julilili42/papers huggingface dataset:
Abstract 2759: Elevated Coronary Calcium Scores Measured by Multi-Slice Computed Tomography are Associated with Low Response to Clopidogrel in Patients with Stable Angina pectoris
2007-10-16

Cardiac multi-detector computed tomography (MDCT) with retrospective ECG-gating permits the determination and quantification of coronary calcifications. High calcium scores are known to be associated with elevated all-cause mortality. Moreover, low response to clopidogrel influences cardiovascular outcome after coronary stent placement. We sought to evaluate whether elevated calcium scores are associated with a low response to clopidogrel. Methods 62 patients were enrolled in this trial (52 male, mean age 64.8 ± 8.9 years). Coronary calcium scoring (expressed as Agatston score equivalent, ASE) was measured with multi-slice computed tomography (Sensation 64TM [n=19] and Somatom Definition TM [n=43], Siemens, Forchheim, Germany) prior to stent implantation. Responsiveness to clopidogrel was assessed by ADP (20 micromol/L)-induced aggregometry at least 6 h after administration of a loading dose of 600 mg clopidogrel. Results Median calcium score was 736 ASE [range 0 –3126] and mean platelet inhibition was 35±19% [range 0 –70]. There was a significant negative correlation between ASE and response to clopidogrel (r 2 =0.135, p=0.0033, slope 7.809 ± 2.549). Patients within the first quartile of ASE had significantly better response to clopidogrel than other patients (p&lt;0.05). Establishing a threshold of 200 ASE responsiveness to clopidogrel could be predicted with a positive predictive value of 80% and a specificity of 91%. Conclusions We could demonstrate that elevated ASE is associated with a low response to clopidogrel. Patients with a low coronary plaque burden are more likely to have a good response to clopidogrel. Coronary calcium scoring might help to identify low responders to clopidogrel prior to stent placement and aggregometry.
Maltose binding protein (MalE) interacts with periplasmic loops P2 and P1 respectively of the MalFG subunits of the maltose ATP binding cassette transporter (MalFGK2) from Escherichia coli/Salmonella during the transport cycle
2007-10-17

Summary The ATP binding cassette (ABC‐) transporter mediating the uptake of maltose/maltodextrins in Escherichia coli/Salmonella enterica serovar Typhimurium is one of the best characterized systems and serves as a model for studying the molecular mechanism by which ABC importers exert their functions. The transporter is composed of a periplasmic maltose binding protein (MalE), and a membrane‐bound complex (MalFGK 2 ), comprising the pore‐forming hydrophobic subunits, MalF and MalG, and two copies of the ABC subunit, MalK. We report on the isolation of suppressor mutations within malFG that partially restore transport of a maltose‐negative mutant carrying the malK809 allele (MalKQ140K). The mutation affects the conserved LSGGQ motif that is involved in ATP binding. Three out of four suppressor mutations map in periplasmic loops P2 and P1 respectively of MalFG. Cross‐linking data revealed proximity of these regions to MalE. In particular, as demonstrated in vitro and in vivo , Gly‐13 of substrate‐free and substrate‐loaded MalE is in close contact to Pro‐78 of MalG. These data suggest that MalE is permanently in close contact to MalG‐P1 via its N‐terminal domain. Together, our results are interpreted in favour of the notion that substrate availability is communicated from MalE to the MalK dimer via extracytoplasmic loops of MalFG, and are discussed with respect to a current transport model.
Noggin blocks invasive growth of murine B16‐F1 melanoma cells in the optic cup of the chick embryo
2007-10-17

Abstract Melanoma cells originate from the neural crest and are characterized by high migratory potential and invasive growth. After transplantation into the neural tube of the chick embryo, melanoma cells spontaneously emigrate along the neural crest pathways without tumor formation or malignant growth. This emigration depends on the constitutive over‐expression of bone morphogenetic protein‐2 (BMP‐2) and can be ablated by the BMP‐antagonist noggin. When transplanted into the embryonic optic cup, melanoma cells invade the host tissue and form malignant tumors. Here, we asked if the invasive growth of melanoma cells in the optic cup could be influenced by BMP‐2 or noggin. Mouse B16‐F1 cells were grown as aggregates, treated with BMP‐2 or noggin during aggregation and transplanted into the optic cup of 3‐day chick embryos. After 3 days of subsequent incubation, embryos were evaluated for melanoma cell invasiveness. Immunohistochemical examination revealed that untreated and BMP‐2‐treated melanoma cells had grown malignantly into the host tissue. However, noggin pretreatment of the aggregates had blocked melanoma cell invasiveness and tumor formation. We conclude that invasive growth of melanoma cells in vivo is BMP‐dependent and can be ablated by noggin, thus rendering noggin a promising agent for the treatment of BMP‐over‐expressing melanoma. © 2007 Wiley‐Liss, Inc.
Multiple sclerosis and the CTLA4 autoimmunity polymorphism CT60: no association in patients from Germany, Hungary and Poland
2007-10-17

Polymorphisms in the CTLA4 gene region have been associated with susceptibility to autoimmune diseases. The recently described single nucleotide polymorphism CT60, located in the 3' untranslated region of CTLA4 is associated with Graves' disease, thyroiditis, autoimmune diabetes and other autoimmune diseases. A case-control association study was conducted in German, Hungarian and Polish multiple sclerosis (MS) patients and regional control individuals for the CTLA4 CT60 and + 49A/G polymorphisms. No significant association of these polymorphisms or respective haplotypes with MS was found. No association of CT60 genotypes with T cell expression of ICOS and CTLA-4 after in vitro stimulation was detected. Multiple Sclerosis 2008; 14: 153—158. http://msj.sagepub.com
Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum1
2007-10-17

Abstract Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long‐term effects of extrinsic denervation on functional non‐adrenergic, non‐cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age‐matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose‐dependently in both groups, greater in NC than in SBT. The VIP antagonist ([ d ‐ p ‐Cl‐Phe 6 ,Leu 17 ]‐VIP) and the nitric oxide synthase inhibitor l ‐ N G ‐nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose‐dependently, greater in NC than in SBT. The substance P antagonist ([ d ‐Pro 2 , d ‐Trp 7,9 ]‐substance P) inhibited effects of exogenous substance P and increased the EFS‐induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.
Reactions of Transition Metal Azido Complexes and Their Reaction Products
2007-10-17

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Two functionally linked amino acids in the stem 2 region of measles virus haemagglutinin determine infectivity and virulence in the rodent central nervous system
2007-10-18

Rodent brain-adapted measles virus (MV) strains, such as CAM/RB and recombinant MVs based on the Edmonston strain containing the haemagglutinin (H) of CAM/RB, cause acute encephalitis after intracerebral infection of newborn rodents. We have demonstrated that rodent neurovirulence is modulated by two mutations at amino acid positions 195 and 200 in the H protein, one of these positions (200) being a potential glycosylation site. In order to analyse the effects of specific amino acids at these positions, we introduced a range of individual and combined mutations into the open reading frame of the H gene to generate a number of eukaryotic expression plasmids. The functionality of the mutant H proteins was assessed in transfected cells and by generating recombinant viruses. Interestingly, viruses caused acute encephalitis only if the amino acid Ser at position 200 was coupled with Gly at position 195, whereas viruses with single or combined mutations at these positions, including glycosylation at position 200, were attenuated. Neurovirulence was associated with virus spread and induction of neuronal apoptosis, whereas attenuated viruses failed to infect brain cells. Similar results were obtained by using primary brain-cell cultures. Our findings indicate that a structural alteration in the stem 2 region of the H protein at position 195 or 200 interferes with infectivity of rodent neurons, and suggest that the interaction of the viral attachment protein with cellular receptors on neurons is affected.
Atypical Type II Silent Corticotrophic Adenoma Developing into Cushing's Disease upon Second Recurrence
2007-10-18

Herein, we report the case of a 73-year old male patient who presented with two recurrences of a pituitary adenoma within a period of 15 years. The first tumor resection 15 years ago revealed a non-functioning pituitary macroadenoma. 11 years later, the first recurrence of the tumor was reoperated. Throughout the early course of the disease, he suffered from secondary adrenal insufficiency and required replacement therapy with hydrocortisone. Currently, he presented with the second recurrence and clinical examination revealed signs of Cushing's disease. This was clearly confirmed by endocrinological evaluation. A retrospective analysis of all histological and immunohistochemical slides rendered an adenoma exhibiting chromophobia, ACTH-positivity and features of atypia such as elevated p53 and Ki67 expression as well as nuclear polymorphism. According to the revised WHO classification it was classified as atypical type II silent corticotroph adenoma at the time of the first and second surgery. The specimen removed during the recent surgery displayed the same histological features and was classified as corticotroph adenoma. The combination of an atypical type II adenoma and the switch in the hormone status to an endocrinologically active adenoma makes this case exceedingly rare.
Cep164, a novel centriole appendage protein required for primary cilium formation
2007-10-22

Primary cilia (PC) function as microtubule-based sensory antennae projecting from the surface of many eukaryotic cells. They play important roles in mechano- and chemosensory perception and their dysfunction is implicated in developmental disorders and severe diseases. The basal body that functions in PC assembly is derived from the mature centriole, a component of the centrosome. Through a small interfering RNA screen we found several centrosomal proteins (Ceps) to be involved in PC formation. One newly identified protein, Cep164, was indispensable for PC formation and hence characterized in detail. By immunogold electron microscopy, Cep164 could be localized to the distal appendages of mature centrioles. In contrast to ninein and Cep170, two components of subdistal appendages, Cep164 persisted at centrioles throughout mitosis. Moreover, the localizations of Cep164 and ninein/Cep170 were mutually independent during interphase. These data implicate distal appendages in PC formation and identify Cep164 as an excellent marker for these structures.
Dual-Source CT with Improved Temporal Resolution in Assessment of Left Ventricular Function: A Pilot Study
2007-10-22

With the improvement of temporal resolution between 42 and 83 milliseconds, dual-source CT not only enables accurate assessment of global functional parameters, but it also allows for quantification of time-dependent variables and reliable evaluation of regional wall motion.
3-O-Methyldopamine (3-O-Methoxytyramine) Interferes with the Internal Standard 3,4-Dihydroxybenzylamine in a Plasma Catecholamine HPLC Method
2007-10-22

Plasma catecholamines are routinely assayed for the detection of pheochromocytoma and in clinical trials evaluating hemodynamic function in intensive care patients (1). HPLC combined with electrochemical detection is widely applied for the quantification of plasma catecholamines(2). We use a commercially available method for plasma catecholamine measurement (Chromsystems), including a pretreatment step for plasma samples that uses the relative nonspecific absorption of analytes onto Al2O3. Isocratic separation is then performed on a reversed-phase C18 column. Assay conditions include a 0.8 mL/min flow rate and a mobile phase containing salts, methanol, and an ion-pairing reagent. Quantification is performed with an L 3500 electrochemical detector (Recipe) at a potential of +500 mV. 3,4-Dihydroxybenzylamine (DHBA) is used as the internal standard. We observed an interference with the internal standard in patients taking part in a clinical study in our intensive care unit. Evaluation of the case histories revealed that these patients have received dopamine intravenously before blood ...
The role of interleukin‐6 in insulin resistance, body fat distribution and energy balance
2007-10-23

Summary Interleukin‐6 (IL‐6) is a central player in the regulation of inflammation, haematopoiesis, immune response and host defense mechanisms. During the last decade, an accumulating amount of data suggested a pivotal role for IL‐6 in metabolic processes, thus fortifying the picture of IL‐6 as a multifaceted, pleiotropic cytokine. Because of its secretion by adipose tissue and contracting skeletal muscle and its broad action on central and peripheral organs, IL‐6 has been termed an adipokine and a myokine. Its quantitative release from adipose tissue results in a subclinical, systemic elevation of IL‐6 plasma levels with increasing body fat content, which may be implicated in the proinflammatory state leading to insulin resistance. On the other hand, IL‐6 produced in the working muscle during physical activity could act as an energy sensor by activating AMP‐activated kinase and enhancing glucose disposal, lipolysis and fat oxidation. In addition, both impaired IL‐6 secretion and action are risk factors for weight gain. Thus, IL‐6 clearly has lipolytic effects and anti‐obesity potential. However, the application of IL‐6 itself is at least limited by a narrow therapeutic range and its important function for a balanced inflammatory response. Further studies on the molecular basis of the metabolic effects of IL‐6 could elucidate novel therapeutic strategies for custom‐designed, IL‐6‐related substances.
Semantic Associations between Signs and Numerical Categories in the Prefrontal Cortex
2007-10-23

The utilization of symbols such as words and numbers as mental tools endows humans with unrivalled cognitive flexibility. In the number domain, a fundamental first step for the acquisition of numerical symbols is the semantic association of signs with cardinalities. We explored the primitives of such a semantic mapping process by recording single-cell activity in the monkey prefrontal and parietal cortices, brain structures critically involved in numerical cognition. Monkeys were trained to associate visual shapes with varying numbers of items in a matching task. After this long-term learning process, we found that the responses of many prefrontal neurons to the visual shapes reflected the associated numerical value in a behaviorally relevant way. In contrast, such association neurons were rarely found in the parietal lobe. These findings suggest a cardinal role of the prefrontal cortex in establishing semantic associations between signs and abstract categories, a cognitive precursor that may ultimately give rise to symbolic thinking in linguistic humans.
How temporal distance from past selves influences self‐perception
2007-10-23

Abstract The present studies examine how perceived temporal distance from past selves influences perceptions of the current self. Participants recalled their past self either at age 9 or 15. These two past selves differ in levels of identification with gender and thus denote different standards of comparison. Three hypotheses were tested. Temporal distance should determine whether recalled past selves produce assimilation or contrast effects on the current self. Second, temporal comparison effects should be weaker when people recall their past in terms of stable, relatively enduring characteristics (e.g. traits). Third, past selves should to a greater extent be biased by stereotypical knowledge about former lifetime periods the farther away individuals feel from past selves. Past selves coloured by stereotypical knowledge are more extreme and should thus produce stronger judgemental effects on the current self. The results supported the hypotheses. Implications for autobiographical remembering are discussed. Copyright © 2007 John Wiley &amp; Sons, Ltd.
The crystal structure of the complex of P II and acetylglutamate kinase reveals how P II controls the storage of nitrogen as arginine
2007-10-24

Photosynthetic organisms can store nitrogen by synthesizing arginine, and, therefore, feedback inhibition of arginine synthesis must be relieved in these organisms when nitrogen is abundant. This relief is accomplished by the binding of the P II signal transduction protein to acetylglutamate kinase (NAGK), the controlling enzyme of arginine synthesis. Here, we describe the crystal structure of the complex between NAGK and P II of Synechococcus elongatus , at 2.75-Å resolution. We prove the physiological relevance of the observed interactions by site-directed mutagenesis and functional studies. The complex consists of two polar P II trimers sandwiching one ring-like hexameric NAGK (a trimer of dimers) with the threefold axes of these molecules aligned. The binding of P II favors a narrow ring conformation of the NAGK hexamer that is associated with arginine sites having low affinity for this inhibitor. Each P II subunit contacts one NAGK subunit only. The contacts map in the inner circumference of the NAGK ring and involve two surfaces of the P II subunit. One surface is on the P II body and interacts with the C-domain of the NAGK subunit, helping widen the arginine site found on the other side of this domain. The other surface is at the distal region of a protruding large loop (T-loop) that presents a novel compact shape. This loop is inserted in the interdomain crevice of the NAGK subunit, contacting mainly the N-domain, and playing key roles in anchoring P II on NAGK, in activating NAGK, and in complex formation regulation by MgATP, ADP, 2-oxoglutarate, and by phosphorylation of serine-49.
The Formation of Resonant Planetary Systems
2007-10-24

This chapter contains sections titled: The Solar System Extrasolar Systems in Mean-motion Resonance Planet–Disk Interaction Resonant Capture Hydrodynamical Studies Forced Migration Second Fundamental Model of Resonance Outcome of Resonant Encounters Specific Systems GJ 876: A Case of Adiabatic Migration Formation of Systems HD 128311 and HD 73526 through Mixed Scenarios Summary
Incidence of Visual Extinction After Left Versus Right Hemisphere Stroke
2007-10-25

Background and Purpose— Generally it is accepted that spatial neglect occurs predominantly after stroke of the human right hemisphere. In contrast, it remained controversial whether extinction follows the same hemispheric asymmetry. The opinion prevails that the laterality of visual extinction is not as pronounced as it is for spatial neglect. Methods— To directly compare the incidence of the 2 disorders within the same sample, spatial neglect and visual extinction were investigated during a 1-year period in 83 consecutively admitted patients with unilateral right or left hemisphere stroke. Results— The incidence of visual extinction and of spatial neglect was not significantly different, neither after left hemisphere (2.4% neglect; 4.9% extinction) nor after right hemisphere (26.2% neglect; 24.3% extinction) stroke. Conclusions— Visual extinction seems to be as asymmetrically associated with the human right hemisphere as is spatial neglect.
Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status
2007-10-26

Abstract Introduction At the time when metastatic disease is identified, assessment of human epidermal growth factor receptor (HER)2 status might help to optimize treatment decisions if HER2 status was not determined at first diagnosis and if HER2 positivity has been acquired during disease progression. Within this context, determination of serum HER2 or evaluation of HER2 status in circulating tumor cells (CTCs) may be of clinical relevance because metastatic tissue may be difficult to obtain for analysis as a result of its localization. The aim of this study was therefore to determine the HER2 status in serum and corresponding CTCs in patients with metastatic breast cancer whose primary tumors were HER2 negative or of unknown HER2 status. Methods Blood samples were obtained from 77 metastatic breast cancer patients with negative ( n = 44) or unknown ( n = 33) HER2 status. Serum HER2 was determined using a commercial HER2/neu ELISA kit. CTCs were detected by slide-based assay using immunomagnetic enrichment and characterized by phenotyping and genotyping. Alternatively, a commercial kit, based on RT-PCR, was used to detect and characterize CTCs. Results Twenty out of 77 patients with metastatic disease had elevated serum levels of HER2. Blood samples could be analyzed for the presence of CTCs in 67 patients. Eight out of 21 patients with detectable CTCs exhibited HER2 amplification. Twenty-three out of 77 patients were HER2 positive using at least one method. Concordance between HER2 status of CTCs and serum HER2 was observed in 15 of 21 patients (71%). In six patients conflicting results were obtained. Three patients with elevated serum HER2 status had HER2-negative CTCs, whereas three patients with HER2-positive CTCs had normal serum HER2 levels. Conclusion A subgroup of patients with initially negative or unknown HER2 status can have elevated serum HER2 levels and/or HER2-positive CTCs at the time of development of metastatic disease. Although only a small number of patients were studied, our observations are of clinical relevance because, currently, these patients do not have access to HER2-targeted therapy.