tbuckley/cabot-search huggingface dataset:
Antimitochondrial autoantibodies in primary biliary cirrhosis recognize cross-reactive epitope(s) on protein X and dihydrolipoamide acetyltransferase of pyruvate dehydrogenase complex
Authors: Charles D. Surh, Thomas E. Roche, Dean J. Danner, Aftab Ansari, Ross L. Coppel, Thomas Prindiville, E. Rolland Dickson, M. Eric Gershwin
Journal: Hepatology (1989)

Antimitochondrial autoantibodies are characteristically present in sera of patients with primary biliary cirrhosis. The antimitochondrial autoantibodies recognize four major antigens from beef heart mitochondria at relative molecular weights of 74, 56, 52 and 48 kD. In the present study, we report that the 56 kD antigen is the protein X of pyruvate dehydrogenase complex and that it possesses cross-reactive antimitochondrial autoantibody epitope(s) with the 74 kD antigen, the acetyltransferase (E2) of the pyruvate dehydrogenase complex. This was demonstrated by comparing the specificities of primary biliary cirrhosis sera with a protein X-specific rabbit antiserum and by absorbing primary biliary cirrhosis sera with recombinant pyruvate dehydrogenase-E2 fusion protein. In the two-dimensional gel analysis, primary biliary cirrhosis sera and protein X-specific rabbit antiserum reacted to the same two isoelectric point polypeptides at 56 kD molecular weight. The absorption of primary biliary cirrhosis sera with the human recombinant pyruvate dehydrogenase-E2 removed reactivity toward both the 74 and 56 kD antigens. Furthermore, analysis of 82 antimitochondrial autoantibody-positive primary biliary cirrhosis sera by immunoblotting did not reveal any sera which reacted solely against either the 74 or 56 kD antigen. Finally, primary biliary cirrhosis sera recognized protein X from human, bovine and porcine sources but not protein X from rat or mouse origin. The identification of protein X as another major target of the autoimmune response in primary biliary cirrhosis suggests that the pyruvate dehydrogenase complex may have a central role in the induction of this enigmatic disease.
Cell Type-Specific Tumor Suppression by <i>Ink4a</i> and <i>Arf</i> in Kras-Induced Mouse Gliomagenesis
Authors: Lene Uhrbom, Marianne Kastemar, Fredrik K. Johansson, Bengt Westermark, Eric C. Holland
Journal: Cancer Research (2005)

Abstract Homozygous deletion of the INK4a-ARF locus is one of the most frequent mutations found in human glioblastoma. We have previously shown that combined Ink4a-Arf loss can increase tumor incidence in both glial progenitor cells and astrocytes during mouse gliomagenesis. Here we have investigated the separate contribution of loss of each of the tumor suppressor genes in glial progenitor cells and astrocytes in Akt + Kras–induced gliomagenesis. We show that Arf is the major tumor suppressor gene in both cell types. Arf loss generated glioblastomas from both nestin-expressing glial progenitor cells and glial fibrillary acidic protein–expressing astrocytes, with a significantly higher incidence in astrocytes. Ink4a loss, on the other hand, could only significantly contribute to gliomagenesis from glial progenitor cells and the induced tumors were of lower malignancy than those seen in Arf-deficient mice. Thus, Ink4a and Arf have independent and differential tumor suppressor functions in vivo in the glial cell compartment.
Freeze-fracture replication of X-granules in cells of cutaneous lesions of histiocytosis-X (Letterer-Siwe disease)
Authors: A.S. BREATHNACH, M. GROSS, F. BASSET, C. NEZELOF
Journal: British Journal of Dermatology (1973)

Journal Article Freeze‐fracture replication of X‐granules in cells of cutaneous lesions of histiocytosis‐X (Letterer‐Siwe disease) Get access A.S. BREATHNACH, A.S. BREATHNACH Department of Anatomy, St Mary's Hospital Medical School, London, W.2 Search for other works by this author on: Oxford Academic Google Scholar M. GROSS, M. GROSS Department of Anatomy, St Mary's Hospital Medical School, London, W.2 Search for other works by this author on: Oxford Academic Google Scholar F. BASSET, F. BASSET Groupe de Recherches U 82 de l'I.N.S.E.R.M., Hôpital Bichat, Paris Search for other works by this author on: Oxford Academic Google Scholar C. NÈZELOF C. NÈZELOF Groupe Hospitalier Necker‐Enfants‐Malades, Paris Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 6, 1 December 1973, Pages 571–585, https://doi.org/10.1111/j.1365-2133.1973.tb07582.x Published: 01 December 1973 Article history Accepted: 24 April 1973 Published: 01 December 1973
Loophole exposed in testing of child medicines
Authors: J. Warden
Journal: BMJ (1997)

Numerous gaps in the health care of children and young people in Britain-notably in the testing of child medicines-have been identified by the House of Commons Health Committee.

In the first two reports the MPs state that the special needs of children are given insufficient priority by policymakers and health service professionals. A main finding is that medicines for children are not controlled in the same way as for adults. Some medicines given to children are not licensed for human administration at all, …
Induction of DNA synthesis in primary cultures of rat hepatocytes by serotonin: Possible involvement of serotonin S2 receptor
Authors: Sudha Balasubramanian, Cheramadathikudyil S. Paulose
Journal: Hepatology (1998)

The involvement of serotonin and its receptor subtype in the induction of hepatocyte DNA synthesis was investigated in primary cultures of adult rat hepatocytes. Serotonin caused a dose-dependent increase in DNA synthesis in primary cultures of rat hepatocytes in the presence of epidermal growth factor (EGF) and insulin, as measured by [3H]thymidine incorporation. The serotonin S2receptor antagonists, ketanserin (10−6 mol/L) and spiperone (10−6 mol/L), blocked stimulation of DNA synthesis by serotonin. Displacement studies on [3H]5-hydroxytryptamine (5-HT) binding to crude membranes from control and regenerating liver tissue, using cold ketanserin and spiperone, showed an increased involvement of S2 receptors of serotonin in the regenerating liver during the DNA-synthetic phase. Serotonin enhanced the phosphorylation of a 40-kd substrate protein of protein kinase C (PKC) in the regenerating liver during the DNA synthetic phase of the hepatocyte cell cycle. This was blocked by ketanserin, indicating that serotonin S2receptor activates PKC, an important second messenger in cell growth and division, during rat liver regeneration. Our results show that serotonin can act as a potent hepatocyte comitogen and induce DNA synthesis in primary cultures of rat hepatocytes, which is suggested to be mediated through the serotonin S2 receptors of hepatocytes.
Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest
Authors: Michael R. Mooney, Barbara T. Unger, Lori L. Boland, M. Nicholas Burke, Kalie Y. Kebed, Kevin J. Graham, Timothy D. Henry, William T. Katsiyiannis, Paul A. Satterlee, Sue Sendelbach, James S. Hodges, William M. Parham
Journal: Circulation (2011)

Therapeutic hypothermia (TH) improves survival and confers neuroprotection in out-of-hospital cardiac arrest (OHCA), but TH is underutilized, and regional systems of care for OHCA that include TH are needed.The Cool It protocol has established TH as the standard of care for OHCA across a regional network of hospitals transferring patients to a central TH-capable hospital. Between February 2006 and August 2009, 140 OHCA patients who remained unresponsive after return of spontaneous circulation were cooled and rewarmed with the use of an automated, noninvasive cooling device. Three quarters of the patients (n=107) were transferred to the TH-capable hospital from referring network hospitals. Positive neurological outcome was defined as Cerebral Performance Category 1 or 2 at discharge. Patients with non-ventricular fibrillation arrest or cardiogenic shock were included, and patients with concurrent ST-segment elevation myocardial infarction (n=68) received cardiac intervention and cooling simultaneously. Overall survival to hospital discharge was 56%, and 92% of survivors were discharged with a positive neurological outcome. Survival was similar in transferred and nontransferred patients. Non-ventricular fibrillation arrest and presence of cardiogenic shock were associated strongly with mortality, but survivors with these event characteristics had high rates of positive neurological recovery (100% and 89%, respectively). A 20% increase in the risk of death (95% confidence interval, 4% to 39%) was observed for every hour of delay to initiation of cooling.A comprehensive TH protocol can be integrated into a regional ST-segment elevation myocardial infarction network and achieves broad dispersion of this essential therapy for OHCA.
Cardiac Chamber Volumes and their Significance in Rheumatic Heart Disease with Isolated Mitral Stenosis
Authors: LOUIS A. SOLOFF, JACOB ZATUCHNI
Journal: Circulation (1959)

The total capacity of the heart and the volume of each of its chambers were determined by the technic of simultaneous biplane stereoscopic venous angiocardiography in 18 persons with surgically confirmed, isolated severe mitral stenosis. Although cardiac capacity and chamber volumes varied greatly, the left atrium was almost always the largest chamber. The left ventricle was not always the smallest chamber. In fact, it was larger than the right ventricle in 7 of the 18 and was the only chamber to be significantly correlated with total cardiac capacity greater than 1,000 ml. The right ventricular volume was found to be significantly correlated with its systolic pressure, or with the pulmonary artery systolic or mean pressures. Disproportionate enlargement of the right atrium can occur in the absence of tricuspid stenosis. Finally, atrial fibrillation was commonly present in patients with a large total cardiac capacity.
Subperiosteal Hematoma
Authors: GERALD A. MANDELL, H THEODORE HARCKE
Journal: Clinical Nuclear Medicine (1986)

The "doughnut" sign has been described frequently in brain and skeletal scintigraphy, but not previously in a subperiosteal hematoma associated with neurofibromatosis and focal gigantism. The primary cause and evolution of this skeletal "doughnut" sign is discussed; a brief review of other causes of this scintigraphic finding also is given.
Comparing apples and oranges: a randomised prospective study
Authors: J. E Barone
Journal: BMJ (2000)

For many years the comparison of apples and oranges was thought to be impossible.Many authors use the analogy of the putative inability to compare apples and oranges as a means of scornfully reviewing the work of others.The titles of some recent publications 1 2 suggest an actual comparison of apples and oranges, but the authors do not, in fact, compare these two fruits.Our laboratory has been interested in this problem for many years.We attempted numerous pilot studies (unpublished data) but had not accomplished a true comparison until now.At last, successful comparison of apples and oranges has been achieved and is the subject of this report. Methods and resultsWe investigated many different varieties of apples and oranges in pilot studies; for this study, however, red delicious apples were compared with navel oranges.A total of 12 objects (6 apples, 6 oranges) made up the experimental population.Measurements were performed using a standard tape measure (Pseudoscientific Instruments, Lodi, NJ).Weight was recorded to the nearest tenth of a gram using a scale.Sweetness was quantified by the Licker scale (1 = kind of sweet; 2 = sweet; 3 = very sweet; 4 = really very sweet).Statistical calculations were performed using FudgeStat (Hypercrunch Corporation, Sunnyvale, CA) on an Apple Macintosh 8500 computer (Apple Computer Inc, Cupertino, CA).No significance should be inferred from the type of computer used, nor was any bias introduced because of this.Six oranges and five apples survived the experiment.(Before the study was completed, the author's 12 year old son, Thomas, inadvertently consumed one of the objects, an apple.)Non-parametric background comparisons are shown in table 1.A striking and heretofore unappreciated similarity was noted.In only one category, that of "involvement of Johnny Appleseed," was a statistically significant difference between the two fruits found.Subjective findings and objective data are presented in table 2. A significant difference between apples and oranges was identified only in the categories of colour and seeds.
Screening for Diabetic Retinopathy: The wide-angle retinal camera
Authors: Jacqueline A Pugh, James M Jacobson, W A J Van Heuven, John A Watters, Michael R Tuley, David R Lairson, Ronald J Lorimor, Asha S Kapadia, Ramon Velez
Journal: Diabetes Care (1993)

OBJECTIVE— To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS— Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physician's assistant through dilated pupils using direct ophthalmoscopy, a single 45° retinal photograph without pharmacological dilation, and a set of three dilated 45° retinal photographs) were compared with a reference standard of stereoscopic 30° retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS— The subjects (352) had complete exams excluding the exam by the physician's assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physician's assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS— Fundus photographs taken by the 45° camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45° camera.
Book: HIV, Health and your Community: A Guide for Action
Authors: J. Collazos
Journal: BMJ (2000)

Reuben Granich, Jonathan Mermin Stanford University Press, £8.95, pp 256 ISBN 08047 3351 1 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> A striking paradox of our time is that, for many conditions, medical resources are not allocated to the most pressing conditions. One of these conditions is, of course, HIV infection. In addition to the extraordinarily limited resources for diagnosis and treatment of HIV infection and its associated complications in the developing world, there is also a lack of basic information available … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Cooperation between the prison medical service and the NHS: a conversation.
Authors: B Edwards, J Gunn, J Kilgour, R Smith
Journal: BMJ (1985)

A great deal has happened with prison health care since we began publishing our series two years ago. ' Dr John Kilgour had then just taken over as director of the prison medical service, and he has now had a chance to make his presence felt. Twenty six new doctors have been recruited, and the service is almost up to full strength.2 A plan has been launched to increase the number of fully trained nurses. The Chief Inspector of Prisons has published a report on preventing suicide in prisons and been trumped by a more radical one from Scotland.34 The physical state of Holloway Prison's psychiatric wing has been described by the Home Secretary as wholly unsatisfactory, and plans have been made to resite and reorganise it.5 Plans have been produced for improving the service offered by Grendon, the psychiatric prison.6 And, perhaps most important of all, Mrs Ren?e Short's House of Commons Select Committee for Social Services has begun an investigation into the prison medical service: huge amounts of written evidence have been received, and the committee is now visiting prisons and taking oral evidence. All of these developments might be seen as steps forward but might be stymied by the continuing problem of overcrowding. Since our articles were published the number of people has risen by 4000?to 48000. Two years ago the Home Office was predicting that this figure would not be reached until the end of the decade. The 16 new prisons that are being built will help but not solve the problem. To make a further contribution to this continuing debate and throw a little more grist into Mrs Short's mill we organised a small meeting in October to discuss cooperation between the prison medical service and the National Health Service, and the rest of this article is a report on the conversation. Undoubtedly the select committee will discuss the possibilities that the prison medical service might either be absorbed into the NHS or that a special health authority directly responsible to the Department of Health and Social Security might be created to oversee the medical services in all secure institutions (including the special hospitals), but the arguments for and against these schemes have been well rehearsed,1 and we did not want to repeat them. Present at the meeting were: Mr Brian Edwards, the general manager of Trent Regional Health Authority; Professor John Gunn, professor of forensic psychiatry at the Institute of Psychiatry; Dr John Kilgour, director of the prison medical service; and Dr Richard Smith, assistant editor of the BMJ and author of our series on prison health care. The article has been written by Dr Smith and approved by the other three. Aptly and ironically we held our discussions at the Caf? Royal, a regular haunt of Oscar Wilde, a man who did not enjoy his stay in either Pen ton ville or Reading prisons.
PROCOAGULANT TISSUE FACTOR EXPRESSION IS LINKED TO DISTINCT SUBTYPES IN GLIOBLASTOMA AND PLAYS A ROLE IN TUMOR DORMANCY
Authors: J. RAK, N. Magnusa, D. Garniera, B. Meehana, S. McGrawa, T. H. Leea, M. Caronb, G. Bourqueb, C. Milsomc, N. Jabadoa, J. Traslera
Journal: Neuro-Oncology (2014)

BACKGROUND: The coagulation system bridges the immediate (hemostatic) and late (inflammation, angiogenesis) tissue responses to disruption of tissue homeostasis. Tissue factor (TF) is the central regulator of these pathways. Glioblastoma (GBM) is associated with a highly procoagulant phenotype, and in some cases with high levels of TF. Here, we interrogate the link between these features and GBM progression. METHODS: We mined human GBM databases for expression of coagulation factors and performed xenograft experiments with GBM cell lines engineered to express either TF or EGFRvIII oncogene. RESULTS: Expression of coagulation factors (coagulome) is subtype-specific in GBM and TF expression correlates with the classical subtype. Inhibition of TF modulates EGFRvIII-driven growth of GBM xenografts. GBM-related human cells undergo tumor dormancy in a manner influenced by tissue factor (TF) expression. Thus, indolent, TF-deficient subline of human glioma, U373, forms viable, but permanently dormant deposits at the injection site. Expression of TF in these cells leads to a stepwise transition to latent and overt tumor growth phases, and this process that is associated with recruitment of vascular (CD105+) and myeloid (CD11b+ and F4/80+) elements. Importantly, the microenvironment orchestrated by TF expression facilitates permanent secondary changes in the phenotype, gene expression profile, DNA copy number and DNA methylation state of tumor cells that escaped from dormancy. CONCLUSIONS: We postulate that there is a degree of specificity in activation of the coagulation system by GBM subtypes driven by defined oncogenic pathways. Thus, TF is regulated by EGFR-dependent transformation. Conversely, we also suggest that procoagulant events in the tissue microenvironment (niche) may affect the fate of occult tumor cells, including biological and genetic progression to a full blown GBM-like malignancy. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
DNA Methylation Pathway Alterations in an Autochthonous Murine Model of Prostate Cancer
Authors: Shannon R. Morey, Dominic J. Smiraglia, Smitha R. James, Jihnhee Yu, Michael T. Moser, Barbara A. Foster, Adam R. Karpf
Journal: Cancer Research (2006)

Abstract We examined the DNA methylation pathway in an autochthonous murine prostate cancer model, transgenic adenocarcinoma of mouse prostate (TRAMP). We observed that, compared with strain-matched normal prostates, primary and metastatic TRAMP tumors display increased cytosine DNA methyltransferase (Dnmt) activity, Dnmt1 and Dnmt3b protein expression, and Dnmt1, Dnmt3a, and Dnmt3b mRNA expression. Increased expression of Dnmt genes correlates with increased expression of cyclin A and E2F target genes, implicating increased cell proliferation and Rb inactivation in Dnmt overexpression. We analyzed DNA methylation in TRAMP and found that global levels of 5-methyl-2′-deoxycytidine are unaltered, whereas specific tumors display centromeric repeat hypomethylation. To interrogate locus-specific methylation, we did restriction landmark genomic scanning (RLGS) on normal prostates and primary tumors. In primary tumors, 2.3% of ∼1,200 analyzed loci display aberrant DNA hypermethylation, whereas a considerably smaller number of events show hypomethylation. The pattern of RLGS changes was nonrandom, indicating a coordinated methylation defect. Two specific genes identified by RLGS were studied in detail. Surprisingly, methylation of a downstream exon of p16(INK4a) (p16) was the highest frequency hypermethylation event identified in TRAMP, where it is associated with increased p16 mRNA and protein expression. In contrast, hypermethylation of the 5′ CpG island region of the homeobox gene Irx3 in TRAMP is associated with reduced gene expression. In summary, our data reveal a systemic DNA methylation pathway defect in TRAMP reminiscent of human prostate cancer, supporting the use of this model to investigate the functional role of DNA methylation pathway alterations in prostate cancer development. (Cancer Res 2006; 66(24): 11659-67)
AUTOMATIC LIGATURE CARRIER
Authors: O. A. Nelson
Journal: JAMA (1924)

About a year ago, I had made a ligature carrier for the renal pedicle, which some of my friends are using to good advantage in gallbladder operations and other inaccessible places. The instrument, which is in the form of forceps, when loaded with the ligature to be used, can, if necessary, be passed by the sense of touch, the blades straddling the object to be ligated. Now, closing the instrument causes a loop of the ligature material to slip under a blunt hook on the opposite blade, so that when the instrument is opened and removed, a double ligature will be found about the object to be ligated. The instrument is made so as to be free from sharp points or hooks, in order that it may be safely used in a wound near blood vessels or other important structures. The blades are curved inward so as to be able