gebhart/patrepeval huggingface dataset:
Successful Use of Enzyme Replacement Therapy in Infantile Hypophosphatasia (2017)

We wish to report the first successful Australian use of enzyme replacement therapy (ERT; asfotase alfa) in a patient with infantile hypophosphatasia. Hypophosphatasia is a metabolic bone disease with a wide spectrum of clinical presentations. The primary defect is a loss-of-function mutation(s) in the gene encoding tissue non-specific alkaline phosphatase (TNSALP), leading to deficient bone and tooth mineralisation and an imbalance in calcium and phosphate metabolism. The clinical manifestations vary and may include skeletal deformity, recurrent poorly healing fractures, chronic debilitating pain/weakness, tooth loss, reduced physical function, seizures, respiratory failure and/or death. Previous therapy for hypophosphatasia has been supportive only. We report a 6-year-old girl, presenting at 20 weeks of gestation with bilateral femoral bowing, with an antenatal diagnosis of osteogenesis imperfecta. At birth, she was found to have an alkaline phosphatase (ALP) level of 31 IU/L (reference interval: 100–350 IU/L age- and gender-adjusted), elevated urinary phosphoethanolamine, consistent radiological features and was homozygous for a known TNSALP gene mutation. She had persistent hypercalcaemia, failure to thrive and at 3 months developed severe bronchiolitis requiring intubation and ventilation for 2 weeks. Following reports of dramatic improvements in mineralization for this previously untreatable disease in animal models1 and humans,2 asfotase alfa was commenced at 4 months (2 mg/kg subcutaneously (SC) three times per week). Biochemical disturbances resolved quickly and a further episode of bronchiolitis at 5.5 months was managed with nasal prong oxygen only; no further invasive ventilation has been required. She showed marked improvement of mineralization on serial radiographs, with straightening of her femori (Fig. 1). Her linear growth has been steady. She has been making excellent developmental progress, with no ongoing issues. She had persistent craniosynostosis, which required cranial advancement surgery at aged 3, which was uncomplicated with resultant normal cranial shape. Calcification was noted on radiography at injection site but nothing was palpable clinically – this had largely resolved on follow-up radiograph 1 year later with increased injection site rotation and switching to 1 mg/kg SC, six times per week. Nephrocalcinosis had been noted on ultrasound prior to commencement of ERT, but had resolved by age 4. This successful outcome is reflected in the clinical trials showing improved survival and respiratory outcomes,3 with no significant side effects reported. We conclude that ERT should be strongly considered for this previously untreatable condition. We thank the family for allowing us to publish their story and to Alexion for ongoing compassionate supply of ERT for this patient.
Aminomethylphosphonic Acid Accumulation in Plant Species Treated with Glyphosate (2008)

Aminomethylphosphonic acid (AMPA) is the most frequently detected metabolite of glyphosate in plants. The objective of this study was to determine if there is any correlation of metabolism of glyphosate to AMPA in different plant species and their natural level of resistance to glyphosate. Greenhouse studies were conducted to determine the glyphosate I 50 values (rate required to cause a 50% reduction in plant growth) and to quantify AMPA and shikimate concentrations in selected leguminous and nonleguminous species treated with glyphosate at respective I 50 rates. Coffee senna [ Cassia occidentalis (L.) Link] was the most sensitive ( I 50 = 75 g/ha) and hemp sesbania [ Sesbania herbacea (P.Mill.) McVaugh] was the most resistant ( I 50 = 456 g/ha) to glyphosate. Hemp sesbania was 6-fold and Illinois bundleflower [ Desmanthus illinoensis (Michx.) MacM. ex B.L.Robins. & Fern.] was 4-fold more resistant to glyphosate than coffee senna. Glyphosate was present in all plant species, and its concentration ranged from 0.308 to 38.7 microg/g of tissue. AMPA was present in all leguminous species studied except hemp sesbania. AMPA concentration ranged from 0.119 to 4.77 microg/g of tissue. Shikimate was present in all plant species treated with glyphosate, and levels ranged from 0.053 to 16.5 mg/g of tissue. Non-glyphosate-resistant (non-GR) soybean accumulated much higher shikimate than glyphosate-resistant (GR) soybean. Although some leguminous species were found to be more resistant to glyphosate than others, and there was considerable variation between species in the glyphosate to AMPA levels found, metabolism of glyphosate to AMPA did not appear to be a common factor in explaining natural resistance levels.
Concomitant Analysis of Salivary Tumor Markers—A New Diagnostic Tool for Oral Cancer (2006)

The increase reported in salivary tumor markers may be used as a diagnostic tool, especially when a concurrent analysis for significantly increased markers is done. Salivary testing is noninvasive, making it an attractive, effective alternative to serum testing, and the possibility of developing home testing kits would further facilitate it as a diagnostic aid, enabling patients to monitor their own health at home and is important for those who live far from their treatment centers and especially for those at risk of developing OSCC.
Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation. (2007)

Detection of only 2 (14-3-3 eta and gamma) out of 7 different isoforms in SF suggests they are specific to the site of inflammation, and that distinguishes them from barely detectable levels of these isoforms found in normal serum. The MMP-1 stimulatory effect of the eta isoform explains its correlation with MMP-1 levels seen in these samples.
Heterogeneous distribution of the cAMP receptor protein RII in the nervous system: evidence for its intracellular accumulation on microtubules, microtubule-organizing centers, and in the area of the Golgi complex. (1986)

The cellular and subcellular distribution of the regulatory subunit RII of cAMP-dependent protein kinase was studied by light and electron microscopy immunocytochemistry in tissue sections from rat brain and in primary cultures of brain cells. RII immunoreactivity was present in most neurons, although at variable concentration. In addition, RII was also detectable in other cell types including glia, neuroepithelial cells, and cells of mesenchymal origin. In the cell cytoplasm, RII immunoreactivity was concentrated at certain sites. An accumulation of RII immunoreactivity was found in all RII-positive cells at the Golgi area, precisely at a region directly adjacent to one of the two major faces of the Golgi complex. RII was also highly concentrated in some microtubule-rich cell processes such as cilia and neuronal dendrites, but was below detectability in most axons. In neurons, its concentration in dendrites is consistent with the previously demonstrated high affinity interaction between RII and the dendritic microtubule-associated protein 2. In addition, RII was accumulated at basal bodies of cilia and at centrosomes, i.e., sites known to act as microtubule organizers. RII-labeled centrosomes, however, were visible only in cells where the Golgi complex had a pericentrosomal organization, and not in cells where the Golgi complex was perinuclear such as in neurons and glia in situ. We hypothesize that centrosomal RII is bound to the pericentriolar microtubule-organizing material and that this material remains associated with the trans region of the Golgi complex when the latter is no longer associated with the centrosome. Our results suggest a key but not obligatory role of cAMP in the Golgi-centrosomal area, the headquarters of cell polarity, mobility and intracellular traffic, and in the function of a subpopulation of microtubules.
Photochromism:  Memories and SwitchesIntroduction (2000)

ADVERTISEMENT RETURN TO ISSUEPREVEditorialNEXTPhotochromism: Memories and SwitchesIntroductionM. IrieCite this: Chem. Rev. 2000, 100, 5, 1683–1684Publication Date (Web):May 10, 2000Publication History Published online10 May 2000Published inissue 1 May 2000https://pubs.acs.org/doi/10.1021/cr980068lhttps://doi.org/10.1021/cr980068leditorialACS PublicationsCopyright © 2000 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views21486Altmetric-Citations764LEARN 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 PDF (14 KB) Get e-AlertscloseSUBJECTS:Analytical apparatus,Circuits,Optical properties,Organic compounds,Photochromism Get e-Alerts
Antitumor Activities of TEM8-Fc: An Engineered Antibody-like Molecule Targeting Tumor Endothelial Marker 8 (2007)

Tumor endothelial marker 8 (TEM8) was discovered as a cell membrane protein that is predominantly expressed in tumor endothelium and identified as a receptor for anthrax toxin. We developed an antibody-like molecule that consists of the protective antigen (PA)-binding domain of human TEM8 linked to the Fc portion of human immunoglobulin G1 (TEM8-Fc). This engineered protein bound to PA in a divalent cation-dependent manner and efficiently protected J774A.1 macrophage-like cells against anthrax toxin challenge in a dose-dependent manner. TEM8-Fc suppressed the growth and metastasis of xenograft human tumors in athymic nude mice (control versus 10 mg/kg TEM8-Fc, mean tumor weight: LS-180, 1.72 versus 0.16 g, difference = 1.56 g, 95% confidence interval [CI] = 0.96 to 2.16 g; P<.001; MCF-7, 1.12 versus 0.08 g, difference = 1.04 g, 95% CI = 0.77 to 1.31 g; P<.001; HepG2, 1.28 versus 0.35 g, difference = 0.93 g, 95% CI = 0.60 to 1.25 g; P<.001). Furthermore, TEM8 interacted with the M2 isoenzyme of pyruvate kinase (M2-PK), which has an important role in tumor growth and metastasis. TEM8-Fc is a novel therapeutic antibody-like agent in the management of solid tumors that may act by trapping M2-PK.
[Multiple hybridization in genome analysis. 1. Reaction of diamine and bisulfite with cytosine for the introduction of nonradioactive markers into DNA]. (1989)

A two-step chemical method has been developed for the introduction of biotin and other low-molecular derivatives into DNA. The method is based on the interaction of aliphatic diamines with cytosine residues of the polynucleotide chain in the presence of sodium bisulfite with subsequent addition of biotin. DNA modified this way may be used as an effective probe for non-isotopic hybridization which can be used simultaneously with 32P-labelled probes.
Vascular Endothelial Growth Factor KDR Receptor Signaling Potentiates Tumor Necrosis Factor-induced Tissue Factor Expression in Endothelial Cells (2001)

Vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-alpha) have been shown to synergistically increase tissue factor (TF) expression in endothelial cells; however, the role of the VEGF receptors (KDR, Flt-1, and neuropilin) in this process is unclear. Here we report that VEGF binding to the KDR receptor is necessary and sufficient for the potentiation of TNF-induced TF expression in human umbilical vein endothelial cells. TF expression was evaluated by Western blot analysis and fluorescence-activated cell sorting. In the absence of TNF-alpha, wild-type VEGF- or KDR receptor-selective variants induced an approximate 7-fold increase in total TF expression. Treatment with TNF alone produced an approximate 110-fold increase in total TF expression, whereas coincubation of TNF-alpha with wild-type VEGF- or KDR-selective variants resulted in an approximate 250-fold increase in TF expression. VEGF lacking the heparin binding domain was also able to potentiate TF expression, indicating that heparin-sulfate proteoglycan or neuropilin binding is not required for TF up-regulation. Neither placental growth factor nor an Flt-1-selective variant was capable of inducing TF expression in the presence or absence of TNF. Inhibition of protein-tyrosine kinase or protein kinase C activity significantly blocked the TNF/VEGF potentiation of TF up-regulation, whereas phorbol 12-myristate 13-acetate, a protein kinase C activator, increased TF expression. These data demonstrate that KDR receptor signaling governs both VEGF-induced TF expression and the potentiation of TNF-induced up-regulation of TF.
Optimization and control of VDD and VTH for low-power, high-speed CMOS design (2002)

It is essential to control VDD and VTH for low-power, high-speed CMOS design. In this paper, it is shown that these two parameters can be controlled by designers as objectives of design optimization to find better trade-offs between power and speed. Quantitative analysis of trade-offs between power and speed is presented. Some of the popular circuit techniques and design examples to control VDD and VTH are introduced. A simple theory to compute optimum multiple VDD's and VTH's is described. Scaling scenarios of variable and/or multiple VDD's and VTH's is discussed to show future technology directions.
Transgenic and Knockout Mice in Diabetes Research: Novel Insights into Pathophysiology, Limitations, and Perspectives (2005)

Insulin resistance and type 2 diabetes are serious public health threats. Although enormous research efforts have been focused on the pathogenesis of these diseases, the underlying mechanisms remain only partly understood. Here we review mouse phenotypes resulting from inactivation of molecules responsible for the control of glucose metabolism that have led to novel insights into insulin action and the development of insulin resistance. In addition, more sophisticated strategies to manipulate genes in mice in the future are presented.
Abnormal Synaptic Plasticity and Impaired Spatial Cognition in Mice Transgenic for Exon 1 of the Human Huntington's Disease Mutation (2000)

Huntington's disease (HD) is an autosomal dominant progressive and fatal neurodegenerative brain disorder caused by an expanded CAG/polyglutamine repeat in the coding region of the gene. Presymptomatic Huntington's disease patients often exhibit cognitive deficits before the onset of classical symptoms. To investigate the possibility that changes in synaptic plasticity might underlie cognitive impairment in HD, we examined hippocampal synaptic plasticity and spatial cognition in a transgenic mouse (R6/2 line) expressing exon 1 of the human Huntington's disease gene containing an expanded CAG repeat. This mouse exhibits a progressive and fatal neurological phenotype that resembles Huntington's disease. We report that R6/2 mice show marked alterations in synaptic plasticity at both CA1 and dentate granule cell synapses, and impaired spatial cognitive performance in the Morris water maze. The changes in hippocampal plasticity were age dependent, appearing at CA1 synapses several weeks before they were observed in the dentate gyrus. Deficits in synaptic plasticity at CA1 synapses occurred before an overt phenotype. This suggests that altered synaptic plasticity contributes to the pre-symptomatic changes in cognition reported in human carriers of the Huntington' disease gene. The temporal and regional changes in synaptic plasticity within the hippocampus mirror the appearance of neuronal intranuclear inclusions, suggesting a relationship between polyglutamine aggregation and dysfunction.
Bio‐affinity characterization mass spectrometry (1995)

A new approach, bio-affinity characterization mass spectrometry (BACMS), aimed at providing a more rapid, sensitive and potentially more flexible alternative to techniques presently employed for the characterization of noncovalent interactions in mixtures, such as would be encountered in combinatorial chemistry, in presented. BACMS avoids some of the difficulties and potential artifacts associated with affinity chromatography since the noncovalent associations occur in solution; thus, BACMS avoids the requirement of solid support media and the development of non-interfering linker species. This paper describes the conceptual basis for the methodology and its potential use in applications which include the screening of high affinity ligands in support of new drug development. BACMS exploits new Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry technologies which, when coupled to electrospray ionization (ESI), allow the investigation of specific noncovalent complexes formed in solution. BACMS utilizes the well-known attributes of FTICR, such as the high resolution mass analysis and (MS)n (n > or = 2) capabilities; however, it is even more directly a result of recently developed techniques involving quadrupolar excitation, such as selected-ion accumulation. These tools are demonstrated and the results illustrate the extraordinary sensitivity achievable (solution concentration of 1 x 10-9 M without the use of separations prior to ESI). Thus, the new capabilities demonstrated here, in conjunction with ESI, will be useful for the investigation of very low relative concentration noncovalent association directly from solution, and promote a faster alternative for combinatorial mixture screening and analysis.
Hessian eigenmaps: Locally linear embedding techniques for high-dimensional data (2003)

We describe a method for recovering the underlying parametrization of scattered data (m(i)) lying on a manifold M embedded in high-dimensional Euclidean space. The method, Hessian-based locally linear embedding, derives from a conceptual framework of local isometry in which the manifold M, viewed as a Riemannian submanifold of the ambient Euclidean Space R(n), is locally isometric to an open, connected subset Θ of Euclidean space R(d). Because Θ does not have to be convex, this framework is able to handle a significantly wider class of situations than the original ISOMAP algorithm. The theoretical framework revolves around a quadratic form H(f) = ∫(M)||H(f)(m)||²(F)dm defined on functions f: M--> R. Here Hf denotes the Hessian of f, and H(f) averages the Frobenius norm of the Hessian over M. To define the Hessian, we use orthogonal coordinates on the tangent planes of M. The key observation is that, if M truly is locally isometric to an open, connected subset of R(d), then H(f) has a (d + 1)-dimensional null space consisting of the constant functions and a d-dimensional space of functions spanned by the original isometric coordinates. Hence, the isometric coordinates can be recovered up to a linear isometry. Our method may be viewed as a modification of locally linear embedding and our theoretical framework as a modification of the Laplacian eigenmaps framework, where we substitute a quadratic form based on the Hessian in place of one based on the Laplacian.
Carbohydrate-active enzymes in completely sequenced genomes (2002)

Conference Abstract| February 01 2002 Carbohydrate-active enzymes in completely sequenced genomes B. Henrissat B. Henrissat 1Architecture et Fonction des Macromolecules Biologiques, UMR6098, CNRS2Universites Aix-Marseille I and II, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 2002 Biochemical Society2002 Biochem Soc Trans (2002) 30 (1): A24. https://doi.org/10.1042/bst030a024b Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation B. Henrissat; Carbohydrate-active enzymes in completely sequenced genomes. Biochem Soc Trans 1 February 2002; 30 (1): A24. doi: https://doi.org/10.1042/bst030a024b Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2002 Biochemical Society2002 Article PDF first page preview Close Modal You do not currently have access to this content.
Role of the brain stem in tibial inhibition of the micturition reflex in cats (2015)

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P < 0.05) increased bladder capacity to 30-60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300-900 μg) eliminated acute TNS inhibition and significantly (P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes.