gebhart/patrepeval huggingface dataset:
New developments in the use of cytokines for cancer therapy. (1998)

Cytokines, the pleiotropic immune regulatory proteins, are involved in the regulation of cell growth, differentiation and functional activation. Novel cytokines have been enumerated in rapid succession and entered the clinical arena. IL-2 is well recognized for its antitumor effects and is accepted therapy for numerous malignancies. IL-l and IL-11 are important as thrombopoetic factors while IL-6 has been introduced in clinical trials as a platelet growth factor and as an antitumor agent. IL-4 has shown growth inhibitory effects against many solid tumor cell lines in vitro, but its direct effect on human tumors in vivo remains to be explored. IL-7 may be an important addition to the current strategies of adoptive immunotherapy. IL-12 plays a fundamental role in activating antitumor cellular immunity. When given with tumor associated antigens, IL-12 has proven effective against many forms of metastatic solid tumors. Immunotoxins appear to be promising, though the antigenicity of the molecule and antibody development aspects remain to be resolved. The current review will focus on the clinical use of novel cytokines for the treatment of cancer.
The selective retardation of NADP+-dependent dehydrogenases by immobilized procion red HE-3B (1978)

The capacities of Procion Red HE-3B and Cibacron Blue F3G-A immobilized to Sepharose CL-4B and Matrex 201R for NAD+-, NADP+- and NAD(P)+-dependent dehydrogenases were measured. Procion Red HE-3B columns retarded NADP+-dependent dehydrogenases more effectively than NAD+-dependent dehydrogenases, whilst immobilized Cibacron Blue F3G-A retarded NAD+-dependent dehydrogenases more effectively than NADP+-dependent dehydrogenases. The capacity of procion Red HE-3B-Sepharose CL-4B for five dehydrogenases was highest in the region of 70nmol of immobilized ligand/ml of settled gel. The effects of using poly(ethyleneimine) as a spacer for both porous and pellicular supports were also examined. Four NADP+-dependent dehydrogenases were purified from yeast extract by using Procion Red HE-3B-Sepharose CL-4B. Two NAD+-dependent dehydrogenases were purified from the same source using Cibacron Blue F3G-A-Sepharose CL-4B. These results are discussed in relation to the use of immobilized Procion Red HE-3B to purify dehydrogenases. This immobilized dye's chromatograhic behaviour is compared with that of immobilized nucleotides. The most important feature of immobilized tirazine dyes seems to be their high operational capacities when compared with group-specific nucleotide adsorbents.
ChemInform Abstract: 3,3′‐ETHYLENEBIS(BENZOTHIAZOLIUM) SALTS AND THEIR BISCYANINE DYES (1978)

Abstract Das Ethan (I) lagert sich" bei erhöhter Temperatur zur Verbindung (II) um und wird zum Bisquartärsalz (III) mit 2 Methylmercaptogruppen in 2‐Stellung quaterniert.
Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages (1997)

Superoxide (O-2) and nitric oxide (NO) act to kill invading microbes in phagocytes. In macrophages NO is synthesized by inducible nitric oxide synthase (iNOS, NOS 2) from L-arginine (L-Arg) and oxygen; however, O-2 was thought to be produced mainly by NADPH oxidase. Electron paramagnetic resonance (EPR) spin trapping experiments performed in murine macrophages demonstrate a novel pathway of O-2 generation. It was observed that depletion of cytosolic L-Arg triggers O-2 generation from iNOS. This iNOS-mediated O-2 generation was blocked by the NOS inhibitor N-nitro-L-arginine methyl ester or by L-Arg, but not by the noninhibitory enantiomer N-nitro-D-arginine methyl ester. In L-Arg-depleted macrophages iNOS generates both O-2 and NO that interact to form the potent oxidant peroxynitrite (ONOO-), which was detected by luminol luminescence and whose formation was blocked by superoxide dismutase, urate, or L-Arg. This iNOS-derived ONOO- resulted in nitrotyrosine formation, and this was inhibited by iNOS blockade. iNOS-mediated O-2 and ONOO- increased the antibacterial activity of macrophages. Thus, with reduced L-Arg availability iNOS produces O-2 and ONOO- that modulate macrophage function. Due to the existence of L-Arg depletion in inflammation, iNOS-mediated O-2 and ONOO- may occur and contribute to cytostatic/cytotoxic actions of macrophages.
The spectrum of behavioral changes in Alzheimer's disease (1996)

We investigated the range of behavioral abnormalities in patients with Alzheimer's disease (AD) compared with normal age-matched control subjects. The range of behavioral disturbances manifested and the relationship between specific abnormalities with the level of cognitive impairment have not been established. Fifty consecutive outpatients with mild (n = 17), moderate (n = 20), and severe (n = 13) AD and 40 age-matched normal controls were evaluated for behavioral abnormalities occurring in the month preceding the interview. The caregivers of the patients and the spouses of the control subjects were interviewed with the Neuropsychiatric Inventory (NPI). The frequency and severity of the following 10 behaviors were assessed: delusions, hallucinations, agitation, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, and aberrant motor behavior. Correlations among these 10 behaviors and their relationship with cognitive impairment were also investigated. Eighty-eight percent of AD patients had measurable behavioral changes. All 10 behaviors were significantly increased in the AD patients compared with normal subjects. The most common behavior was apathy, which was exhibited by 72% of patients, followed by agitation (60%), anxiety (48%), irritability (42%), dysphoria and aberrant motor behavior (both 38%), disinhibition (36%), delusions (22%), and hallucinations (10%). Agitation, dysphoria, apathy, and aberrant motor behavior were significantly correlated wit cognitive impairment.
Expression and assembly of a fully active antibody in algae (2003)

Although combinatorial antibody libraries have solved the problem of access to large immunological repertoires, efficient production of these complex molecules remains a problem. Here we demonstrate the efficient expression of a unique large single-chain (lsc) antibody in the chloroplast of the unicellular, green alga, Chlamydomonas reinhardtii. We achieved high levels of protein accumulation by synthesizing the lsc gene in chloroplast codon bias and by driving expression of the chimeric gene using either of two C. reinhardtii chloroplast promoters and 5' and 3' RNA elements. This lsc antibody, directed against glycoprotein D of the herpes simplex virus, is produced in a soluble form by the alga and assembles into higher order complexes in vivo. Aside from dimerization by disulfide bond formation, the antibody undergoes no detectable posttranslational modification. We further demonstrate that accumulation of the antibody can be modulated by the specific growth regime used to culture the alga, and by the choice of 5' and 3' elements used to drive expression of the antibody gene. These results demonstrate the utility of alga as an expression platform for recombinant proteins, and describe a new type of single chain antibody containing the entire heavy chain protein, including the Fc domain.
Cardiac Natriuretic Peptides Are Related to Left Ventricular Mass and Function and Predict Mortality in Dialysis Patients (2001)

This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.
GR24, a Synthetic Analog of Strigolactones, Stimulates the Mitosis and Growth of the Arbuscular Mycorrhizal FungusGigaspora roseaby Boosting Its Energy Metabolism (2008)

Arbuscular mycorrhizal (AM) fungi are obligate biotrophs that participate in a highly beneficial root symbiosis with 80% of land plants. Strigolactones are trace molecules in plant root exudates that are perceived by AM fungi at subnanomolar concentrations. Within just a few hours, they were shown to stimulate fungal mitochondria, spore germination, and branching of germinating hyphae. In this study we show that treatment of Gigaspora rosea with a strigolactone analog (GR24) causes a rapid increase in the NADH concentration, the NADH dehydrogenase activity, and the ATP content of the fungal cell. This fully and rapidly (within minutes) activated oxidative metabolism does not require new gene expression. Up-regulation of the genes involved in mitochondrial metabolism and hyphal growth, and stimulation of the fungal mitotic activity, take place several days after this initial boost to the cellular energy of the fungus. Such a rapid and powerful action of GR24 on G. rosea cells suggests that strigolactones are important plant signals involved in switching AM fungi toward full germination and a presymbiotic state.
Postnatal Age and Protein Tyrosine Phosphorylation at Synapses in the Developing Rat Brain (1991)

The relationship between postnatal age and protein tyrosine kinase activity in synaptosomes prepared from the rat forebrain was studied. Synaptosomal particulate and soluble fractions, as well as total homogenates, the cell soluble fraction, and P3, were prepared from rats ranging in postnatal age from 5 to 60 days and analyzed for (a) tyrosine kinase activity using polyglutamyltyrosine (4:1) as the substrate, (b) the presence of endogenous substrates for tyrosine phosphorylation using polyclonal antibodies specific for phosphotyrosine, and (c) levels of pp60src. Enzyme activity, expressed per milligram of protein, in the total homogenate, P3, and both the cell and synaptosomal soluble fractions was highest in the brains of young animals (postnatal days 5-10) and decreased thereafter to adult levels. In contrast, tyrosine kinase activity in the synaptosomal particulate fraction exhibited a unique biphasic developmental profile, increasing to maxima at postnatal days 10 and 20 before decreasing to adult values. Endogenous substrates for tyrosine phosphorylation were identified by incubating subcellular fractions with 2 mM ATP in the presence of sodium orthovanadate and probing nitrocellulose blots of proteins separated by gel electrophoresis with antiphosphotyrosine antibodies. Several phosphotyrosine-containing proteins were detected in the synaptosomal particulate and P3 fractions, including proteins of Mr 180K, 145K, 120K, 100K, 77K, 68K, 62K, 54K, 52K, and 42K. In the cell soluble fraction a protein doublet of Mr 54/52K and a 120K protein were the major phosphotyrosine-containing proteins. The 54/52K doublet was the major protein tyrosine kinase substrate in the synaptosomal soluble fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
beta 2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface. (1996)

The objective of this study was to determine whether beta 2-glycoprotein I (beta 2GPI) has procoagulant activity by inhibiting the anticoagulant activity of activated protein C (APC). beta 2GPI inhibited significantly the APC-catalyzed inactivation of factor Va in an assay using factor V-deficient plasma and physiological levels of protein S and factor Va. This inhibitory effect was diminished by the addition of increasing concentrations of phospholipids, suggesting that beta 2GPI competitively inhibits the binding of APC to the phospholipid surface. beta 2GPI inhibited weakly factor Va- and phospholipid-dependent prothrombinase activity at concentrations similar to those to inhibit APC activity. The depletion of beta 2GPI from plasma led to only a slight shortening of the diluted Russell's viper venom-dependent clotting time, but to a strong and significant potentiation of the anticoagulant activity of APC. These results suggest that under certain physiological conditions beta 2GPI has procoagulant property by inhibiting the phospholipid-dependent APC anticoagulant activity.
Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (2002)

The full text of this document is available on the Website of the European Society of Cardiology: www.escardio.org in the section ‘Scientific Information’, Guidelines. Introduction 1809 Pathophysiology 1810 Plaque rupture and erosion 1810 Inflammation 1812 Thrombosis 1812 Vasoconstriction 1812 Myocardium 1813 Diagnosis 1813 Clinical presentation 1813 Physical examination 1813 Electrocardiogram 1813 Biochemical markers of myocardial damage 1814 Recommendations 1815 Risk assessment 1815 Risk factors 1815 Clinical presentation 1815 Electrocardiogram 1816 Markers of myocardial damage 1816 Markers of inflammatory activity 1816 Markers of thrombosis 1817 Echocardiography 1817 Predischarge stress testing 1817 Coronary angiography 1817 Recommendations for risk stratification 1818 Treatment options 1818 Anti-ischaemic agents 1818 Beta-blockers 1818 Nitrates 1818
Products of heme oxygenase and their potential therapeutic applications (2006)

Heme oxygenase 1 (HO-1) is induced in response to cellular stress and is responsible for converting the prooxidant heme molecule into equimolar quantities of biliverdin (BV), carbon monoxide (CO), and iron. BV is then converted to bilirubin (BR) by the enzyme biliverdin reductase. Experimental evidence suggests that induction of the HO system is an important endogenous mechanism for cytoprotection and that the downstream products of heme degradation, CO, BR, and BV, may mediate these powerful beneficial effects. These molecules, which were once considered to be toxic metabolic waste products, have recently been shown to have dose-dependent vasodilatory, antioxidant, and anti-inflammatory properties that are particularly desirable for tissue protection during organ transplantation. In fact, recent work has demonstrated that administration of exogenous CO, BR, or BV may offer a simple, inexpensive method to substitute for the cytoprotective effects of HO-1 in a variety of clinically applicable models. This review will attempt to summarize the relevant biochemical and cytoprotective properties of CO, BR, and BV, and will discuss emerging studies involving the therapeutic applications of these molecules in the kidney and other organ systems.
Reliability and Validity of the Ocular Surface Disease Index (2000)

The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials.
Polydopamine-Based Simple and Versatile Surface Modification of Polymeric Nano Drug Carriers (2014)

The surface of a polymeric nanoparticle (NP) is often functionalized with cell-interactive ligands and/or additional polymeric layers to control NP interaction with cells and proteins. However, such modification is not always straightforward when the surface is not chemically reactive. For this reason, most NP functionalization processes employ reactive linkers or coupling agents or involve prefunctionalization of the polymer, which are complicated and inefficient. Moreover, prefunctionalized polymers can lose the ability to encapsulate and retain a drug if the added ligands change the chemical properties of the polymer. To overcome this challenge, we use dopamine polymerization as a way of functionalizing NP surfaces. This method includes brief incubation of the preformed NPs in a weak alkaline solution of dopamine, followed by secondary incubation with desired ligands. Using this method, we have functionalized poly(lactic-co-glycolic acid) (PLGA) NPs with three representative surface modifiers: a small molecule (folate), a peptide (Arg-Gly-Asp), and a polymer [poly(carboxybetaine methacrylate)]. We confirmed that the modified NPs showed the expected cellular interactions with no cytotoxicity or residual bioactivity of dopamine. The dopamine polymerization method is a simple and versatile surface modification method, applicable to a variety of NP drug carriers irrespective of their chemical reactivity and the types of ligands.
Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules (2005)

The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K(b) or D(d) conveyed strong rejection of MHC class I-deficient cells, whereas the expression of D(b) or L(d) resulted in weaker responses. The educating impact of weak ligands (D(b) and L(d)) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K(b) and D(d)) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I-Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.
Catalytic Asymmetric Synthesis of Chiral Allylic Esters (2005)

Trichloroacetimidate derivatives of prochiral (&lt;i&gt;Z&lt;/i&gt;)-2-alken-1-ols react at room temperature with carboxylic acids to give chiral 3-acyloxy-1-alkenes in high enantiopurity in the presence of di-μ-acetatobis[(η&lt;sup&gt;5&lt;/sup&gt;-(&lt;i&gt;S&lt;/i&gt;)-(p&lt;i&gt;R&lt;/i&gt;)-2-(2‘-(4‘-methylethyl)oxazolinyl)cyclopentadienyl,1-C,3‘-&lt;i&gt;N&lt;/i&gt;)(η&lt;sup&gt;4&lt;/sup&gt;-tetraphenylcyclobutadiene)cobalt]dipalladium (COP-OAc) or its enantiomer. This reaction has broad scope, proceeds with predictable high stereoinduction, is accomplished at room temperature using high substrate concentrations and low catalyst loadings, and likely proceeds by a novel mechanism.
Histone H2A-mediated transient cytokine gene delivery induces efficient antitumor responses in murine neuroblastoma (2000)

A major goal of cancer immunotherapy is the induction of a cell-mediated antitumor response in poorly immunogenic malignancies. We tested the hypothesis that this can be achieved by cytokine gene therapy with a novel histone H2A-based transient transfection procedure. This was tested by using cytokine genes encoding for IL-2 and a single chain IL-12 (scIL-12) fusion protein in a recently developed murine neuroblastoma model. Here, we demonstrate that cytokine gene transfer of IL-2 and scIL-12 with histone H2A results in the induction of an antitumor immune response that is superior in some respects to gene transfer with Superfect, a commercially available activated dendrimer commonly used to effect transfection with plasmids. Three lines of evidence support this contention. First, histone H2A-mediated transfection of IL-2 induces a natural killer cell-induced rejection of primary tumors in contrast to Superfect, which produces only a partial reduction in primary tumor growth. Second, the induction of a T cell-mediated protective tumor immunity following gene transfer of scIL-12 is more efficient with the histone H2A-mediated gene transfer because rejection of a lethal wild-type tumor cell challenge is accompanied by the greatest degree of MHC class I-restricted tumor cell killing in vitro. Third, histone H2A-mediated scIL-12 gene therapy induces the greatest release of mIFN-gamma from splenocytes of vaccinated animals in contrast to Superfect and other controls.
INACTIVATION ACTION SPECTRA OF BACILLUS SUBTILIS SPORES IN EXTENDED ULTRAVIOLET WAVELENGTHS (50–300nm) OBTAINED WITH SYNCHROTRON RADIATION (1991)

Five types of Bacillus subtilis spores (UVR, UVS, UVP, RCE, and RCF) differing in repair and/or recombinational capabilities were exposed to monochromatic radiations at 13 wavelengths from 50 to 300 nm in vacuum. An improved biological irradiation system connected to a synchrotron radiation source was used to produce monochromatic UV radiation in this extended wavelength range with sufficient fluence to inactivate bacterial spores. From the survival curves obtained, the action spectra for the inactivation of the spores were depicted. Recombination-deficient RCE (recE) and RCF (recF) spores were more sensitive than the wild-type UVR spores in the entire range of wavelengths. This was considered to mean that DNA was the major target for the inactivation of the spores. Vacuum-UV radiations of 125-175 nm were effective in killing the spores, and distinct peaks of the sensitivity were seen with all types of the spores. Insensitivities at 190 and 100 nm were common to all five types of spores, indicating that these wavelengths were particularly impenetrant and absorbed by the outer layer materials. The vacuum-UV peaks centering at 150 nm were prominent in the spores defective in recombinational repair, while the far-UV peaks at around 235 and 270 nm were prominent in the UVS (uvrA ssp) and UVP (uvrA ssp polA) spores deficient in removal mechanisms of spore photoproducts. Thus, the profiles of the action spectra were explained by three factors; the penetration depth of each radiation in a spore, the efficiency of producing DNA damage that could cause inactivation, and the repair capacity of each type of spore.
A New Highly Selective H2 Sensor Based on TiO2/PtO−Pt Dual-Layer Films (2002)

A new highly selective hydrogen sensor based on TiO2/PtO−Pt dual-layer films has been prepared. At 180−200 °C, the prepared nanostructured sensor exhibits an excellent selectivity and good sensitivity to H2 in air but is immune to many other kinds of reductive gases such as CO, NH3, and CH4. The sensor can give a faithful response to 1% H2 in air, while the limitation for detecting H2 in nitrogen is less than 1000 ppm. Influences of operation temperature and humidity on the sensing performance of the sensor were also investigated. The mechanism of the present sensor was attributed to the partial reduction of Ti4+ to Ti3+ by hydrogen catalyzed by a thin film of surface-oxidized Pt nanoparticles.