tbuckley/cabot-search huggingface dataset:
Hyaluronan production in human rheumatoid fibroblastic synovial lining cells is increased by interleukin 1beta but inhibited by transforming growth factor beta 1
Authors: M. Kawakami, K. Suzuki, Y. Matsuki, T. Ishizuka, T. Hidaka, T. Konishi, M. Matsumoto, K. Kataharada, H. Nakamura
Journal: Annals of the Rheumatic Diseases (1998)

To investigate the regulatory roles of interleukin 1 beta (IL1 beta), tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or transforming growth factor beta 1 (TGF beta 1) on hyaluronan (HA) synthesis by human fibroblastic synovial lining cells.Concentrations of HA in culture supernatants of fibroblastic synovial lining cell line (RAMAK-1 cell line) with or without stimulation by IL1 beta, TNF alpha, IFN gamma or TGF beta 1 were measured by sandwich binding protein assay. Levels of HA synthase mRNA of the cells with or without stimulation were detected by reverse transcribed polymerase chain reaction. Molecular weights of HA in the culture supernatants of the cells with or without stimulation were measured using high performance gel permeation liquid chromatography.HA synthesis by the cells was not significantly augmented by TNF alpha or by IFN gamma. It was significantly stimulated by IL1 beta but inhibited by TGF beta 1. Molecular weights of HA in the culture supernatants of the cells were unchanged by stimulation with TNF alpha. They were remarkably increased by stimulation with IL1 beta and IFN gamma, but reduced with TGF beta 1.IL 1 beta is an up regulator of HA synthesis, while TGF beta 1 is a down regulator. HA production in the synovial lining cells of inflamed joints (for example, rheumatoid arthritis) might be regulated by the balance of these cytokines.
A randomized, controlled trial of acupuncture self-needling as maintenance therapy for cancer-related fatigue after therapist-delivered acupuncture
Authors: A. Molassiotis, J. Bardy, J. Finnegan-John, P. Mackereth, W.D. Ryder, J. Filshie, E. Ream, D. Eaton, A. Richardson
Journal: Annals of Oncology (2013)
Pancreatic Cancer–Derived Exosomes Cause Paraneoplastic β-cell Dysfunction
Authors: Naureen Javeed, Gunisha Sagar, Shamit K. Dutta, Thomas C. Smyrk, Julie S. Lau, Santanu Bhattacharya, Mark Truty, Gloria M. Petersen, Randal J. Kaufman, Suresh T. Chari, Debabrata Mukhopadhyay
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Pancreatic cancer frequently causes diabetes. We recently proposed adrenomedullin as a candidate mediator of pancreatic β-cell dysfunction in pancreatic cancer. How pancreatic cancer–derived adrenomedullin reaches β cells remote from the cancer to induce β-cell dysfunction is unknown. We tested a novel hypothesis that pancreatic cancer sheds adrenomedullin-containing exosomes into circulation, which are transported to β cells and impair insulin secretion. Experimental Methods: We characterized exosomes from conditioned media of pancreatic cancer cell lines (n = 5) and portal/peripheral venous blood of patients with pancreatic cancer (n = 20). Western blot analysis showed the presence of adrenomedullin in pancreatic cancer-exosomes. We determined the effect of adrenomedullin-containing pancreatic cancer exosomes on insulin secretion from INS-1 β cells and human islets, and demonstrated the mechanism of exosome internalization into β cells. We studied the interaction between β-cell adrenomedullin receptors and adrenomedullin present in pancreatic cancer-exosomes. In addition, the effect of adrenomedullin on endoplasmic reticulum (ER) stress response genes and reactive oxygen/nitrogen species generation in β cells was shown. Results: Exosomes were found to be the predominant extracellular vesicles secreted by pancreatic cancer into culture media and patient plasma. Pancreatic cancer-exosomes contained adrenomedullin and CA19-9, readily entered β cells through caveolin-mediated endocytosis or macropinocytosis, and inhibited insulin secretion. Adrenomedullin in pancreatic cancer exosomes interacted with its receptor on β cells. Adrenomedullin receptor blockade abrogated the inhibitory effect of exosomes on insulin secretion. β cells exposed to adrenomedullin or pancreatic cancer exosomes showed upregulation of ER stress genes and increased reactive oxygen/nitrogen species. Conclusions: Pancreatic cancer causes paraneoplastic β-cell dysfunction by shedding adrenomedullin+/CA19-9+ exosomes into circulation that inhibit insulin secretion, likely through adrenomedullin-induced ER stress and failure of the unfolded protein response. Clin Cancer Res; 21(7); 1722–33. ©2014 AACR. See related commentary by Korc, p. 1508
Cause of Exercise Associated Muscle Cramps (EAMC) — altered neuromuscular control, dehydration or electrolyte depletion?
Authors: M P Schwellnus
Journal: British Journal of Sports Medicine (2008)

Exercise Associated Muscle Cramps (EAMC) is one of the most common conditions that require medical attention during or immediately after sports events. Despite the high prevalence of this condition the aetiology of EAMC in athletes is still not well understood. The purpose of this review is to examine current scientific evidence in support of (1) the “electrolyte depletion” and “dehydration” hypotheses and (2) the “altered neuromuscular control” hypothesis in the aetiology of EAMC. In this review, scientific evidence will, as far as possible, be presented using evidence-based medicine criteria. This is particularly relevant in this field, as the quality of experimental methodology varies considerably among studies that are commonly cited in support of hypotheses to explain the aetiology of EAMC. Scientific evidence in support of the “electrolyte depletion” and “dehydration” hypotheses for the aetiology of EAMC comes mainly from anecdotal clinical observations, case series totalling 18 cases, and one small (n = 10) case–control study. Results from four prospective cohort studies do not support these hypotheses. In addition, the “electrolyte depletion” and “dehydration” hypotheses do not offer plausible pathophysiological mechanisms with supporting scientific evidence that could adequately explain the clinical presentation and management of EAMC. Scientific evidence for the “altered neuromuscular control” hypothesis is based on evidence from research studies in human models of muscle cramping, epidemiological studies in cramping athletes, and animal experimental data. Whilst it is clear that further evidence to support the “altered neuromuscular control” hypothesis is also required, research data are accumulating that support this as the principal pathophysiological mechanism for the aetiology of EAMC.
Chronic Obstructive Pulmonary Disease and Intake of Catechins, Flavonols, and Flavones
Authors: CORA TABAK, ILJA C. W. ARTS, HENRIETTE  A. SMIT, DICK HEEDERIK, DAAN KROMHOUT
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Flavonoids have been suggested to protect against chronic lung disease. We studied intake of catechins, flavonols, and flavones in relation to pulmonary function and COPD symptoms in 13,651 adults from three Dutch cities examined from 1994 to 1997. Dietary intake was estimated using a food frequency questionnaire, and flavonoid intake was calculated using specific food composition tables. Pulmonary function (FEV1) was determined by spirometry and COPD symptoms by questionnaire. Associations were presented for the fifth versus the first quintile of intake (Q5-Q1), adjusted for age, height (for FEV1 only), sex, smoking, BMI, and energy intake. Smoking was strongly associated with COPD, independent of dietary effects. Average catechin, flavonol, and flavone intake was 58 mg/d (SD = 46) with tea and apples as main sources. Total catechin, flavonol, and flavone intake was positively associated with FEV1 ( βQ5-Q1 = 44 ml, 95% CI = 18–69) and inversely associated with chronic cough (ORQ5-Q1 = 0.80, 95% CI = 0.66–0.97) and breathlessness (ORQ5-Q1 = 0.74, 95% CI = 0.58– 0.94), but not chronic phlegm. Catechin intake was independently associated with FEV1 ( βQ5-Q1 = 130 ml, 95% CI = 101–159) and all three COPD symptoms (ORQ5-Q1 = 0.60–0.72, p < 0.001). Flavonol and flavone intake was independently associated with chronic cough only. Solid fruit, but not tea, intake was beneficially associated with COPD. Our results suggest a beneficial effect of a high intake of catechins and solid fruits against COPD.
Signaling through FcγRIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation
Authors: Hozefa S. Bandukwala, Bryan S. Clay, Jiankun Tong, Purvi D. Mody, Judy L. Cannon, Rebecca A. Shilling, J. Sjef Verbeek, Joel V. Weinstock, Julian Solway, Anne I. Sperling
Journal: The Journal of Experimental Medicine (2007)

Although inhibitory Fcγ receptors have been demonstrated to promote mucosal tolerance, the role of activating Fcγ receptors in modulating T helper type (Th)2-dependent inflammatory responses characteristic of asthma and allergies remains unclear. Here, we demonstrate that signaling via activating Fcγ receptors in conjunction with Toll-like receptor 4 stimulation modulated cytokine production from bone marrow–derived dendritic cells (DCs) and augmented their ability to promote Th2 responses. Ligation of the low affinity receptor FcγRIII was specifically required for the enhanced Th2 responses, as FcγRIII−/− DCs failed to augment Th2-mediated airway inflammation in vivo or induce Th2 differentiation in vitro. Further, FcγRIII−/− mice had impaired Th2 cytokine production and exhibited reduced airway inflammation, whereas no defect was found in FcγRI−/− mice. The augmentation of Th2 immunity was regulated by interleukin 10 production from the DCs but was distinct and independent of the well-established role of FcγRIII in augmenting antigen presentation. Thus, our studies reveal a novel and specific role for FcγRIII signaling in the regulation of Th cell responses and suggest that in addition to immunoglobulin (Ig)E, antigen-specific IgG also contributes to the pathogenesis of Th2-mediated diseases such as asthma and allergies.
Isolation and Characterization of Coenzyme A Glutathione Disulfide as a Parathyroid-Derived Vasoconstrictive Factor
Authors: Joachim Jankowski, Anna Schröter, Martin Tepel, Markus van der Giet, Nina Stephan, Jiankai Luo, Walter Zidek, Hartmut Schlüter
Journal: Circulation (2000)

Background —Coenzyme A glutathione disulfide (CoA-SSG) was recently isolated from bovine adrenal glands and was shown to be a renal vasoconstrictor. The identification of CoA-SSG in human parathyroid glands and its action on cultured vascular smooth muscle cells (VSMCs) are described here. Methods and Results —After purification to homogeneity by several chromatographic steps, CoA-SSG was identified by matrix-assisted laser desorption/ionization mass spectrometry and enzymatic analysis. The dose-dependent growth-stimulating effect of CoA-SSG on VSMCs, measured by the [ 3 H]thymidine method, is characterized by a threshold of 10 − 8 mol/L and a maximum effect of 10 μmol/L, increasing VSMC proliferation 254±21% above control. A dose of 10 μmol/L methylmalonyl-CoA and 10 μmol/L CoA increased the rate of proliferation of VSMCs only by 178±43% and 50±42% above control, respectively. Glutathione has no proliferative effect on VSMCs. The growth-stimulating effect of CoA-SSG (1 μmol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 μmol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 μmol/L) (48% compared with CoA-SSG without antagonist; each P &lt;0.05 versus control), indicating that the effect is mediated partly via A 2 and partly via P 2 Y 1 and/or P 2 Y 4 receptor. Conclusions —CoA-SSG may play a regulatory role in VSMC growth as a progression factor and thereby could play an important role in development of hypertension.
Maternal Family History of Diabetes Is Associated With a Reduced Risk of Cardiovascular Disease in Women With Type 2 Diabetes
Authors: David G. Bruce, Kylie Van Minnen, Wendy A. Davis, Jaspreet Mudhar, Michael Perret, Dayani P. Subawickrama, Stephanie Venkitachalam, David Ravine, Timothy M.E. Davis
Journal: Diabetes Care (2010)

OBJECTIVE To investigate whether parental family history of diabetes influences cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS We studied 1,294 type 2 diabetic patients (mean age 64.1 years, 51.2% female) recruited to a community-based cohort study from 1993 to 1996 and followed until mid-2006. A data linkage system assessed all-cause and cardiac mortality, incident myocardial infarction, and stroke. Cox proportional hazards modeling was used to determine the influence of maternal or paternal family history on these outcomes. RESULTS A maternal family history of diabetes was reported by 20.4% of the cohort, 8.3% reported paternal family history, and 2.0% reported both parents affected. Maternal and paternal family history was associated with earlier age of diabetes onset, and maternal family history was associated with worse glycemic control. For all patients, maternal family history was significantly associated with reduced risk of all-cause mortality and cardiac mortality. When analyzed by sex, maternal family history had no effect on male patients, whereas female patients with diabetic mothers had significantly reduced hazard ratios for death from all causes (0.63 [95% CI 0.41–0.96]; P = 0.033), for death from cardiac causes (0.32 [0.14–0.72]; P = 0.006), and for first myocardial infarction (0.45 [0.26–0.76]; P = 0.003). Paternal family history status was not associated with these outcomes. CONCLUSIONS A maternal family history of diabetes confers relative protection against cardiovascular disease in female patients but not in male patients with type 2 diabetes. Paternal family history is associated with risks equivalent to those without a family history of diabetes. Some of the clinical heterogeneity of type 2 diabetes is related to maternal transmission effects with differential impact on male and female patients.
Effects of Glycemic Control on Protective Responses Against Hypoglycemia in Type 2 Diabetes
Authors: Anna Korzon-Burakowska, David Hopkins, Krystyna Matyka, Jill Lomas, Andrew Pernet, IAN Macdonald, Stephanie Amiel
Journal: Diabetes Care (1998)

To determine the effects of glycemic control on the counterregulatory responses to hypoglycemia in type 2 diabetes.Seven poorly controlled type 2 diabetes patients (mean HbA1c, 11.3 +/- 1.1%) were studied by stepped hyperinsulinemic hypoglycemic clamp (nadir, 2.4 mmol/l) before and after improving glycemic control with insulin treatment. Counterregulatory hormones, symptoms, and four-choice reaction time were measured at each glucose plateau.In patients with poorly controlled type 2 diabetes, counterregulatory hormone responses began at higher plasma glucose levels than did those in healthy subjects (epinephrine, 4.4 +/- 0.2 vs. 3.7 +/- 0.2 mmol/l, P = 0.011). After significant improvement in glycemic control (mean HbA1c, 8.1 +/- 0.9%, P < 0.001) was achieved without severe hypoglycemia, hormonal responses started at much lower plasma glucose levels (e.g., epinephrine, 3.5 +/- 0.3 mmol/l, P = 0.005) and were significantly reduced in magnitude (e.g., area under epinephrine response curve, 306 +/- 93 vs. 690 +/- 107 nmol.min-1.l-1, P = 0.012). This was accompanied by a change in the plasma glucose threshold at which hypoglycemic symptoms first developed from 3.6 +/- 0.2 to 3.0 +/- 0.2 mmol/l (P = 0.019). In contrast, the plasma glucose threshold at which four-choice reaction time deteriorated did not change significantly (3.1 +/- 0.1 vs. 2.9 +/- 0.1 mmol/l, P = 0.125).Counterregulatory responses begin at normoglycemia in poorly controlled type 2 diabetes. Improving glycemic control with insulin therapy normalizes hormonal responses but lowers the plasma glucose levels at which hypoglycemic symptoms develop to levels associated with impairment of four-choice reaction time, a marker of cognitive function. This process potentially increases the risk of severe hypoglycemia, but to a lesser extent than occurs in type 1 disease.
SI, moles, and drugs.
Authors: G Ball
Journal: BMJ (1978)

to belittle Harvey's great contributions to the discovery of the circulation of the blood, but is it not time that we in Britain stopped perpetuating what at least is an oversimplified claim, that it was Harvey and Harvey alone who made this great discovery?It would be most interesting, especially to me, to learn the views of professional medical historians-British, Italian, and Dutch.
Respiratory muscle training with normocapnic hyperpnoea (RMNH) improves ventilatory pattern, thoraco-abdominal coordination and reduces oxygen desaturation during exercise in COPD patients
Authors: Eva Bernardi, Luca Pomidori, Gaia Mandolesi, Faisy Bassal, Annalisa Cogo
Journal: European Respiratory Journal (2014)

Few data are available about the effect of RMNH in COPD patients.  Aim: evaluate the effect of 4 weeks RMNH (Spirotiger ® ) on QoL, exercise capacity and ventilation in COPD.  Materials and Methods: 25 COPD (3F), age 42-80. Respiratory function tests (FEV 1 , FVC, MIP), QoL (St George9s Questionnaire), 6MWT and endurance symptom limited test (75-80% of peak-work rate, tLIM) were performed before and after RMNH. 12 patients were instrumented with a portable inductive plethysmografhy (Lifeshirt System) to evaluate breathing pattern and thoraco-abdominal coordination (phase angle, PhA) during tLIM. After 4 supervised sessions, they trained at home for 4 weeks: 10 min twice a day at 50% of MVV.  Results, Tab 1. 6 patients dropped out.  During tLIM we found: lower VE, lower RR and higher TV; lower oxygen desaturation; lower increase in PhA and lower dyspnea Borg Score for the same work intensity (p 2 , before and after RMNH, were significantly related (R 2 =0.65, p=0.003).  Conclusion: As expected RMNH improves exercise capacity and QoL. New results are: the significantly change in breathing pattern which improves SpO 2  and the better thoraco-abdominal coordination (lower PhA). These facts can have a role in the improvement of exercise capacity and the lower dyspnea perception. All these data show the clinical importance of these functional improvements in COPD.
Mental imagery is simultaneously symbolic and analog
Authors: John R. Pani
Journal: Behavioral and Brain Sciences (2002)

With admirable clarity, Pylyshyn shows that there is little evidence that mental imagery is strongly constrained to be analog. He urges that imagery must be considered part of a more general symbolic system. The ultimate solution to the challenges of image theory, however, rest on understanding the manner in which mental imagery is both a symbolic and an analog system.
European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis
Authors: W Zhang, M Doherty, T Bardin, V Barskova, P-A Guerne, T L Jansen, B F Leeb, F Perez-Ruiz, J Pimentao, L Punzi, P Richette, F Sivera, T Uhlig, I Watt, E Pascual
Journal: Annals of the Rheumatic Diseases (2011)

Objectives To agree terminology and to develop recommendations for the diagnosis of calcium pyrophosphate deposition (CPPD). Methods The European League Against Rheumatism (EULAR) CPPD Task Force, comprising 15 experts from 10 countries, agreed the terms and recommendations for diagnosis of CPPD using a Delphi consensus approach. Evidence was systematically reviewed and presented in terms of sensitivity, specificity and positive likelihood ratio (LR) to support diagnosis; ORs were used for association. Strength of recommendation (SOR) was assessed by the EULAR visual analogue scale. Results It was agreed that ‘CPPD’ should be the umbrella term that includes acute calcium pyrophosphate (CPP) crystal arthritis, osteoarthritis (OA) with CPPD and chronic CPP crystal inflammatory arthritis. Chondrocalcinosis (CC) defines cartilage calcification, most commonly due to CPPD and detected by imaging or histological examination. A total of 11 key recommendations were generated on the topics of clinical features, synovial fluid (SF) examination, imaging, comorbidities and risk factors. Definitive diagnosis of CPPD relies on identification of SF CPP crystals. Rapid onset inflammatory symptoms and signs are suggestive but not definitive for acute CPP crystal arthritis. Radiographic CC is not highly sensitive or specific, whereas ultrasonography appears more useful (LR=24.2, 95% CI 3.51 to 168.01) for peripheral joints. Recognised risk factors for CPPD include ageing, OA and metabolic conditions such as primary hyperparathyroidism, haemochromatosis and hypomagnesaemia; familial forms are rare. SORs varied from 53 to 99 (maximum 100). Conclusion New terms for CPPD were agreed and 11 key recommendations for diagnosis of CPPD were developed using research evidence and expert consensus.
Red flags for back pain
Authors: M. Underwood, R. Buchbinder
Journal: BMJ (2013)

A popular idea that didn’t work and should be removed from guidelines 

Nearly all guidelines on low back pain have stressed the importance of red flag signs—positive answers to key questions about medical history that indicate the possibility of a serious underlying condition—since the publication of influential reports in the United Kingdom and United States in 1994.1 2 In a linked systematic review (doi:10.1136/bmj.f7095), Downie and colleagues challenge this orthodoxy by investigating the accuracy of red flags to screen for fracture or cancer in people presenting with low back pain.3

Although intended to prompt clinicians to think about the possibility of serious conditions such as cancer, infection, or fracture, it is worrying that doctors are advised to investigate or refer patients on the basis of the presence or absence of red flags alone. For example, a BMJ 10 Minute Consultation on chronic back pain advised that “If red flag signs are present refer [patient] to a specialist for further evaluation.”4 NHS clinical knowledge summaries advise “Further investigation and referral with appropriate urgency may be indicated, and should always be considered, if one or more red …