tbuckley/cabot-search huggingface dataset:
Lack of NF-κB1 (p105/p50) attenuates unloading-induced downregulation of PPARα and PPARα-regulated gene expression in rodent heart
Authors: P RAZEGHI, M WANG, K YOUKER, L GOLFMAN, S STEPKOWSKI, H TAEGTMEYER
Journal: Cardiovascular Research (2007)

Objective: Unloading of the rodent heart activates the fetal gene program, decreases peroxisome proliferator-activated receptor α (PPARα) and PPARα-regulated gene expression (MCAD), and induces cardiomyocyte atrophy. NF-κB regulates the fetal gene program and PPARα-regulated gene expression during cardiac hypertrophy and induces atrophy in skeletal muscle. Our objective was to test the hypothesis that NF-κB is the regulator for activation of the fetal gene program, for downregulation of PPARα and PPARα-regulated gene expression, and for cardiomyocyte atrophy in the heart subjected to mechanical unloading. Methods: Activation of the inhibitory κ B kinase β (IKKβ)/NF-κB pathways were measured in the heterotopically transplanted rat heart using Western blotting of total and phospho-IKKβ and using transcription factor ELISA's for the five members of the NF-κB family (p65 (Rel A), p105/p50, c-Rel, RelB, and p100/p52). In loss of function experiments, we transplanted hearts of p105/p50 knockout mice into wildtype mice and compared changes in gene expression and cardiomyocyte size with wildtype hearts transplanted into wildtype mice. Results: Total and phospho-IKKβ levels significantly increased in the transplanted heart seven days after surgery. The activation of IKKβ was paralleled by increased DNA binding activity of p65 and p105/p50. Mechanical unloading induced myosin heavy chain β expression and decreased cardiomyocyte size in hearts of both wildtype and p105/p050 knockout animals. In contrast, the downregulation of PPARα and MCAD was significantly attenuated or prevented in the hearts of p105/p50 knockout mice. Conclusions: The IKKβ/p65/p50 pathway is activated in the unloaded rodent heart and a likely regulator for the downregulation of PPARα and PPARα-regulated gene expression.
Some reactions to a dry-land training programme for dinghy sailors.
Authors: G. Wright, J. Clarke, V. Niinimaa, R. J. Shephard
Journal: British Journal of Sports Medicine (1976)

A dry-land winter training programme for dinghy-sailors is described. Individual elements include circuit training, specific exercises for muscle strength and endurance, and distance running. Ten international-class sailors followed a progressive regimen of this type for 14 weeks after completion of the 1973 season. Excess weight and skinfold thicknesses were reduced, while muscle strength, endurance and anaerobic capacity increased. Aerobic power remained substantially unchanged, although a smaller oxygen debt was incurred in reaching maximum effort. Team members were enthusiastic about the benefits gained from the training, commenting on their greater tolerance of the hiking position and all proposed to continue or to increase their efforts during subsequent winters. Racing results during 1974 were also an improvement on the 1973 record. However, it was difficult to link physiological gains to improvements in the relative rankings of individual competitors under either light or high wind conditions; the main factor changing relative standings seems to have been the additional year of competitive experiences in younger team members.
Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease.
Authors: L Biancone, G Andres, H Ahn, A Lim, C Dai, R Noelle, H Yagita, C De Martino, I Stamenkovic
Journal: The Journal of Experimental Medicine (1996)

We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28-B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L and CTLA4/CD28-B7s interactions by anti-CD40-L antibody and soluble CTLA4-immunoglobulin (Ig) fusion protein, respectively, abrogated the autoimmune disease without affecting interleukin 4 (IL-4) production, showing the importance of physical contact between T and B lymphocytes in the Th2-mediated process. In contrast, two anti-CD2 antibodies that have been shown to induce immunosuppression of Th1-mediated events exacerbated the autoantibody response and augmented IgG1, IgE, and IL-4 production, transforming a mild mesangial glomerulopathy into a severe systemic immune complex disease. These observations demonstrate that manipulation of lymphocyte accessory counterreceptor interactions may affect the course of Th2-associated autoimmune disease and suggest that signals resulting from CD2 engagement play an essential role in the regulation of the Th1-Th2 effector equilibrium.
Hepatitis C virus serotype II responds more favorably to interferon-α therapy
Authors: Etsuro Orito, Masashi Mizokami, Naoto Mizoguchi, Ken-Ichi Ohba, Miyako Tohnai, Hiromichi Yamanaka, Takashi Oguri, Noboru Hirashima, Tsuneo Koide, Hideyuki Kano, Kyoko Tsukiyama-Kohara, Michinori Kohara, Johnson Y.N. Lau
Journal: Journal of Hepatology (1994)
Kinetic analysis in single, intact cells by microspectrophotometry: Evidence for two populations of erythrocytes in an individual heterozygous for glucose‐6‐phosphate dehydrogenase deficiency
Authors: Richard A. Ashmun, Donald E. Hultquist, Jerome S. Schultz
Journal: American Journal of Hematology (1986)

Abstract A microspectrophotometric technique was used to measure the kinetics of methemoglobin reduction in intact, unaltered human erythrocytes. Reduction was catalyzed by endogenous NADPH‐methemoglobin reductase in the presence of Nile Blue. The technique was applied to the study of erythrocytes from a female donor with decreased glucose‐6‐phosphate dehydrogenase (G‐6‐PD) activity. The individual was shown to be heterozygous for deficiency of G‐6‐PD. The kinetic study revealed two distinct populations of erythrocytes that were nearly equal in number. One cell population showed reduction rates between 0 and 25% of normal, whereas the second cell population displayed rates within the range seen for normal cells. Single‐cell indices of cell size, cell hemoglobin content, and ratio of cell hemoglobin to cell size did not correlate with single‐cell reduction rates and were not significantly different between the two populations. These results provide quantitative support for the X‐inactivation hypothesis in G‐6‐PD deficiency.
Compliance with nedocromil sodium and a nedocromil sodium/salbutamol combination. Compliance Working Group
Authors: GL Braunstein, G Trinquet, AE Harper
Journal: European Respiratory Journal (1996)

Nonadherence to prescribed preventive medication is common in asthma. We wanted to assess whether the combination of a beta 2-bronchodilator with an anti-inflammatory treatment in the same metered-dose inhaler (MDI) with a regular dosing schedule might improve compliance. A double-blind study was used to compare use (two actuations four times daily for 12 weeks) of 2 mg nedocromil sodium (n = 101) with a combination of 2 mg nedocromil sodium and 100 micrograms salbutamol (n = 100) in mild-to-moderate asthma patients (mean age 42 +/- 14 yrs; 98 males and 103 females). Compliance was measured using the electronic Nebulizer Chronolog (NC) device, change in MDI canister weight, patient questionnaire and physician assessment. The mean +/- SD number of actuations per day for nedocromil sodium and the combination during the primary period of assessment (Weeks 11-12) was 4.2 +/- 2.6 and 4.6 +/- 2.5 (NC), 5.3 +/- 2.1 and 5.3 +/- 2.0 (canister weight), and 7.5 +/- 1.3 and 7.4 +/- 1.3 (questionnaire), respectively. Physician assessment rated compliance as "good" to "excellent". The first and final days of the period were not used in the NC analysis to exclude part-days of treatment and drug-dumping (repeated actuations without inhalation), and may account for the difference between NC and canister weight results. The mean number of two-actuation doses per day determined from the NC was 2.1 +/- 1.3 for nedocromil sodium and 2.4 +/- 2.1 for the combination. Thirty five percent (nedocromil sodium) and 34% (combination) of the patients were compliant (6-10 actuations per day for &gt; or = 60% of the days). We conclude that compliance is poor in asthma, electronic recording revealed the dumping phenomenon and, in this study, the combination of an inhaled beta 2-bronchodilator with a preventive treatment did not improve compliance over a three month period in patients with mild-to-moderate asthma.
Effects of increased sodium delivery on distal tubular sodium reabsorption with and without volume expansion in man
Authors: Vardaman M. Buckalew, Barry R. Walker, Jules B. Puschett, Martin Goldberg
Journal: Journal of Clinical Investigation (1970)

The separate effects of volume expansion and of increased delivery of sodium on sodium reabsorption in the diluting segment of the distal nephron were studied in man. In six normal subjects during a sustained water diuresis, sodium delivery to the distal nephron was increased without volume expansion by the administration of acetazolamide. In these subjects, free water clearance rose linearly as a function of urine flow. In five patients with complete, central diabetes insipidus, distal sodium delivery was increased by the infusion of hypertonic saline during a sustained water diuresis. In four of these five patients, changes in free water clearance were also observed during hypertonic saline diuresis in the presence of distal blockade of sodium reabsorption with chlorothiazide. At high rates of distal delivery the following observations were made: (a) free water clearance was lower and fractional sodium excretion higher during saline diuresis compared to acetazolamide diuresis; (b) although free water clearance was moderately reduced by chlorothiazide at low rates of urine flow, there was no difference in free water clearance between saline loading alone and saline plus chlorothiazide at high rates of urine flow; and (c) during saline loading free water clearance rose without evidence of a limit when increased distal delivery was accompanied by spontaneous increases in glomerular filtration rate, but tended toward a limit when glomerular filtration rate remained constant.
Issues at the interface between primary and secondary care in the management of common respiratory disease bullet 5: The challenge of providing better care for patients with chronic obstructive pulmonary disease: the poor relation of airways obstruction?
Authors: P. Calverley
Journal: Thorax (2000)

Chronic obstructive pulmonary disease (COPD) is a major cause of ill health and death in adults and straddles the interface between primary and secondary care. There are at least 600 000 people in the UK with COPD, a prevalence of around 1%. The diagnosis is usually made relatively late in the natural history, after the age of 40, when symptoms start to appear.1 The prevalence rises to approximately 5% of men aged 65–74 and 10% of men older than 75. Historically, more men have been affected but women are rapidly catching up. Prevalence figures for COPD from Denmark, where women have smoked longer than men, show that the prevalence is now equal.2 COPD is the fifth most common cause of death in the UK, causing 5.4% of male and 3.2% of female deaths, and is a contributory factor on a further 4% of death certificates.3 In a typical district health authority with a population of 250 000, consultations with general practitioners (GPs) for COPD are similar in number to asthma but more patients with COPD will be admitted to hospital and they will stay in hospital for approximately three times as long . The mortality caused by COPD is at least 14 times that of asthma. It is reaching almost epidemic proportions in the Third World, principally as a result of increased tobacco consumption.4 

Despite progress in reducing cigarette smoking, the mortality from COPD in the UK has remained constant for the last 20 years (fig 1). Figure 2illustrates some theoretical rates of decline of lung function (and hence disease progression). Approximately 20% of cigarette smokers are susceptible to progressive lung damage for reasons which remain unclear. The accelerated loss of lung function declines when they quit smoking, even in advanced disease. However, the absolute loss of …
Identification of Cholangiocarcinoma by Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection
Authors: Ali A. Siddiqui, Vaibhav Mehendiratta, Whitney Jackson, David E. Loren, Thomas E. Kowalski, Mohamad A. Eloubeidi
Journal: Clinical Gastroenterology and Hepatology (2011)
Motor and cognitive improvements in patients with Huntington's disease after neural transplantation
Authors: Anne-Catherine Bachoud-Lévi, Philippe Rémy, Jean-Paul Nǵuyen, Pierre Brugières, Jean-Pascal Lefaucheur, Catherine Bourdet, Sophie Baudic, Véronique Gaura, Patrick Maison, Bassam Haddad, Marie-Françoise Boissé, Thierry Grandmougin, Roland Jény, Paolo Bartolomeo, Gianfranco Dalla Barba, Jean-Denis Degos, Fabrice Lisovoski, Anne-Marie Ergis, Edwige Pailhous, Pierre Cesaro, Philippe Hantraye, Marc Peschanski
Journal: The Lancet (2000)
How to Screen for Colon Cancer
Authors: David Lieberman
Journal: Annual Review of Medicine (1998)

The biology of colorectal cancer provides a unique opportunity for early detection and prevention. There is now evidence that screening of asymptomatic average-risk individuals over 50 years of age can reduce mortality resulting from colorectal cancer. New recommendations from the US Preventive Services Task Force endorse screening with fecal occult blood tests or sigmoidoscopy. The best method for population screening remains uncertain. The cost of screening is an important issue in the development of public policy. This review discusses the various screening options, examines the “downstream” effects of screening, and reviews the anticipated costs and effectiveness. Ultimately, the effectiveness of any screening program depends on patient compliance. Further research is needed to determine the best methods of enhancing patient adherence to a screening program.
Profile of patients who drop out a pulmonary rehabilitation program
Authors: Virginia Almadana, Concepción Romero, Agustín Valido, Ana Paulina Gómez-Bastero, Jesús Sánchez, Teodoro Montemayor
Journal: European Respiratory Journal (2013)

Objectives:To identify the characteristics of patients with poor adherence to a specific COPD RR.Methods:A prospective study of consecutive COPD patients who underwent a RR program in the last year. Inclusion criteria: symptomatic COPD despite optimal treatment. Programme type:36 sessions:10 min warm up + resistance exercise bike and force + respiratory physiotherapy. If needed, access to the hospital is provided by ambulance to transport the patient. Results: n: 83:Exclusion 26,Abandonment 22,Complete program 35;38.5% dropout rate. The reasons for excluding patients were: refusal to attend 13, unstable angina 1, mental illness 2, severe musculoskeletal disease 2, mild symptoms 3, did not attend screening tests 5. The causes of dropping out were: low motivation 8, family problems 1, transportation problems 4, severe concomitant disease 3, death 3, trauma pathology 2, frequent exacerbations 1. Characteristics of patients are in figure 1.  Significant differences between the drop-out and those who finished the programm were found in the use of oral steroids(OS) 23.8 vs 2,9%, p 0.014.Conclusions:-The dropout rate was similar to that described in the literature(approximately 1 in 3). -The causes of abandonment of the program are varied, though poor motivation and transportation problems are the most common. -The patient profile leaving the programme seems to be related to those in more impaired functional status(worst result in stress tests) and OS.
Helicobacter pylori infection rates in relation to age and social class in a population of Welsh men.
Authors: F Sitas, D Forman, J W Yarnell, M L Burr, P C Elwood, S Pedley, K J Marks
Journal: Gut (1991)

The seroprevalence of IgG antibodies to Helicobacter pylori was determined using a standard enzyme linked immunosorbent assay in a population of 749 randomly selected men, aged 30-75 years, from Caerphilly, South Wales. The overall prevalence of H pylori was 56.9%, increasing sharply in middle age from 29.8% in those aged 30-34 to over 59% in those aged 45 or older (p less than 0.0001). Age standardised seroprevalence rates were lowest in combined social class categories I and II (49.2%), intermediate in categories IIIN and M (57.5%), and highest in categories IV and V (62.2%) (p = 0.01). In those aged 30-34 years, the prevalence rate for those in combined social class categories IV and V was 57.9% - double the rate for social class categories IIIM and N (28.3%) and five times the prevalence rate in those in social class categories I and II (11.1%). These differences in the infection patterns of H pylori by social class are consistent with patterns of peptic ulcer disease and gastric cancer.
Peripheral Neuropathy Defined by Monofilament Insensitivity and Diabetes Status
Authors: Jodie G. Katon, Gayle E. Reiber, Karin M. Nelson
Journal: Diabetes Care (2012)

To determine whether diabetes status, including prediabetes, is associated with increased risk of peripheral neuropathy as defined by monofilament insensitivity.This study used data from the 1999-2004 National Health and Nutrition Examination Survey (n = 7,818). Peripheral neuropathy was defined as one or more insensate sites detected by a Semmes-Weinstein 10-g monofilament. Generalized linear models were used to directly estimate relative risks (RRs) for the association of diabetes status and peripheral neuropathy.After adjustment compared with no diabetes, prediabetes [RR 1.11 (95% CI 0.92-1.34)] and undiagnosed diabetes [1.08 (0.73-1.61)] were associated with modest increases in risk of peripheral neuropathy, and diabetes was associated with a 74% higher risk of peripheral neuropathy [1.74 (1.50-2.01)].Diabetes is associated with increased risk of peripheral neuropathy defined by monofilament insensitivity, but prediabetes and undiagnosed diabetes may be associated with only a modest increase in risk.
The New Kid on the Block: RET in Lung Cancer
Authors: Justin F. Gainor, Alice T. Shaw
Journal: Cancer Discovery (2013)

Abstract Summary: RET has recently been identified as a potential new oncogenic driver in a subset of patients with non–small cell lung cancer (NSCLC). In this issue of Cancer Discovery, Drilon and colleagues report preliminary trial data with a RET inhibitor in RET fusion-positive NSCLC, validating RET as a therapeutic target in lung cancer. Cancer Discov; 3(6); 604–6. ©2013 AACR. See related article by Drilon et al., p. 630
Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice
Authors: Kazunobu Ishikawa, Daisuke Sugawara, Xu-ping Wang, Kazunori Suzuki, Hiroyuki Itabe, Yukio Maruyama, Aldons J. Lusis
Journal: Circulation Research (2001)

Abstract —Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.
THE THERAPEUTIC USE OF PROLONGED SODIUM AMYTAL NARCOSIS
Authors: THOS. J. HELDT
Journal: American Journal of Psychiatry (1947)

During the past 8 years we have used prolonged sodium amytal narcosis in the treatment of border-line neuropsychiatric disorders. The therapeutic technique is usually so planned as to produce a toxic delirium after the cessation of drug administration. This therapeutic delirium is judged to be reliably restorative and reconstructive. Various degrees of narcoanalysis and narcosynthesis are permitted, but most benefit follows delirious abreaction. All patients to whom the treatment was administered were helped, some more than others. Dissolution of the faulty personality behavior and constructive recasting of the psychiatric problem probably occur through improved physiological rest and a remobilization of thought processes during an irresponsible and impersonal state of psychomotor activity which is temporarily out of volitional control, and is thereafter always reintegrated at a more acceptable level.
Assessment of Disease Dissemination in Gastric Compared With Extragastric Mucosa-Associated Lymphoid Tissue Lymphoma Using Extensive Staging: A Single-Center Experience
Authors: Markus Raderer, Stefan Wöhrer, Berthold Streubel, Marlene Troch, Karl Turetschek, Ulrich Jäger, Cathrin Skrabs, Alexander Gaiger, Johannes Drach, Andreas Puespoek, Michael Formanek, Martha Hoffmann, Wolfgang Hauff, Andreas Chott
Journal: Journal of Clinical Oncology (2006)

Molecular data and preliminary clinical findings have suggested mucosa-associated lymphoid tissue (MALT) lymphoma as a multifocal disease in a high percentage of patients. We report our findings with an extensive staging routine applied in patients diagnosed with MALT lymphoma at our institution.A total of 140 consecutive patients (61 with gastric and 79 with extragastric MALT lymphoma) underwent staging according to a standardized protocol. Staging included gastroscopy with multiple biopsies, endosonography of the upper GI tract, computed tomography of thorax and abdomen, lymph node sonography, colonoscopy with multiple biopsies, otorhinolaryngologic assessment, magnetic resonance imaging of salivary and lacrimal glands, and bone marrow biopsy. All lesions suggestive of lymphoma involvement were subjected to biopsy, if accessible, and biopsies were evaluated for MALT lymphoma-specific genetic aberrations by means of reverse transcriptase polymerase chain reaction and/or fluorescent in situ hybridization.Fifteen (25%) of 61 patients with gastric MALT lymphoma had multiorgan involvement, with dissemination beyond the GI tract in six patients. By contrast, significantly more patients with extragastric MALT lymphoma had dissemination to another MALT organ (37 of 79 patients, 46%; P = .045). Nine of these 37 patients had dissemination to the stomach. Only three (2%) of 140 patients had bone marrow involvement. Multifocality was significantly associated with t(11;18)(q21;q21) in gastric lymphomas (P = .045) and with trisomy 18 in extragastric lymphomas (P = .011).Our findings suggest that MALT lymphoma frequently presents as a multifocal disease. Extragastric MALT lymphomas are significantly more prone to dissemination than gastric MALT lymphomas.