tbuckley/cabot-search huggingface dataset:
SOME MOTOR ASPECTS OF SCHIZOPHRENIA: AN EMG STUDY
Authors: GEORGE B. WHATMORE, RICHARD M. ELLIS
Journal: American Journal of Psychiatry (1958)

1. The value of studying motor activity in mental illness should not be overlooked. Motor activity within the central nervous system is intimately tied up with sensation, emotion, and thinking. An understanding of the neurophysiology of any one of these, as well as their deviations in illness, must include a description of the motor component. 2. Multi-channel electromyographic measurements on 21 schizophrenic patients and 10 control subjects are here reported. An electromyograph giving both integrated and instantaneous readings and capable of measuring minute amounts of motor activity was employed. Residual motor activity was recorded while the subjects endeavored to relax as completely as possible in the supine position. This residual motor activity is for the most part invisible to the naked eye. Records were taken simultaneously from 4 muscle areas, namely forehead, jaw, forearm, and leg, for 30-minute periods. The patients exhibit higher levels of motor activity in all 4 muscle areas and the differences between these and the values for the control group are highly significant (P=<0.00l for forehead and jaw, and P=<0.01 for forearm and leg). Quantitatively these differences are remarkably similar for each muscle area. The grand mean for the patient group is 54.9 units of motor activity and for the control group 19.9 units. 3. This exaggerated motor activity is most likely accompanied by increased activity in efferent neurons of the motor cortex and/or premotor cortex. Such increased pyramidal cell activity could have widespread influence on the functioning of the cerebral cortex, as well as subcortical structures, through the agency of the many collateral fibers given off by these neurons. Since there is evidence that both thinking and emotion have motor components, it is reasonable that hyperactivity in the motor system might lead to disturbances of thinking and emotion. The possibility of motor system hyperactivity playing an etiological role of some type in the onset of schizophrenia should be kept in mind. 4. The term "hyperponesis" is suggested to refer to exaggerated activity within the motor portion of the central nervous system. This exaggerated activity may be localized to a portion of the motor system or generalized to include the whole motor system, it may be intermittent or continuous, static or phasic, overt or invisible.
Integrins and cell structure: powerful determinants of heart development and heart function
Authors: J Hescheler
Journal: Cardiovascular Research (2000)

See article by Maitra et al. [12] (pages 715–725) in this issue. 

Integrins comprise a family of cell surface receptors known to attach cells to the extracellular matrix (ECM) and to mediate mechanical as well as chemical signals. Beyond ECM-mediated signalling to the cytosol (outside–in), extracellular binding activities are regulated through integrin-mediated signalling in the opposite direction (inside–out). Because integrins assemble large signalling complexes and activate multiple signalling pathways they are involved in an array of elementary biological functions such as control of cell cycle, proliferation as well as apoptosis [1].

Integrins are heterodimers composed of non-covalently associated α- and β-subunits. In mammals at least eight β- and 16 α-subunits combining for 22 different receptors have been identified so far [2]. The β1-subunit composes the largest subfamily of integrins since it can associate with at least ten different α-subunits [3]. Integrins are widely expressed and dynamically regulated during development [4–6]. Their important role during early organotypic development has been unequivocally demonstrated in knock out models. For instance, deletion of the β1-integrin gene has resulted in early embryonic death during or shortly after implantation. Using a variety of elegant animal and cell models, deletion of the β1-integrin gene was further found to result in severe defects of migration and homing of cells of the hematopoietic system [7], alterations in neuronal development [8,9] and defective vasculo/angiogenesis [10]. Moreover, using β1-integrin deficient embryonic stem cells for the in vitro … 

* Corresponding author. Tel.: +49-221-478-6960; fax: +49-221-478-6965 j.hescheler{at}uni-koeln.de
Antigen-specific peripheral shaping of the natural regulatory T cell population
Authors: Stephanie K. Lathrop, Nicole A. Santacruz, Dominic Pham, Jingqin Luo, Chyi-Song Hsieh
Journal: The Journal of Experimental Medicine (2008)

Although regulatory T (T reg) cells are thought to develop primarily in the thymus, the peripheral events that shape the protective T reg cell population are unclear. We analyzed the peripheral CD4(+) T cell receptor (TCR) repertoire by cellular phenotype and location in mice with a fixed TCRbeta chain. We found that T reg (Foxp3(+)) cells showed a marked skewing of TCR usage by anatomical location in a manner similar to antigen-experienced (CD44(hi)Foxp3(-)) but not naive (CD44(lo)Foxp3(-)) cells, even though CD44(hi) and T reg cells used mostly dissimilar TCRs. This was likely unrelated to peripheral conversion, which we estimate generates only a small percentage of peripheral T reg cells in adults. Conversion was readily observed, however, during the immune response induced by Foxp3(-) cells in lymphopenic hosts. Interestingly, the converted Foxp3(+) and expanded Foxp3(-) TCR repertoires were different, suggesting that generation of Foxp3(+) cells is not an automatic process upon antigen activation of Foxp3(-) T cells. Retroviral expression of these TCRs in primary monoclonal T cells confirmed that conversion did not require prior cellular conditioning. Thus, these data demonstrate that TCR specificity plays a crucial role in the process of peripheral conversion and in shaping the peripheral T reg cell population to the local antigenic landscape.
Genomic Approaches to Lung Cancer
Authors: Roman K. Thomas, Barbara Weir, Matthew Meyerson
Journal: Clinical Cancer Research (2006)

The last decade has seen remarkable success in clinical targeting of activated oncogenes in cancer. We have applied gene expression profiling, high-density single-nucleotide polymorphism arrays, and systematic resequencing of genes to identify novel oncogenes and signaling pathways in lung cancer that might represent therapeutic targets. Systematic resequencing of tyrosine kinase genes has led to the discovery of somatic mutations in the epidermal growth factor receptor (EGFR) gene in lung adenocarcinomas. These mutations range in frequency from 10% in Caucasian to 40% in East Asian patients. Lung cancer-derived EGFR mutations are oncogenic and are tightly associated with clinical response to the EGFR kinase inhibitors erlotinib and gefitinib. Furthermore, gene expression profiling has been shown to classify patients according to their clinical outcome, indicating that the application of this technique may help in guiding patient selection for therapy in the future. Finally, genome-wide analyses of copy number gains and losses were successfully applied to detect gene amplifications and deletions. Taken together, the application of genomics technologies has led to important discoveries with clinical implications in lung cancer that might help to improve clinical care for patients suffering from this highly fatal tumor.
Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints
Authors: M D Smith
Journal: Annals of the Rheumatic Diseases (2003)

Synovial biopsies are used to study synovial immunopathology and are increasingly applied for the evaluation of new therapeutic strategies in chronic arthritis. Therefore, it is essential to be informed on the complete spectrum of synovial immunopathology.To describe the cellular content, cytokine and cell adhesion molecule expression in synovial tissue from clinically and arthroscopically normal knees.Synovial tissue was obtained from 20 normal subjects at the time of knee joint arthroscopy for unexplained knee pain. Tissue sections were studied for basic histopathology and for a range of cell surface markers, cytokines, and cell adhesion molecules by immunoperoxidase staining. Stained sections were evaluated by semiquantitative scoring and digital image analysis.Normal synovial tissue is composed predominantly of fibrofatty areolar tissue, with a variable thickness of intimal lining, composed of both CD68 positive macrophages and CD55 positive fibroblast-like synoviocytes. Interleukin 1 receptor antagonist (IL1Ra) was frequently detected in the synovial membrane of normal subjects (mean (SD) integrated optical density (IOD)=3809.6 (3893.9)), but both tumour necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta) were rarely detected. In addition, cell adhesion molecules were rarely detected in the normal synovial membrane, with the exception of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Osteoprotegerin (OPG) expression was abundant on synovial lining macrophages (mean (SD) IOD=5276 (4716) as well as endothelial cells (mean (SD) IOD=557 (226)), but receptor activator of nuclear factor kappa ligand (RANKL) expression was rarely seen.The normal synovial membrane has a variable architecture, including thickness of the lining and the subintimal cell infiltrate, with little inflammatory cytokine production or expression of cell adhesion molecules. The excess of OPG expression over RANKL and IL1Ra over IL1 may be important for protection against joint damage
<scp>l</scp> -Methionine Augments Mammalian Myocardial Contraction by Sensitizing the Myofilament to Ca <sup>2+</sup>
Authors: Yasuki Kihara, Moriaki Inoko, Shigetake Sasayama
Journal: Circulation Research (1995)

Abstract l -Methionine is an essential amino acid that has been reported to have a potent positive inotropic effect on the mammalian myocardium. We studied the mechanisms of the inotropic effect in ventricular myocardium from the rabbit. In the isolated coronary-perfused whole heart, l -methionine in a millimolar range exerted concentration-dependent positive inotropic effects on the isovolumic left ventricle, which were associated with negative lusitropic effects (prolonged time course of relaxation). The chronotropic state and the coronary perfusion pressure were not affected. These complex effects on the isolated whole heart were not blocked by pretreatment with (μmol/L) propranolol 1, prazosin 1, carbachol 3, staurosporine 1, or [Ser 1 ,Ile 8 ]angiotensin II 0.1. To further study the subcellular mechanisms, isolated ventricular papillary muscles from the same species were loaded with a bioluminescent indicator, aequorin, to monitor [Ca 2+ ] i . In the presence of 3 mmol/L l -methionine, the isometric tension showed a similar combination of the positive inotropic and negative lusitropic effects as observed in the whole heart. In contrast, the simultaneously recorded intracellular Ca 2+ signals did not increase in amplitude but instead decreased. The [Ca 2+ ] i -tension relation shifted to the left compared with that obtained in response to [Ca 2+ ] o . In saponin (250 μg/mL)–treated skinned preparations, 3 mmol/L l -methionine also shifted the force-pCa curve to the left by 0.16 pCa units. This is the first demonstration that an essential amino acid directly acts on the myofilaments and modulates their responsiveness to Ca 2+ , thereby producing a positive inotropic effect.
Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo
Authors: Vladimir R. Babaev, Sergio Fazio, Linda A. Gleaves, Kathy J. Carter, Clay F. Semenkovich, MacRae F. Linton
Journal: Journal of Clinical Investigation (1999)

Expression of lipoprotein lipase (LPL) by the macrophage has been proposed to promote foam cell formation and atherosclerosis, primarily on the basis of in vitro studies. LPL-deficient mice might provide a model for testing the role of LPL secretion by the macrophage in an in vivo system. Unfortunately, homozygous deficiency of LPL in the mouse is lethal shortly after birth. Because the fetal liver is the major site of hematopoiesis in the developing fetus, transplantation of C57BL/6 mice with LPL–/– fetal liver cells (FLCs) was used to investigate the physiologic role of macrophage LPL expression in vivo. Thirty-four female C57BL/6 mice were lethally irradiated and reconstituted with FLCs from day 14 LPL+/+, LPL+/–, and LPL–/– donors. No significant differences were detected in plasma levels of post-heparin LPL activity or in serum cholesterol or triglyceride levels between the 3 groups on either a chow diet or an atherogenic diet. After 19 weeks on the atherogenic diet, aortae were collected for quantitative analysis of the extent of aortic atherosclerosis. LPL expression was detected by immunocytochemistry and in situ hybridization in macrophages of aortic atherosclerotic lesions of LPL+/+→C57BL/6 and LPL+/–→C57BL/6 mice, but not in LPL–/–→C57BL/6 mice, whereas myocardial cells expressed LPL in all groups. The mean aortic lesion area was reduced by 55% in LPL–/–→C57BL/6 mice compared with LPL+/+→C57BL/6 mice and by 45% compared with LPL+/–→C57BL/6 mice, respectively. These data demonstrate in vivo that LPL expression by macrophages in the artery wall promotes foam cell formation and atherosclerosis.
Treat-to-target in systemic lupus erythematosus: recommendations from an international task force
Authors: Ronald F van Vollenhoven, Marta Mosca, George Bertsias, David Isenberg, Annegret Kuhn, Kirsten Lerstrøm, Martin Aringer, Hendrika Bootsma, Dimitrios Boumpas, Ian N Bruce, Ricard Cervera, Ann Clarke, Nathalie Costedoat-Chalumeau, László Czirják, Ronald Derksen, Thomas Dörner, Caroline Gordon, Winfried Graninger, Frédéric Houssiau, Murat Inanc, Søren Jacobsen, David Jayne, Anna Jedryka-Goral, Adrian Levitsky, Roger Levy, Xavier Mariette, Eric Morand, Sandra Navarra, Irmgard Neumann, Anisur Rahman, Jozef Rovenský, Josef Smolen, Carlos Vasconcelos, Alexandre Voskuyl, Anne Voss, Helena Zakharova, Asad Zoma, Matthias Schneider
Journal: Annals of the Rheumatic Diseases (2014)

The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.
Neuroprotective Effect of Vitamin E Supplementation in Patients Treated With Cisplatin Chemotherapy
Authors: Andrea Pace, Antonella Savarese, Mauro Picardo, Vittoria Maresca, Umberto Pacetti, Girolamo Del Monte, Annamaria Biroccio, Carlo Leonetti, Bruno Jandolo, Francesco Cognetti, Loredana Bove
Journal: Journal of Clinical Oncology (2003)

The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy.Between April 1999 and October 2000, forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E.Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P <.01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P <.01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone.Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.
Induction of Ornithine Decarboxylase Activity Is a Necessary Step for Mitogen-Activated Protein Kinase Kinase–Induced Skin Tumorigenesis
Authors: David J. Feith, David K. Bol, Joan M. Carboni, Mark J. Lynch, Suzanne Sass-Kuhn, Paula L. Shoop, Lisa M. Shantz
Journal: Cancer Research (2005)

A transgenic mouse line overexpressing a constitutively active mutant of MEK1, a downstream effector of Ras, driven by the keratin 14 (K14) promoter, has been used to test the hypothesis that ornithine decarboxylase (ODC) induction during tumor promotion following a single initiating event [i.e., the activation of the Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) pathway], is a necessary step in skin carcinogenesis. K14-MEK mice exhibit moderate hyperplasia, with spontaneous skin tumor development within 5 weeks of birth. Analysis of epidermis and dermis showed induction of MEK protein and ERK1/ERK2 phosphorylation, but no change in Akt-1, suggesting that the PI 3-kinase pathway, another pathway downstream of ras, is not activated. Examination of tumors revealed high levels of ODC protein and activity, indicating that activation of signaling cascades dependent on MEK activity is a sufficient stimulus for ODC induction. When K14-MEK mice were given alpha-difluoromethylornithine (DFMO), a suicide inactivator of ODC, in the drinking water from birth, there was a dramatic delay in the onset of tumor growth ( approximately 6 weeks), and only 25% of DFMO-treated mice developed tumors by 15 weeks of age. All untreated K14-MEK mice developed tumors by 6 weeks of age. Treatment of tumor-bearing mice with DFMO reduced both tumor size and tumor number within several weeks. Tumor regression was the result of both inhibition of proliferation and increased apoptosis in tumors. The results establish ODC activation as an important component of the Raf/MEK/ERK pathway, and identify K14-MEK mice as a valuable model with which to study the regulation of ODC in ras carcinogenesis.
Human-human hybridoma autoantibodies with both anti-DNA and rheumatoid factor activities.
Authors: J Rauch, H Tannenbaum, K Straaton, H Massicotte, J Wild
Journal: Journal of Clinical Investigation (1986)

Human hybridomas have been produced by fusing peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with the GM 4672 human cell line. 262 hybridoma clones from the fusions of four RA and five SLE patients were screened for binding to denatured DNA (dDNA), native DNA, and the Fc fragment of human IgG (HIgG). Of the 17 hybridoma antibodies (nine RA, eight SLE) selected for strong binding to denatured DNA, Fc, or both, five reacted with dDNA only, one with Fc only, and eight with both dDNA and Fc. Hybridoma supernatants exhibiting dual reactivity were absorbed over HIgG and bovine serum albumin (BSA)-Sepharose immunoabsorbent columns. The reactivities to both DNA and HIgG were completely removed by the HIgG column but unaffected by passage over the BSA column, and both DNA binding and rheumatoid factor activities were recovered in the acid eluates from the Sepharose-IgG column. The binding of dual reactive hybridoma autoantibodies to the Fc fragment of HIgG was specifically competed by dDNA and HIgG, providing additional evidence that one antibody may be capable of reacting both as a rheumatoid factor and as an anti-DNA antibody.
CHARACTERIZATION OF GLYCOSYLPHOSPHATIDYLINOSITIOL-ANCHORED, SECRETED, AND INTRACELLULAR VERTEBRATE MONO-ADP-RIBOSYLTRANSFERASES
Authors: Ian J. Okazaki, Joel Moss
Journal: Annual Review of Nutrition (1999)

▪ Abstract Mono-ADP-ribosylation is a posttranslational modification of proteins in which the ADP-ribose moiety of nicotinamide adenine dinucleotide is transferred to an acceptor amino acid. Five mammalian ADP-ribosyltransferases (ART1–ART5) have been cloned and expression is restricted to tissues such as cardiac and skeletal muscle, leukocytes, brain, and testis. ART1 and ART2 are glycosylphosphatidylinositol (GPI)-anchored ectoenzymes. ART5 appears not to be GPI-linked and may be secreted. In skeletal muscle and lymphocytes, ART1 modifies specific members of the integrin family of adhesion molecules, suggesting that ADP-ribosylation affects cell-matrix or cell-cell interactions. In lymphocytes, ADP-ribosylation of surface proteins is associated with changes in p56 lck tyrosine kinase-mediated signaling. The catalytic sites of bacterial toxins and vertebrate transferases have conserved structural features, consistent with a common reaction mechanism. ADP-ribosylation can be reversed by ADP-ribosylarginine hydrolases, resulting in the regeneration of free arginine. Thus, an ADP-ribosylation cycle may play a regulatory role in vertebrate tissues.
RADIUM IN THE TREATMENT OF CARCINOMA CERVICIS AND INTRACTABLE MENORRHAGIA
Authors: E. F. Murray
Journal: BMJ (1928)

<h3>Abstract</h3> Recent single-cell multi-modal data reveal multi-scale characteristics of single cells, such as transcriptomics, morphology, and electrophysiology. However, our understanding of functional genomics and gene regulation leading to various cellular characteristics remains elusive. To address this, we applied multiple machine learning methods to align gene expression and electrophysiological data of single neuronal cells in the mouse brain. We found that nonlinear manifold learning outperforms other methods. After manifold alignment, the cell clusters highly correspond to transcriptomic and morphological cell-types, suggesting a strong nonlinear relationship between gene expression and electrophysiology at the cell-type level. The aligned cells form developmental trajectories and show continuous changes of electrophysiological features, implying the underlying developmental process. We also found that the manifold-aligned cell clusters’ differentially expressed genes can predict many electrophysiological features. Functional enrichment and gene regulatory network analyses for those cell clusters revealed potential genome functions and molecular mechanisms from gene expression to neuronal electrophysiology.