tbuckley/cabot-search huggingface dataset:
Parallel Evolution of Genes and Languages in the Caucasus Region
Authors: Oleg Balanovsky, Khadizhat Dibirova, Anna Dybo, Oleg Mudrak, Svetlana Frolova, Elvira Pocheshkhova, Marc Haber, Daniel Platt, Theodore Schurr, Wolfgang Haak, Marina Kuznetsova, Magomed Radzhabov, Olga Balaganskaya, Alexey Romanov, Tatiana Zakharova, David F. Soria Hernanz, Pierre Zalloua, Sergey Koshel, Merritt Ruhlen, Colin Renfrew, R. Spencer Wells, Chris Tyler-Smith, Elena Balanovska
Journal: Molecular Biology and Evolution (2011)

We analyzed 40 single nucleotide polymorphism and 19 short tandem repeat Y-chromosomal markers in a large sample of 1,525 indigenous individuals from 14 populations in the Caucasus and 254 additional individuals representing potential source populations. We also employed a lexicostatistical approach to reconstruct the history of the languages of the North Caucasian family spoken by the Caucasus populations. We found a different major haplogroup to be prevalent in each of four sets of populations that occupy distinct geographic regions and belong to different linguistic branches. The haplogroup frequencies correlated with geography and, even more strongly, with language. Within haplogroups, a number of haplotype clusters were shown to be specific to individual populations and languages. The data suggested a direct origin of Caucasus male lineages from the Near East, followed by high levels of isolation, differentiation, and genetic drift in situ. Comparison of genetic and linguistic reconstructions covering the last few millennia showed striking correspondences between the topology and dates of the respective gene and language trees and with documented historical events. Overall, in the Caucasus region, unmatched levels of gene–language coevolution occurred within geographically isolated populations, probably due to its mountainous terrain.
Nuclear Factor (NF)-κB2 (p100/p52) Is Required for Normal Splenic Microarchitecture and B Cell–mediated Immune Responses
Authors: Jorge H. Caamaño, Cheryl A. Rizzo, Stephen K. Durham, Debra S. Barton, Carmen Raventós-Suárez, Clifford M. Snapper, Rodrigo Bravo
Journal: The Journal of Experimental Medicine (1998)

The nfkb2 gene is a member of the Rel/NF-κB family of transcription factors. COOH-terminal deletions and rearrangements of this gene have been associated with the development of human cutaneous T cell lymphomas, chronic lymphocytic leukemias, and multiple myelomas. To further investigate the function of NF-κB2, we have generated mutant mice carrying a germline mutation of the nfkb2 gene by homologous recombination. NF-κB2–deficient mice showed a marked reduction in the B cell compartment in spleen, bone marrow, and lymph nodes. Moreover, spleen and lymph nodes of mutant mice presented an altered architecture, characterized by diffuse, irregular B cell areas and the absence of discrete perifollicular marginal and mantle zones; the formation of secondary germinal centers in spleen was also impaired. Proliferation of NF-κB2–deficient B cells was moderately reduced in response to lipopolysaccharide, anti-IgD-dextran, and CD40, but maturation and immunoglobulin switching were normal. However, nfkb2 (−/−) animals presented a deficient immunological response to T cell–dependent and –independent antigens. These findings indicate an important role of NF-κB2 in the maintenance of the peripheral B cell population, humoral responses, and normal spleen architecture.
Effects of Cyclic AMP, Sympathomimetic Amines, and Adrenergic Receptor Antagonists on Renin Secretion
Authors: Nathaniel Winer, Deenbandhu S. Chokshi, Walter G. Walkenhorst
Journal: Circulation Research (1971)

Renal vein renin activity was measured by bioassay of plasma obtained from anesthetized dogs during renal arterial infusion of sympathomimetic amines, cyclic AMP, and other nucleotides. Renin secretion was calculated as the product of renal blood flow and the arterial-renal venous renin difference. Infusion of cyclic AMP significantly increased renin secretion, while administration of ATP, ADP, 5'AMP, and adenosine in quantities equimolar to cyclic AMP had no effect. Phentolamine, an α -receptor antagonist, and dl- propranolol, a β -receptor blocker, abolished the cyclic AMP-induced rise in renin secretion. Paradoxically, the increase in renin production induced by infusion of norepinephrine, a predominantly α -receptor agonist, was suppressed by propranolol administration, and the renin-stimluating effect of isoproterenol, a β -receptor stimulator, was blocked by phentolamine administration. In addition, the d - and l -isomers of propranolol were equipotent in suppressing the isoproterenol-induced rise in renin secretion. Administration of AY-21,O11, a β -receptor antagonist which lacks local anesthetic properties, also prevented the isoproterenol-induced rise in renin secretion, but lidocaine had no suppressive effect. The effects on renin secretion of cyclic AMP and sympathomimetic amines alone and in combination with adrenergic receptor antagonists were independent of changes in glomerular filtration rate, sodium excretion, urine flow, systemic blood pressure, and heart rate. The data suggest that cyclic AMP acts within the kidney as an intracellular mediator of renin secretion, and that phentolamine and propranolol suppress ream secretion at a site distal to cyclic AMP production, rather than by blockade of plasma membrane adrenergic receptors or inhibition of adenyl cyclase.
A prospective study of change in bone mineral density over one year in adults with cystic fibrosis
Authors: C S Haworth
Journal: Thorax (2002)

<b>Background:</b> Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. To identify appropriate therapeutic strategies and the optimal time for intervention, it is necessary to document the natural history of cystic fibrosis related low BMD. <b>Methods:</b> 114 adults with cystic fibrosis underwent bone densitometry a median (25–75% interquartile range) of 12 (12–13) months after initial assessment of bone density. BMD was measured in the lumbar spine, femoral neck, total hip, and distal forearm on recruitment to the trial and at follow up. <b>Results:</b> In patients ≤24 years of age (n=55, mean (SD) age 19.5 (2.6) years) in whom an annual increase in BMD would normally be expected, BMD increased by a mean (95% CI) 2.9% (1.6 to 4.2) per year in the distal forearm (p&lt;0.001), but decreased by 2.5% (95% CI –3.8 to –1.2) per year in the femoral neck (p&lt;0.001) and by 2.2% (95% CI –3.3 to –1.0) per year in the total hip (p&lt;0.001). In patients ≥25 years of age (n=59, mean (SD) age 30.3 (5.4) years) in whom no annual change in BMD would normally be expected, BMD decreased by 1.9% (95% CI –2.9 to –0.8) per year in the femoral neck (p&lt;0.001), by 1.5% (95% CI –2.4 to –0.6) per year in the total hip (p=0.001), and by 0.8% (95% CI –1.5 to –0.1) per year in the distal forearm (p=0.026). There was no significant annual change in lumbar spine BMD in either patient cohort. <b>Conclusions:</b> Reduced rates of bone accretion and accelerated rates of bone loss explain the high prevalence of low BMD in adults with cystic fibrosis.
A Phase I and Pharmacologic Study of Belotecan in Combination with Cisplatin in Patients with Previously Untreated Extensive-Stage Disease Small Cell Lung Cancer
Authors: Dae Ho Lee, Sang-We Kim, Kyun-Seop Bae, Jeong-Sook Hong, Cheolwon Suh, Yoon-Koo Kang, Jung-Shin Lee
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Belotecan (Camtobell, CKD602) is a novel camptothecin derivative. This study was designed to determine the maximum tolerated dose (MTD), toxicity profile, and dose-limiting toxicity of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer (SCLC). Furthermore, pharmacokinetics and preliminary antitumor activity against SCLC were evaluated. Experimental Design: Belotecan was administered i.v. as intermittent 30-min infusions on days 1 to 4, starting dose of 0.40 mg/m2/d with increment of 0.05 mg/m2/d. Intrapatient dose escalation was not allowed. Cisplatin (60 mg/m2) was given on day 1. The treatments were repeated every 3 weeks. Pharmacokinetics was determined during the first cycle using noncompartmental pharmacokinetic analysis. Results: Seventeen chemotherapy-naive patients with extensive-stage disease SCLC were treated. The MTD of belotecan was 0.50 mg/m2/d with the dose-limiting toxicity of grade 4 neutropenia with fever. A partial response was seen in 13 of 17 patients (76.5%). The most common toxicity was neutropenia but nonhematologic toxicity was very favorable. Pharmacokinetic analysis revealed that, at the dose of 0.50 mg/m2/d, plasma clearance of belotecan was 5.78 ± 1.32 L/h and terminal half-life was 8.55 ± 2.12 h. Fraction of excreted amount in urine was 37.36 ± 5.55%. Pharmacokinetics of belotecan was not altered by administration of cisplatin compared with historical control. Conclusions: The MTD and recommended dose of belotecan for phase II studies was 0.50 mg/m2/d on days 1 to 4 in combination with 60 mg/m2 cisplatin on day 1 every 3 weeks.
Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism
Authors: Bernhard Meier, Bindu Kalesan, Heinrich P. Mattle, Ahmed A. Khattab, David Hildick-Smith, Dariusz Dudek, Grethe Andersen, Reda Ibrahim, Gerhard Schuler, Antony S. Walton, Andreas Wahl, Stephan Windecker, Peter Jüni
Journal: New England Journal of Medicine (2013)

The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy.
Evidence based case report: Helping an obese patient make informed choices
Authors: C. D Mulrow
Journal: BMJ (1998)

Not long ago, a patient, whom I will call Mrs Bariatrico, asked me to prescribe a diet pill for her. Mrs Bariatrico is a middle class woman aged 48 years. She is 1.6 m tall and weighs 77.2 kg. Her body mass index is 30.2 and her waist to hip ratio is 1.0. Mrs Bariatrico is healthy and does not smoke. She told me she plans to enrol in a commercial diet programme and believes her ability to change her lifestyle is good.1 Her main concern is cosmetic—she values “looking good” and considers weight loss an important outcome.

As her primary care provider, I had several concerns. I knew the health insurance system that serves Mrs Bariatrico has no formal weight loss programmes, and the cost of appetite suppressing drugs is not reimbursed. I had some doubts about my own ability to manage obesity and asked the following questions:

Obesity is a chronic condition associated with hyperlipidaemia, hypertension, non-insulin dependent diabetes, gall bladder disease, some cancers, sleep apnoea, and degenerative joint disease. 23Assessing the magnitude of risk …
Adverse effects of spinal manipulation
Authors: Jennifer Bolton, Haymo Thiel
Journal: Journal of the Royal Society of Medicine (2007)

Professor Ernst has published a so-called ‘systematic’ review1 of adverse events following spinal manipulation based on low quality evidence including, for the most part, case reports (JRSM 2007;100:330-338). The whole point of systematic reviews is to get away from an author's often strong prior beliefs and opinions, and instead present an impartial and even-handed review of the evidence. Essential ingredients are that the evidence is critically appraised and the recommendations based firmly on the quality of the evidence presented. In this case, all of the evidence was included indiscriminately and the findings of a causal link between spinal manipulation and adverse events based on unsupportive low-level evidence. Moreover, Professor Ernst makes a judgement on this apparent causation as either ‘certain’, ‘likely’ or ‘possible’. There are no criteria presented in this paper for how such judgements were made.

Of course, the absence of high-quality evidence is not to say there is no risk associated with spinal manipulation: there are safety issues with all interventions. What we need to know is the nature and the size of those risks. In the UK, there are estimated to be well over two million cervical spine manipulations by chiropractors each year.2 Given the number of cervical spine manipulations done worldwide it is likely, even if under-reporting is as high as Professor Ernst suggests, that the level of risk of a serious adverse event is extremely low. To turn Professor Ernst's point on under-reporting and publication bias around, could it be that journals of medicine are unlikely to publish findings which might be considered ‘positive’? Good evidence on safety is of paramount importance; what we have here is poor quality evidence and unsubstantiated claims masquerading as a systematic review.
Musings on genome medicine: cholesterol and coronary artery disease
Authors: David G Nathan, Stuart H Orkin
Journal: Genome Medicine (2009)

Cholesterol levels and not inflammatory markers are the major variables that pose a risk of coronary artery disease. Diabetes greatly increases the risk at any cholesterol level. Coronary artery disease and cancer are linked by a common protein - an apoptotic protein that also functions as a regulator of insulin secretion.
A MICROSPECTROPHOTOMETRIC STUDY OF RED CELL NUCLEI DURING PYKNOSIS
Authors: Roy Korson
Journal: The Journal of Experimental Medicine (1951)

1. A microspectrophotometric apparatus was used to measure nuclear absorption in fixed and stained human bone marrow smears. 2. The validity of the measurements was established. 3. The total and polymerized desoxyribose nucleic acid (DNA) of erythroblast nuclei were measured in relative units, and a gradual loss of DNA from the red cell nucleus during maturation was noted. 4. The loss in DNA is comparable quantitatively to that occurring during pathological pyknosis in sarcoma cells. 5. The continual loss of nuclear material during erythropoiesis supports the conception that the nucleus disappears by intracellular dissolution, not by extrusion in the intact form.
Cytolytic activity and regulatory functions of inhibitory NK cell receptor–expressing T cells expanded from granulocyte colony-stimulating factor–mobilized peripheral blood mononuclear cells
Authors: Junji Tanaka, Tomomi Toubai, Yutaka Tsutsumi, Yoko Miura, Naoko Kato, Shintarou Umehara, Kaoru Kahata, Akio Mori, Nobuyasu Toyoshima, Shuichi Ota, Takahiko Kobayashi, Masanobu Kobayashi, Masaharu Kasai, Masahiro Asaka, Masahiro Imamura
Journal: Blood (2004)
A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies
Authors: S. Terakura, Y. Atsuta, M. Sawa, H. Ohashi, T. Kato, S. Nishiwaki, N. Imahashi, T. Yasuda, M. Murata, K. Miyamura, R. Suzuki, T. Naoe, T. Ito, Y. Morishita
Journal: Annals of Oncology (2011)
Site of initial excitation and current threshold as a function of electrode radius in heart muscle
Authors: F. W. LINDEMANS, R. M. HEETHAAR, J. J. D. van der GON, A. N. E. ZIMMERMAN
Journal: Cardiovascular Research (1975)

End-diastolic current thresholds have been measured in 13 open chested dogs as a function of electrode radius by stimulating the left ventricle with epicardial disc electrodes ranging in a radius from 0-3 mm to 9 mm. Thresholds for cathodal rectangular short stimuli as well as specifically for cathodal make stimulation, proved to be proportional to the electrode radius to the power 1-5. This relationship between radius and threshold can be explained theoretically, assuming that electrical stimulation results in a propagated depolarization front if a critical current density is reached somewhere in the myocardium. The current distribution measured over the electrode and the site of initial depolarization in the tissue are in accordance with this theoretical explanation.
Ontogeny of the Somatosensory System: Origins and Early Development of Primary Sensory Neurons
Authors: A M Davies, A Lumsden
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
High-dose corticosteroids during bleomycin-induced alveolitis in the rat do not suppress the accumulation of hyaluronan (hyaluronic acid) in lung tissue
Authors: O Nettelbladt, A Tengblad, R Hallgren
Journal: European Respiratory Journal (1990)

A single intratracheal injection of bleomycin in rats induced, 4 days later, a considerable accumulation of hyaluronan (hyaluronate, hyaluronic acid) in the lung tissue. This connective tissue reaction was quantified biochemically by analysing hyaluronan (HA) in bronchoalveolar lavage fluid (BAL) and lung tissue extracts. The molecular weight of the HA recovered during lavage was 0.2-0.3 X 10(6) daltons. The HA accumulation was related to an increase in lung water content and associated with an increased influx of eosinophils, neutrophils and lymphocytes into BAL fluid. High-dose corticosteroid treatment (prednisolone 15 mg.kg-1 bw per day) to bleomycin injured rats had no effect on the lung tissue content of HA, the recovery of HA during BAL or the molecular weight of HA accumulated in the alveolar space. Furthermore, steroids did not influence the increased lung water content, or the appearance of inflammatory cells in lavage fluid. These findings indicate that the early connective tissue response to the bleomycin lung injury is mediated by a mechanism which is unaffected by systemic high-dose corticosteroids.
Clinical Utility of a Plasma-Based miRNA Signature Classifier Within Computed Tomography Lung Cancer Screening: A Correlative MILD Trial Study
Authors: Gabriella Sozzi, Mattia Boeri, Marta Rossi, Carla Verri, Paola Suatoni, Francesca Bravi, Luca Roz, Davide Conte, Michela Grassi, Nicola Sverzellati, Alfonso Marchiano, Eva Negri, Carlo La Vecchia, Ugo Pastorino
Journal: Journal of Clinical Oncology (2014)

Purpose Recent screening trial results indicate that low-dose computed tomography (LDCT) reduces lung cancer mortality in high-risk patients. However, high false-positive rates, costs, and potential harms highlight the need for complementary biomarkers. The diagnostic performance of a noninvasive plasma microRNA signature classifier (MSC) was retrospectively evaluated in samples prospectively collected from smokers within the randomized Multicenter Italian Lung Detection (MILD) trial. Patients and Methods Plasma samples from 939 participants, including 69 patients with lung cancer and 870 disease-free individuals (n = 652, LDCT arm; n = 287, observation arm) were analyzed by using a quantitative reverse transcriptase polymerase chain reaction–based assay for MSC. Diagnostic performance of MSC was evaluated in a blinded validation study that used prespecified risk groups. Results The diagnostic performance of MSC for lung cancer detection was 87% for sensitivity and 81% for specificity across both arms, and 88% and 80%, respectively, in the LDCT arm. For all patients, MSC had a negative predictive value of 99% and 99.86% for detection and death as a result of disease, respectively. LDCT had sensitivity of 79% and specificity of 81% with a false-positive rate of 19.4%. Diagnostic performance of MSC was confirmed by time dependency analysis. Combination of both MSC and LDCT resulted in a five-fold reduction of LDCT false-positive rate to 3.7%. MSC risk groups were significantly associated with survival (χ 1 2 = 49.53; P &lt; .001). Conclusion This large validation study indicates that MSC has predictive, diagnostic, and prognostic value and could reduce the false-positive rate of LDCT, thus improving the efficacy of lung cancer screening.
Tim-3 fosters HCC development by enhancing TGF-β-mediated alternative activation of macrophages
Authors: Wenjiang Yan, Xiao Liu, Hongxin Ma, Hualin Zhang, Xiaojia Song, Lifen Gao, Xiaohong Liang, Chunhong Ma
Journal: Gut (2015)

<h3>Objective</h3> Tumour-associated macrophages (TAMs) and their alternative activation contribute greatly to the development of hepatocellular carcinoma (HCC). Tim-3 is highly expressed on macrophages and regulates macrophage functions in several conditions. However, whether Tim-3 is involved in the activation and the function of TAMs has not been reported. <h3>Design</h3> Tim-3 expression in HCC samples was evaluated by flow cytometry, immunohistochemistry and confocal analysis. We analysed the effects of Tim-3 knockdown on macrophages in growth of H22 tumour homografts in BALB/c mice. Tim-3 interference was performed by neutralising antibody, small interfering RNA or short hairpin RNA-expressing lentivirus. Cytokine production was evaluated by reverse transcription PCR, ELISA or Cytometric Bead Array. The effects of Tim-3 interference in macrophages were examined with regard to alternative activation of macrophages and proliferation and migration of Hepa1-6 cells. Cell growth curve, colony formation and transwell assays were involved to estimate cell proliferation and migration. <h3>Results</h3> Tim-3 expression was significantly increased in both peripheral blood monocytes and TAMs in patients with HCC. The Tim-3 expression in monocytes/TAMs strongly correlated with higher tumour grades and the poor survival of patients with HCC. Consistently, HCC conditioned medium or transforming growth factor-β fostered Tim-3 expression and the alternative activation of macrophages. Moreover, Tim-3 interference in macrophages significantly inhibited the alternative activation of macrophages and suppressed HCC cell growth both in vitro and in vivo. Blocking interleukin 6 reversed the Tim-3-mediated effects on HCC cell growth in vitro. <h3>Conclusions</h3> Tim-3 displays critical roles in microenvironment-induced activation and protumoral effects of TAMs in HCC. Interference of Tim-3 might be great potential in HCC therapy.
HURLER'S SYNDROME
Authors: B. Shannon Danes, Alexander G. Bearn
Journal: The Journal of Experimental Medicine (1966)

Seven families affected with Hurler's syndrome have been studied using the methods of cell culture. Skin fibroblasts obtained from the skin of 7 patients with Hurler's syndrome contained metachromatic granules when stained for mucopolysaccharides with toluidine blue O and alcian blue, whereas fibroblasts from normal subjects contained no metachromatic granules. In four families skin cultures of the clinically normal parents showed fibroblasts which contained demonstrable metachromatic granules and "gargoyle" cells and were considered to be heterozygous for the abnormal gene. Fibroblast cultures from certain other members of these families showed metachromasia. These findings were also considered to indicate heterozygosity for the abnormal gene. Three families of the X-linked type of the disease were studied. Fibroblasts cultured from the father contained no metachromatic granules whereas those of the hemizygous mother contained both metachromatic granules and "gargoyle" cells. In one family the abnormal gene could be traced through unaffected individuals for three generations. The prolonged preservation of the biochemical trait in tissue culture will permit studies to be performed designed to clarify the primary action of the abnormal genes which result in Hurler's syndrome, as well as to increase the usefulness of this trait in mapping the human X chromosome.