tbuckley/cabot-search huggingface dataset:
Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth
Authors: Katharina M. Michalik, Xintian You, Yosif Manavski, Anuradha Doddaballapur, Martin Zörnig, Thomas Braun, David John, Yuliya Ponomareva, Wei Chen, Shizuka Uchida, Reinier A. Boon, Stefanie Dimmeler
Journal: Circulation Research (2014)

The human genome harbors a large number of sequences encoding for RNAs that are not translated but control cellular functions by distinct mechanisms. The expression and function of the longer transcripts namely the long noncoding RNAs in the vasculature are largely unknown.Here, we characterized the expression of long noncoding RNAs in human endothelial cells and elucidated the function of the highly expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT1).Endothelial cells of different origin express relative high levels of the conserved long noncoding RNAs MALAT1, taurine upregulated gene 1 (TUG1), maternally expressed 3 (MEG3), linc00657, and linc00493. MALAT1 was significantly increased by hypoxia and controls a phenotypic switch in endothelial cells. Silencing of MALAT1 by small interfering RNAs or GapmeRs induced a promigratory response and increased basal sprouting and migration, whereas proliferation of endothelial cells was inhibited. When angiogenesis was further stimulated by vascular endothelial growth factor, MALAT1 small interfering RNAs induced discontinuous sprouts indicative of defective proliferation of stalk cells. In vivo studies confirmed that genetic ablation of MALAT1 inhibited proliferation of endothelial cells and reduced neonatal retina vascularization. Pharmacological inhibition of MALAT1 by GapmeRs reduced blood flow recovery and capillary density after hindlimb ischemia. Gene expression profiling followed by confirmatory quantitative reverse transcriptase-polymerase chain reaction demonstrated that silencing of MALAT1 impaired the expression of various cell cycle regulators.Silencing of MALAT1 tips the balance from a proliferative to a migratory endothelial cell phenotype in vitro, and its genetic deletion or pharmacological inhibition reduces vascular growth in vivo.
Chemotherapy Options for Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck
Authors: A. Dimitrios Colevas
Journal: Journal of Clinical Oncology (2006)

The purpose of this review is to provide readers with guidance concerning treatment of patients with advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in the context of clinical trial data. We discuss issues surrounding the treatment of patients with SCCHN, with an emphasis on recommendations based on results from phase II and III clinical trials published since 1980. Many options exist for the treatment of patients with SCCHN. The most important decisions involve determining which patients are in need of treatment and which are most likely to benefit from treatment. Although many chemotherapy treatments have been shown to induce responses, survival improvement remains an unfulfilled goal. Definitive data do not exist on the effects of chemotherapy on quality of life or progression-free survival as measures of clinical benefit in this setting. Performance status, history of prior treatment, extent of tumor, and need for palliation are the most important factors in the decision to treat a patient with chemotherapy for incurable SCCHN. Single-agent treatment with conventional doses of methotrexate remains a standard for most patients with advanced, recurrent or metastatic SCCHN. Cisplatin plus fluorouracil, cisplatin plus a taxane, and single-agent taxane are the most widely studied alternatives. There is a need for further trials with end points other than overall survival or tumor response in this patient population. Guidelines for patient selection and treatment options are provided.
Hypothermic protection (26-25 degrees C) without perfusion cooling for surgery of congenital cardiac defects using prolonged occlusion.
Authors: E E Litasova, V N Lomivorotov
Journal: Thorax (1988)

Open heart surgery was performed without perfusion under deep hypothermia in 343 patients with congenital heart defects aged from 1 year 3 months to 44 years. Cooling to a temperature of 26-25 degrees C in the oesophagus was achieved by covering the body with crushed ice. The patients were maintained under superficial ether narcosis and they were given morphine (0.5 mg/kg) and tubocurarine (0.5-1.0 mg/kg). The duration of circulatory arrest was 30 minutes in 190 and longer in 153 patients--60-77 minutes in 10 patients. It took an average of 7.6 minutes for resumption of normal cardiac activity after circulatory arrest prolonged beyond 60 minutes. Of the 343 patients operated on 32 (9.3%) died. Analysis of the mortality pattern showed that patients with acute cardiac insufficiency contributed most to the total number of deaths (19 patients, 5.5%); those with pulmonary oedema ranked second (4 patients, 1.2%) and those with brain oedema third (3 patients, 0.9%). Neurological complications were observed in 13 patients (3.8%). Their frequency was significantly related to the duration of circulatory arrest. Circulatory inadequacy in patients with poor myocardial function who had undergone extensive repair appeared to be a contributory factor. The results obtained without perfusion under deep (26-25 degrees C) hypothermic protection suggest that 75 minutes is a safe time, in terms of brain damage, for circulatory arrest. Under these conditions complex cardiac defects can be repaired.
Cytokeratin 18 Fragment Levels as a Noninvasive Biomarker for Nonalcoholic Steatohepatitis in Bariatric Surgery Patients
Authors: Dima L. Diab, Lisa Yerian, Philip Schauer, Sangeeta R. Kashyap, Rocio Lopez, Stanley L. Hazen, Ariel E. Feldstein
Journal: Clinical Gastroenterology and Hepatology (2008)
Muscle weakness in extremities and diffuse centrilobular nodules in lungs
Authors: M. Fujii, Y. Sumi, K. Atarashi, T. Takemura, N. Inase
Journal: Thorax (2011)

A 72-year-old female was admitted to our hospital because of abnormal lung shadows. Two years before admission, she had complained of paraesthesia in her hands. A gait disturbance appeared a year later and gradually worsened resulting in her losing the ability to walk altogether. She had also become constipated and developed a urinary disorder.

She had undergone total gastrectomy for gastric cancer 15 years ago and had received a blood transfusion at that time. On physical examination, she presented with muscle weakness in all four extremities, thermal hypoesthesia, an inability to sense vibration and dysautonomia.

She had no fever. Laboratory findings indicated high lysozyme. Purified protein derivative (PPD) skin test was negative (table 1). MRI revealed T2 high-intensity areas in the …
The renal response to acid loads in metabolic alkalosis; an assessment of the mechanisms regulating acid excretion.
Authors: R L Tannen, H L Bleich, W B Schwartz
Journal: Journal of Clinical Investigation (1966)

It is widely recognized that in chronic metabolic alkalosis acid excretion persists despite the alka- linity of the extracellular fluid.In most instances this paradoxical behavior has been attributed to potassium depletion (1), although depletion of so- dium has also been held responsible for restricting the excretion of surplus bicarbonate (2).There have, however, been no systematic attempts to ex- amine critically the factors that regulate acid ex- cretion in the presence of metabolic alkalosis.In the present study, hydrochloric acid and nitric acid were administered to alkalotic dogs under experi- mental circumstances designed to explore the mechanisms that control excretion of hydrogen. MethodsSeventeen balance studies were carried out on 13 fe- male mongrel dogs weighing between 13.1 and 25.3 kg.Before study each dog received commercial dog chow for at least 2 weeks.During each study the dogs were fed approximately 25 g per kg per day of a synthetic diet, the composition of which has been described previously (3).The intrinsic electrolyte content of the diet was approximately 1 mEq of sodium, 0.2 mEq of chloride, and 0.1 mEq of potassium per 100 g of diet.The diet was homogenized with 1.5 times its weight of water and fed in two approximately equal portions daily.Dogs that did not eat spontaneously were fed by tube.The following technique, similar to that which has been described previously, was employed to induce meta- bolic alkalosis (4).Dogs were fed the low electrolyte, synthetic diet supplemented with sodium and potassium as the neutral phosphate (4 HPO4/1 H2PO4).After 4 days of prefeeding, gastric juice was drained twice each *
PTH-170 Five Year follow up of Patients with Asymptomatic Iron Deficiency Anaemia following Normal Investigations in a Nurse Led Protocol Driven Pathway
Authors: S A Townsend, D Cheung, R Ransford, E Horne, J Burdsall, H Griffiths
Journal: Gut (2013)

<h3>Introduction</h3> Systematic investigation of patients with iron deficiency anaemia has been proven to yield a 12% diagnosis for colorectal cancer and 5% for coeliac disease<sup>1</sup>. Following publication of BSG guidelines, a nurse led protocol driven pathway was established at a district general hospital. We report the 5-year outcome of 122 patients with normal investigations entered onto this pathway and assess its efficacy in identifying GI pathology. This is the largest study to date in this field, and no other nurse led 5 year follow up studies have been published. <h3>Methods</h3> Between 2001 and 2004, 271 cases of asymptomatic iron deficiency anaemia were referred to the pathway and 212 met the inclusion criteria. From initial investigations, 43% were diagnosed with an underlying cause of anaemia and we have now followed up the remaining 122 patients for a minimum of 5 years. Data collected at presentation included: haemoglobin, mean cell volume, ferritin, creatinine, iron-binding capacity, CRP, drug use (aspirin, clopidogrel, warfarin, NSAIDs), co-morbidities, smoking status, BMI, and the results of investigations carried out (gastroscopy, colonoscopy, barium enema). Iron supplementation was recorded and haemoglobin level at 3 months. Patients were divided into 2 groups: those that died or developed malignancy and those that were well at 5 years. The data was analysed for significant differences between the 2 groups and to identify risk factors for poor prognosis. <h3>Results</h3> Analysis of primary and secondary care records generated outcome data of 97% (118) patients. 69% were female and 31% were male, mean age of 69 years. At 5 years, 20% had died or developed malignancy and 80% were alive and well. With the exception of diabetes, OR 0.24 (95%CI 0.1–0.8, p = 0.02), no other factors were found to be a significant risk factor for poor prognosis when the two groups were compared, including age, gender, haemoglobin level at presentation, persistent anaemia at 3 months, or other co-morbidities. Only 3 patients developed colonic malignancy; in all 3 patients the anaemia had resolved at 3 months. Two patients had diverticular disease only at initial barium enema but presented 4 years later with colorectal cancer. One patient declined lower GI investigation and presented with metastatic colon cancer on CT scanning at 1 year. No other GI cancers were diagnosed at 5 year follow up. <h3>Conclusion</h3> This study demonstrates that this nurse led, protocol driven pathway is a highly effective and safe system for the exclusion of GI cancer with 5 years follow up and we would recommend implementation throughout the NHS. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Goddard A<i> et al.</i> Guidelines for the management of iron deficiency anaemia. GUT 2010; 60: 1309–1316.
Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach
Authors: Mark N Lee, Matthew Roy, Shao-En Ong, Philipp Mertins, Alexandra-Chloé Villani, Weibo Li, Farokh Dotiwala, Jayita Sen, John G Doench, Megan H Orzalli, Igor Kramnik, David M Knipe, Judy Lieberman, Steven A Carr, Nir Hacohen
Journal: Nature Immunology (2012)
Regulation and characterization of IL-17A expression in patients with chronic rhinosinusitis and its relationship with eosinophilic inflammation
Authors: Seiichiro Makihara, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Yohei Noda, Takaya Higaki, Kazunori Nishizaki
Journal: Journal of Allergy and Clinical Immunology (2010)
Localization of TFF3, a New Mucus-associated Peptide of the Human Respiratory Tract
Authors: ANTJE WIEDE, WOLFGANG JAGLA, TOBIAS WELTE, THOMAS KÖHNLEIN, HENNING BUSK, WERNER HOFFMANN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Trefoil factor family (TFF)-domain peptides (formerly P-domain peptides, trefoil factors) represent major mucin-associated peptides of the gastrointestinal tract. Here, the first localization studies on TFF3 in the lower respiratory tract of human material are presented. Immunohistochemistry revealed significant accumulation of TFF3 to mucous cells in the acini of submucosal glands and varying amounts in goblet cells at the ductular portions and the surface epithelium. TFF3 appears also as a component of the mucus, for example from patients with chronic bronchitis. Expression of TFF3 was also shown by use of the polymerase chain reaction. In contrast, TFF1 and TFF2 transcripts were hardly detectable in the human respiratory tract. Thus, a structural function of TFF3 for the airway mucus is discussed, possibly together with the mucins MUC5B and MUC5AC.
Splenectomy in Rheumatoid Arthritis
Authors: Francis Bach, J.H. Jacobs
Journal: Annals of the Rheumatic Diseases (1951)

Chevallier (1930) emphasized the similarity of the Chauffard-Still's disease to the " rhumatisme bilaire " described by Gilbert and by Fournier, and to the arthritic manifestations of the " cirrhoses bilaires " mentioned by Hanot.After describing the ineffectiveness of various forms of medical treatment, he noted that, as far as he knew, in no instance had the spleen been removed, although it was known that in patients with splenic enlargement the associated symptoms often abated after removal of the spleen, and commented that splenectomy might be worth trying.Hanrahan and Miller (1932), and Craven (1934), reported the result of splenectomy in Felty's syndrome in two women aged 50 and 40 respectively.After the operation a clinical improvement was noted with reduction of pain and joint stiffness.Fitz (1935), however, in a discussion on Felty's syndrome, stated that both these patients had died within 18 months of the operation.Loeper, Lemaire, and Patel (1937) reported the successful removal of the spleen in a woman aged 28 who was suffering from advanced rheumatoid arthritis; but 35 days after the operation she developed pneumonia and died.Pointing out that in this disease there is a diffuse mesenchymal reaction character- istic of an infective disease, they suggested that it might be looked on as one of the " reticulo-endothelioses " and that although the aetiology might be unknown, this would give a reason for the clinical improvement following splenectomy.In 1938, at my instigation, the spleen was removed in three patients under my care at St. Stephen's Hospital, who were suffering from rheumatoid arthritis in an active and advanced stage.In reporting this, we stated (Bach and Savage, 1940) that we did not know the aetiology of rheumatoid arthritis, and were not prepared to estimate the role of the spleen in this disease.As the clinical improve- ment following splenectomy impressed me, two more patients in the unit were subjected to this operation in 1944-45, and two or three elsewhere, of whom I have no further record.I then stopped this somewhat drastic treatment until after my return from the United States in 1949.The work of Hench and Thorn had now given us much to think about, though I was not convinced that cortisone was the final answer, nor that the adrenal cortex was the only " villain of the piece ".I reviewed my splenectomy patients, and seeing that they had not done too badly,
Association of A1C and Fasting Plasma Glucose Levels With Diabetic Retinopathy Prevalence in the U.S. Population
Authors: Yiling J. Cheng, Edward W. Gregg, Linda S. Geiss, Giuseppina Imperatore, Desmond E. Williams, Xinzhi Zhang, Ann L. Albright, Catherine C. Cowie, Ronald Klein, Jinan B. Saaddine
Journal: Diabetes Care (2009)

To examine the association of A1C levels and fasting plasma glucose (FPG) with diabetic retinopathy in the U.S. population and to compare the ability of the two glycemic measures to discriminate between people with and without retinopathy.This study included 1,066 individuals aged >or=40 years from the 2005-2006 National Health and Nutrition Examination Survey. A1C, FPG, and 45 degrees color digital retinal images were assessed. Retinopathy was defined as a level >or=14 on the Early Treatment Diabetic Retinopathy Study severity scale. We used joinpoint regression to identify linear inflections of prevalence of retinopathy in the association between A1C and FPG.The overall prevalence of retinopathy was 11%, which is appreciably lower than the prevalence in people with diagnosed diabetes (36%). There was a sharp increase in retinopathy prevalence in those with A1C >or=5.5% or FPG >or=5.8 mmol/l. After excluding 144 people using hypoglycemic medication, the change points for the greatest increase in retinopathy prevalence were A1C 5.5% and FPG 7.0 mmol/l. The coefficients of variation were 15.6 for A1C and 28.8 for FPG. Based on the areas under the receiver operating characteristic curves, A1C was a stronger discriminator of retinopathy (0.71 [95% CI 0.66-0.76]) than FPG (0.65 [0.60 - 0.70], P for difference = 0.009).The steepest increase in retinopathy prevalence occurs among individuals with A1C >or=5.5% and FPG >or=5.8 mmol/l. A1C discriminates prevalence of retinopathy better than FPG.
Intracoronary Injection of CD133-Positive Enriched Bone Marrow Progenitor Cells Promotes Cardiac Recovery After Recent Myocardial Infarction
Authors: Jozef Bartunek, Marc Vanderheyden, Bart Vandekerckhove, Samer Mansour, Bernard De Bruyne, Pieter De Bondt, Inge Van Haute, Nele Lootens, Guy Heyndrickx, William Wijns
Journal: Circulation (2005)

Background— Bone marrow CD133-postive (CD133 + ) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133 + progenitor cells after intracoronary administration in patients with recent myocardial infarction. Methods and Results— Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133 + progenitor cells (12.6±2.2×10 6 cells) 11.6±1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0±2.6% to 52.1±3.5%, P &lt;0.05), but only tended to increase in case-matched group 2 patients (from 44.3±3.1% to 48.6±3.6%, P =NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5±1.0% to 16.1±1.3%, P &lt;0.05) but remained unchanged in group 2 patients (from 11.1±1.1% to 12.7±1.3%, P =NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0±4.1% to 22.5±4.1%, P &lt;0.05) and no change in group 2 (from 25.0±3.0% to 22.6±4.1%, P =NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with 18 fluorodeoxyglucose in the infarct-related territory increased from 51.2±2.6% to 57.5±3.5% ( P &lt;0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months. Conclusion— In patients with recent myocardial infarction, intracoronary administration of enriched CD133 + cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.
Instantiated rules and abstract analogy: Not a continuum of similarity
Authors: Lee R. Brooks, Samuel D. Hannah
Journal: Behavioral and Brain Sciences (2005)

We agree that treating rules and similarity as dichotomous opposites is unproductive. However, describing all categorization operations as a continuum of varied similarity process obscures a multidimensional contrast. We describe two processes, instantiated rules and abstract analogy, both of which have aspects of rules and similarity, and question whether they can be compared informatively as points on a continuum.
Incidence of Malignant Thyroid Tumors in Humans After Exposure To Diagnostic Doses Of Iodine-131. II. Estimation of Thyroid Gland Size, Thyroid Radiation Dose, and Predicted Versus Observed Number of Malignant Thyroid Tumors&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: L E Holm, G Eklund, G Lundell
Journal: JNCI Journal of the National Cancer Institute (1980)

The size of the thyroid glands was analyzed for 10% of the patients in a selected group that had been exposed to diagnostic doses of 131I. The mean thyroid gland weight +/- SD was 50 +/- 33 g for patients 20 or more years of age and 10 +/- 5 g for patients less than 20 years of age. With the present follow-up, diagnostic doses of 131I appeared not to be associated with an increased risk for later development of malignant thyroid tumors. Possible reasons for the difference between the observed number of such tumors and the number expected (47-124) on the basis of risk estimates of the United Nations Scientific Committee on the Effects of Atomic Radiation are discussed.
Evidence for increased synthesis of complement C4 in the renal epithelium of rats with passive Heymann nephritis.
Authors: W Zhou, P A Andrews, Y Wang, J Wolff, J Pratt, B R Hartley, P Verroust, S H Sacks
Journal: Journal of the American Society of Nephrology (1997)

Passive Heymann nephritis (PHN) is a complement-dependent model of immune complex glomerulonephritis. This study investigated the contribution of local complement synthesis by studying gene expression of the classical pathway component C4 in relation to the site of the tissue injury and the development of proteinuria induced by the pathogenic antibody (sheep anti-GP330). This study, using in situ hybridization, found that C4 mRNA expression was increased in the glomerular epithelium and the proximal renal tubular epithelium in a distribution similar to that of the targeted GP330 antigen. The total cortical C4 mRNA expression assessed by semiquantitative polymerase chain reaction (PCR) increased in a time-dependent manner (P < 0.05), coincident with the onset and progression of proteinuria, and peaking 11 to 14 days after the induction of the disease. These data suggest a link, in place and time, between local complement gene expression and glomerular barrier dysfunction induced by anti-GP330. It is postulated that increased epithelial synthesis of C4 stimulated by the engagement of GP330 enhances the formation of the membrane attack complex of complement through its classical pathway, and, hence, the formation of complement-mediated injury.