gebhart/patrepeval huggingface dataset:
Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy. (1982)

Sodium valproate is often used with phenytoin when epilepsy cannot be controlled by a single drug. Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements. Plasma and saliva phenytoin and plasma valproate concentrations were measured in 42 patients with epilepsy receiving both drugs. Phenytoin protein binding was also measured by ultrafiltration in 19 of these patients and 19 patients taking phenytoin alone. Saliva phenytoin concentration bore the same close correlation to unbound (therapeutically active) phenytoin in patients receiving both drugs as it did in patients receiving phenytoin alone, whereas plasma total phenytoin did not. The same therapeutic range for saliva phenytoin (4-9 mumol/1; 1-2 microgram/ml) was therefore valid in both groups. The depression of phenytoin binding was directly related to the plasma concentration of valproate both in random samples taken from the 42 patients and in samples taken throughout the day in two of these patients. This was confirmed in vitro. Even when the concentration of valproate is known the degree of binding cannot be predicted. Saliva rather than plasma monitoring of phenytoin treatment is therefore valuable in the presence of valproate and with reduced phenytoin binding from any cause.
Elevated natural killer cell responses in mice infected with recombinant vaccinia virus encoding murine IL-2. (1990)

The role of cytotoxic T cells and NK cells in the recovery of immunodeficient, athymic, nude mice infected with a recombinant vaccinia virus (VV) encoding murine IL-2 was investigated. Kinetic studies with the IL-2-encoding recombinant (VV-HA-IL2) and control (VV-HA-TK) viruses excluded a role for cytotoxic T cells but suggested the possible involvement of NK cells. In athymic nude mice given VV-HA-IL2, NK activity was at least threefold higher than mice infected with VV-HA-TK and this activity persisted for at least 6 days after infection. The effectors mediating the NK-like activity were asialo-GM1+ (as-GM1+), Thy1.2+/-, CD4- and CD8-, the phenotype of conventional NK cells. Elevated NK activity coincided with the rapid clearance of VV-HA-IL2 from ovaries of infected normal CBA/H mice but not from ovaries of CBA beige mice which had no detectable NK activity in spleens or ovaries. The expression of IL-2 in recombinant VV infection probably induces a cascade of immunologic effects of which elevated NK activity is one. We speculate that the chemoattractant and NK activity augmenting effects of IL-2 may contribute to recovery from VV-infection.
Secretion of Human Serum Albumin by Kluyveromyces lactis Overexpressing KlPDI1 and KlERO1 (2005)

The control of protein conformation during translocation through the endoplasmic reticulum is often a bottleneck for heterologous protein production. The core pathway of the oxidative folding machinery includes two conserved proteins: Pdi1p and Ero1p. We increased the dosage of the genes encoding these proteins in the yeast Kluyveromyces lactis and evaluated the secretion of heterologous proteins. KlERO1, an orthologue of Saccharomyces cerevisiae ERO1, was cloned by functional complementation of the ts phenotype of an Scero1 mutant. The expression of KlERO1 was induced by treatment of the cells with dithiothreitol and by overexpression of human serum albumin (HSA), a disulfide bond-rich protein. Duplication of either PDI1 or ERO1 led to a similar increase in HSA yield. Duplication of both genes accelerated the secretion of HSA and improved cell growth rate and yield. Increasing the dosage of KlERO1 did not affect the production of human interleukin 1beta, a protein that has no disulfide bridges. The results confirm that the ERO1 genes of S. cerevisiae and K. lactis are functionally similar even though portions of their coding sequence are quite different and the phenotypes of mutants overexpressing the genes differ. The marked effects of KlERO1 copy number on the expression of heterologous proteins with a high number of disulfide bridges suggests that control of KlERO1 and KlPDI1 is important for the production of high levels of heterologous proteins of this type.
Accelerated Radiosity Method for Complex Environments (1989)

As form-factor calculation costs about 90% of the computing time when applying radiosity approach for realistic image synthesis, it is of great significance to reduce the required computation, An accelerated radiosity algorithm for general complex environments, based on environment localization and the directional form-factor concept, is presented in this paper. First we subdivide the object space into many regions. Objects contained in each region are adjacent to each other and pose more illumination effects to their neighbours. Then form-factors are calculated in each local environment,. The radiant light energy transfer between different regions is evaluated at their common boundaries. Directional form-factors are introduced to simulate the interaction of light between local environments and between non-diffuse surfaces. Comparison is made to existing algorithms. Statistic results and theoretical analysis show that the new algorithm is much faster than previous ones. The technique is especially fit for interactive design and animation sequence since modification to the shape or location of objects usually happens in local environments.
Vascular changes have a primary role in migraine (2012)

In the ongoing debate about migraine pathogenesis it is crucial whether vascular factors are of primary importance or the blood vessels are just ‘bystanders’. In Edward Liveing’s the first monograph on migraine entitled ‘On Megrim, Sick-headache, and Some Allied Disorders: A Contribution to the Pathology of Nerve-Storms’ (1) he proposed the neural theory of migraine, ascribing the problem to ‘disturbances of the autonomic nervous system’, and that ‘vasomotor disturbance is secondary in origin’. The ‘neural’ theory has been revived in recent decades and some researchers have even proposed that migraine pain is caused by abnormal central interpretation of normal sensory input in the trigeminal sensory system. However, no scientific evidence supporting the theory of ‘abnormal central interpretation’ has yet emerged. Following a debate format I would like to present the scientific evidence supporting a primary role of vascular changes in migraine.
Thyroid hormone treatment of primary unipolar depression: a review (2000)

A substantial number of depressed patients will fail to respond to standard antidepressant therapy. Thyroid hormones, particularly T3, may be particularly useful in enhancing response to antidepressants. This review focuses on the use of T3 augmentation in unipolar major depression. The study clearly suggests that approximately half of patients will respond to T3 augmentation of antidepressants. There are several limitations to the literature including the fact that most studies have used T3 in tricyclic rather than SSRI failure and most are of relatively short duration, up to 3 wk. Further studies are required of T3 efficacy with newer classes of antidepressants, optimal dose of T3 to be used and the duration of T3 augmentation, particularly if the acute trial is successful.
Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG, RANKL and M-CSF (2007)

Our results suggest that inhibited Wnt/beta-catenin signaling in BMP2-induced osteoprogenitors in vivo promotes, on balance, the heightened formation of osteoclasts. Focally increased Dkk1 production by tumor cells in the bone may thus lead to focal bone loss.
Production of Highly Sialylated Monoclonal Antibodies (2012)

The first monoclonal antibody (Mab), developed against kidney transplant rejection, was accepted by the FDA in 1986 [1]. Today, Mabs are leading the biotherapeutics market as 28 have been approved in Europe and the USA, and hundreds are in clinical trials [2-4]. Most of them are of IgG1 subtype, developed for cancer and immune disease treatments. Mabs clinical efficacy not only relies on specific target binding provided by their variable region, but also on their ability to trigger defense mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). These effector functions are mediated by the interaction between the antibody Fc fragment and the Fcγ-receptors expressed on immune cell surfaces or the molecules of the complement involved in ADCC and CDC respectively. In the last decade, these interactions were found to be highly dependent on on the presence and structure of the N-glycan linked to the Fc fragment [5, 6].
Self-assembled cellular microarrays patterned using DNA barcodes (2007)

The successful integration of living cells into synthetic devices requires precise control over cell patterning. Here we describe a versatile platform that can accomplish this goal through DNA hybridization. Living cells functionalized with exogenous cell-surface DNA strands bind to cognate sequences of DNA printed on glass slides. Attachment via these "cell-adhesion barcodes" is rapid and specific, with close-packed arrays of cells forming within minutes. The biophysical properties of the system are characterized, and the technique is used to form complex cellular patterns with single-cell line widths and self-assembled cellular microarrays. Key advantages of DNA-directed cell binding include the ability to immobilize both adherent and non-adherent cells, to capture cells selectively from a mixed population, to tune the binding properties of the cells, and to reuse substrates prepared with widely available DNA printing technologies.
Tyrosine phosphorylation coupled to IgE receptor-mediated signal transduction and histamine release. (1990)

Antigen-induced cross-linking of IgE bound to its receptors at the surface of basophils or mast cells initiates a number of biochemical events culminating in the release of histamine-containing granules. In the present study, we investigated the possible involvement of tyrosine phosphorylation in signaling by the high-affinity IgE receptor (Fc epsilon RI). Cross-linking of Fc epsilon RI in rat basophilic leukemia cells (RBL-2H3) led to the phosphorylation of several proteins on tyrosine, the most prominent having a mass of 72 kDa. Tyrosine phosphorylation was rapid, detectable 1 min after stimulation, and correlated with both the time course and antigen dose for histamine release. Reversal of Fc epsilon RI cross-linking prevented continuation of the degranulation process and resulted in rapid loss of tyrosine phosphorylation. The receptor-mediated tyrosine phosphorylation was still induced in the absence of calcium in the medium. Depletion of protein kinase C with phorbol 12-myristate 13-acetate did not dramatically affect the tyrosine phosphorylation signal or the release of histamine. In contrast, the calcium ionophore A23187 induced histamine release in the absence of a perceptible increase in protein tyrosine phosphorylation. Thus, tyrosine phosphorylation is an early signal following Fc epsilon RI aggregation, independent of the exocytotic process itself. Taken together, our findings functionally link protein phosphorylation on tyrosine residues to Fc epsilon RI-mediated signal transduction leading to histamine release.
TV shearography: quantitative measurement of shear-magnitude fields by use of digital speckle photography (2000)

Digital speckle photography combined with TV shearography is developed for precise measurement of the magnitude of the shear field in a linear shear configuration. As an application the method is implemented to determine the slope-change variations of a three-dimensional object with TV shearography in which the shear magnitude is obtained with the digital speckle photography technique.
Proteolysis of insulin-like growth factor binding protein-5 by pregnancy serum and amniotic fluid. (1994)

Incubation of iodinated recombinant human insulin-like growth factor binding protein (rhIGFBP)-5 with pregnancy serum or amniotic fluid resulted in the formation of 22- and 15 kDa fragments. Non-pregnancy serum did not contain IGFBP-5 proteolytic activity. Size fractionation revealed the proteolytic activity both in serum and amniotic fluid in a > 100 kDa fraction which co-eluted in gel filtration with proteins of approx. 200 kDa. The IGFBP-5 protease activity was inhibited by EDTA, phenanthroline and PMSF. The formation of proteolytic fragments was also observed using 125I labeled rhIGFBP-3 and -4 but not with rhIGFBP-1 or -6 as substrate. The data demonstrate that pregnancy serum and amniotic fluid contain a very similar cation-dependent serine protease which degrades IGFBP-3, -4 and -5.
Modulation of beta-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family. (2006)

Amyloid-beta peptide (Abeta) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Abeta is produced by proteolytic processing of a transmembrane protein, beta-amyloid precursor protein (APP), by beta- and gamma-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to Abeta. Recent studies have shown that members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apolipoprotein E (apoE) receptor 2, interact with APP and regulate its endocytic trafficking. Another common feature of these receptors is their ability to bind apoE, which exists in three isoforms in humans and the presence of the epsilon4 allele represents a genetic risk factor for AD. In this review, we summarize the current understanding of the function of these apoE receptors with a focus on their role in APP trafficking and processing. Knowledge of the interactions between these distinct low-density lipoprotein receptor family members and APP may ultimately influence future therapies for AD.
Novel Inhibitors of the Nuclear Factor of Activated T Cells (NFAT)-Mediated Transcription of .beta.-Galactosidase: Potential Immunosuppressive and Antiinflammatory Agents (1995)

The preparation of a series of quinazoline-2,4-diones, 1-3, and pyrrolo[3,4-d]pyrimidine-2,4-diones, 4-8 is described. A small number of quinazolinedione analogs were identified from random screening to possess low micromolar (1.3-4.4 microM) potency in the nuclear factor of activated T cells-1-regulated beta-galactosidase expression assay. An expanded analog search resulted in identifying pyrrolopyrimidinedione 4b which is 5-10-fold (0.26 microM) more potent than the quinazolinediones. Replacement of the benzyl group with naphthyl led to greater potency and conformationally restricted analogs 4u-w. The naphthyl and acenaphthyl analogs are 10-100 times more potent inhibitors of beta-galactosidase expression than 4b. Binding affinity data for displacement of radiolabeled 4s from Jurkat cell membranes reflected an excellent correlation with the IC50 value for inhibition of beta-galactosidase activity. These products, whose structure-activity relationships are discussed, are of interest as potential agents for preventing interleukin-2 gene transcription.
Solid-state supramolecular chemistry of porphyrins. Hydrogen-bonded networks and porous crystals ofmeso-tetra[4-(3,5-diaminotriazino)phenyl]porphyrin (2000)

Tesselation of new porphyrin-based network motifs was demonstrated in crystals by incorporation of the diaminotriazine functions in the molecular building blocks. The title compound was synthesized and successfully applied in the construction of a uniquely structured solid which consists of flat multiporphyrin networks with very large voids, 2.2 × 2.2 nm2. These assemblies mutually interpenetrate each other, yielding a spectacular concatenated arrangement sustained in three dimensions by cooperative hydrogen bonding. The resulting multiporphyrin architecture resembles a molecular-sieve material, having 0.6 nm wide channels which propagate through the crystal and are accessible to other molecules. Copyright © 2000 John Wiley & Sons, Ltd.
Monospecific Inhibitors Show That Both Mannan-binding Lectin-associated Serine Protease-1 (MASP-1) and -2 Are Essential for Lectin Pathway Activation and Reveal Structural Plasticity of MASP-2 (2012)

The lectin pathway is an antibody-independent activation route of the complement system. It provides immediate defense against pathogens and altered self-cells, but it also causes severe tissue damage after stroke, heart attack, and other ischemia reperfusion injuries. The pathway is triggered by target binding of pattern recognition molecules leading to the activation of zymogen mannan-binding lectin-associated serine proteases (MASPs). MASP-2 is considered as the autonomous pathway-activator, while MASP-1 is considered as an auxiliary component. We evolved a pair of monospecific MASP inhibitors. In accordance with the key role of MASP-2, the MASP-2 inhibitor completely blocks the lectin pathway activation. Importantly, the MASP-1 inhibitor does the same, demonstrating that MASP-1 is not an auxiliary but an essential pathway component. We report the first Michaelis-like complex structures of MASP-1 and MASP-2 formed with substrate-like inhibitors. The 1.28 Å resolution MASP-2 structure reveals significant plasticity of the protease, suggesting that either an induced fit or a conformational selection mechanism should contribute to the extreme specificity of the enzyme.
Cell Therapy and Muscle Regeneration: Skeletal Myogenic Differentiation of Urine-Derived Stem Cells for Potential Use in Treatment of Urinary Incontinence (2013)

Cell Therapy and Muscle Regeneration: Skeletal Myogenic Differentiation of Urine-Derived Stem Cells for Potential Use in Treatment of Urinary Incontinence
Vagal Atrial Fibrillation (2007)

The autonomic nerve system plays an important role in atrial fibrillation (AF). Vagal AF refers AF (generally paroxysmal) arising in contexts of enhanced parasympathetic tone. Heterogeneity of refractoriness and action potential abbreviation resulting from spatially variable parasympathetic enhancement of the acetylcholine-dependent K(superscript +)-current (I(subscript KACh)) underlie vagal AF. Adrenergic influences may also contribute to the occurrence of vagal AF. Cholinergic stimulation may enhance ectopic firing from pulmonary vein cardiomyocytes, which potentially contribute to the occurrence of vagal AF. On the other hand, underlying heart disease modulates cholinergic regulation of atrial myocytes. Careful history taking in AF patients is important for vagal AF management. Vagal denervation may play a role in the efficacy of ablation procedures, but the results are conflicting. Specific I(subscript KACh) channel blockers may become the treatment of choice in the future.
Synthetic Studies of the Tunicamycin Antibiotics. Preparation of (+)-Tunicaminyluracil, (+)-Tunicamycin-V, and 5'-epi-Tunicamycin-V (1994)

A concise synthetic route to the tunicamycin antibiotics is described, illustrated by the preparation of (+)-tunicamycin-V (1-V), Key features of the synthesis include (1) the development and application of a silicon-mediated reductive coupling of aldehydes and allylic alcohols to construct the undecose core of the natural product and (2) the development of an efficient procedure for the synthesis of the trehalose glycosidic bond within the antibiotic. These innovations allow for the coupling of a uridine-derived aldehyde fragment with a performed trehalose-linked disaccharide allylic alcohol to form the carbohydrate core (1) of the natural product in a highly covergent manner. The resultant amino polyol is a versatile intermediate for the synthesis of any of the homologous tunicamycin antibiotics.
Conformational Analysis of a Cyclic RGD Peptide Containing a .psi.[CH2-NH] Bond: A Positional Shift in Backbone Structure Caused by a Single Dipeptide Mimetic (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformational Analysis of a Cyclic RGD Peptide Containing a .psi.[CH2-NH] Bond: A Positional Shift in Backbone Structure Caused by a Single Dipeptide MimeticArmin Geyer, Gerhard Mueller, and Horst KesslerCite this: J. Am. Chem. Soc. 1994, 116, 17, 7735–7743Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/ja00096a034https://doi.org/10.1021/ja00096a034research-articleACS PublicationsRequest reuse permissionsArticle Views371Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Expression of chemokines and their receptors in nephrotoxic serum nephritis (2000)

These results show that chemokines and their specific chemokine receptors are increased in parallel in this model of glomerulonephritis, consistent with the potential role of the chemokine system in leukocyte recruitment to the immune injured kidney.
Molecular Design of the Cαβ Interface Favors Specific Pairing of Introduced TCRαβ in Human T Cells (2008)

A promising approach to adoptive transfer therapy of tumors is to reprogram autologous T lymphocytes by TCR gene transfer of defined Ag specificity. An obstacle, however, is the undesired pairing of introduced TCRalpha- and TCRbeta-chains with the endogenous TCR chains. These events vary depending on the individual endogenous TCR and they not only may reduce the levels of cell surface-introduced TCR but also may generate hybrid TCR with unknown Ag specificities. We show that such hybrid heterodimers can be generated even by the pairing of human and mouse TCRalpha- and TCRbeta-chains. To overcome this hurdle, we have identified a pair of amino acid residues in the crystal structure of a TCR that lie at the interface of associated TCR Calpha and Cbeta domains and are related to each other by both a complementary steric interaction analogous to a "knob-into-hole" configuration and the electrostatic environment. We mutated the two residues so as to invert the sense of this interaction analogous to a charged "hole-into-knob" configuration. We show that this inversion in the CalphaCbeta interface promotes selective assembly of the introduced TCR while preserving its specificity and avidity for Ag ligand. Noteworthily, this TCR modification was equally efficient on both a Mu and a Hu TCR. Our data suggest that this approach is generally applicable to TCR independently of their Ag specificity and affinity, subset distribution, and species of origin. Thus, this strategy may optimize TCR gene transfer to efficiently and safely reprogram random T cells into tumor-reactive T cells.