tbuckley/cabot-search huggingface dataset:
The role of matrix metalloproteinases in cystic fibrosis lung disease
Authors: A. Gaggar, A. Hector, P.E. Bratcher, M.A. Mall, M. Griese, D. Hartl
Journal: European Respiratory Journal (2011)

Significant airway remodelling is a major component of the increased morbidity and mortality observed in cystic fibrosis (CF) patients. These airways feature ongoing leukocytic inflammation and unrelenting bacterial infection. In contrast to acute bacterial pneumonia, CF infection is not cleared efficiently and the ensuing inflammatory response causes tissue damage. This structural damage is mainly a result of free proteolytic activity released by infiltrated neutrophils and macrophages. Major proteases in this disease are serine and matrix metalloproteases (MMPs). While the role of serine proteases, such as elastase, has been characterised in detail, there is emerging evidence that MMPs could play a key role in the pathogenesis of CF lung disease. This review summarises studies linking MMPs with CF lung disease and discusses the potential value of MMPs as future therapeutic targets in CF and other chronic lung diseases.
Role of Fast Data Acquisition Method with Tc-99m HMPAO Brain SPECT in Patients with Acute Stroke
Authors: MOTOO OSHIMA, MASANORI TADOKORO, NAOKI MAKINO, SADAYUKI SAKUMA
Journal: Clinical Nuclear Medicine (1990)

The fast data acquisition method for Tc-99m hexamethyl-propyleneamineoxime (Tc-99m HMPAO) brain SPECT was used in two patients with acute stroke 5 and 8 hours after the event. In one patient Tc-99m HMPAO fast SPECT showed perfusion defects before the same was manifested on CT. In the other patient, Tc-99m HMPAO fast SPECT showed larger defects than the edema seen on CT. The Tc-99m HMPAO fast SPECT might be feasible for the evaluation of acute stroke patients. Since the time required for fast SPECT is much shorter than usual SPECT, it appears to be more suitable for some patients with acute stroke who are brought to the hospital in a very critical condition.
TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
Authors: Manohar Pilli, John Arko-Mensah, Marisa Ponpuak, Esteban Roberts, Sharon Master, Michael A. Mandell, Nicolas Dupont, Wojciech Ornatowski, Shanya Jiang, Steven B. Bradfute, Jack-Ansgar Bruun, Tom Egil Hansen, Terje Johansen, Vojo Deretic
Journal: Immunity (2012)
830 Hydroxyfasudil, a RHO-kinase (ROCK) inhibitor, suppresses cell growth and collagen production in rat hepatic stellate cells
Authors: M FUKUSHIMA, S OHTA, M KUNIYOSHI, M ENJOJI, M NAKAMUTA
Journal: Hepatology (2003)

The hallmarks of type 2 diabetes are pancreatic β-cell dysfunction and insulin resistance. It has been suggested that Rho/Rho-kinase is a mediator of insulin signaling, and thereby involved in the development of insulin resistance, regulation of insulin action, and glucose homeostasis, but the role of Rho/Rho-kinase in β-cells remained unknown. The aim of this study was to examine the possible role of Rho/Rho-kinase in β-cell function. Immunostaining showed that RhoA was expressed in mature β-cells, with higher expression observed in β-cells of diabetic C57BL/KsJ-db/db mice compared to non-diabetic mice. In addition, to examine the functional role of Rho/Rho-kinase in β-cells, we evaluated the effect of Rho-kinase inhibitors on insulin biosynthesis. Northern blot analysis showed that insulin mRNA levels were markedly increased by Rho-kinase inhibitors, Y-27632 and fasudil, in β-cell-derived HIT-T15 cells. Furthermore, using the luciferase reporter gene assay, insulin promoter activity was also dramatically increased by Y-27632, which was associated with an increase in the insulin mRNA level. These results suggest that suppression of Rho/Rho-kinase increases insulin promoter activity, which leads to an increase in insulin mRNA level. Taken together, Rho/Rho-kinase is activated in β-cells under diabetic conditions and suppression of the Rho/Rho-kinase pathway increases insulin gene transcription. These results imply that Rho/Rho-kinase activation is involved in the suppression of insulin expression found in diabetes and that suppression of the Rho/Rho-kinase pathway could be a useful tool to augment insulin gene transcription.
Efficacy and toxicity of dexamethasone vs methylprednisolone—long-term results in more than 1000 patients from the Russian randomized multicentric trial ALL-MB 2002
Authors: A Karachunskiy, J Roumiantseva, S Lagoiko, C Bührer, G Tallen, O Aleinikova, O Bydanov, N Korepanova, L Bajdun, T Nasedkina, A von Stackelberg, G Novichkova, A Maschan, D Litvinov, N Myakova, N Ponomareva, K Kondratchik, L Fechina, O Streneva, N Judina, G Scharapova, A Shamardina, I Gerbek, A Shapochnik, A Rumjanzew, G Henze
Journal: Leukemia (2015)
Outbreak of E coli O157 is linked to Surrey open farm
Authors: J. Wise
Journal: BMJ (2009)

A large outbreak of Escherichia coli O157 at a farm in Surrey has resulted in 12 children needing hospital treatment. Three of them remain seriously ill.

The Health Protection Agency said that 36 cases of E coli O157 have been linked to Godstone farm, near Redhill in Surrey. The farm, which lets children pet and feed animals, receives up to 2000 visitors a day during school holidays.

Hugh Pennington, emeritus professor of microbiology at Aberdeen University, said: “This is a very large outbreak for an open farm; usually there are only one or two cases. It is a puzzle why there have been so many cases.”

Questions are being asked as to why the farm …
Future Cardiovascular Risk
Authors: Suttira Intapad, Barbara T. Alexander
Journal: Circulation (2013)

C ardiovascular (CV) disease is the leading cause of death in women over the age of 50.Risk factors related to the increase in CV disease after transition into menopause include an increase in abdominal obesity, dyslipidemia, insulin resistance, and hypertension. 13][4] Based on these findings, the National Institutes of Health sponsored a workshop in 2010 entitled, "Bridging Preeclampsia and Future Cardiovascular Disease." 5 The aims of the workshop were to "identify knowledge gaps and research opportunities" to facilitate the prevention of future CV risk in women who develop preeclampsia during pregnancy. 5Recommendations provided to the National Heart, Lung and Blood Institute from the workshop initiated with an aim to use "already established cohort studies."It was suggested that studies or trials with well-defined diagnoses of preeclampsia could be used to prospectively follow patients long-term to assess CV outcome and to determine the progression of chronic disease.
Prediction of sudden death in patients with dilated cardiomyopathy receiving angiotensin converting enzyme inhibitors and beta-blockers: the extent of intercellular myocardial fibrosis and the presence of nonsustained ventricular tachycardia
Authors: Takahisa Yamada, Masatake Fukunami, Tsuyoshi Shimonagata, Kazuaki Kumagai, Akio Hirata, Mitsutoshi Asai, Nobuhiko Makino, Hidetaka Kloka, Noritake Hoki
Journal: Journal of the American College of Cardiology (2002)
Lack of Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Signaling Shows a New Type of Melanoma
Authors: Janiel M. Shields, Nancy E. Thomas, Melissa Cregger, Aaron J. Berger, Michael Leslie, Chad Torrice, Honglin Hao, Shannon Penland, Jack Arbiser, Glynis Scott, Tong Zhou, Menashe Bar-Eli, James E. Bear, Channing J. Der, William K. Kaufmann, David L. Rimm, Norman E. Sharpless
Journal: Cancer Research (2007)

Abstract The majority of human melanomas harbor activating mutations of either N-RAS or its downstream effector B-RAF, which cause activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase and the ERK MAPK cascade. The melanoma-relevant effectors of ERK activation, however, are largely unknown. In this work, we show that increased ERK activation correlates strongly with mutational status of N-RAS or B-RAF in 21 melanoma cell lines. Melanoma lines that were wild-type for RAS/RAF showed low levels of ERK activation comparable with primary human melanocytes. Through supervised analysis of RNA expression profiles, we identified 82 genes, including TWIST1, HIF1α, and IL-8, which correlated with ERK activation across the panel of cell lines and which decreased with pharmacologic inhibition of ERK activity, suggesting that they are ERK transcriptional targets in melanoma. Additionally, lines lacking mutations of N-RAS and B-RAF were molecularly distinct and characterized by p53 inactivation, reduced ERK activity, and increased expression of epithelial markers. Analysis of primary human melanomas by tissue microarray confirmed a high correlation among expression of these epithelial markers in a heterogeneous sample of 570 primary human tumors, suggesting that a significant frequency of primary melanomas is of this “epithelial-like” subtype. These results show a molecularly distinct melanoma subtype that does not require ERK activation or epithelial-mesenchymal transformation for progression. [Cancer Res 2007;67(4):1502–12]
Does closing branch surgeries affect home visiting?
Authors: B R McAvoy
Journal: BMJ (1985)

Home visiting rates in a rural general practice were compared for 12 months before and 12 months after five branch surgeries were closed. In villages whose surgeries were closed no statistically significant change occurred in the new or repeat visiting rates. The consulting rate at the main surgery remained constant over the two years. Although visiting rates to villages that had had a branch surgery did not change after the closures, the pattern of visiting to these villages became more rational.
Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes
Authors: Tian Xue, Hee Cheol Cho, Fadi G. Akar, Suk-Ying Tsang, Steven P. Jones, Eduardo Marbán, Gordon F. Tomaselli, Ronald A. Li
Journal: Circulation (2004)

Background— Human embryonic stem cells (hESCs) derived from blastocysts can propagate indefinitely in culture while maintaining pluripotency, including the ability to differentiate into cardiomyocytes (CMs); therefore, hESCs may provide an unlimited source of human CMs for cell-based therapies. Although CMs can be derived from hESCs ex vivo, it remains uncertain whether a functional syncytium can be formed between donor and recipient cells after engraftment. Methods and Results— Using a combination of electrophysiological and imaging techniques, here we demonstrate that electrically active, donor CMs derived from hESCs that had been stably genetically engineered by a recombinant lentivirus can functionally integrate with otherwise-quiescent, recipient, ventricular CMs to induce rhythmic electrical and contractile activities in vitro. The integrated syncytium was responsive to the β-adrenergic agonist isoproterenol as well as to other pharmacological agents such as lidocaine and ZD7288. Similarly, a functional hESC-derived pacemaker could be implanted in the left ventricle in vivo. Detailed optical mapping of the epicardial surface of guinea pig hearts transplanted with hESC-derived CMs confirmed the successful spread of membrane depolarization from the site of injection to the surrounding myocardium. Conclusions— We conclude that electrically active, hESC-derived CMs are capable of actively pacing quiescent, recipient, ventricular CMs in vitro and ventricular myocardium in vivo. Our results may lead to an alternative or a supplemental method for correcting defects in cardiac impulse generation, such as cell-based pacemakers.
Cow's milk allergy and the association between fatty acids and childhood asthma risk
Authors: Mirka Lumia, Päivi Luukkainen, Hanna-Mari Takkinen, Minna Kaila, Bright I. Nwaru, Jaakko Nevalainen, Irma Salminen, Liisa Uusitalo, Sari Niinistö, Jetta Tuokkola, Onni Niemelä, Anna-Maija Haapala, Jorma Ilonen, Olli Simell, Mikael Knip, Riitta Veijola, Suvi M. Virtanen
Journal: Journal of Allergy and Clinical Immunology (2014)
Tuberculous spondylitis in the elderly: a potential diagnostic pitfall.
Authors: J S Mann, R B Cole
Journal: BMJ (1987)

complications are rare. Major textbooks and specialised books on osteoporosis either do not mention spinal cord compression as a complication of senile osteoporosis13 or state that it is rare or does not occur.4* Thus one book states, Nerve root compression is rare and spinal cord damage does not occur even in the presence of severe deformity5; another that, Spinal cord compression does not occur and classical root pain is atypical6; while another does not completely exclude the possibility of paraplegia in stating that, Radiation of pain down one leg is uncommon and symptoms or signs of spinal cord compression are very rare.4 There was both clinical and radiological support for the diagnosis of metastatic bone disease in both of our patients, with no other differential diagnosis being considered to be likely. Necropsy was expected to confirm this, but pathological and histol?gica! examination showed only osteoporosis in each case. It is interesting that both patients were men as ?he condition is rarer in men, but we cannot propose any explanation for this other than chance. These two cases should alert physicians to the possibility of osteoporotic vertebral collapse as a cause of spinal cord compression and encourage its mention in future editions of the relevant textbooks.
Minimally Invasive Surgery: Future developments
Authors: J E A Wickham
Journal: BMJ (1994)

The rapid development of minimally invasive surgery means that there will be fundamental changes in interventional treatment. Technological advances will allow new minimally invasive procedures to be developed. Application of robotics will allow some procedures to be done automatically, and coupling of slave robotic instruments with virtual reality images will allow surgeons to perform operations by remote control. Miniature motors and instruments designed by microengineering could be introduced into body cavities to perform operations that are currently impossible. New materials will allow changes in instrument construction, such as use of memory metals to make heat activated scissors or forceps. With the reduced trauma associated with minimally invasive surgery, fewer operations will require long hospital stays. Traditional surgical wards will become largely redundant, and hospitals will need to cope with increased through-put of patients. Operating theatres will have to be equipped with complex high technology equipment, and hospital staff will need to be trained to manage it. Conventional nursing care will be carried out more in the community. Many traditional specialties will be merged, and surgical training will need fundamental revision to ensure that surgeons are competent to carry out the new procedures.
C-Reactive Protein Is an Independent Predictor of the Rate of Increase in Early Carotid Atherosclerosis
Authors: Hiroyuki Hashimoto, Kazuo Kitagawa, Hidetaka Hougaku, Yoshiomi Shimizu, Manabu Sakaguchi, Yoji Nagai, Shigeru Iyama, Hachiro Yamanishi, Masayasu Matsumoto, Masatsugu Hori
Journal: Circulation (2001)

An elevated plasma concentration of high-sensitivity C-reactive protein (hs-CRP) is a strong predictor of cardiovascular events. However, there have been no longitudinal studies of the relations between development of atherosclerotic lesions and hs-CRP concentrations. Furthermore, it remains unknown whether increased hs-CRP concentrations result in the development of atherosclerosis.The study included 179 outpatients 40 to 79 years of age who were treated at our institute for traditional risk factors for cardiovascular disease. The patients had no evidence of advanced carotid atherosclerosis at the time of baseline examination. Patients underwent repeated ultrasonographic evaluation of the carotid arteries for 35+/-10 months. Blood samples were collected for hs-CRP measurements. Based on focal intima-media thickening >/=1.1 mm representing plaque, plaque number (PN) and plaque score (PS; the sum of all plaque thicknesses) were calculated. The development of atherosclerosis was estimated by the formula Deltavalue/year=(last value-baseline value)/number of follow-up years. Multivariate linear regression analysis revealed that the log-transformed value for hs-CRP concentration was not related to baseline PN or PS but was related to DeltaPN/year and DeltaPS/year (beta=0.29 and 0.30; P<0.001 for both) independently of the effect of traditional risk factors.During the early stages of carotid atherosclerosis, the hs-CRP concentration is a marker of carotid atherosclerotic activity rather than extent of atherosclerosis.
CD34<sup>+</sup> and CFU‐GM progenitors are significantly decreased in sivsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction
Authors: Christopher D. Hillyer, Dixon A. Lackey, Francois Villinger, Elliott F. Winton, Harold M. McClure, Aftab A. Ansari
Journal: American Journal of Hematology (1993)

Abstract Hematologic abnormalities in the peripheral blood and bone marrow are associated with human immunodeficiency and simian immunodeficiency virus (HIV, SIV) infection. The reasons for these abnormalities remain unclear. Bone marrow specimens collected from uninfected animals (Group A, Controls) and from rhesus macaques experimentally infected with SIVsmm9 during the asymptomatic stage (Group B, SIV + “well”) and during the clinically ill stage (Group C, SIV + “sick”), underwent a variety of in vitro assays of hematopoiesis. Colony forming unit‐granulocyte/macrophage (CFU‐GM) per plate growth was 46.7 ± 7.7, 31.9 ± 8.4 and 6.5 ± 5.0 (means ± sd, P &lt;.02 each mean compared to the others) in the 3 groups respectively. Burst forming unit‐erythroid (BFU‐E) growth was similarly decreased in bone marrow samples from the SIV + animals. There was no change in the number of CFU‐GM per plate with the removal of plastic adherent or T‐cell mononuclear cell fractions. There was no increase in CFU‐GM per plate growth with the addition of low dose GM‐CSF (1 or 5 ng/mL) though there was a near 67% increase (48 to 80 CFU‐GM per plate) with the addition of 100 ng/mL recombinant rhesus IL‐3 and 100 ng/mL GM‐CSF in SIV + 'sick' animals. Variation in frequency of CD34 + progenitor cells in SIV + animals was seen, with 3.0% CD34 cells in SIV − controls, 4.9% CD34 + cells in SIV + 'well' animals and 0.5% CD34 + progenitor cells in SIV + 'sick' monkeys ( P &lt;.01, each mean compared to the others). Finally, there was minimal evidence of SIV sequences by polymerase chain reaction in pooled cultured CFU‐GM, and no evidence in flowcytometrically sorted CD34 + progenitor cells from selected animals. Thus, the SIV seropositive rhesus monkey appears to have similar hematopoietic aberrations as are found in HIV infected human subjects and may be an excellent model for studying the interaction of lentiviruses on the kinetics of blood formation.
INTRAPERITONEAL AND INTRACEREBRAL ROUTES IN SERUM PROTECTION TESTS WITH THE VIRUS OF EQUINE ENCEPHALOMYELITIS
Authors: Peter K. Olitsky, Carl G. Harford
Journal: The Journal of Experimental Medicine (1938)

Minute amounts of antiserum injected intraperitoneally protect against large doses of equine encephalomyelitis virus given intramuscularly or intraperitoneally in 12 to 15 day old mice. Antiserum given intraperitoneally with virus intracerebrally or intranasally results in little or no protection. These phenomena occur as well when serum-virus mixtures are injected at the different sites. The marked variation of the protective capacity of antiserum as thus displayed would appear to be dependent upon the differing pathways of progression of the virus from the site of injection to the central nervous system.
Abstract 609: Targeting IGF-I receptor for hepatocellular carcinoma
Authors: Yasushi Adachi, Yasutaka Matsunaga, Hiroyuki Yamamoto, Katsuhiko Nosho, Hiromu Suzuki, Yoshiaki Arimura, Takao Endo, Yasuo Kato, David P. Carbone, Yasuhisa Shinomura
Journal: Cancer Research (2014)

Abstract Aims; Hepatocellular carcinoma (HCC) is one of worse prognostic diseases. Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling is required for carcinogenicity and tumor development of many malignancies and is thought to be a next molecular target. We have previously shown successful therapy for gastrointestinal carcinomas, including colon, stomach, esophageal, pancreatic, and biliary tract cancers, using recombinant adenoviruses expressing dominant negative IGF-IR (IGF-IR/dn). In this study, we want to assess the roles of IGF axis on HCC and to develop potential targeted therapeutics for HCC. Methods; We assessed mRNA expressions of IGFs and those receptors in HCC cell lines. We assessed the effect of IGF-IR blockade on signal-transduction, growth, apoptosis-induction, and migration. To block IGF signals, we used IGF-IR/dn, short hairpin RNA, monoclonal antibody, and tyrosin kinase inhibitor for IGF-IR. Results; IGF-I messages expressed in 63%, IGF-II mRNA in 44%, and IGF-IR in 89% of HCC cell lines. All IGF-IR blockades suppressed significantly both in vitro cell growth and colony formation. Each anti-IGF-IR up-regulated both stressor- and chemotherapy-induced apoptosis. IGF-IR inhibitor down-regulated cell migration. IGF-IR targeting strategies effectively blocked ligands induced receptor activation and the downstream signals. Conclusions; IGF axis might play a key role in tumor progression of human HCC. Every strategy to block IGF-IR shows a useful anticancer therapeutic for HCC, indicating that IGF-IR may be a candidate molecular target for HCC. Citation Format: Yasushi Adachi, Yasutaka Matsunaga, Hiroyuki Yamamoto, Katsuhiko Nosho, Hiromu Suzuki, Yoshiaki Arimura, Takao Endo, Yasuo Kato, David P. Carbone, Yasuhisa Shinomura. Targeting IGF-I receptor for hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 609. doi:10.1158/1538-7445.AM2014-609
Glutamate Metabolism in Major Depressive Disorder
Authors: Chadi G. Abdallah, Lihong Jiang, Henk M. De Feyter, Madonna Fasula, John H. Krystal, Douglas L. Rothman, Graeme F. Mason, Gerard Sanacora
Journal: American Journal of Psychiatry (2014)

Research on novel treatments for major depressive disorder focuses quite deeply on glutamate function, and this research would benefit from a brain-imaging technique that precisely quantified glutamate function. Signs of a specific form of glutamate-related dysfunction that could be targeted by novel therapies were found using novel, state-of-the-art techniques to address this issue.
Rubber Tube Percussion.
Authors: F. M. Pottenger
Journal: JAMA (1907)

Monrovia, Cal., May 25, 1907. <h3>To the Editor:</h3> —In replying to Dr. Klebs' article inThe Journal, April 6, 1907, page 1187, relative to "Rubber Tube Percussion," I prefer to discuss the merits of the question only, as sarcasm has no bearing on scientific truths. I am aware of the fact that I did not enter into a careful discussion of all the minute details connected with the theories of percussion in the short article in which I described the use of the new method. I simply called attention to the method in the hope that other men might give it a fair trial and determine its value. Percussion of the chest by ordinary methods is at best unsatisfactory; and, as practiced by many physicians, is unreliable and worthless. During recent years I have acquainted myself with most of the different varieties of percussion and have compared my findings by