tbuckley/cabot-search huggingface dataset:
Eosinophilia and cellular cytokine responsiveness in hemodialysis patients.
Authors: J Hertel, P L Kimmel, T M Phillips, J P Bosch
Journal: Journal of the American Society of Nephrology (1992)

Eosinophilia in hemodialysis (HD) patients has been associated with allergy to dialyzers and exaggerated activation of complement during HD. Its etiology, however, remains unknown. Complement activation can lead to cytokine production, and interleukin-2 (IL-2) administration has been shown to cause eosinophilia. Because abnormalities in cellular cytokine production in renal patients were previously demonstrated, the relationship between dialysis-associated eosinophilia and IL production in this HD population was studied. Twelve patients on chronic HD therapy with normal eosinophil counts (mean, 0.23 +/- 0.03 cells/nL) were compared with nine patients with eosinophilia (mean, 0.85 +/- 0.17 cells/nL). Measurements of cellular IL-1 and IL-2 production were performed before (pre) and after (post) HD with cuprammonium dialyzers. In patients with eosinophilia, stimulated cellular IL-1 production increased by 117 +/- 40% (P < 0.01) when post-HD measurements were compared with pre-HD values and IL-2 production increased by 127 +/- 65% (P < 0.05). In contrast, there was no difference in stimulated cellular cytokine production when values before and after HD were compared in patients without eosinophilia. Individual responses were reproducible during subsequent dialysis. It was concluded that cellular cytokine production in response to HD is not uniform. Eosinophilia is a clinically useful marker of exaggerated HD-associated cytokine production. Cytokine production depends on individual responsiveness and is probably related to atopy.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of hepatic injury on adjuvant arthritis.
Authors: R S Pinals
Journal: Annals of the Rheumatic Diseases (1973)

Hench(1933) described theameliorating effect of hepatic disease onrheumatoid arthritis. Although jaundice wasthought tobethedetermining factor in these remissions, itwasnotpossible toreproduce the phenomenon byadministration ofbilirubin andbile salts (Hench, 1940), andasatisfactory explanation of itsmechanism hasneverbeenoffered (Hill and Holley, 1966). Thiswasinvestigated inthepresent study using theratadjuvant arthritis (AA)model. Withthehepatotoxin dimethylnitrosamine (DMN), itispossible toproduce anecrotizing hepatitis, which resolves rapidly, resulting inavirtually normal histological appearance inabout2weeks(Barnes and Magee, 1954). Since DMN isconverted bytheaction ofliver enzymes toanalkylating intermediate which, inturn, israpidly inactivated, itfunctions asaselective hepatotoxin (MageeandSwann,1969). Thusa brief butsevere episode ofliver injury maybesuperimposed onAA atvarious points during its induction andcourse.
Minisymposium on Obesity: Overview and Some Strategic Considerations
Authors: Shiriki K Kumanyika
Journal: Annual Review of Public Health (2001)

▪ Abstract The high and still increasing prevalence of obesity in US children, adolescents, and adults poses a major economic and health threat to our society. The three reviews in this minisymposium on obesity explore the health issues by: 1) describing the public health impact of obesity; 2) examining the multiple and complex environmental influences on eating and physical activity patterns; and 3) considering how the development of obesity during childhood and adolescence can be prevented through interventions in school, family, and primary care settings. This overview explains the importance, for effective long-term obesity prevention and control, of intersectoral policy and environmental initiatives—in addition to behavior change approaches aimed at individuals. The need for public health professionals to influence and operate within a variety of non-health sectors such as transportation, education, urban planning, and commerce may be seen as the greatest barrier but may also be the greatest opportunity.
Body mass index and asthma
Authors: I Eneli
Journal: Thorax (2002)

IL-5 in asthmaWe have recently published two manuscripts on the effects of interleukin (IL)-5 administration to patients with mild asthma in the American Journal of Respiratory & Critical Care Medicine 1 and in Thorax. 2 We are addressing this letter to the Editors of both journals.The data described in both papers have been obtained from one experiment performed in the same group of patients with mild asthma.While the paper in the American Journal of Respiratory & Critical Care Medicine reports primarily on the phenotypic changes in circulating blood eosinophils and CD34+ cells, the Thorax paper describes the changes in the airways with measurements of bronchial responsiveness and of eosinophil counts in sputum, together with eotaxin levels in the serum.Both manuscripts, however, detail the changes in blood eosinophil counts and serum
Intermedin inhibits vascular calcification by increasing the level of matrix γ-carboxyglutamic acid protein
Authors: Yan Cai, Ming-Jiang Xu, Xu Teng, Ye Bo Zhou, Li Chen, Yi Zhu, Xian Wang, Chao Shu Tang, Yong Fen Qi
Journal: Cardiovascular Research (2009)

Vascular calcification (VC) is highly associated with increased morbidity and mortality in patients with advanced chronic kidney disease. Paracrine/autocrine factors such as vasoactive peptides are involved in VC development. Here, we investigated the expression of the novel peptide intermedin (IMD) in the vasculature, tested its ability to prevent VC in vivo and in vitro, and examined the mechanism involved.Rat VC was induced by administration of vitamin D3 plus nicotine (VDN). IMD (100 ng kg(-1) h(-1)) was systemically administered by a mini-osmotic pump. VDN-treated rat aortas showed lower IMD content and increased expression of its receptors, along with increased vascular calcium deposition and alkaline phosphatase (ALP) activity. Low IMD levels were accompanied by increased calcium deposition in human atherosclerotic plaques. In vivo administration of IMD greatly reduced vascular calcium deposition and ALP activity in VDN-treated rats when compared with vehicle treatment, which was further confirmed in cultured vascular smooth muscle cells. Concurrently, the loss of smooth-muscle lineage markers and matrix gamma-carboxyglutamic acid (Gla) protein (cMGP) in aortas was ameliorated by administering IMD to rats with VC, and the increased phosphor-Smad(1/5/8) and core binding factor alpha-1 levels in calcified vasculature were also reduced. However, the inhibitory effects of IMD on VC were eliminated upon pre-treatment with warfarin or small interfering RNA to reduce cMGP.Reduced endogenous IMD levels are associated with increased mineralization in vivo, and administration of IMD inhibits VC development by increasing cMGP levels. IMD may be an endogenous vasoprotective factor for VC.
UPTAKE, LOCALIZATION, AND NONCARBOXYLASE ROLES OF BIOTIN
Authors: Janos Zempleni
Journal: Annual Review of Nutrition (2005)

Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene expression, and chromatin structure have been identified in recent years. Human cells accumulate biotin by using both the sodium-dependent multivitamin transporter and monocarboxylate transporter 1. These transporters and other biotin-binding proteins partition biotin to compartments involved in biotin signaling: cytoplasm, mitochondria, and nuclei. The activity of cell signals such as biotinyl-AMP, Sp1 and Sp3, nuclear factor (NF)-kappaB, and receptor tyrosine kinases depends on biotin supply. Consistent with a role for biotin and its catabolites in modulating these cell signals, greater than 2000 biotin-dependent genes have been identified in various human tissues. Many biotin-dependent gene products play roles in signal transduction and localize to the cell nucleus, consistent with a role for biotin in cell signaling. Posttranscriptional events related to ribosomal activity and protein folding may further contribute to effects of biotin on gene expression. Finally, research has shown that biotinidase and holocarboxylase synthetase mediate covalent binding of biotin to histones (DNA-binding proteins), affecting chromatin structure; at least seven biotinylation sites have been identified in human histones. Biotinylation of histones appears to play a role in cell proliferation, gene silencing, and the cellular response to DNA repair. Roles for biotin in cell signaling and chromatin structure are consistent with the notion that biotin has a unique significance in cell biology.
Tumor-mediated liver X receptor-α activation inhibits CC chemokine receptor-7 expression on dendritic cells and dampens antitumor responses
Authors: Eduardo J. Villablanca, Laura Raccosta, Dan Zhou, Raffaella Fontana, Daniela Maggioni, Aurora Negro, Francesca Sanvito, Maurilio Ponzoni, Barbara Valentinis, Marco Bregni, Alessandro Prinetti, Knut R. Steffensen, Sandro Sonnino, Jan Ake Gustafsson, Claudio Doglioni, Claudio Bordignon, Catia Traversari, Vincenzo Russo
Journal: Nature Medicine (2009)
Screening for Prostate Cancer
Authors: Joseph Presti, Stacey Alexeeff, Andrew L Avins
Journal: New England Journal of Medicine (2023)

Epidemiologically, screening is justified by the importance of the disease and the lack of prospects for primary prevention, but evidence from natural history is unhelpful since men are more likely to die with, rather than from, prostate cancer. The available screening tests do not always detect men whose lesions could result in future morbidity or mortality. Evidence is limited for the benefits of treatment for localised cancers detected through screening, whereas the evidence for harm is clear. Observational evidence for the effect of population screening programmes is mixed, with no clear association between intensity of screening and reduced prostate cancer mortality. Screening for prostate cancer cannot be justified in low-risk populations, but the balance of benefit and harm will be more favourable after risk stratification. Prostate cancer screening can be justified only in research programmes designed to assess its effectiveness and help identify the groups who may benefit.
Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma.
Authors: A Jatakanon, S Lim, S A Kharitonov, K F Chung, P J Barnes
Journal: Thorax (1998)

BACKGROUND: Eosinophils in induced sputum and exhaled nitric oxide (NO) are currently used as non-invasive markers in the assessment of airway inflammation in asthma. As both sputum eosinophils (%) and exhaled NO are raised in asthmatic subjects not receiving inhaled steroids and decreased following corticosteroid therapy, a relationship between them is plausible. METHODS: Exhaled NO was measured by chemiluminescence analyser, sputum induction by 3.5% saline inhalation, and bronchial responsiveness was measured as PC20FEV1 methacholine in 35 stable asthmatic patients using beta 2 agonist alone and the correlation between these non-invasive markers of airway inflammation was studied. RESULTS: There were significant correlations between exhaled NO and PC20 (r = -0.64), exhaled NO and sputum eosinophils (%) (r = 0.48), and also between sputum eosinophils (%) and PC20 (r = -0.40). CONCLUSION: The correlation between exhaled NO and PC20 suggests that exhaled NO or the mechanisms leading to its increase may contribute to airway hyperresponsiveness in asthma. Furthermore, the relationship between sputum eosinophils (%), exhaled NO, and PC20 highlight the potential use of eosinophils (%) in induced sputum and exhaled NO to monitor the severity of asthma.
Domiciliary ventilatory support: an analysis of outcome.
Authors: E H Sawicka, L Loh, M A Branthwaite
Journal: Thorax (1988)

Prolonged ventilatory support has been used to treat 51 patients with respiratory failure secondary to skeletal (22) or neuromuscular (29) disease. Symptomatic relief was achieved in five patients with rapidly progressive neurological disease who died within 27 months. The remaining 46 patients, aged 11-69 years at presentation, have been followed for more than two and a half years. All but 10 were treated with negative pressure ventilation from the outset, intermittent positive pressure ventilation being used initially in the others and continued at home in three. Nocturnal negative pressure ventilation has been used at home by 39 patients. A permanent tracheostomy has been maintained in 14, to facilitate positive pressure ventilation in three and to circumvent upper airway obstruction during sleep in 11. Sustained improvement in symptoms and arterial blood gas tensions has been maintained, independence and the capacity for gainful employment have been regained in those of an appropriate age, and the incidence of subsequent hospital admissions has been low. Neither the mode of presentation nor the aetiology of the restrictive ventilatory defect influenced outcome in patients with stable or only slowly progressive primary disease.
Comparison of MRI and CT for Detection of Acute Intracerebral Hemorrhage
Authors: Chelsea S. Kidwell
Journal: JAMA (2004)

ONCONTRAST COMPUTED TOmography (CT) has been the standard imaging modality for the initial evaluation of patients presenting with acute stroke symptoms. 1,2The primary diagnostic advantage of CT in the hyperacute phase (0 to 6 hours) is its ability to rule out See also p 1883 and Patient Page.
Medicinal chemistry approaches for the treatment and prevention of Alzheimer's disease
Authors: S.O. Bachurin
Journal: Medicinal Research Reviews (2002)

Abstract Alzheimer's disease (AD) is the most common form of dementia, which is characterised by progressive deterioration of memory and higher cortical functions that ultimately result in total degradation of intellectual and mental activities. Modern strategies in the search of new therapeutic approaches are based on the morphological and biochemical characteristics of AD, and focused on following directions: agents that compensate the hypofunction of cholinergic system, agents that interfere with the metabolism of beta‐amyloid peptide, agents that protect nerve cells from toxic metabolites formed in neurodegenerative processes, agents that activate other neurotransmitter systems that indirectly compensate for the deficit of cholinergic functions, agents that affect the process of the formation of neurofibrillary tangles, anti‐inflammatory agents that prevent the negative response of nerve cells to the pathological process. The goal of the present review is the validation and an analysis from the point of view of medicinal chemistry of the principles of the directed search of drugs for the treatment and prevention of AD and related neurodegenerative disorders. It is based on systematization of the data on biochemical and structural similarities in the interaction between physiologically active compounds and their biological targets related to the development of such pathologies. The main emphasis is on cholinomimetic, anti‐amyloid and anti‐metabolic agents, using the data that were published during the last 3 to 4 years, as well as the results of clinical trials presented on corresponding websites. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 48–88, 2003; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/med.10026
Enhanced Myosin Light Chain Phosphorylations as a Central Mechanism for Coronary Artery Spasm in a Swine Model With Interleukin-1β
Authors: Naoki Katsumata, Hiroaki Shimokawa, Minoru Seto, Toshiyuki Kozai, Tohru Yamawaki, Kouichi Kuwata, Kensuke Egashira, Ichiro Ikegaki, Toshio Asano, Yasuharu Sasaki, Akira Takeshita
Journal: Circulation (1997)

Background Although coronary artery spasm plays an important role in a wide variety of ischemic heart diseases, the intracellular mechanism for the spasm remains to be clarified. We examined the role of myosin light chain (MLC) phosphorylations, a key mechanism for contraction of vascular smooth muscle, in our swine model with interleukin-1β (IL-1β). Methods and Results IL-1β was applied chronically to the porcine coronary arteries from the adventitia to induce an inflammatory/proliferative lesion. Two weeks after the operation, intracoronary serotonin repeatedly induced coronary hyperconstrictions at the IL-1β-treated site both in vivo and in vitro, which were markedly inhibited by fasudil, an inhibitor of protein kinases, including protein kinase C and MLC kinase. Western blot analysis showed that during serotonin-induced contractions, MLC monophosphorylation was significantly increased and sustained in the spastic segment compared with the control segment, whereas MLC diphosphorylation was noted only in the spastic segment. A significant correlation was noted between the serotonin-induced contractions and MLC phosphorylations. Both types of MLC phosphorylation were markedly inhibited by fasudil. In addition, MLC diphosphorylation was never induced by a simple endothelium removal in the normal coronary artery, whereas enhanced MLC phosphorylations in the spastic segment were noted regardless of the presence or absence of the endothelium. Conclusions These results indicate that enhanced MLC phosphorylations in the vascular smooth muscle play a central role in the pathogenesis of coronary spasm in our swine model.
Fellowship in Sports Medicine
Authors: Jack E Taunton
Journal: British Journal of Sports Medicine (2000)

The fellowship, first offered in 1982, is multifaceted and includes clinical exposure, course work, research, teaching, community work, and medical education. The clinical time is split between primary care sports medicine, orthopaedics, and physiotherapy, with the emphasis on primary care. The fellow, once familiar with the specific sports oriented history and physical, assesses and reviews the cases with one of the primary care doctors and is available …
<i>p53CSV</i>, a Novel p53-Inducible Gene Involved in the p53-Dependent Cell-Survival Pathway
Authors: Woong-Ryeon Park, Yusuke Nakamura
Journal: Cancer Research (2005)

Abstract Although a number of p53 target genes have been identified, the mechanisms of p53-dependent activities that determine cellular survival or death are still not fully understood. Here we report isolation of a novel p53 target gene, designated p53-inducible cell-survival factor (p53CSV). p53CSV contains a p53-binding site within its second exon and the reduction of expression by small interfering RNA enhanced apoptosis, whereas overexpression protected cells from apoptosis caused by DNA damage. p53CSV is induced significantly when cells have a low level of genotoxic stresses, but not when DNA damage is severe. p53CSV can modulate apoptotic pathways through interaction with Hsp70 that probably inhibits activity of apoptosis protease activating factor-1. Our results imply that under specific conditions of stress, p53 regulates transcription of p53CSV and that p53CSV is one of the important players in the p53-mediated cell survival.
Siblings, multiple births, and the incidence of allergic disease: a birth cohort study using the West Midlands general practice research database
Authors: T M McKeever
Journal: Thorax (2001)

<h3>BACKGROUND</h3> The presence of older siblings reduces the risk of developing hay fever, eczema and atopy, but findings for asthma have been inconsistent. Whether twins have a reduced risk of allergic disease is also unclear. We have investigated these questions in a birth cohort analysis of the West Midlands General Practice Research Database (GPRD). <h3>METHODS</h3> Our birth cohort included 29 238 children. The incidence of allergic disease was examined according to the number of siblings, multiple births, and parental allergic disease and smoking habit using Cox regression. <h3>RESULTS</h3> There was a dose related decrease in the incidence of eczema and hay fever with increasing number of older siblings (hazard ratio for children with three or more older siblings compared with none 0.70 (95% CI 0.64 to 0.76) for eczema and 0.67 (95% CI 0.52 to 0.86) for hay fever). In contrast, the presence of older siblings increased the incidence of asthma (HR 1.17, 95% CI 1.06 to 1.29), although this effect was strongly dependent on age of diagnosis. For children diagnosed over the age of 2 years the presence of older siblings was protective (HR 0.66, 95% CI 0.52 to 0.82), while below this age the reverse was true (HR 1.38, 95% CI 1.24 to 1.54). Members of a multiple birth had a reduced incidence of all three allergic diseases. Birth order and multiple birth effects were independent of sex, maternal age, consulting behaviour, and parental allergy and smoking habit. <h3>CONCLUSIONS</h3> The presence of older siblings and being a member of a multiple birth appears to protect against the development of eczema, hay fever, and asthma diagnosed after the age of 2. In contrast, the presence of older siblings increases the incidence of early asthma.
Inferior outcome after allogeneic transplant in first remission in high‐risk <scp>AML</scp> patients who required more than two cycles of induction therapy
Authors: Sara J. Lim, Matthew J. Lim, Anastasios Raptis, Jing‐Zhou Hou, Rafic Farah, Stanley M. Marks, Annie Im, Kathleen Dorritie, Alison Sehgal, Mounzer Agha, Raymond Felgar, Seah H. Lim
Journal: American Journal of Hematology (2015)

While some patients with high-risk acute myeloid leukemia (AML) require one or two cycles of induction chemotherapy to achieve a complete remission (CR), others require more than two cycles. We examined the outcomes of patients with high-risk AML who received allogeneic HPC transplant in CR1. Forty five consecutive high-risk AML patients in CR1 were included. All 45 patients had adverse cytogenetics, FLT 3 mutations, or secondary AML. Group A patients (n = 33) received one or two cycles, and Group B (n = 12) three or more cycles of induction chemotherapy. The patients were comparable in age, sex, white cell count at presentation, and time from diagnosis and from last chemotherapy to transplant. The 100-day mortality rate was higher in Group B patients (50% vs. 9%, P = 0.006). They had a higher non-relapse mortality (33% vs. 6%, P = 0.035) and a longer length of hospital stay from the day of stem cell infusion (median 21 vs. 20, P = 0.02; third quartile 22 vs. 28, P = 0.02). There was also a trend toward inferior event-free survival and overall survival. High-risk AML patients undergoing allogeneic transplant in CR1 after three or more cycles of induction chemotherapy have an inferior outcome and higher mortality when compared to those who only needed one or two cycles of induction chemotherapy. Novel strategies are needed to reduce the transplant-related mortality in high-risk AML patients needing more than two cycles of induction chemotherapy prior to allogeneic transplant in CR1.
Thyroid Scintigram
Authors: U. Yun Ryo
Journal: JAMA (1976)

To evaluate the reliability of thyroid scintigraphy in the diagnosis of nodular growths, scintigrams of patients who later underwent thyroidectomy were reviewed and correlated with pathologic findings. The scintigrams were all obtained with a 5-mm single-hole collimator-equipped gamma-scintillation camera after intravenous injection of 5 millicuries of sodium pertechnetate Tc 99m. In the group of 92 patients, six of whom had two histologically different lesions, 149 nodules were identified pathologically. There were 26 nodules 2 to 5 mm in diameter, of which 22 were benign and four were malignant. None of the 22 benign nodules were delineated scintigraphically. Superior image quality and resolution, low radiation dose, technical simplicity, and speed make Tc pinhole-camera scintigraphy the best procedure available for routine thyroid imaging. (<i>JAMA</i>235:1235-1238, 1976)