gebhart/patrepeval huggingface dataset:
Minocycline in Rheumatoid Arthritis (1995)

Letters1 September 1995Minocycline in Rheumatoid ArthritisHarold W. Clark, PhDHarold W. Clark, PhDMycoplasma Research Institute; Beverly Hills, FL 34464-0040Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-5-199509010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The recent editorial by Dr. Paulus [1], although of great interest, was flawed by inaccurate and missing information.Dr. Paulus stated that in 1968, Sanchez … first reported the use of tetracycline to treat 14 patients with rheumatoid arthritis, with favorable results. Apparently, the author was unaware that Dr. Thomas McPherson Brown started to treat patients with rheumatoid arthritis 20 years earlier, in 1947, with aureomycin when the drug was first available and provided by Lederle Laboratories. Dr. Brown and colleagues first reported the beneficial effects of tetracyclines in 1949 at the Seventh International Congress on Rheumatic ...References1. Paulus HE. Minocycline treatment of rheumatoid arthritis [Editorial]. Ann Intern Med. 1995; 122:147-8. Google Scholar2. Brown TM, Wichelhauser RH, Robinson LB, Merchant WR. The in vivo action of aureomycin on pleuropneumonia-like organisms associated with various rheumatic disease. J Lab Clin Med. 1949; 34:1404-10. Google Scholar3. Brown TM, Wichelhauser RH, Merchant WR, Robinson LB. A study of the antigen-antibody mechanism in rheumatic diseases. Am J Med Sci. 1951; 221:618-24. Google Scholar4. Brown TM, Clark HW, Bailey JS, Gry CW. A Mechanistic approach of rheumatoid-type arthritis naturally occurring in a gorilla. Trans Am Clin Climatol Assoc. 1970; 82:227-47. Google Scholar Author, Article, and Disclosure InformationAffiliations: Mycoplasma Research Institute; Beverly Hills, FL 34464-0040 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCritical data-based re-evaluation of minocycline as a putative specific microglia inhibitor 1 September 1995Volume 123, Issue 5Page: 393KeywordsClinical trialsDoxycyclineDrugsImmunosuppressivesMycoplasmaMycoplasma pneumoniaePneumoniaRheumatoid arthritisSwineTetracyclines Issue Published: 1 September 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Skeletal Muscle Triglyceride (2001)

Recent evidence derived from four independent methods indicates that an excess triglyceride storage within skeletal muscle is linked to insulin resistance. Potential mechanisms for this association include apparent defects in fatty acid metabolism that are centered at the mitochondria in obesity and in type 2 diabetes. Specifically, defects in the pathways for fatty acid oxidation during postabsorptive conditions are prominent, leading to diminished use of fatty acids and increased esterification and storage of lipid within skeletal muscle. These impairments in fatty acid metabolism during fasting conditions may be related to a metabolic inflexibility in insulin resistance that is not limited to defects in glucose metabolism during insulin-stimulated conditions. Thus, there is substantial evidence implicating perturbations in fatty acid metabolism during accumulation of skeletal muscle triglyceride and in the pathogenesis of insulin resistance. Weight loss by caloric restriction improves insulin sensitivity, but the effects on fatty acid metabolism are less conspicuous. Nevertheless, weight loss decreases the content of triglyceride within skeletal muscle, perhaps contributing to the improvement in Insulin action with weight loss. Alterations in skeletal muscle substrate metabolism provide insight into the link between skeletal muscle triglyceride accumulation and insulin resistance, and they may lead to more appropriate therapies to improve glucose and fatty acid metabolism in obesity and in type 2 diabetes.
Measurement of Human and Mouse Interleukin‐12 (1995)

This unit describes functional assays for measurement of bioactive IL-12 and ELISAs for measurement of IL-12 protein. The functional assays are based on the ability of IL-12 to stimulate proliferation of PHA-activated T lymphoblasts ("PHA blasts"). The ELISAs are technically simpler to perform than the functional assays, but cannot distinguish bioactive from inactive cytokine.
The quest for the simplest possible organogelators and some properties of their organogels (2000)

The search for the simplest structural class of organic molecules capable of gelling large amounts of organic liquids is reviewed with an emphasis on the approach taken by the authors. The properties of several of the gelators, as well as their gels with various organic liquids, are presented. Some challenges to future developments in the field are mentioned.
Conformation of the Human Immunoglobulin G2 Hinge Imparts Superagonistic Properties to Immunostimulatory Anticancer Antibodies (2014)

Monoclonal antibody (mAb) drugs that stimulate antitumor immunity are transforming cancer treatment but require optimization for maximum clinical impact. Here, we show that, unlike other immunoglobulin isotypes, human IgG2 (h2) imparts FcγR-independent agonistic activity to immune-stimulatory mAbs such as anti-CD40, -4-1BB, and -CD28. Activity is provided by a subfraction of h2, h2B, that is structurally constrained due its unique arrangement of hinge region disulfide bonds. Agonistic activity can be transferred from h2 to h1 by swapping their hinge and CH1 domains, and substitution of key hinge and CH1 cysteines generates homogenous h2 variants with distinct agonistic properties. This provides the exciting opportunity to engineer clinical reagents with defined therapeutic activity regardless of FcγR expression levels in the local microenvironment.
Isolation of nuclear pore complexes in association with a lamina. (1975)

Nuclear pore complexes have been isolated in association with a 150 A thick lamina by detergent and salt fractionation of nuclear envelopes from rat liver. The pore complexes exhibit characteristic morphology and appear to be attached in a highly specific orientation to the lamina, which extends over relatively large areas. The pore complex-lamina fraction is composed of three major and several minor polypeptides with little or no DNA, RNA, or phospholipid. It is suggested that the association of the pore complexes and the lamina reflects the structural arrangement of the nuclear periphery in vivo.
GFAP promoter directs astrocyte-specific expression in transgenic mice (1994)

Glial fibrillary acidic protein (GFAP) is an intermediate-filament protein expressed abundantly and almost exclusively in astrocytes of the CNS. We are studying transcriptional regulation of the GFAP gene to gain insight into astrocyte function and also to develop an astrocyte-specific expression system for manipulating brain physiology. In this work, we have produced transgenic mice carrying the bacterial lacZ reporter gene linked to a 2.2 kilobase 5'-flanking sequence derived from the human GFAP gene that previously was shown to direct astrocyte-specific transcription in cultured cells. We report that this promoter directs expression to astrocytes in the CNS. In addition, the upregulation of GFAP gene activity that follows injury to the brain was mimicked by the transgene. One of the transgenes was found to be X-linked and appeared to undergo the usual random inactivation that achieves gene dosage compensation in females. The brains of hemizygous females stained uniformly rather than displaying mosaic patches, indicating that astrocytes intermingle following their formation. The specific expression of the GFAP-lacZ transgene means that it is now possible to target expression of other heterologous genes to astrocytes in vivo, and to study the mechanisms for reactive gliosis at the DNA level.
Deep learning assessment of tumor proliferation in breast cancer histological images (2017)

Current analysis of tumor proliferation, the most salient breast cancer prognostic biomarker, is limited to subjective mitosis counting by pathologists in localized regions of tissue images. This study presents the first data-driven integrative approach to characterize the severity of tumor growth and spread on a categorical and molecular level, utilizing multiple biologically salient deep learning classifiers to develop a comprehensive prognostic model. Our approach achieves pathologist-level performance on three-class categorical tumor severity prediction. It additionally pioneers prediction of molecular expression data from a tissue image, obtaining a Spearman's rank correlation coefficient of 0.60 with ex vivo mean calculated RNA expression. Furthermore, our framework is applied to identify over two hundred unprecedented biomarkers critical to the accurate assessment of tumor proliferation, validating our proposed integrative pipeline as the first to holistically and objectively analyze histopathological images.
Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. (1988)

Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.
Characterization of cytokine responses to retinal detachment in rats. (2006)

Retinal glial cells, including astrocytes and Müller cells, are a major source of cytokine induction after RD. The increased expression and release of MCP-1 may be an important cause of photoreceptor degeneration associated with RD. This study helps to understand the mechanisms of RD-induced photoreceptor degeneration. Our results may provide new therapeutic targets to prevent photoreceptor degeneration following RD.
Dynamic decision modeling in medicine: a critique of existing formalisms. (1993)

Dynamic decision models are frameworks for modeling and solving decision problems that take into explicit account the effects of time. These formalisms are based on structural and semantical extensions of conventional decision models, e.g., decision trees and influence diagrams, with the mathematical definitions of finite-state semi-Markov processes. This paper identifies the common theoretical basis of existing dynamic decision modeling formalisms, and compares and contrasts their applicability and efficiency. It also argues that a subclass of such dynamic decision problems can be formulated and solved more effectively with non-graphical techniques. Some insights gained from this exercise on automating the dynamic decision making process are summarized.
Quick scan chain diagnosis using signal profiling (2006)

In this paper we address the scan chain diagnosis problem. We propose a new diagnosis flow based on the concept of signal profiling to accurately pinpoint the location of a faulty flip-flop in a scan chain. As compared to the conventional cause-effect or effect-cause analysis, this approach is much more computationally efficient because it does not have to simulate the behaviors of a large number of fault candidates. Also, it is general and applicable to all kinds of faults because it does not assume any specific fault model. Experimental results indicate that this approach can instantly catch a fault within a scan chain quite accurately in most cases.
First-in-human, robotic-assisted neuroendovascular intervention (2020)

Robotic-assisted technology has been used as a tool to enhance open and minimally invasive surgeries as well as percutaneous coronary and peripheral vascular interventions. It offers many potential benefits, including increased procedural and technical accuracy as well as reduced radiation dose during fluoroscopic procedures. It also offers the potential for truly "remote" procedures. Despite these benefits, robotic technology has not yet been used in the neuroendovascular field, aside from diagnostic cerebral angiography. Here, we report the first robotic-assisted, therapeutic, neuroendovascular intervention performed in a human. This was a stent-assisted coiling procedure to treat a large basilar aneurysm. All intracranial steps, including stent placement and coil deployment, were performed with assistance from the CorPath<sup>©</sup> GRX Robotic System (Corindus, a Siemens Healthineers Company, Waltham, MA, USA). This represents a major milestone in the treatment of neurovascular disease and opens the doors for the development of remote robotic neuroendovascular procedures.
New Achievements on CVD Based Methods for SiC Epitaxial Growth (2005)

The results of a new epitaxial process using an industrial 6x2” wafer reactor with the introduction of HCl during the growth have been reported. A complete reduction of silicon nucleation in the gas phase has been observed even for high silicon dilution parameters (Si/H2&gt;0.05) and an increase of the growth rate until about 20 µm/h has been measured. No difference has been observed in terms of defects, doping uniformity (average maximum variation 8%) and thickness uniformity (average maximum variation 1.2 %) with respect to the standard process without HCl.
Tissue- and site-specific DNA recombination in transgenic mice. (1992)

We have developed a method of specifically modifying the mammalian genome in vivo. This procedure comprises heritable tissue-specific and site-specific DNA recombination as a function of recombinase expression in transgenic mice. Transgenes encoding the bacteriophage P1 Cre recombinase and the loxP-flanked beta-galactosidase gene were used to generate transgenic mice. Genomic DNA from doubly transgenic mice exhibited tissue-specific DNA recombination as a result of Cre expression. Further characterization revealed that this process was highly efficient at distinct chromosomal integration sites. These studies also imply that Cre-mediated recombination provides a heritable marker for mitoses following the loss of Cre expression. This transgene-recombination system permits unique approaches to in vivo studies of gene function within experimentally defined spatial and temporal boundaries.
Effects of ritanserin on the behavioral, neuroendocrine, and cardiovascular responses to meta-chlorophenylpiperazine in healthy human subjects (1991)

Ten healthy male subjects were administered i.v. meta-chlorophenylpiperazine (MCPP) (0.1 mg/kg) after oral ritanserin (5-10 mg), a putative 5HT1c/5HT2 (serotonin) antagonist, or placebo. Behavioral responses, cardiovascular effects, and neuroendocrine responses (cortisol, growth hormone, and prolactin) were measured serially for 4 hours after MCPP infusion. Premedication with ritanserin attenuated the MCPP-induced increases in self-rated anxiety and prolactin, and completely antagonized MCPP cortisol elevations. In contrast, ritanserin did not significantly alter growth hormone response to MCPP. These findings suggest a role for 5-HT1c/5-HT2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans.
Relationship between Group-Specific Component Protein and the Development of Asthma (2010)

Gc may be involved in the development of asthma, and the neutralization of Gc protein could be a therapeutic strategy for asthma.
Electrophysiological Basis of Arrhythmogenicity of QT/T Alternans in the Long-QT Syndrome (1998)

Tachycardia-dependent QT/T alternans occurs in patients with the congenital or idiopathic form of long-QT syndrome (LQTS) and may presage the onset of polymorphic ventricular tachyarrhythmias. To examine the electrophysiological basis of arrhythmogenicity of QT/T alternans in LQTS, the tridimensional repolarization pattern of QT/T alternans was studied in the anthopleurin-A model of LQTS, a surrogate for LQT3. In 11 anesthetized mongrel puppies, tridimensional repolarization and activation patterns were analyzed from 256 to 384 unipolar electrograms. Cardiac repolarization was evaluated as the activation-recovery interval (ARI) of local electrograms. To induce QT/T alternans, the pacing cycle length (CL) was abruptly shortened in steps of 50 ms from a basic drive of 1000 ms. ARIs were calculated at epicardial (Epi), midmyocardial (Mid), and endocardial (End) sites. ARI restitution at each site was assessed by using a single premature stimulation delivered after the basic drive. ARI alternans occurred at longer CLs at Mid sites compared with End and Epi sites, and the magnitude of alternans at Mid sites was greater. Two factors contributed to the modulation of ARI during QT/T alternans: (1) differences in restitution kinetics at Mid sites, characterized by larger DeltaARI and a slower time constant (tau), and (2) differences in diastolic intervals resulting in different input to restitution at the same constant CL. These 2 factors could explain not only the onset of alternans at Mid sites at longer CLs but also the critical observation that ARI dispersion between Epi and Mid sites during alternans was greater than during the slower basic CL. Marked ARI alternans could be present in local electrograms without manifest alternation of the QT/T segment in the surface ECG. The latter was seen at critically short CLs associated with reversal of the gradient of ARI between Epi and Mid sites, with a consequent reversal of polarity of the intramyocardial QT wave in alternate cycles. The arrhythmogenicity of QT/T alternans was primarily due to the greater degree of spatial dispersion of repolarization during alternans than during slower rates not associated with alternans. This could result in functional conduction block and reentrant ventricular tachyarrhythmias during the fixed drive associated with alternans.
Role of phosphorylation in p34cdc2 activation: identification of an activating kinase. (1992)

Phosphorylation of p34cdc2 can both positively and negatively regulate its kinase activity. We have mapped two phosphorylation sites in Xenopus p34cdc2 to Thr-14 and Tyr-15 within the putative ATP-binding region of p34cdc2. Mutation of these sites to Ala-14 and Phe-15 has no effect on the final histone H1 kinase activity of the cyclin/p34cdc2 complex. Phosphopeptide analysis shows that there is at least one more site of phosphorylation on p34cdc2. When Thr-161 is changed to Ala, two phosphopeptide spots disappear and it is no longer possible to activate the H1 kinase activity of p34cdc2. We suggest that Thr-161 is a third site of phosphorylation, which is required for kinase activity. All three phosphorylations are induced by cyclin. None of the phosphorylations appears to be required for binding to cyclin, as indicated by the ability of the triple mutant, Ala-14, Phe-15, Ala-161, to bind cyclin. The activating phosphorylation that requires Thr- or Ser-161 occurs even in a catalytically inactive K33R mutant of p34cdc2 and hence does not appear to be the result of intramolecular autophosphorylation. We have detected an activity in Xenopus extracts required for activation of p34cdc2 and present evidence that this is a p34cdc2 activating kinase which, in a cyclin-dependent manner, probably directly phosphorylates Thr-161.
Electrical compensation in CdTe andCd0.9Zn0.1Teby intrinsic defects (2000)

The effects of two intrinsic deep levels on electrical compensation in semi-insulating CdTe and Cd-Zn-Te crystals are reported here. These levels were found in samples grown by conventional Bridgman and high-pressure Bridgman techniques. The levels were observed with thermoelectric effect spectroscopy at distinct temperatures corresponding to thermal ionization energies of ${E}_{d1}{=E}_{v}+0.735\ifmmode\pm\else\textpm\fi{}0.005\mathrm{eV}$ and ${E}_{d2}{=E}_{v}+0.743\ifmmode\pm\else\textpm\fi{}0.005\mathrm{eV}.$ The first level is associated with the doubly ionized Cd vacancy acceptor and the second level was tentatively identified as the Te antisite $({\mathrm{Te}}_{\mathrm{Cd}}),$ which is thought to be complexed with a vacancy. The second level was found to electrically compensate CdTe and Cd-Zn-Te to produce high resistivity crystals, provided that the Cd vacancy concentration is sufficiently reduced during crystal growth or by post-growth thermal processing.
HD Photo: a new image coding technology for digital photography (2007)

This paper introduces the HD Photo coding technology developed by Microsoft Corporation. The storage format for this technology is now under consideration in the ITU-T/ISO/IEC JPEG committee as a candidate for standardization under the name JPEG XR. The technology was developed to address end-to-end digital imaging application requirements, particularly including the needs of digital photography. HD Photo includes features such as good compression capability, high dynamic range support, high image quality capability, lossless coding support, full-format 4:4:4 color sampling, simple thumbnail extraction, embedded bitstream scalability of resolution and fidelity, and degradation-free compressed domain support of key manipulations such as cropping, flipping and rotation. HD Photo has been designed to optimize image quality and compression efficiency while also enabling low-complexity encoding and decoding implementations. To ensure low complexity for implementations, the design features have been incorporated in a way that not only minimizes the computational requirements of the individual components (including consideration of such aspects as memory footprint, cache effects, and parallelization opportunities) but results in a self-consistent design that maximizes the commonality of functional processing components.
Functional characterization of two isoforms of the P2Y-like receptor GPR17: [35S]GTPγS binding and electrophysiological studies in 1321N1 cells (2009)

The previously "orphan" G protein-coupled receptor GPR17 is structurally related to both P2Y nucleotide receptors and to receptors for cysteinyl leukotrienes. Genomic analysis revealed two putative open reading frames encoding for a "short" and a "long" receptor isoform of 339- and 367-amino acids, respectively, with the latter displaying a 28-amino acid longer NH(2) terminus. The short isoform has been recently "deorphanized," revealing dual responses to uracil nucleotides and cysteinyl leukotrienes. No information regarding the ligand specificity, tissue distribution, or pathophysiological roles of the long receptor isoform is available. In the present study, we cloned human long-GPR17, determined its tissue distribution, and characterized its pharmacological specificity in 1321N1 cells by [35S]GTPgammaS binding (which measures the ability of G protein-coupled receptor agonists to increase GTP binding to G proteins) and whole cell patch-clamp recording measuring receptor coupling to K+ channels. [35S]GTPgammaS binding in long-GPR17-expressing 1321N1 cells revealed concentration-dependent responses to uracil nucleotides (UDP-galactose = UDP > UDP-glucose) and cysteinyl leukotrienes (LTC4 > LTD4), which were counteracted by a purinergic (cangrelor) and a cysteinyl leukotriene antagonist (montelukast), respectively. The nonhydrolyzable ATP analog ATPgammaS also acted as an antagonist. GPR17 coupled to Gi and, to a lesser extent, Gq proteins. UDP-glucose and LTD(4) also induced increases in overall outward K+ currents, which were antagonized by the purinergic antagonists MRS2179 and cangrelor and by montelukast. We conclude that the previously uncharacterized long-GPR17 isoform is a functional receptor that is stimulated by both uracil nucleotides and cysteinyl leukotrienes. We also show that the signaling pathway of GPR17 involves the generation of outward K+ currents, an important protective mechanism that, in brain, is specifically aimed at reducing neuronal hyperexcitability and resultant neuronal injury.