tbuckley/cabot-search huggingface dataset:
CXCL10/IP-10 Is a Biomarker and Mediator for Kawasaki Disease
Authors: Tai-Ming Ko, Ho-Chang Kuo, Jeng-Sheng Chang, Shih-Ping Chen, Yi-Min Liu, Hui-Wen Chen, Fuu-Jen Tsai, Yi-Ching Lee, Chien-Hsiun Chen, Jer-Yuarn Wu, Yuan-Tsong Chen
Journal: Circulation Research (2015)

Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult.To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD.We enrolled 214 children with fever and clinical features suggestive of KD. Of those, only 100 were diagnosed with KD. Their plasma samples were globally analyzed for cytokines, chemokines, and cell adhesion molecules using an unbiased, large-scale, quantitative protein array. This study was conducted in 3 stages: discovery, replication, and blinded validation. During the discovery phase (n [KD]=37; n [control]=20), the expression of interleukin-17F, sCD40L, E-selectin, CCL23 (myeloid progenitor inhibitory factor 1), and CXCL10 (IFN-γ-inducible protein 10 [IP-10]) were upregulated during the acute phase in patients with KD when compared with that in the controls. A notable increase was observed in the IP-10 levels (KD, 3037 ± 226.7 pg/mL; control, 672 ± 130.4 pg/mL; P=4.1 × 10(-11)). Receiver-operating characteristic analysis of the combined discovery and replication data (n [KD]=77; n [control]=77) showed that the IP-10 level had high area under the curve values (0.94 [95% confidence interval, 0.9055-0.9778]; sensitivity, 100%; and specificity, 77%). With 1318 pg/mL as the optimal cutoff, the blinded validation study confirmed that the IP-10 levels were a good predictor of KD. With intravenous immunoglobulin treatment, the IP-10 levels returned to normal. The downstream receptor of IP-10, CXCR3, was activated in the T cells of patients with acute KD.IP-10 may be used as a biomarker to facilitate KD diagnosis, and it may provide clues about the pathogenesis of KD.
Changes in Chinese Policies to Promote the Rational Use of Antibiotics
Authors: Yonghong Xiao, Jing Zhang, Beiwen Zheng, Lina Zhao, Sujuan Li, Lanjuan Li
Journal: PLoS Medicine (2013)

Xonghong Xiao and colleagues analyze the challenge of antimicrobial resistance in China. A government strategy to promote rational use of antimicrobials in health care reduced antibiotic sales and percentage of prescriptions for antimicrobials for both hospitalized patients and outpatients, and offers insights to shape future initiatives. Please see later in the article for the Editors' Summary
Changes in Pulmonary Mechanics with Increasing Disease Severity in Children and Young Adults with Cystic Fibrosis
Authors: Nicholas Hart, Michael I. Polkey, Annick Clément, Michèle Boulé, John Moxham, Frédéric Lofaso, Brigitte Fauroux
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

As forced expiratory volume in 1 second (FEV1) is a major predictor of outcome in patients with cystic fibrosis (CF), we investigated the effect of FEV1 on pulmonary mechanics in children and young adults with CF. We measured respiratory rate; tidal volume; minute ventilation; arterial blood gases; sniff esophageal pressure; dynamic lung compliance; total pulmonary resistance; intrinsic positive end expiratory pressure; and total, elastic, and resistive work of breathing in 32 patients (FEV1 range: 12–49% predicted). We observed correlations between FEV1 and PaO2 (r = 0.76, p < 0.0001) and PaCO2 (r = −0.70, p < 0.0001), FEV1 and respiratory rate/tidal volume (r = −0.41, p = 0.02), FEV1 and dynamic lung compliance (r = 0.64, p < 0.0001), and FEV1 and total work of breathing (r = −0.52, p = 0.002) and elastic work of breathing (r = −0.60. p = 0.0003). No correlations were observed between FEV1 and sniff esophageal pressure (p = 0.5), minute ventilation (p = 0.9), total pulmonary resistance (p = 0.3), intrinsic positive end expiratory pressure (p = 0.3), or resistive work of breathing (p = 0.1). As FEV1 declines in children and young adults with CF, there is an increase in the elastic load and work of breathing, resulting in a rapid shallow breathing pattern, that is associated with further impairment of gas exchange.
Disappearance of microspherocytes in peripheral circulation and normalization of decreased lipids in plasma and in red cells of patients with hereditary spherocytosis after splenectomy
Authors: Takashi Sugihara, Kosuke Miyashima, Yoshihito Yawata
Journal: American Journal of Hematology (1984)

A possible mechanism of the formation of microspherocytosis in unsplenectomized patients with hereditary spherocytosis (HS) was investigated in relation to lipid metabolism in plasma and in red cells of these patients. Plasma lipids (total cholesterol, free cholesterol, high density lipoprotein cholesterol, free fatty acids, and phospholipids) were markedly reduced in unsplenectomized HS patients with microspherocytosis. Red cell membrane lipids (free cholesterol and phospholipids such as phosphatidyl ethanolamine, sphingomyelin, phosphatidyl choline, and lysophosphatidyl choline) were also decreased in these unsplenectomized HS patients. After splenectomy, microspherocytosis disappeared concomitant to substantial normalization of plasma and red cell membrane lipids. These observations suggest that plasma lipid decrement in the unsplenectomized HS patients is at least one of the causative factors in pathogenesis of the formation of microspherocytosis. So-called "splenic conditioning" may not imply a physical "loss" of membrane by fragmentation or pitting of the once-formed HS red cells in the peripheral circulation. Instead, the decreased plasma lipids in the presence of the spleen may affect the de novo synthesis of red cell membrane lipids, resulting in the formation of microspherocytosis.
Randomized Phase II Study of Dulanermin in Combination With Paclitaxel, Carboplatin, and Bevacizumab in Advanced Non–Small-Cell Lung Cancer
Authors: Jean-Charles Soria, Zsuzsanna Márk, Petr Zatloukal, Barna Szima, István Albert, Erzsébet Juhász, Jean-Louis Pujol, Jerzy Kozielski, Nigel Baker, Dominic Smethurst, Yong-jiang Hei, Avi Ashkenazi, Howard Stern, Lukas Amler, Yang Pan, Fiona Blackhall
Journal: Journal of Clinical Oncology (2011)

To evaluate the efficacy and safety of dulanermin combined with paclitaxel and carboplatin (PC) and bevacizumab (PCB) as first-line treatment for advanced or recurrent non-small-cell lung cancer (NSCLC).Patients with squamous NSCLC and/or CNS metastases received PC every 3 weeks alone (arm 1) or with dulanermin 8 mg/kg for 5 days (arm 2). Patients with nonsquamous NSCLC received PCB alone (arm 3) or with dulanermin 8 mg/kg for 5 days (arm 4) or 20 mg/kg for 2 days (arm 5). The primary end point was the objective response rate (ORR).Overall, 213 patients were randomly assigned (arm 1, n = 41; arm 2, n = 39; arm 3, n = 42; arm 4, n = 40; arm 5, n = 41). The ORR in arms 1 to 5 was 39% (95% CI, 24% to 56%), 38% (95% CI, 24% to 54%), 50% (95% CI, 35% to 65%), 40% (95% CI, 25% to 56%), and 40% (95% CI, 25% to 56%), respectively. The odds ratio for ORR was 1.04 (P = 1.000) for arm 1 versus arm 2, 1.53 (P = .391) for arm 3 and versus arm 4, and 1.53 (P = .391) for arm 3 versus arm 5. The most common grade ≥ 3 adverse events were neutropenia, asthenia, anemia, thrombocytopenia, and hemoptysis. Of 161 available serum samples, a trend toward increased caspase-cleaved cytokeratin-18 was observed after dulanermin treatment in cycles 1 and 2. Among 84 patients evaluated for GalNT14 expression, there was a trend toward favorable progression-free survival and overall survival with dulanermin treatment in those with high GalNT14 expression.The addition of dulanermin to PC and PCB did not improve outcomes in unselected patients with previously untreated advanced or recurrent NSCLC.
Rabbit heart fatty acid-binding protein. Isolation, characterization, and application of a monoclonal antibody.
Authors: A A Knowlton, R E Burrier, P Brecher
Journal: Circulation Research (1989)

A fatty acid-binding protein (FABP) was purified from rabbit heart and characterized with respect to size, isoelectric point, and tissue distribution. This protein was found in red muscle, diaphragm, and aorta, as well as in the heart. Amino acid composition of rabbit heart FABP differed only slightly from the human and rat proteins. Rabbit heart FABP was shown to bind two molecules of fatty acid. A monoclonal antibody was developed and used to demonstrate the feasibility of a one-step purification with affinity chromatography. Cross-reactivity was found between the human protein and the rabbit antibody, and an immunoassay was developed to human heart FABP. Levels of human heart FABP in the plasma of patients with acute myocardial infarction were significantly elevated (83 +/- 9 micrograms/ml) compared with patients with pulmonary edema (52 +/- 7 micrograms/ml) and normal volunteers (28 +/- 5 micrograms/ml; p less than 0.05, mean +/- SEM).
Coordinate Expression and Trans Presentation of Interleukin (IL)-15Rα and IL-15 Supports Natural Killer Cell and Memory CD8+ T Cell Homeostasis
Authors: Patrick R. Burkett, Rima Koka, Marcia Chien, Sophia Chai, David L. Boone, Averil Ma
Journal: The Journal of Experimental Medicine (2004)

The high affinity interleukin (IL)-15 receptor, IL-15Rα, is essential for supporting lymphoid homeostasis. To assess whether IL-15Rα's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Rα– and IL-2/15Rβ–deficient mice. We find that IL-15Rα–competent, IL-2/15Rβ–deficient cells are able to support IL-15Rα–deficient natural killer (NK) and memory CD8+ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Rα–mediated presentation of IL-15 in trans is the primary mechanism by which IL-15Rα functions in vivo. Surprisingly, using IL-15– and IL-15Rα–deficient mixed chimera, we also find that IL-15 and IL-15Rα must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Rα is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15Rα defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells.
Changes in Physical Fitness Predict Improvements in Modifiable Cardiovascular Risk Factors Independently of Body Weight Loss in Subjects With Type 2 Diabetes Participating in the Italian Diabetes and Exercise Study (IDES)
Authors: Stefano Balducci, Silvano Zanuso, Patrizia Cardelli, Laura Salvi, Giulia Mazzitelli, Alessandra Bazuro, Carla Iacobini, Antonio Nicolucci, Giuseppe Pugliese
Journal: Diabetes Care (2012)

OBJECTIVE Physical fitness is inversely related to mortality in the general population and in subjects with type 2 diabetes. Here, we present data concerning the relationship between changes in physical fitness and modifiable cardiovascular risk factors in subjects with type 2 diabetes from the Italian Diabetes and Exercise Study. RESEARCH DESIGN AND METHODS Sedentary patients with type 2 diabetes (n = 606) were enrolled in 22 outpatient diabetes clinics and randomized to twice-a-week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months. Baseline to end-of-study changes in cardiorespiratory fitness, strength, and flexibility, as assessed by Vo2max estimation, a 5–8 maximal repetition test, and a hip/trunk flexibility test, respectively, were calculated in the whole cohort, and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors. RESULTS Changes in Vo2max, upper and lower body strength, and flexibility were significantly associated with the variation in the volume of physical activity, HbA1c, BMI, waist circumference, high-sensitivity C-reactive protein (hs-CRP), coronary heart disease (CHD) risk score, and inversely, HDL cholesterol. Changes in fitness predicted improvements in HbA1c, waist circumference, HDL cholesterol, hs-CRP, and CHD risk score, independent of study arm, BMI, and in case of strength, also waist circumference. CONCLUSIONS Physical activity/exercise-induced increases in fitness, particularly muscular, predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss, thus indicating the need for targeting fitness in these individuals, particularly in subjects who struggle to lose weight.
Evaluation of Human Papillomavirus Antibodies and Risk of Subsequent Head and Neck Cancer
Authors: Aimée R. Kreimer, Mattias Johansson, Tim Waterboer, Rudolf Kaaks, Jenny Chang-Claude, Dagmar Drogen, Anne Tjønneland, Kim Overvad, J. Ramón Quirós, Carlos A. González, Maria José Sánchez, Nerea Larrañaga, Carmen Navarro, Aurelio Barricarte, Ruth C. Travis, Kay-Tee Khaw, Nick Wareham, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Petra H.M. Peeters, Salvatore Panico, Giovanna Masala, Sara Grioni, Rosario Tumino, Paolo Vineis, H. Bas Bueno-de-Mesquita, Göran Laurell, Göran Hallmans, Jonas Manjer, Johanna Ekström, Guri Skeie, Eiliv Lund, Elisabete Weiderpass, Pietro Ferrari, Graham Byrnes, Isabelle Romieu, Elio Riboli, Allan Hildesheim, Heiner Boeing, Michael Pawlita, Paul Brennan
Journal: Journal of Clinical Oncology (2013)

Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.
Is Low Dietary Intake of Omega-3 Fatty Acids Associated With Depression?
Authors: Reeta Hakkarainen, Timo Partonen, Jari Haukka, Jarmo Virtamo, Demetrius Albanes, Jouko Lönnqvist
Journal: American Journal of Psychiatry (2004)

This study examined the association between the dietary intake of omega-3 fatty acids and low mood, major depression, and suicide.A total of 29,133 men ages 50 to 69 years participated in a population-based trial in Finland. The intake of fatty acids and fish consumption were calculated from a diet history questionnaire. Self-reported depressed mood was recorded three times annually, data on hospital treatments due to a major depressive disorder were derived from the National Hospital Discharge Register, and suicides were identified from death certificates.There were no associations between the dietary intake of omega-3 fatty acids or fish consumption and depressed mood, major depressive episodes, or suicide.Dietary intake of omega-3 fatty acids showed no association with low mood level.
Evolution of Genes, Evolution of Species: The Case of Aminoacyl-tRNA Synthetases
Authors: Y. Diaz-Lazcoz, J-C Aude, P. Nitschke, H. Chiapello, C. Landes-Devauchelle, J-L Risler
Journal: Molecular Biology and Evolution (1998)

All of the aminoacyl-tRNA synthetase (aaRS) sequences currently available in the data banks have been subjected to a systematic analysis aimed at finding gene duplications, genetic recombinations, and horizontal transfers. Evidence is provided for the occurrence (or probable occurrence) of such phenomena within this class of enzymes. In particular, it is suggested that the monomeric PheRS from the yeast mitochondrion is a chimera of the alpha and beta chains of the standard tetrameric protein. In addition, it is proposed that the dimeric and tetrameric forms of GlyRS are the result of a double and independent acquisition of the same specificity within two different subclasses of aaRS. The phylogenetic reconstructions of the evolutionary histories of the genes encoding aaRS are shown to be extremely diverse. While large segments of the population are consistent with the broad grouping into the three Woesian domains, some phylogenetic reconstructions do not place the Archae and the Eucarya as sister groups but, rather, show a gram-negative bacteria/eukaryote clustering. In addition, many individual genes pose difficulties that preclude any simple evolutionary scheme. Thus, aaRS's are clearly a paradigm of F. Jacob's "odd jobs of evolution" but, on the whole, do not call into question the evolutionary scenario originally proposed by Woese and subsequently refined by others.
Surgical excision of skin cancer: the importance of training
Authors: P. Salmon, N. Mortimer, M. Rademaker, L. Adams, A. Stanway, S. Hill
Journal: British Journal of Dermatology (2009)

Background Skin cancers are the most common malignancy in New Zealand and their treatment imparts a huge burden on the healthcare system both in terms of the cost of surgical intervention and in treatment delivery (estimates are in excess of NZ$33 million per annum for the year 2000). Currently in New Zealand, skin cancers are excised by dermatologists, general practitioners (GPs), GPs with a special interest in skin surgery (GPSIs) and specialist surgeons with diverse training backgrounds including ear, nose and throat, ophthalmic and general surgeons. To date there is scant literature evaluating complete excision rates following surgical treatment of skin cancer between these vocational groups. Objectives To review retrospectively pathology reports from all skin excisions sent to one private pathology laboratory over three consecutive months. The aim was to investigate the margins of excision and completeness of skin cancer surgery performed by each vocational group. Methods A retrospective analysis of skin pathology reports was undertaken for a 3-month period between April and June 2007. Raw data obtained from the pathology reports included diagnosis, completeness of excision, size of specimens, body site and vocational group of the medical practitioner performing the surgery. Results In total, 1532 lesions were excised: 432 benign and 1100 malignant. Six hundred and seven were from the head and neck. Dermatologists excised 276 lesions of which 93% were malignant, 55% were from the head and neck, and 0% were incompletely excised. GPs excised 633 lesions: 63% malignant, 30% head and neck, 23% incomplete excision of malignant lesions. GPSIs excised 368 lesions: 71% malignant, 35% head and neck, 21·5% incomplete malignant excision. Specialist surgeons excised 255 lesions: 72% malignant, 53% head and neck, 20% incomplete malignant excision. Conclusion GPs and GPSIs excised more benign lesions and had higher incomplete excision rates of skin cancer surgery than dermatologists. Incomplete excision rates for the vocational groups ranged from 0% to 45% depending on site and pathology.
Effects of Age on Sleep Apnea in Men
Authors: EDWARD O. BIXLER, ALEXANDROS N. VGONTZAS, THOMAS TEN HAVE, KATHY TYSON, ANTHONY KALES
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The effects of age on the prevalence of sleep apnea in the general population remain unclear, because previous studies have focused on specific populations. The effects of age on the severity of apnea are unknown. This study was based on a two-stage general random sample of men (aged 20 to 100 yr), consisting of a telephone survey (n = 4,364) and a sleep laboratory evaluation of a survey subsample (n = 741). Obstructive sleep apnea (OSA), based on both sleep laboratory and clinical criteria (apnea/hypopnea index [AHI] ⩾ 10 and the presence of daytime symptoms) was found in 3.3% of the sample, with its maximum prevalence in the middle age group (45 to 64 yr). Also, based solely on laboratory criteria, the prevalence of OSA (obstructive AHI ⩾ 20) showed an age distribution similar to that of OSA diagnosed by laboratory and clinical criteria. The prevalence of any type of sleep apnea (central and obstructive) increased monotonically with age. However, central apnea appeared to account for this monotonic relationship with age. Severity of sleep apnea, as indicated by both number of events and minimum oxygen saturation, decreased with age when any sleep apnea criteria were used and when controlling for body mass index (BMI). The study shows that the prevalence of sleep apnea tends to increase with age but that the clinical significance (severity) of apnea decreases. On the basis of these findings, the sleep laboratory criteria used for diagnosis of sleep apnea should be adjusted for age.
Distinct Responses of Xenografted Gliomas to Different Alkylating Agents Are Related to Histology and Genetic Alterations
Authors: Pascal Leuraud, Luc Taillandier, Jacques Medioni, Lucinda Aguirre-Cruz, Emmanuelle Crinière, Yannick Marie, Michèle Kujas, Jean-Louis Golmard, Adrien Duprez, Jean-Yves Delattre, Marc Sanson, Marie-France Poupon
Journal: Cancer Research (2004)

Abstract A series of 12 human gliomas was established as xenografts in nude mice and used to evaluate the relationship between histology, genetic parameters, and response to alkylating agents. Eight were high-grade oligodendroglial tumors, and four were glioblastoma. They were characterized for their genetic alterations, including those considered as “early” alterations, namely loss of chromosome 1 ± loss of chromosome 19q, TP53 mutation, and those considered as “late” alterations, namely loss of chromosome 10, loss of chromosome 9p, EGFR genomic amplification, PTEN mutation, CDKN2A homozygous deletion, and telomerase reactivation. Chemosensitivity of xenografts to four alkylating agents, temozolomide (42 mg/kg, days 1–5, p.o.), 1,3-bis(2-chloroethyl)-1-nitrosourea (5 mg/kg, day 1, i.p.), Ifosfamide (90 mg/kg, days 1–3, i.p.), and carboplatin (66 mg/kg, day 1, i.p.) was tested by administration of drugs to tumor-bearing mice. Although each tumor presented an individual response pattern, glioblastoma had a lower chemosensitivity than oligodendrogliomas, and temozolomide was the most effective drug. Deletion of 1p ± 19q was associated with higher chemosensitivity, whereas late molecular alterations, particularly EGFR amplification, were associated with chemoresistance. These results suggest that the combined use of histology and molecular markers should eventually be helpful selecting the most appropriate agents for treatment of malignant oligodendrogliomas and astrocytomas.