tbuckley/cabot-search huggingface dataset:
Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL)
Authors: Takashi Sasayama, Satoshi Nakamizo, Masamitsu Nishihara, Atsufumi Kawamura, Hirotomo Tanaka, Katsu Mizukawa, Shigeru Miyake, Masaaki Taniguchi, Kohkichi Hosoda, Eiji Kohmura
Journal: Neuro-Oncology (2011)

The diagnosis of primary central nervous system lymphoma (PCNSL) by radiographical examination is often difficult because of its similarity to other brain tumors. To test whether interleukin-10 (IL-10) and IL-6 can be used to distinguish PCNSL from other brain tumors that are radiographically similar, cerebrospinal fluid (CSF) levels of IL-10 and IL-6 were measured in 66 patients with intracranial tumors (PCNSLs: 26 cases; other brain tumors: 40 cases). In the patients with PCNSLs, the median CSF levels of IL-10 and IL-6 were 27 pg/mL and 5.4 pg/mL, respectively. The CSF IL-10 and IL-6 levels were significantly higher in PCNSLs than in the other brain tumors. To validate the diagnostic value of CSF IL-10 in PCNSL, we prospectively examined 24 patients with brain lesions that were suspected to be PCNSL. We observed that the CSF IL-10 levels were significantly higher in PCNSLs than in other brain tumors. At an IL-10 cutoff level of 9.5 pg/mL, the sensitivity and specificity were 71.0% and 100%, respectively. After therapy, the CSF IL-10 levels were decreased in all patients and were increased at relapse in most of these patients. Immunohistochemically, all PCNSLs, except for 1 unclassified PCNSL, expressed both IL-10 and IL-10 receptor-A. In the patients with high CSF IL-10, IL-10 expression levels in tumor were relatively higher, compared with low CSF IL-10; however, there was no significant difference between these groups. In addition, elevated CSF level of IL-10 was significantly associated with having a shorter progression-free survival (hazard ratio, 3.37; 95% confidence interval, 0.985–11.528; log-rank, P= .038). These results indicate that the CSF level of IL-10 may be a useful diagnostic and prognostic biomarker in patients with PCNSLs.
LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro
Authors: Tien-sheng Huang, Line M Myklebust, Endre Kjarland, Bjørn Tore Gjertsen, Frederic Pendino, Øystein Bruserud, Stein Ove Døskeland, Johan R Lillehaug
Journal: Molecular Cancer (2007)

Abstract Background Relapse due to chemoresistant residual disease is a major cause of death in acute myelogenous leukemia (AML). The present study was undertaken to elucidate the molecular mechanisms of chemoresistance by comparing differential gene expression in blasts from patients with resistant relapsing AML and chemosensitive AML. Results About 20 genes were identified as preferentially expressed in blasts pooled from patients with resistant disease, as compared to chemosensitive AML blasts, based on differential gene expression screening. Half of these genes encoded proteins related to protein translation, of these a novel protein related to the ribosomal stalk protein P0. Other upregulated mRNAs coded for cytochrome C oxidase III, the transcription factors ERF-2/TIS11d, and the p75 and p52 splice variants of Lens Epithelial Derived Growth Factor (LEDGF). Analysis of blasts from single patients disclosed that LEDGF/p75 was the most consistently upregulated mRNA in resistant AML. Transfection experiments demonstrated that LEDGF/p75 and p52b antagonized daunorubicin-induced and cAMP-induced apoptosis in an AML cell line. Also HEK-293 cells were protected against daunorubicin by LEDGF/p75 and p52b, whereas LEDGF/p52 splice variants lacking exon 6 had proapoptotic effects. Interestingly, full length LEDGF/p75 protected against truncated pro-apoptotic LEDGF/p75. Conclusion Our results provide evidence for an association between the overexpression of genes encoding survival proteins like LEDGF/p75 and chemo-resistance in acute myelogenous leukemia. LEDGF/p75 has previously not been shown to protect against chemotherapy, and is a potential drug target in AML.
Selective activation of the mitogen-activated protein kinase subgroups c-Jun NH2 terminal kinase and p38 by IL-1 and TNF in human articular chondrocytes.
Authors: Y Geng, J Valbracht, M Lotz
Journal: Journal of Clinical Investigation (1996)

Previous studies suggested that tyrosine kinase activation is an important signal transduction event in the IL-1 response of chondrocytes. The present study identifies the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK)-1 and ERK-2 as major tyrosine phosphorylated proteins in IL-1 stimulated chondrocytes. Kinase assays on immunoprecipitates with myelin basic protein as substrate showed that ERK-1 and ERK-2 activation was detectable within 5 min after IL-1 stimulation and decreased to baseline within 60 min. Analysis of other members of the MAP kinase family showed that chondrocytes also express c-Jun NH2 terminal kinase (JNK)-1, JNK-2, and p38 proteins. These kinases were time-dependently activated by IL-1. Among other chondrocyte activators tested, only TNF activated all three of the MAP kinase subgroups. JNK and p38 were not activated by any of the other cytokines and growth factors tested. However, ERK was also activated by PDGF, IGF-1, and IL-6. Phorbol 12-myristate 13-acetate, calcium ionophore, and cAMP analogues only increased ERK activity but had no significant effects on JNK or p38. These results suggest differential activation of MAP kinase subgroups by extracellular stimuli. ERK is activated in response to qualitatively diverse extracellular stimuli and various second messenger agonists. In contrast, JNK and p38 are only activated by IL-1 or TNF, suggesting that these kinases participate in the induction of the catabolic program in cartilage.
ABC of mental health: Common mental health problems in hospital
Authors: A. Ramirez, A. House
Journal: BMJ (1997)

The prevalence of mental health problems in patients attending acute general hospitals is high. The three main types of clinical problem are #### Prevalence of mental health problems in general hospitals All doctors have a role in addressing the mental health needs of their patients. However, the mental health problems of general hospital patients are closely tied to their physical illness, and specialist units (such as cancer, renal, pain, neurology, or AIDS services) may experience a high level of psychiatric disorder. Patients, and staff, benefit from specific psychiatric liaison support to facilitate integration of their psychological and physical care. #### Key features of a liaison psychiatry service
Management of acute bronchiolitis: can evidence based guidelines alter clinical practice?
Authors: J Barben, C E Kuehni, D Trachsel, J Hammer
Journal: Thorax (2008)

<h3>Background:</h3> Acute bronchiolitis is the most common lower respiratory tract infection in infants and there is no evidence that drug treatment alters its natural course. Despite this, most Swiss paediatricians reported in 2001 prescribing bronchodilators and inhaled corticosteroids (ICS). This situation led to the creation of national guidelines followed by a tailored implementation programme. The aim of this study was to examine if treatment practices changed after the implementation of the new guidelines. <h3>Methods:</h3> A questionnaire on treatment of bronchiolitis was sent to all Swiss paediatricians before (2001) and after (2006) creation and implementation of national guidelines (2003–2005). Guidelines were created in collaboration with all paediatric pulmonologists and implemented carefully using a multifaceted approach. <h3>Results:</h3> Questionnaires were returned by 541 paediatricians (58%) in 2001 and by 639 (54%) in 2006. While both surveys showed a wide variation in the treatment of bronchiolitis between physicians, reported drug prescription decreased significantly between the two surveys. For outpatients, general use (for all patients) of bronchodilators dropped from 60% to 23%, and general use of ICS from 34% to 6%. For inpatients, general use of bronchodilators and ICS dropped from 55% to 18% and from 26% to 6%, respectively (all p&lt;0.001). The decrease was evident in all regions, among hospital and primary care physicians, and among general paediatricians and paediatric pulmonologists. <h3>Conclusions:</h3> National guidelines together with a tailored implementation programme can have a major impact on medical management practices in a country.
Expression of Interleukin (IL)-18 and Functional IL-18 Receptor on Human Vascular Endothelial Cells, Smooth Muscle Cells, and Macrophages
Authors: Norbert Gerdes, Galina K. Sukhova, Peter Libby, Rebecca S. Reynolds, James L. Young, Uwe Schönbeck
Journal: The Journal of Experimental Medicine (2002)

Although considerable evidence implicates the cytokine interferon (IFN)-γ in atherogenesis, the proximal inducers and the range of sources of its expression remain unknown. This study tested the hypothesis that interleukin (IL)-18 regulates IFN-γ expression during atherogenesis. Indeed, human atheroma in situ expressed IL-18 and elevated levels of its receptor subunits, IL-18Rα/β, compared with nondiseased arterial tissue. IL-18 occurred predominantly as the mature, 18-kD form and colocalized with mononuclear phagocytes (MØ), while endothelial cells (ECs), smooth muscle cells (SMCs), and MØ all expressed IL-18Rα/β. Correspondingly in vitro, only MØ expressed IL-18, while all three cell types displayed the IL-18Rα/β complex constitutively, exhibiting enhanced expression upon stimulation with LPS, IL-1β, or tumor necrosis factor (TNF)-α. IL-18 signaling evoked effectors involved in atherogenesis, e.g., cytokines (IL-6), chemokines (IL-8), intracellular adhesion molecules (ICAM)-1, and matrix metalloproteinases (MMP-1/-9/-13), demonstrating functionality of the receptor on ECs, SMCs, and MØ. Finally, IL-18, particularly in combination with IL-12, induced the expression of IFN-γ in cultured MØ and, surprisingly, in SMCs (but not in ECs). The expression of functional IL-18 and IL-18 receptor on human atheroma-associated ECs, SMCs, and MØ, and its unexpected ability to induce IFN-γ expression in SMCs, suggests a novel paracrine proinflammatory pathway operating during atherogenesis.
Failure of an Internet-Based Health Care Intervention for Colonoscopy Preparation: A Caveat for Investigators
Authors: Aarti Kakkar, Brian C. Jacobson
Journal: JAMA Internal Medicine (2013)

With respect to sodium, more than 80% of meals exceeded the daily adequate intake level (1500 mg), with more than 50% exceeding the daily upper tolerable intake level (2300 mg).Only 1% of meals had less than 600 mg of sodium, the "healthy level" for meals, according to the Food and Drug Administration. 7Almost 50% of meals exceeded the daily value for fat (65 g) and 25% exceeded the daily value for saturated fat and cholesterol.Furthermore, a dessert, if ordered, would add an additional 549 calories, 27 g of fat (43%DV), 13 g of saturated fat, 0.6 g of trans fat (68%DV), and 46 g of sugar.Meals identified by the restaurants as being "healthy" contained on average 474 calories, 13 g of fat (20%DV), 3 g of saturated fat (17%DV), and 752 mg of sodium (50% of the daily adequate intake level).Discussion | This study presents the average nutrient levels in a variety of different breakfast, lunch, and dinner meals from the major SDR chains.On average, meals contained more than a full day's worth of sodium and nearly a day's worth of fat and saturated fat.The high level of saturated fat is worrisome because according to the Institute of Medicine, intakes of saturated fat should be kept as low as possible. 3Furthermore, though recommendations suggest that approximately 20% to 35% of energy should come from fat; in this study, 45% was derived from fat. 3 On a positive note, the results showed that trans fat levels were commendably low.Furthermore, meals advertised as being "healthy" were substantially healthier compared with average meals.At present there is no data on the nutritional profile of meals from SDRs.Previous research on meals purchased from fast food chains reported an average of 1751 mg of sodium and 881 calories, 8 which is lower than the levels seen in SDR meals in this study.Limitations include the fact that the data represented meals available in restaurants and did not reflect actual meals consumed by restaurant patrons.Furthermore, beverages, appetizers, and condiments that are often added by the consumer, and would further increase intake levels, were not accounted for.Overall, the results of this study demonstrate that calorie, fat, saturated fat, and sodium levels are alarmingly high in breakfast, lunch, and dinner meals from multiple chain SDRs.Therefore, addressing the nutritional profile of restaurant meals should be a major public health priority.
Albuminuria and Racial Disparities in the Risk for ESRD
Authors: William M. McClellan, David G. Warnock, Suzanne Judd, Paul Muntner, Reshma Kewalramani, Mary Cushman, Leslie A. McClure, Britt B. Newsome, George Howard
Journal: Journal of the American Society of Nephrology (2011)

The causes of the increased risk for ESRD among African Americans are not completely understood. Here, we examined whether higher levels of urinary albumin excretion among African Americans contributes to this disparity. We analyzed data from 27,911 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who had urinary albumin-to-creatinine ratio (ACR) and estimated GFR (eGFR) measured at baseline. We identified incident cases of ESRD through linkage with the United States Renal Data System. At baseline, African Americans were less likely to have an eGFR <60 ml/min per 1.73 m(2) but more likely to have an ACR ≥ 30 mg/g. The incidence rates of ESRD among African Americans and whites were 204 and 58.6 cases per 100,000 person-years, respectively. After adjustment for age and gender, African Americans had a fourfold greater risk for developing ESRD (HR 4.0; 95% CI 2.8 to 5.9) compared with whites. Additional adjustment for either eGFR or ACR reduced the risk associated with African-American race to 2.3-fold (95% CI 1.5 to 3.3) or 1.8-fold (95% CI 1.2 to 2.7), respectively. Adjustment for both ACR and eGFR reduced the race-associated risk to 1.6-fold (95% CI 1.1 to 2.4). Finally, in a model that further adjusted for both eGFR and ACR, hypertension, diabetes, family income, and educational status, African-American race associated with a nonsignificant 1.4-fold (95% CI 0.9 to 2.3) higher risk for ESRD. In conclusion, the increased prevalence of albuminuria may be an important contributor to the higher risk for ESRD experienced by African Americans.
Chromosomal position of a <i>VH</i> gene segment determines its activation and inactivation as a substrate for V(D)J recombination
Authors: Jamie Geier Bates, Dragana Cado, Hector Nolla, Mark S. Schlissel
Journal: The Journal of Experimental Medicine (2007)

Complete IgHC gene rearrangement occurs only in B cells in a stage-specific and ordered manner. We used gene targeting to reposition a distal V(H) gene segment to a region just 5' of the D(H) gene cluster and found its activation to be highly dependent on the chromosomal domain within which it resides. The targeted V(H) gene segment rearranged at a higher frequency than its endogenous counterpart, its rearrangement was no longer ordered, and its ability to be silenced by allelic exclusion was lost. Additionally, the targeted V(H) gene segment lost lineage specificity, as VDJ(H) rearrangement was observed in thymocytes. These data suggest that locus contraction, mimicked by proximal targeting, can override any regulation imposed by DNA sequences immediately surrounding V(H) gene segments.
Dwarfism, Hormones, and Dieting
Authors: S. L. Simpson
Journal: BMJ (1947)

pitocin " can be given after the third dose of ascorbic acid if desirable, often with a very notable oxytocic effect.Higher doses of ascorbic acid are useless.Intravenous use may lead to tonic contractions.Intramuscular administration is of no advantage.Ascorbic acid proved especially useful in patients with uterine inertia, in which posterior-pituitary extracts were contraindicated.There were no ill effects in mother or baby.In malpresentation, trial labour, antepartum haemorrhage, and foetal distress, where the use of other oxytocics needs greatest supervision and caution in dosage, ascorbic acid is safe and deserves a trial before any other oxytocic agent.Toxaemias of pregnancy are a great field for the use of ascorbic acid as an oxytocic.It is worth noting that, with the above qualifications, ascorbic acid seems to me an active oxytocic drug which is preferable to posterior-pituitary extract, especially for patients with hypo- tonia in the dilatation period.The object of this communication is to call for further experimental and practical investigations of a relatively simple and safe chemical substance which appears to yegulate and stimulate contractions on the already active gravid uterus.-Iam, etc.,
In Vitro And In Vivo Activation of Rat Hepatic Stellate Cells Results In De Novo Expression of L–Type Voltage–Operated Calcium Channels
Authors: Ramón Bataller, Xavier Gasull, Pere Ginès, Karine Hellemans, Nieves M. Görbig, Josep M. Nicolás, Pau Sancho-Bru, Dara De Las Heras, Arcadi Gual, Albert Geerts, Vicente Arroyo, Juan Rodés
Journal: Hepatology (2001)

Following chronic liver injury, hepatic stellate cells (HSCs) transdifferentiate into myofibroblast-like cells, which develop contractile properties and contribute to increased resistance to blood flow. We investigated whether this phenotypic activation includes changes in the expression of L-type voltage-operated Ca2+ channels (VOCC), which mediate Ca2+ influx and regulate cell contraction in vascular cell types. Rat HSCs were studied in the quiescent phenotype and after their activation in vitro (cultured on plastic for 14 days) and in vivo (isolated from rats with CCl(4)-induced cirrhosis). Patch-clamp studies showed Ca2+ currents through L-type VOCC in HSCs activated both in vitro and in vivo, whereas no currents were detected in quiescent HSCs. Moreover, binding studies with (3)H-isradipine, a specific L-type VOCC antagonist, showed a large number of binding sites in activated HSCs, while no specific binding was found in quiescent HSCs. Finally, messenger RNA (mRNA) encoding L-type VOCC was not detected in quiescent HSCs as assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis, whereas it was present in activated HSCs. Stimulation of L-type VOCC with KCl resulted in a marked increase in [Ca2+](i) followed by cell contraction in HSCs activated both in vitro and in vivo, whereas no effects were observed in quiescent HSCs. We conclude that the activation of HSCs is associated with up-regulation of L-type VOCC that mediate Ca2+ influx and cell contraction. These results may be relevant to the pathogenesis of portal hypertension.
A Longitudinal Study of GAD65 and ICA512 Autoantibodies During the Progression to Type 1 Diabetes in Diabetes Prevention Trial–Type 1 (DPT-1) Participants
Authors: Jay M. Sosenko, Jay S. Skyler, Jerry P. Palmer, Jeffrey P. Krischer, David Cuthbertson, Liping Yu, Desmond A. Schatz, Tihamer Orban, George Eisenbarth
Journal: Diabetes Care (2011)

OBJECTIVE We examined changes in GAD65 and ICA-512 autoantibodies (GADA and IA-2A) during progression to type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Diabetes Prevention Trial–Type 1 (DPT-1) participants were assessed for changes in positivity and titers of GADA and IA-2A during the progression to T1D. RESULTS Among 99 progressors to T1D with GADA and IA-2A measurements at baseline and diagnosis (mean interval = 3.3 ± 1.5 years), GADA positivity changed little and GADA titers decreased (P &amp;lt; 0.01). In contrast, both IA-2A positivity and titers increased substantially (P &amp;lt; 0.001). Even among those positive at baseline, IA-2A titers increased from baseline to diagnosis (n = 57; P &amp;lt; 0.001), whereas GADA titers decreased (n = 80; P &amp;lt; 0.01). The same patterns of change were also evident among those positive for both autoantibodies (n = 48) at baseline. CONCLUSIONS IA-2A titers increase during the years before the diagnosis of T1D, even among those positive for IA-2A. In contrast, GADA titers tend to decline during those years.
Platelet Activation and Aggregation Promote Lung Inflammation and Influenza Virus Pathogenesis
Authors: Vuong Ba Lê, Jochen G. Schneider, Yvonne Boergeling, Fatma Berri, Mariette Ducatez, Jean-Luc Guerin, Iris Adrian, Elisabeth Errazuriz-Cerda, Sonia Frasquilho, Laurent Antunes, Bruno Lina, Jean-Claude Bordet, Martine Jandrot-Perrus, Stephan Ludwig, Béatrice Riteau
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown.To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza.We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza virus infection in mice.Lungs of infected mice were massively infiltrated by aggregates of activated platelets. Platelet activation promoted influenza A virus pathogenesis. Activating protease-activated receptor 4, a platelet receptor for thrombin that is crucial for platelet activation, exacerbated influenza-induced acute lung injury and death. In contrast, deficiency in the major platelet receptor glycoprotein IIIa protected mice from death caused by influenza viruses, and treating the mice with a specific glycoprotein IIb/IIIa antagonist, eptifibatide, had the same effect. Interestingly, mice treated with other antiplatelet compounds (antagonists of protease-activated receptor 4, MRS 2179, and clopidogrel) were also protected from severe lung injury and lethal infections induced by several influenza strains.The intricate relationship between hemostasis and inflammation has major consequences in influenza virus pathogenesis, and antiplatelet drugs might be explored to develop new antiinflammatory treatment against influenza virus infections.
The Distributions of "New" and "Old" Alu Sequences in the Human Genome: The Solution of a "Mystery"
Authors: M. Costantini, F. Auletta, G. Bernardi
Journal: Molecular Biology and Evolution (2011)

The distribution in the human genome of the largest family of mobile elements, the Alu sequences, has been investigated for the past 30 years, and the vast majority of Alu sequences were shown to have the highest density in GC-rich isochores. Ten years ago, it was discovered, however, that the small "youngest" (most recently transposed) Alu families had a strikingly different distribution compared with the "old" families. This raised the question as to how this change took place in evolution. We solved what was considered to be a "mystery" by 1) revisiting our previous results on the integration and stability of retroviral sequences, and 2) assessing the densities of acceptor sites TTTT/AA in isochore families. We could conclude 1) that the open state of chromatin structure plays a crucial role in allowing not only the initial integration of retroviral sequences but also that of the youngest Alu sequences, and 2) that the distribution of old Alus can be explained as due to Alu sequences being unstable in the GC-poor isochores but stable in the compositionally matching GC-rich isochores, again in line with what happens in the case of retroviral sequences.