gebhart/patrepeval huggingface dataset:
MR findings in Leigh syndrome with COX deficiency and SURF-1 mutations. (2002)

The MR pattern in LS SURF-1 patients is characteristic. Brain stem and subthalamic nuclei lesions may suggest the specific diagnosis. These patients die soon, probably because of lower brain stem involvement. Basal ganglial abnormalities are common only in LS non-SURF-1 patients. The absence of putaminal lesions, therefore, does not exclude the diagnosis of LS.
Antibodies to sm in patients with systemic lupus erythematosus. correlation of sm antibody titers with disease activity and other laboratory parameters (1981)

Thirty patients with systemic lupus erythematosus (SLE) were studied over a 2.5-year period. The group was divided into 14 patients with antibodies to Sm and a control group that failed to exhibit antibodies to Sm over the study period. The titer of antibodies to Sm fluctuated in all 14. A rising titer of antibodies to Sm 1) predicted a flare disease in 50% an 2) correlated with an exacerbation of disease in 60%. Patients with antibodies to Sm had a comparable incidence of severe disease, renal disease, and central nervous system disease. They exhibited significantly more leukopenia and antibodies to non-Sm, non-RNP extractable nuclear antigen. In only 1 patient, a rise in titer of antibodies to Sm did not correlate with or predict a disease flare in contradistinction to other serologic markers of SLE, specifically antibodies to double-stranded DNA and cryoglobulins. Though infrequently detected, antibodies to Sm can help in the management of patients with SLE.
A Common PDGF rEceptor Is Activated by Homodimeric A and B Forms of PDGF (1988)

The human platelet-derived growth factor (PDGF) receptor complementary DNA was cloned and expressed by transfection of Chinese hamster ovary (CHO) fibroblasts. The ability of CHO cells expressing the human receptor complementary DNA (CHO-HR5) to interact with different recombinant forms of PDGF (AA and BB homodimers) was tested. Both forms of PDGF bind to the transfected receptor, stimulate the receptor tyrosine kinase activity, and elicit a mitogenic response in a manner that was indistinguishable from the responses of Balb/c 3T3 cells to AA and BB forms of PDGF can be attributed to a single type of receptor and show that the AA form, like the BB form, is a true mitogen.
Intracellular Features Predicted by Extracellular Recordings in the Hippocampus In Vivo (2000)

Multichannel tetrode array recording in awake behaving animals provides a powerful method to record the activity of large numbers of neurons. The power of this method could be extended if further information concerning the intracellular state of the neurons could be extracted from the extracellularly recorded signals. Toward this end, we have simultaneously recorded intracellular and extracellular signals from hippocampal CA1 pyramidal cells and interneurons in the anesthetized rat. We found that several intracellular parameters can be deduced from extracellular spike waveforms. The width of the intracellular action potential is defined precisely by distinct points on the extracellular spike. Amplitude changes of the intracellular action potential are reflected by changes in the amplitude of the initial negative phase of the extracellular spike, and these amplitude changes are dependent on the state of the network. In addition, intracellular recordings from dendrites with simultaneous extracellular recordings from the soma indicate that, on average, action potentials are initiated in the perisomatic region and propagate to the dendrites at 1.68 m/s. Finally we determined that a tetrode in hippocampal area CA1 theoretically should be able to record electrical signals from approximately 1, 000 neurons. Of these, 60-100 neurons should generate spikes of sufficient amplitude to be detectable from the noise and to allow for their separation using current spatial clustering methods. This theoretical maximum is in contrast to the approximately six units that are usually detected per tetrode. From this, we conclude that a large percentage of hippocampal CA1 pyramidal cells are silent in any given behavioral condition.
Synthesis and Odor Properties of Substituted Indane‐2‐carboxaldehydes. Discovery of a New Floral (Muguet) Fragrance Alcohol (2005)

Abstract Eight substituted indane‐2‐carboxaldehydes (= 2,3‐dihydro‐1 H ‐indene‐2‐carboxaldehydes), related to conformationally constrained analogues of floral‐type odorants, were synthesized in order to examine the effect of modifying the lipophilic part of the odorants ( Schemes 1 and 2 ). None of the modified compounds showed better olfactive properties than the original ones ( Tables 1 and 2 ), but an intermediate alcohol, 29 , revealed itself as a valuable new member in the family of floral muguet (lily‐of‐the‐valley)‐type odorants.
Promotion of Collateral Growth by Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Coronary Artery Disease (2001)

This first clinical study investigating the potential of GM-CSF to improve collateral flow in patients with coronary artery disease documents its efficacy in a short-term administration protocol.
A domain containing the Cdc42/Rac interactive binding (CRIB) region of p65PAK inhibits transcriptional activation and cell transformation mediated by the Ras‐Rac pathway (1997)

The molecular bases of the versatile functions of Rho-like GTPases are still unknown. Using luciferase assays with rat 3Y1 cells, we found that Rac1 is integrated downstream of Ras in the TRE (TPA response element) activation pathway. Coexpression of a mutant of p65PAK, PAK/RD, lacking the kinase domain but containing the Cdc42/Rac interactive binding (CRIB) region, suppressed the TRE activation and cell transformation caused by constitutively activated forms of Ras (RasV12) and Rac1 (Rac1V12). PAK/RD is a good tool to investigate the signaling pathways in which Rac and Cdc42 are involved.
Processing, catalytic activity and crystal structures of kumamolisin‐As with an engineered active site (2006)

Kumamolisin-As is an acid collagenase with a subtilisin-like fold. Its active site contains a unique catalytic triad, Ser278-Glu78-Asp82, and a putative transition-state stabilizing residue, Asp164. In this study, the mutants D164N and E78H/D164N were engineered in order to replace parts of the catalytic machinery of kumamolisin-As with the residues found in the equivalent positions in subtilisin. Unlike the wild-type and D164N proenzymes, which undergo instantaneous processing to produce their 37-kDa mature forms, the expressed E78H/D164N proenzyme exists as an equilibrated mixture of the nicked and intact forms of the precursor. X-ray crystallographic structures of the mature forms of the two mutants showed that, in each of them, the catalytic Ser278 makes direct hydrogen bonds with the side chain of Asn164. In addition, His78 of the double mutant is distant from Ser278 and Asp82, and the catalytic triad no longer exists. Consistent with these structural alterations around the active site, these mutants showed only low catalytic activity (relative k(cat) at pH 4.0 1.3% for D164N and 0.0001% for E78H/D164N). pH-dependent kinetic studies showed that the single D164N substitution did not significantly alter the logk(cat) vs. pH and log(k(cat)/Km) vs. pH profiles of the enzyme. In contrast, the double mutation resulted in a dramatic switch of the logk(cat) vs. pH profile to one that was consistent with catalysis by means of the Ser278-His78 dyad and Asn164, which may also account for the observed ligation/cleavage equilibrium of the precursor of E78H/D164N. These results corroborate the mechanistic importance of the glutamate-mediated catalytic triad and oxyanion-stabilizing aspartic acid residue for low-pH peptidase activity of the enzyme.
Amyloid-β peptide–Receptor for Advanced Glycation Endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: A proinflammatory pathway in Alzheimer disease (1997)

In Alzheimer disease (AD), neurons are thought to be subjected to the deleterious cytotoxic effects of activated microglia. We demonstrate that binding of amyloid-beta peptide (Abeta) to neuronal Receptor for Advanced Glycation Endproduct (RAGE), a cell surface receptor for Abeta, induces macrophage-colony stimulating factor (M-CSF) by an oxidant sensitive, nuclear factor kappaB-dependent pathway. AD brain shows increased neuronal expression of M-CSF in proximity to Abeta deposits, and in cerebrospinal fluid from AD patients there was approximately 5-fold increased M-CSF antigen (P < 0.01), compared with age-matched controls. M-CSF released by Abeta-stimulated neurons interacts with its cognate receptor, c-fms, on microglia, thereby triggering chemotaxis, cell proliferation, increased expression of the macrophage scavenger receptor and apolipoprotein E, and enhanced survival of microglia exposed to Abeta, consistent with pathologic findings in AD. These data delineate an inflammatory pathway triggered by engagement of Abeta on neuronal RAGE. We suggest that M-CSF, thus generated, contributes to the pathogenesis of AD, and that M-CSF in cerebrospinal fluid might provide a means for monitoring neuronal perturbation at an early stage in AD.
Absence of Effect of Somatostatin Analogue (SMS 201‐995) in Diarrhea Associated with Inflammatory Bowel Disease (1989)

The octapeptide long acting somatostatin analogue, SMS 201‐995 promotes intestinal fluid and electrolyte absorption and inhibits anion secretion. It is more potent than native somatostatin and does not exhibit tachyphylaxsis. SMS 201‐995 was used to treat two patients with severe diarrhea associated with Crohn’s disease after other treatments had failed. The volume and frequency of ileostomy output in one patient and stool output in the other did not respond to therapy with SMS 201‐995. ln fact, diarrhea appeared to increase in both patients while on treatment.
The Localization and Expression of the Class II Starch Synthases of Wheat1 (1999)

Abstract The starch granules of hexaploid wheat (Triticum aestivum) contain a group of three proteins known as SGP-1 (starch granule protein-1) proteins, which have apparent molecular masses of 100, 108, and 115 kD. The nature and role of these proteins has not been defined previously. We demonstrate that these polypeptides are starch synthases that are present in both the starch granule and the soluble fraction at the early stages of wheat endosperm development, but that are exclusively granule bound at mid and late endosperm development. A partial cDNA clone encoding a fragment of the 100-kD protein was obtained by screening a wheat endosperm cDNA expression library using monoclonal antibodies. Three classes of cDNA were subsequently isolated from a wheat endosperm cDNA library by nucleic acid hybridization and were shown to encode the 100-, 108-, and 115-kD proteins. The cDNA sequences are highly homologous to class II starch synthases and have the highest homology with the maize SSIIa (starch synthase IIa) gene. mRNA for the SGP-1 proteins was detected in the leaf, pre-anthesis florets, and endosperm of wheat and is highly expressed in the leaf and in the grain during the early to mid stages of development. We discuss the roles of the SGP-1 proteins in starch biosynthesis in wheat.
Regulatory T-Cell Responses to Low-Dose Interleukin-2 in HCV-Induced Vasculitis (2011)

The trial showed that low-dose interleukin-2 was not associated with adverse effects and led to Treg recovery and concomitant clinical improvement in patients with HCV-induced vasculitis, an autoimmune condition. (Funded by the French Agency for Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT00574652.).
Curable, biodegradable elastomers: emerging biomaterials for drug delivery and tissue engineering (2007)

Biodegradable elastomers have a number of potential applications in the biomedical area, especially in the emerging field of soft-tissue engineering where the mechanical properties of the polymer scaffold should match those of the tissue to be grown. An increasing number of synthesis strategies have been employed in order to prepare such elastomers. In this review, these synthesis strategies and the properties of these elastomers are outlined. The factors that influence the characteristics of these elastomers including mechanical properties, degradation rate, and mechanical property change during degradation, are discussed in terms of the design of the elastomer and their advantages and disadvantages for the biomedical applications considered.
Experimental murine Trypanosoma congolense infections. I. Administration of anti-IFN-gamma antibodies alters trypanosome-susceptible mice to a resistant-like phenotype. (1998)

The mechanisms regulating resistance or susceptibility to African trypanosomes have been enigmatic. In this study, we assessed the production of several cytokines (IL-4, IFN-gamma, and TNF-alpha) in vivo and in vitro using genetically susceptible (BALB/c) or resistant (C57BL/6) mice infected with cloned Trypanosoma congolense and the role of these cytokines in pathogenesis of this infection. Plasma of infected BALB/c mice contained higher levels of IL-4 and IFN-gamma than the plasma of infected C57BL/6 mice. Conversely, plasma TNF-alpha levels were elevated significantly in the resistant mice relative to the susceptible ones. Splenic IFN-gamma mRNA appeared earlier and were maintained at higher levels in infected BALB/c than in C57BL/6 mice. Both spontaneous and Con A-induced secretions of IL-4 and IFN-gamma by splenocytes from infected BALB/c mice were significantly higher than those from their C57BL/6 counterparts. Con A-induced proliferation of splenocytes from infected BALB/c mice was progressively suppressed. Nitric oxide was not involved in this suppression, but the suppression was positively correlated with IFN-gamma secretion. Addition of neutralizing Abs to IFN-gamma to cultures of Con A-stimulated spleen cells from infected BALB/c mice effectively reversed this suppression. Furthermore, administration of anti-IFN-gamma Abs to BALB/c mice early during infection dramatically shifted the phenotype of these susceptible mice to a more resistant-like phenotype, as expressed by a low and undulating parasitemia and a >300% increase in survival period. These results strongly suggest that the enhanced induction and secretion of IFN-gamma during T. congolense infections contribute to the relative susceptibility of BALB/c mice to the disease.
Progressive use of medical therapies in type 2 diabetes (2001)

Korzyści wynikające z bardziej intensywnego leczenia hiperglikemii, nadciśnienia tetniczego, dyslipidemii i nadkrzepliwości u chorych na cukrzyce typu 2 są oczywiste. Wciąz nowe doniesienia i rozwoj badan klinicznych sprawiają, ze kryteria wyrownania metabolicznego stają sie coraz bardziej wymagające. Artykul ten zawiera przegląd metod leczenia skojarzonego, prowadzących do minimalizacji czynnikow ryzyka u chorych na cukrzyce typu 2.
 W ostatniej dekadzie nastąpily rewolucyjne zmiany dotyczące leczenia cukrzycy, spowodowane postepem w wielu dziedzinach. Wyniki 4 znaczących badan klinicznych [1–8] udowodnily hipoteze hiperglikemii, wskazując, ze optymalna glikemia u osob chorych na cukrzyce powinna byc tak niska, jak to mozliwe, bez nadmiernego ryzyka hipoglikemii i innych dzialan niepoządanych. 
Do 1995 roku insulina i pochodne sulfonylomocznika byly jedynymi lekami w Stanach Zjednoczonych, dopuszczonymi do stosowania w leczeniu cukrzycy. Nastepnie zaakceptowano analogi insulin, nowe pochodne sulfonylomocznika oraz 4 inne grupy lekow [9]. Towarzyszyly temu takze znaczne postepy technologiczne dotyczące monitorowania glikemii, ulatwiające prowadzenie samokontroli [10]. 
Wyniki badan klinicznych potwierdzily korzyści interwencji eliminujących czynniki ryzyka chorob sercowo-naczyniowych w leczeniu makroangiopatii — glownej przyczyny śmierci i niepelnosprawności chorych na cukrzyce [11, 12]. Zmiany systemu ubezpieczen zdrowotnych oraz federalnych i stanowych aktow prawnych przyczynily sie do poprawy finansowania lekow, zaopatrzenia medycznego i edukacji, co pozwolilo na obnizenie docelowych wartości glikemii, ciśnienia tetniczego i stezenia lipidow. Artykul ten opisuje praktyczne i konstruktywne wytyczne dotyczące opieki diabetologicznej. Cele kontroli glikemii i metody modyfikacji trybu zycia nie są tu przedmiotem dyskusji. Na początku zostaly omowione dostepne klasy lekow stosowanych w cukrzycy oraz sugerowane sposoby progresywnego leczenia hiperglikemii. Nastepnie przedstawiono poglądy na temat zwalczania czynnikow ryzyka chorob sercowo-naczyniowych z krotkim omowieniem lekow i ich zastosowania.
Fas-induced apoptosis of T cells occurs independently of ceramide generation (1997)

The Fas receptor is one of a number of important physiological inducers of programmed cell death (apoptosis). Current models for regulation of this process involve rapid conversion of sphingomyelin to ceramide by cellular sphingomyelinases. Induced changes in cellular levels of such sphingosine-based ceramides are normally extrapolated from measurements of sphingomyelinase activity or following their conversion to ceramide phosphate by treatment of cellular lipid extracts with bacterial diacylglycerol kinase (DAGK). To allow direct study of cellular sphingosine- and sphinganine-based ceramide levels, we developed a mass spectrometric technique capable of determining inducible changes in both overall ceramide levels and species distribution in cellular lipid preparations. Contrary to current models, we detected no changes in cellular ceramide levels up to 2 hr poststimulation of Jurkat T cells with an anti-Fas IgM, although this treatment did induce apoptosis. We also determined in the same system that, when utilizing the DAGK assay, increased phosphorylation of substrates that comigrated with ceramide standards was apparent but that this effect was due to an enhancement of DAGK activity rather than increases in levels of cellular ceramides as substrates per se. Thus, the first direct measurement of ceramides present in cells undergoing apoptosis indicates that, insofar as it can be measured, the induction of apoptosis does not involve the generation of sphingosine-based ceramides, contrary to many published accounts.
Latent Membrane Protein 2A of Epstein-Barr Virus Binds WW Domain E3 Protein-Ubiquitin Ligases That Ubiquitinate B-Cell Tyrosine Kinases (2000)

The latent membrane protein (LMP) 2A of Epstein-Barr virus (EBV) is implicated in the maintenance of viral latency and appears to function in part by inhibiting B-cell receptor (BCR) signaling. The N-terminal cytoplasmic region of LMP2A has multiple tyrosine residues that upon phosphorylation bind the SH2 domains of the Syk tyrosine kinase and the Src family kinase Lyn. The LMP2A N-terminal region also has two conserved PPPPY motifs. Here we show that the PPPPY motifs of LMP2A bind multiple WW domains of E3 protein-ubiquitin ligases of the Nedd4 family, including AIP4 and KIAA0439, and demonstrate that AIP4 and KIAA0439 form physiological complexes with LMP2A in EBV-positive B cells. In addition to a C2 domain and four WW domains, these proteins have a C-terminal Hect catalytic domain implicated in the ubiquitination of target proteins. LMP2A enhances Lyn and Syk ubiquitination in vivo in a fashion that depends on the activity of Nedd4 family members and correlates with destabilization of the Lyn tyrosine kinase. These results suggest that LMP2A serves as a molecular scaffold to recruit both B-cell tyrosine kinases and C2/WW/Hect domain E3 protein-ubiquitin ligases. This may promote Lyn and Syk ubiquitination in a fashion that contributes to a block in B-cell signaling. LMP2A may potentiate a normal mechanism by which Nedd4 family E3 enzymes regulate B-cell signaling.
Synthesis of hypoxanthine, guanine, and 6-thiopurine nucleosides of 6-deoxy-D-allofuranose (1983)

Hypoxanthine, guanine, and 6-thiopurine nucleosides of 6-deoxy-D-allofuranose have been prepared as potential antitumor agents. Thus, reaction of 6-deoxy-|8-D-allofuranosyl bromide (1) with the trimethylsilyl derivatives of hypoxanthine and guanine afforded mixtures of the 9- and the 7-substituted bases, which were separated and deblocked with ammonia to give 9-(6′-deoxy-|9-D-allofuranosyl)hypoxanthine (6), 7-(6′-deoxy-β-D-allofuranosyl)hypoxanthine (7), 9-(6′-deoxy-/3-D-allofuranosyl)guanine (8), and 7-(6′-deoxy-/3-D-allofuranosyl)guanine (9). The two nucleosides with the purine joined at the N-9 position, namely, 6 and 8, are easily distinguished from the other two nucleosides (7 and 9), having N-7 junctions, by their NMR spectra. Reaction of 1 with the trimethylsilyl derivative of 6-chloropurine afforded 10, which upon treatment with thiourea and deblocking gave 9-(6′-deoxy-/3-D-allofuranosyl)-6-thiopurine (12). The hypoxanthine and guanine nucleosides showed no inhibition of mouse leukemia L1210 when tested in vivo, but the thiopurine nucleoside 12 showed strong inhibition of growth of L1210 both in vivo and in vitro. Compound 7 strongly inhibited purine nucleoside phosphorylase (KI = 8.8 X 10-5 M), while compounds 8, 9, 6, and 12 were inactive. © 1983, American Chemical Society. All rights reserved.
Two Plasmodium falciparum genes express merozoite proteins that are related to Plasmodium vivax and Plasmodium yoelii adhesive proteins involved in host cell selection and invasion (2000)

Two related Plasmodium falciparum genes and their encoded proteins have been identified by comparative analyses with Plasmodium vivax reticulocyte binding protein 2 (PvRBP-2). The P. falciparum genes have a structure which suggests that they may be the result of an evolutionary duplication event, as they share more than 8 kb of closely related nucleotide sequence but then have quite divergent unique 3' ends. Between these shared and unique regions is a complex set of repeats, the nature and number of which differs between the two genes, as well as between different P. falciparum strains. Both genes encode large hydrophilic proteins, which are concentrated at the invasive apical end of the merozoite and are predicted to be more than 350 kDa, with an N-terminal signal sequence and a single transmembrane domain near their C termini. Importantly, they also share gene structure and amino acid homology with the Plasmodium yoelii 235-kDa rhoptry protein family, which is also related to PvRBP-2. Together these Plasmodium proteins define an extended family of proteins that appear to function in erythrocyte selection and invasion. As such, they may prove to be essential components of malaria vaccine preparations.
Color-tuned Channelrhodopsins for Multiwavelength Optogenetics (2012)

Channelrhodopsin-2 is a light-gated ion channel and a major tool of optogenetics. It is used to control neuronal activity via blue light. Here we describe the construction of color-tuned high efficiency channelrhodopsins (ChRs), based on chimeras of Chlamydomonas channelrhodopsin-1 and Volvox channelrhodopsin-1. These variants show superb expression and plasma membrane integration, resulting in 3-fold larger photocurrents in HEK cells compared with channelrhodopsin-2. Further molecular engineering gave rise to chimeric variants with absorption maxima ranging from 526 to 545 nm, dovetailing well with maxima of channelrhodopsin-2 derivatives ranging from 461 to 492 nm. Additional kinetic fine-tuning led to derivatives in which the lifetimes of the open state range from 19 ms to 5 s. Finally, combining green- with blue-absorbing variants allowed independent activation of two distinct neural cell populations at 560 and 405 nm. This novel panel of channelrhodopsin variants may serve as an important toolkit element for dual-color cell stimulation in neural circuits.
Production and Evaluation of Antibody to the Heat-Stable Enterotoxin from a Human Strain of Enterotoxigenic Escherichia coli (1981)

Escherichia coli heat-stable enterotoxin was coupled to bovine serum albumin by a carbodiimide reagent. Antibody to the conjugate was produced by immunization of rabbits. Data from radioimmunoassay and infant mouse tests indicate the presence of antibody to the enterotoxin. The antisera can be used in a radioimmunoassay to measure enterotoxin in various fluids.