gebhart/patrepeval huggingface dataset:
Management of Crohn's disease--a practical approach. (2003)

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that affects up to 480,000 persons in the United States. Symptoms include abdominal pain, diarrhea, fever, malaise, and arthralgias, and cause considerable morbidity. Speculation about genetic, environmental, dietary, infectious, and immunologic etiologies has led to treatment modalities directed at each theoretic cause, but therapy guidelines are determined by the severity of disease. Use of salicylates and/or antibiotics can be effective in mild to moderate disease, while steroids are the accepted therapy for more severe active disease. Azathioprine and other immunosuppresant drugs can be used as adjunctive therapy for active Crohn's disease and may help to maintain remission. Infliximab, an antibody to human tumor necrosis factor alpha, has proved successful in the treatment of severe refractory disease and generally causes only mild side effects. Therapy for Crohn's disease must involve treating comorbid conditions to improve the quality of life of patients.
Antitumor agents. 141. Synthesis and biological evaluation of novel thiocolchicine analogs: N-acyl, N-aroyl-, and N-(substituted benzyl)deacetylthiocolchicines as potent cytotoxic and antimitotic compounds (1993)

Three series of novel thiocolchicine analogs, N-acyl-, N-aroyl-, and N-(substituted benzyl)-deacetylthiocolchicinoids, have been synthesized and evaluated for their cytotoxicity against various tumor cell lines, especially solid tumor cell lines, and for their inhibitory effects on tubulin polymerization in vitro. Most of these compounds showed strong inhibitory effects on tubulin polymerization comparable to that obtained with thiocolchicine and greater than that obtained with colchicine. Only compounds with a long side chain at the C(7) position, such as 22-24, did not inhibit tubulin polymerization. Several of the active N-aroyldeacetylthiocolchicine analogs had positive optical rotations, in contrast to the negative optical rotation observed with most colchicinoids. This property might be attributed to a reversal of biaryl configuration from the normal aS to aR. Therefore, the N-aroyl analogs were further evaluated by circular dichroism, which readily distinguishes between the aS and aR biaryl configurations. This latter technique demonstrated that the active N-aroyl analogs do have an aS configuration despite their positive optical rotations. However, comparison of 1H NMR and UV spectral data of N-(substituted benzyl)-deacetylthiocolchicines with those of corresponding N-aroyldeacetylthiocolchicines suggested a different biaryl dihedral angle [even though these compounds have the same aS biaryl configuration]. The similar tubulin binding properties of these compounds suggest that a biaryl dihedral angle of 53 degrees is not essential for colchicinoid-tubulin interaction. The increased cytotoxicity of N-(substituted benzyl)deacetylthiocolchicines compared to the N-aroyldeacetylthiocolchicines may be attributed to different lipophilicity, drug uptake, or drug metabolism in the tumor cells. The side chain at the C(7) position affects inhibition of tubulin polymerization and the cytotoxic activity of colchicinoids as a function of its size and its contribution to lipophilicity.
Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura (2012)

ALX-0681 is a therapeutic Nanobody targeting the A1-domain of VWF. It inhibits the interaction between ultra-large VWF and platelet GpIb-IX-V, which plays a crucial role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In the present study, we report the efficacy and safety profile of ALX-0681 in a baboon model of acquired TTP. In this model, acute episodes of TTP are induced by administration of an ADAMTS13-inhibiting mAb. ALX-0681 completely prevented the rapid onset of severe thrombocytopenia and schistocytic hemolytic anemia. After induction of TTP, platelet counts also rapidly recovered on administration of ALX-0681. This effect was corroborated by the full neutralization of VWF activity. The schistocytic hemolytic anemia was also halted and partially reversed by ALX-0681 treatment. Brain CT scans and post mortem analysis did not reveal any sign of bleeding, suggesting that complete neutralization of VWF by ALX-0681 under conditions of thrombocytopenia was not linked with an excessive bleeding risk. The results obtained in this study demonstrate that ALX-0681 can successfully treat and prevent the most important hallmarks of acquired TTP without evidence of a severe bleeding risk. Therefore, ALX-0681 offers an attractive new therapeutic option for acquired TTP in the clinical setting.
Hybridization of fluorescein-labeled DNA oligomers detected by fluorescence anisotropy with protein binding enhancement (1995)

Fundamental aspects of the application of fluorescence anisotropy to detect the hybridization of fluorescein-labeled DNA oligomers were explored. The oligomers included a binding site for the EcoRI restriction enzyme, which binds to double-stranded DNA and is used in this work to enhance the difference between the anisotropies of the single-stranded and double-stranded oligomers by increasing the effective volume of the latter. The fluorescence anisotropy increases upon hybridization and further upon binding of EcoRI to the double strand. By varying the length of the tether used to attach the fluorescein to the 5' end of the oligonucleotide, it was found that a 6-carbon tether was optimal, providing the most dramatic increases in anisotropy in the presence of EcoRI. Dynamic fluorescence anisotropy (DFA) provided insight into the increases in steady-state anisotropy. In most cases, the best fits to the DFA data were obtained using a biexponential decay model, which describes an anisotropic rotator. Upon hybridization, the faster rotational motion is more hindered, and the contribution of the slower rotational component is increased. This effect is enhanced by binding of EcoRI to the double strand, especially when the EcoRI binding site is near the fluorescein at the 5' end and the tether length is in the optimal range. Because the rotational correlation time of the slower anisotropy decay component is much longer than the fluorescence lifetime, it is possible in some cases to reduce the anisotropic rotator model to the special limiting case of a hindered rotator.
Calcitonin Gene‐Related Peptide (CGRP) and Migraine (2006)

The neuropeptide calcitonin gene-related peptide (CGRP) has long been postulated to play an integral role in the pathophysiology of migraine. While clinical findings are consistent with such a role, the specific pathogenic mechanisms of CGRP in migraine have remained speculative until recently. Through advances in molecular neuroscience, the pathogenic mechanisms of CGRP in migraine have begun to be elucidated. This paper discusses the hypothesized role of CGRP in migraine and reviews recent findings on the molecular mechanisms of this neuropeptide in migraine pathophysiology. Studies in cultured trigeminal neurons demonstrate that CGRP is released from trigeminal ganglia cells, that CGRP transcription is increased under conditions mimicking neurogenic inflammation, that migraine pharmacotherapies can both reduce CGRP release and inhibit CGRP transcription, and that tumor necrosis factor-alpha (TNF-alpha), an endogenous inflammatory mediator implicated in migraine, can stimulate CGRP transcription. Together, the results suggest that, in migraine, activation of trigeminal nerves release CGRP and other peptides that cause the release of proinflammatory mediators. These mediators further increase CGRP synthesis and release over hours to days in correspondence with the 4- to 72-hour duration of a typical migraine episode. The increased CGRP synthesis and release might be mediated by activation of mitogen-activated protein kinase pathways, which, in turn, can be modulated by endogenous inflammatory substances such as TNF-alpha and affected by drugs such as sumatriptan.
Multiloop optoelectronic oscillator (2000)

We describe and demonstrate a multiloop technique for single-mode selection in an optoelectronic oscillator (OEO). We present experimental results of a dual loop OEO, free running at 10 GHz, that has the lowest phase noise (-140 dBc/Hz at 10 kHz from carrier) of all free-running room-temperature oscillators to date. Finally, we demonstrate the first fiber-optic implementation of the carrier suppression technique to further reduce the close-to-carrier phase noise of the oscillator by at least 20 dB.
Capillary versus venous bedside blood glucose estimations (2005)

There is a small but significant difference in the blood glucose results analysed on a bedside glucometer when the samples are taken from capillary or venous sources. Although good correlation is the norm between venous and capillary derived samples, caution must be exercised in accepting the results as equivalent or using either as substitutes for a laboratory blood glucose result.
Capillary Condensation and Desorption of Binary Mixtures of N2−Ar Confined in a Mesoporous Medium (2000)

The adsorption and desorption of the binary system N2xAr1-x confined in the cylindrical 4 nm diameter pores of Vycor glass has been studied using positron annihilation spectroscopy. When the Vycor sample was suspended in the gaseous mixture, the gas−liquid and liquid−gas phase transitions of the confined fluid exhibit hysteresis which varies little with composition, indicating that the confined mixture behaves like a simple fluid. However, if bulk mixture surrounding the samples was allowed to condense, the liquid−gas transition exhibited a much larger degree of hysteresis for the mixtures, although unchanged for either pure gas. The observed behavior indicates that bulk liquid condensed around the Vycor samples is able to interact with the confined fluid, causing the confined mixture to become Ar rich.
Acute Toxicity of Carbaryl, Methiocarb, and Carbosulfan to the Rainbow Trout (Oncorhynchus mykiss) and Guppy (Poecilia reticulata) (2007)

The acute toxicity of carbaryl, methiocarb and carbosulfan to juvenile rainbow trout (Oncorhynchus mykiss; 1.92 ± 0.5 g) and guppies (Poecilia reticulata; 0.45 ± 0.04 g) was evaluated in 96-h toxicity tests under static conditions. Concentrations in the toxicity test ranged from 0.85 to 8.5 mg/l for carbaryl, from 0.7 to 28.0 mg/l for methiocarb, and from 0.031 to 12.5 mg/l for carbosulfan. Carbaryl and methiocarb were more toxic to rainbow trout than to guppies. However, compared with rainbow trout, guppies were more sensitive to carbosulfan. The incidence of mortality in fish increased significantly (P &amp;amp;lt; 0.05) with increasing pesticide concentrations. The time required to kill 50% (LT50) of the rainbow trout at the lowest concentrations of carbaryl, methiocarb, and carbosulfan was 51 h 12 min, 74 h 35 min, and 107 h 57 min, respectively. As insecticide concentrations were increased, LT50 values decreased (P &amp;amp;lt; 0.05).
New Chemical Synthesis of the Promising Cancer Chemotherapeutic Agent 12,13-Desoxyepothilone B: Discovery of a Surprising Long-Range Effect on the Diastereoselectivity of an Aldol Condensation (1999)

The epothilones are naturally occurring cytotoxic molecules that possess the remarkable ability to arrest cell division through the stabilization of microtubule assemblies. Our in vivo studies with 12,13-desoxyepothilone B (dEpoB), have established that the desoxy compound is well tolerated and virtually curative against a variety of sensitive and resistant xenograft tumors in animal models. In light of these discoveries, we sought a chemical synthesis of dEpoB that would be able to support a serious and substantial discovery research program directed toward the clinical development of this molecule. The overall strategy for this endeavor assumed the ability to synthesize dEpoB from three constructs which include an achiral β,δ-diketo ester construct A, an (S)-2-methylpentenal moiety B, and the thiazoyl-containing vinyl iodide moiety C. We envisioned that a diastereoselective aldol condensation between an achiral C5−C6 (Z)-metalloenolate derived from construct A and an (S)-2-methylalkanal fragment, B, would generate the desired C6−C7 bond. Second, a B-alkyl Suzuki coupling between the vinyl iodide construct C and an alkyl borane would form the C11−C12 bond. Finally, a late-stage reduction of the C3 ketone to the requisite C3 alcohol with high asymmetric induction would permit us to introduce the β,δ-diketo ester fragment A, into the synthesis as a readily accessible achiral building block. The governing concepts for our new synthesis are described herein.
A sensitive and specific erythropoietin immunoprecipitation assay: application to pharmacokinetic studies. (1992)

Previous pharmacokinetic studies with radiolabeled erythropoietin have relied on results of nonspecific methods to derive pharmacokinetic parameters. Dependence on nonspecific protein precipitation or total radioactivity may result in falsely high determinations of plasma radiolabeled erythropoietin and erroneous determinations of pharmacokinetic elimination and distribution parameters. In the present study pharmacokinetic parameters were derived by using a specific, sensitive, and reproducible immunoprecipitation assay for biologically active iodine 125-labeled recombinant human erythropoietin (125I-rhEp) and compared with those obtained by using nonspecific protein precipitation with trichloroacetic acid (TCA). Tracer amounts of 125I-rhEp were administered by bolus injection to six newborn lambs. Plasma-precipitable radioactivity assayed by the immunoprecipitation method became progressively lower with time relative to those observed with the TCA method. Pharmacokinetic parameters derived from the immunoprecipitation assay demonstrated significantly more rapid plasma and elimination clearances, shorter terminal half-life, shorter mean body residence time, and shorter distribution time when compared with the TCA assay (p less than 0.01). Volume of distribution was not different. Comparison of immunoprecipitation and TCA assay results from gel permeation fractions of iodinated erythropoietin demonstrated that immunoprecipitation assay results provide a better evaluation of biologically active hormone as determined by comparisons with SDS-PAGE and erythropoietin radioreceptor data. We conclude that 125I-rhEp pharmacokinetic parameters derived by using the immunoprecipitation assay more accurately reflect physiologic conditions than do those derived by using TCA precipitation.
Quantification of histochemical staining by color deconvolution. (2001)

This image analysis algorithm provides a robust and flexible method for objective immunohistochemical analysis of samples stained with up to three different stains using a laboratory microscope, standard RGB camera setup and the public domain program NIH Image.
Side-effects of desferrioxamine in dialysis patients (1993)

Journal Article Side-effects of desferrioxamine in dialysis patients Get access J. R. Boelaert, J. R. Boelaert 1Unit for Renal and Infectious DiseasesAlgemeen Ziekenhuis St Jan, Brugge Correspondence and offprint requests to : Dr J. Boelaert, Algemeen Ziekenhuis Sint Jan, Unit for Renal and Infectious Diseases, Ruddershove 10,8000 Brugge, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar M. de Locht M. de Locht 2Laboratory of Cellular Biochemistry, Catholic University of LouvainLouvain-la-Neuve, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar Nephrology Dialysis Transplantation, Volume 8, Issue supp1, 1993, Pages 43–46, https://doi.org/10.1093/ndt/8.supp1.43 Published: 01 January 1993
Interaction of culture-derived macrophages with the fibroblast-binding domain of fibronectin is a necessary but inefficient signal for fibronectin enhancement of CR1-mediated phagocytosis. (1986)

Human plasma fibronectin (Fn) enhances ingestion of opsonized particles through its interaction with phagocytic cells. To better characterize the site or sites on Fn responsible for this effect, we subjected Fn to limited proteolytic cleavage by chymotrypsin and used affinity and gel filtration chromatography to isolate a 110,000 dalton cell-binding fragment, a 60,000 dalton fragment that bound both heparin and gelatin, and 50,000 and 45,000 dalton fragments that bound to gelatin but not heparin. The cell-binding fragment mediated adhesion and spreading of fibroblasts on glass slides, whereas the heparin-gelatin and gelatin-binding fragments failed to cause fibroblast spreading. At high concentrations, the cell-binding fragment doubled phagocytosis of C4b-coated sheep erythrocytes by human monocyte-derived macrophages, whereas equal concentrations of the other fragments had minimal enhancing effect on phagocytosis. Interestingly, the effect of the cell-binding fragment on CR1-mediated phagocytosis was always less than the effect of intact Fn, even when a 40-fold higher molar concentration of the cell-binding fragment was used. Fab of a monoclonal anti-Fn, HFn 7.1, which recognizes the 110,000 dalton cell-binding fragment of Fn and inhibits fibroblast binding, blocked enhancement of CR1-mediated phagocytosis by intact Fn. Fab of Fn 8, a monoclonal anti-Fn that binds the heparin-gelatin-binding fragment, failed to inhibit the Fn effect. These data suggest that interaction of the macrophage with the cell-binding domain of Fn is critical for the Fn effect on CR1-mediated phagocytosis. In addition, there may be other domains of the Fn molecule that have a role in augmenting the Fn-phagocyte interaction.
Risks of Testosterone-Replacement Therapy and Recommendations for Monitoring (2004)

Although some reports suggest that testosterone-replacement therapy may provide benefits for aging men, considerable controversy remains regarding indications for its use. Neither large-scale nor long-term studies have been initiated, in part because of theoretical concern regarding the risks associated with testosterone therapy, especially the possible stimulation of prostate cancer. This article discusses what is known (and not known) about the risks of testosterone-replacement therapy and provides recommendations for monitoring men who are receiving testosterone.
Zone-Plate-Array Lithography (ZPAL): Simulations for system design (2000)

We present a simulation study which examines the use of zone plates for lithography. Zone-Plate-Array Lithography (ZPAL) is a maskless lithography scheme that uses an array of shuttered zone plates to print arbitrary patterns in resist on a substrate. We have demonstrated a working ZPAL system in the UV regime, and are pursuing further experiments with the 4.5 nm X-ray to obtain smaller feature sizes. A general numerical simulation tool, based on the Fresnel-Kirchhoff diffraction theory, has been developed. A pattern will consist of many pixels exposed independently in the resist. Various zone plate and system parameters will affect the intensity distribution at the focal plane. We present simulation results which show the effect of these parameters on both the individual spots and exposed patterns.
Analysis of ETV6/AML1 abnormalities in acute lymphoblastic leukaemia: incidence, alternative spliced forms and minimal residual disease value (2000)

The t(12;21)(p13;q22) translocation, resulting in the fusion of the ETV6 and AML1 genes, occurs in 20-25% of paediatric B-lineage acute lymphoblastic leukaemias (ALL). The identification of the fusion product has important prognostic and therapeutic implications as the translocation has been associated with a favourable clinical outcome. The aim of this study was threefold: (i) to assess the frequency and clinical association of the fusion gene in patients with and without a cytogenetically detectable chromosome 12 and/or 21 abnormality or failed cytogenetic results, (ii) to characterize alternative forms of ETV6/AML1 transcripts, and (iii) to use ETV6/AML1 as a molecular marker for the investigation of minimal residual disease (MRD). ETV6/AML1 fusion was detected in 22 (39%) of 56 cases studied by reverse transcriptase polymerase chain reaction (RT-PCR). ETV6/AML1 fusion was found in nine out of 16 (56%) cases with a cytogenetically visible chromosome 12 abnormality, but also in nine out of 29 patients (31%) without a chromosome 12 abnormality or patients with failed cytogenetics (four out of 11 patients, 36%), making this the most common cytogenetic abnormality in childhood ALL. Alternatively spliced ETV6/AML1 forms were investigated in 14 of the positive patients. Exon 5 of ETV6 was fused in frame to all AML1 exons, except exon 4. Fusion to exon 6 of AML1 resulted in one amino acid change. The presence of ETV6/AML1 was associated with a lower white blood cell count (Student's t-test; P = 0.009) and common (c)ALL phenotype (chi(2) test; P > 0.001), but no better disease-free survival. Our study shows that (i) RT-PCR is the most effective approach for the detection of t(12;21) in childhood ALL, (ii) the association of ETV6/AML1 and chromosome 12 and/or 21, seen in 56% of our cases, further confirms existing data, (iii) overall survival of patients with t(12;21) was not better than other cytogenetics groups, and (d) MRD analysis using ETV6/AML1 fusion is specific, but not sensitive enough to avoid false negative results.
A Magnetically Recyclable Nanocomposite Catalyst for Olefin Epoxidation (2007)

“Attractive” catalyst: Molybdenum oxide nanoparticles have been incorporated into a mesoporous silica shell and coated on silica-coated magnetite nanoparticles for use as a magnetically separable heterogeneous epoxidation catalyst. This catalyst, which has a low Mo loading of 1 mol %, can be recycled and reused six times in the epoxidation of cis-cyclooctene with no major loss of activity (see picture). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z702386_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.