tbuckley/cabot-search huggingface dataset:
Relationship between obesity and maximal insulin-stimulated glucose uptake in vivo and in vitro in Pima Indians.
Authors: C Bogardus, S Lillioja, D Mott, G R Reaven, A Kashiwagi, J E Foley
Journal: Journal of Clinical Investigation (1984)

Previous studies have left unanswered whether human obesity, independent of glucose intolerance, is associated with a "postreceptor" defect in insulin action. We have studied the relationship between the degree of obesity (as estimated by underwater weighing) and the maximal insulin-stimulated glucose disposal rate (M) in vivo in 52 glucose-tolerant Pima Indian males. The relationship was examined independently of differences in age and maximal oxygen uptake (an estimate of "physical fitness"). The maximal insulin-stimulated glucose transport rate (MTR) was also measured in isolated abdominal adipocytes from the same subjects to determine whether differences in M could be explained by differences in glucose transport. The results showed that there was a large variance in M and MTR among these glucose-tolerant subjects. M was better correlated with glucose storage rates than with oxidation rates, as estimated by indirect calorimetry. The most obese subjects had only a 20% lower mean M and 30% lower MTR than the most lean subjects. The lower M in the obese subjects was due to both lower glucose oxidation and storage rates. There was no significant, independent correlation between age or degree of obesity and M or MTR. The maximal oxygen uptake (VO2 max) appeared to independently account for 20% of the variance observed in M. MTR was only weakly correlated with M (r = 0.36, P less than 0.02). We concluded that differences in M in these glucose-tolerant subjects must be explained by factor(s) other than maximal oxygen uptake, age, maximal insulin-stimulated glucose transport in vitro, or degree of adiposity per se.
Distinct MicroRNA Alterations Characterize High- and Low-Grade Bladder Cancer
Authors: James W.F. Catto, Saiful Miah, Helen C. Owen, Helen Bryant, Katie Myers, Ewa Dudziec, Stéphane Larré, Marta Milo, Ishtiaq Rehman, Derek J. Rosario, Erica Di Martino, Margaret A. Knowles, Mark Meuth, Adrian L. Harris, Freddie C. Hamdy
Journal: Cancer Research (2009)

Urothelial carcinoma of the bladder (UCC) is a common disease that arises by at least two different molecular pathways. The biology of UCC is incompletely understood, making the management of this disease difficult. Recent evidence implicates a regulatory role for microRNA in cancer. We hypothesized that altered microRNA expression contributes to UCC carcinogenesis. To test this hypothesis, we examined the expression of 322 microRNAs and their processing machinery in 78 normal and malignant urothelial samples using real-time rtPCR. Genes targeted by differentially expressed microRNA were investigated using real-time quantification and microRNA knockdown. We also examined the role of aberrant DNA hypermethylation in microRNA downregulation. We found that altered microRNA expression is common in UCC and occurs early in tumorogenesis. In normal urothelium from patients with UCC, 11% of microRNAs had altered expression when compared with disease-free controls. This was associated with upregulation of Dicer, Drosha, and Exportin 5. In UCC, microRNA alterations occur in a tumor phenotype-specific manner and can predict disease progression. High-grade UCC were characterized by microRNA upregulation, including microRNA-21 that suppresses p53 function. In low-grade UCC, there was downregulation of many microRNA molecules. In particular, loss of microRNAs-99a/100 leads to upregulation of FGFR3 before its mutation. Promoter hypermethylation is partly responsible for microRNA downregulation. In conclusion, distinct microRNA alterations characterize UCC and target genes in a pathway-specific manner. These data reveal new insights into the disease biology and have implications regarding tumor diagnosis, prognosis and therapy.
Therapeutic receptor targets of ischemic preconditioning
Authors: Ryan M Fryer, John A Auchampach, Garrett J Gross
Journal: Cardiovascular Research (2002)

This review focuses on target receptors that have been shown to have the potential to mimic the cardioprotective effect of ischemic preconditioning (IPC). There is an abundance of information concerning the intracellular mechanisms and membrane-bound receptors responsible for IPC. Important intracellular mediators of this cardioprotection likely reside in the activation of multiple kinase cascades. The major players in IPC are thought to include protein kinase C, tyrosine kinases, and members of the mitogen-activated protein kinase signaling family and these topics will be covered in more detail in other papers of this focused issue. However, many of these kinase-mediated mechanisms are triggered by the activation of transmembrane spanning receptors, some of which may be manipulated therapeutically to induce cardioprotection in humans with unstable angina or who are at risk for myocardial infarction. In this review, we will discuss the evidence supporting the possibility of manipulating several of these G protein-coupled receptors as potential therapeutic targets. Stimulation of numerous receptors has been targeted as possible triggers for IPC. Some of those that have been identified include A(1) adenosine, alpha(1) adrenergic, M(2) muscarinic, B(2) bradykinin, delta(1) opioid, AT(1) angiotensin, and endothelin-1 receptors. In general, these receptors are thought to couple to inhibitory G proteins. In this review, we will focus on the most likely therapeutic candidates for cardioprotection, namely adenosine, opioid, and bradykinin receptors since selective agonists and antagonists, either alone or in combination, have most often been shown to mimic or block IPC in numerous animal models and man, respectively. This is not meant to completely rule out other receptors since it is clear that IPC is a phenomenon with multiple pathways that appear to be responsible for the cardioprotection observed.
Voluntary Control of Drug Promotion in Sweden
Authors: Einar Perman
Journal: New England Journal of Medicine (1990)

Ethical aspects of the interaction between doctors and the pharmaceutical industry are often discussed in the Journal,1 2 3 and the suggestion was recently made that a commission be established to develop guidelines for ethical behavior.2 Sweden has had a voluntary commission of this type for more than 20 years. The commission sets guidelines for the marketing activities of pharmaceutical companies and monitors their adherence to these guidelines.The initiative came from the pharmaceutical industry itself. Almost all pharmaceutical companies in Sweden are members of either the Association of the Swedish Pharmaceutical Industry or the Association of Representatives of Foreign Pharmaceutical . . .
Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis.
Authors: A Haimovitz-Friedman, C C Kan, D Ehleiter, R S Persaud, M McLoughlin, Z Fuks, R N Kolesnick
Journal: The Journal of Experimental Medicine (1994)

Recent investigations provided evidence that the sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor alpha (TNF-alpha) in several hematopoietic and nonhematopoietic cells. In this pathway, TNF-receptor interaction initiates sphingomyelin hydrolysis to ceramide by a sphingomyelinase. Ceramide acts as a second messenger stimulating a ceramide-activated serine/threonine protein kinase. The present studies show that ionizing radiation, like TNF, induces rapid sphingomyelin hydrolysis to ceramide and apoptosis in bovine aortic endothelial cells. Elevation of ceramide with exogenous ceramide analogues was sufficient for induction of apoptosis. Protein kinase C activation blocked both radiation-induced sphingomyelin hydrolysis and apoptosis, and apoptosis was restored by ceramide analogues added exogenously. Ionizing radiation acted directly on membrane preparations devoid of nuclei, stimulating sphingomyelin hydrolysis enzymatically through a neutral sphingomyelinase. These studies provide the first conclusive evidence that apoptotic signaling can be generated by interaction of ionizing radiation with cellular membranes and suggest an alternative to the hypothesis that direct DNA damage mediates radiation-induced cell kill.
Transportation and Public Health
Authors: Todd Litman
Journal: Annual Review of Public Health (2013)

This article investigates various ways that transportation policy and planning decisions affect public health and better ways to incorporate public health objectives into transport planning. Conventional planning tends to consider some public health impacts, such as crash risk and pollution emissions measured per vehicle-kilometer, but generally ignores health problems resulting from less active transport (reduced walking and cycling activity) and the additional crashes and pollution caused by increased vehicle mileage. As a result, transport agencies tend to undervalue strategies that increase transport system diversity and reduce vehicle travel. This article identifies various win-win strategies that can help improve public health and other planning objectives.
Large Trials vs Meta-analysis of Smaller Trials-Reply
Authors: John P. A. Ioannidis
Journal: JAMA (1997)

In Reply.  —Dr Klebanoff and colleagues bring into focus the controversy of fixed vs random effects models of combining data. 1 We think it was fair and reasonable for us to report both effects and to point out that, when diversity is present, a random effects model is probably more appropriate. It is puzzling why these authors attribute to us an a priori belief that large trials usually support the results of meta-analyses of small trials.  Their second concern is imprecise. We reported that a higher event rate was associated with a greater benefit of treatment in 4 cases (not 5 cases), but with a smaller benefit in 1 case. Klebanoff et al seem to believe that de facto all treatments should work the same for all patients regardless of the underlying risk of the disease. We do not share this notion and believe that most clinicians would not either. 2,3 More
Isohemagglutinins in Pooled Plasma
Authors: K. B. McCall
Journal: JAMA (1967)

To the Editor:—  The Journal( 198 :323, 1966) published Erythrocyte Sensitization and Anemia Due to Isoantibodies in Lyophilized Pooled Plasma by Oberman, Barnes, and Ginther.  The high titers (both saline and immune) of isohemagglutinins reported by Oberman et al for the lyophilized pooled plasma are indeed surprising, particularly in view of the classical and accepted data 1-3 which have demonstrated that if pools are prepared of a sufficient number of serums or plasmas selected indiscriminately, one can be certain that the isohemagglutinin titers of these pools will be extremely low (not over 1:28). In fact, this is considered to be the basis for the requirement, established by the Division of Biologics Standards, National Institutes of Health, that the plasma pool shall contain plasma from not less than eight donors. The technical specifications of the American Association of Blood Banks 4 further state,  The distribution of the blood groups in each
Hypercalcemia With Seizures --A Clinical Paradox
Authors: D. E. Bauermeister, E. R. Jennings, D. R. Cruse, V. D. Sedgwick
Journal: JAMA (1967)

ALTHOUGH elevation of the serum calcium level is associated with a variety of conditions, the most pronounced alterations occur in hyperparathyroidism. This disease process is characterized by anorexia, nausea, vomiting, thirst, and polyuria, with associated muscular weakness, confusion, and drowsiness which may progress to lethargy and coma. The symptoms are attributed directly to "calcium intoxication," and the syndrome constitutes medical and surgical emergency since it represents the only potentially lethal hypercalcemic state than can be cured.<sup>1</sup>This report describes a case in which the correct clinical diagnosis was clouded by the occurrence of convulsions with hypercalcemic coma. Since seizures have never been included in the symptom complex of hyperparathyroidism, this paper reports a case in which hypercalcemia indirectly resulted in central nervous system hyperactivity and relates these symptoms to the underlying disease. <h3>Report of a Case</h3> A 56-year-old white man was admitted to Memorial Hospital of Long Beach Calif
Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation
Authors: Rieneke van de Ven, Mari F. C. M. van den Hout, Jelle J. Lindenberg, Berbel J. R. Sluijter, Paul A. M. van Leeuwen, Sinéad M. Lougheed, Sybren Meijer, M. Petrousjka van den Tol, Rik J. Scheper, Tanja D. de Gruijl
Journal: Blood (2011)
Frequency of Sensitization to Egg and Cow's Milk in Children with Atopic Dermatitis and Associated Factors
Authors: N.P.M. Rubini, F.L.B. Limongi, B.O. Figueiredo, N.A. Costa, N.S. Santos, N.M. Almeida, F.S. Sion, C. Morais-de-Sa
Journal: Journal of Allergy and Clinical Immunology (2012)
EMERGENCY MEDICAL SERVICE CALL WITH ACUTE MYOCARDIAL INFARCTION IN TOKYO METROPOLITAN AREA
Authors: Masao Yamasaki, Atsushi Takagi, Katsumi Miyauchi, Hiroyuki Tanaka, Masatomo Yoshikawa, Hideki Miyachi, Jun Yamashita, Takeshi Yamamoto, Ken Nagao, Morimasa Takayama
Journal: Journal of the American College of Cardiology (2014)
1108. High Rate of Anti-Tumor Immune Responses in a Phase 1 Clinical Trial of Adenoviral-Interferon-Beta Gene Transfer for Malignant Mesothelioma (MM) and Malignant Pleural Effusions (MPE)
Authors: Steven M. Albelda, Andrew Haas, Collin Gillespie, Andriana Recio, Jing Sun, Veena Kapoor, Jennifer Brown, Parr Michael, Mitchell Ho, Ira Pastan, Robert H. Vonderheide, Richard Carroll, Carl June, Larry R. Kaiser, Daniel H. Sterman
Journal: Molecular Therapy (2006)

Our group recently completed a Phase 1 trial of intrapleural interferon-beta gene transfer of Ad.huIFNbeta (Biogen-IDEC) in 10 patients with MM and MPE. Vector doses of 9x1011 and 3x1012 viral particles were used. Here, we report the anti-tumor immunologic responses observed. The presence of a catheter within the pleural space allowed us to monitor the response to Ad gene transfer in 7 patients who had pleural effusions. Interestingly, the presence of the vector did not elicit a marked cellular infiltrate in the pleural space. The average fold-increase in total leukocytes (comparing pre-instillation to the peak count in the next four days) was 3.3 fold. Detectable levels of INFbeta (from 200 pg/ml to 160 ng/ml) were found in all but two patients. Intrapleural levels of cytokines (IL-6, IL-1, IL-10, VEGF, MCP-1, IL-8, RANTES, and IFNgamma) were highly variable at baseline and after response to gene transfer. Some patients had dramatic increases in IL-6 levels after gene transfer, while others did not. The only other cytokine to show an increase in multiple patients was the chemokine RANTES. Levels of serum cytokines were also monitored. Only 4 patients showed low levels of serum levels of IL-6. Low levels of IL-8 and MCP-1 were also detected in serum after gene transfer. Humoral responses to the mesothelioma tumor antigens SV40 Virus Large T-antigen (SV40-Tag) and mesothelin were evaluated by using sera from before and after gene transfer to immunoblot purified proteins. One patient had a strong increase in antibody response to SV40-Tag after gene transfer. We also evaluated anti-mesothelin antibody reactivity using an ELISA assay. Four patients had significant baseline levels of anti-mesothelin antibodies. Two patients had a marked increase in levels after therapy. Additionally, we analyzed serum to identify new or increased intensity bands on extracts of mesothelioma, lung cancer, or ovarian cancer cell lines. The sera from six of eight patients examined recognized new antigens in the post-treatment samples. Utilizing stimulated PBMCs from the patient as effectors, chromium release assays showed cytotoxic effects against an HLA- matched in vitro tumor cell line in one patient of six tested. Tetramer analysis was performed in the two HLA-A2+ patients, with one showing staining with survivin and SV40-Tag tetramers. In summary, injection of one intrapleural dose of Ad.IFNbeta induced clear evidence of humoral and/or cellular anti-tumor immune responses in 8 of the 10 patients studied. Of particular interest were antibody responses against SV40-Tag and mesothelin. Future studies will determine if these anti-tumor immune reactions correlate to clinical responses.
THE TECHNIC OF GASTRO-ENTEROSTOMY
Authors: WILLARD BARTLETT
Journal: JAMA (1913)

For years I have performed gastro-enterostomies in a manner that permits the position and direction of the incision in both stomach and bowel to be accurately located. I have felt that this is not always accomplished, as the operation is ordinarily performed, because a relatively large amount of each viscus is drawn up between the jaws of the Moynihan clamp before the sutures are placed. In performing a gastro-enterostomy, there is an anatomic status which should be obtained—a status which William J. Mayo considers most satisfactory—namely, the establishment of an opening starting about the middle of the posterior wall of the stomach and running obliquely downward and to the left, as shown in Figure 1. After the abdomen has been opened I expose the highest part of the jejunum, without altering its normal direction, as it passes out from under the peritoneum. Two guide sutures are then placed in the
STRANGULATED HERNIA IN CHILDREN.
Authors: W. B. COLEY
Journal: JAMA (1900)

Strangulated hernia in infants and children is by no means so rare as one might be led to suppose from various text-books and monographs on hernia. I have operated on eight patients under the age of 2. years, with one death. The one fatal case was an infant of 8 weeks, and almost moribund at the time of operation. Strangulation had existed for two days. The patient was operated on after midnight, in a poorly-lighted room and under most unfavorable circumstances. The cecum and appendix were present in the sac. The patient rallied after operation, but died two days later. This is the only case in which no attempt at radical cure was made. It was very interesting to note that a considerable portion of my cases were of the cecal variety. In four, or 50 per cent., the sac contained cecum, and in three of these four the appendix
HER2-negative (1+) breast cancer with unfavorable prognostic features: to FISH or not to FISH?
Authors: M. Iorfida, S. Dellapasqua, V. Bagnardi, A. Cardillo, N. Rotmensz, M.G. Mastropasqua, L. Bottiglieri, A. Goldhirsch, G. Viale, M. Colleoni
Journal: Annals of Oncology (2012)
MPL mutation effect on JAK2 46/1 haplotype frequency in JAK2V617F-negative myeloproliferative neoplasms
Authors: M M Patnaik, T L Lasho, C M Finke, N Gangat, D Caramazza, S Siragusa, C A Hanson, A Pardanani, A Tefferi
Journal: Leukemia (2010)
A MEMORABLE OUTPATIENT
Authors: H. Ellis
Journal: BMJ (1995)

If sister says so

My outpatient sister in those days was of the old school. Tall, majestic, and Scottish, she ruled the clinic. All of us feared her. As a result outpatients ran like clockwork. Sister ushered the patients into the cubicles, commanded them to get undressed, and I was then ordered into the appropriate cubicle with my students in strict rotation.

One day, in the usual …
841 EFFICACY AND SAFETY OF 2 YEARS MAINTENANCE THERAPY WITH PEGINTERFERON ALPHA-2A IN CHRONIC HEPATITIS C: RESULTS OF A RANDOMIZED CONTROLLED TRIAL (FIBROSYS)
Authors: J.P. Zarski, N. Sturm, H. Desmorat, P. Melin, J.J. Raabe, C. Bonny, P. Sogni, A. Pinta, S. Rouanet, A. Cheveau, M. Chevallier
Journal: Journal of Hepatology (2008)
Long term survival after intensive care.
Authors: S Ridley, R Jackson, J Findlay, P Wallace
Journal: BMJ (1990)

To examine the long term survival of critically ill patients admitted to an intensive therapy unit and to ascertain the effects of age, severity of illness, and diagnostic category at admission on survival.Retrospective observational study with prospectively gathered data on all patients admitted to the unit between June 1985 and July 1987 and followed up until 1 January 1989.Regional intensive therapy unit.513 critically ill adult patients, 16 of whom were excluded because measurements on severity of illness scoring were not available.Age, severity of illness (determined with the acute physiology and chronic health evaluation (APACHE) II score), and diagnostic category on admission; deaths in the unit; and long term survival after discharge. Details of the survivors were sent to the Registrar General for Scotland, who issued copies of death certificates for the patients who had died between discharge and 1 January 1989.Of 497 patients, 119 (24%) died in the intensive therapy unit and 120 (24%) after discharge, leaving 258 (52%) who were still alive at two years. The median (APACHE II) score was 13 and about half of the patients were aged 55 years or more. A wide range of critical illnesses, except neurosurgical emergencies, were treated. Survival analysis showed that only 41 (34%) of 122 patients with an APACHE II score of greater than or equal to 20 were alive at one year (95% confidence interval 25 to 42) compared with 124 (80%) of 155 patients with a score of less than 10 (73 to 87). Of the 144 patients aged 65 or more, only 68 (47%) survived to one year (39 to 55) but 90 (83%) of the 109 patients aged between 18 and 34 survived a similar period (76 to 71). Mortality was also related to diagnostic category; 71% of trauma victims survived to one year compared with only 41% of those admitted with gastrointestinal pathology. Univariate analysis of the results showed that age, severity of illness, and diagnosis were all predictors of long term survival. Multivariate analysis, however, showed that only age and severity of illness were independent prognostic factors.Long term survival of patients treated in an intensive therapy unit is related to severity of illness and to age. The outcome from critical illness in the elderly population is poor.
Erratum: Corrigendum: Multiple common variants for celiac disease influencing immune gene expression
Authors: Patrick C A Dubois, Gosia Trynka, Lude Franke, Karen A Hunt, Jihane Romanos, Alessandra Curtotti, Alexandra Zhernakova, Graham A R Heap, Róza Ádány, Arpo Aromaa, Maria Teresa Bardella, Leonard H van den Berg, Nicholas A Bockett, Emilio G de la Concha, Bárbara Dema, Rudolf S N Fehrmann, Miguel Fernández-Arquero, Szilvia Fiatal, Elvira Grandone, Peter M Green, Harry J M Groen, Rhian Gwilliam, Roderick H J Houwen, Sarah E Hunt, Katri Kaukinen, Dermot Kelleher, Ilma Korponay-Szabo, Kalle Kurppa, Padraic MacMathuna, Markku Mäki, Maria Cristina Mazzilli, Owen T McCann, M Luisa Mearin, Charles A Mein, Muddassar M Mirza, Vanisha Mistry, Barbara Mora, Katherine I Morley, Chris J Mulder, Joseph A Murray, Concepción Núñez, Elvira Oosterom, Roel A Ophoff, Isabel Polanco, Leena Peltonen, Mathieu Platteel, Anna Rybak, Veikko Salomaa, Joachim J Schweizer, Maria Pia Sperandeo, Greetje J Tack, Graham Turner, Jan H Veldink, Wieke H M Verbeek, Rinse K Weersma, Victorien M Wolters, Elena Urcelay, Bozena Cukrowska, Luigi Greco, Susan L Neuhausen, Ross McManus, Donatella Barisani, Panos Deloukas, Jeffrey C Barrett, Paivi Saavalainen, Cisca Wijmenga, David A van Heel
Journal: Nature Genetics (2010)
A NEW TECHNIC FOR BLADDER DRAINAGE
Authors: Harvey P. Jack
Journal: JAMA (1918)

This technic is an adaptation of the use of the Murphy button, similar to its use in enterostomy, as suggested by Dr. William D. Johnson of Batavia, N. Y. As will be noted, one half of the Murphy button is inserted into the end of a large rubber tube, the rubber end surrounding the button closely about its shank, just as the end of an intestine would be made to surround it by the purse-string in end-to-end anastomosis. The other half of the button, surrounded down to its shank by a soft rubber ring, if desired, so that it will not cut through too quickly, is placed inside the bladder through a small slit. The bladder tissues are brought firmly about the shank of this half of the button, and the two halves are pushed together as closely as desired. It will be noted at once that we have a