gebhart/patrepeval huggingface dataset:
II. Regulation of CFTR by small molecules including (1998)

Cystic fibrosis (CF) affects a number of epithelial tissues, including those in the gastrointestinal tract. The goal of this review is to summarize data related to regulation of the protein product of the CF gene, CF transmembrane conductance regulator (CFTR), by a variety of small molecules. There has been a surge of interest in discovering small molecules that could be exogenously added to cells and tissues to regulate CFTR and could potentially be used alone or in combination with genetic approaches for therapy in CF. We will discuss the apparent mechanisms of action of genistein, milrinone, 8-cyclopentyl-1,3-dipropylxanthine, IBMX, and NS-004; several of which appear to interact directly with one or both nucleotide binding domains of CFTR. We also discuss how ![Formula][1] interacts with CFTR as both a permeating anion and a potential regulator of Cl− permeation through the CFTR ion channel. It is likely that there are complicated interactions between Cl− and![Formula][2] in the secretion of both ions through the CFTR and the anion exchanger in intestinal cells, and these may yield a role of CFTR in regulation of intestinal![Formula][3] secretion as well as of intra- and extracellular pH.

 [1]: /embed/mml-math-2.gif
 [2]: /embed/mml-math-3.gif
 [3]: /embed/mml-math-4.gif
Requirement and role of C5a in acute lung inflammatory injury in rats. (1996)

The complement activation product, C5a, may play a key role in the acute inflammatory response. Polyclonal antibody to rat C5a was used to define the requirements for C5a in neutrophil-dependent inflammatory lung injury after systemic activation of complement by cobra venom factor (CVF) or after intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous infusion (but not intratracheal instillation) of anti-C5a produced a dose-dependent reduction in lung permeability and in lung content of myeloperoxidase. In C6-deficient rats, CVF infusion caused the same level of lung injury (measured by leak of 125I-albumin) as found in C6-sufficient rats. In the IgG immune complex model of lung injury, anti-C5a administered intratracheally (but not intravenously) reduced in a dose-dependent manner both the increase in lung vascular permeability as well as the buildup of lung myeloperoxidase. Treatment with anti-C5a greatly suppressed upregulation of lung vascular intercellular adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in levels of TNFalpha in bronchoalveolar fluids. These data demonstrate the requirement for C5a in the two models of injury. In the IgG immune complex model, C5a is required for the full production of TNFalpha and the corresponding upregulation of lung vascular ICAM-1.
Febuxostat: a non-purine, selective inhibitor of xanthine oxidase for the management of hyperuricaemia in patients with gout (2005)

Febuxostat is a non-purine, selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. With febuxostat 10-120 mg, the pharmacokinetics are linear. No dose adjustment appears to be necessary in those with renal insufficiency or mild-to-moderate hepatic impairment. Febuxostat 10-120 mg/day rapidly and sustainably reduces serum uric acid by 25-70% in uric acid underexcretors and overproducers. Prophylaxis with colchicine or a non-steroidal anti-inflammatory drug can mitigate the gout-flare risk from the rapid urate lowering after febuxostat initiation. Febuxostat is well tolerated, the majority of treatment-related adverse events are transient and mild-to-moderate in severity. Febuxostat can broaden the therapeutic options for urate-lowering therapy in those with gout.
Aflibercept in wet AMD beyond the first year of treatment: recommendations by an expert roundtable panel (2015)

This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for ≥3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.
Bladder cancer. Human leukocyte antigen II, interleukin-6, and interleukin-6 receptor expression determined by the polymerase chain reaction (1991)

The prediction of tumour biology rarely rests upon a single characteristic of the malignancy. The analysis of a single gene can complement standard histologic evaluation. The investigation of new parameters as well as the routine clinical analysis of gene expression is often limited because of the small amount of tissue available. This is particularly true of de novo human bladder cancers because they are generally small or handled in such a way as to hinder the analysis of multiple different parameters. Analysis of expressed mRNA by the polymerase chain reaction (RNA/PCR) is a method that allows the development of a profile of bladder cancer gene expression. The authors report the use of the RNA/PCR method to examine in bladder cancer the expression of the human leukocyte antigen (HLA) class II gene family (HLA-DR, DQ, and DP) as well as interleukin-6 (IL-6) and the interleukin-6 receptor (IL-6R). All de novo transitional cell carcinomas, one squamous carcinoma, and two transitional cell carcinoma cell lines expressed the majority of HLA class II genes. All samples expressed IL-6R RNA whereas production of IL-6 message was limited to one of the cell lines and to the high-grade bladder cancers. These results were combined with stage, grade, and DNA content to develop a profile of the cancers examined. Although an improved predictive index based on gene expression analysis by RNA/PCR has not been realized, a broader survey of human tumors for expression of these genes and others is likely to refine the classification of bladder cancer.
A hairpin ribozyme inhibits expression of diverse strains of human immunodeficiency virus type 1. (1993)

Ribozymes have enormous potential as antiviral agents. We have previously reported that a hairpin ribozyme expressed under the control of the beta-actin promoter that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence can inhibit HIV-1 (pHXB2gpt) expression. For such a ribozyme in a retroviral vector delivery system to be useful in gene therapy for the treatment of HIV-1 infection, it must be able to inhibit the expression of multiple HIV-1 strains. We have now cloned this ribozyme into various regular expression vectors (including retroviral vectors) by using various gene expression control strategies. Here we show by transient transfection that inhibition of expression of diverse strains of HIV-1 can be achieved by this ribozyme expressed in the proper vectors. These data further support the potential of this hairpin ribozyme as a therapeutic agent for HIV-1.
Enhancement of RNAi activity by improved siRNA duplexes (2003)

RNA interference (RNAi) is a powerful tool for suppressing the expression of a gene of interest, in which 21-25 nucleotide short interfering RNA (siRNA) duplexes homologous to the silenced gene function as sequence-specific RNAi mediators. The present study shows that newly designed siRNA duplexes, 'fork-siRNA duplexes', whose sense-stranded siRNA elements carry one to four nucleotide mismatches at the 3'-ends against the antisense-stranded siRNA elements, can enhance RNAi activity over conventional siRNA duplexes in cultured mammalian cells.
Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients (2015)

Three-dimensional (3D) printing offers the potential for rapid customization of medical devices. The advent of 3D-printable biomaterials has created the potential for device control in the fourth dimension: 3D-printed objects that exhibit a designed shape change under tissue growth and resorption conditions over time. Tracheobronchomalacia (TBM) is a condition of excessive collapse of the airways during respiration that can lead to life-threatening cardiopulmonary arrests. We demonstrate the successful application of 3D printing technology to produce a personalized medical device for treatment of TBM, designed to accommodate airway growth while preventing external compression over a predetermined time period before bioresorption. We implanted patient-specific 3D-printed external airway splints in three infants with severe TBM. At the time of publication, these infants no longer exhibited life-threatening airway disease and had demonstrated resolution of both pulmonary and extrapulmonary complications of their TBM. Long-term data show continued growth of the primary airways. This process has broad application for medical manufacturing of patient-specific 3D-printed devices that adjust to tissue growth through designed mechanical and degradation behaviors over time.
Electrodeless dielectrophoresis for micro total analysis systems (2003)

Several examples where a sample-to-answer, lab-on-a-chip chemical analysis system may benefit from EDEP technology in upstream sample preparation (cell sorting, cell lysing, DNA concentration, and purification) and in a back-end detection platform for hybridization and sensitivity enhancement were presented. The simplicity of the device and the lack of metallic electrodes at the trap, which cause electrochemical reactions involving gas evolution, made possible the investigation of the response of biological objects in a wide range of frequencies, especially the low-frequency regime. Above all, EDEP may be seamlessly integrated with the metallic DEP layout, this increasing the flexibility in custom-tailored chip design.
Molecular Engineering of Semiconductor Surfaces and Devices (2002)

Grafting organic molecules onto solid surfaces can transfer molecular properties to the solid. We describe how modifications of semiconductor or metal surfaces by molecules with systematically varying properties can lead to corresponding trends in the (electronic) properties of the resulting hybrid (molecule + solid) materials and devices made with them. Examples include molecule-controlled diodes and sensors, where the electrons need not to go through the molecules (action at a distance), suggesting a new approach to molecule-based electronics.
[Disposal of insulin syringes by diabetic patients. Report of 100 patients]. (2005)

Elimination of syringes and needles is regulated in hospitals. However, the regulations remain unknown of diabetic patients who do not eliminate correctly their syringes of insulin. We propose to analyze the present situation concerning the management of used syringes of insulin by diabetic patients. This study was conducted in a clinic for diabetics and it involved 100 diabetic patients treated with insulin. The results of this study shaved an insufficiency in the management of syringes of insulin by diabetic patients. Thus, education and a conscionsness-raising of diabetic patients on management and correct use of syringes are necessary.
Variation in Essential Oil Content and Composition in Turkish Anise (Pimpinella anisum L.) Populations* (2004)

This research was carried out at the University of Ankara, Faculty of Agriculture, Field Crops Department and the laboratories of the Food Engineering Department. Twenty-nine anise seed samples were collected from different locations in 9 producer provinces in Turkey and were used as the study materials in order to determine essential oil and essential oil compositions. According to the results, essential oil levels varied from 1.3% to 3.7%. The major component of the essential oil was trans-anethole. This compound ranged from 78.63% to 95.21%. Population 26 may be recommended for trans-anethole percentage and populations 8 and 22 for essential oil content.
Heparin effect on red blood cell aggregation (1994)

We studied the effect of relatively high dosages of heparin (25-150 U/ml) on some rheological parameters of donor blood. It was found that heparin increased the erythrocyte sedimentation rate (ESR) and low shear blood viscosity at all concentrations studied. The increase of these parameters indicates an elevation in RBC aggregation. In all samples with a heparin concentration of 100 U/ml, the average ESR was increased by approximately 75% (p < 0.001); whole blood viscosity increased under shear rate, gamma = 0.277 sec-1, by approximately 30% (p < 0.001). Since bolus injection of heparin may result in transient high local concentration, these results suggest a possible additional adverse effect to the well known heparin effect on platelet aggregation.
Acoustic microscopy: resolution of subcellular detail. (1979)

Recent advances now permit the use of scanning acoustic microscopy for the analysis of subcellular components. By sequential viewing of identified fixed cells with acoustic, light, and electron microscopy, we have established that the acoustic microscope can readily detect such features as nuclei and nucleoli, mitochondria, and actin cables. Under optimal conditions, images can even be obtained of filopodia, slender projections of the cell surface that are approximately 0.1-0.2 micron in diameter. Small objects separated by as little as 0.5-0.7 micron can successfully be resolved. Three aspects of the acoustic micrographs prepared in this preliminary survey seem especially prominent. These are, first, the extraordinary level of acoustic contrast that can differentiate the various cytoplasmic organelles, even in regions of very thin cytoplasm; second, the reversals in acoustic contrast that occur when altering the plane of focus; and third, the sensitivity of the acoustic response to overall cytoplasmic thickness. The acoustic microscope uses a novel source of contrast that is based on local mechanical properties. In addition, it can provide a degree of resolution that is comparable to that of the light microscope.
Advanced technologies for optimized sub-quarter-micrometer SOI CMOS devices (1998)

Two manufacturable technologies of fully-depleted (FD) thin-film silicon-on-insulator (SOI) MOSFET's for low-power applications are proposed in this paper. To maintain high current drive while aggressively thinning down the SOI film, silicide is to be formed on Ge-damaged silicon layers. Ge preamorphization facilitates silicide formation at low temperature (/spl sim/450/spl deg/C) and effectively controls the silicide depth without void formation. It also reduces the floating body effect. In addition, a reliable gate work-function engineering is introduced for good threshold voltage management. A p/sup +/SiGe/Si stack gate alleviates the threshold voltage instability of SOI due to film thickness nonuniformity and broadens the design window for channel doping. These advanced technologies, compatible with existing bulk CMOS technology, are integrated into SOI CMOS process. Excellent electrical device results are presented.
Microscopic platelet size and morphology in various hematologic disorders (1978)

Microscopic evaluation of apparent platelet size and morphology was examined in a variety of hematologic disorders. The time of preparation of the blood smear was important. An artifactual increase in platelet size was noted on blood films from 20 normal individuals that were prepared either immediately or 180 min after venipuncture. The clearest differentiation of patient categories was obtained with smears prepared 60 min after venipuncture using blood anticoagulated with K3EDTA. Under these conditions, normal size and morphology values were found in thrombocytopenic patients with aplasia or with increased splenic pooling. In contrast, large size values were a reliable finding in idiopathic thrombocytopenic purpura patients, whose platelet counts were less than 50,000/microleter. Large size values were also noted in patients with infiltrated bone marrows or myeloproliferative syndromes regardless of the platelet count. The last two groups usually showed abnormal platelet morphology with greater than 10% hypogranular platelets. Normal platelet size and morphology were observed in patients with iron-deficiency and megaloblastic anemias and in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus who had normal platelet counts.
D‐TAT transporter as an ocular peptide delivery system (2005)

The retro-inverso form of the TAT sequence is effective in transducing cells from various compartments of the eye. After 14 days, the D-TAT FITC was clearly visible in the retina whereas L-TAT FITC had almost disappeared. The D-TAT peptide represents an interesting molecular transporter that, when coupled to a specific effector, may have potential therapeutic future, especially when a long-lasting action is needed.
THE HISTOLOGICAL LESIONS OF EXPERIMENTAL GLANDERS (1907)

The bacillus of glanders may be so modified in virulence as to produce experimentally lesions differing widely in their histological features. The highly virulent culture causes primary necrosis and disintegration of the tissue followed by the invasion of the injured area by polymorphonuclear leucocytes. The bacilli of moderate virulence give rise to a primary lesion of an acute inflammatory nature in which the cells show no evidence of necrosis or disintegration. The attenuated bacilli produce primary tissue proliferation with the formation of epithelioid and giant cells. There is every grade of lesion between the acute exudative and the chronic proliferative depending upon the toxicity of the cultures. The glanders lesion whether exudative or proliferative is focal in character. The strong toxins of the glanders bacilli cause degeneration or necrosis of cells and exudation, while the dilute and weak toxins produce proliferation. The giant cell of glanders undoubtedly originates from the endothelial cell of the blood and lymph channels and is formed by division of the nucleus of the endothelial cell and not by cell fusion. Histologically the lesion of glanders resulting from the culture of a low degree of virulence is proliferative and is analogous to tuberculosis; the lesions are focal and bear an intimate relation to the glanders bacillus.
CMV REACTIVATION AND SPECIFIC CD4+ T-CELL RESPONSE IN PATIENTS WITH SEPTIC SHOCK (2004)

Muller, L. v.*; Klemm, A.*; Durmus, N.*; Schneider, M.#; Wei, M.#ß; Wiedeck, H.#; Georgieff, M.#; Mertens, Th.* Author Information
Can isotype switch modulate antigen-binding affinity and influence clonal selection? (2000)

Four different monoclonal Ig (MIg) (IgA1kappa, IgG1kappa, IgG2kappa and IgG4kappa) displaying anti-tubulin activity were detected in the serum from a lymphoma patient. The complete sequence of three of these MIg showed identical V(H) and V(L) domains and the presence of mutations compatible with an antigen-driven process. Surprisingly, despite complete homology in their variable domains, IgA1kappa, IgG1kappa, or their Fab fragments bound to a common motif recognized in beta tubulin, with significant differences in affinity (IgA1kappa 1.52x10(-8) M, and IgG1kappa 2.09x10(-7) M). To substantiate these results, the V(H) and V(L) domains from IgA1kappa were cloned and introduced into expression vectors containing the constant kappa exon and either the mu or the gamma1 constant exon, and complete recombinant IgMkappa and IgG1kappa were obtained. Like the IgA1kappa, the IgMkappa construction bound to the tubulin epitope with consistent affinity (7.7x10(-9) M), whereas the IgG1kappa construction displayed a significantly lower affinity (3.28x10(-7) M). These results provide definitive evidence that isotype can influence binding affinity to antigen and suggest that malignant transformation occurred at the germinal center once the mutational process was achieved and the switch process was still active.
Hippocampal Shape Analysis of Alzheimer Disease Based on Machine Learning Methods (2007)

Subtle and spatially complex deformation patterns of hippocampus between patients with AD and healthy control subjects can be detected by machine learning methods.
Abstract 4345: AZD8055, a combined TORC1/TORC2 inhibitor regulates Mycn protein expression and prevents neuroblastoma growth in vitro and in vivo (2011)

Abstract Neuroblastoma is the most common and deadly solid tumour of childhood (Brodeur, 2003). Amplification of the MYCN oncogene occurs in 25% of NBs correlating with poor clinical outcome. High risk neuroblastoma responds to current therapies but rapidly acquires chemoresistance; therefore alternative treatment strategies are required. Because of the importance of MYCN amplification in high risk neuroblastoma and specific expression of Mycn protein in tumour tissue, we have examined indirect methods of destabilising Mycn by targeting key components of upstream signalling pathways, responsible for maintenance of Mycn protein levels. Mycn protein stability is maintained by the RAS (RAF/MEK/ERK) and PI3K (PI3K/AKT/mTOR) pathways. The mammalian target of rapamycin (mTOR) plays an important role in cell proliferation, metabolism and tumourigenesis, and is frequently altered in cancer. Rapamycin and its analogues target the TORC1 complex and are effective against tumour xenografts but are limited by consequent up regulation of PI3K activity. Inhibition of TORC1 alleviates a TORC1 dependent negative feedback loop, with resulting activation of PI3K and AKT-dependent survival pathways. AZD8055 is an mTOR kinase inhibitor that inhibits both TORC complexes with IC50 values in the nanomolar (nM) range. Treatment of N-myc wild-type or phosphomutant expressing neuroblastoma cell lines with AZD8055 inhibited mTOR-dependent phosphorylation of key pathway components, coincident with selective inhibition of wild-type but not phospho-mutated N-myc protein. Cell proliferation was reduced and sensitive cells accumulated in G1 as shown by flow cytometric analysis. Cells expressing N-myc phosphomutant proteins showed less sensitivity to AZD8055, with GI50 values above mechanistic range for targeted effects of this drug. The ability of AZD8055 to inhibit neuroblastoma tumour progression was tested in a transgenic model of neuroblastoma (TH-MYCN) that over expresses Mycn protein and is predisposed to spontaneous tumour formation (Weiss, 97). We present data showing that AZD8055 inhibits tumour progression, reduces tumour cell proliferation and targets the mTOR complex in vivo. In conclusion, inhibition of mTOR signalling is highly effective against MYCN-driven cell lines and tumours, and therefore could be a promising therapeutic strategy for targeted treatment of MYCN-amplified neuroblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4345. doi:10.1158/1538-7445.AM2011-4345