tbuckley/cabot-search huggingface dataset:
Association of Deep Gray Matter Damage With Cortical and Spinal Cord Degeneration in Primary Progressive Multiple Sclerosis
Authors: Serena Ruggieri, Maria Petracca, Aaron Miller, Stephen Krieger, Rezwan Ghassemi, Yadira Bencosme, Claire Riley, Jonathan Howard, Fred Lublin, Matilde Inglese
Journal: JAMA Neurology (2015)

The investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS.To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability.Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking Test. We collected data from January 1, 2012, through December 31, 2013. Data analysis was performed from January 21 to April 10, 2015.Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability).The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm3 [P < .001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm3; cortical lesion number, 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm3; r = -0.52; P < .01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = -0.60; P < .01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage.In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype.
Effects of &lt;sc&gt;d&lt;/sc&gt;-Glucosamine and 6-Azauridine on Nucleotide Contents, 5-Fluorouridine Uptake, and Cytotoxicity in TA3 Mammary Tumor Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A Holstege, D Keppler
Journal: JNCI Journal of the National Cancer Institute (1986)

In TA3 mammary carcinoma cells in suspension culture, D-glucosamine X HCl (GlcN) induced a diversion of uridylate from UTP into UDP-N-acetylhexosamines, reducing the intracellular pool of UTP and eliciting an increased rate of de novo uridylate synthesis. This rise in de novo synthesis was completely suppressed by addition of 6-azauridine (6-AzaUrd) to the cell suspension in vitro or in the solid TA3 mammary tumor in NMRI mice in vivo. A synergistic depletion of UTP pools to less than 6% of the UTP in controls was observed in TA3 cell suspensions exposed to GlcN and 6-AzaUrd. In solid TA3 tumors in vivo, UTP was reduced by this combination to 19% of the control value. A high sensitivity of the solid tumor to inhibition of pyrimidine synthesis de novo was indicated by the reduction of the UTP content after administration of 6-AzaUrd alone. UTP deficiency in TA3 tumor cells was accompanied by CTP deficiency. In addition, 6-AzaUrd caused a lowering of GTP in the neoplastic tissue. Host liver was resistant to 6-AzaUrd but responded to treatment with GlcN with a decrease in UTP to 67%. Uridine-cytidine kinase was less inhibited in the presence of lowered UTP and CTP, which are potent feedback inhibitors of the enzyme, and enabled an enhanced formation of phosphorylated derivatives of 5-fluorouridine (FUrd). Aside from the formation of 5-fluoro-UTP, we have identified 5-fluoro-UDP-N-acetylhexosamines (FUDPHexNAc), which accumulated when FUrd and GlcN were sequentially administered. Treatment of TA3 cells with FUrd after a pretreatment with 6-AzaUrd and GlcN resulted in a 2.5-fold increase in [14C]FUrd uptake and a duplication of 5-fluorouridylate incorporation into the RNA. The proportion of FUDPHexNAc increased to 58% of the phosphorylated FUrd metabolites, as compared to 6% in TA3 cells exposed exclusively to FUrd. In vivo chemotherapy of mice bearing TA3 ascites tumors was most effective with respect to tumor growth inhibition and animal survival when GlcN and FUrd were combined.
Acid-induced Lung Injury
Authors: KATHARINA MODELSKA, JEAN-FRANÇOIS PITTET, HANS G. FOLKESSON, V. COURTNEY BROADDUS, MICHAEL A. MATTHAY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Although prior experimental work has demonstrated that anti-interleukin-8 (anti-IL-8) therapy reduces lung endothelial injury after acid instillation, there is no information regarding the effect of anti-IL-8 on the function of the alveolar epithelial barrier after acid-induced lung injury. Therefore, the primary objective of this study was to determine the effect of acid-induced lung injury on the function of the alveolar epithelium, and secondly to determine whether pretreatment with anti-IL-8 attenuates acid-induced injury to the lung epithelial barrier. Hydrochloric acid (pH = 1.5 in 1/3 normal saline) was instilled into the lungs of anesthetized, ventilated rabbits. Anti-IL-8 monoclonal antibody (2 mg/kg) or saline was given intravenously 5 min before acid instillation. Acid instillation into the distal airspaces caused an increase in the alveolar epithelial permeability to protein and an approximately 50% reduction in net alveolar fluid clearance. Because a decrease in net alveolar fluid clearance could be due to lung endothelial injury and increased fluid flux from the blood into the airspaces, additional experiments were carried out in which pulmonary blood flow was eliminated. In the absence of pulmonary blood flow, acid instillation led to a 50% decrease in net alveolar fluid clearance. Pretreatment with anti-IL-8 antibody significantly reduced the acid-mediated increase in bi-directional transport of protein across the alveolar epithelium and restored alveolar fluid clearance to normal. The results indicate that acid instillation causes injury to the alveolar epithelial barrier that can be distinguished from the injury to the lung endothelium. Furthermore, pretreatment with anti-IL-8 therapy prevents acid-induced alveolar epithelial injury, a finding of potential clinical importance. Modelska K, Pittet JF, Folkesson HG, Broaddus VC, Matthay MA. Acid-induced lung injury: protective effect of anti-interleukin-8 pretreatment on alveolar epithelial barrier function in rabbits.
Allelic polymorphism of IL-4 and IL-10 genes as underlying factor in the production of cytokines and rate of recurrent pulmonary tuberculosis(RPTB)
Authors: Dmytro Butov, Mykhaylo Kuzhko, Tatyana Butova, Hanna Stepanenko
Journal: European Respiratory Journal (2014)

Background:To study the allelic polymorphism of IL-4 and IL-10genes in relation to serum levels of cytokines and prevalence of RPTB.Methods:The study comprised 80 individuals in Kharkiv region including 59patientsRPTB(group1) and21healthy donors(group2).Serum levels of cytokines IL-4and IL-10were evaluated by ELISA.Investigations of gene polymorphisms of these cytokines were performed using restriction analysis of the amplification products of specific regions of the genome.Two polymorphic variants were examined:promoter regionC-589T ofIL-4 gene and G-1082A-IL-10.Results:1group-IL-4and IL-10 were 9.55±0.24pg/L and 40.04±0.74pg/L, while in 2group-29.99±1.27pg/L and 50.25±1.26pg/L respectively(p
Impact of increasing dialysis volume on adequacy targets
Authors: J Harty, H Boulton, M Venning, R Gokal
Journal: Journal of the American Society of Nephrology (1997)

Failure to achieve target values for both urea (Kt/V) and creatinine clearance has been associated with increased morbidity and mortality in continuous ambulatory peritoneal dialysis patients. The conventional continuous ambulatory peritoneal dialysis regimen, which uses four 2-L exchanges per day, has resulted in up to 40% of such patients failing to achieve proposed targets for weekly Kt/V of 1.7 and weekly creatinine clearance (WCC) of 50 L. In a prospective study, the impact of increasing prescribed volumes by 0.5 L per exchange was evaluated on attaining urea and creatinine clearance targets over a 1-yr period. At 1 yr, 17 patients remaining on the increased dialysis prescription were compared with 18 patients remaining on an unchanged regimen. The mean increase in daily prescribed volume was 1.5 L (22%). This resulted in a significant increase in both peritoneal dialysis Kt/V (1.59 to 1.78 L = 12%) and peritoneal dialysis WCC (45.8 to 50.1 L = 10%) by 1 yr. Because of loss of renal function, there was no significant increase in total clearance at 1 yr, but this loss of renal clearance was offset by the gain in peritoneal clearance. Residual renal function fell at a similar rate in both the increased dialysis and control groups. In the latter, although peritoneal clearance remained stable over the 1-yr period, loss of renal function resulted in reductions in both total Kt/V and WCC. In conclusion, exchange volume can be increased to compensate for loss of renal function over a 1-yr period. Progressive loss of renal clearance resulted in only a modest gain in total solute clearance. It was the larger patients who tolerated the increase in exchange volumes. However, such patients (by virtue of their size) tended not to achieve target values for solute clearance, and the modest gain in peritoneal clearance was insufficient to increase the number of patients in this group achieving such targets for dialysis adequacy.
Quality of life of paediatric patients with cystic fibrosis and their caregivers
Authors: Reka Bodnar, Klara Holics, Rita Ujhelyi, Lajos Kovacs, Agnes Meszaros, Laszlo Kadar
Journal: European Respiratory Journal (2011)

Introduction:  Cystic fibrosis (CF) is the most common fatal genetic disease which has a significant impact on patient9s and their caregiver9s daily life.   Objective:  The aim of the study was to determine the quality of life (QoL) of children with CF and their parents and to compare the impact of CF on daily life to that of asthma.   Methods:  The  Cystic Fibrosis Questionnaire  (CFQ) was used to measure the QoL of children with CF and their caregivers.  PedsQL   TM   4.0 Generic Core Scale  was used to compare QoL of paediatric CF patients and their caregivers to the QoL of asthmatic children and their parents.   Results:  54 (n CF =22, n asthma =32) children9s data were collected (mean age: 13.05±3.13 years). Total score of PedsQL was 71.53±13.26 by CF patients, while total score of PedsQL was 77.35±16.61 in asthmatic patients (p=0.2). CF caregivers9 score was 71.17±15.26 while total score of asthmatic patients9 caregivers was 71.07±14.93 (p=0.98). CFQ results are shown in the table.   Conclusion:  QoL scores were not significantly lower in children with CF than in asthmatic patients.
Sensitization to three mites in Cuban children with allergic respiratory diseases
Authors: Mirta Alvarez, Raul Castro, Alexis Labrada, Irene Enríquez, Mercedes Ronquillo, José Rodríguez
Journal: European Respiratory Journal (2014)

Introduction: According to published results of the study ISAAC phase III, the prevalence of allergic diseases as rhinitis and asthma have increased in our country. The dust mites are the main agents that can trigger or contribute to respiratory diseases and Dermatophagoides pteronyssinus (DP), Blomia tropicalis (BT) and Dermatophagoides siboney (DS) are the most prevalents. Objective: to determine the sensitization to 3 domestic mite species in allergic children and its relation with respiratory diseases.  Method: A cross-sectional analytical study was carried out. The study group included 93 children (mean age 9, 4, range 1-18 years) with male predominance ( 53,7%) attended in the allergy department of the University Hospital Calixto Garcia of Havana, Cuba from June to August 2013. For each subject, a clinical history was compiled and skin testing was performed. Results: Allergic rhinitis was the most allergic illness reported (49%), followed by asthma (34%) coexisting both of them in 30% of studied children. Ninety five percent was sensitized to mites and 75 percent was sensitized to three mites. Althoug the higher geometric mean of wheal was to B.tropicales did there was not significant difference in respect to DP and DS. It was found that the age has influence in the cutaneous reactivity being bigger the size of the wheal in older children(p
Serum Bank for Biological Markers for Breast Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: I J Masnyk, M Sears, D Corle, V L Go, M Dunsmore
Journal: JNCI Journal of the National Cancer Institute (1983)

A bank of serum specimens from women at varying risks of breast cancer has been established. Panels of test specimens can be secured by qualified investigators to evaluate newly discovered biological markers for breast cancer, to verify preliminary data, and to compare performance of established assays among different laboratories. Panels consisting of coded 1-ml vials of sera will be sent upon request to approved investigators. The procedure for application for serum panels is described.
Creating an Effort Tracking Tool to Improve Therapeutic Cancer Clinical Trials Workload Management and Budgeting
Authors: Pam James, Patty Bebee, Linda Beekman, David Browning, Mathew Innes, Jeannie Kain, Theresa Royce-Westcott, Marcy Waldinger
Journal: Journal of the National Comprehensive Cancer Network (2011)

Quantifying data management and regulatory workload for clinical research is a difficult task that would benefit from a robust tool to assess and allocate effort. As in most clinical research environments, The University of Michigan Comprehensive Cancer Center (UMCCC) Clinical Trials Office (CTO) struggled to effectively allocate data management and regulatory time with frequently inaccurate estimates of how much time was required to complete the specific tasks performed by each role. In a dynamic clinical research environment in which volume and intensity of work ebbs and flows, determining requisite effort to meet study objectives was challenging. In addition, a data-driven understanding of how much staff time was required to complete a clinical trial was desired to ensure accurate trial budget development and effective cost recovery. Accordingly, the UMCCC CTO developed and implemented a Web-based effort-tracking application with the goal of determining the true costs of data management and regulatory staff effort in clinical trials. This tool was developed, implemented, and refined over a 3-year period. This article describes the process improvement and subsequent leveling of workload within data management and regulatory that enhanced the efficiency of UMCCC's clinical trials operation.
PRELIMINARY REPORT OF A CONTROLLED MENTAL HEALTH WORKSHOP IN A PUBLIC SCHOOL SYSTEM
Authors: BENJAMIN H. BALSER, FRED BROWN, MINERVA L. BROWN, EDWARD D. JOSEPH, DONALD K. PHILLIPS
Journal: American Journal of Psychiatry (1955)

1. A control mental health workshop was set up in a public school system. A volunteer group of teachers and the administrative group of principals, assistant principals and heads of departments were separately exposed to 15-week 1 ½hour seminars on mental health under the guidance of a qualified psychiatrist. 2. A control group was set up matching teachers as to age, sex, duration of service, and grade taught; also a control group of administrators from a neighboring community. 3. All 4 groups were given the same battery of psychological tests before and after the seminars. 4. Studies of the psychological test responses show that although there were statistically significant changes for the experimental group, these were also found in the control group. 5. It should be noted that if the pre-and posttesting of the experimental groups were evaluated without control groups the results could have been interpreted as excellent. 6. Further control studies are projected with varying size groups, different instructors, different methods of selecting participants, and varying the content of the lecture and discussion material.
Mammary Tumor Virus (MTV) Infection of CBA/Bin Mice Involving Production of Antibodies to MTV
Authors: Martin Müller, Stefan Zotter
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Mammary Tumor Virus (MTV) Infection of CBA/Bin Mice Involving Production of Antibodies to MTV Get access Martin Müller, Martin Müller Pathological Institute of Medical Academy “Carl Gustav Carus,”, Dresden GDR, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Stefan Zotter Stefan Zotter Pathological Institute of Medical Academy “Carl Gustav Carus,”, Dresden GDR, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 3, March 1973, Pages 713–717, https://doi.org/10.1093/jnci/50.3.713 Published: 01 March 1973 Article history Received: 18 July 1972 Accepted: 04 October 1972 Published: 01 March 1973
Chronic Obstructive Pulmonary Disease: A Forgotten Killer
Authors: J. Vestbo
Journal: European Respiratory Journal (2009)

Edited by C. Midgley    Published by Oxford University Press, Oxford, UK    Pages: 108. Price: £18.99. ISBN: 978-0-1992-3732-6

Chronic Obstructive Pulmonary Disease: A Forgotten Killer    This book (and accompanying DVD) is part of a series of seven books forming an Open University course for students in the first year of an undergraduate programme in Health Sciences. For this reason …
Treatment outcome of multi-drug resistant tuberculosis treated as outpatient in a tertiary care center
Authors: Irfan Muhammad, Ahmed Suleman Haque, Zeeshan Waheed, Javaid A. Khan
Journal: European Respiratory Journal (2011)

Introduction: Community-based out-patient treatment for multidrug-resistant tuberculosis (MDR TB) is relatively new concept with reported successful outcomes.

Objective: To assess the treatment outcomes of HIV negative MDR TB patients treated as outpatient at a tertiary care center in Karachi, Pakistan.

Methods: Observational study of culture proven HIV negative MDR TB patients treated at Aga Khan University Hospital, Karachi. Data were collected on predesigned performa regarding patient's demography, clinical features, drug sensitivity, treatment and outcome.

Results: A total of 53 HIV negative patients (27 males), with mean age of 37±15 years (range 15-76 years), received treatment as outpatient for culture proven MDR TB. 51 patients (96.2%) had pulmonary while 3 patients (5.6%) had extra-pulmonary TB. History of exposure to tuberculosis patients was found in 36 (67.9%) patients. Treatment regimen with 2nd line drugs was decided on individual basis according to DST on sputum culture results. The mean duration of treatment was 18 months. Successful outcome was seen in 25 patients (47.2%), 25 patients (47.2%) were loss to follow up and defaulted while 3 (5.6%) patients remain smear positive at the end of treatment. Success rate was 89.2% in those who completed the treatment.

Conclusion: Community-based out-patient treatment strategy is both feasible and safe for the treatment of MDR-TB patients in resource limited country like Pakistan and this strategy should be integrated into the routine approach to treatment of MDR-TB patients in the country where the expertise are available. High default rate is this strategy is the main challenge which should be addressed.
Effect of curcumin on LPS-induced neutrophil activation and acute lung injury
Authors: Hyejin Jeong, Chihyeong Yun
Journal: European Respiratory Journal (2012)

Curcumin has antioxidant, antitumor, and anti-inflammatory properties. Neutrophils play an important role in the development of organ dysfunction associated with severe infection. This study was performed to evaluate the effects of curcumin on lipopolysaccharide (LPS) - induced neutrophil activation and acute lung injury.  To assess the anti-inflammatory effect of curcumin on LPS induced neutrophil activation, neutrophils from human blood were incubated with various concentrations of curcumin (0, 1, 10, 50 and 100 nM) and LPS (100 ng/ml). The protein levels for interleukin (IL)-6, 8 and tumor necrosis factor (TNF)-α were measured using ELISA 4 hr after incubation period. To elucidate the intracellular signaling pathway, We measured the levels of phosphorylation of p38 mitogen activated protein kinases (p38), extracelluar signal-regulated kinase (ERK)1/2 and c-Jun amino-terminal kinases (JNK) with western blot analysis and nuclear levels of nuclear factor (NF)-κB with electrophoretic mobility shift assays 0.5 hr after incubation period. We also examined the effect of curcumin (60mg/kg, IP) on acute lung injury and mortality of mouse treated with LPS(20 mg/kg, IP) to determine whether these effects of curcumin also have in vivo significance.  Curcumin attenuated LPS - induced neutrophils activation including expression of p38, JNK, NF-κB, IL-6, 8 and TNF-α. Mouse treated by Curcumin were protected from LPS-induced lung injury, as determined by wet/dry weight ratio, lung injury score and IL-6, 8 and TNF-α in bronchoalveolar lavage fluid (BALF) levels and mortality.Curcumin can attenuate LPS - induced acute lung injury and mortality via the attenuation of neutrophil activation caused by LPS.
Tissue-Specific Cell Cycle Indicator Reveals Unexpected Findings for Cardiac Myocyte Proliferation
Authors: Maretoshi Hirai, Ju Chen, Sylvia M. Evans
Journal: Circulation Research (2015)

Discerning cardiac myocyte cell cycle behavior is challenging owing to commingled cell types with higher proliferative activity.To investigate cardiac myocyte cell cycle activity in development and the early postnatal period.To facilitate studies of cell type-specific proliferation, we have generated tissue-specific cell cycle indicator BAC transgenic mouse lines. Experiments using embryonic fibroblasts from CyclinA2-LacZ-floxed-EGFP, or CyclinA2-EGFP mice, demonstrated that CyclinA2-βgal and CyclinA2-EGFP were expressed from mid-G1 to mid-M phase. Using Troponin T-Cre;CyclinA2-LacZ-EGFP mice, we examined cardiac myocyte cell cycle activity during embryogenesis and in the early postnatal period. Our data demonstrated that right ventricular cardiac myocytes exhibited reduced cell cycle activity relative to left ventricular cardiac myocytes in the immediate perinatal period. Additionally, in contrast to a recent report, we could find no evidence to support a burst of cardiac myocyte cell cycle activity at postnatal day 15.Our data highlight advantages of a cardiac myocyte-specific cell cycle reporter for studies of cardiac myocyte cell cycle regulation.