tbuckley/cabot-search huggingface dataset:
Pulmonary Hypertension in Cystic Fibrosis with Advanced Lung Disease
Authors: Don Hayes, Joseph D. Tobias, Heidi M. Mansour, Stephen Kirkby, Karen S. McCoy, Curt J. Daniels, Bryan A. Whitson
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The impact of pulmonary hypertension (PH) on survival in cystic fibrosis (CF) remains unclear.To determine the influence of PH on survival in the CF population.The United Network for Organ Sharing database was queried from 1987 to 2013 to identify first-time lung transplant candidates who were tracked from wait list entry date until death or censoring to determine influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure greater than or equal to 25 mm Hg and severe greater than or equal to 35 mm Hg.Of 2,781 CF patients, 2,100 were used for univariate analysis, 764 for Kaplan-Meier survival function, 687 for multivariate Cox models, and 576 and 132 for matching on the propensity of mild PH and severe PH, respectively. Univariate Cox analysis found significant differences in survival for mild PH (hazard ratio [HR], 1.747; 95% confidence interval [CI], 1.387-2.201; P < 0.001) and severe PH (HR, 2.299; 95% CI, 1.639-3.225; P < 0.001). Further assessment by multivariate Cox models identified significant risk for death associated with mild PH (HR, 1.757; 95% CI, 1.367-2.258; P < 0.001) and severe PH (HR, 2.284; 95% CI, 1.596-3.268; P < 0.001). Cox regression stratified on matched pairs of PH cases and control subjects confirmed the risk for death for mild PH (HR, 1.919; 95% CI, 1.290-2.85; P = 0.001) and severe PH (HR, 4.167; 95% CI, 1.709-10.157; P = 0.002).The manifestation of PH is associated with significantly increased risk for death in CF patients with advanced lung disease.
Progression to Type 2 Diabetes Among Hign-Risk Groups in Kin-Chen, Kinmen: Exploring the natural history of type 2 diabetes
Authors: Pesus Chou, Chia-Lin Li, Gin-Son Wu, Shih-Tzer Tsai
Journal: Diabetes Care (1998)

OBJECTIVE To examine the natural history of 654 high-risk subjects (340 men and 314 women) with fasting hyperglycemia (first fasting plasma glucose [FPG] level 5.6–7.8 mmol/1) who also exhibited 2-h postload glucose concentrations &amp;lt;11.1 mmol/1 and an FPG level &amp;lt;7.8 mmol/1 in a 75-g oral glucose tolerance test (OGTT). We were particularly interested in comparing the likelihood of developing type 2 diabetes for those with persistent fasting hyperglycemia (PFH), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). PFH is a relatively new definition, and those with PFH used to be defined as NGT according to WHO criteria. RESEARCH DESIGN AND METHODS Subjects were located in a 1992–1994 community-based population survey and followed up and reexamined during 1995–1996. An OGTT was used to determine who had progressed to type 2 diabetes. Risk factors predictive of subsequent progression to type 2 diabetes were determined by comparing baseline variables from the 1992–1994 survey with data of those who had or had not progressed to type 2 diabetes in 1995–1996. RESULTS Of 654 high-risk subjects screened in the baseline survey 481 (73.5%, 255 men and 226 women) were followed up. Of these, 8.1% had progressed to diabetes (4.1% progression/year, 95% Cl 2.3–5.9). Of 131 baseline IGT subjects, 17.6% progressed to diabetes (8.8% progression/year, 6.3–11.3), but only 7.4% of 95 PFH subjects (3.7% progression/year, 2.0–5.4) and 3.5% of 255 NGT subjects (1.8% progression/year, 0.1–3.0) progressed to diabetes. CONCLUSIONS The rates of progression to type 2 diabetes were lowest from the NGT subgroup, highest from the IGT group, with the PFH group in the middle, suggesting that PFH might be a transitional condition that precedes IGT and diabetes. Other significant predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia, baseline FPG, and 2-h plasma glucose concentration.
Japanese study is more evidence that MMR does not cause autism
Authors: Andrew Cole
Journal: BMJ (2005)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Japanese study is more evidence that MMR does not cause autism Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
NHS should develop bioinformatics to make best use of whole genome sequencing, expert group says
Authors: S. Mayor
Journal: BMJ (2011)

The NHS needs to improve its capacity in bioinformatics, by developing information systems, analytical expertise, and infrastructure, to make the best use of whole genome sequencing as it becomes suitable for clinical use, an expert group has recommended.

The group of leading UK clinical geneticists, oncologists, and research scientists evaluated the implications of whole genome sequencing technologies for improving diagnosis, clinical outcomes, and disease prevention by health services, focusing particularly on the NHS.

Coordinated by the PHG Foundation, a charitable organisation that works to improve health through the evidence based application of science, the group has published the first comprehensive overview of the short to medium term medical ramifications of human genome sequencing.

Development of new, …
Do black patients with chronic kidney disease benefit equally from all blood pressure lowering agents?
Authors: J. A. Ladapo, G. Ogedegbe
Journal: BMJ (2014)

The Blood Pressure Lowering Treatment Trialists’ Collaboration performed a rigorous and insightful analysis of the impact of antihypertensive agents on cardiovascular outcomes in patients with and without chronic kidney disease.1 However, we believe the study’s conclusion that “there is little evidence to support the preferential choice of particular drug classes for the prevention of cardiovascular events in people with chronic kidney disease” should be treated with …
Leucocyte function in patients with rheumatoid arthritis: quantitative in-vivo leucocyte mobilisation and in-vitro functions of blood and exudate leucocytes.
Authors: J H Wandall
Journal: Annals of the Rheumatic Diseases (1985)

The 58th Meeting of the Society of British Neurological Surgeons was held at the Walton Hospital, Liverpool, on December 5 and 6, 1958. The President, G. S. Clark-Maxwell (Derby), was in the Chair. Dr. J. Poppen (Boston, Mass.) attended as the special guest of the Society.
Privately financed hospital faces £100m debt
Authors: Roger Dobson
Journal: BMJ (2006)

Queen Elizabeth Hospital NHS Trust in London could be £100m ($172m; €145m) in the red within five years, auditors have warned. The cumulative debt could climb to £99.8m by 2009, say the auditors in a public interest report which says the trust is likely to fail to meet its duty to break even. “The trust's cash position is extremely serious. The trust faces a very severe challenge to balance its recurring income and expenditure,” says the report, compiled by PricewaterhouseCoopers.

Queen Elizabeth Hospital NHS Trust, an acute trust …
New figures show major increase in alcohol related hospital admissions in England
Authors: S. Mayor
Journal: BMJ (2010)

The number of hospital admissions for alcohol related harm increased by 47%—representing an increase of more than 800 each day—over the five years between 2004 and 2009, show latest figures for England.

In England in 2008-9 there were 945 469 admissions to hospital for alcohol related harm. Alcohol related harm was defined as conditions directly related to alcohol, such as liver disease or mental health conditions associated with alcohol, and not including acute injury or illness caused by alcohol.

The increase represents an average of 825 alcohol related admissions a day more than five years ago, with a total of 644 185 admissions to hospital in 2004-5.

The figures showed a marked north-south divide, with two thirds of the local authorities …
Morphogenetic roles of acetylcholine.
Authors: J M Lauder, U B Schambra
Journal: Environmental Health Perspectives (1999)

In the adult nervous system, neurotransmitters mediate cellular communication within neuronal circuits. In developing tissues and primitive organisms, neurotransmitters subserve growth regulatory and morphogenetic functions. Accumulated evidence suggests that acetylcholine, (ACh), released from growing axons, regulates growth, differentiation, and plasticity of developing central nervous system neurons. In addition to intrinsic cholinergic neurons, the cerebral cortex and hippocampus receive extensive innervation from cholinergic neurons in the basal forebrain, beginning prenatally and continuing throughout the period of active growth and synaptogenesis. Acute exposure to ethanol in early gestation (which prevents formation of basal forebrain cholinergic neurons) or neonatal lesioning of basal forebrain cholinergic neurons, significantly compromises cortical development and produces persistent impairment of cognitive functions. Neonatal visual deprivation alters developmental expression of muscarinic acetylcholine receptors (mAChR) in visual cortex, whereas local infusion of mAChR antagonists impairs plasticity of visual cortical neurons. These findings raise the possibility that exposure to environmental neurotoxins that affect cholinergic systems may seriously compromise brain development and have long-lasting morphologic, neurochemical, and functional consequences.
Can SOCS make arthritis better?
Authors: Lionel B. Ivashkiv, Ioannis Tassiulas
Journal: Journal of Clinical Investigation (2003)

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoimmunity and infiltration of joint synovium by activated inflammatory cells, including neutrophils, macrophages, lymphocytes, plasma cells, and osteoclasts (reviewed in ref. 1). Morbidity in RA occurs secondary to the destruction of cartilage and bone by an inflammatory mass termed the pannus, which consists predominantly of activated macrophages and proliferating synovial fibroblasts. Synovial inflammation is regulated by cytokines (1). Pro-inflammatory cytokines implicated in RA pathogenesis include TNF-α, IL-1, IL-6, IL-12, IL-15, IL-18, IFN-γ, and GM-CSF. A key role for TNF-α and IL-1 in RA pathogenesis has been confirmed by the success of TNF and IL-1 neutralization in the treatment of RA. RA synovium is also characterized by the expression of anti-inflammatory cytokines and cytokine antagonists, including TGF-β, IL-10, the IL-1 receptor antagonist, and soluble TNF receptors. Production of these factors reflects an attempt to control inflammation and achieve homeostasis. The idea that the balance between pro- and anti-inflammatory factors is important in regulating the rate of progression, and thus the eventual severity and morbidity, of RA has gained broad acceptance among RA researchers (1).
β-Arrestin-2 Deficiency Attenuates Abdominal Aortic Aneurysm Formation in Mice
Authors: Darshini B. Trivedi, Charles D. Loftin, James Clark, Page Myers, Laura M. DeGraff, Jennifer Cheng, Darryl C. Zeldin, Robert Langenbach
Journal: Circulation Research (2013)

Abdominal aortic aneurysms (AAAs) are a chronic inflammatory vascular disease for which pharmacological treatments are not available. A mouse model of AAA formation involves chronic infusion of angiotensin II (AngII), and previous studies indicated a primary role for the AngII type 1a receptor in AAA formation. β-arrestin (βarr)-2 is a multifunctional scaffolding protein that binds G-protein-coupled receptors such as AngII type 1a and regulates numerous signaling pathways and pathophysiological processes. However, a role for βarr2 in AngII-induced AAA formation is currently unknown.To determine whether βarr2 played a role in AngII-induced AAA formation in mice.Treatment of βarr2(+/+) and βarr2(-/-) mice on the hyperlipidemic apolipoprotein E-deficient (apoE(-/-)) background or on normolipidemic C57BL/6 background with AngII for 28 days indicated that βarr2 deficiency significantly attenuated AAA formation. βarr2 deficiency attenuated AngII-induced expression of cyclooxygenase-2, monocyte chemoattractant protein-1, macrophage inflammatory protein 1α, and macrophage infiltration. AngII also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 in apoE(-/-)/βarr2(+/+) aortas, whereas βarr2 deficiency diminished this increase. Furthermore, inhibition of extracellular signal-regulated kinase 1/2 activation with CI1040 (100 mg/kg per day) reduced the level of AngII-induced cyclooxygenase-2 expression in apoE(-/-)/βarr2(+/+) mice to the level observed in apoE(-/-)/βarr2(-/-) mice. AngII treatment also increased matrix metalloproteinase expression and disruption of the elastic layer in apoE(-/-)/βarr2(+/+) aortas, and βarr2 deficiency reduced these effects.βarr2 contributes to AngII-induced AAA formation in mice by phosphorylated extracellular signal-regulated kinase 1/2-mediated cyclooxygenase-2 induction and increased inflammation. These studies suggest that for the AngII type 1a receptor, G-protein-independent, βarr2-dependent signaling plays a major role in AngII-induced AAA formation.
Abstract 3704: Diindolylmethane induces ER stress mediated autophagy in ovarian cancer cells
Authors: Prabodh K. Kandala, Sanjay K. Srivastava
Journal: Cancer Research (2011)

Abstract Endoplasmic reticulum (ER) is responsible for biosynthesis, folding assembly and modification of various soluble and membrane proteins. ER stress is the imbalance in protein folding resulting in the accumulation of misfolded proteins in ER lumen. In our study, we observed that Diindolylmethane (DIM), a compound present in cruciferous vegetables induces ER stress in ovarian cancer cells. Treatment of SKOV-3, OVCAR-3 and TOV-21G ovarian cancer cells with varying concentrations of DIM for 24hours resulted in the upregulation of Bip, a molecular chaperone. Bip or Grp78 binds to IRE1α, ATF6 and PERK under normal condition, however, during ER stress, Bip dissociates and releases all the three proteins. DIM treatment also significantly increased the expression of IRE1α, ER oxidase (ERO1) and CHOP. CHOP translocate to nucleus and initiate apoptotic stimuli in cells undergoing ER stress. Moreover, DIM induced ER stress also lead to the activation of eIF2α by phosphorylation. Activation of eIF2α inhibits protein translation to avoid further protein accumulation in ER. The release of calcium by DIM treatment in ovarian cancer cells was evaluated by Accuri C6 flowcytometer. The advantage with Accuri C6 is that calcium levels can be monitored without interruption. DIM treatment increased the cytosolic calcium levels in SKOV3 cells. Increase in cytosolic calcium is known to cause ER stress. In addition, our flowcytometry results indicate that DIM induces autophagy in all the ovarian cancer cells in a concentration dependent manner. Exposure of SKOV-3, OVCAR-3 and TOV-21G cells to DIM upregulated the expression of LC3B, a potent indicator of autophagy. DIM induced autophagy was blocked by bafilomycin, an autophagy inhibitor. Treatment of cells with mithramycin (ER stress inhibitor) blocked ER stress proteins activated by DIM. Interestingly, we also observed that blocking DIM-induced ER stress by mithramycin blocked autophagy in ovarian cancer cells. Taken together these results suggest that induction of autophagy in ovarian cancer cells was associated with ER stress caused by DIM. Further mechanistic studies are in progress. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3704. doi:10.1158/1538-7445.AM2011-3704
Drug Prescribing and Use in an American Community
Authors: PAUL D. STOLLEY
Journal: Annals of Internal Medicine (1972)

The overall patterns of drug prescribing and use in an entire community were studied for a year. A substantial proportion of the drugs prescribed were psychotropic agents that either sedate or stimulate. These psychotropic drugs accounted for 17% of all prescriptions, with almost 13% of all patients receiving one of these agents through a doctor's prescription. The amphetamines were the eighth most frequently dispensed class of drugs, with almost 3% of all patients who received a prescription being given an amphetamine. The general impression that there is a high rate of psychotropic drug use in the United States was substantiated in this community study.
In vivo relation of intramyocardial blood volume to myocardial perfusion. Evidence supporting microvascular site for autoregulation.
Authors: X S Wu, D L Ewert, Y H Liu, E L Ritman
Journal: Circulation (1992)

BACKGROUND The goal of this study was to explore the role of several factors that affect intramyocardial blood volume by using minimally invasive computed tomography. Anesthetized dogs were scanned with the dynamic spatial reconstructor, a high-speed tomographic scanner, during injection of a bolus of iohexol into the aortic root. METHODS AND RESULTS In control dogs, it is indicated that the fraction of myocardium that is blood (FMB, %) relates to myocardial perfusion (F, milliliters per gram per minute) in that region as FMB congruent to a.F1/2, where a = 9.5 +/- 1.2% (milliliters times minute per gram)1/2 (mean +/- SD) in the subendocardium and a = 9.6 +/- 1.1% in the subepicardium. In another group of dogs, for the myocardium perfused by a stenosed epicardial artery, a increased to approximately 10 for a 25-43% stenosis (or pressure gradient of 9 mm Hg across narrowing) and to greater than 11 for a 50-55% stenosis (or pressure gradient of 40 mm Hg across narrowing). In these dogs, flow was not impaired under control hemodynamic conditions, but the usual increase of flow (i.e., flow reserve) observed under maximum vasodilation conditions was impaired. In another group of dogs, progressive embolization (using 15-microns-diameter microspheres) of the left ventricular myocardial microcirculation caused the value of a to remain at approximately 9.5 with embolization up to 50% of the fatal dose of microspheres, but it then decreased progressively with embolization to 4.6 at the fatal dose. CONCLUSIONS We conclude that the FMB/F relation reflects hemodynamic conductance at the microvascular level.
Bowel dysfunction in young women with urinary retention.
Authors: M C Lemieux, M A Kamm, C J Fowler
Journal: Gut (1993)

Urinary retention in young women is rare, but a syndrome has recently been described in which urinary retention is associated with abnormal periurethral electromyography. The incidence of bowel dysfunction in these women was investigated, in an attempt to determine whether this might be a more widespread disorder. Of 12 patients with this urological abnormality, eight were constipated. No consistent anorectal abnormality was identified on anorectal physiological testing. The electromyographic abnormality was not seen in the external anal sphincter. One patient had an abnormality of the internal anal sphincter smooth muscle, while another had a generalised disorder of the gastrointestinal tract and urinary bladder resembling a visceral myopathy. Bowel symptoms are common in this group of women with urinary retention, but abnormalities of bowel function are not specific. A common mechanism for bladder and bowel symptoms remains a possibility.
A REVIEW OF RECENT WORK ON THE MECHANISM OF URINE FORMATION.
Authors: TORALD SOLLMANN
Journal: JAMA (1907)

<h3>PREFACE.</h3> The study of the mechanism of urine formation is still one of the most fascinating fields of physiologic research, as is witnessed by the output of papers. Aside from its direct practical application, the kidney owes its chief interest to the fact that, of all the glands, its functions seem best adapted to a simple physicochemical explanation; which, being once found, might furnish a key to the more complicated so-called vital phenomena. On the other hand, its anatomic structure is peculiarly complex and makes a complete isolation of its functions a problem which continues to elude the utmost ingenuity of skilful investigators. Recourse must be had, therefore, to indirect methods, to deductions and theories, which in turn rest on assumptions more or less definitely proved, or more or less probable. Such methods are peculiarly exposed to the danger of "reasoning around a circle." The temptation is ever present to
Abstract 5020: Characterization of epidermal stem cells in SKH1 hairless mice, a widely used mouse model to investigate ultraviolet radiation carcinogenesis.
Authors: Ashok Singh, Anupama Singh, Ajit K. Verma
Journal: Cancer Research (2013)

Abstract Human cutaneous squamous cell carcinoma (SCC) is the second most common type of non-melanoma skin cancer (NMSC) after basal cell carcinoma (BCC) in US. Evidence indicates that the precursor cells are the precursor cells for the origin of SCC. The SCCs probably arise from bulge stem cell niche of hair follicle but not from the transit amplifying cells of epidermis. The SKH1 hairless mice is a widely used mouse model for ultraviolet radiation (UV)-induced carcinogenesis. However, SKH1 mice have never been evaluated for status of skin stem cell probably due to absence of hair and other associated hairless phenotype. It has recently become possible to isolate living hair follicle stem and progenitor cells from mouse skin because of the discovery of cell surface marker (CD34) that facilitate enrichment. The cell surface protein CD34, more widely known as a hematopoietic stem and progenitor cell marker, was found to be uniquely expressed in the mouse hair follicle bulge region using immunohistochemistry staining techniques. In addition, CD34 expression was restricted to the hair follicle regardless of hair follicle stage, making this a potentially important tool for selected enrichment of hair follicle bulge region keratinocytes. In combination with alpha 6-integrin staining and fluorescence activated cell sorting (FACS), CD34 is used to successfully isolate a small population of CD34+/alpha 6-integrin+ cells from a single cell preparation of mouse keratinocytes. CD34-expressing keratinocytes were confirmed to have properties consistent with stem and progenitor cells in that they were shown to be slowly cycling and have a high proliferative capacity in culture, growing larger colonies relative to those from CD34− keratinocytes. In the present experiments, the SKH1 mouse skin stem cell population was identified using stem cell markers (CD34+/α6-integrin+, Keratin-15, Gli1, and Sox9). The results of FACS analysis of live cells, isolated from untreated SKH1 mouse skin, indicate that there are 0.23% CD34+ and 1.05% CD34+/α6-integrin+ cells. The FACS sorted double positive (CD34+/α6-integrin+) stem cells of SKH1 are also observed to be positive for K15, Gli1, and Sox9 markers of stem cells in cytospin slides. In summary, the quantitative FACS analysis and qualitative immunofluorescence data in skin tissues confirms the presence of the stem cell populations in SKH1 mice. Support: (RO1CA102431). Citation Format: Ashok Singh, Anupama Singh, Ajit K. Verma. Characterization of epidermal stem cells in SKH1 hairless mice, a widely used mouse model to investigate ultraviolet radiation carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5020. doi:10.1158/1538-7445.AM2013-5020