191-fold increase in albumin secretion, 70.5-fold increase in cytochrome P450 IA1/2 capacity, 20.9-fold increase in ammonia removal, and 18.0-fold increase in urea synthesis were obtained. These functions were 2.0-3.3-fold higher than those obtained by the same period of monolayer culture. In addition, final attained unit cell-based functions on day 15 were almost comparable to the levels reported for cultures of adult porcine hepatocytes in both monolayer and 3D spheroid cultures. These results demonstrate that the use of a biodegradable polymer-based 3D culture with an appropriate combination of biofactors is a promising approach to maximize functional maturation of hepatocyte progenitors from large animals. In addition, the established culture conditions are worth using to engineer large liver tissue equivalents for pigs in large-animal-based preclinical studies.
Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis (2017)

Ammonia-lowering therapy results in improvement in skeletal muscle phenotype and function and molecular perturbations of hyperammonemia; these preclinical studies complement previous studies on ammonia-induced skeletal muscle loss and lay the foundation for prolonged ammonia-lowering therapy to reverse sarcopenia of cirrhosis. (Hepatology 2017;65:2045-2058).
Janus Micelles (2001)

A novel strategy to synthesize amphiphilic surface-compartmentalized nanoparticles based on linear ABC triblock copolymers is presented. These so-called Janus micelles consist of a cross-linked core and a corona with a “northern” and a “southern” hemisphere. Selectively cross-linking spherical domains of the polybutadiene middle block in a well-ordered bulk morphology of a polystyrene-block-polybutadiene-block-poly(methyl methacrylate) triblock copolymer (SBM) leads to the conservation of the compartmentalization of the outer blocks after dissolution of the material. Multi-angle laser light scattering gel permeation chromatography, fluorescence correlation spectroscopy, small-angle neutron scattering, and static and dynamic light scattering, as well as scanning force microscopy, indicate the existence of an equilibrium between molecularly dissolved Janus micelles (unimers) and aggregates (multimers), so-called supermicelles.
High level expression of mammalian protein farnesyltransferase in a baculovirus system. The purified protein contains zinc (1993)

The mammalian enzyme protein farnesyltransferase is a heterodimeric protein that catalyzes the addition of a farnesyl isoprenoid to a cysteine in ras proteins. Since oncogenic forms of ras proteins require the farnesyl group for transforming activity, the structure and mechanism of this enzyme are important to define. However, such studies have been difficult to approach because of the low abundance of the enzyme in mammalian tissues and hence the problems of obtaining large quantities of the protein. We report here the co-expression of the two subunits of protein farnesyltransferase by Sf9 cells infected with a recombinant baculovirus containing the coding sequences of both polypeptides. This results in the production of milligram quantities of enzyme which can be readily purified by conventional chromatographic methods. The individual subunits of the enzyme can also be expressed in the Sf9 cells, but the ability to reconstitute active enzyme from extracts containing individual subunits is quite low. In contrast, the enzyme produced by co-expression of the two subunits is fully active and retains the properties of the mammalian form, including the specificity for the COOH-terminal amino acid of substrate proteins and the ability to bind short peptides encompassing the prenylation site of a ras protein. Furthermore, through atomic absorption analysis of the purified protein, we have confirmed the previous tentative assignment of protein farnesyltransferase as a zinc metalloenzyme by demonstrating that it contains an essentially stoichiometric amount of zinc. The ability to produce and purify milligram quantities of protein farnesyltransferase readily will allow detailed mechanistic and structural studies on this enzyme.
Association of Cigarette Smoking With Superoxide Dismutase Enzyme Levels in Subjects With Chronic Periodontitis (2009)

There was a progressive reduction in SOD levels from healthy non-smokers to light smokers to heavy smokers. These findings highlight the need to augment the efforts of smoking-cessation programs. The benefits of reduced smoking and improved antioxidant levels may motivate smoking cessation.
The Lone Ranger Lied: Tonto Wasn't Real (1984)

Whenever Hadley Irwin speaks to school children or to adults, for that matter, someone always asks, “Did the things in the book really happen to you? Are the characters in your books real people?” Writing is full of bits and pieces of the past, but what goes on paper is an amalgam of thousands of things, consciously and unconsciously remembered—experiences, overheard conversations, stories, imagined events. For a child, at least this writer as a child, all things had equal validity; all were equally true, even though she finally learned that growing up was a mixture of reality and myth.
Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. (1991)

Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor-containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture.
Regulation of Neuronal Cell Death and Neurodegeneration by Members of the Bcl-2 Family: Therapeutic Implications (2005)

The Bcl-2 family of proteins contains both anti and pro-apoptotic members that have been shown to regulate neuronal cell death during development and in many models of acute and chronic neurodegeneration. This family of proteins can be divided into three distinct classes based on structure and function: the anti-apoptotic sub-group; the pro-apoptotic, multi-domain sub-group; and the pro-apoptotic, BH3 domain-only sub-group. Alterations in the expression of Bcl-2 family members occur in several animal and human neurodegenerative diseases including Alzheimer's, Huntington's and Parkinson's diseases and Amyotrophic Lateral Sclerosis. Similar changes are seen in in vivo and in vitro models of acute neurodegeneration, including stroke and traumatic brain injury. Methods to increase the overall expression and/or function of anti-apoptotic Bcl-2 family members, and thus promote neuron survival, have been studied extensively in these models. Most treatment efforts focus on either the targeted delivery via viral vectors of anti-apoptotic members of Bcl-2 family members into the affected brain regions of interest, the generation of direct interactions of small molecule inhibitors with Bcl-2 family members, or the induced expression of Bcl-2 family members secondary to pharmacological manipulation. Although many challenges exist in the design of safe and efficacious Bcl-2 family mimetics for the treatment of neurodegeneration, such strategies offer great promise for preserving neuron viability, and hopefully function, in a variety of human neurological diseases.