tbuckley/cabot-search huggingface dataset:
Increased Proteolysis, Myosin Depletion, and Atrophic AKT-FOXO Signaling in Human Diaphragm Disuse
Authors: Sanford Levine, Chhanda Biswas, Jamil Dierov, Robert Barsotti, Joseph B. Shrager, Taitan Nguyen, Seema Sonnad, John C. Kucharchzuk, Larry R. Kaiser, Sunil Singhal, Murat T. Budak
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Patients on mechanical ventilation who exhibit diaphragm inactivity for a prolonged time (case subjects) develop decreases in diaphragm force-generating capacity accompanied by diaphragm myofiber atrophy.Objectives: Our objectives were to test the hypotheses that increased proteolysis by the ubiquitin-proteasome pathway, decreases in myosin heavy chain (MyHC) levels, and atrophic AKT-FOXO signaling play major roles in eliciting these pathological changes associated with diaphragm disuse.Methods: Biopsy specimens were obtained from the costal diaphragms of 18 case subjects before harvest (cases) and compared with intraoperative specimens from the diaphragms of 11 patients undergoing surgery for benign lesions or localized lung cancer (control subjects). Case subjects had diaphragm inactivity and underwent mechanical ventilation for 18 to 72 hours, whereas this state in controls was limited to 2 to 4 hours.Measurements and Main Results: With respect to proteolysis in cytoplasm fractions, case diaphragms exhibited greater levels of ubiquitinated-protein conjugates, increased activity of the 26S proteasome, and decreased levels of MyHCs and α-actin. With respect to atrophic signaling in nuclear fractions, case diaphragms exhibited decreases in phosphorylated AKT, phosphorylated FOXO1, increased binding to consensus DNA sequence for Atrogin-1 and MuRF-1, and increased supershift of DNA-FOXO1 complexes with specific antibodies against FOXO1, as well as increased Atrogin-1 and MuRF-1 transcripts in whole myofiber lysates.Conclusions: Our findings suggest that increased activity of the ubiquitin-proteasome pathway, marked decreases in MyHCs, and atrophic AKT-FOXO signaling play important roles in eliciting the myofiber atrophy and decreases in diaphragm force generation associated with prolonged human diaphragm disuse.
Biochemical Studies on the Regulation of Myocardial Contractility
Authors: Howard L. Bleich, Emily S. Boro, Eugene Morkin, Paul J. LaRaia
Journal: New England Journal of Medicine (1974)

NEW information regarding the chemical basis for adjustments in cardiac performance has recently come to light. Short-term augmentation of contractility may be mediated by cyclic AMP through a mechanism that involves membrane phosphorylation. In addition, studies of biochemical changes that occur in cardiac hypertrophy indicate that contractile proteins are rapidly replaced in response to work overload. It has also been suggested that an abnormal myosin species underlies the defective performance of hypertrophied and failing hearts; no structural abnormality in myosin or other contractile proteins has been identified, however. Before the evidence of multiple biochemical defects in these hearts is discussed, . . .
Asbestos-Related Diseases-Reply
Authors: David W. Cugell
Journal: JAMA (1985)

<h3>In Reply—</h3> The specific issues posed by members of the Diagnostic Criteria Committee of the American Public Health Association Occupational Health Section focus on several current controversies concerned with the asbestos-associated diseases. At the outset, we emphasize that our report was prepared for physicians addressing the problems of individual patients. Thus, we did not consider broad public health issues in detail. The finding of a characteristic x-ray picture, even when accompanied by rales and associated with functional evidence of restrictive lung disease, does not permit a definitive clinical diagnosis of asbestosis. Asbestosis occurs after prolonged exposure to high concentrations of dust in the ambient air. Rarely is there sufficient information available to the physician to permit an assessment of the duration and severity of exposure to asbestos. Thus, the physician usually must depend on the patient for such information. All too often, a history of workplace exposure is based
FIRST AID TO THE INJUREDITS IMPORTANCE TO RAILROADS FROM A HUMANE AND ECONOMIC STANDPOINT.
Authors: MARCUS H. THOMAS
Journal: JAMA (1906)

<h3>THE RAILWAY ACCIDENT.</h3> The instruction of railway employés in first aid to the injured is just in the advent of its practical employment. It is at this time a matter of comment with the secular press and the public that, in spite of modern inventions and appliances, the railway accident is apparently inevitable and, paradoxical as it may seem, is on the increase. The block signal system, the patent coupler, the airbrake were all heralded as life-saving devices that would practically eliminate the danger to the employé and the passenger, and while unquestionably much has been accomplished by these inventions toward minimizing the casualty list of the modern railroad, yet other influences have counteracted their good results, and the fact remains that the railroads daily maim and kill a much larger per cent. of employés and traveling public than they should for their own moral and economic welfare. In time
THE ROENTGEN RAY IN INTRATHORACIC GOITER AND THYMUS HYPERPLASIA
Authors: ANDRE CROTTI
Journal: JAMA (1913)

By an intrathoracic goiter, we understand a goiter that lies within the thorax. It may be totally intrathoracic, or partially so. Theoretically we should call partially intrathoracic any goiter extending below the superior opening of the thorax and lying more or less deeply in the mediastinal space. According to this a goiter whose inferior limits lie behind the incisura lowing would be called an "intrathoracic goiter." Following Kocher, however, we do not call such cases "partially intrathoracic," but "struma profunda" or "deep goiter," and reserve the term of "partially intrathoracic goiter" for goiters whose greater part lies in the mediastinal space, or to goiters with an intrathoracic prolongation large enough to cause symptoms. These intrathoracic goiters originate in the lower pole of one lobe or in the isthmus, or in an accessory thyroid gland. In the majority of cases, however, the intrathroacic goiter is developed in a preexisting goiter, localized in the isthmus or one or both lobes of the thyroid gland, which has gradually become intrathoracic.
A multi-center study of high dose Aldesleukin (Proleukin® (HD IL-2) + Vemurafenib Zelboraf® ) therapy in patients with BRAFV600 mutation positive metastatic melanoma (proclivity 01)
Authors: Joseph Clark, Lawrence Flaherty, Marc Ernstoff, Henry Koon, Mohammed Milhem, Gerald Militello, Sanjiv Agarwala, Brendan Curti, Lee Cranmer, Christopher D Lao, Theodore F Logan, Jose Lutzky, Venkatesh Rudrapatna, Gregory Daniels, Bret Taback, Sandra Aung, James Lowder, David Lawson
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts To investigate whether the Vemurafenib-induced increased tumor antigen expression, T lymphocyte infiltration and tumor debulking improve the complete response rate induced by HD IL-2 in metastatic melanoma and if there is synergistic toxicity using the drugs in close approximation
Literature and Medicine, vol 9, Fictive Ills: Literary Perspectives on Wounds and Diseases
Authors: Richard E. Peschel
Journal: JAMA (1991)

On many levels, this volume is a successful experiment. The book's format is unique, with eight pairs of scientists and humanists commenting on various literary works about diseases or wounds. Each of the eight sections has two essays (one by a medical professional, the other by a humanist), discussing works of Sophocles, John Donne, George Eliot, Charles Dickens, Henry James, Anton Chekhov, Leo Tolstoy, Tillie Olsen, Charlotte Perkins Gilman, and Evelyn Waugh. Several sections are striking. Section VII, with essays by Julia Connelly, a practicing internist, and Joanne Trautmann Banks, an adjunct professor of literature, reflects on Tolstoy's<i>The Death of Ivan Ilych</i>and Olsen's "Tell Me a Riddle." Connelly reveals the physician's practical perspective as she tries to relate Tolstoy's protagonist and Olsen's Eva to patients she has treated: "As I consider... [them], I recall two patients who asked me for help during their lives and for whom I
SURFACE ANTIGENS OF IMMUNOCOMPETENT CELLS
Authors: T. Takahashi, E. A. Carswell, G. J. Thorbecke
Journal: The Journal of Experimental Medicine (1970)

Spleen cell transfer studies were done in BALB/c strain mice in an attempt to define the role of theta-antigen-bearing lymphoid cells in immune responses to SE. Incubation with alloantiserum to theta-C3H and rabbit C' virtually completely abolished the ability of the cells to transfer both primary and secondary (IgM and IgG) responses to 650 R irradiated recipients. Normal thymus cells partially reconstituted the ability of such treated cells to transfer the primary but not the secondary response. The results are interpreted as showing immunological memory for SE in the theta-bearing thymus-derived cells. Incubation of the spleen cells with alloantiserum to the PC.1 antigen present on antibody-forming cells did not significantly affect the ability to transfer either primary or secondary response.
[354] THE SELECTIVE INHIBITION OF THE NA+/H+ EXCHANGER BY CARIPORIDE INCREASES THE ANTINEOPLASTIC EFFECT OF GEMCITABINE IN HUMAN CHOLANGIOCARCINOMA CELLS THROUGH MODULATION OF PHARMACORESISTANCE
Authors: A. Di Sario, A. Omenetti, C. Candelaresi, E. Bendia, S. Cascinu, H.W. Kleemann, G. Fava, A. Benedetti
Journal: Journal of Hepatology (2007)
Event-free hospitalization after early and sustained patency using combination thrombolytic therapy in acute myocardial infarction
Authors: E.Magnus Ohman, Barry S. George, Dean J. Kereiakes, Joseph K Samaha, Eric J. Topol, Eric D. Berrios, Kristina N. Sigmon, Robert M. Califf
Journal: Journal of the American College of Cardiology (1991)
Yankee Surgeon: The Life and Times of Usher Parsons (1788-1868)
Authors: Claude E. Welch
Journal: JAMA (1989)

Usher Parsons, the subject of this biography, lived from 1788 to 1868, years in which medicine and surgery had begun the slow transformation from empirical crafts to professions based on science. To recognize the era before the transition, the reader need read only one of the verbose consultation opinions quoted in this volume or consider the routine use of clysters, puking, and bloodletting as standard methods of therapy in the early days of Usher's career. Usher became the outstanding member of the surgical profession in the early days of the state of Rhode Island. His fame as a physician and historian also spread to neighboring states. Because no definitive biography had been written about him, Dr Goldowsky was given an excellent opportunity to combine a detailed survey of Usher's life with a description of medical care as it existed at that time. The author has allowed contemporary events and records
Robot helps perform open heart surgery
Authors: A. Dorozynski
Journal: BMJ (1998)

A team of French surgeons has performed six open heart operations by remote control using a computer linked robot.

The new technique allows surgical treatment of coronary or valvar defects with much smaller incisions than needed for standard interventions, and it is much less traumatic and less painful for the patient than standard methods.

The surgical robots and a miniaturised camera are introduced into the heart or coronary vessels through a small thoracic opening. Surgeons have an enlarged view of …
Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura and disseminated intravascular coagulation
Authors: Hideo Wada, Michiaki Ohiwa, Toshihiro Kaneko, Shigehisa Tamaki, Motoaki Tanigawa, Shigeru Shirakawa, Masato Koyama, Tatsuya Hayashi, Koji Suzuki
Journal: American Journal of Hematology (1992)

Plasma thrombomodulin (TM) levels were significantly elevated at disease onset in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC), but was not in those with essential thrombocythemia and idiopathic thrombocytopenic purpura. However, in patients with TTP and DIC, TM levels decreased significantly after they achieved complete remission. In both TTP and DIC patients, plasma TM levels at onset in those with poor prognosis were higher than that in those with good prognosis. Among DIC patients, the plasma TM level was higher in those with organ failure than in those without, but there were no differences among patients with various underlying diseases associated with DIC. It is speculated that the plasma TM level reflects damage to vascular endothelial cells or organ failure and that it is useful in assessing prognosis for patients with DIC and TTP.
THE DUODENOGRAM: A NEW METHOD OF VISUALIZING THE ENTIRE DUODENAL CONTOUR
Authors: Jacob Buckstein
Journal: JAMA (1925)

Figure 1 represents an intestinal tube in situ, the end having reached just beyond the duodenojejunal junction. The distal 8 inches of this tube have been perforated by numerous small openings. A suspension of barium is injected through the proximal end. When this suspension reaches the distal end, it escapes through all of the numerous perforations at practically the same time, and fills the entire duodenum in an unobstructed, isolated and homogeneous manner (Fig. 2). This simple method obviates the necessity of employing any special apparatus or of producing unphysiologic distal obstruction, in filling the duodenal curve. The method is of value for a roentgen-ray study of the normal duodenal curve and of pathologic variations (Figs. 3 and 4).<sup>1</sup>
B cell receptor repertoire analysis in clinically involved and uninvolved skin of systemic sclerosis patients treated with CD20 depletion therapy: baseline and follow-up
Authors: S. Alivernini, P. L. Klarenbeek, S. L. Bosello, M. E. Doorenspleet, B. D. van Schaik, R. E. Esveldt, A. H. van Kampen, F. Baas, P. P. Tak, G. Ferraccioli, N. de Vries
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> B cells may play an important role in the pathogenesis of systemic sclerosis (SSc), as suggested by reports in the effectiveness of rituximab (RTX). To find support for a role of clonal B cell activation in SSc we studied the presence of clonal B cell expansions in the involved skin using newly developed next generation sequencing protocols, which provide quantitative data on up to 1 000 000 clones in one run. <h3>Objective</h3> investigate whether expanded B cell clones are present in involved and uninvolved skin of SSc patients, and how they are influenced by RTX therapy. <h3>Methods</h3> mRNA was isolated from involved and uninvolved skin samples of 3 SSc patients (with active diffuse disease) taken before and after 12 months after RTX-therapy. A linear amplification with multiplex primers for all V(ariable)-families of the heavy-chain (BCR) was performed. The amplified products contain the CDR3 of the BCRs of all cells which can be used as 'clonal fingerprint' for each cell. The samples were analysed using a Genome Sequencer FLX (454). The frequency of each clone was determined by its CDR3 frequency (% of all CDR3s analysed). Clones with a frequency of &gt;1% were arbitrarily considered as highly expanded clones (HECs). <h3>Results</h3> Both involved and uninvolved skin showed similar amounts of HECs at baseline (14.3±4.2 vs 15.0±0.0 respectively; p = 0.9). However, at baseline BCR repertoires found in involved skin were clearly different from those in uninvolved skin; BCR clonal sequences were not shared between both compartments. Strikingly, RTX treatment led to a non-significant decrease of the number of HECs only in the involved skin (14.3±4.2 vs 9.0±4.2; p = 0.22) before and after RTX respectively). The uninvolved skin did not show a decrease in HECs at all. Comparing the HECs in the involved skin before and after RTX, hardly any overlap could be detected between both time points. Similar results were found in the uninvolved skin samples. <h3>Conclusions</h3> This high-resolution technique provides the first detailed characterisation of the BCR repertoire in SSc. The number of highly expanded clones (HECs) was not different when comparing involved versus uninvolved skin. This suggests that here is no BCR driven clonal expansion in involved skin. RTX treatment had a marginal effect on number of B cell HECs in involved skin, but no effect on the number of HECs in uninvolved skin.
Effects of vitamin D supplementation on the calcium–phosphate balance in renal transplant patients
Authors: Marie Courbebaisse, Eric Thervet, Jean Claude Souberbielle, Julien Zuber, Dominique Eladari, Frank Martinez, Marie-France Mamzer-Bruneel, Pablo Urena, Christophe Legendre, Gerard Friedlander, Dominique Prié
Journal: Kidney International (2008)
Herpes simplex encephalitis treated with intravenous idoxuridine.
Authors: A. D. Evans, O. P. Gray, M. H. Miller, E. R. Jones, R. D. Weeks, C. E. Wells
Journal: BMJ (1967)

Death from Neuroblastoma-Lee MEDITALJOIUHNA 407 find any example among cycles of this type that could provide a starting-point for an explanation of the observations on acute leukaemia and neuroblastoma.As well as these imposed responses, there are seasonal cycles in a number of physiological factors which are controlled by biological clocks within man himself.Seasonal cycles in the degree of platelet stickiness, the level of antidiuretic hormone, the excretion of the metabolic products of steroid hormones, etc. (Tromp, 1963), are likely to be the result of internal cycles whose only reference to the environment is for synchronization.It is unknown whether these cycles affect disease, but they are large enough and occur in substances that are known to affect the progress of neoplastic disease.It is in such physiological cycles that the explanation of the observed changes in neuro- blastoma seems likely to be found. SummaryDeaths from neuroblastoma are more common in the summer months in England and Wales than in the winter.The summer excess in mortality for all patients is 32 % ; it is found in males and females, and in children and adults.The seasonal pattern may be due to a physiological mechanism which influences the activity of certain forms of neoplastic disease.ADDENDUM.-Since this paper was written two series of patients with neuroblastoma have been analysed where the date of diagnosis was recorded.At the Children's Orthopaedic Hospital and Medical Centre, Seattle (72 cases), there were 5.7% more diagnoses in the months April-September than in October-March.At the Los Angeles Children's Hospital (111 cases) there were 13.4% more diagnoses in the months April-September than in October-March.
The association between beta-blockers and melanoma survival: evidence of absence or absence of evidence?
Authors: L.M. Hollestein, T. Nijsten
Journal: British Journal of Dermatology (2014)

Journal Article The association between beta‐blockers and melanoma survival: evidence of absence or absence of evidence? Get access L.M. Hollestein, L.M. Hollestein Department of Dermatology Erasmus MC University Medical Center P.O. Box 2040 Rotterdam 3000 CA the Netherlands Search for other works by this author on: Oxford Academic Google Scholar T. Nijsten T. Nijsten Department of Dermatology Erasmus MC University Medical Center P.O. Box 2040 Rotterdam 3000 CA the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 4, 1 April 2014, Pages 764–765, https://doi.org/10.1111/bjd.12955 Published: 01 April 2014
Emergency arteriography in acute gastrointestinal bleeding.
Authors: J D Irving, T C Northfield
Journal: BMJ (1976)

Emergency arteriography was carried out on 35 patients with acute gastrointestinal bleeding, in 31 of them within two hours of active bleeding (a haematemisis; a diagnostic change in central venous pressure, pulse rate, or blood pressure; or gastric aspiration of fresh blood). A definite site of bleeding was identified in 27 patients (77%)-this being a small-intestinal vascular abnormality in three--and a probable site in three. Confirmation of the bleeding site was obtained in 20 out of 23 patients treated surgically. An intra-arterial vasoconstrictor infusion was given as a temporary measure before surgery in seven patients, only one of whom showed active bleeding at operation. An intra-arterial vasoconstrictor infusion was tried as definitive treatment in an additional 10 patients, but in four out of seven with a chronic ulcer bleeding recurred after 5-68 hours and was therefore treated surgically. We recommend the diagnostic use of arteriography in patients with reliable evidence of active bleeding if its site cannot be determined by endoscopy. We do not recommend its therapeutic use in those with a chronic ulcer, except to facilitate resuscitation before surgery; further studies are needed to define its role in those with an acute lesion.
Inhibition of the TGF-β receptor I kinase promotes hematopoiesis in MDS
Authors: Li Zhou, Aaron N. Nguyen, Davendra Sohal, Jing Ying Ma, Perry Pahanish, Krishna Gundabolu, Josh Hayman, Adam Chubak, Yongkai Mo, Tushar D. Bhagat, Bhaskar Das, Ann M. Kapoun, Tony A. Navas, Simrit Parmar, Suman Kambhampati, Andrea Pellagatti, Ira Braunchweig, Ying Zhang, Amittha Wickrema, Satyanarayana Medicherla, Jacqueline Boultwood, Leonidas C. Platanias, Linda S. Higgins, Alan F. List, Markus Bitzer, Amit Verma
Journal: Blood (2008)
Comparison of the phenacetin and aminopyrine breath tests: Effect of liver disease, inducers and cobaltous chloride
Authors: Dale A. Schoeller, Alvin N. Kotake, George H. Lambert, Patricia S. Krager, Alfred L. Baker
Journal: Hepatology (1985)

The phenacetin breath test (PBT) has been proposed as an alternative to the aminopyrine breath test (ABT) for the assessment of hepatic function. To investigate the clinical utility of the PBT, we compared the PBT with the ABT in 9 healthy subjects and 18 patients with biopsy–proven liver disease. We also investigated the effects of cytochrome P–450 inducers in humans and rats, and the effect of cobaltous chloride (CoCl 2 ) in rats on the PBT to elucidate the relationship between the rate of phenacetin deethylation and exhaled labeled CO 2 derived from phenacetin. In humans with abnormal ABTs, the PBT correlated with the ABT (r = 0.77), but in healthy humans there was no correlation between the two breath tests. Rifampin pretreatment in healthy humans induced the ABT by 27%, but did not induce the PBT. In rats the PBT was not induced by 3–methylcholanthrene pretreatment at phenacetin doses of 1 mg per kg, but was induced by both 3–methylcholanthrene (178%) and phenobarbital (142%) at 10 mg per kg phenacetin. Pretreatment of rats with CoCl 2 , which reduces cytochrome P–450 content, decreased the PBT by 40% and the ABT by 84%. The insensitivity of the PBT to induction except at high doses of phenacetin suggests that phenacetin deethylation is not the rate–limiting process modulating exhaled labeled CO 2 in healthy subjects, and that the PBT does not generally reflect normal or induced phenacetin dealkylation rates. The PBT, however, did reflect hepatic damage and may even be better than the ABT for grading the severity of hepatic damage.