gebhart/patrepeval huggingface dataset:
Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression (2001)

Large granular lymphocyte (LGL) leukemia is characterized by the expansion of antigen-activated cytotoxic T lymphocytes. These leukemic cells are resistant to Fas-mediated apoptosis despite expressing high levels of Fas. We found that leukemic LGL from 19 patients displayed high levels of activated STAT3. Treatment of leukemic LGL with the JAK-selective tyrosine kinase inhibitor AG-490 induced apoptosis with a corresponding decrease in STAT-DNA binding activity. Moreover, using an antisense oligonucleotide approach to diminish STAT3 expression, we found that Fas sensitivity was restored in leukemic LGL. AG-490-induced apoptosis in leukemic LGL was independent of Bcl-xL or Bcl-2 expression. However, we found that the Bcl-2-family protein Mcl-1 was significantly reduced by AG-490 treatment. Activated STAT3 was shown to bind an SIE-related element in the murine mcl-1 promoter. Using a luciferase reporter assay, we demonstrated that v-src overexpression in NIH3T3 induced STAT3-dependent transcriptional activity from the mcl-1 promoter and increased endogenous Mcl-1 protein levels. We conclude that STAT3 activation contributed to accumulation of the leukemic LGL clones. These findings suggest that investigation should focus on novel strategies targeting STAT3 in the treatment of LGL leukemia.
Motion artifacts in optical coherence tomography with frequency-domain ranging (2004)

We describe results of theoretical and experimental investigations of artifacts that can arise in spectral-domain optical coherence tomography (SD-OCT) and optical frequency domain imaging (OFDI) as a result of sample or probe beam motion. While SD-OCT and OFDI are based on similar spectral interferometric principles, the specifics of motion effects are quite different because of distinct signal acquisition methods. These results provide an understanding of motion artifacts such as signal fading, spatial distortion and blurring, and emphasize the need for fast image acquisition in biomedical applications.
Insulin markedly potentiates the capacity of parathyroid hormone to increase expression of 25‐hydroxyvitamin D3‐24‐hydroxylase in rat osteoblastic cells in the presence of 1,25‐dihydroxyvitamin D3 (1996)

We have previously shown that insulin alters the renal metabolism of 25-hydroxyvitamin D. To examine the effect of insulin on vitamin D metabolism in bone, we have used UMR-106 osteoblast-like cells to study the regulation of 25(OH)D3-24-hydroxylase (24-hydroxylase) expression by insulin. The 24-hydroxylase is an important enzyme in degrading 1,25-dihydroxyvitamin D3 (1,25(OH)2D) in target tissues. Insulin alone had no effect on mRNA levels of the cytochrome P450 component (CYP24) of the 24-hydroxylase or on 24-hydroxylase activity itself in UMR cells. However, insulin increased the capacity of parathyroid hormone (PTH) to elevate CYP24 mRNA levels by 3-4-fold and to increase 24-hydroxylase activity by 2-fold in the presence of 1,25(OH)2D. Insulin increased the maximal responsiveness of UMR cells to PTH without altering their sensitivity. The action of insulin required the presence of 1,25(OH)2D and was partly dependent on new protein synthesis. Insulin-like growth factor 1 also potentiated the effects of PTH. This marked stimulation of the 24-hydroxylase by PTH and insulin may serve to regulate 1,25(OH)2D action and/or to produce 24,25-dihydroxyvitamin D in bone cells.
A Novel Gene, hKCa4, Encodes the Calcium-activated Potassium Channel in Human T Lymphocytes (1997)

We have isolated a novel gene, hKCa4, encoding an intermediate conductance, calcium-activated potassium channel from a human lymph node library. The translated protein comprises 427 amino acids, has six transmembrane segments, S1-S6, and a pore motif between S5 and S6. hKCa4 shares 41-42% similarity at the amino acid level with three small conductance calcium-activated potassium channels cloned from brain. Northern blot analysis of primary human T lymphocytes reveals a 2.2-kilobase transcript that is highly up-regulated in activated compared with resting cells, concomitant with an increase in KCa current. hKCa4 transcript is also detected by Northern blots or by polymerase chain reaction in placenta, prostate, thymus, spleen, colon, and many cell lines of hematopoietic origin. Patch-clamp recordings of hKCa4-transfected HEK 293 cells reveal a large voltage-independent, inwardly rectifying potassium current that is blocked by externally applied tetraethylammonium (Kd = 30 +/- 7 mM), charybdotoxin (Kd = 10 +/- 1 nM), and clotrimazole (Kd = 387 +/- 34 nM), but is resistant to apamin, iberiotoxin, kaliotoxin, scyllatoxin (Kd > 1 microM), and margatoxin (Kd > 100 nM). Single hKCa4 channels have a conductance of 33 +/- 2 picosiemens in symmetrical potassium solutions. The channel is activated by intracellular calcium (Kd = 270 +/- 8 nM) with a highly cooperative interaction of approximately three calcium ions per channel. These properties of the cloned channel are very similar to those reported for the native KCa channel in activated human T lymphocytes, indicating that hKCa4 encodes this channel type.
Inter-Subject Variability in Human Atrial Action Potential in Sinus Rhythm versus Chronic Atrial Fibrillation (2014)

Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP duration and morphology in SR versus cAF.
Regulation of Carcinogenesis by IL-5 and CCL11: A Potential Role for Eosinophils in Tumor Immune Surveillance (2007)

The role of the immune system in the surveillance of transformed cells has seen a resurgence of interest in the last 10 years, with a substantial body of data in mice and humans supporting a role for the immune system in host protection from tumor development and in shaping tumor immunogenicity. A number of earlier studies have demonstrated that eosinophils, when recruited into tumors, can very effectively eradicate transplantable tumors. In this study, we investigated whether eosinophils also play a role in tumor immune surveillance by determining the incidence of methylcholanthrene (MCA)-induced fibrosarcomas in IL-5 transgenic mice that have greatly enhanced levels of circulating eosinophils, CCL11 (eotaxin-1)-deficient mice that lack a key chemokine that recruits eosinophils into tissues, and the eosinophil-deficient mouse strains, IL-5/CCL11(-/-) and DeltadblGATA. It was found that MCA-induced tumor incidence and growth were significantly attenuated in IL-5 transgenic mice of both the BALB/c and C57BL/6 backgrounds. Histological examination revealed that the protective effect of IL-5 was associated with massively enhanced numbers of eosinophils within and surrounding tumors. Conversely, there was a higher tumor incidence in CCL11(-/-) BALB/c mice, which was associated with a reduced eosinophil influx into tumors. This correlation was confirmed in the eosinophil-deficient IL-5/CCL11(-/-) and DeltadblGATA mouse strains, where tumor incidence was greatly increased in the total absence of eosinophils. In addition, subsequent in vitro studies found that eosinophils could directly kill MCA-induced fibrosarcoma cells. Collectively, our data support a potential role for the eosinophil as an effector cell in tumor immune surveillance.
Susceptibility of enterococci, methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae to the glycylcyclines (1995)

The in-vitro activities of two glycylcyclines, DMG-MINO and DMG-DMDOT, and several comparative agents were determined against 263 enterococci, 102 methicillin-resistant Staphylococcus aureus and 55 Streptococcus pneumoniae recent clinical isolates. The glycylcyclines and teicoplanin were the most active agents against the enterococcal isolates. All methicillin-resistant S. aureus were susceptible to the glycylcyclines. Only DMG-DMDOT, ciprofloxacin, teicoplanin and vancomycin exhibited comparable activity against penicillin-susceptible, -intermediate and -resistant S. pneumoniae strains.
Multifunctional Electrode Arrays: Towards a Universal Detection Platform (2008)

Abstract In this article we review recent work in our laboratory towards the realization of a multianalyte microelectrode detection platform capable of discriminating chemicals and different biomolecules simultaneously. The functionalization of electrodes with aryl diazonium salts provides an electrically addressable deposition procedure capable of immobilizing a wide range of molecules. We demonstrate control over surface density and electron transfer kinetics as well as the activation of individual electrodes in an array. The direct electrically‐addressable immobilization of diazonium‐modified proteins is shown to be suitable for the construction of multianalyte immunosensors and the immobilization of horseradish peroxidase leading to the direct electron transfer between the redox enzyme and the electrode. The use of catalytic nanoparticles leads to the construction of a reagent‐less immunosensor and the simultaneous detection of DNA and proteins on the same electrode array is demonstrated.
Molecular Cloning of a Major Cockroach (Blattella germanica) Allergen, Bla g 2 (1995)

Inhalation of allergens produced by the German cockroach (Blattella germanica) elicits IgE antibody formation and the development of asthma in genetically predisposed individuals. We compared the allergenic importance of two cockroach (CR) allergens, Bla g 1 and Bla g 2, and determined the complete amino acid sequence of the major 36-kDa allergen, Bla g2. A survey of 106 sera from CR allergic patients showed the prevalence of IgE antibodies to Bla g 1 and Bla g 2 to be 30.2% and 57.6%, respectively. Immediate skin tests on 7 selected patients gave positive reactions using 10(-3) micrograms/ml either allergen, whereas controls showed no response to 10 micrograms/ml. Natural Bla g 2 was purified and the sequence of the NH2 terminus and tryptic peptides, comprising 36% of the molecule, was determined. The cDNA for Bla g 2 was cloned from a B. germanica expression library and encoded a 24-amino acid signal peptide and a 328-amino acid mature protein, which showed the highest degree of identity to mosquito (Aedes aegypti) lysosomal aspartic protease (30.8%), with similar identity to pepsin, cathepsins D and E, renin, and chymosin. Bla g 2 mRNA and protein were detected in B. germanica, but not in Periplaneta americana, the other principal domiciliary CR species in the U.S. High concentrations of Bla g 2 were found in CR digestive organs (esophagus, gut, and proventriculus). The results show that Bla g 2 is a major species-specific allergen of B. germanica and suggest that the allergen functions as a digestive enzyme in the cockroach.
A Novel Anti-Inflammatory Role of Simvastatin in a Murine Model of Allergic Asthma (2004)

Statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, are effective serum cholesterol-lowering agents in clinical practice, and they may also have anti-inflammatory properties. Asthma is characterized by chronic eosinophilic inflammation in the airways, which is thought to be regulated by the activity of T lymphocytes. We therefore examined the anti-inflammatory activity of simvastatin in a murine model of allergic asthma. In mice previously sensitized to OVA, simvastatin treatment, either orally or i.p., reduced the total inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid in response to inhaled OVA challenge. Simvastatin therapy i.p. was also associated with a reduction in IL-4 and IL-5 levels in bronchoalveolar lavage fluid and, at higher doses, a histological reduction in inflammatory infiltrates in the lungs. OVA-induced IL-4, IL-5, IL-6, and IFN-gamma secretion was reduced in thoracic lymph node cultures from simvastatin-treated mice. Simvastatin treatment did not alter serum total IgE or OVA-specific IgG1 and IgG2a levels. These data demonstrate the therapeutic potential of statin-sensitive pathways in allergic airways disease.
Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene. (1991)

We have cloned a novel human intronless gene encoding a G-protein-coupled receptor of the dopamine receptor family. Expression of this receptor in Cos-7 cells led to the high affinity binding of a number of dopamine D1 antagonists, with a binding profile similar to that of the previously described dopamine D1 receptor. In contrast, the agonist binding profile of this new receptor did not exactly match any previously defined dopamine D1 receptor and was notable for its unusually high affinity for dopamine. This new receptor caused a 13-fold increase in adenylylcyclase activity in transfected Cos-7 cells, following addition of dopamine. Messenger RNA encoding this new receptor appears to be widely distributed in the human brain, including cortical regions, choroid plexus, hippocampus, and brain stem. This new receptor appears to be identical to the recently described dopamine D5 receptor. A second closely related gene, GL39, was isolated and shown to represent a pseudogene, the first to be described in the G-protein-coupled receptor superfamily. This pseudogene exhibits 94% nucleotide sequence homology to the GL30 sequence and may have arisen from a gene duplication event followed by a mutation approximately 8 million years ago, prior to the emergence of man. This recently evolved pseudogene is transcribed in the human brain with a tissue distribution similar to that for its closely related functional gene.
Phytoestrogen-rich diets modulate expression of Brca1 and Brca2 tumor suppressor genes in mammary glands of female Wistar rats. (2003)

Phytoestrogens are natural compounds with anticancer, proliferation, differentiation, and chemopreventive effects, for which several mechanisms have been proposed. In the present study, modulation of Brca1 and Brca2 expression by different phytoestrogen-rich diets has been investigated in ovariectomized Wistar rats. Two hundred mammary glands were harvested in three independent experiments. Brca1 and Brca2 mRNAs were quantified by real-time quantitative reverse transcription-PCR, and their proteins by immunohistochemistry. The first experiment compared the influence of different phytoestrogens [flax-seed, isoflavones (IFs), or rutin]. A 10% increase in Brca1 mRNA expression was shown after flax-seed consumption, whereas no variation was noted for Brca2 mRNA, nor for Brca1 and Brca2 proteins. In the second experiment, two soy IFs sources (Novasoy or Soylife) were given at different concentrations to the animals. Only Brca2 mRNA was increased and only at high doses. Finally, the effect of IFs was compared with that of estradiol. An increase in mRNA for both genes was noted after estradiol treatment and with the highest dose of IFs. In conclusion, our results show that IFs, given in the diet at different doses, are able to increase Brca1 and Brca2 mRNA in ovariectomized female Wistar rat. However, no variation in Brca1 or Brca2 protein expression was demonstrated, whatever the experimental conditions were.
Optimized use of the firefly luciferase assay as a reporter gene in mammalian cell lines. (1990)

The enzymatic activity of firefly luciferase provides a sensitive, rapid means to assay transcriptional activity of regulated activation sequences of DNA when fused to the protein coding sequence of the luciferase gene. We have developed several modifications of the luciferase assay and have characterized certain parameters of the assay, resulting in optimization of conditions for the preparation and storage of cell lysates and establishment of substrate concentrations. These findings should be useful to investigators interested in applying the luciferase assay to studies of the transcriptional activity of test DNAs incorporating the luciferase reporter.
Genetic Unmasking of an Epigenetically Silenced microRNA in Human Cancer Cells (2007)

The mechanisms underlying microRNA (miRNA) disruption in human disease are poorly understood. In cancer cells, the transcriptional silencing of tumor suppressor genes by CpG island promoter hypermethylation has emerged as a common hallmark. We wondered if the same epigenetic disruption can "hit" miRNAs in transformed cells. To address this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in combination with a miRNA expression profiling. We have observed that DNA hypomethylation induces a release of miRNA silencing in cancer cells. One of the main targets is miRNA-124a, which undergoes transcriptional inactivation by CpG island hypermethylation in human tumors from different cell types. Interestingly, we functionally link the epigenetic loss of miRNA-124a with the activation of cyclin D kinase 6, a bona fide oncogenic factor, and the phosphorylation of the retinoblastoma, a tumor suppressor gene.
The effect of age on energy metabolism and resistance to ischaemic conduction failure in rat peripheral nerve. (1986)

Caudal nerve conduction velocity and amplitude of nerve action potential increased progressively with age to 8 months after which time no further increases were demonstrated. Rat peripheral nerve was progressively more resistant to ischaemic-anoxic conduction failure with increasing age. This resistance to ischaemic conduction failure was paralleled by a progressive age-related decline in endoneurial O2 consumption. Endoneurial adenosine triphosphate and creatine phosphate values were also progressively reduced with age. 15 min of anoxia resulted in progressively smaller reductions in these nucleotide phosphates with increasing age to 8 months after which time little further change occurred. Nerve lactate response to anoxia was higher in young rats (1 and 2 months) than in older animals (8 and 21 months). High energy phosphate expenditure progressively declined with age to 8 months, then stabilized. These findings indicate that the major mechanism of resistance to ischaemic conduction failure is a progressive decline in energy requirements.
Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. (2000)

Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic growth factor that is a primary stimulant of the development and maintenance of a vascular network in embryogenesis and the vascularization of solid tumors. At the present time there are two well-characterized receptors for VEGF that are selectively expressed on endothelium. VEGF receptor 2 [VEGFR2 (KDR/Flk-1)] mediates endothelial cell mitogenesis and permeability increases, whereas the role of VEGF receptor 1 [VEGFR1 (Flt-1)] has not been clearly defined. In the present study, a monoclonal antibody, 2C3, is shown to block the interaction of VEGF with VEGFR2 but not with VEGFR1 through ELISA, receptor binding assays, and receptor activation assays. 2C3 blocks the VEGF-induced vascular permeability increase in guinea pig skin. 2C3 has potent antitumor activity, inhibiting the growth of newly injected and established human tumor xenografts in mice. These findings demonstrate the usefulness of 2C3 in dissecting the pathways that are activated by VEGF in cells that express both VEGFR1 and VEGFR2, as well as highlighting the dominant role of VEGFR2 in mediating VEGF-induced vascular permeability increase and tumor angiogenesis.
Automatic Artifact Removal from Electroencephalogram Data Based on A Priori Artifact Information (2015)

Electroencephalogram (EEG) is susceptible to various nonneural physiological artifacts. Automatic artifact removal from EEG data remains a key challenge for extracting relevant information from brain activities. To adapt to variable subjects and EEG acquisition environments, this paper presents an automatic online artifact removal method based on a priori artifact information. The combination of discrete wavelet transform and independent component analysis (ICA), wavelet-ICA, was utilized to separate artifact components. The artifact components were then automatically identified using a priori artifact information, which was acquired in advance. Subsequently, signal reconstruction without artifact components was performed to obtain artifact-free signals. The results showed that, using this automatic online artifact removal method, there were statistical significant improvements of the classification accuracies in both two experiments, namely, motor imagery and emotion recognition.
Nerve grafting for peripheral nerve injuries with extended defect sizes (2018)

Artificial and non-artificial nerve grafts are the gold standard in peripheral nerve reconstruction in cases with extensive loss of nerve tissue, particularly where a direct end-to-end suture or an autologous nerve graft is inauspicious. Different materials are marketed and approved by the US Food and Drug Administration (FDA) for peripheral nerve graft reconstruction. The most frequently used materials are collagen and poly(DL-lactide-ε-caprolactone). Only one human nerve allograft is listed for peripheral nerve reconstruction by the FDA. All marketed nerve grafts are able to demonstrate sufficient nerve regeneration over small distances not exceeding 3.0 cm. A key question in the field is whether nerve reconstruction on large defect lengths extending 4.0 cm or more is possible. This review gives a summary of current clinical and experimental approaches in peripheral nerve surgery using artificial and non-artificial nerve grafts in short and long distance nerve defects. Strategies to extend nerve graft lengths for long nerve defects, such as enhancing axonal regeneration, include the additional application of Schwann cells, mesenchymal stem cells or supporting co-factors like growth factors on defect sizes between 4.0 and 8.0 cm.
Species- and Strain-Specific Control of a Complex, Flexible Regulon by Bordetella BvgAS (2006)

The Bordetella master virulence regulatory system, BvgAS, controls a spectrum of gene expression states, including the virulent Bvg(+) phase, the avirulent Bvg(-) phase, and at least one Bvg-intermediate (Bvg(i)) phase. We set out to define the species- and strain-specific features of this regulon based on global gene expression profiling. Rather than functioning as a switch, Bvg controls a remarkable continuum of gene expression states, with hundreds of genes maximally expressed in intermediate phases between the Bvg(+) and Bvg(-) poles. Comparative analysis of Bvg regulation in B. pertussis and B. bronchiseptica revealed a relatively conserved Bvg(+) phase transcriptional program and identified previously uncharacterized candidate virulence factors. In contrast, control of Bvg(-)- and Bvg(i)-phase genes diverged substantially between species; regulation of metabolic, transporter, and motility loci indicated an increased capacity in B. bronchiseptica, compared to B. pertussis, for ex vivo adaptation. Strain comparisons also demonstrated variation in gene expression patterns within species. Among the genes with the greatest variability in patterns of expression, predicted promoter sequences were nearly identical. Our data suggest that the complement of transcriptional regulators is largely responsible for transcriptional diversity. In support of this hypothesis, many putative transcriptional regulators that were Bvg regulated in B. bronchiseptica were deleted, inactivated, or unregulated by BvgAS in B. pertussis. We propose the concept of a "flexible regulon." This flexible regulon may prove to be important for pathogen evolution and the diversification of host range specificity.
Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: Macrophage harbingers of disease severity (2011)

Because elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, the present observations suggest that macrophages have potential immunopathologic involvement in SS and that the tissue macrophage transcription profile reflects multiple genes induced by IFNα.