tbuckley/cabot-search huggingface dataset:
Dysregulated serum response factor triggers formation of hepatocellular carcinoma
Authors: Stefan Ohrnberger, Abhishek Thavamani, Albert Braeuning, Daniel B. Lipka, Milen Kirilov, Robert Geffers, Stella E. Authenrieth, Michael Römer, Andreas Zell, Michael Bonin, Michael Schwarz, Günther Schütz, Peter Schirmacher, Christoph Plass, Thomas Longerich, Alfred Nordheim
Journal: Hepatology (2014)

The ubiquitously expressed transcriptional regulator serum response factor (SRF) is controlled by both Ras/MAPK (mitogen‐activated protein kinase) and Rho/actin signaling pathways, which are frequently activated in hepatocellular carcinoma (HCC). We generated SRF‐VP16iHep mice, which conditionally express constitutively active SRF‐VP16 in hepatocytes, thereby controlling subsets of both Ras/MAPK‐ and Rho/actin‐stimulated target genes. All SRF‐VP16iHep mice develop hyperproliferative liver nodules that progresses to lethal HCC. Some murine (m)HCCs acquire Ctnnb1 mutations equivalent to those in human (h)HCC. The resulting transcript signatures mirror those of a distinct subgroup of hHCCs, with shared activation of oncofetal genes including Igf2 , correlating with CpG hypomethylation at the imprinted Igf2/H19 locus. Conclusion: SRF‐VP16iHep mHCC reveal convergent Ras/MAPK and Rho/actin signaling as a highly oncogenic driver mechanism for hepatocarcinogenesis. This suggests simultaneous inhibition of Ras/MAPK and Rho/actin signaling as a treatment strategy in hHCC therapy. (H epatology 2015;61:979–989)
Biochemistry of Nonheme Iron
Authors: Clement Finch
Journal: JAMA (1981)

This book represents somewhat of a tour de force for a single author in the scope of literature reviewed. It contains nine chapters, all but one by Bezkorovainy: "Tissue Iron and an Overview on Nonheme Iron Biochemistry," "Ferrokinetics," "Absorption of Nonheme Iron" (by Doris Narins), "Chemistry and Metabolism of Transferrins," "Chemistry and Biology of Iron Storage," "The Interaction of Nonheme Iron With Immature Red Cells," "Microbial Iron Uptake and Antimicrobial Properties of the Transferrins," "Iron Sulfur Proteins," and "Miscellaneous Aspects of Iron Metabolism." Each chapter begins with biochemical background, discusses contemporary work, and ends with an extensive reference section. The 435 pages provide a comprehensive review of the biochemistry and physiological behavior of the iron-binding proteins, including the often neglected iron sulfur proteins. In addition to numerous typographical mistakes, there are certain limitations to the way the material is handled. The book is inclusive, rather than critical, and outdated concepts
492 REGULATION OF LIVER GRAFT CHOLESTEROL SYNTHESIS AND UPTAKE AFFECTS THE OUTCOME OF HUMAN LIVER TRANSPLANTATION
Authors: S. Ginanni Corradini, M. Siciliano, A. Cantafora, I. Blotta, C. Pirazzi, L. Parlati, A. Molinaro, M. Giusto, G. Mennini, F. Pugliese, M. Merli, A.F. Attili, P.B. Berloco, M. Rossi
Journal: Journal of Hepatology (2010)
Reginald Seymour Lawrie
Authors: R. Spicer
Journal: BMJ (2011)

Reginald Seymour Lawrie (“Rex”), who died aged 93, was one of the most outstanding surgeons of his generation. He eschewed honours and titles, but if the measure of surgical excellence is the esteem of peers and colleagues it is difficult to think of anyone who was in his league.

Rex Lawrie was born in Helensburgh, Scotland. His father was an officer in the Royal Engineers. He was educated at Wellington College and obtained his medical degree (with many honours and prizes) from the Middlesex Hospital Medical School in 1939 and, after early surgical training, the FRCS in 1942. He was one of a very small, select group of surgeons who, in addition to the FRCS and MS, also obtained the postgraduate qualifications of MRCP and MD.

During the second world war he served in North Africa and Italy with the Royal Army Medical Corps, working with a small but pioneering maxillofacial unit treating serious, …
Cholestasis protects the liver from ischaemic injury and post-ischaemic inflammation in the mouse
Authors: P Georgiev, A A Navarini, J J Eloranta, K S Lang, G A Kullak-Ublick, A Nocito, F Dahm, W Jochum, R Graf, P-A Clavien
Journal: Gut (2006)

<b>Background and hypothesis:</b> Cholestasis is associated with high morbidity and mortality in patients undergoing major liver surgery, but the mechanisms responsible remain elusive. Increased ischaemic liver injury and inflammation may contribute to the poor outcome. <b>Methods:</b> Common bile duct ligation (biliary obstruction with hyperbilirubinaemia) or selective ligation of the left hepatic duct (biliary obstruction without hyperbilirubinaemia) was performed in C57BL/6 mice before 1 h of hepatic ischaemia and 1, 4 or 24 h of reperfusion. Infection with the intracellular hepatic pathogen <i>Listeria monocytogenes</i> for 12 and 48 h was used to study ischaemia-independent hepatic inflammation. <b>Results:</b> Cholestatic mice showed considerable protection from ischaemic liver injury as determined by transaminase release, histological liver injury and neutrophil infiltration. In cholestatic mice, reduced injury correlated with a failure to activate nuclear factor κB (NFκB) and tumour necrosis factor α (TNFα) mRNA synthesis, two key mediators of post-ischaemic liver inflammation. After selective bile duct ligation, both the ligated and the non-ligated lobes showed blocked activation of NFκB as well as reduced induction of TNFα mRNA synthesis and neutrophil infiltration. By contrast, infection with <i>L monocytogenes</i> showed comparable activation of NFκB and hepatic recruitment of neutrophils 12 h after infection. <b>Conclusion:</b> Cholestasis does not increase but rather dramatically protects the liver from ischaemic injury and inflammation. This effect is mediated by a systemic factor, but not bilirubin, and is associated with a preserved capacity to trigger an inflammatory response to other stimuli such as a bacterial pathogen.
Depression and Abnormal Endocrinologic Tests
Authors: Joel S. Steinberg
Journal: JAMA (1981)

<h3>To the Editor.—</h3> In the article "Diagnosis of Depression in the 1980s" (1981;245:1562) by Mark S. Gold, MD, et al two laboratory observations are described as confirmatory for a diagnosis of primary unipolar depression. These are the failure of dexamethasone to suppress blood cortisol secretion and the inability of thyrotropinreleasing hormone (TRH) to cause a rise of thyroid-stimulating hormone (TSH). However, these laboratory abnormalities are supportive of diagnoses of Cushing's syndrome and dysfunction of the hypothalamic-pituitary-thyroid axis, eg, primary hyperthyroidism. Do the patients classified as having a laboratoryconfirmed primary depression actually have endocrine disorders that warrant, but are not receiving, treatment? Please resolve this apparent dilemma.
The control of cell adhesion and detachment on thin films of thermoresponsive poly[(N-isopropylacrylamide)-r-((3-(methacryloylamino)propyl)-dimethyl(3-sulfopropyl)ammonium hydroxide)]
Authors: Bokyung Kong, Joon S. Choi, Saewha Jeon, Insung S. Choi
Journal: Biomaterials (2009)
CORONARY VASCULAR DYSFUNCTION IS ASSOCIATED WITH INCREASED EPICARDIAL ADIPOSE TISSUE AND MAJOR ADVERSE CARDIOVASCULAR EVENTS
Authors: Naser Ahmadi, Vahid Nabavi, Reuben J. Ram, Fereshteh Hajsadeghi, Michael Baskett, Ferdinand Flores, Matthew Budoff, Ramin Ebrahimi
Journal: Journal of the American College of Cardiology (2012)
Admission of old people to psychiatric units
Authors: J Andrews
Journal: BMJ (1980)

2) The bacteriological method used for isolation ofKlebsiella was as follows: Standard aliquots of faecal samples were cultured on a differential medium containing 1 °inositol, 1%,/ Lab Lemco, 1%X bacteriological peptone, 1 2%V agar, and bromothymol blue indicator incubated at 37°C for 18 hours.Inositol fermenting colonies were identified using API 20E.(3) There was no difference between the average number of visits from rheumatoid arthritis patients with one positive sample and the number of visits from patients who provided only negative samples.(4) Analysis of positive cultures in males and females was carried out on a patient and not a sample basis: 13 out of 33 men who provided samples on two or more occasions had two positive cultures compared with six out of 58 women who were examined in a similar way.This difference is significant.(5) The comparison among rheumatoid arthritis patients with HLA-B7 CREG antigens was carried on a patient and not a sample basis.(6) The reference to the work of Eastmond and coworkers' was misquoted as this group clearly found an association between isolation of faecal Klebsiella and uveitis (p <001) and peripheral synovitis (p < 0 05) in HLA-B27- positive patients with ankylosing spondylitis.Since we took the presence of uveitis and peripheral synovitis in ankylosing spondylitis as clinical evidence of disease activity we consider the results of this group as providing independent confirmation of our observations.( 7) The association of faecalKlebsiella with disease activity in ankylosing spondylitis has been made not only on clinical but also on biochemical criteria such as elevated erythrocyte sedimentation rate and C-reactive protein levels.2We agree that further studies are clearly indicated, and currently we are carrying out a survey on the prevalence ofKlebsiella in faecal samples obtained from tissue-typed healthy controls not associated with a hospital environment.
UK government endorses national exercise regime
Authors: Stephen Pincock
Journal: BMJ (2004)

The British government's top medical adviser has recommended that adults have 30 minutes of physical activity, five days a week, to maintain general health and reduce their risk of developing cardiovascular disease, diabetes, and cancer.

Professor Liam Donaldson, the chief medical officer, made the recommendation in a new report, At Least Five a Week , which gathers medical evidence on the impact of physical activity and health.

“We need to combat the couch potato culture, and this means building moderate everyday …
Genetic analysis of axon guidance and mapping in the zebrafish
Authors: Rolf O. Karlstrom, Torsten Trowe, Friedrich Bonhoeffer
Journal: Trends in Neurosciences (1997)

Systematic genetic screens have been powerful tools in identifying genes responsible for axon guidance in fruitflies and nematodes. This approach has now been extended to the study of axon guidance and the formation of topographic neuronal connections in the vertebrate brain. A systematic genetic screen was used to identify genes responsible for precise axon pathfinding and targeting in the retinotectal system of the zebrafish (Danio rerio). Over 30 genes were found that affect either: (1) retinal axon pathfinding to the contralateral tectal lobe; or (2) the topographic connection between the eye and the tectum. The zebrafish retinotectal mutants represent a new resource for the study of axon guidance in the vertebrate brain. Systematic genetic screens have been powerful tools in identifying genes responsible for axon guidance in fruitflies and nematodes. This approach has now been extended to the study of axon guidance and the formation of topographic neuronal connections in the vertebrate brain. A systematic genetic screen was used to identify genes responsible for precise axon pathfinding and targeting in the retinotectal system of the zebrafish (Danio rerio). Over 30 genes were found that affect either: (1) retinal axon pathfinding to the contralateral tectal lobe; or (2) the topographic connection between the eye and the tectum. The zebrafish retinotectal mutants represent a new resource for the study of axon guidance in the vertebrate brain.
Deaths From Hypothermia-Reply
Authors: Lee Sanderson
Journal: JAMA (1986)

In Reply.—  The concern expressed by Drs Zumwalt and Kicklighter that death certificates may not reflect the true incidence of hypothermia-associated deaths is also applicable to other causes of death. Death certificates have long been used as a surveillance tool in epidemiology, and their limitations are well known. These limitations, however, affected neither our objectives nor the conclusions we reached. Any adjustment for underascertainment of cases increases rather than decreases the importance of this public health problem, and we welcome any suggestions for improving the accuracy of effect estimates for mortality statistics, especially for hypothermia.  We agree that bias may be expected among mortality statistics, but we disagree with several conclusions in their letter. On the basis of pathological considerations, they contend that hypothermia is a mechanism and not a legitimate cause of death. Protocols for completing and coding death certificates, however, do identify hypothermia as a cause of death
AB0882 Coexistence of systemic lupus eryhematosus and ankylosing spondylitis a case report and review of the literature
Authors: F. Tarhan, M. Argın, G. Can, M. Ozmen, G. Keser
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown etiology that may affect the skin, joints, kidneys, lungs, nervous system, serous membranes, and/or other organs of the body. Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton manifested by inflammatory back pain and progressive stiffness of the spine. These two autoimmune rheumatologic diseases, which have different etiopathogenesis, as well as diverse clinical and genetic characteristics, are seldom seen together. <h3>Objectives</h3> Hereby, we present a 55-year-old female patient, being followed up with the diagnosis of SLE with locomotor, skin, renal and hematopoetic system involvement for eight years, who also suffered from inflammatory low back pain approximately for the last four months. <h3>Results</h3> Sacroiliac magnetic resonance imaging (MRI) confirmed the presence of bilateral sacroiliitis and HLA-B27 was positive. So, additional diagnosis of AS was made eight years after the diagnosis of SLE. Her laboratory test results were as follows: white blood cell count 3.85/μl (4.60-10.2), hemoglobin10.4g/dL (12.2-18.1), antinuclear antibody test 1/320 granular, anti-double-stranded DNA positive, Complement 3 65 mg/dl (83-193), Complement 4: 3 mg/dl (15-57). Renal biopsy was performed, and histopathological examination showed membranous glomerulonephritis, consistent with class V lupus nephritis. Inflammatory low back pain responded to treatment with non-steroidal anti-inflammatory drugs. <h3>Conclusions</h3> Including the present case, most of the reported cases of SLE and AS coexistance are females and generally SLE precedes the occurence of AS[1]. The present case is also notable with having MRI confirmation of bilateral active sacroiliitis with bone marrow edema. The coexistance of these two diseases with different genetic bacgrounds and clinical symptoms may implicate the importance of shared enviromental factors. <h3>References</h3> Mrabet D, Rekik S, Sahli H, Trojet S, Cheour I, Eleuch M et al (2011) Ankylosing spondylitis in female systemic lupus erythematosus: a rare combination. Lupus 20(14):777-8 <h3>Disclosure of Interest</h3> None Declared
Gamma Probe–Guided Lymph Node Dissection (‘Gamma Picking’) in Differentiated Thyroid Carcinoma
Authors: SEZA A. GULEC, MICHELLE ECKERT, EUGENE A. WOLTERING
Journal: Clinical Nuclear Medicine (2002)

The prognostic significance and the optimal management of regional lymph node metastases in patients with well-differentiated thyroid carcinoma continue to be controversial. The current surgical approach for nodal metastases is removal of grossly involved lymph nodes (“berry picking”). In patients with papillary thyroid cancer, this intraoperative sampling technique reveals tumor in only 15% to 60% of excised nodes. However, if a more extensive nodal dissection is undertaken, at least 70% of patients are found to have nodal disease. The authors have successfully used a gamma probe–guided lymph node dissection technique (“gamma picking”) to identify visually undetectable micrometastatic lymph nodes at the time of surgical exploration. The authors used this technique in a 52-year-old man with papillary carcinoma of the thyroid that was diagnosed by fine-needle aspiration. Eighteen hours before the planned total thyroidectomy, the patient was given 1 mCi I-123 orally. Operative exploration revealed multiple tumor nodules in both lobes but no palpable lymph nodes in the neck. Total thyroidectomy was performed with complete extracapsular removal of both lobes and isthmus. The thyroid bed and the central and lateral nodal basins were scanned using a gamma probe (Neoprobe). Hot spots were identified, and these counts were compared with that of the background activity in the strap muscles. The gamma probe revealed four distinct foci of increased activity (10 times more than the background). These were resected and labeled separately for histopathologic study. Histologic analysis revealed bilateral, multifocal well-differentiated papillary carcinoma, with the largest tumor focus measuring 0.6 cm. Two of the four hot spots proved to be metastatic foci in small lymph nodes measuring less than 0.5 cm. The other two hot spots were thyroid remnants with no associated nodal tissue.
CLINICAL, ANGIOGRAPHIC, AND VISUAL CORRELATION WITH THE (SIEMENS) CEDARS-SINAI CTQ STRESS/DELAYED SPECT THALLIUM QUANTITATIVE PROGRAM
Authors: W. R. Hetge, S. J. Sood, T. E. Vasquez, P. Y. Lai, G. G. Erwin, E. I. Dovichi
Journal: Clinical Nuclear Medicine (1991)

Hetge, W. R.; Sood, S. J.; Vasquez, T. E.; Lai, P. Y.; Erwin, G. G.; Dovichi, E. I. Author Information
Immunohistochemical demonstration of substance P in the lower respiratory tract of the rabbit and not of man.
Authors: L A Laitinen, A Laitinen, P A Panula, M Partanen, K Tervo, T Tervo
Journal: Thorax (1983)

Substance P (SP)-immunoreactive nerve fibres were searched for at all levels of both fetal and adult human lower respiratory tract. Because the demonstrability of substance P immunoreactivity varies between different animal species, rabbit pulmonary tissue was also subjected to SP immunohistochemistry. Human irises and corneas served as positive human controls. The specimens were taken from 10 human lungs during pulmonary operations. Tracheal tissue was obtained from three patients during bronchoscopy. Five fetal human lungs were examined. Human specimens examined included the trachea, main bronchi, segmental bronchi, and peripheral pulmonary tissue. In addition, the tracheobronchial tissues of four rabbits were studied. SP immunoreaction was demonstrated in formaldehyde-fixed cryostat sections by either the indirect immunofluorescence technique or the peroxidase-antiperoxidase procedure. Both monoclonal and conventional antibodies to SP were tested. In the rabbit SP-immunoreactive nerves were found in both the submucosa and the smooth muscle layer of the main bronchi and trachea. Specimens from human trachea, bronchi, and bronchioli were all negative. Since the SP immunoreaction was easily demonstrated in both human cornea and human iris, it was concluded that there are no SP-immunoreactive nerves in the human pulmonary tissues or that their SP content is very low and below the sensitivity of all the techniques used.
Myocardial adenylate cyclase activity in acute murine Chagas' disease.
Authors: S A Morris, H Tanowitz, S M Factor, J P Bilezikian, M Wittner
Journal: Circulation Research (1988)

We have studied the influence of myocardial infection with Trypanosoma cruzi on the beta-adrenergic adenylate cyclase complex in mouse myocardial membranes. The maximal rate of cAMP generation (Vmax) and the concentration of agonist associated with 50% of the maximal activity (apparent Kact) were determined for a series of agents. Six days after infection, the Vmax for isoproterenol significantly declines without a change in the apparent Kact. After 21 days of infection, both the Vmax and apparent Kact for isoproterenol are reduced. At 6 and 21 days of infection, the affinity of the beta-receptor for [125I]iodocyanopindolol declines from 0.84 to 3.6 and 3 nM, respectively, while the receptor density increases with the duration of infection from 33 to 57 and 82 fmol/mg protein, respectively. The Vmax (but not the apparent Kact) for forskolin and Mg2+- and Mn2+-associated activities declines also after 21 days. Another adenylate cyclase activity, which was stimulated by the nonhydrolyzable guanine nucleotide Gpp(NH)p, declines in relation to the duration of infection. Inhibitors of adenylate cyclase activity were also studied. Inhibition of adenylate cyclase activity by adenosine and by Gpp(NH)p (in the presence of forskolin) declines after 21 days of infection. The results suggested that the coupling proteins Ns and Ni, which mediate stimulatory or inhibitory control of receptors to adenylate cyclase activity, might be altered by infection. As monitored by cholera toxin- and pertussis toxin-dependent ADP ribosylation of their respective substrates, which include Ns and Ni proteins, respectively, there are declines in the availability of both substrates as a result of T. cruzi infection. For infected membranes, the addition of NADP enhances the magnitude of cholera toxin-dependent ADP ribosylation and renders the magnitude of pertussis toxin-dependent ADP ribosylation equal to that observed in uninfected membranes. The results support the hypothesis that infection with T. cruzi results in profound generalized alterations of the adenylate cyclase complex at several different sites.
Interleukin-12 prevents antigen-induced eosinophil recruitment into mouse airways.
Authors: I Iwamoto, K Kumano, M Kasai, K Kurasawa, A Nakao
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Interleukin-12 (IL-12) is a key cytokine that promotes Th1-type cell-mediated immunity and inhibits Th2-type responses. We have previously shown that antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by Th2-type CD4+ T cells that produce IL-5. Therefore, to determine whether IL-12 regulates antigen-induced eosinophil recruitment into the airways, we studied the effect of recombinant murine IL-12 on antigen-induced eosinophil infiltration into the tracheas of sensitized mice, and also the effect of IL-12 on IL-5 and interferon-gamma (IFN-gamma) levels in bronchoalveolar lavage fluid (BALF) from the mice. The intraperitoneal administration of recombinant IL-12 (rIL-12) inhibited antigen-induced eosinophil infiltration into the mouse trachea in a dose-dependent manner. The administration of rIL-12 suppressed IL-5 levels but enhanced IFN-gamma levels in the BALF of the mice after antigen inhalation. The administration of rIL-12 also decreased in vitro antigen-induced IL-4 and IL-5 production, but not IFN-gamma production, in spleen cells of the mice. Furthermore, pretreatment with anti-IFN-gamma monoclonal antibody prevented the IL-12 inhibition of antigen-induced eosinophil infiltration into the tracheas of the mice. These results indicate that IL-12 downregulates antigen-induced eosinophil recruitment into the airways by inhibiting IL-5 production in sensitized animals.