tbuckley/cabot-search huggingface dataset:
Abstract LB-358: Heme oxygenase-1 and carbon monoxide arrest tumor growth via modulation of cellular respiration
Authors: Barbara Wegiel, David Gallo, Eva Czismadia, Kellie Cunningham, Pankaj Seth, Jenny Persson, Leszek Helczynski, Leo Otterbein
Journal: Cancer Research (2012)

Abstract Heme oxygenase-1 (HO-1) and carbon monoxide (CO) are endogenous cytoprotective molecules yet their role in tumor growth, metastasis, cell death and DNA damage has not been elucidated. HO-1 expression was assessed in prostate cancer biopsies from 482 patients and strong nuclear staining, indicative of loss of enzymatic activity was observed in moderately differentiated tumors. Employing prostate cancer (PCa) as our model we treated PCa cells with the chemotherapeutics camptothecin or doxorubicin and observed an increase in cytosolic HO-1 activity that correlated with increased cell death. Overexpression of HO-1 or exogenous pretreatment with CO increased tumor cell sensitivity to chemotherapeutics one thousand fold. In contrast, CO blocked chemotherapeutic-induced cell death of normal prostate epithelial cells. In vivo, CO exposure of mice with established PC3 xenografts resulted in complete growth arrest and sensitization of tumors to doxorubicin with mitotic blockade and enhanced apoptosis of the tumor cells. Exposure to CO showed similar effects in a model of PC3 orthotopic tumors with significant inhibition in markers of invasion. Further, CO blocked development of PIN and prostate tumors in the model of TRAMP mice with concomitant targeting of mitochondria. Further, CO inhibited growth of lung adenocarcinoma in the inducible KRas model of carcinogenesis. Collectively, our data demonstrate the importance of cellular localization of HO-1 in human PCa progression and importantly that CO in part, regulates cellular sensitivity to DNA damaging agents and offers a novel therapeutic adjuvant for the treatment of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-358. doi:1538-7445.AM2012-LB-358
Spontaneous Remission or Response to Methotrexate in Sarcoidosis
Authors: MORTIMER J. LACHER
Journal: Annals of Internal Medicine (1968)

A patient with sarcoidosis could not be controlled with prednisone alone. Six months of additional intermittent intravenous vinblastine therapy had no effect on the course of the disease. When biweekly oral methotrexate therapy was added to the prednisone therapy, the peripheral and mediastinal adenopathy, fever, resting tachycardia, and skin lesions all receded rapidly. No toxicity was encountered. The prednisone was tapered and stopped. Methotrexate was continued, and the remission continued. The possibility that a spontaneous remission occurred simulta neously with the addition of methotrexate cannot be ruled out. The response of a single patient to methotrexate must not be acclaimed as a successful new treatment method for sarcoidosis. It does suggest that a serious clinical trial might be undertaken by those physicians with access to numerous patients with sarcoidosis.
Expression and localization of dystrophin in human cardiac Purkinje fibers.
Authors: R D Bies, D Friedman, R Roberts, M B Perryman, C T Caskey
Journal: Circulation (1992)

BACKGROUND Mutations in the dystrophin gene produce clinical manifestations of disease in heart, brain, and skeletal muscle in patients with Duchenne and Beckers muscular dystrophy (DMD/BMD). Conduction disturbances and heart block contribute to cardiac decompensation in these patients, which suggests an important role for dystrophia in the cardiac conduction system. We therefore examined the messenger RNA (mRNA) expression and protein localization of dystrophin in normal human cardiac Purkinje fibers. METHODS AND RESULTS Polymerase chain reaction amplification of isolated Purkinje fiber complementary DNA identified several alternatively spliced mRNA transcripts encoding for carboxy-terminal isoforms of the dystrophin protein. The predominant mRNA transcript detected was a splice form previously detected in the brain. Antipeptide antibodies specific for a carboxy-terminal dystrophin sequence were used for Western blot analysis and immunocytochemical localization. These antisera detect approximately 400,000-d immunoreactive band or bands on Western blot in normal heart and Purkinje fibers but not in DMD heart. Immunocytochemical staining showed that dystrophin was localized to the membrane surface of the Purkinje fiber. CONCLUSIONS These results suggest that dystrophin may be an important molecule for membrane function in the Purkinje conduction system of the heart and support the hypothesis that defective dystrophin expression contributes to the cardiac conduction disturbances seen in DMD/BMD:
The Yin and Yang of Indoor Airborne Exposures to Endotoxin
Authors: Christopher H. Goss, Nicole Mayer-Hamblett
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

racial/ethnic group and the loss of protective lifestyle factors in another group.In a high-risk sample of families, Kimbro and colleagues found that Mexican immigrant women had threefold increased odds of initiating breastfeeding, whereas Mexican American women had 40% decreased odds of initiating breastfeeding, compared with white women (16).Mexican immigrant status was also associated with lower maternal educational attainment ( 16).The findings of Thakur and colleagues of potential complex relationships between SES and asthma are intriguing and if confirmed will be important for generating hypotheses to better understand the associations.Larger longitudinal studies, with socioeconomic and racial/ethnic diversity or larger samples of defined racial/ethnic groups, measurement of potential mediators or confounders, and inclusion of cumulative SES exposures and measures of social support, will help to further delineate the association between factors such as SES, acculturation, and child asthma and atopy outcomes.
Nuremberg and the Issue of Wartime Experiments on US Prisoners
Authors: Jon M. Harkness
Journal: JAMA (1996)

Defense attorneys at the Nuremberg Medical Trial argued that no ethical difference existed between experiments in Nazi concentration camps and research in US prisons. Investigations that had taken place in an Illinois prison became an early focus of this argument. Andrew C. Ivy, MD, whom the American Medical Association had selected as a consultant to the Nuremberg prosecutors, responded to courtroom criticism of research in his home state by encouraging the Illinois governor to establish a committee to evaluate prison research. The governor named a committee and accepted Ivy's offer to chair the panel. Late in the trial, Ivy testified--drawing on the authority of this committee--that research on US prisoners was ethically ideal. However, the governor's committee had never met. After the trial's conclusion, the committee report was published in JAMA, where it became a source of support for experimentation on prisoners.
Remembrances of the War and the Bomb
Authors: Taro Takemi
Journal: JAMA (1983)

<h3>The Ending of the War</h3> ON THE morning of Aug 6, 1945, an awesome explosion destroyed the city of Hiroshima in the south of the island of Honshu, Japan. Blast and heat devastation from the<i>pikadon</i>were followed by an all-consuming firestorm (<i>pika</i>[bright flash of light];<i>don</i>[loud sound];<i>pikadon</i>came to mean to the people of Hiroshima an explosion consisting of a flash and a boom). There had been severe bombing of many cities in Japan earlier, especially by incendiary bombs, and many sweeping fires had destroyed large areas of cities. The people of Japan were told only that the destruction of Hiroshima was caused by a new kind of bomb. In 1945, I was the only physician studying nuclear physics at the Institute of Physical and Chemical Researches in Tokyo. Dr Yoshio Nishina was our professor. We at the institute immediately surmised that the Hiroshima explosion may
Dean's Welcome Remarks to the Class of 1986
Authors: John Bernard Henry
Journal: JAMA (1983)

THIS WEEK, you will begin formal studies leading to the degree of Doctor of Medicine. We have no doubt, based on the screening and scrutiny you have undergone, that you will be doctors. We know you have the ability. You must demonstrate the discipline and dedication. Today, you have vision, a goal, an ideal. In the next few weeks, you may only be able to see as far as an anatomy practical or a biochemistry quiz. Somehow, being a doctor has been replaced by becoming one, and all too quickly the lofty thoughts and humane motivations almost amorphously disappear. We don't discard them, we just lack the time to tend to them, and, like a garden, untended and uncultivated, our dreams become overgrown, tangled, and choked. Daydream for a moment. Fantasize and let your mind wander. What are you doing here? What do you want to accomplish? What is your
Extra-articular manifestations of rheumatoid arthritis.
Authors: A L Wells
Journal: BMJ (1969)

the National Drugs Advisory Board in Dublin in March, 1968.A full report is being prepared.While the association of bulk sales of these aerosols to occasional asthma deaths appears established, the exact nature of causation is not known.There is a need for more basic research on the effect of isoprenaline in man.It may well be that certain asthmatics develop an idiosyncrasy to it rather than a dose- dependent effect on a hypoxic myoiardium in severe airways obstruction.This thought has occurred because of the beneficial use of intravenous isoprenaline in some low output states not always with a healthy myocardium or fully oxygenated arterial blood, and because of the apparently innocuous or moderate airways-obstruction present in many asthmatics shortly before an unexpected death.-Iam, etc.
Postmarketing surveillance of the safety of cimetidine.
Authors: I K Crombie
Journal: BMJ (1983)

<b>1535</b> <b>Objectives</b>: Multihole collimators are the most important piece of instrumentation in determining the trade-off between spatial resolution and noise of nuclear medicine images. When high-energies (HE) are involved, the problem is even more difficult because the penetration of septa and the shadows due to hole-pattern artifacts (HPA) become non negligible effects. Recently, we found that the collimator-to-detector gap B influences very much the HPA and that specific values of B exist that minimize the artifacts. We call this phenomenon Penumbral Masking (PM). Here we study the matter in more detail, taking into account PM in the problem of designing HE collimators. <b>Methods</b>: The most thorough approach to parallel holes collimators design is that of Gunter: once the material, the holes shape and the holes lattice are chosen, the optimal collimator is sought in a 3D space whose dimensions are collimator thickness, hole diameter and hole separation. The solution is found by requiring a given spatial resolution at a given distance and by maximizing sensitivity. The problem is constrained by two inequalities describing the need to maintain the penetration and the HPA within an acceptable level. Gunter found that below a certain energy threshold (300 KeV for lead) an optimal solution can be found while respecting both the penetration and the HPA constraints. Within an intermediate energy range just beyond this threshold (300-320 KeV) a suboptimal solution can be found in order to respect both constraints and no solution at all exists for higher energies, unless one violates one or both the constraints. While this study gave definite criteria for designing low energy collimators, at the same time it let one conclude that the design of HE collimators is a virtually impossible task. Here we took into account PM in the problematic context of designing HE collimators, basically, by substituting the conventional HPA constraint with a mathematical expression of the PM effect: the value of B is determined in order to nullify the harmonic terms of the periodic collimator response function with order greater than zero. The solution was completely computed for a uniform planar source parallel to the image plane. <b>Results</b>: With this approach we found that an optimal solution to the problem always exists, even if a somewhat lower sensitivity has to be accepted: 10% at 364 Kev and 20% at 511 KeV with lead. Very thick collimators are required (16 cm at 511 KeV). <b>Conclusions</b>: HE collimators that present substantially reduced hole pattern artifacts can be designed. The collimator weight is a major problem, but weight is determined by the necessity to avoid penetration and is not affected by the introduction of PM. However, even when the theoretically optimal solution may not be feasible, this approach enlightens the design of HE collimators.
A Novel Hypoxia-Inducible Spliced Variant of Mitochondrial Death Gene Bnip3 Promotes Survival of Ventricular Myocytes
Authors: Hongying Gang, Yan Hai, Rimpy Dhingra, Joseph W. Gordon, Natalia Yurkova, Yaron Aviv, Hongzhao Li, Floribeth Aguilar, Aaron Marshall, Etienne Leygue, Lorrie A. Kirshenbaum
Journal: Circulation Research (2011)

Alternative splicing provides a versatile mechanism by which cells generate proteins with different or even antagonistic properties. Previously, we established hypoxia-inducible death factor Bnip3 as a critical component of the intrinsic death pathway.To investigate alternative splicing of Bnip3 pre-mRNA in postnatal ventricular myocytes during hypoxia.We identify a novel previously unrecognized spliced variant of Bnip3 (Bnip3Δex3) generated by alternative splicing of exon3 exclusively in cardiac myocytes subjected to hypoxia. Sequencing of Bnip3Δex3 revealed a frame shift mutation that terminated transcription up-stream of exon5 and exon6 ablating translation of the BH3-like domain and critical carboxyl-terminal transmembrane domain crucial for mitochondrial localization and cell death. Notably, although the 26-kDa Bnip3 protein (Bnip3FL) encoded by full-length mRNA was localized to mitochondria and provoked cell death, the 8.2-kDa Bnip3Δex3 protein encoded by the truncated spliced mRNA was defective for mitochondrial targeting but interacted with Bnip3FL resulting in less association of Bnip3FL with mitochondria and diminished apoptotic and necrotic cell death. Forced expression of Bnip3FL in cardiac myocytes or Bnip3(-/-) mouse embryonic fibroblasts triggered widespread cell death that was inhibited by coexpression of Bnip3Δex3. Conversely, RNA interference targeted against sequences encompassing the unique exon2-exon4 junction of the Bnip3Δex3 sensitized cardiac myocytes to mitochondrial perturbations and cell death induced by Bnip3FL.Given the otherwise lethal consequences of deregulated Bnip3FL expression in postmitotic cells, our findings reveal a novel intrinsic defense mechanism that opposes the mitochondrial defects and cell death of ventricular myocytes that is obligatorily linked and mutually dependent on alternative splicing of Bnip3FL during hypoxia or ischemic stress.
Association of Early Imaging for Back Pain With Clinical Outcomes in Older Adults
Authors: Jeffrey G. Jarvik, Laura S. Gold, Bryan A. Comstock, Patrick J. Heagerty, Sean D. Rundell, Judith A. Turner, Andrew L. Avins, Zoya Bauer, Brian W. Bresnahan, Janna L. Friedly, Kathryn James, Larry Kessler, Srdjan S. Nedeljkovic, David R. Nerenz, Xu Shi, Sean D. Sullivan, Leighton Chan, Jason M. Schwalb, Richard A. Deyo
Journal: JAMA (2015)

In contrast to the recommendations for younger adults, many guidelines allow for older adults with back pain to undergo imaging without waiting 4 to 6 weeks. However, early imaging may precipitate interventions that do not improve outcomes.To compare function and pain at the 12-month follow-up visit among older adults who received early imaging with those who did not receive early imaging after a new primary care visit for back pain without radiculopathy.Prospective cohort of 5239 patients 65 years or older with a new primary care visit for back pain (2011-2013) in 3 US health care systems. We matched controls 1:1 using propensity score matching of demographic and clinical characteristics, including diagnosis, pain severity, pain duration, functional status, and prior resource use.Diagnostic imaging (plain films, computed tomography [CT], magnetic resonance imaging [MRI]) of the lumbar or thoracic spine within 6 weeks of the index visit.back or leg pain-related disability measured by the modified Roland-Morris Disability Questionnaire (score range, 0-24; higher scores indicate greater disability) 12 months after enrollment.Among the 5239 patients, 1174 had early radiographs and 349 had early MRI/CT. At 12 months, neither the early radiograph group nor the early MRI/CT group differed significantly from controls on the disability questionnaire. The mean score for patients who underwent early radiography was 8.54 vs 8.74 among the control group (difference, -0.10 [95% CI, -0.71 to 0.50]; mixed model, P = .36). The mean score for the early MRI/CT group was 9.81 vs 10.50 for the control group (difference,-0.51 [-1.62 to 0.60]; mixed model, P = .18).Among older adults with a new primary care visit for back pain, early imaging was not associated with better 1-year outcomes. The value of early diagnostic imaging in older adults for back pain without radiculopathy is uncertain.
THE EFFECT OF ELECTRIC SHOCK THERAPY UPON CEREBROSPINAL FLUID PRESSURE, PROTEIN AND CELLS
Authors: JAMES S. L. JACOBS
Journal: American Journal of Psychiatry (1944)

The cerebrospinal fluid protein and cell content and pressure was obtained before, during and after a series of electric shock treatments performed upon a group of 21 psychotics. In only one case, a diabetic, hypertensive, arteriosclerotic woman, was a significant change noted in protein and cellular constituents. This occurred after the first shock treatment and disappeared within 10 days after 5 subsequent treatments. Occasional elevations of cerebrospinal fluid pressure were noted. These could be correlated with the patients' psychomotor status. It is concluded that the cerebrospinal fluid protein and cell contents should be ascertamed, before and after electric shock treatment, in patients who exhibit significant degrees of arteriosclerotic or hypertensive vascular disease.
Agricultural exposures and cancer trends in developed countries.
Authors: D L Davis, A Blair, D G Hoel
Journal: Environmental Health Perspectives (1993)

Recent increases have been reported in industrial countries for several sites of cancer. The causes of these increases remain unknown. Efforts should proceed to identify those occupational groups with increases in the same sites, as these may indicate relevant exposures. Two analyses were undertaken: trends in cancer mortality in industrial countries were reviewed to identify recently increasing sites and summaries were compiled of studies on farmers which have shown increased risks for these same sites of cancer. Using data provided by the World Health Organization, age-specific rates were developed for a number of sites of cancer from 1968 to 1986. Trends in the ratio of male to female cancer mortality were also assessed for several of these countries. Based on a literature review by the National Cancer Institute, patterns of cancer in farmers reported in 20 studies from 8 countries are summarized, weighting each study by its size to create combined relative risks. In industrial countries, rates of cancer mortality increased for a number of sites, including melanoma, prostate, non-Hodgkin's lymphoma, multiple myeloma, breast, brain, and kidney cancer. The ratio of male to female cancer mortality (for all sites of cancer excluding lung) has generally increased in several countries during this same time period. Many of the same sites that have increased in the general population have also been found to be increasing in farmers. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain in many surveys.(ABSTRACT TRUNCATED AT 250 WORDS)
Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation
Authors: Ton Lisman, Frank W.G. Leebeek, Karina Meijer, Jan Van Der Meer, Karel H. Nieuwenhuis, Philip G. De Groot
Journal: Hepatology (2002)

Cirrhosis is associated with a bleeding tendency, which is particularly pronounced during orthotopic liver transplantation (OLT). A novel approach to treating the bleeding diathesis of patients with cirrhosis is administration of recombinant factor VIIa (rFVIIa). This study examined whether the efficacy of rFVIIa in cirrhosis might be explained in part by enhanced down-regulation of fibrinolysis by thrombin-activatable fibrinolysis inhibitor (TAFI). Addition of therapeutic or supratherapeutic doses of rFVIIa to plasma of 12 patients with stable cirrhosis did not result in a prolongation of clot lysis time, though clotting times were significantly reduced. Also, clot lysis assays of plasma samples taken during and after OLT, which was performed with or without a single bolus dose of rFVIIa, did not show any effect of rFVIIa on plasma fibrinolytic potential. In conclusion, this study shows no evidence for an antifibrinolytic effect of rFVIIa in cirrhotic patients or in patients undergoing OLT.
Abstract 15792: HIV-Infected Patients Have an Increased Risk of Recurrent Ischemic Events as Compared to the General Population After an Acute Coronary Syndrome
Authors: Franck Boccara, Murielle Mary-Krause, Emmanuel Teiger, Sylvie Lang, Pascal Lim, Karim Wahbi, Farzin Beygui, Olivier Milleron, Philippe Gabriel Steg, Christian Funck-Brentano, Michel Slama, Pierre-Marie Girard, Dominique Costagliola, Ariel Cohen
Journal: Circulation (2011)

Purpose: The PACS-HIV study was designed to determine the 3-year prognosis of acute coronary syndrome (ACS) in HIV-infected patients (HIV+) as compared to HIV-uninfected patients (HIV-) in a prospe...
Solar flares and the Concorde.
Authors: F J Ensell
Journal: BMJ (1971)

the risk of mutual interference between folic acid and anticonvulsants in the intestine.89If our interpretation of our findings is correct, then we have found a simple, harm- less, and very cheap method for the treat- ment and prevention of folic acid deficiency in chronic epileptics, which would also re- move the necessity for very large numbers of tedious time-consuming laboratory estimations of serum and red cell folate concentra- tions in such patients.This treatment might also have a place in the treatment of chronic psychiatric patients and geriatric patients admitted in a poor dietary state.-Weare, etc.,