tbuckley/cabot-search huggingface dataset:
Truncal Pruritus of Unknown Origin May Be a Symptom of Diabetic Polyneuropathy
Authors: Hiroyuki Yamaoka, Hideyuki Sasaki, Hiroshi Yamasaki, Kenichi Ogawa, Takayuki Ohta, Hiroto Furuta, Masahiro Nishi, Kishio Nanjo
Journal: Diabetes Care (2009)

OBJECTIVE Our goal was to ascertain the prevalence of pruritus in diabetic and nondiabetic subjects and the relevance of symptoms, signs, and nerve functions of diabetic polyneuropathy (DPN) of pruritus. RESEARCH DESIGN AND METHODS A large-scale survey of 2,656 diabetic outpatients and 499 nondiabetic subjects was performed. In diabetic subjects, the relationship between pruritus and age, sex, diabetic duration, A1C, Achilles tendon reflex (ATR), and abnormal sensation in legs was evaluated. In 105 diabetic subjects, nerve conduction studies, quantitative vibratory threshold (QVT), heart rate variability, and a fall of systolic blood pressure at a head-up tilt test (ΔBP) were performed, and the relationships between pruritus and nerve functions were evaluated. RESULTS Although the prevalence of truncal pruritus of unknown origin (TPUO) in diabetic subjects was significantly higher than that in age-matched nondiabetic subjects (11.3 vs. 2.9%, P = 0.0001), the prevalence of other pruritus was not different between the two groups. Multiple logistic regression analysis revealed that abnormal sensation and ATR areflexia were independent risk factors for TPUO in age, sex, duration of diabetes, and A1C. ΔBP in diabetic subjects with TPUO was significantly impaired compared with that in those without TPUO. Larger ΔBP was identified as a significant risk factor of TPUO independent of other nerve dysfunctions by multiple logistic regression analysis. CONCLUSIONS TPUO is significantly more frequent in diabetic than in nondiabetic individuals. TPUO is significantly associated with symptoms and signs of DPN, including impaired blood pressure response in a head-up tilt test. TPUO, therefore, might be a newly recognized symptom of DPN.
Recombinant Surfactant Protein C–based Surfactant for Patients with Severe Direct Lung Injury
Authors: Roger G Spragg, Friedemann J H Taut, James F Lewis, Peter Schenk, Clemens Ruppert, Nathan Dean, Kenneth Krell, Andreas Karabinis, Andreas Günther
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Patients with acute lung injury have impaired function of the lung surfactant system. Prior clinical trials have shown that treatment with exogenous recombinant surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation and have suggested that treatment of patients with severe direct lung injury may decrease mortality.Determine the clinical benefit of administering an rSP-C-based synthetic surfactant to patients with severe direct lung injury due to pneumonia or aspiration.A prospective randomized blinded study was performed at 161 centers in 22 countries. Patients were randomly allocated to receive usual care plus up to eight doses of rSP-C surfactant administered over 96 hours (n = 419) or only usual care (n = 424).Mortality to 28 days after treatment, the requirement for mechanical ventilation, and the number of nonpulmonary organ failure-free days were not different between study groups. In contrast to prior studies, there was no improvement in oxygenation in patients receiving surfactant compared with the usual care group. Investigation of the possible reasons underlying the lack of efficacy suggested a partial inactivation of rSP-C surfactant caused by a step of the resuspension process that was introduced with this study.In this study, rSP-C-based surfactant was of no clinical benefit to patients with severe direct lung injury. The unexpected lack of improvement in oxygenation, coupled with the results of in vitro tests, suggest that the administered suspension may have had insufficient surface activity to achieve clinical benefit.
Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma
Authors: P. Bhavsar, N. Khorasani, M. Hew, M. Johnson, K. F. Chung
Journal: European Respiratory Journal (2009)

Patients with severe asthma respond less well to corticosteroids than those with non-severe asthma. Increased p38 mitogen-activated protein kinase (MAPK) activation in alveolar macrophages (AMs) from severe asthma patients has been associated with a reduced inhibition of cytokine release by dexamethasone. We determined whether p38 MAPK inhibitors would modulate corticosteroid suppression of cytokine release from AMs and peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from venous blood and AMs by bronchoalveolar lavage in severe and non-severe asthma patients. PBMCs and AMs were exposed to lipopolysaccharide (LPS) with and without the p38 MAPK inhibitor, SD282, or dexamethasone. We determined the concentration-dependent effects of another p38 MAPK inhibitor, GW-A, on dexamethasone-induced inhibition of interleukin (IL)-8 release from PBMCs. Cytokines were assayed using an ELISA-based method. SD282 (10 −7 M), with dexamethasone (10 −6 M), caused a greater inhibition of release of IL-1β, IL-6, macrophage inflammatory protein-1α and IL-10, than with dexamethasone alone in AMs from severe and non-severe asthma. At 10 −9 and 10 −10 M, GW-A, that had no direct effects, increased the inhibitory activity of dexamethasone (10 −8 and 10 −6 M) on LPS-induced IL-8 release in PBMCs from severe asthma. Corticosteroid insensitivity in severe asthma patients may be improved by inhibitors of p38 MAPK.
Physiological effects and optimisation of nasal assist-control ventilation for patients with chronic obstructive pulmonary disease in respiratory failure
Authors: C. Girault, V. Chevron, J. C. Richard, I. Daudenthun, P. Pasquis, J. Leroy, G. Bonmarchand
Journal: Thorax (1997)

BACKGROUND: A study was undertaken to investigate the effects of non-invasive assist-control ventilation (ACV) by nasal mask on respiratory physiological parameters and comfort in acute on chronic respiratory failure (ACRF). METHODS: Fifteen patients with chronic obstructive pulmonary disease (COPD) were prospectively and randomly assigned to two non-invasive ventilation (NIV) sequences in spontaneous breathing (SB) and ACV mode. ACV settings were always optimised and therefore subsequently adjusted according to patient9s tolerance and air leaks. RESULTS: ACV significantly decreased all the total inspiratory work of breathing (WOBinsp) parameters, pressure time product, and oesophageal pressure variation in comparison with SB mode. The ACV mode also resulted in a significant reduction in surface diaphragmatic electromyographic activity to 36% of the control values and significantly improved the breathing pattern. SB did not change the arterial blood gas tensions from baseline values whereas ACV significantly improved both the PaO2 from a mean (SD) of 8.45 (2.95) kPa to 13.31 (2.15) kPa, PaCO2 from 9.52 (1.61) kPa to 7.39 (1.39) kPa, and the pH from 7.32 (0.03) to 7.40 (0.07). The respiratory comfort was significantly lower with ACV than with SB. CONCLUSIONS: This study shows that the clinical benefit of non-invasive ACV in the management of ACRF in patients with COPD results in a reduced inspiratory muscle activity providing an improvement in breathing pattern and gas exchange. Despite respiratory discomfort, the muscle rest provided appears sufficient when ACV settings are optimised.
Infections of the Central Nervous System
Authors: G C Townsend, W M Scheld
Journal: Annals of Internal Medicine (1991)

Part 1 Viral infections of the central nervous system and related disorders: pathogenesis and pathophysiology of viral infections of the central nervous system, M. Schlitt et al viral meningitis and the aseptic meningitis syndrom, H.A. Rotbart encephalitis caused by herpesviruses, including B virus, R.J. Whitley and M. Schlitt arthropod-borne encephalitides, R.J. Whitley meningitis and encephalitis caused by mumps virus, J.W. Gnann, Jr et al slow viral infections of the human nervous system, D.M. Asher perinatal viral infections R.J. Whitley and S. Stagno neurological manifestations of infection with the human immunodeficiency viruses, B.K. Evans et al viral vaccines that protect the central nervous system, M.F. Mangano and S.A. Plotkin Guillain-Barre syndrome, G. Tenorio et al. Part 2 Mycoplasmal infections of the central nervous system: mycoplasmal diseases of the central nervous system, W.A. Clyde, Jr. Part 3 Bacterial infections of the central nervous system: pathogenesis and pathophysiology of bacterial infections of the central nervous system, A.R. Tunkel and W.M. Scheld neonatal bacterial meningitis, A.L. Smith and J. Haas acute bacterial meningitis in children and adults, K.L. Roos et al rickettsiae and the central nervous system, J.H. Kim and D.T. Durack tuberculosis of the central nervous system, A. Zuger and F.D. Lowy brain abscess, B. Wispelwey et al subdural empyema, D.C. Hefgott et al epidural abscess, B.G. Gellin et al central nervous system complications of infective endocarditis, P. Francioli infections of the cerebrospinal fluid shunts, B.A. Kaufman and D.G. McLone. Part 4 Central nervous system syndromes mediated by bacterial toxins: botulism, J.M. Hughes tetanus, T.P. Bleck bordetella pertussis and the central nervous system, E.L. Hewlett. Part 5 Spriochetal infections of the central nervous system: central nervous system syphilis, E.W. Hook, III Lyme disease, L. Reik, Jr. Part 6 Fungal infections of the central nervous system: pathogenesis and pathophysiology of fungal infections, J. R. Perfect and D.T. Durack chronic meningitis, T. Tucker and J.J. Ellner diagnosis and treatment of fungal meningitis, J.R. Perfect space-occupying fungal lesions of the central nervous system, K. Sepkowitz and D. Armstrong. Part 7 Protozoal and helminthic infections of the central nervous system: protozoal infections, J.P. Cegielski and D.T. Durack toxoplasmosis, C.S. Dukes et al helminthic infections, M.L. Cameron and D.T. Durack.
Neural blackboard architectures of combinatorial structures in cognition
Authors: Frank van der Velde, Marc de Kamps
Journal: Behavioral and Brain Sciences (2006)

Human cognition is unique in the way in which it relies on combinatorial (or compositional) structures. Language provides ample evidence for the existence of combinatorial structures, but they can also be found in visual cognition. To understand the neural basis of human cognition, it is therefore essential to understand how combinatorial structures can be instantiated in neural terms. In his recent book on the foundations of language, Jackendoff described four fundamental problems for a neural instantiation of combinatorial structures: the massiveness of the binding problem, the problem of 2, the problem of variables, and the transformation of combinatorial structures from working memory to long-term memory. This paper aims to show that these problems can be solved by means of neural “blackboard” architectures. For this purpose, a neural blackboard architecture for sentence structure is presented. In this architecture, neural structures that encode for words are temporarily bound in a manner that preserves the structure of the sentence. It is shown that the architecture solves the four problems presented by Jackendoff. The ability of the architecture to instantiate sentence structures is illustrated with examples of sentence complexity observed in human language performance. Similarities exist between the architecture for sentence structure and blackboard architectures for combinatorial structures in visual cognition, derived from the structure of the visual cortex. These architectures are briefly discussed, together with an example of a combinatorial structure in which the blackboard architectures for language and vision are combined. In this way, the architecture for language is grounded in perception. Perspectives and potential developments of the architectures are discussed.
Importin-β mediates Cdc7 nuclear import by binding to Kinase Insert II, which can be antagonized by importin-α
Authors: Byung Ju Kim, Hoyun Lee
Journal: Cancer Research (2006)

4899   The Cdc7-Dbf4 kinase (aka, DDK for Dbf4-dependent kinase) functions as a molecular switch connecting cell cycle engine (Cdks) and the replication machinery, and is essential for the activation of DNA replication throughout S phase. However, excessive levels of Cdc7 can elevate mutation rates or cause abnormal cell-cycle arrest, which may lead to genome instability and, eventually, to tumorigenesis. To be functional, both the catalytic Cdc7 and regulatory Dbf4 subunits must be located in the nucleus. The nuclear import of Dbf4 protein is mediated by the classical importin-α/-β pathway. However, it is currently unknown about how Cdc7 is translocated into the nucleus. Since Cdc7 does not contain any known nuclear localization sequence, it was initially suggested that Cdc7 may be imported into the nucleus by Dbf4. However, we and others subsequently found that Cdc7 is nuclear localized even when Dbf4 is not produced. Here, we report that importin-β directly binds to the Kinase insert II domain of human Cdc7, and promotes its nuclear import. Interestingly, both importin-α and -β can bind to Cdc7 through the Kinase Insert II. However, the binding affinity of Cdc7 for the importin-β is considerably higher than for importin-α at low protein concentrations. Immunodepletion of importin-β, but not importin-α, abrogates Cdc7 nuclear import in digitonin-permeabilized cells. Adding purified recombinant importin-β, but not importin-α, to the importin-depleted cytosol restores Cdc7 nuclear import. Furthermore, transduction of anti-importin-β antibodies, but not -importin-α antibodies, into live cells inhibits Cdc7 nuclear import. Most interestingly, we have found that the importin-β mediated Cdc7 nuclear import is inhibited by competitive binding of Cdc7 by importin-α. This inhibition of Cdc7 nuclear import by importin-α is independent of its ability to bind to importin-β. Thus, the role of importin-α in the Cdc7 nuclear localization regulation is exactly opposite to its role in the classical nuclear import of proteins containing a nuclear localization sequence. This paper, for the first time, reports a mechanism of how importin-α can impede importin-β-mediated protein nuclear import.
Target-Treatment and Patients' Selection: Can We Still Neglect the Timing of Tissue Collection?
Authors: Tommaso De Pas, Carlo Putzu, Giuseppe Pelosi, Giuseppe Curigliano, Cristina Noberasco, Giulia Zampino, Nicola Fazio, Vincenzo Formica, Lorenzo Spaggiari, Filippo de Braud
Journal: Journal of Clinical Oncology (2005)
Focal neurological deficits after trauma
Authors: R. Nandhagopal
Journal: BMJ (2014)

A 38 year old woman developed headache (without neck pain) and weakness of her left upper and lower limbs after a concussive head trauma with scalp lacerations in a motor vehicle crash. On examination (more than 4.5 hours after the trauma), she was conscious, alert, and in cardiac sinus rhythm. There was no carotid bruit. She scored 7 points on the National Institute of Health stroke scale (maximum possible score 42). Positive neurological findings included mild blunting of the left nasolabial fold; left hemiparesis, with extensor muscles being weaker (3/5) than flexors in the left upper limb (4+/5), flexors being weaker (4 to 4+/5) than extensors in the left lower limb (4+ to 5/5), and distal more than proximal weakness in the left arm and leg. She also had brisk deep tendon reflexes in the limbs on the left side; a left extensor plantar response; left hemianopia; and left hemisensory (including the face) hypoaesthesia for pain, cold, and touch. Eyelid ptosis or paresis of extraocular movements were not present, and pupillary size and light reaction were normal. She had no history of hypertension, diabetes, cigarette smoking, polyarthritis, stroke, or cardiac disease. Plain computed tomography of the brain did not detect acute parenchymal or extraparenchymal injury. In view of her persistent left hemiparesis, she underwent cranial magnetic resonance imaging (fig 1A-E⇓) and computed tomographic cerebral angiography (fig 1F) two days after the trauma. Fig 1 (A-E) Cranial magnetic resonance imaging. (A) Diffusion weighted image. (B) Corresponding apparent diffusion coefficient map. (C) Axial fluid attenuated inversion recovery sequence. (D) Susceptibility weighted image. (E) Fluid attenuated inversion recovery image of the skull base with fat suppression. (F) Computed tomographic angiogram of the cervical portion of the carotid and vertebral arteries
Recombinant Human Erythropoietin Antagonizes Trastuzumab Treatment of Breast Cancer Cells via Jak2-Mediated Src Activation and PTEN Inactivation
Authors: Ke Liang, Francisco J. Esteva, Constance Albarracin, Katherine Stemke-Hale, Yang Lu, Giampaolo Bianchini, Ching-Yi Yang, Yong Li, Xinqun Li, Chun-Te Chen, Gordon B. Mills, Gabriel N. Hortobagyi, John Mendelsohn, Mien-Chie Hung, Zhen Fan
Journal: Cancer Cell (2010)
Comparison of Different Models of Diabetes Care on Compliance with Self-Monitoring of Blood Glucose by Memory Glucometer
Authors: Penelope L Hoskins, Jan B Alford, David J Handelsman, Dennis K Yue, John R Turtle
Journal: Diabetes Care (1988)

The modern management of diabetes relies heavily on self-monitoring of blood glucose (SMBG), and therefore SMBG records are an important source of clinical data for management decision making. The development of a memory Glucometer has provided the opportunity to verify the validity of glucose records thus generated and observe the effects of different educational approaches on compliance with SMBG. Thirty-four patients without previous experience of SMBG were randomized into one of the following experimental groups differing in the model of diabetes care: mutual decision making, didactic, and authoritarian. Patients, unaware of the memory capacity of the glucose meter, were required to perform four glucose measurements per day over a 14-day observation period. Patient-generated blood glucose records were then compared with objective records stored in the glucose-meter memory. Patients with gestational diabetes mellitus recorded a lower proportion of correct results (63 vs. 79%, P = .049) and exhibited a tendency to invent results with lower blood glucose levels (5.3 vs. 7.5 mM, P &amp;lt; .0001) than the results omitted compared with patients with non-insulin-dependent diabetes mellitus. Predictors of greater validity of records were perceived intelligence of the subject (χ2 = 4.56, P &amp;lt; .02) and private health-insurance status (χ2 = 4.52, P &amp;lt; .04), whereas the experimental group assignment was not significant. These findings reflect potential motivational and sociodemographic limitations in the validity of SMBG recordings within the management and education of patients with gestational and nongestational diabetes.
Induction of Autoimmune Myocarditis in Interleukin-2–Deficient Mice
Authors: Gerhard Grässl, Christian L. Pummerer, Ivan Horak, Nikolaus Neu
Journal: Circulation (1997)

Background Interleukin (IL)-2 is an important growth and survival factor for T cells and plays a crucial role in inflammation. Myosin-induced myocarditis is strictly dependent on activated T cells and is a model for postinfectious inflammatory heart disease in humans. To explore the role of IL-2 in myocarditis, we injected mice genetically deficient for IL-2 with cardiac myosin. Because it is conceivable that the lack of IL-2 either promotes or ameliorates the disease, we selected mouse strains that differ in their susceptibility to cardiac myosin–induced myocarditis. Methods and Results Mice from a susceptible strain (C3H) that were rendered IL-2 deficient by gene targeting (IL-2 −/ − mice) and littermate controls were immunized twice with purified cardiac myosin at a 7-day interval. Three weeks after the first immunization, hearts were obtained for histopathological and immunohistochemical analysis. Sera were tested for autoantibodies to the cardiac myosin isoform by enzyme-linked immunosorbent assay. The majority of C3H IL-2 −/ − mice developed severe myocarditis accompanied by high-titer myosin autoantibodies. In C57BL/6 mice, which develop only little myocarditis on myosin immunization, lack of IL-2 did not increase susceptibility to the disease. Moreover, the composition of the inflammatory infiltrate in C3H IL-2 −/ − mice was virtually identical to that seen in the wild-type strain. Conclusions Our data provide the first genetic evidence that in cardiac myosin–immunized mice, IL-2 has no essential role for the development of autoimmune heart disease and the generation of myosin autoantibodies.
microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder
Authors: Diana O Perkins, Clark D Jeffries, L Fredrik Jarskog, J Michael Thomson, Keith Woods, Martin A Newman, Joel S Parker, Jianping Jin, Scott M Hammond
Journal: Genome biology (2007)

Abstract Background microRNAs (miRNAs) are small, noncoding RNA molecules that are now thought to regulate the expression of many mRNAs. They have been implicated in the etiology of a variety of complex diseases, including Tourette's syndrome, Fragile × syndrome, and several types of cancer. Results We hypothesized that schizophrenia might be associated with altered miRNA profiles. To investigate this possibility we compared the expression of 264 human miRNAs from postmortem prefrontal cortex tissue of individuals with schizophrenia ( n = 13) or schizoaffective disorder ( n = 2) to tissue of 21 psychiatrically unaffected individuals using a custom miRNA microarray. Allowing a 5% false discovery rate, we found that 16 miRNAs were differentially expressed in prefrontal cortex of patient subjects, with 15 expressed at lower levels (fold change 0.63 to 0.89) and 1 at a higher level (fold change 1.77) than in the psychiatrically unaffected comparison subjects. The expression levels of 12 selected miRNAs were also determined by quantitative RT-PCR in our lab. For the eight miRNAs distinguished by being expressed at lower microarray levels in schizophrenia samples versus comparison samples, seven were also expressed at lower levels with quantitative RT-PCR. Conclusion This study is the first to find altered miRNA profiles in postmortem prefrontal cortex from schizophrenia patients.
Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007–2011
Authors: Catherine A Ison, Katy Town, Chinelo Obi, Stephanie Chisholm, Gwenda Hughes, David M Livermore, Catherine M Lowndes
Journal: The Lancet Infectious Diseases (2013)
Protein Glycosylation in Cancer
Authors: Sean R. Stowell, Tongzhong Ju, Richard D. Cummings
Journal: Annual Review of Pathology Mechanisms of Disease (2015)

Neoplastic transformation results in a wide variety of cellular alterations that impact the growth, survival, and general behavior of affected tissue. Although genetic alterations underpin the development of neoplastic disease, epigenetic changes can exert an equally significant effect on neoplastic transformation. Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of neoplastic progression. Alterations in glycosylation appear to not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Many of these changes may support neoplastic progression, and unique alterations in tumor-associated glycosylation may also serve as a distinct feature of cancer cells and therefore provide novel diagnostic and even therapeutic targets.