tbuckley/cabot-search huggingface dataset:
Allergic rhinoconjunctivitis in children
Authors: Hans de Groot, Paul L P Brand, Wytske F Fokkens, Marjolein Y Berger
Journal: BMJ (2007)

Allergic rhinoconjunctivitis is a common chronic disorder in children, especially in developed countries. It does not cause nasal symptoms only (such as congestion and sneezing) but may also cause general complaints such as fatigue and cough (box 1). It can also cause learning problems1 and has a great impact on quality of life. Uncontrolled allergic rhinoconjunctivtis may aggravate the symptoms of asthma.2 Although classic "hay fever" is easily recognised in children who have a runny nose, sneezing, and itchy eyes during the pollen season, the diagnosis of allergic rhinoconjunctivitis is often missed in children with perennial nasal congestion. #### Box 1: Key symptoms of allergic rhinoconjunctivitis in children ##### Nasal ##### General The term allergic rhinoconjunctivitis is preferable to allergic rhinitis because most patients also have ocular symptoms. In this review, we discuss the prevalence of allergic rhinoconjunctivitis in children, its causes, how it is diagnosed, and how it can be treated. We used the Cochrane library to identify relevant systematic reviews on drugs for allergic rhinoconjunctivitis in children. Medline was searched for systematic reviews on diagnosis and treatment of allergic rhinoconjunctivitis in children using the keywords "rhinoconjunctivitis", "systematic review", "meta-analysis", "diagnosis", and "treatment". We limited our searches to "all child". We took additional references from our personal files. #### SUMMARY POINTS
Factors Controlling Nanoparticle Pharmacokinetics: An Integrated Analysis and Perspective
Authors: S.M. Moghimi, A.C. Hunter, T.L. Andresen
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Intravenously injected nanoparticulate drug carriers provide a wide range of unique opportunities for site-specific targeting of therapeutic agents to many areas within the vasculature and beyond. Pharmacokinetics and biodistribution of these carriers are controlled by a complex array of interrelated core and interfacial physicochemical and biological factors. Pertinent to realizing therapeutic goals, definitive maps that establish the interdependency of nanoparticle size, shape, and surface characteristics in relation to interfacial forces, biodistribution, controlled drug release, excretion, and adverse effects must be outlined. These concepts are critically evaluated and an integrated perspective is provided on the basis of the recent application of nanoscience approaches to nanocarrier design and engineering. The future of this exciting field is bright; some regulatory-approved products are already on the market and many are in late-phase clinical trials. With concomitant advances in extensive computational knowledge of the genomics and epigenomics of interindividual variations in drug responses, the boundaries toward development of personalized nanomedicines can be pushed further.
LRP1 is critical for the surface distribution and internalization of the NR2B NMDA receptor subtype
Authors: Wladislaw Maier, Mariola Bednorz, Sabrina Meister, Anton Roebroek, Sascha Weggen, Ulrich Schmitt, Claus U Pietrzik
Journal: Molecular Neurodegeneration (2013)

Abstract Background The N-methyl-D-aspartate receptors are key mediators of excitatory transmission and are implicated in many forms of synaptic plasticity. These receptors are heterotetrameres consisting of two obligatory NR1 and two regulatory subunits, usually NR2A or NR2B. The NR2B subunits are abundant in the early postnatal brain, while the NR2A/NR2B ratio increases during early postnatal development. This shift is driven by NMDA receptor activity. A functional interplay of the Low Density Lipoprotein Receptor Related Protein 1 (LRP1) NMDA receptor has already been reported. Such abilities as interaction of LRP1 with NMDA receptor subunits or its important role in tPa-mediated NMDA receptor signaling were already demonstrated. Moreover, mice harboring a conditional neuronal knock-out mutation of the entire Lrp1 gene display NMDA-associated behavioral changes. However, the exact role of LRP1 on NMDA receptor function remains still elusive. Results To provide a mechanistic explanation for such effects we investigated whether an inactivating knock-in mutation into the NPxY2 motif of LRP1 might influence the cell surface expression of LRP1 and NMDA receptors in primary cortical neurons. Here we demonstrate that a knock-in into the NPxY2 motif of LRP1 results in an increased surface expression of LRP1 and NR2B NMDA receptor subunit due to reduced endocytosis rates of LRP1 and the NR2B subunit in primary neurons derived from LRP1ΔNPxY2 animals. Furthermore, we demonstrate an altered phosphorylation pattern of S1480 and Y1472 in the NR2B subunit at the surface of LRP1ΔNPxY2 neurons, while the respective kinases Fyn and casein kinase II are not differently regulated compared with wild type controls. Performing co-immunoprecipitation experiments we demonstrate that binding of LRP1 to NR2B might be linked by PSD95, is phosphorylation dependent and this regulation mechanism is impaired in LRP1ΔNPxY2 neurons. Finally, we demonstrate hyperactivity and changes in spatial and reversal learning in LRP1ΔNPxY2 mice, confirming the mechanistic interaction in a physiological readout. Conclusions In summary, our data demonstrate that LRP1 plays a critical role in the regulation of NR2B expression at the cell surface and may provide a mechanistic explanation for the behavioral abnormalities detected in neuronal LRP1 knock-out animals reported earlier.
Transferable Drug Resistance (R Factor) in Enteric Bacteria: Relationship to Nosocomial Infections.
Authors: Theodore C. Salzman
Journal: Annals of Internal Medicine (1967)

s1 May 1967Transferable Drug Resistance (R Factor) in Enteric Bacteria: Relationship to Nosocomial Infections.Theodore C. Salzman, M.D.Theodore C. Salzman, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1048_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAntibiotic-resistant enteric bacteria (Escherichia coli, Klebsiella-Aerobacter-Serratia, Salmonella, and Shigella) can transfer resistance to sensitive bacteria during bacterial conjugation (mating). The genetic element, responsible for both mating and resistance, is extrachromosomal deoxyribonucleic acid, known as an R factor. Genes responsible for resistance to ampicillin, tetracyclines, chloramphenicol, kanamycin, streptomycin, and sulfonamides may be linked on a single R factor.Nosocomial infections with antibiotic-resistantE. coliandKlebsiella-Aerobacter-Serratiaare common at our hospital. In the resistant bacteria causing these infections, 27% of the ampicillin, 72% of the tetracycline, 91% of the chloramphenicol, 72% of the streptomycin, and 81% of the kanamycin resistance were... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAntibiotic Resistance in Intestinal BacteriaInfectious diseases. Annual review of significant publications. 1 May 1967Volume 66, Issue 5Page: 1048-1048KeywordsBacteriaChloramphenicolGeneticsNosocomial infectionsSalmonellaShigellaStreptococcal infectionsStreptomycinSulfonamideTetracyclines Issue Published: 1 May 1967 PDF downloadLoading ...
Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease
Authors: P Ljubuncic
Journal: Gut (2000)

<h3>BACKGROUND</h3> There is considerable evidence indicating that the severity of hepatic damage in individuals with cholestatic liver disease is causally associated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid peroxidation have been reported in the plasma of individuals with chronic liver disease and animal models of liver disease. Hence, by virtue of their increased presence in the circulation, it is not unreasonable to suppose that they may account for extrahepatic tissue damage in chronic liver disease. <h3>MATERIALS AND METHODS</h3> This hypothesis was tested by determining plasma levels of the ubiquitous antioxidant glutathione (GSH) and lipid peroxides (LP), together with assessment of the extent of lipid peroxidation in the kidney, brain, and heart, in 24 day chronically bile duct ligated (CBDL) rats. The extent of lipid peroxidation in tissues was based on measurement of conjugated dienes, lipid peroxides, and malondialdehyde (MDA) content. Data were compared with identical data collected from unoperated control, pair fed, 24 day bile duct manipulated (sham operated), and pair fed sham operated rats. <h3>RESULTS</h3> In CBDL rats, total and reduced plasma GSH levels were almost half those determined in all control rats. Plasma, kidney, and heart LP levels were significantly increased in CBDL rats compared with controls. MDA levels were significantly higher in the kidney, brain, and heart homogenates prepared from CBDL rats compared with MDA content measured in tissue homogenates prepared from the four groups of control rats. <h3>CONCLUSIONS</h3> Our data show that experimental cholestatic liver disease is associated with increased lipid peroxidation in the kidney, brain, and heart. Hence we have concluded that the oxidative stress in cholestatic liver disease is a systemic phenomenon probably encompassing all tissues and organs, even those separated by the blood-brain barrier.
Kaposi's sarcoma, angioimmunoblastic lymphadenopathy, and antibody to HIV-1 p24 antigen in a patient nonreactive for HIV-1 with use of ELISA
Authors: Thomas N. Helm, Willard D. Steck, Max R. Proffitt, Wilma F. Bergfeld, Raymond R. Tubbs, Jacob Lo
Journal: Journal of the American Academy of Dermatology (1990)
Nested sets theory, full stop: Explaining performance on Bayesian inference tasks without dual-systems assumptions
Authors: David R. Mandel
Journal: Behavioral and Brain Sciences (2007)

Abstract Consistent with Barbey &amp; Sloman (B&amp;S), it is proposed that performance on Bayesian inference tasks is well explained by nested sets theory (NST). However, contrary to those authors' view, it is proposed that NST does better by dispelling with dual-systems assumptions. This article examines why, and sketches out a series of NST's core principles, which were not previously defined.
Inverse Relationship of Perinatal Complications and Eye Tracking Dysfunction in Relatives of Patients With Schizophrenia: Evidence for a Two-Factor Model
Authors: Dennis K. Kinney, Deborah L. Levy, Deborah A. Yurgelun-Todd, Sharon J. Tramer, Philip S. Holzman
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Because both smooth pursuit eye tracking dysfunction and obstetrical complications are significant risk factors for schizophrenia, the authors tested the predictions of a two-factor model of how eye tracking dysfunction and obstetrical complications covary in patients with schizophrenia, their siblings, and comparison subjects. METHOD: Psychiatric diagnoses, eye tracking dysfunction, and obstetrical complications noted in birth records were independently assessed in 18 patients with schizophrenia, 16 of their siblings without schizophrenia, and 49 comparison subjects with neither personal nor family histories of schizophrenia. RESULTS: As hypothesized, 1) the combination of eye tracking dysfunction and perinatal obstetrical complications discriminated patients with schizophrenia significantly from subjects without schizophrenia, including siblings of patients with schizophrenia, and 2) eye tracking dysfunction and perinatal obstetrical complications manifested a significant inverse association in the nonschizophrenic siblings of patients with schizophrenia. CONCLUSIONS: These results support a two-factor model in which obstetrical complications often interact with genetic liability, indicated by eye tracking dysfunction, to produce schizophrenia. (Am J Psychiatry 1998; 155:976–978)
Pressure Therapy for Hypertrophic Scarring: Preliminary Communication
Authors: J C Robertson, B Hodgson, J E Druett, Jane Druett
Journal: Journal of the Royal Society of Medicine (1980)

A six-point programme for the prevention and pressure therapy of hypertrophic scarring started in 1975 at Odstock Hospital. The work reported here includes a pressure calibration of batches of the material chosen for pressure bandaging; a pressure study of the bandages on volunteers’ limbs; and the formation of a pressure therapy clinic. The clinic results were similar to those reported by Thomson (1974) and were considered sufficiently favourable to justify continuing the clinic and instituting a policy of close review and early therapy for all burns patients. The programme proved the accuracy of the pressure sensor and attempted to develop an objective method of recording progress. Arguments for pressure versus occlusion as the therapeutic agent are discussed and supported by a case report. It is suggested that a controlled trial of pressure therapy should be carried out.
Subarachnoid hemorrhage induced sympathoexcitation arises due to changes in endothelin and/or nitric oxide activity
Authors: E. Lambert, Gavin Lambert, Celine Fassot, Peter Friberg, Jean-Luc Elghozi
Journal: Cardiovascular Research (2000)

Objective: The demonstration of the effectiveness of endothelin antagonists and nitric oxide donors in managing vasospasm following subarachnoid hemorrhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the present report. Methods: Subarachnoid hemorrhage was induced in conscious rats by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arterial plasma catecholamines with the spectral analysis of blood pressure variability in order to examine sympathetic nervous activation following subarachnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside. Results: Indicative of a pronounced sympathoexcitation, the 0.2–0.6 Hz frequency components of blood pressure were markedly elevated following subarachnoid hemorrhage (2.5±0.5 vs. 8.9±2.6 mmHg2, P<0.01). Parallel changes in plasma norepinephrine concentration were observed (1.0±0.2 vs. 2.4±0.4 nmol/l, P<0.01). The subarachnoid injection of saline did not modify blood pressure variability or plasma norepinephrine concentrations. Pretreatment with either bosentan or sodium nitroprusside completely prevented the subarachnoid hemorrhage induced sympathoexcitation. Conclusions: Experimental subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation has its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation.
Novel Mechanism of P-Fimbriated Escherichia coli Virulence in Pyelonephritis
Authors: Ann Stapleton
Journal: Journal of the American Society of Nephrology (2005)

Urinary tract infections (UTI) are among the most frequently encountered community-acquired or nosocomial infections. The disease burden of UTI is estimated to be 150 million cases annually worldwide ([1][1]). Catheter-associated UTI is the most frequent source of Gram-negative sepsis in
Effects of Beta-Sitosterol on Regression of Cholesterol Atherosclerosis in Rabbits
Authors: WILLIAM T. BEHER, WILLIAM L. ANTHONY, GIZELLA D. BAKER
Journal: Circulation Research (1956)

Feeding β-sitosterol to atherosclerotic rabbits slightly increased the regression of plasma and liver cholesterol. However, β-sitosterol had no effect on aorta lipid, cholesterol or plaque regression.
Mitotic Checkpoints and Chromosome Instability Are Strong Predictors of Clinical Outcome in Gastrointestinal Stromal Tumors
Authors: Pauline Lagarde, Gaëlle Pérot, Audrey Kauffmann, Céline Brulard, Valérie Dapremont, Isabelle Hostein, Agnès Neuville, Agnieszka Wozniak, Raf Sciot, Patrick Schöffski, Alain Aurias, Jean-Michel Coindre, Maria Debiec-Rychter, Frédéric Chibon
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The importance of KIT and PDGFRA mutations in the oncogenesis of gastrointestinal stromal tumors (GIST) is well established, but the genetic basis of GIST metastasis is poorly understood. We recently published a 67 gene expression prognostic signature related to genome complexity (CINSARC for Complexity INdex in SARComas) and asked whether it could predict outcome in GISTs. Experimental Design: We carried out genome and expression profiling on 67 primary untreated GISTs. Results: We show and validate here that it can predict metastasis in a new data set of 67 primary untreated GISTs. The gene whose expression was most strongly associated with metastasis was AURKA, but the AURKA locus was not amplified. Instead, we identified deletion of the p16 (CDKN2A) and retinoblastoma (RB1) genes as likely causal events leading to increased AURKA and CINSARC gene expression, to chromosome rearrangement, and ultimately to metastasis. On the basis of these findings, we established a Genomic Index that integrates the number and type of DNA copy number alterations. This index is a strong prognostic factor in GISTs. We show that CINSARC class, AURKA expression, and Genomic Index all outperform the Armed Forces Institute of Pathology (AFIP) grading system in determining the prognosis of patients with GISTs. Interestingly, these signatures can identify poor prognosis patients in the group classified as intermediate-risk by the AFIP classification. Conclusions: We propose that a high Genomic Index determined by comparative genomic hybridization from formalin-fixed, paraffin-embedded samples could be used to identify AFIP intermediate-risk patients who would benefit from imatinib therapy. Clin Cancer Res; 18(3); 826–38. ©2011 AACR.
Transduction of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand into Hematopoietic Cells Leads to Inhibition of Syngeneic Tumor Growth<i>In vivo</i>
Authors: Keli Song, Nordine Benhaga, Robin L. Anderson, Roya Khosravi-Far
Journal: Cancer Research (2006)

Abstract Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines and has been shown to induce cell death in many types of tumor and transformed cells but not in normal cells. This tumor-selective property has made TRAIL a promising candidate for the development of cancer therapy. However, safety issues are a concern because certain preparations of recombinant TRAIL protein were reported to induce toxicity in normal human hepatocytes in culture. In addition, previous studies on tumor selectivity of exogenous TRAIL protein were carried out in xenograft models, which do not directly address the tumor selectivity issue. It was not known whether exogenous or overexpression of TRAIL in a syngeneic system could induce tumor cell death while leaving normal tissue cells unharmed. Thus, the tumor selectivity of TRAIL-induced apoptosis remains to be further characterized. In our study, we established mice that overexpress TRAIL by retroviral-mediated gene transfer in bone marrow cells followed by bone marrow transplantation. Our results show that TRAIL overexpression is not toxic to normal tissues, as analyzed by hematologic and histologic analyses of tissue samples from TRAIL-transduced mice. We show for the first time that TRAIL overexpression in hematopoietic cells leads to significant inhibition of syngeneic tumor growth in certain tumor lines. This approach may be used further to identify important molecules that regulate the sensitivity of tumor cells to TRAIL-induced cell death in vivo. (Cancer Res 2006; 66(12): 6304-11)
Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney
Authors: Scott A. Reisman, Glenn M. Chertow, Sudarshan Hebbar, Nosratola D. Vaziri, Keith W. Ward, Colin J. Meyer
Journal: Journal of the American Society of Nephrology (2012)

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2–related factor 2 (Nrf2)–mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl–induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl–induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.
INVESTIGATIONS INTO THE PATHOGENESIS OF ACUTE CUTANEOUS ANGIITIS
Authors: P. W. M. COPEMAN
Journal: British Journal of Dermatology (1970)

SUMMARY.– In this study of necrotizing (polymorphonuclear) angiitis, immunoglobulins and complement are often traceable in and about the superficial dermal blood vessels, serum immunoglobulins are raised, and during cropping of the lesions the serum complement may be low. The commoner lymphocytic angiitis differs in that abnormalities of serum immunoglobulins and of organ-specific and non-specific circulating antibodies are seldom found. Three experimental varieties of polymorphonuclear angiitis are considered in the pathogenesis of necrotizing angiitis: (1) The Arthus reaction with circulating antibodies of high specificity to the antigen; (2) The local Shwartzman reaction, probably a non-immune phenomenon but triggered by endotoxin release, immune complexes, and other non-specific materials; and (3) Circulating immune complexes sludging out in vessels where the flow of blood is sluggish. Clinical and experimental data implicate each of these. Some contributions of individual cell types other than polymorphonuclear cells and lymphocytes in the angiitic infiltrate are mentioned: the mast cell may not be degranulated; the red cell may be inert; the eosinophil's role remains mysterious; the platelet probably provides vasoactive substances and encourages early fibrin deposition. For the rash of necrotizing angiitis to develop, perhaps a specific Arthus type reaction initiates the process in the cutaneous vessels and then the inflammatory response is perpetuated by non-specific factors as in the local Shwartzman reaction.
Investigation of the ability of the Pneumonia Severity Index to accurately predict clinically relevant outcomes: a European study
Authors: B. Renaud, E. Coma, J. Hayon, M. Gurgui, C. Longo, M. Blancher, I. Jouannic, S. Betoulle, E. Roupie, M.J. Fine
Journal: Clinical Microbiology and Infection (2007)