tbuckley/cabot-search huggingface dataset:
Loss of tumor-specific and idiotype-specific immunity with age.
Authors: P M Flood, J L Urban, M L Kripke, H Schreiber
Journal: The Journal of Experimental Medicine (1981)

The ultraviolet light-induced fibrosarcoma 1591 undergoes "first-set rejection" when transplanted into normal syngeneic mice. We found, however, that the primary resistance of normal mice decreases with age, beginning at 9--12 mo, equivalent to middle age for mice. Mice lose with age the capacity to mount both idiotypic and anti-idiotypic responses responsible for controlling the growth of tumor. This loss was correlated with quantitative as well as qualitative changes in the response, such as changes in specificity and clonotype. Normal young mice regularly expressed a dominant common anti-1591 "idiotype" as defined by an anti-idiotypic probe. The capability of normal mice to respond with lymphocytes of this dominant common idiotype began to decline at about 8 mo of age. At this time, animals still generated tumor-specific lymphocytes, but these lymphocytes appear to be idiotypically different lymphocyte clones. With further increase in age, animals responded with tumor-reactive lymphocytes that showed a marked cross-reactivity to other tumor target cell lines. Both in vivo and in vitro, the capability of normal mice to mount an immune response that was specific for the 1591 tumor cells decreased between 9 and 14 mo, which was the age individual mice became increasingly susceptible to a challenge with 1591 tumor cells. Thus, our data suggest that clones of tumor-specific T cells provide primary and early protection of young animals against challenge with malignant 1591 cells. However, the dominance of these tumor-specific T cell clones in a primary immune response is lost in middle-age. Because the ability of animals to mount anti-idiotypic immune response also declined in middle-aged animals, it is possible that the observed loss of clonal dominance of tumor-specific clones with increasing age is at least partially related to age-dependent changes in the anti-idiotypic compartment.
Patients With End-Stage Congestive Heart Failure Treated With β-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance
Authors: Hajime Kubo, Kenneth B. Margulies, Valentino Piacentino, John P. Gaughan, Steven R. Houser
Journal: Circulation (2001)

Background Alterations in Ca 2+ -handling proteins are thought to underlie the deranged Ca 2+ transients that contribute to deterioration of cardiac function in congestive heart failure (CHF). Clinical trials in CHF patients have shown that treatment with β-adrenergic receptor antagonists (βB) improves cardiac performance. The present study determined whether the abundance of Ca 2+ -handling proteins is different in failing hearts from patients treated or untreated with β B. Methods and Results Ca 2+ regulatory protein abundance was compared in LV myocardium of 10 nonfailing hearts (NF group) and 44 failing hearts (CHF group) removed at transplantation. Analysis was performed in βB-treated (βB-CHF) and non–βB treated (non-βB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n=10), nonischemic dilated cardiomyopathy (DCM, n=10), ICM with βB therapy (βB-ICM, n=12), and DCM with βB therapy (βB-DCM, n=12). Sarcoplasmic reticulum Ca 2+ ATPase, phospholamban, and Na + -Ca 2+ exchanger protein abundance were determined by use of Western blot analysis. Ca 2+ transients were measured with fluo-3. Sarcoplasmic reticulum Ca 2+ ATPase was significantly less abundant whereas phospholamban and Na + -Ca 2+ exchanger were not significantly altered in non-βB-CHF versus NF. Sarcoplasmic reticulum Ca 2+ ATPase in the βB-ICM and βB-DCM was greater than in non-βB-CHF and were not different than in NF. Ca 2+ transients in non-βB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca 2+ transients from βB-CHF myocytes had shorter durations than in βB-CHF myocytes. Conclusions βB treatment in CHF patients can normalize the abundance of myocyte Ca 2+ regulatory proteins and improve Ca 2+ -handling.
NICE issues draft guideline on end of life care:
Authors: Ingrid Torjesen
Journal: BMJ (2015)

<h3>Introduction</h3> Japanese government introduced behavioural approach for modifying unfavourable life styles leading to metabolic syndrome (MetS) into community health promotion in 2008. Previous studies have reported its efficacy in community settings. However, few studies examined effectiveness of work-site behavioural intervention for employees. <h3>Methods</h3> A total of 311 male workers of a health insurance company were recruited. They were classified as high risk group of Mets by measuring BMI, blood pressure, HbA1c, HDL and LDL cholesterol levels at the annual health examination in 2008. A subgroup of them were recommended to participate in a health promotion activity with behavioural approach aiming diet and physical activity modification (intervention group; 86 persons). After 1-year follow-up, prevalence of MetS and levels of the previous factors were compared between the intervention group and non-intervention group (225 persons). <h3>Results</h3> After adjusting for age, no statistically significant difference of the prevalence of MetS and levels of the previous factors was found between the group at the baseline examination. In the 2009 examination, BMI, systolic and diastolic blood pressure and LDL cholesterol levels decreased significantly in the intervention group while HbA1c level increased and HDL cholesterol level decreased in the non-intervention group. Prevalence of Mets decreased in the intervention group (−23.3%: 95% CI −34.2 to −12.2%) and also did in the non-intervention group (−16.8%: −23.5 to −10.3%). Difference in change of the prevalence in each group (6.5%: −3.7 to 16.7%) was in borderline significance. <h3>Conclusion</h3> This quasi-experimental study at worksite suggested effectiveness of work-site behavioural intervention for employees with MetS in Japan.
Regional Brain Volume Abnormalities and Long-term Cognitive Outcome in Preterm Infants
Authors: Bradley S. Peterson
Journal: JAMA (2000)

Preterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits.To determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes.Case-control study conducted in 1998 and 1999 at 2 US university medical schools.A consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status.Volumes of cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children.Regional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6%; right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2%; right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P =.01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P =.01]; right, 7.4% [P =.005]), and subgenual (left, 8.9% [P =.03]; right, 11.7% [P =.01]) cortices. Preterm children's brain volumes were significantly larger (by 105. 7%-271.6%) in the occipital and temporal horns of the ventricles (P<. 001 for all) and smaller in the cerebellum (6.7%; P =.02), basal ganglia (11.4%-13.8%; P</=.005), amygdala (left, 20.2% [P =.001]; right, 30.0% [P<.001]), hippocampus (left, 16.0% [P =.001]; right, 12.0% [P =.007]), and corpus callosum (13.1%-35.2%; P</=.01 for all). Volumes of sensorimotor and midtemporal cortices were associated positively with full-scale, verbal, and performance IQ scores (P<.01 for all).Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome. JAMA. 2000;284:1939-1947.
Does This Patient Have an Acute Thoracic Aortic Dissection?
Authors: Michael Klompas
Journal: JAMA (2002)

ContextThe diagnosis of acute thoracic aortic dissection is difficult to make and often missed.ObjectiveTo review the accuracy of clinical history taking, physical examination, and plain chest radiograph in the diagnosis of acute thoracic aortic dissection.Data SourcesA comprehensive review of the English-language literature was conducted using MEDLINE for the years 1966 through 2000. Additional sources were identified from the references of retrieved articles.Study SelectionThe search revealed 274 potential sources, which were reviewed for pertinence and quality. Articles included were original investigations describing the clinical findings for 18 or more consecutive patients with confirmed thoracic aortic dissection. Twenty-one studies were identified that met selection criteria.Data ExtractionCritical appraisal and data extraction were performed by the author.Data SynthesisMost patients with thoracic aortic dissection have severe pain (pooled sensitivity, 90%) of sudden onset (sensitivity, 84%). The absence of sudden pain onset lowers the likelihood of dissection (negative likelihood ratio [LR], 0.3; 95% confidence interval [CI], 0.2-0.5). On examination, 49% of patients have an elevated blood pressure, 28% have a diastolic murmur, 31% have pulse deficits or blood pressure differentials, and 17% have focal neurological deficits. Presence of a diastolic murmur does little to change the pretest probability of dissection (positive LR, 1.4; 95% CI, 1.0-2.0), whereas pulse or blood pressure differentials and neurological deficits increase the likelihood of disease (positive LRs, 5.7 and 6.6-33.0, respectively). The plain chest radiograph results are usually abnormal (sensitivity, 90%); hence, the presence of a normal aorta and mediastinum decreases the probability of dissection (negative LR, 0.3; 95% CI, 0.2-0.4). Combinations of findings increase the likelihood of disease.ConclusionsThe presence of pulse deficits or focal neurological deficits increases the likelihood of an acute thoracic aortic dissection in the appropriate clinical setting. Conversely, a completely normal chest radiograph result or the absence of pain of sudden onset lowers the likelihood. Overall, however, the clinical examination is insufficiently sensitive to rule out aortic dissection given the high morbidity of missed diagnosis.
Emphysema and Airway Obstruction as Risk Factors for Lung Cancer
Authors: Juan P. de Torres, Javier J. Zulueta, Juan P. Wisnivesky
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

We read with great interest the article by Dr. Wilson and colleagues entitled ‘‘Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer’’ (1). Regarding the relationship between emphysema and risk of lung cancer, we are delighted that this work reproduces the results previously published by our group, thus validating their significance (2). There are a few comments we would like to make about this important study. First, although we acknowledge the differences in the study populations (age, smoking history and status, and clinical characterization), the higher prevalence of emphysema (47%) and chronic obstructive pulmonary disease (COPD) (47%) in comparison to our cohort is somewhat surprising. The higher prevalence of emphysema may be explained by the age (older) and smoking history (greater) of Wilson and coworkers’ population. Perhaps the higher prevalence of COPD is due to the fact that in their study, Wilson and coworkers performed spirometry without bronchodilator to diagnose and grade COPD. Lack of use of bronchodilators has elsewhere been associated with overdiagnosis of COPD in as many as 33% of individuals (3). In Wilson and coworkers’ group, many individuals may not have COPD according to current defining criteria, and many others may have less severe COPD, both of which results could seriously influence the statistical analysis. We wonder whether a correct diagnosis of COPD by post-bronchodilator spirometry would also result in a negative association between airway obstruction and risk of lung cancer, as we found in our cohort. Second, we encourage the authors to analyze the association between the pathologic characterization of the 99 lung cancers diagnosed in their cohort and the presence of emphysema. In our study, emphysema was associated more commonly with adenocarcinoma, and the tumors were located in the emphysematous areas in the majority of patients. Finally, we feel that a more detailed description of the protocol for the diagnosis of lung cancer in this screening trial is warranted. We find that the drop in compliance to 25% by the third year is quite striking. In spite of these discrepancies, we believe that studies such as Wilson and coworkers’ and the one published by our group underline the importance of the relationship between two of the most common and deadly diseases among smokers.
Integrating Y-Chromosome, Mitochondrial, and Autosomal Data to Analyze the Origin of Pig Breeds
Authors: O. Ramirez, A. Ojeda, A. Tomas, D. Gallardo, L.S. Huang, J.M. Folch, A. Clop, A. Sanchez, B. Badaoui, O. Hanotte, O. Galman-Omitogun, S.M. Makuza, H. Soto, J. Cadillo, L. Kelly, I.C. Cho, S. Yeghoyan, M. Perez-Enciso, M. Amills
Journal: Molecular Biology and Evolution (2009)

We have investigated the origin of swine breeds through the joint analysis of mitochondrial, microsatellite, and Y-chromosome polymorphisms in a sample of pigs and wild boars with a worldwide distribution. Genetic differentiation between pigs and wild boars was remarkably weak, likely as a consequence of a sustained gene flow between both populations. The analysis of nuclear markers evidenced the existence of a close genetic relationship between Near Eastern and European wild boars making it difficult to infer their relative contributions to the gene pool of modern European breeds. Moreover, we have shown that European and Far Eastern pig populations have contributed maternal and paternal lineages to the foundation of African and South American breeds. Although West African pigs from Nigeria and Benin exclusively harbored European alleles, Far Eastern and European genetic signatures of similar intensity were detected in swine breeds from Eastern Africa. This region seems to have been a major point of entry of livestock species in the African continent as a result of the Indian Ocean trade. Finally, South American creole breeds had essentially a European ancestry although Asian Y-chromosome and mitochondrial haplotypes were found in a few Nicaraguan pigs. The existence of Spanish and Portuguese commercial routes linking Asia with America might have favored the introduction of Far Eastern breeds into this continent.
Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis
Authors: Ronald J. Wapner, Christa Lese Martin, Brynn Levy, Blake C. Ballif, Christine M. Eng, Julia M. Zachary, Melissa Savage, Lawrence D. Platt, Daniel Saltzman, William A. Grobman, Susan Klugman, Thomas Scholl, Joe Leigh Simpson, Kimberly McCall, Vimla S. Aggarwal, Brian Bunke, Odelia Nahum, Ankita Patel, Allen N. Lamb, Elizabeth A. Thom, Arthur L. Beaudet, David H. Ledbetter, Lisa G. Shaffer, Laird Jackson
Journal: New England Journal of Medicine (2012)

Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis.
Natriuretic Peptides Enhance the Production of Adiponectin in Human Adipocytes and in Patients With Chronic Heart Failure
Authors: Osamu Tsukamoto, Masashi Fujita, Mahoto Kato, Satoru Yamazaki, Yoshihiro Asano, Akiko Ogai, Hidetoshi Okazaki, Mitsutoshi Asai, Yoko Nagamachi, Norikazu Maeda, Yasunori Shintani, Tetsuo Minamino, Masanori Asakura, Ichiro Kishimoto, Tohru Funahashi, Hitonobu Tomoike, Masafumi Kitakaze
Journal: Journal of the American College of Cardiology (2009)
Local anaesthesia for fibreoptic bronchoscopy: transcricoid injection or the "spray as you go" technique?
Authors: A R Webb, S S Fernando, H R Dalton, J E Arrowsmith, M A Woodhead, A R Cummin
Journal: Thorax (1990)

Local anaesthesia for fibreoptic bronchoscopy should be given by a safe technique that is not unpleasant to the patient and should provide acceptable conditions for the bronchoscopist. Single injection transcricoid local anaesthesia was compared with the "spray as you go" technique in patients having day case fibreoptic bronchoscopy. Patients were randomised to receive either 100 mg lignocaine by a single cricothyroid puncture or 240 mg lignocaine instilled through the bronchoscope under direct vision. Further doses were given by the operator to both groups as required. The 30 patients receiving transcricoid lignocaine coughed less (3.56 (SD 3.1) coughs/min) than the 32 patients receiving lignocaine through the bronchoscope (5.89 (4.8)/min) despite receiving a lower total dose of lignocaine (322 (25.9) v 451 (20.9) mg). Cricothyroid puncture was not associated with any complications and was not unpleasant for the patients.
Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial
Authors: Jeremy Chataway, Nadine Schuerer, Ali Alsanousi, Dennis Chan, David MacManus, Kelvin Hunter, Val Anderson, Charles R M Bangham, Shona Clegg, Casper Nielsen, Nick C Fox, David Wilkie, Jennifer M Nicholas, Virginia L Calder, John Greenwood, Chris Frost, Richard Nicholas
Journal: The Lancet (2014)

Secondary progressive multiple sclerosis, for which no satisfactory treatment presently exists, accounts for most of the disability in patients with multiple sclerosis. Simvastatin, which is widely used for treatment of vascular disease, with its excellent safety profile, has immunomodulatory and neuroprotective properties that could make it an appealing candidate drug for patients with secondary progressive multiple sclerosis.We undertook a double-blind, controlled trial between Jan 28, 2008, and Nov 4, 2011, at three neuroscience centres in the UK. Patients aged 18-65 years with secondary progressive multiple sclerosis were randomly assigned (1:1), by a centralised web-based service with a block size of eight, to receive either 80 mg of simvastatin or placebo. Patients, treating physicians, and outcome assessors were masked to treatment allocation. The primary outcome was the annualised rate of whole-brain atrophy measured from serial volumetric MRI. Analyses were by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00647348.140 participants were randomly assigned to receive either simvastatin (n=70) or placebo (n=70). The mean annualised atrophy rate was significantly lower in patients in the simvastatin group (0·288% per year [SD 0·521]) than in those in the placebo group (0·584% per year [0·498]). The adjusted difference in atrophy rate between groups was -0·254% per year (95% CI -0·422 to -0·087; p=0·003); a 43% reduction in annualised rate. Simvastatin was well tolerated, with no differences between the placebo and simvastatin groups in proportions of participants who had serious adverse events (14 [20%] vs nine [13%]).High-dose simvastatin reduced the annualised rate of whole-brain atrophy compared with placebo, and was well tolerated and safe. These results support the advancement of this treatment to phase 3 testing.The Moulton Foundation [charity number 1109891], Berkeley Foundation [268369], the Multiple Sclerosis Trials Collaboration [1113598], the Rosetrees Trust [298582] and a personal contribution from A Pidgley, UK National Institute of Health Research (NIHR) University College London Hospitals/UCL Biomedical Research Centres funding scheme.
Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes.
Authors: R C Atkins, W L Ford
Journal: The Journal of Experimental Medicine (1975)

A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a "third party" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex.