gebhart/patrepeval huggingface dataset:
Expression of transformation-associated protease(s) that degrade fibronectin at cell contact sites. (1984)

Virus-transformed fibroblasts show an increased production of proteases as well as loss of extracellular adhesive proteins. To determine whether these transformation-associated events are related, we investigated the capacity of Rous sarcoma virus-transformed cells (embryonic chick fibroblasts and mouse BALB/c 3T3) to degrade fibronectin by using a novel cross-linked protein substratum: fluorescence-labeled or radiolabeled fibronectin covalently linked to the surface of a fixed gelatin film. In serum-containing medium, the coupled fibronectin was not released when incubated without cells, and only a small amount was released when incubated with nontransformed cells. However, when transformed cells were seeded on the radiolabeled fibronectin-coupled substratum, there was a threefold increase in the time-dependent release of radioactivity into the medium. The released material was characterized as peptides with molecular sizes of less than 30,000 daltons. Correspondingly, growth of transformed cells on the rhodamine-fibronectin substratum resulted in the appearance of discrete negative fluorescent spots beneath the cells and along their migratory paths, whereas a uniform fluorescent carpet was detected with nontransformed cells. The release of radioactivity was partially inhibited by protease inhibitors, including alpha 2-macroglobulin, leupeptin, and benzamidine, but the negative fluorescent spots appeared unaffected by any of these inhibitors. However, both the release of radiolabeled peptides and the appearance of fluorescence-negative spots were inhibited by 1,10-phenanthroline at concentrations that did not affect cellular attachment and protein synthesis, thus supporting a role for proteases in localized degradation of fibronectin substratum. These fluorescence-negative spots coincided with sites of fibronectin disappearance as judged by indirect labeling with antibodies to cellular fibronectin. In addition, immunofluorescent analyses showed a correlation between vinculin localization and the negative fibronectin spots found under transformed cells, indicating that degradation occurs at cell substratum contact sites. These results can be correlated with other transformation-associated phenotypic changes, and are discussed in terms of the invasion of tumor cells into the extracellular matrix.
One Stage Full‐ Versus Partial‐Mouth Disinfection in the Treatment of Chronic Adult or Generalized Early‐Onset Periodontitis. I. Long‐Term Clinical Observations (1999)

These findings suggest that a one stage full-mouth disinfection results in an improved clinical outcome for the treatment of chronic adult or early-onset periodontitis as compared to scaling and root planing per quadrant at 2-week intervals.
Metabolic Effects of Sodium Dichloroacetate in Normal and Diabetic Dogs (1979)

The effects of acute and chronic administration of sodium dichloroacetate (DCA) were studied in the normal and diabetic dog. In the normal dog, a single oral injection of DCA (150 mg/kg) provoked a rapid decrease of the lactate, pyruvate, and triglyceride concentrations and a progressive decrease of blood glucose. These effects lasted longer than 24 h. In the alloxan-diabetic dog deprived of insulin for 72 h, DCA induced a decrease of blood glucose, lactate, and pyruvate concentrations as well as of glucosuria. In these ketotic animals, the plasma lipid compounds and the blood and urinary ketone bodies were not significantly changed by DCA. In the normal dog, the chronic administration of DCA (150 mg/kg daily for 7 days) provoked a decrease in blood glucose, lactate, pyruvate, and oxaloacetate concentrations, which returned to starting values only within 2 to 5 days after the end of the treatment, depending on the compounds studied. A decrease of cholesterol was also noted. During the chronic administration of DCA, blood β-hydroxybutyrate and acetoacetate concentrations strongly increased. When treated with insulin alone, the alloxan-diabetic dogs had a high blood glucose concentration; the blood lactate, pyruvate, and oxaloacetate concentrations did not differ significantly from those of the normal animals, however. In these diabetic dogs, the lipid compounds and, particularly, the ketone compounds were increased. The addition of DCA (75 mg/kg daily for 7 days) provoked a drop in blood lactate, pyruvate, and oxaloacetate levels, and a reduction of blood glucose and plasma cholesterol, triglyceride, and total lipids was also noted. Blood β-hydroxybutyrate and acetoacetate concentrations, which were already high at the start, were not affected when DCA was associated to insulin. This addition of DCA provoked a rapid and marked reduction in glucosuria, which was concomitant with an increase in urinary β-hydroxybutyrate and acetone.
Interleukin-21 is a growth and survival factor for human myeloma cells (2002)

Interleukin-21 (IL-21) is a recently cloned cytokine with homology to IL-2, IL-4, and IL-15. In this study we examined the effects of IL-21 on human myeloma cells. We found that IL-21 induced proliferation and inhibited apoptosis of the IL-6-dependent human myeloma cell lines ANBL-6, IH-1, and OH-2. The potency of IL-21 was close to that of IL-6 in the OH-2 cell line. Neutralizing antibodies to IL-6 or the IL-6 receptor transducer chain (gp130) did not affect IL-21-induced DNA synthesis, indicating that IL-21-induced proliferation was not mediated through these proteins. Tumor necrosis factor (TNF), another stimulator of myeloma cell growth, up-regulated the expression level of IL-21 receptor (IL-21R), and combinations of TNF and IL-21 gave synergistic effects on myeloma cell proliferation. Furthermore, 4 of 9 purified samples of primary myeloma cells showed a significant increase in DNA synthesis on stimulation of the cells by IL-21. By Western blot analysis, we demonstrated that the intracellular signaling pathways of IL-21 in myeloma cells involved phosphorylation of Jak1, Stat3, and Erk1/2 (p44/42 mitogen-activated protein kinase). IL-21 is a novel growth and survival factor in multiple myeloma and may represent a target for future therapy.
Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury (2007)

Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia.
Conjugated Macrocycles: Concepts and Applications (2011)

One of the most important objectives in materials, chemical, and physical sciences is the creation of large conjugated macrocycles with well-defined shapes, since such molecules are not only theoretically and experimentally interesting but also have potential applications in nanotechnology. Fully unsaturated macrocycles are regarded as models for infinitely conjugated π systems with inner cavities, and exhibit unusual optical and magnetic behavior. Macrocycles have interior and exterior sites, and site-specific substitution at both or either site can afford attractive structures, such as 1D, 2D, and 3D supramolecular nanostructures. These nanostructures could be controlled through the use of π-extended large macrocycles by a bottom-up strategy. Numerous shape-persistent π-conjugated macrocycles have been synthesized, but only a few are on the nanoscale. This Review focuses on nanosized π-conjugated macrocycles (>1 nm diameter) and giant macrocycles (>2 nm diameter), and summarizes their syntheses and properties.
Role of interferon alfa-2b in the induction and maintenance treatment of low-grade non-Hodgkin's lymphoma: results from a prospective, multicenter trial with double randomization. (1998)

Adding IFN alfa-2b to induction CVP in low-grade NHL did not induce a higher response rate, but it significantly increased the duration of the responses. We found significant differences in PFS that favored the patients who received CVP + IFN, but not in OS. To date, no additional benefit has been seen from the administration of IFN for maintenance.
Synthesis ofS-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines (2015)

S-nitrosothiols are a class of NO-donors currently under investigation for the treatment of various diseases. In this study, we developed a novel NO-donor (S-nitrosoglutathione-alginate, SNA) by cross-linking alginate with S-nitrosothiols, which can deliver NO in a sustained manner. This compound can be further evaluated for oral delivery to treat Crohn's disease. This new compound was prepared using a two-step procedure involving (I) linkage of reduced glutathione to alginate and (II) post-nitrosation with sodium nitrite (NaNO<sub>2</sub>). The amount of linked thiol moieties for the possible nitrosation was calculated using Ellman's method, and the amount of NO abducted on the polymer was calculated using the Griess-Saville method. An ex vivo model (i.e. Ussing chamber) was used to investigate the permeation of this new NO-donor across the rat intestinal barrier. We obtained polymers with different numbers of abducted NOs (174 ± 21 μmol/g for SNA F1 and 468 ± 23 μmol/g for SNA F2) depending on the procedure used for nitrosation. In the ex vivo studies in the Ussing chamber, SNA F2 exhibited a sustained release for at least 10 h. The effect of pH on the stability of the new compound was also investigated, and the new compound was more stable at a mildly basic pH of 8.4 where 73% remained after 1 week. However, only 50% remained after 1 week at an acidic pH of 1.2. In the cytotoxicity studies (Caco2), this compound was nontoxic at concentrations of less than 200 μM.
Induction of Heat Shock Protein 47 Synthesis by TGF-β and IL-1β Via Enhancement of the Heat Shock Element Binding Activity of Heat Shock Transcription Factor 1 (2002)

With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF- beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.
Failures in Clinical Treatment of Staphylococcus aureus Infection with Daptomycin Are Associated with Alterations in Surface Charge, Membrane Phospholipid Asymmetry, and Drug Binding (2007)

Increasingly frequent reports have described the in vivo loss of daptomycin susceptibility in association with clinical treatment failures. The mechanism(s) of daptomycin resistance is not well understood. We studied an isogenic set of Staphylococcus aureus isolates from the bloodstream of a daptomycin-treated patient with recalcitrant endocarditis in which serial strains exhibited decreasing susceptibility to daptomycin. Since daptomycin is a membrane-targeting lipopeptide, we compared a number of membrane parameters in the initial blood isolate (parental) with those in subsequent daptomycin-resistant strains obtained during treatment. In comparison to the parental strain, resistant isolates demonstrated (i) enhanced membrane fluidity, (ii) increased translocation of the positively charged phospholipid lysyl-phosphotidylglycerol to the outer membrane leaflet, (iii) increased net positive surface charge (P < 0.05 versus the parental strain), (iv) reduced susceptibility to daptomycin-induced depolarization, permeabilization, and autolysis (P < 0.05 versus the parental strain), (v) significantly lower surface binding of daptomycin (P < 0.05 versus the parental strain), and (vi) increased cross-resistance to the cationic antimicrobial host defense peptides human neutrophil peptide 1 (hNP-1) and thrombin-induced platelet microbicidal protein 1 (tPMP-1). These data link distinct changes in membrane structure and function with in vivo development of daptomycin resistance in S. aureus. Moreover, the cross-resistance to hNP-1 and tPMP-1 may also impact the capacity of these daptomycin-resistant organisms to be cleared from sites of infection, particularly endovascular foci.
A Panel of Monoclonal Antibodies against Human Polycomb Group Proteins (2002)

Polycomb-group (PcG) proteins are chromatin-associated proteins that heritably repress gene activity in many organisms, including man. Two distinct human PcG complexes have been identified. The HPC/HPH PcG complex I contains the HPC, HPH, RING1, and BMI1 proteins, the EED/EZH2 PcG complex II contains the EED, EZH2, and YY1 proteins. Previously we found that the relative expression levels of proteins of the human PcG complexes I and II are severely deregulated in human tumors. These findings signify an important role for antibodies against human PcG proteins as diagnostic tools. To be able to produce standardized anti-human PcG antibodies, we developed a panel of five mouse monoclonal antibodies (MAbs) against the human PcG proteins HPC2, BMI1, RING1A, EED, and EZH2. All MAbs can be used for Western blot analysis and immunofluorescence labeling of tissue culture cells. With the exception of the MAb against HPC2, all MAbs can also be used in immunoprecipitation experiments and immunohistochemistry of human tissues. The novel MAbs are therefore valuable tools for the cell biological, biochemical, and pathological analysis of human PcG proteins.
The Effect of Active Living and Physical Activity on Post-prandial IL-6 and CRP (2011)

Aims: Post-prandial increases in inflammatory markers IL-6 and C-reactive protein (CRP) have been observed following high fat and high carbohydrate meals. Inflammation is associated with increased risk of chronic diseases such as cancer. In addition, sedentary behaviour is also associated with negative health outcomes. Meanwhile, elevated IL-6 and CRP have been associated with a negative mood. The study aim was to compare the effects of continuous physical activity to breaks in sedentary behaviour on post-prandial IL-6 and CRP. The secondary aim was to compare the impact of these patterns (as detailed above) on measures of mood states. &#13;\n&#13;\nMethods: Twenty four healthy sedentary participants (15 female, nine male, mean ± SD, age 25.8 ± 5.8 yr, BMI, 23.6 ± 5.0 kg/m2) completed three, 9 h testing days. These were: sedentary (SE), participants remained seated for 9 h; physical activity (PA), participants performed 30 min of exercise at a speed and incline to elicit 60% VO2max prior to the first meal replacement beverage and were then seated for the remainder of the 9 h; active living (AL), participants walked for 1 min 40s every 30 min throughout the day (this equals 30 min of physical activity spread out over 9 h) at the same speed and incline as the PA condition. For each condition participants received three meal replacement beverages at 1, 4 and 7 h. Each meal provided 0.46 g fat/kg BW, 0.54 g protein/kg BW and 1.12 g CHO/kg BW. Venous blood samples were collected at baseline, 4 and 8 h to measure IL-6 and CRP. Mood was assessed using the Brunel University Mood Scale at 0 and 9 h. &#13;\n&#13;\nResults: In the SE and PA conditions there was a post-prandial increase in IL-6 at 4 and 8 h compared to baseline (SE p&lt;0.0001, 4 and 8 h; PA p&lt;0.001 and p&lt;0.0001, 4 and 8 h respectively. In the AL condition, IL-6 increased at 8 h compared to baseline (p&lt;0.05). The IL-6 concentration at 8 h in AL was significantly lower than the 8 h concentration in the SE and PA conditions (p&lt;0.05). There was no change in CRP from baseline, nor was there a difference between conditions. No correlation existed between mood and CRP. Increases in IL-6 correlated with a more depressed mood. Both PA and SE conditions decreased tension. There was no effect of AL on mood. &#13;\n&#13;\nConclusions: Interleukin-6 increased 4 and 8 h post-prandially when sedentary. Thirty min of moderate continuous physical activity following an overnight fast and prior to a meal does not decrease the post-prandial IL-6 response. Breaking sedentary behaviour by as little as 1 min 40 s every 30 min attenuates the post-prandial IL-6 response and thereby, may reduce the risk of chronic diseases. Practical applications from these findings include the use of computer prompts or television advertising to promote standing and walking in individuals with desk jobs or when watching television for long periods of time.
Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. (1992)

Advanced glycosylation end products of proteins (AGEs) are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. A approximately 35-kDa polypeptide with a unique NH2-terminal sequence has been isolated from bovine lung and found to be present on the surface of endothelial cells where it mediates the binding of AGEs (receptor for advanced glycosylation end product or RAGE). Using an oligonucleotide probe based on the amino-terminal sequence of RAGE, an apparently full-length cDNA of 1.5 kilobases was isolated from a bovine lung cDNA library. This cDNA encoded a 394 amino acid mature protein comprised of the following putative domains: an extracellular domain of 332 amino acids, a single hydrophobic membrane spanning domain of 19 amino acids, and a carboxyl-terminal domain of 43 amino acids. A partial clone encoding the human counterpart of RAGE, isolated from a human lung library, was found to be approximately 90% homologous to the bovine molecule. Based on computer analysis of the amino acid sequence of RAGE and comparison with databases, RAGE is a new member of the immunoglobulin superfamily of cell surface molecules and shares significant homology with MUC 18, NCAM, and the cytoplasmic domain of CD20. Expression of the RAGE cDNA in 293 cells allowed them to bind 125I-AGE-albumin in a saturable and dose-dependent manner (Kd approximately 100 nM), blocked by antibody to RAGE. Western blots of 293 cells transfected with RAGE cDNA probed with anti-RAGE IgG demonstrated expression of immunoreactive protein compared to its absence in mock-transfected cells. These results suggest that RAGE functions as a cell surface receptor for AGEs, which could potentially mediate cellular effects of this class of glycosylated proteins.
Evaluation of the impact of six different DNA extraction methods for the representation of the microbial community associated with human chronic wound infections using a gel-based DNA profiling method (2017)

Infected chronic wounds are polymicrobial in nature which include a diverse group of aerobic and anaerobic microorganisms. Majority of these communal microorganisms are difficult to grow in vitro. DNA fingerprinting methods such as polymerase chain reaction-denaturation gradient gel electrophoresis (PCR-DGGE) facilitate the microbial profiling of complex ecosystems including infected chronic wounds. Six different DNA extraction methods were compared for profiling of the microbial community associated with chronic wound infections using PCR-DGGE. Tissue debris obtained from chronic wound ulcers of ten patients were used for DNA extraction. Total nucleic acid was extracted from each specimen using six DNA extraction methods. The yield, purity and quality of DNA was measured and used for PCR amplification targeting V2-V3 region of eubacterial 16S rRNA gene. QIAGEN DNeasy Blood and Tissue Kit (K method) produced good quality genomic DNA compared to the other five DNA extraction methods and gave a broad diversity of bacterial communities in chronic wounds. Among the five conventional methods, bead beater/phenol-chloroform based DNA extraction method with STES buffer (BP1 method) gave a yield of DNA with a high purity and resulted in a higher DGGE band diversity. Although DNA extraction using heat and NaOH had the lowest purity, DGGE revealed a higher bacterial diversity. The findings suggest that the quality and the yield of genomic DNA are influenced by the DNA extraction protocol, thus a method should be carefully selected in profiling a complex microbial community.
Precise Robust Positioning with Inertially Aided RTK (2006)

ABSTRACT: This paper addresses the problem of “robust” positioning, which is the ability of a positioning system to determine position with continuous accuracy in spite of GPS outages. The paper describes an aided INS (AINS) with inertially aided RTK (IARTK) as one solution to a robust RTK positioning problem. It describes the design of the IARTK-AINS and discusses the factors that control the maximum outage duration for rapid fixed integer ambiguity recovery and the position accuracy during the outage. The IARTK-AINS implements tightly coupled inertial/GPS integration with floated ambiguity estimation and fixed integer search in a single Kalman filter. The IARTK-AINS is able to recover L1 integer ambiguities within seconds of a short-duration GPS outage while maintaining decimeter-level accuracy throughout the outage. The paper then describes the performance of the IARTK-AINS during various tests involving controlled GPS outages and uncontrolled GPS availability during navigation in a demanding urban canyon environment.