gebhart/patrepeval huggingface dataset:
Assembly of the Platelet Prothrombinase Complex Is Linked to Vesiculation of the Platelet Plasma Membrane (1989)

Activation of human platelets by complement proteins C5b-9 is accompanied by the release of small plasma membrane vesicles (microparticles) that are highly enriched in binding sites for coagulation factor Va and exhibit prothrombinase activity. We have now examined whether assembly of the prothrombinase enzyme complex (factors VaXa) is directly linked to the process of microparticle formation. Gel-filtered platelets were incubated without stirring with various agonists at 37 degrees C, and the functional expression of cell surface receptors on platelets and on shed microparticles was analyzed using specific monoclonal antibodies and fluorescence-gated flow cytometry. In addition to the C5b-9 proteins, thrombin, collagen, and the calcium ionophore A23187 were each found to induce formation of platelet microparticles that incorporated plasma membrane glycoproteins GP Ib, IIb, and IIIa. These microparticles were enriched in binding sites for factor Va, and their formation paralleled the expression of catalytic surface for the prothrombinase enzyme complex. Little or no microparticle release or prothrombinase activity were observed when platelets were stimulated with epinephrine and ADP, despite exposure of platelet fibrinogen receptors by these agonists. When platelets were exposed to thrombin plus collagen, the shed microparticles contained activated GP IIb-IIIa complexes that bound fibrinogen. By contrast, GP IIb-IIIa incorporated into C5b-9 induced microparticles did not express fibrinogen receptor function. Platelets from a patient with an isolated defect in inducible procoagulant activity (Scott syndrome) were found to be markedly impaired in their capacity to generate microparticles in response to all platelet activators, and this was accompanied by a comparable decrease in the number and function of inducible factor Va receptors. Taken together, these data indicate that the exposure of the platelet factor Va receptor is directly coupled to plasma membrane vesiculation and that this event can be dissociated from other activation-dependent platelet responses. Since a catalytic membrane surface is required for optimal thrombin generation, platelet microparticle formation may play a role in the normal hemostatic response to vascular injury.
Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients (2007)

Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the alpha-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2alpha have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2alpha were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2alpha (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2alpha. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2alpha (correlation coefficient 0.77, P=0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients.
Micellar Growth, Network Formation, and Criticality in Aqueous Solutions of the Nonionic Surfactant C12E5 (2000)

We used cryo-TEM and light scattering to study the micellar growth and subsequent network formation in aqueous solutions of the nonionic surfactant C12E5. Cryo-TEM shows the first direct evidence for the existence of connected topology in the vicinity of the critical point and the two-phase separation curve of the C12E5/water micellar system. The coexisting phases within the two-phase region consist of one concentrated and one dilute network of interconnected cylindrical micelles. These findings are consistent with the recent theoretical explanation of criticality and phase separation in certain nonionic surfactant systems as resulting from entropic attraction between network junctions. Away from the two-phase separation curve, we have identified uniaxial micellar growth, with increasing temperature and concentration, into long threadlike micelles. From the power-law dependence of the radius of gyration, RG,z, and the hydrodynamic diameter, D̄H, on the molecular weight (RG,z, D̄H ∼ Mwν), we find that these threadlike micelles have properties resembling those of flexible polymers in a good solvent (ν ∼ 0.6). Static and dynamic light scattering show that the mean micelle contour length L⃗ increases as c0.5 (c is the surfactant concentration) in agreement with theory. Finally, we show that the end-cap energy Ec increases linearly with temperature.
Characterization ofemb, a Gene Encoding the Major Adhesin ofStreptococcus defectivus (1999)

Streptococcus defectivus is one of the nutritionally variant streptococci, a class of viridans group streptococci first isolated from patients with endocarditis and otitis media. In previous studies, NVS-47, a clinical isolate of S. defectivus, was shown to bind to the extracellular matrix. A high-molecular-weight surface protein was identified and proposed to be responsible for mediating this binding. In the present study, the gene encoding this protein was identified by transposon mutagenesis and characterized. The gene (emb) was found to be larger than 14 kb and was partially sequenced. It encodes a protein containing at least 50 repeats of 77 amino acids predicted to assume an alternating coiled-coil conformation. The domain responsible for extracellular matrix binding was mapped to the N terminus of the protein. From sequence analysis, Emb is proposed to be the prototype of a new family of streptococcal fibrillar proteins.
The role of mass spectrometry in vitamin D research (1995)

Abstract 1,25‐dihydroxyvitamin D 3 is the active metabolite of vitamin D 3 , and has been found to play important roles in mineral balance and immunological regulation. Recently, 1,25‐dihydroxyvitamin D 3 and similar synthetic analogs in development have been found to possess potential therapeutic values in the treatment of proliferative diseases, including leukemia, breast cancer, and psoriasis. Current methods for the analysis of these compounds may either lack the necessary sensitivity (i.e., UV detection) or specificity (i.e., receptor binding assay). In addition, the synthetic analogs developed to date have not been found to uniformly bind with receptors in binding assays, a property that may render them to be difficult for measurement at the trace levels. Methods utilizing mass spectrometry (MS) have been used for either structural identification or quantification. Electron impact ionization has been the technique of choice for structural analysis, whereas newer ionization techniques have been utilized for the quantification of metabolites, often in conjunction with on‐line separation. In this review, MS and non‐MS based methods for vitamin D analysis will be discussed, with an emphasis on the former. Historical perspectives, the present state, and the future role of MS in vitamin D research will be discussed. © 1996 John Wiley &amp; Sons, Inc.
The Bcl-2 Protein Family (2000)

Apoptosis, oxidative stress, and neuroinflammation have been linked to the onset of Parkinson's disease (PD). Although the pre-treatment effects of Silibinin on a PD model have been evaluated, in the current study we investigated the chronic therapeutic effects of Silibinin microinjection on a rat model of established parkinsonism along with behavioral and laboratory markers assessments.Parkinsonism was induced by 6-hydroxydopamine (6-OHDA, 8 μg/2μl/rat). 21 days after that, animals were treated with Silibinin (100, 200, and 300 mg/kg for 15 consecutive days). Every two days, the bar test was used to evaluate Silibinin's anti-cataleptic properties. At the end, myeloperoxidase (MPO) activity and toll-like receptor 4 (TLR4) expression in the substantia nigra pars compacta (SNc), along with cerebrospinal fluid (CSF) levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, caspase-3, Bax and Bcl-2 levels were assessed. We used homology modeling to predict the 3D structure of TLR4.Silibinin's Chronic treatment, dose-dependently decreased catalepsy. MPO activity and levels of TNF-α, IL-6, and IL-1β were reduced in Silibinin-treated rats in all three doses. Silibinin decreased Bax/Bcl-2 ratio, caspase-3, and downregulated TLR4 expression. Molecular docking revealed that there were hydrophobic and hydrogen bond interactions between the studied ligand and TLR4. Silibinin formed a stable complex with both monomer and dimer forms of TLR4.In accordance with molecular modeling and alleviation of TLR4 activity with a consequent reduction in oxidative stress, restoration of CSF inflammatory cytokine, and minimization of SNc neuronal apoptosis, long-term therapy with Silibinin offers a potential opportunity for symptomatic PD treatment.
Expression of a cytoplasmic transhydrogenase in Saccharomyces cerevisiae results in formation of 2‐oxoglutarate due to depletion of the NADPH pool (2001)

The intracellular redox state of a cell is to a large extent defined by the concentration ratios of the two pyridine nucleotide systems NADH/NAD+ and NADPH/NADP+ and has a significant influence on product formation in microorganisms. The enzyme pyridine nucleotide transhydrogenase, which can catalyse transfer of reducing equivalents between the two nucleotide systems, occurs in several organisms, but not in yeasts. The purpose of this work was to analyse how metabolism during anaerobic growth of Saccharomyces cerevisiae might be altered when transfer of reducing equivalents between the two systems is made possible by expression of a cytoplasmic transhydrogenase from Azotobacter vinelandii. We therefore cloned sth, encoding this enzyme, and expressed it under the control of a S. cerevisiae promoter in a strain derived from the industrial model strain S. cerevisiae CBS8066. Anaerobic batch cultivations in high-performance bioreactors were carried out in order to allow quantitative analysis of the effect of transhydrogenase expression on product formation and on the intracellular concentrations of NADH, NAD+, NADPH and NADP+. A specific transhydrogenase activity of 4.53 U/mg protein was measured in the extracts from the strain expressing the sth gene from A. vinelandii, while no transhydrogenase activity could be detected in control strains without the gene. Production of the transhydrogenase caused a significant increase in formation of glycerol and 2-oxoglutarate. Since NADPH is used to convert 2-oxoglutarate to glutamate while glycerol formation increases when excess NADH is formed, this suggested that transhydrogenase converted NADH and NADP+ to NAD+ and NADPH. This was further supported by measurements of the intracellular nucleotide concentrations. Thus, the (NADPH/NADP+):(NADH/NAD+) ratio was reduced from 35 to 17 by the transhydrogenase. The increased formation of 2-oxoglutarate was accompanied by a two-fold decrease in the maximal specific growth rate. Also the biomass and ethanol yields were significantly lowered by the transhydrogenase. Copyright © 2000 John Wiley & Sons, Ltd.
Polymerase Chain Reaction-Based Detection of Circulating Melanoma Cells as an Effective Marker of Tumor Progression (1999)

Our data establish the existence of a significant correlation among clinical stages, tumor progression, and presence of circulating melanoma-associated antigens in peripheral blood of MM patients. Preliminary assessment of a subset of patients with a higher risk of recurrence needs longer follow-up and further studies to define the role of RT-PCR in monitoring MM patients.
Agent-based resource discovery (2002)

Presents a distributed discovery method allowing individual nodes to gather information about resources in a wide-area distributed system made up of autonomous systems linked together by a network technology substrate. We introduce an algorithm and a model for distributed awareness and a framework for the dynamic assembly of agents monitoring network resources. Whenever an agent needs detailed information about the individual components of another system, it uses the information gathered by the distributed awareness mechanism to identify the target system, then creates a description of a monitoring agent that is capable of providing the information about remote resources, and sends this description to the remote site. There, an agent factory dynamically assembles the monitoring agent. This solution is scalable and is suitable for heterogeneous environments where the architecture and the hardware resources of individual nodes differ, where the services provided by the system are diverse, and where the bandwidth and latency of the communication links cover a broad range.
DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy (2015)

NK cells are emerging as new effectors for immunotherapy of cancer. In particular, the genetic engraftment of chimeric Ag receptors (CARs) in NK cells is a promising strategy to redirect NK cells to otherwise NK cell-resistant tumor cells. On the basis of DNAX-activation protein 12 (DAP12), a signaling adaptor molecule involved in signal transduction of activating NK cell receptors, we generated a new type of CAR targeting the prostate stem cell Ag (PSCA). We demonstrate in this article that this CAR, designated anti-PSCA-DAP12, consisting of DAP12 fused to the anti-PSCA single-chain Ab fragment scFv(AM1) confers improved cytotoxicity to the NK cell line YTS against PSCA-positive tumor cells when compared with a CAR containing the CD3ζ signaling chain. Further analyses revealed phosphorylation of the DAP12-associated ZAP-70 kinase and IFN-γ release of CAR-engineered cells after contact with PSCA-positive target cells. YTS cells modified with DAP12 alone or with a CAR bearing a phosphorylation-defective ITAM were not activated. Notably, infused YTS cells armed with anti-PSCA-DAP12 caused delayed tumor xenograft growth and resulted in complete tumor eradication in a significant fraction of treated mice. The feasibility of the DAP12-based CAR was further tested in human primary NK cells and confers specific cytotoxicity against KIR/HLA-matched PSCA-positive tumor cells, which was further enhanced by KIR-HLA mismatches. We conclude that NK cells engineered with DAP12-based CARs are a promising tool for adoptive tumor immunotherapy.
Resveratrol and Myopathy (2016)

Resveratrol is a natural polyphenolic compound produced by plants under various stress conditions. Resveratrol has been reported to exhibit antioxidant, anti-inflammatory, and anti-proliferative properties in mammalian cells and animal models, and might therefore exert pleiotropic beneficial effects in different pathophysiological states. More recently, resveratrol has also been shown to potentially target many mitochondrial metabolic pathways, including fatty acid β-oxidation or oxidative phosphorylation, leading to the up-regulation of the energy metabolism via signaling pathways involving PGC-1α, SIRT1, and/or AMP-kinase, which are not yet fully delineated. Some of resveratrol beneficial effects likely arise from its cellular effects in the skeletal muscle, which, surprisingly, has been given relatively little attention, compared to other target tissues. Here, we review the potential for resveratrol to ameliorate or correct mitochondrial metabolic deficiencies responsible for myopathies, due to inherited fatty acid β-oxidation or to respiratory chain defects, for which no treatment exists to date. We also review recent data supporting therapeutic effects of resveratrol in the Duchenne Muscular Dystrophy, a fatal genetic disease affecting the production of muscle dystrophin, associated to a variety of mitochondrial dysfunctions, which likely contribute to disease pathogenesis.
Gastrointestinal Symptoms in Middle-Aged Diabetic Patients (1993)

Occurrence of gastrointestinal symptoms was investigated in a questionnaire-based survey of 89 randomly selected patients with insulin-dependent diabetes mellitus, 481 patients with noninsulin-dependent diabetes mellitus, and 635 nondiabetic control subjects. The prevalences of upper gastrointestinal symptoms, abdominal pain, diarrhea, and constipation were similar in diabetic patients and control subjects. Women with noninsulin-dependent diabetes melitus had a significantly higher and women with insulin-dependent diabetes mellitus a significantly lower prevalence of gallstone disease than control women (29%, 5%, and 19%, respectively). We conclude that the occurrence and spectrum of gastrointestinal symptoms in middle-aged subjects with insulin-and noninsulin-dependent diabetes mellitus do not differ from those of the general population.
Increased sophistication of immunotoxins. (2002)

The article by Salvatore et al. [(1)][1] in this issue of Clinical Cancer Research describes the synthesis and biological activity of an improved, recombinant immunotoxin targeted to the CD22 B-cell antigen. This particularly well-performed study is one of a large series of significant innovations
[Fasudil improves cognition of APP/PS1 transgenic mice via inhibiting the activation of microglia and shifting microglia phenotypes from M1 to M2]. (2017)

Objective To examine the regulatory effects of Rho kinase inhibitor fasudil on cognition and microglia polarization in APP/PS1 transgenic (APP/PS1 Tg) mice, a widely used model of Alzheimer's disease (AD). Methods Male APP/PS1 Tg mice at 8 months of age were randomly divided into two groups: Fasudil (25 mg/kg) and saline, i.p., once daily for 2 months; age- and gender-matched wild type (WT) mice without treatment were used as the controls. The Morris water maze (MWM) test was applied to examine spatial cognition of mice. Aβ<sub>1-42</sub> deposition, the microglia surface marker CD11b, and the M1 and M2 microglia surface markers [iNOS, arginase 1 (ARG1) and CD206] in the hippocampus and cerebral cortex were analyzed by immunohistochemistry and Western blotting. Results Compared with WT controls, APP/PS1 Tg mice (10 months old at the time of testing) treated with saline displayed increases in the latency to target, mean distance to target, latency 1st entrance to SW quadrant during the MWM test; they also showed increased latency and mean distance entering to the target in the MWM test, indicating their impaired cognition, which was reversed by fasudil. In addition, fasudil decreased the expressions of Aβ<sub>1-42</sub> and iNOS and increased ARG1/CD206 in the hippocampus and cerebral cortex. further, the microglia marker CD11b had an overlap with the M1 marker iNOS or the M2 markers ARG1/CD206 in the cerebral cortex of the AD mice following fasudil treatment. Conclusion Fasudil reverses spatial cognitive dysfunction in APP/PS1 Tg mice via facilitating the transformation of Aβ<sub>1-42</sub>-activated microglia from the M1 to M2 phenotype.
The editor replies (1980)

Diseases of the Colon & Rectum: January 1980 - Volume 23 - Issue 1 - p 60 doi: 10.1007/BF02587206
Cutting Edge: Human Th17 Cells Are Identified as Bearing CCR2+CCR5− Phenotype (2007)

Recent reports have shown that IL-17-producing CD4+ T cells (Th17 cells) belong to a distinct helper T cell lineage and are critically involved in the pathogenesis of autoimmune diseases and allergies. However, the chemokine receptor profile of Th17 cells remains to be clarified. In this study, we report that human Th17 cells are identified as CCR2+CCR5- memory CD4+ T cells. Analysis of PBMC from healthy donors showed that CCR2+ cells produce much larger amounts of IL-17 than CCR2- cells, indicating the preferential expression of CCR2 on Th17 cells. Notably, CCR2+CCR5- memory CD4+ T cells produced a large amount of IL-17 and little IFN-gamma, whereas CCR2+CCR5+ cells reciprocally produced an enormous amount of IFN-gamma but little IL-17. Moreover, a higher expression of T-bet was seen in the CCR5+ memory T cells. These results indicate that absence of CCR5 distinguishes human Th17 cells from Th1 cells.
Myelofibrosis revisited: characterization and classification of myelofibrosis in the setting of myeloproliferative disease. (1984)

In describing the various forms of myeloproliferative disease in which myelofibrosis develops, it becomes clear that certain cellular and biochemical abnormalities are shared by all forms of reactive myelofibrosis. Of possible etiologic significance are megakaryocytosis, monocyte-macrophage hyperplasia and activation, altered immunologic status, and proliferation of mast cells and basophils. The mechanisms by which these abnormalities could mediate fibrosis and the methodology that makes assessment and monitoring of fibrosis possible during the course of myeloproliferative disease are discussed in the subsequent contributions to this volume. Opportunities for further study and elucidation of the pathogenesis of myelofibrosis abound and should stimulate the generation of new knowledge that has direct relevance to the management of myeloproliferative disease.
Heart-rate variability in chronic traumatic brain injury (1997)

Heart-rate variability (HRV), a measure of fluctuation around the mean heart rate, reflects the sympathetic and parasympathetic balance of the autonomic nervous system, and is an excellent technique to study cardiovascular tone in patients with neurological injuries. The purpose of this study was to determine whether abnormal HRV is present in patients with traumatic brain injury (TBI) during the post-acute recovery phase. Using a prospective, case/control design, we performed 24-h ambulatory ECG monitoring in seven TBI patients and in seven controls (C). There was a significant difference in root mean squared successive difference of RR intervals (C 40.4 +/- 10.3, TBI 23.3 +/- 16.5, p = 0.04) between TBI and C. Four patients with TBI (compared to one control) had abnormal standard deviation of the RR interval. When these four patients were compared to their matched controls, significant differences were found in frequency domain measure (In total power: TBI 4.4 +/- 0.9 ms2, C 7.1 +/- 1.4 ms2, In low frequency: TBI 3.3 +/- 1.1 ms2, C 6.4 +/- 1.4 ms2; In high frequency TBI 2.0 +/- 1.0 ms2, C 4.8 +/- 1.3 ms2, all p < 0.05). Thus, abnormalities in both time and frequency domains of HRV are present in TBI during the post-acute recovery phase.
Plasma Cell Infiltrates in Atherosclerotic Abdominal Aortic Aneurysms (1986)

Thirty-one of 156 abdominal aortic resection specimens containing atherosclerotic aneurysm wall had an inflammatory infiltrate with a prominent plasma cell component of the media or of plaque replacing the media. The specimens in general were not examples of the so-called "inflammatory variant" of atherosclerotic aneurysm. No association between the infiltrate and syphilis, collagen vascular disease, furosemide exposure, chronic aneurysm leakage, aneurysm diameter, or duration of symptoms was found. The plasmacytic inflammation may be part of an immune response to atherosclerosis.