gebhart/patrepeval huggingface dataset:
Characterisation and cellular localisation of the immunodominant 47-Kda antigen of Candida albicans (1988)

The 47-Kda component of Candida albicans is an immunodominant antigen in the serology of systemic candidosis. Immuno-electronmicroscopy with an affinity-purified antibody to the 47-Kda antigen showed that it was present in the cytoplasm and cell wall of both yeast and mycelial cells. It was found in discrete areas on the inner and outer borders of the cell wall and was mainly located within the wall rather than exposed on the outer surface. Sometimes it appeared to be in channels across the cell wall. In the cytoplasm, it was usually near the cytoplasmic membrane and occasionally appeared in vesicular areas. It was not detected in the nucleus or mitochondria. The 47-Kda antigen did not bind to Concanavalin A, and antigenicity was lost after protease digestion. Peptide mapping suggested that the antigen was highly conserved between different strains of C. albicans.
DNA Dynamics in a Microchannel (2003)

An extended Brownian dynamics simulation method is used to characterize the dynamics of long DNA molecules flowing in microchannels. The relaxation time increases due to confinement in agreement with scaling predictions. During flow the molecules migrate toward the channel center line, and thereby segregate according to molecular weight. Capturing these effects requires the detailed incorporation of solvent flow in the simulation method, demonstrating the importance of hydrodynamic effects in the dynamics of confined macromolecules.
Tyrosine kinase activity in Pseudomonas aeruginosa (1994)

Previous evidence showed that b- and a-type flagellins of Pseudomonas aeruginosa are modified in vivo by phosphorylation at tyrosine. This research was designed to demonstrate phosphorylation of flagellin at tyrosine in vitro. Evidence presented showed that flagellin is labelled by [gamma-32P]-ATP, but not by [alpha-32P]-ATP, when incubated with cell envelope fractions. Results suggested that autophosphorylation of a 42 kDa membrane protein occurred. No activity was detected in cytoplasmic fractions. Flagellin protein was identified by flagella-specific monoclonal antibody (mAb) and was labelled with anti-phosphotyrosine mAb. Confirmation of tyrosine kinase activity was shown by labelling of synthetic poly(Glu:Tyr) as a substrate with [gamma-32P]-ATP. Labelling of poly(Glu:Tyr) was heat sensitive and time dependent. Labelled phosphotyrosine was observed in partial acid hydrolysates of substrates. Using poly(Glu:Tyr) as substrate, tyrosine kinase activity was shown to be inhibited by sulphydryl reagents. It appears that tyrosine kinase and flagellin phosphorylation occur in several Pseudomonas spp. Location of phosphotyrosine in a conserved region of flagellin may serve as a cell signal so that intact flagellin is appropriately exported.
Effect of the Serine Protease Inhibitor, Aprotinin, on Systemic Haemodynamics and Renal Function in Patients with Hepatic Cirrhosis and Ascites (1994)

1. Previous studies have documented activation of protease enzymes, such as the plasma kallikrein-kinin system, in hepatic cirrhosis. Increased plasma kinin generation could contribute to pathological systemic vasodilatation in cirrhosis, and reduced systemic vascular resistance has been suggested as a trigger to renal sodium retention in this disease. We investigated the effect of aprotinin, a protease inhibitor which binds to plasma kallikrein, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites. 2. Aprotinin was infused intravenously in high dosage (2 x 10(6) kallikrein inhibitory units loading, 1 x 10(6) kallikrein inhibitory units/h). 3. Of 13 patients, 10 had a low systemic vascular resistance (< 1200 dyn s cm-5) at baseline. In this group, eight showed an increase in systemic vascular resistance during aprotinin infusion. Overall, the increase in systemic vascular resistance was significant, and there was a small but significant increase in mean arterial pressure. In all patients, there were increases in renal plasma flow, glomerular filtration rate, and absolute and fractional urinary sodium excretion during aprotinin infusion. 4. Plasma renin activity, plasma angiotensin II and plasma aldosterone fell significantly during aprotinin infusion. Plasma prekallikrein, plasma noradrenaline and plasma atrial natriuretic peptide did not change. Plasma aprotinin concentration was 209 +/- 11 kallikrein inhibitory units/ml at the end of the infusion. 5. Before and during the infusion, there was a significant negative correlation between systematic vascular resistance and plasma renin activity. There was a positive correlation between the change in systemic vascular resistance and the change in renal plasma flow during aprotinin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Preoperative endoscopic ultrasound-guided fine needle aspiration does not impair survival of patients with resected pancreatic cancer (2015)

Preoperative EUS-FNA was not associated with increased risk of mortality. These data suggest that EUS-FNA can be safely performed for the work-up of suspicious pancreatic lesions.
Reproduction of Lesions of Postweaning Multisystemic Wasting Syndrome in Gnotobiotic Piglets (1999)

Neonatal gnotobiotic piglets were inoculated with tissue homogenates and low- and high-passage cell culture material to determine if the lesions of the newly described porcine postweaning multisystemic wasting syndrome (PMWS) could be reproduced. For this, 17 3-day-old gnotobiotic piglets were inoculated intranasally with pelleted chloroform-treated, filtered extracts from cell cultures, filter-sterilized homogenates of lymphoid tissue from PMWS-affected piglets, or control materials. Piglets were maintained in germ-free isolators for up to 5 weeks after infection prior to euthanasia and collection of samples for analysis. All piglets inoculated with the viral inocula developed lesions typical of PMWS, including generalized lymphadenopathy, hepatitis, nephritis, interstitial pneumonia, myocarditis, and gastritis. Porcine circovirus (PCV), as well as porcine parvovirus (PPV), was detected in tissues by virus reisolation, polymerase chain reaction analysis, or immunohistochemistry. All infected piglets developed moderate to high titers of antibody to PCV and moderate titers to PPV. No lesions, virus, or virus-specific antibodies were detected in sham-inoculated or uninoculated control piglets. These studies demonstrate that the lesions of PMWS can be experimentally reproduced in gnotobiotic piglets using filterable viral agents derived from pigs with PMWS and provide an experimental basis for further investigation into the pathogenesis and control of this emerging infectious disease in swine.
A comparative in vitro evaluation of the fermentation properties of prebiotic oligosaccharides (2001)

The study provides comparative data on the properties of commercial prebiotics, allowing targeting of dietary intervention for particular applications and blending of oligosaccharides to enhance overall functionality.
The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver (1967)

1. The concentrations of the oxidized and reduced substrates of the lactate-, beta-hydroxybutyrate- and glutamate-dehydrogenase systems were measured in rat livers freeze-clamped as soon as possible after death. The substrates of these dehydrogenases are likely to be in equilibrium with free NAD(+) and NADH, and the ratio of the free dinucleotides can be calculated from the measured concentrations of the substrates and the equilibrium constants (Holzer, Schultz & Lynen, 1956; Bücher & Klingenberg, 1958). The lactate-dehydrogenase system reflects the [NAD(+)]/[NADH] ratio in the cytoplasm, the beta-hydroxybutyrate dehydrogenase that in the mitochondrial cristae and the glutamate dehydrogenase that in the mitochondrial matrix. 2. The equilibrium constants of lactate dehydrogenase (EC 1.1.1.27), beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30) and malate dehydrogenase (EC 1.1.1.37) were redetermined for near-physiological conditions (38 degrees ; I0.25). 3. The mean [NAD(+)]/[NADH] ratio of rat-liver cytoplasm was calculated as 725 (pH7.0) in well-fed rats, 528 in starved rats and 208 in alloxan-diabetic rats. 4. The [NAD(+)]/[NADH] ratio for the mitochondrial matrix and cristae gave virtually identical values in the same metabolic state. This indicates that beta-hydroxybutyrate dehydrogenase and glutamate dehydrogenase share a common pool of dinucleotide. 5. The mean [NAD(+)]/[NADH] ratio within the liver mitochondria of well-fed rats was about 8. It fell to about 5 in starvation and rose to about 10 in alloxan-diabetes. 6. The [NAD(+)]/[NADH] ratios of cytoplasm and mitochondria are thus greatly different and do not necessarily move in parallel when the metabolic state of the liver changes. 7. The ratios found for the free dinucleotides differ greatly from those recorded for the total dinucleotides because much more NADH than NAD(+) is protein-bound. 8. The bearing of these findings on various problems, including the following, is discussed: the number of NAD(+)-NADH pools in liver cells; the applicability of the method to tissues other than liver; the transhydrogenase activity of glutamate dehydrogenase; the physiological significance of the difference of the redox states of mitochondria and cytoplasm; aspects of the regulation of the redox state of cell compartments; the steady-state concentration of mitochondrial oxaloacetate; the relations between the redox state of cell compartments and ketosis.
Predicting Protein Complex Membership Using Probabilistic Network Reliability (2004)

Evidence for specific protein-protein interactions is increasingly available from both small- and large-scale studies, and can be viewed as a network. It has previously been noted that errors are frequent among large-scale studies, and that error frequency depends on the large-scale method used. Despite knowledge of the error-prone nature of interaction evidence, edges (connections) in this network are typically viewed as either present or absent. However, use of a probabilistic network that considers quantity and quality of supporting evidence should improve inference derived from protein networks. Here we demonstrate inference of membership in a partially known protein complex by using a probabilistic network model and an algorithm previously used to evaluate reliability in communication networks.
Cloning of the human homologue of the murine flt3 ligand: a growth factor for early hematopoietic progenitor cells (1994)

Using a fragment of the murine flt3 ligand as a probe, we have succeeded in cloning a human flt3 ligand from a human T-cell lambda gt10 cDNA library. The human and murine ligands are 72% identical at the amino acid level. Analysis of multiple cDNA clones shows that alternative splicing of the human flt3 mRNA can occur at a number of positions. A recombinant soluble form of the human flt3 ligand stimulates the proliferation and colony formation of a subpopulation of human bone marrow cells that are CD34+ and are enriched for primitive hematopoietic cells. In addition, the human flt3 ligand also stimulates the proliferation of cells expressing murine flt3 receptors. Northern blot analysis shows widespread expression of flt3 ligand mRNA transcripts in human tissues.
Ocular Preparations: The Formulation Approach (2002)

The main aim of pharmacotherapeutics is the attainment of an effective drug concentration at the intended site of action for a sufficient period of time to elicit the response. A major problem being faced in ocular therapeutics is the attainment of an optimal concentration at the site of action. Poor bioavailability of drugs from ocular dosage forms is mainly due to the tear production, non-productive absorption, transient residence time, and impermeability of corneal epithelium. This article reviews: the barriers that decrease the bioavailability of an ophthalmic drug; the objectives to be considered in producing optimal formulations; and the approaches being used to improve the corneal penetration of a drug molecule and delay its elimination from the eye. The focus of this review is on the recent developments in topical ocular drug delivery systems, the rationale for their use, their drug release mechanism, and the characteristic advantages and limitations of each system. In addition, the review attempts to give various analytical procedures including the animal models and other models required for bioavailability and pharmacokinetic studies. The latter can aid in the design and predictive evaluation of newer delivery systems.The dosage forms are divided into the ones which affect the precorneal parameters, and those that provide a controlled and continuous delivery to the pre- and intraocular tissues. The systems discussed include: (a) the commonly used dosage forms such as gels, viscosity imparting agents, ointments, and aqueous suspensions; (b) the newer concept of penetration enhancers, phase transition systems, use of cyclodextrins to increase solubility of various drugs, vesicular systems, and chemical delivery systems such as the prodrugs; (c) the developed and under-development controlled/continuous drug delivery systems including ocular inserts, collagen shields, ocular films, disposable contact lenses, and other new ophthalmic drug delivery systems; and (d) the newer trends directed towards a combination of drug delivery technologies for improving the therapeutic response of a non-efficacious drug. The fruitful resolution of the above-mentioned technological suggestions can result in a superior dosage form for both topical and intraocular ophthalmic application.
Oxidative Modification of Brain Proteins in Alzheimer's Disease: Perspective on Future Studies Based on Results of Redox Proteomics Studies (2012)

Aging is the major risk factor associated with neurodegenerative diseases, including Alzheimer's disease (AD). Until now no clear understanding of the mechanisms of initiation and progression of this dementing disorder exists. Based on the studies th
Repurposing the anthelmintic drug niclosamide to combat Helicobacter pylori (2018)

There is an urgent need to discover novel antimicrobial therapies. Drug repurposing can reduce the time and cost risk associated with drug development. We report the inhibitory effects of anthelmintic drugs (niclosamide, oxyclozanide, closantel, rafoxanide) against Helicobacter pylori strain 60190 and pursued further characterization of niclosamide against H. pylori. The MIC of niclosamide against H. pylori was 0.25 μg/mL. Niclosamide was stable in acidic pH and demonstrated partial synergy with metronidazole and proton pump inhibitors, such as omeprazole and pantoprazole. Niclosamide administration at 1 × MIC concentration, eliminated 3-log<sub>10</sub> CFU of H. pylori adhesion/invasion to AGS cells. Interestingly, no resistance developed even after exposure of H. pylori bacteria to niclosamide for 30 days. The cytotoxic assay demonstrated that niclosamide is not hemolytic and has an IC<sub>50</sub> of 4 μg/mL in hepatic and gastric cell lines. Niclosamide administration decreased transmembrane pH as determined by DiSC<sub>3</sub>(5) assay indicating that the mechanism of action of the anti-H. pylori activity of niclosamide was the disruption of H. pylori proton motive force. Niclosamide was effective in the Galleria mellonella-H. pylori infection model (p = 0.0001) and it can be develop further to combat H. pylori infection. However, results need to be confirmed with other H. pylori and clinical strains.
N2-1H-Benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines as potential antifilarial agents (1983)

A series of N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines (XI) was synthesized for antifilarial evaluation. Condensation of the requisite beta-keto ester (VI) with N-cyanoguanidine afforded 2-pyrimidinylcyanamides (VIIa,b) and (5,6,7,8-tetrahydro-4-hydroxy-2-quinazolinyl)cyanamide (VIIc). Reaction of VII with a substituted o-phenylenediamine gave 2-(1H-benzimidazol-2-ylamino)-4-pyrimidinols and 2-[(5,6-dichloro-1H-benzimidazol-2-yl)amino]-5,6,7, 8-tetrahydro-4-quinazolinol (IX). Chlorination with phosphoryl chloride, followed by condensation with the appropriate substituted benzenamine, gave the desired N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines (XI). None of these compounds possessed antifilarial activity against Litomosoides carinii or Brugia pahangi infections in jirds.
Amniocentesis: Indications and Risks (2008)

Amniocentesis is an invasive procedure that requires removing a sample of amniotic fluid to obtain fetal cells for chromosome analysis. Generally not performed earlier than 15 weeks gestation, the procedure is done under ultrasound guidance. Although some pain is associated with amniocentesis, it is generally well tolerated without the need for anesthesia. Five to 10 percent of pregnant women choose to have the test [1, 2]. Maternal age over 35 is the most common current indication for amniocentesis [3].
An innovative monopole antenna for mobile-phone handsets (2000)

An innovative monopole antenna with a parasitic helix mounted on the ground plane is designed for installation on mobile-phone handsets. Unlike the conventional monopole antenna, measurements showed that the added parasitic helix could result in a wider bandwidth for the whole antenna. The radiation patterns and the polarization properties of the monopole antenna are also shown to be relatively unchanged. Results at 1.8 GHz,which is the operating frequency of PCS (personal communications services) or GSM1800, will be presented. © 2000 John Wiley & Sons, Inc. Microwave Opt Technol Lett 25: 119–121, 2000.
Monoclonal Antibodies: Their Importance to Surgeons (1989)

A tremendous technological advance occurred in 1975 when a method was developed to fuse two cells producing a "hybridoma" which secretes a single clone of antibody, having one immunoglobulin (Ig) class, one structure, one affinity, and one specificity for an antigenic determinant. Because monoclonal antibodies are more precise reagents than conventional antisera they open new doors to diagnosis and therapy of disease, and they are useful tools in research. The pathologist uses monoclonals in immunocytochemistry to determine tumor type; the surgeon uses monoclonals for immunosuppression in renal transplantation; the immunologist uses monoclonals to decipher cellular and humoral interactions that could not be appreciated with polyclonal reagents. This review outlines the background of monoclonal antibodies and some of their clinically important uses, both in vitro and in vivo. We also project into the future and describe chimeric antibodies and their possible uses.
The inhibition of DNA synthesis by cannabinoids. (1976)

Several of the cannabinoids found in marihuana have been shown to inhibit tumor growth and increase the life-span of mice bearing the Lewis lung adenocarcinoma. When trypsin-dispersed isolated Lewis lung cells are incubated in vitro, they maintain their capacity to carry out macromolecular synthesis (RNA, DNA, protein). This process can be inhibited by cytosine arabinoside, actinomycin D, or methyl-1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas cyclophosphamide, an agent that must be bioactivated, was inactive. Inhibition of DNA synthesis as measured by [3H]thymidine uptake into acid-insoluble material was used as an index of cannabinoid activity against isolated Lewis lung cells, L1210 leukemia cells, and bone marrow cells incubated in vitro delta9-, delta8-, 1-hydroxy-3-n pentyl-, and 1-delta8-tetrahydrocannabinol, and cannabinol demonstrated a dose-dependent inhibition of DNA synthesis whereas cannabidiol and 1-hydroxy-3-n-pentylcannabidiol were markedly less inhibitory in our in vitro cell systems. Furthermore, our in vitro observations with these cannabinoids are supported by in vivo tumor inhibition studies. Ring modifications as in cannabichromene or cannabicyclol abolish in vitro activity as does dihydroxylation at the 8beta and 11 positions of 1-delta9-trans-tetrahydrocannabinol. Delta9-trans-tetrahydrocannabinol demonstrated the least toxicity of all inhibitory cannabinoids in vivo; this is supported by its lesser effect on bone marrow DNA synthesis in vitro.
Resistance to mitoxantrone in multidrug-resistant MCF7 breast cancer cells: evaluation of mitoxantrone transport and the role of multidrug resistance protein family proteins. (2001)

We examined the role of multidrug resistance protein (MRP) 1 (ABCC1) in the emergence of mitoxantrone (MX) cross-resistance in a MCF7 breast cancer cell line selected for resistance to etoposide. The resistant cell line, MCF7/VP, expresses high levels of MRP1, whereas the parental cell line, MCF7/WT, does not. MCF7/VP cells are 6-10-fold cross-resistant to MX when compared with MCF7/WT cells. Drug transport studies in intact MCF7/VP cells revealed that MX resistance is associated with reduced MX accumulation due to enhanced MX efflux. MX efflux is ATP dependent and inhibited by sulfinpyrazone and cyclosporin A. Inhibition of MX efflux with these agents sensitizes cells to MX cytotoxicity and partially reverses MX resistance in MCF7/VP cells. Whereas resistance is partially attributable to increased MX efflux in MRP1-expressing MCF7/VP cells, we found no evidence for glutathione or other conjugates of MX in these cells. Moreover, glutathione depletion with buthionine sulfoximine had no effect on MX transport or sensitivity in MCF7/VP cells. MRP1 substrates are generally amphiphilic anions such as glutathione conjugates or require the presence of physiological levels of glutathione for MRP1-mediated transport. Therefore we conclude that MRP1 overexpression is unlikely to be responsible for increased MX efflux and resistance in MCF7/VP cells. In considering the potential involvement of other MRP family isoforms, a 3-fold increase in the expression of MRP5 was observed in MCF7/VP cells. However, stable expression of a transduced MRP5 expression vector in MCF7/WT cells failed to confer MX resistance. Because other transporters known to be associated with MX resistance, including P-glycoprotein and BCRP/MXR (ABCG2), are not expressed in MCF7/VP cells, we conclude that increased MX efflux and resistance in MCF7/VP cells is attributable to a novel transport mechanism or that MX represents a novel class of cationic, glutathione-independent MRP1 substrates.