gebhart/patrepeval huggingface dataset:
Inhibition of Activator Protein-1, NF-κB, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid (2005)

Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenols in the human diet. The antioxidant and anticarcinogenic properties of chlorogenic acid have been established in animal studies. However, little is known about the molecular mechanisms through which chlorogenic acid inhibits carcinogenesis. In this study, we found that chlorogenic acid inhibited the proliferation of A549 human cancer cells in vitro. The results of the soft agar assay indicated that chlorogenic acid suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells in a dose-dependent manner. Pretreatment of JB6 cells with chlorogenic acid blocked UVB- or TPA-induced transactivation of AP-1 and NF-kappaB over the same dose range. At low concentrations, chlorogenic acid decreased the phosphorylation of c-Jun NH2-terminal kinases, p38 kinase, and MAPK kinase 4 induced by UVB/12-O-tetradecanoylphorbol-13-acetate, yet higher doses were required to inhibit extracellular signal-regulated kinases. Chlorogenic acid also increased the enzymatic activities of glutathione S-transferases (GST) and NAD(P)H: quinone oxidoreductase. Further studies indicated that chlorogenic acid could stimulate the nuclear translocation of Nrf2 (NF-E2-related factor) as well as subsequent induction of GSTA1 antioxidant response element (ARE)-mediated GST activity. The phosphatidylinositol 3-kinase pathway might be involved in the activation of Nrf2 translocation. These results provide the first evidence that chlorogenic acid could protect against environmental carcinogen-induced carcinogenesis and suggest that the chemopreventive effects of chlorogenic acid may be through its up-regulation of cellular antioxidant enzymes and suppression of ROS-mediated NF-kappaB, AP-1, and MAPK activation.
Effect of Asparagine and Glutamine Deficiency on Normal and Leukemic Cells 2 (1973)

Normal and leukemic human blood cells and cells from mouse lymphoma 6C3HED were incubated in media that lacked L-asparagine or L-glutamine or both. Viable cell counts and the incorporation of radioactive L-leucine into cell proteins were measured before and after incubation. The absence of either L-asparagine or L-glutamine from the media produced a delayed cytocidal effect on 6C3HED cells and caused a decreased uptake of L-leuclne, Cells from patients with acute leukemia also required L-asparagine and Lglutamine for survival at 37° C for 2–5 days, but seemed less sensitive than the 6C3HED cells. L-Glutamine but not L-asparagine deficiency killed lymphocytes from 5 of 6 patients with chronic leukemia and inhibited the uptake of LL-leucine. L-Asparagine deficiency had no effect, and L-glutamine deficiency only minimal effect, on normal lymphocytes as measured by percent survival or L-leucine uptake. Transformation of normal lymphocytes by pokeweed mitogen was, however, completely inhibited by a deficiency of L-glutamine but not by a deficiency of L-asparagine.
Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study. (1993)

Metalloproteases appear to play an important role in the pathophysiology of osteoarthritis (OA) and their expression is believed to be regulated by cytokines such as interleukin-1 (IL-1). Nuclear oncogene products are suggested as mediators through which IL-1 induces metalloprotease gene expression. Little data are available on the in vivo involvement of these agents in the pathophysiology of OA. This study examined by immunohistochemistry, using specific antibodies, the distribution of stromelysin, IL-1 alpha, IL-1 beta, and oncogene products (c-FOS, c-JUN, and c-MYC) in synovium and cartilage from normal and experimental canine models of OA. In the OA synovium, stromelysin and IL-1 were localized in the cytoplasm of superficial synovial lining cells, infiltrating mononuclear cells, and endothelial and smooth muscle cells of the blood vessels, whereas oncoproteins were detected predominantly in the synovial lining cells. Normal synovial membranes demonstrated low levels of specific staining in synovial lining cells with occasional staining of blood vessel cells for IL-1 alpha, IL-1 beta, and stromelysin. In OA cartilage, chondrocytes at the superficial and middle layers as well as in fibrillated areas were found to be involved in the synthesis of stromelysin, IL-1, and oncoproteins. Diffuse staining of stromelysin and IL-1 beta in OA cartilage matrix was also identified. In normal cartilage, only a few chondrocytes at the superficial layer showed a low level of antigens. These results demonstrate the in vivo concomitant cellular and/or matrical presence of stromelysin, IL-1, and oncogene proteins in tissues from experimentally induced OA with the most intense staining at the sites of cartilage erosion and synovial proliferation. These findings suggest that they may be involved in the pathophysiology of OA, and that the regulatory mechanisms involved in the expression of these proteins may be associated.
AuraMirror (2003)

We present AuraMirror, a system that visualizes virtual windows of attention: the commodity of visual attention people exchange during interactions in small groups. AuraMirror acts as a dynamic 'painting' that passively gathers and displays attentional data by superimposing auras over each viewer's head in a real time video mirror. This permits users to see how they distribute their attention in group interactions, and the effect of interruption on this process. Finally, we describe how AuraMirror can be extended to model attention among both participants and ubiquitous devices.
<title>Adhesives deliver low-shrink low-stress bonds and fast UV cure</title> (2001)

Lower stress, higher quality assemblies as well as quantum increases in productivity are now possible with `new generation', light curing adhesives. This new technology makes obsolete the industry-accepted assumption that low strain requires slow curing UV adhesives, epoxies and cements. Curing in only seconds and without the need for secondary thermal cure, these new light curing adhesives produce laminates which are essentially strain-free, and edge bonds with shrinkage as low as 0.2%. This paper will compare and contrast these new adhesives with existing bonding technologies in typical applications. Included are comparison between epoxies, UV curing mercaptoesters, and the new light curing Aerobic Acrylates, as well as the incorporation of adhesives into optical component design.
Effect of Inhaled Heparin on Allergen-Induced Early and Late Asthmatic Responses in Patients With Atopic Asthma (1996)

Heparin possesses anti-inflammatory properties, which appeared to be dependent on the dose, timing, and the route of administration in animal studies. In asthma, a single dose of inhaled heparin only slightly reduced the early asthmatic response (EAR) but failed to protect against the late asthmatic response (LAR) to inhaled allergen. We studied the effect of multiple doses of inhaled heparin on the EAR and LAR to inhaled house-dust mite extract in eight stable asthmatics in a two-period, randomized, double-blind, crossover study. During both study periods, a standardized allergen challenge was performed and PC20 histamine was measured 24 h before and 24 h postallergen. Five doses of unfractionated heparin sodium (1,000 U/kg/dose) or placebo were inhaled 90 and 30 min preallergen, and 2, 4, and 6 h postallergen. Airway response was measured by FEV1, and the EAR (0-3 h) and LAR (3-10 h) were expressed as corresponding areas under the time-response curves (AUC). The acute effects of heparin and placebo on baseline FEV1 were not different (p > 0.07). Although not reaching significance, heparin attenuated the EAR by an average of 40% (mean AUC(0-3) +/- SEM: 29.5 +/- 6.0 [placebo] and 17.8 +/- 5.5% fall x h [heparin]; p = 0.08), while it significantly reduced the LAR by an average of 36% (AUC(3-10) +/- SEM: 169.3 +/- 20.0 [placebo] and 109.1 +/- 23.6% fall x h [heparin]; p = 0.005). We conclude that inhaled heparin reduces the LAR to allergen in asthmatic subjects, which may be due to its anti-inflammatory activity. Our finding suggests that heparin may have potential as anti-asthma therapy.
Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin (2009)

Nimotuzumab is a humanized therapeutic monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate nimotuzumab in different indications. Nimotuzumab has been granted approval for use in squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal cancer in different countries. This review focuses on the unique functional characteristics of nimotuzumab. Also, it discusses the safety and efficacy data obtained from the Phase IIb clinical trial conducted in India in SCCHN. Post marketing surveillance data from Cuba for the use of nimotuzumab in pediatric and adult glioma is also discussed. Overall, nimotuzumab has immense therapeutic potential in cancers of epithelial origin.
RNAI AS AN EXPERIMENTAL AND THERAPEUTIC TOOL TO STUDY AND REGULATE PHYSIOLOGICAL AND DISEASE PROCESSES (2004)

Over the past four years RNA interference (RNAi) has exploded onto the research scene as a new approach to manipulate gene expression in mammalian systems. More recently, RNAi has garnered much interest as a potential therapeutic strategy. In this review, we briefly summarize the current understanding of RNAi biology and examine how RNAi has been used to study the genetic basis of physiological and disease processes in mammalian systems. We also explore some of the new developments in the use of RNAi for disease therapy and highlight the key challenges that currently limit its application in the laboratory, as well as in the clinical setting.
Model of the cAMP activation of chloride transport by CFTR channel and the mechanism of potentiators (2009)

Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, a hereditary lethal disease. CFTR is a chloride channel expressed in the apical membrane of epithelia. It is activated by cAMP dependent phosphorylation and gated by the binding of ATP. The impaired chloride transport of some types of cystic fibrosis mutations could be pharmacologically solved by the use of chemical compounds called potentiators. Here it is undertaken the construction of a model of the CFTR activation pathways, and the possible modification produced by a potentiator application. The model yields a novel mechanism for the potentiator action, describing the activatory and inhibitory activities on two different positions in the CFTR activation pathway.
Kinetic Factors Control Efficiencies of Cell Entry, Efficacies of Entry Inhibitors, and Mechanisms of Adaptation of Human Immunodeficiency Virus (2005)

Replication of human immunodeficiency virus type 1 (HIV-1) in diverse conditions limiting for viral entry into cells frequently leads to adaptive mutations in the V3 loop of the gp120 envelope glycoprotein. This has suggested that the V3 loop limits the efficiencies of HIV-1 infections, possibly by directly affecting gp120-coreceptor affinities. In contrast, V3 loop mutations that enable HIV-1(JR-CSF) to use the low-affinity mutant coreceptor CCR5(Y14N) are shown here to have negligible effects on the virus-coreceptor affinity but to dramatically accelerate the irreversible conformational conversion of the envelope gp41 subunits from a three-stranded coil into a six-helix bundle. This slow step is blocked irreversibly by the inhibitor T-20. To further evaluate the role of entry rates in controlling infection efficiencies and viral adaptations, we developed methods to quantitatively measure viral entry kinetics. The virions were adsorbed by spinoculation at 4 degrees C onto HeLa-CD4/CCR5 cell clones that either had limiting or saturating concentrations of CCR5. After warming to 37 degrees C, the completion of entry was monitored over time by the resistance of infections to the competitive CCR5 inhibitor TAK-779. Our results suggest that the efficiency of entry of cell-attached infectious HIV-1 is principally controlled by three kinetic processes. The first is a lag phase that is caused in part by the concentration-dependent reversible association of virus with CD4 and CCR5 to form an equilibrium assemblage of complexes. Second, this assembly step lowers but does not eliminate a large activation energy barrier for a rate-limiting, CCR5-dependent conformational change in gp41 that is sensitive to blockage by T-20. The rate of infection therefore depends on the fraction of infectious virions that are sufficiently saturated with CCR5 to undergo this conformational change and on the magnitude of the activation energy barrier. Although only a small fraction of fully assembled viral complexes overcome this barrier per hour, the ensuing steps of entry are rapidly completed within 5 to 10 min. Thus, this barrier limits the overall flow rate at which the attached virions enter cells, but it has no effect on the lag time that precedes this entry flow. Third, a relatively rapid and kinetically dominant process of viral inactivation, which may partly involve endocytosis, competes with infectious viral entry. Our results suggest that the V3 loop of gp120 has a major effect on the rate-limiting coreceptor-dependent conformational change in gp41 and that adaptive viral mutations, including V3 loop mutations, function kinetically by accelerating this inherently slow step in the entry pathway.
The Clinical Implications of First‐Pass Metabolism: Treatment Strategies for the 1990s (1993)

The first-pass effect is real. It may pose obstacles to the treatment of disease, and strategies need to be developed to address the problem that first pass can cause. First we have to look at identifying the problem, and this symposium has helped to further emphasize that the problem exists and awareness is increasing. The first-pass effect has been a basic tenant of pharmacology but an area not receiving active research interest and one that is often overlooked in the clinical arena. Avoiding drug interactions is a consideration, and that is a major challenge to the field of clinical pharmacology. Clinicians need to be aware of the problem, aware of the danger areas with drugs, and first pass. Another alternative is to turn to chemical modification of a drug that avoids needing to take first pass into consideration.
Optical palpation: optical coherence tomography-based tactile imaging using a compliant sensor (2014)

We present optical palpation, a tactile imaging technique for mapping micrometer- to millimeter-scale mechanical variations in soft tissue. In optical palpation, a stress sensor consisting of translucent, compliant silicone with known stress-strain behavior is placed on the tissue surface and a compressive load is applied. Optical coherence tomography (OCT) is used to measure the local strain in the sensor, from which the local stress at the sample surface is calculated and mapped onto an image. We present results in tissue-mimicking phantoms, demonstrating the detection of a feature embedded 4.7 mm below the sample surface, well beyond the depth range of OCT. We demonstrate the use of optical palpation to delineate the boundary of a region of tumor in freshly excised human breast tissue, validated against histopathology.
Effect of Adjunctive Treatment With Serotonin-1A Agonist Tandospirone on Memory Functions in Schizophrenia (2000)

Sumiyoshi, Tomiki MD, PhD; Matsui, Mie MS, PhD; Yamashita, Ikiko ME; Nohara, Shigeru MD, PhD; Uehara, Takashi MD, PhD; Kurachi, Masayoshi MD, PhD; Meltzer, Herbert Y. MD Author Information
Changes in phenotype and proliferative potential of human acute myeloblastic leukemia cells in culture with stem cell factor. (1993)

The interaction of the proto-oncogene c-kit product with its ligand (stem cell factor or SCF) is considered to play crucial roles in hematopoiesis. In a series of human acute myeloblastic leukemia (AML) cells, the effects of recombinant human (rh) SCF on AML cells were examined in short-term and long-term cultures. c-kit expression was detected in 26 of 31 AML cases, and short-term treatment of AML cells with rhSCF led to proliferation in 13 of 18 AML cases that expressed the c-kit product. In seven of the 13 cases showing proliferative response to rhSCF, AML cells were exclusively composed of immature blast cells. We therefore used the seven AML cases for examining the effect of rhSCF on the differentiation and proliferation of AML cells in a long-term culture. Proliferation of AML cells was found to be maintained with rhSCF more than 2 weeks in five of seven cases and 4 weeks in two cases, whereas most of the AML cells died before 2 weeks in the absence of rhSCF. Further, in four of five AML cases, all of which expressed the CD34 antigen and showed a proliferative response to rhSCF in a long-term culture, rhSCF appeared to promote differentiation of blast cells toward lineages of various cell types, such as granulocytic and/or monocytic and mast-cell lineages. These results suggest that, at least in a fraction of AML cases, rhSCF can induce not only proliferation but also differentiation of AML cells, and also that phenotypic manifestation of AML cells may not mean definite cell commitment but can be changed by stimulation with rhSCF.
Expression of glycosylated and nonglycosylated human transferrin in mammalian cells. Characterization of the recombinant proteins with comparison to three commercially available transferrins (1993)

The coding sequence for human serum transferrin was assembled from restriction fragments derived from a full-length cDNA clone isolated from a human liver cDNA library. The assembled clone was inserted into the expression vector pNUT and stably transfected into transformed baby hamster kidney (BHK) cells, leading to secretion of up to 125 mg/L recombinant protein into the tissue culture medium. As judged by mobility on NaDodSO4-PAGE, immunoreactivity, spectral properties (indicative of correct folding and iron binding), and the ability to bind to receptors on a human cell line, initial studies showed that the recombinant transferrin, is identical to three commercial human serum transferrin samples. Electrospray mass spectrometry (ESMS), anion-exchange chromatography, and urea gel analysis showed that the recombinant protein has an extremely complex carbohydrate pattern with 16 separate masses ranging from 78,833 to 80,802 daltons. Mutation of the two asparagine carbohydrate linkage sites to aspartic acid residues led to the expression and secretion of up to 25 mg/L nonglycosylated transferrin. ESMS, anion-exchange chromatography, and urea gel analysis showed a single molecular species that was consistent with the expected theoretical mass of 75,143 daltons. In equilibrium binding experiments, the nonglycosylated mutant bound to HeLa S3 cells with the same avidity and to the same extent as the glycosylated protein and the three commercial samples. These studies demonstrate conclusively that carbohydrate has no role in this function.
Structure and sequence of the human c-sis/platelet-derived growth factor 2 (SIS/PDGF2) transcriptional unit. (1986)

The structure of the normal human c-sis/platelet-derived growth factor 2 (SIS/PDGF2) transcript was determined by a combination of cDNA cloning, nuclease S1 mapping, and primer extension. Nucleotide sequence analysis revealed that the 3373-nucleotide SIS/PDGF2 mRNA contained only a 723-base-pair (bp) coding sequence for the PDGF2 precursor polypeptide. The coding sequence was flanked by long 5' (1022 bp) and 3' (1625 bp) untranslated regions. The 5' noncoding region, as well as upstream flanking genomic sequences, contained clusters of specific short repeat sequences. A consensus transcriptional promoter sequence, TATAAA, was identified 24 bp upstream of the mRNA start site and an enhancer-like "TG element" was detected about 180 bp downstream from the site of polyadenylylation. These findings identify putative regulatory elements of the SIS/PDGF2 gene.
iBH3: simple, fixable BH3 profiling to determine apoptotic priming in primary tissue by flow cytometry (2016)

Dysregulation of the mitochondrial pathway of apoptosis, controlled by the BCL-2 family of proteins, leads to disease states including cancer. Rapid analysis of a cell's dependency on the BCL-2 family of proteins is hindered by the complex interactions of more than a dozen proteins. Transcript or even protein levels are therefore generally insufficient to predict a cell's response to perturbations like chemotherapy. Previously, we developed the JC-1 BH3 method to provide a same day functional assay to assess a cell's propensity to undergo apoptosis and demonstrated its utility in predicting response to chemotherapy. We have now improved upon these methods to create a robust assay amenable to high throughput platforms using cytochrome c retention in formaldehyde fixed cells to remove the time sensitivity of JC-1 potential measurements. BH3 profiling by intracellular staining (iBH3) is suitable for 96- and 384-well formats, and can be used to directly screen candidate BH3-mimetic compounds for activity. When used as the final component of dynamic BH3 profiling (DBP), which uses a drug pretreatment prior to iBH3 to assess the change in profile due to treatment, it can predict the response of cells to chemotherapy days before they show signs of death.
Captopril Inhibits the Proliferation of Hematopoietic Stem and Progenitor Cells in Murine Long‐Term Bone Marrow Cultures (1999)

Drugs used mainly for the treatment of hypertension, such as angiotensin I-converting enzyme (ACE) inhibitors, can cause pancytopenia. The underlying cause of this side effect remains unknown. In the present study, long-term bone marrow cultures (LTBMCs) were utilized to evaluate the role of captopril (D-3-mercapto-2-methylpropionyl-L-proline), one of the potent ACE inhibitors, in regulating hematopoietic stem/progenitor cell proliferation. Captopril (10(-6) M final concentration) was added to LTBMCs at the beginning of the culture period and at weekly intervals for six weeks. There was no toxicity to the bone marrow cells as measured by the unchanged cell number in the nonadherent layer during the whole culture period, and there was an increased cellularity of the adherent layer at the end of the six weeks of treatment. However, captopril decreased the proportion of granulocyte-macrophage colony-forming cells (GM-CFCs) in S phase at weeks 2 and 3 as well as that of high proliferative potential colony-forming cells (HPP-CFCs) at week 3 in the nonadherent layer. There was no change in the kinetics of the GM-CFCs and HPP-CFCs present in the adherent layer. These results suggest that captopril causes myelosuppression by inhibiting hematopoietic cell proliferation of progenitor and stem cells rather than depleting cells of the bone marrow microenvironment.