gebhart/patrepeval huggingface dataset:
The Glucocorticoid Receptor Gene and Its Association to Metabolic Syndrome (2002)

In recent decades, there has been an increasing interest in the role of endogenous glucocorticoids such as cortisol in the pathogenesis of metabolic syndrome. Studies in humans have suggested a positive association between obesity, hypertension, and insulin resistance, with alleles at the glucocorticoid receptor (GR) gene. For instance, the BclI polymorphism within the intron upstream of GR exon 2 has been associated with cardiovascular risk factors such as visceral obesity, hypertension, insulin resistance, and elevated cortisol concentrations. However, the location of the BclI polymorphism is not known, and the variant has so far not been compared with the wild-type receptor for its ability to be activated by glucocorticoids. Although several other mutations in the GR gene have been postulated as being relevant to the progression to type 2 diabetes and cardiovascular diseases, conflicting results makes it difficult to determine exactly what effect these GR variations have on metabolic syndrome incidence and progression. Further studies focusing on the most compelling GR mutations might offer a better understanding of metabolic syndrome pathogenesis and progression, aiding in the development of more effective treatments for this condition.
Prevention and Treatment of Hepatic Venocclusive Disease after High-Dose Cytoreductive Therapy (1998)

Venocclusive disease of the liver (VOD) is one of the most common and serious complications following stem cell transplantation. High-dose chemotherapy or chemoradiotherapy injures the structures of Zone 3 of the liver acinus and produces the clinical syndrome of hepatomegaly or right upper quadrant pain, jaundice, and fluid retention. VOD occurs in up to 54% of stem cell transplant recipients and is fatal in 25-50% of them. While the clinical signs of VOD usually manifest during the first post-transplant week, late presentation can occur. The purpose of this review is to discuss the manifestations and pathophysiology of VOD and the options for prevention and treatment.
B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose‐escalation trial of rituximab (2004)

Rituximab therapy appears to be safe for the treatment of SLE and holds significant therapeutic promise, at least for the majority of patients experiencing profound B cell depletion. Based on these results, controlled trials of rituximab appear to be warranted.
StreaMon (2004)

StreaMon is the adaptive query processing engine of the STREAM prototype Data Stream Management System (DSMS) [4]. A fundamental challenge in many DSMS applications (e.g., network monitoring, financial monitoring over stock tickers, sensor processing) is that conditions may vary significantly over time. Since queries in these systems are usually long-running, or continuous [4], it is important to consider adaptive approaches to query processing. Without adaptivity, performance may drop drastically as stream data and arrival characteristics, query loads, and system conditions change over time.StreaMon uses several techniques to support adaptive query processing [1, 2, 3]; we demonstrate three of them:•Reducing run-time memory requirements for continuous queries by exploiting stream data and arrival patterns.•Adaptive join ordering for pipelined multiway stream joins, with strong quality guarantees.•Placing subresult caches adaptively in pipelined multiway stream joins to avoid recomputation of intermediate results.
Effects of Dexamethasone and Vitamin D3on Cartilage Differentiation in a Clonal Chondrogenic Cell Population (1989)

We have investigated the regulation of chondroblast/chondrocyte differentiation using a unique clonal cell population, designated RCJ 3.1C5 (C5), which differentiates into discrete three-dimensional cartilage nodules when grown in the presence of 15% fetal calf serum. Histologically, the nodules resembled hyaline cartilage; they contained large rounded chondrocytes surrounded by a refractile matrix which stained intensely with Alcian blue, exhibited metachromasia after Toluidine blue staining, and stained with an antibody against type II collagen. The cartilage nodules that formed did not mineralize, despite the presence of organic phosphate in the culture medium. The synthetic glucocorticoid dexamethasone (DEX) increased the number of cartilage nodules formed in a dose-dependent manner (ED50, approximately 10(-9) M), with a maximal stimulatory dose of 10(-8) M. DEX had no effect on the population doubling time and saturation density. The effects of DEX on the number of cartilage nodules were similar whether it was added from the beginning of the culture period (starting during exponential growth) or at confluence. In contrast, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited cartilage nodule formation in a dose-dependent manner (IC50, approximately 5 x 10(-10) M), with maximum inhibition at 10(-7) M. In addition, 1,25-(OH)2D3 decreased cell proliferation and saturation density. Equimolar doses of the vitamin D3 metabolites 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 had no effect. C5 cells treated with 1,25-(OH)2D3 in the absence of DEX during the exponential growth phase exhibited a reduced capacity to form cartilage nodules upon subsequent exposure to DEX. At confluence, before cartilage nodules had formed, C5 cells responded to PTH and prostaglandin-E2 with increases in intracellular cAMP of about 10- and 95-fold respectively. After cartilage nodules were present, prostaglandin-E2 responsiveness decreased to about 25-fold, whereas there was no significant change in PTH responsiveness. DEX decreased the population alkaline phosphatase levels at all times measured, whereas 1,25-(OH)2D3 had a biphasic effect: an increase at 5 days in culture, followed by a decrease at later times in culture. These data indicate that the clonal cell line RCJ 3.1C5 is a useful model system in which to investigate cartilage differentiation.
Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients (2002)

Regeneration of hematopoiesis after allogeneic hematopoietic cell transplantation (HCT) involves conversion of the recipient's immune system to donor type. It is likely that distinct cell lineages in the recipient reconstitute at different rates. Dendritic cells (DCs) are a subset of hematopoietic cells that function as a critical component of antigen-specific immune responses because they modulate T-cell activation, as well as induction of tolerance. Mature DCs are transferred with hematopoietic grafts and subsequently arise de novo. Little information exists about engraftment kinetics and turnover of this cell population in patients after allogeneic HCT. This study examined the kinetics of DC chimerism in patients who underwent matched sibling allogeneic HCT. T-cell, B-cell, and myelocytic and monocytic chimerism were also studied. Peripheral blood cells were analyzed at defined intervals after transplantation from 19 patients with various hematologic malignancies after treatment with myeloablative or nonmyeloablative preparatory regimens. Cell subsets were isolated before analysis of chimerism. Despite the heterogeneity of the patient population and preparatory regimens, all showed rapid and consistent development of DC chimerism. By day +14 after transplantation approximately 80% of DCs were of donor origin with steady increase to more than 95% by day +56. Earlier time points were examined in a subgroup of patients who had undergone nonmyeloablative conditioning and transplantation. These data suggest that a major proportion of blood DCs early after transplantation is donor-derived and that donor chimerism develops rapidly. This information has potential implications for manipulation of immune responses after allogeneic HCT.
Synthesis and Isolation of Cobalt Hexacyanoferrate/Chromate Metal Coordination Nanopolymers Stabilized by Alkylamino Ligand with Metal Elemental Control (2004)

This Communication describes the novel isolation with metal elemental control of cobalt hexacyanoferrate/chromate metal coordination polymers, stabilized by stearylamine (Co-Fe/Cr-SA) as a protecting coordination ligand in a reverse micelle technique. Each Co-Fe/Cr-SA can be isolated with high uniformity of particle size and elemental composition, and the ratio of the metal component depends on the fundamental characteristics of Co-Fe/Cr-SA: the nanopolymer's shape, color, and magnetism.
Primary chemical reactions in pulsed electrical discharge channels in water (2007)

A mathematical model for the primary chemical processes occurring in 1 J/pulse electrical discharges in water has been developed. The discharge channel is divided into two zones: the core and the recombination region. The core is a very narrow (ca 10 µm) part of the channel where high temperature initiation reactions take place and where the majority of molecular hydrogen and 47% of the molecular oxygen are formed. The recombination region is a 200 µm radius zone where additional reactions such as hydrogen peroxide formation take place. The temperature in the core ranged from 5000 K at the centre to 2000 K at the boundary and the pressure, the only adjustable parameter in the system, was found to be 14 atm. The model describes for the first time how molecular oxygen is formed in an underwater discharge and it is also able to describe the experimentally observed stoichiometry of H2, O2 and H2O2 formation. The concentration and temperature profiles inside the discharge channel as well as a general scheme for the water dissociation and molecular species formation are also reported.
NLRP3 Inflammasome Activation in Dialyzed Chronic Kidney Disease Patients (2015)

To assess whether NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multiprotein complex that mediates the activation of caspase-1 (CASP-1) and pro-inflammatory cytokines IL-18 and IL-1β, could be involved in the chronic inflammatory state observed in chronic kidney disease patients undergoing hemodialysis treatment (CKD-HD), we employed several biomolecular techniques including RT-PCR, western blot, FACS analysis, confocal microscopy and microarray. Interestingly, peripheral blood mononuclear cells from 15 CKD-HD patients showed higher mRNA levels of NLRP3, CASP-1, ASC, IL-1β, IL-18 and P2X7 receptor compared to 15 healthy subjects. Western blotting analysis confirmed the above results. In particular, active forms of CASP-1, IL1-β and IL-18 resulted significantly up-regulated in CKD-HD versus controls. Additionally, elevated mitochondrial ROS level, colocalization of NLRP3/ASC/mitochondria in peripheral blood mononuclear cells from CKD-HD patients and down-regulation of CASP-1, IL1-β and IL-18 protein levels in immune-cells of CKD-HD patients stimulated with LPS/ATP in presence of mitoTEMPO, inhibitor of mitochondrial ROS production, suggested a possible role of this organelle in the aforementioned CKD-associated inflammasome activation. Then, microarray analysis confirmed, in an independent microarray study cohort, that NLRP3 and CASP-1, along with other inflammasome-related genes, were up-regulated in 17 CKD-HD patients and they were able to clearly discriminate these patients from 5 healthy subjects. All together these data showed, for the first time, that NLRP3 inflammasome was activated in uremic patients undergoing dialysis treatment and they suggested that this unphysiological condition could be possibly induced by mitochondrial dysfunction.
Humoral immune response to the E2 protein of hepatitis G virus is associated with long-term recovery from infection and reveals a high frequency of hepatitis G virus exposure among healthy blood donors (1997)

The second envelope protein (E2) of the hepatitis G virus (HGV) was expressed in Chinese hamster ovary (CHO) cells and showed a molecular weight of approximately 60 to 70 kd, with 15 to 25 kd of the size contributed by N-linked glycosylation. An enzyme-linked immunosorbent assay (ELISA) using HGV-E2 was developed to test for antibodies to this protein (anti-E2) in human sera. High sensitivity was achieved by developing monoclonal antibodies (mAbs) to HGV-E2, which were used as capture antibodies in the ELISA. Our studies revealed that 16% of healthy Spanish blood donors were exposed to HGV, indicating that additional routes of viral transmission besides parenteral exposure might exist. An even higher prevalence of exposure to HGV (52%-73%) was found in several groups at risk of parenteral exposure to infectious agents, i.e., intravenous drug users, transfusion history, hemophiliacs, and hepatitis C virus (HCV)-positive patients. Most anti-E2-positive patients were HGV-RNA-negative and vice versa, indicating an inverse correlation of these two viral markers. A panel of 16 posttransfusion patients followed for up to 16 years revealed that patients who develop an anti-E2 response become HGV-RNA-negative, while patients who do not develop anti-E2 are persistently infected. Immunity to HGV seems to be long-lasting, because circulating antibody to E2 could still be detected 14 years after seroconversion. Sequence comparisons showed that E2 is highly conserved among isolates collected worldwide, indicating that immune escape variants are not common in HGV infections. This reflects on a molecular level why HGV infections usually are cleared spontaneously by the host. However, possible mechanisms of HGV persistence, as found in some patients, remain to be elucidated.
Flt3 Y591 duplication and Bcl-2 overexpression are detected in acute myeloid leukemia cells with high levels of phosphorylated wild-type p53 (2006)

Loss or mutation of the TP53 tumor suppressor gene is not commonly observed in acute myeloid leukemia (AML), suggesting that there is an alternate route for cell transformation. We investigated the hypothesis that previously observed Bcl-2 family member overexpression suppresses wild-type p53 activity in AML. We demonstrate that wild-type p53 protein is expressed in primary leukemic blasts from patients with de novo AML using 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and phospho-specific flow cytometry. We found that p53 was heterogeneously expressed and phosphorylated in AML patient samples and could accumulate following DNA damage. Overexpression of antiapoptosis protein Bcl-2 in AML cells was directly correlated with p53 expression and phosphorylation on serine residues 15, 46, and 392. Within those patients with the highest levels of Bcl-2 expression, we identified a mutation in FLT3 that duplicated phosphorylation site Y591. The presence of this mutation correlated with greater than normal Bcl-2 expression and with previously observed profiles of potentiated STAT and MAPK signaling. These results support the hypothesis that Flt3-mediated signaling in AML enables accumulation of Bcl-2 and maintains a downstream block to p53 pathway apoptosis. Bcl-2 inhibition might therefore improve the efficacy of existing AML therapies by inactivating this suppression of wild-type p53 activity.
Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. (1990)

The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti-DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors (19), are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) anti-idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.
Mitochondrial reactive oxygen species trigger hypoxia-induced transcription (1998)

Transcriptional activation of erythropoietin, glycolytic enzymes, and vascular endothelial growth factor occurs during hypoxia or in response to cobalt chloride (CoCl2) in Hep3B cells. However, neither the mechanism of cellular O2 sensing nor that of cobalt is fully understood. We tested whether mitochondria act as O2 sensors during hypoxia and whether hypoxia and cobalt activate transcription by increasing generation of reactive oxygen species (ROS). Results show (i) wild-type Hep3B cells increase ROS generation during hypoxia (1. 5% O2) or CoCl2 incubation, (ii) Hep3B cells depleted of mitochondrial DNA (rho0 cells) fail to respire, fail to activate mRNA for erythropoietin, glycolytic enzymes, or vascular endothelial growth factor during hypoxia, and fail to increase ROS generation during hypoxia; (iii) rho0 cells increase ROS generation in response to CoCl2 and retain the ability to induce expression of these genes; and (iv) the antioxidants pyrrolidine dithiocarbamate and ebselen abolish transcriptional activation of these genes during hypoxia or CoCl2 in wild-type cells, and abolish the response to CoCl2 in rho degrees cells. Thus, hypoxia activates transcription via a mitochondria-dependent signaling process involving increased ROS, whereas CoCl2 activates transcription by stimulating ROS generation via a mitochondria-independent mechanism.
Source of oncofetal ED-B-containing fibronectin: implications of production by both tumor and endothelial cells. (2000)

ED-B fibronectin (FN) is a FN isoform derived from alternative splicing of the primary transcript of a single gene. Its expression on tumor stroma and neoformed tumor vasculature and its absence, with few exceptions, in normal adult tissues imply a prognostic and diagnostic value for ED-B FN. We investigated the location and source of ED-B FN because this will be of importance both in understanding its role in tumor development and in designing strategies to target this molecule. We have confirmed that ED-B FN is expressed in the majority of breast and colorectal carcinoma tissue samples, with strong immunohistochemical staining around the tumor cells and in the tumor stroma. No staining of tumor neovasculature was seen. ED-B FN is produced by a range of tumor and endothelial (both primary and transformed) cell lines, as detected by reverse transcription-PCR, but is not expressed at the plasma membrane. Strong expression of human ED-B FN is seen in tumor xenografts. These data indicate that neoplastic cells can act as the source of ED-B FN in tumors. The lack of cell surface expression on tumor cell lines has clear implications for the design of therapeutic strategies which target this molecule.
PML nuclear bodies are general targets for inflammation and cell proliferation. (1995)

Acute promyelocytic leukemia is associated with a t(15;17) translocation that generates a fusion product between PML and the retinoic acid receptor alpha. Recently, PML was shown to concentrate within subnuclear domains, referred to as nuclear bodies, that are disorganized in acute promyelocytic leukemia cells. This observation provided the first evidence that alteration of a nuclear structure may play a role in human pathogenesis. In an attempt to clarify the role of PML and, more generally, of the associated nuclear bodies, we used immunohistochemistry to explore the expression of PML in normal, inflammatory, and neoplastic human tissues. With the exception of endothelial cells and macrophages that contain a high amount of PML protein, a weak speckled labeling pattern was observed in the nucleus of all cell types analyzed. By contrast to normal tissues, the level of PML expression was considerably enhanced in inflammatory tissues, predominantly around the mononuclear cell infiltrate, as well as during either normal or pathological proliferative states, in particular in tumoral pathology. Surprisingly, in most hepatocellular carcinoma, a cytoplasmic delocalization of PML was observed. Finally, the number of PML nuclear bodies increased up to twice their normal value as quiescent cultured cells were stimulated to grow upon serum addition. Altogether these results strongly suggest that the PML-associated nuclear bodies are implicated both in the inflammatory process and in cell growth control.
Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non‐anticoagulated blood in vitro (2003)

Contact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37 degrees C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6-12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits.
Physiological role of alkaline phosphatase explored in hypophosphatasia (2010)

Hypophosphatasia (HPP) is the instructive rickets or osteomalacia caused by loss-of-function mutation(s) within TNSALP, the gene that encodes the "tissue nonspecific" isoenzyme of alkaline phosphatase (TNSALP). HPP reveals a critical role for this enzyme in skeletal mineralization. Increased extracellular levels of pyridoxal 5'-phosphate and inorganic pyrophosphate (PP(i)) demonstrate that TNSALP is a phosphomonoester phosphohydrolase and a pyrophosphatase that hydrolyzes much lower concentrations of natural substrates than the artificial substrates of laboratory assays. Clearly, TNSALP acts at physiological pH and "alkaline phosphatase" is a misnomer. Aberrations of vitamin B(6) metabolism in HPP revealed that TNSALP is an ectoenzyme. PP(i) excesses cause chondrocalcinosis and sometimes arthropathy. The skeletal disease is due to PP(i) inhibition of hydroxyapatite crystal growth extracellularly so that crystals form within matrix vesicles but fail to enlarge after these structures rupture. Trials of alkaline phosphatase replacement therapy for HPP suggest that TNSALP functions at the level of skeletal tissues.
Natural Killer (NK) Cell–mediated Cytotoxicity: Differential Use of  TRAIL and Fas Ligand by Immature and Mature Primary Human NK Cells (1998)

Mature natural killer (NK) cells use Ca2+-dependent granule exocytosis and release of cytotoxic proteins, Fas ligand (FasL), and membrane-bound or secreted cytokines (tumor necrosis factor [TNF]-alpha) to induce target cell death. Fas belongs to the TNF receptor family of molecules, containing a conserved intracytoplasmic "death domain" that indirectly activates the caspase enzymatic cascade and ultimately apoptotic mechanisms in numerous cell types. Two additional members of this family, DR4 and DR5, transduce apoptotic signals upon binding soluble TNF-related apoptosis-inducing ligand (TRAIL) that, like FasL, belongs to the growing TNF family of molecules. Here, we report that TRAIL produced or expressed by different populations of primary human NK cells is functional, and represents a marker of differentiation or activation of these, and possibly other, cytotoxic leukocytes. During differentiation NK cells, sequentially and differentially, use distinct members of the TNF family or granule exocytosis to mediate target cell death. Phenotypically immature CD161(+)/CD56(-) NK cells mediate TRAIL-dependent but not FasL- or granule release-dependent cytotoxicity, whereas mature CD56(+) NK cells mediate the latter two.