tbuckley/cabot-search huggingface dataset:
P679Ultrastructural and electron tomography analyses of cardiac muscle: normal muscle compared to presence and absence of myosin binding protein C-phosphorylation
Authors: I Torre, M Jeddi, I Amat-Roldan, S Hunter, S Sadayappan, J Robbins, RL Moss, PK Luther
Journal: Cardiovascular Research (2014)

Purpose: Myosin binding protein C is an accessory protein of vertebrate striated muscle thick filaments. Many studies have aimed to elucidate both its structure and function since mutations in the cardiac isoform (cMyBP-C) gene (MYBPC3) are known to be a leading cause of familial hypertrophic cardiomyopathy (HCM) affecting millions of people worldwide. There is strong evidence that phosphorylation of N-terminus M-domain of cMyBP-C is essential for normal cardiac function and that their dephosphorylation is associated with contractile dysfunction and HCM. However, the details of the underlying molecular-level ultrastructure are still poorly understood. The aim of this work is to provide details of the ultrastructure of thick filaments in different states of cMyBP-C phosphorylation. Methods: Two transgenic mouse strains expressing a constitutive phosphorylation or a non-phosphorylatable cMyBP-C have been compared to a homozygous knockout mouse for cMyBP-C and a wild-type (WT) control. We have carried out detailed transmission electron microscopy (TEM) in intact cardiac muscles, and electron tomography (ET) combined with sub-tomographic averaging. Results: TEM shows that cardiomyocyte ultrastructure is relatively well maintained under the total deletion of cMyBP-C from the heart and due to the expression of constitutive phosphorylation of cMyBP-C. However, the constitutive expression of non-PKA-phosphorylatable cMyBP-C leads to both sarcomeric disarray and mitochondria disruption. Longitudinal views of the average 3D reconstructions employing ET illustrate the surface density features of thick filaments. In the WT, two projection masses can be identified originating from cMyBP-C. Both the absence of cMyBP-C and the presence of constitutive non-phosphorylatable cMyBP-C seem to be associated with poorer structural preservation of the thick filaments. Conclusions: This study shows that cMyBP-C constitutive phosphorylation effectively preserves the intracellular arrangement of cardiac myocytes. However, non-PKA-phosphorylatable cMyBP-C leads to a dramatic overall decrease of tissue organization which is much more deleterious than the total deletion of cMyBP-C. This finding provides a structural explanation for cardiac dysfunction in this sample. This study shows that chemically fixed samples can be used for ET to reveal 3D structural information of thick filaments. Results obtained by using this methodology are in good agreement with previous studies using isolated filament approaches. However, in order to obtain higher resolution, advanced methods of sample processing will be required.
Cytokine network in the first 6 weeks of rheumatoid arthritis onset
Authors: R Cascao, R A Moura, H Canhao, E Sousa, A F Mourao, A M Rodrigues, J Polido-Pereira, M V Queiroz, H S Rosario, M M Souto-Carneiro, L Graca, J E Fonseca
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly characterised by synovial hyperplasia and joint destruction. Although the aetiopathology of this autoimmune disease is not completely understood, it is known that it is associated with a misregulation of both the cellular immune system and the cytokine network. Nevertheless, little is known about the blood cytokine milieu in the first few weeks of RA.

To determine …
Artemin, a Novel Member of the GDNF Ligand Family, Supports Peripheral and Central Neurons and Signals through the GFRα3–RET Receptor Complex
Authors: Robert H Baloh, Malú G Tansey, Patricia A Lampe, Timothy J Fahrner, Hideki Enomoto, Kelli S Simburger, Melanie L Leitner, Toshiyuki Araki, Eugene M Johnson, Jeffrey Milbrandt
Journal: Neuron (1998)
Obsessive-Compulsive Symptom Dimensions as Predictors of Compliance with and Response to Behaviour Therapy: Results from a Controlled Trial
Authors: David Mataix-Cols, Isaac M. Marks, John H. Greist, Kenneth A. Kobak, Lee Baer
Journal: Psychotherapy and Psychosomatics (2002)

&lt;i&gt;Background:&lt;/i&gt; Recent factor-analytic studies in obsessive-compulsive disorder (OCD) identified consistent symptom dimensions. Support for the validity of these dimensions comes from studies of psychiatric comorbidity, functional brain imaging, genetic transmission, and treatment response to medications. This study examined whether previously identified OCD symptom dimensions are associated with treatment compliance and response to behaviour therapy (BT) for OCD. &lt;i&gt;Methods:&lt;/i&gt; One hundred and fifty-three OCD outpatients who participated in a multi-centre randomised controlled trial of computer- versus clinician-guided BT for OCD were included in the study. Logistic and multiple regression models tested for significant predictors of compliance with and response to BT and relaxation. &lt;i&gt;Results:&lt;/i&gt; The patients studied were phenomenologically comparable (including the presence of ‘pure’ obsessions and mental rituals) to those in previous serotonin reuptake inhibitor (SRI) trials and those in clinical epidemiology studies. High scorers on the ‘hoarding’ dimension were more likely to drop out prematurely from the study and tended to improve less. For those completing treatment, the strongest predictor of outcome was pre-treatment severity. Initial depression scores were unrelated to outcome. After controlling for symptom severity, higher scores on the ‘sexual/religious obsessions’ factor predicted poorer outcome with BT, especially when computer-guided. &lt;i&gt;Conclusions:&lt;/i&gt; BT is especially indicated for OCD patients with aggressive/checking, contamination/cleaning and symmetry/ordering symptoms. Previous accounts of unsuccessful BT in patients with hoarding symptoms may be due in part to their propensity to drop out earlier from treatment. Patients with sexual/religious obsessions, but not those with mental rituals, might respond less well to traditional BT techniques. Existing treatments need to be refined and/or new treatments developed to improve these patients’ adherence and response to treatment.
Autopsy Findings in a Long-Surviving Liver Recipient
Authors: Thomas Starzl, Kendrick A. Porter, Gerhard Schroter, Jacques Corman, Carl-Gustav Groth, Harvey L. Sharp
Journal: New England Journal of Medicine (1973)

IT has been a little more than five years since the first extended survival was achieved after human liver transplantation, and for that reason individual cases are still of special interest. For a...
Comparison of the Prognostic Value of Normal Regadenoson With Normal Adenosine Myocardial Perfusion Imaging With Propensity Score Matching
Authors: Fahad M. Iqbal, Fadi G. Hage, Ali Ahmed, Phillip J. Dean, Saleem Raslan, Jaekyeong Heo, Ami E. Iskandrian
Journal: JACC. Cardiovascular imaging (2012)
SOME QUESTIONS OF RESPONSIBILITY IN OPIUM AND COCAIN INEBRIETY.
Authors: T. D. CROTHERS
Journal: JAMA (1895)

Within a recent period the question of responsibility and accountability for conduct and acts of persons who are known as opium, cocain and other inebriates has been raised in courts, and referred to medical men to answer. The confusing character of the medical evidence offered suggests the need of a more careful study of some of the general facts common to these cases. So far, the contested cases have been disputed wills, strange criminal assaults, thefts and defalcations, and other crimes usually devoid of premeditation and ordinary judgment in the execution. The larger number of these cases have none of the symptoms of insanity as understood in courts and text-books. The prominent manias and delusions and eccentricities of talk and conduct are wanting. The opium cases in public are quiet, secretive, abstract and harmless. The cocain takers are talkative and excited, but equally shrinking and retiring. The other drug takers
Gene Mutation Revelation Points to New Target for Myeloma Treatment, Studies Say
Authors: K. Garber
Journal: JNCI Journal of the National Cancer Institute (2007)

Multiple myeloma is a disease in the spotlight. Although it is relatively rare, accounting for about 2% of all cancers in the U.S., new treatments arrive almost every year. Bortezomib, thalidomide, and lenalidomide have all been approved since 2003, and new bone marrow transplant regimens have extended survival. The multiple myeloma field “has exploded,” said Louis Staudt, M.D., Ph.D. , of the National Cancer Institute. But the disease is still considered incurable. Now two papers in the August issue of Cancer Cell mark another advance in myeloma biology, as well as a promising new approach to treatment. Groups led by Staudt and Leif Bergsagel, M.D. , of the Mayo Clinic in Scottsdale, Ariz., independently identifi ed a variety of gene mutations and other genetic abnormalities in the NF- B signaling pathway in myeloma. The Staudt group concluded that 82% of patients with myeloma have activated NF- B. This result, Staudt said, “rockets it up the list of pathways you’d have to consider as targets in myeloma.” The Bergsagel report suggests that NFB pathway mutations can be used to select patients for bortezomib treatment. And myeloma patients may eventually benefi t from direct NF- B inhibitors now under development by many drug companies.
Prehospital trial of emergency transcutaneous cardiac pacing.
Authors: J R Hedges, S A Syverud, W C Dalsey, S Feero, R Easter, B Shultz
Journal: Circulation (1987)

A prospective alternate-day controlled trial of prehospital transcutaneous cardiac pacing (PACE) of hemodynamically significant bradycardia and asystole was undertaken. All patients had a Glasgow coma scale score of 12 or less. Patients in the control group (n = 101) received standard advanced cardiac life support (ACLS) care. Patients in the pacing group (n = 101) were to receive PACE in addition to standard ACLS treatment; 89 patients were actually paced. The two groups were comparable in terms of age, sex, presenting rhythm, and mean times to cardiopulmonary resuscitation (CPR) and ACLS. For the 144 patients in whom the time of arrest could be estimated, the mean times to CPR and ACLS were 5.3 +/- 4.0 and 10.9 +/- 7.1 min, respectively. For the 65 paced patients in whom the time of arrest could be estimated, the mean time from arrest to pacing was 21.8 +/- 8.8 min (range 2 to 43). Multivariate analysis of outcome variables (presentation to emergency department with a pulse, admission to the hospital, and discharge from the hospital) revealed that an initial rhythm of ventricular tachycardia or fibrillation and a short time to ACLS were correlated with a favorable outcome (p less than .05; logistic regression analysis). A short time to PACE was associated with admission to the hospital (p = .20; logistic regression analysis). The use of a stand-alone transcutaneous pacing device in the prehospital arrest setting was associated with generally long times until pacing and did not appreciably improve outcome. Use of PACE in patients demonstrating prehospital bradycardia without neurologic impairment remains to be evaluated.
Apo2 Ligand/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Chemotherapy to Inhibit Orthotopic Lung Tumor Growth and Improve Survival
Authors: Hongkui Jin, Renhui Yang, Sharon Fong, Klara Totpal, David Lawrence, Zhong Zheng, Jed Ross, Hartmut Koeppen, Ralph Schwall, Avi Ashkenazi
Journal: Cancer Research (2004)

Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a tumor necrosis factor superfamily member that induces apoptosis through the death receptors DR4 and/or DR5 in various cancer cell types but not in most normal cells. Several lung cancer cell lines express DR4 and DR5 and undergo apoptosis in vitro in response to Apo2L/TRAIL. We investigated the efficacy of recombinant soluble human Apo2L/TRAIL and its interaction with chemotherapy in xenograft models based on human NCI-H460 non-small cell lung carcinoma cells. In vitro, Taxol enhanced caspase activation and apoptosis induction by Apo2L/TRAIL. In vivo, Apo2L/TRAIL or Taxol plus carboplatin chemotherapy partially delayed progression of established subcutaneous tumor xenografts, whereas combined treatment caused tumor regression and a substantially longer growth delay. Apo2L/TRAIL, chemotherapy, or the combination of both inhibited growth of preformed orthotopic lung parenchymal tumors versus control by 60%, 57%, or 97%, respectively (all P < 0.01; n = 8-10). Furthermore, combination treatment improved day-90 survival relative to control (7 of 15 versus 1 of 15; P = 0.0003 by Mantel-Cox) as well as to Apo2L/TRAIL (3 of 14; P = 0.031) or chemotherapy (3 of 15; P = 0.035). These studies provide evidence for in vivo activity of Apo2L/TRAIL against lung tumor xenografts and underscore the potential of this ligand for advancing current lung cancer treatment strategies.
Prescription Opioids and Overdose Deaths
Authors: Michael Merrick
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Nucleophosmin Mediates Mammalian Target of Rapamycin–Dependent Actin Cytoskeleton Dynamics and Proliferation in Neurofibromin-Deficient Astrocytes
Authors: Danielle K. Sandsmark, Huabiao Zhang, Balazs Hegedus, Corey L. Pelletier, Jason D. Weber, David H. Gutmann
Journal: Cancer Research (2007)

Abstract Neurofibromatosis type 1 (NF1) is a common autosomal dominant tumor predisposition syndrome in which affected individuals develop astrocytic brain tumors (gliomas). To determine how the NF1 gene product (neurofibromin) regulates astrocyte growth and motility relevant to glioma formation, we have used Nf1-deficient primary murine astrocytes. Nf1−/− astrocytes exhibit increased protein translation and cell proliferation, which are mediated by Ras-dependent hyperactivation of the mammalian target of rapamycin (mTOR) protein, a serine/threonine protein kinase that regulates ribosomal biogenesis, protein translation, actin cytoskeleton dynamics, and cell proliferation. In this study, we show that Nf1-deficient astrocytes have fewer actin stress fibers and exhibit increased cell motility compared with wild-type astrocytes, which are rescued by pharmacologic and genetic mTOR inhibition. We further show that mTOR-dependent regulation of actin stress fiber formation, motility, and proliferation requires rapamycin-sensitive activation of the Rac1 GTPase but not elongation factor 4E-binding protein 1/S6 kinase. Nf1−/− astrocytes also exhibit increased protein translation and ribosomal biogenesis through increased expression of the nucleophosmin (NPM) nuclear-cytoplasmic shuttling protein. We found that NPM expression in Nf1−/− astrocytes was blocked by rapamycin in vitro and in vivo and that expression of a dominant-negative NPM mutant protein in Nf1−/− astrocytes rescued actin stress fiber formation and restored cell motility and proliferation to wild-type levels. Together, these data show that neurofibromin regulates actin cytoskeleton dynamics and cell proliferation through a mTOR/Rac1-dependent signaling pathway and identify NPM as a critical mTOR effector mediating these biological properties in Nf1-deficient astrocytes. [Cancer Res 2007;67(10):4790–9]
FRACTURES OF THE HIP
Authors: C. E. RUTH
Journal: JAMA (1930)

Fractures in and around the hip joint arise from so many varying applications of force that we shall not attempt to describe the mechanism of such fractures at this time. Nor shall we repeat here the methods by which a diagnosis was arrived at in former days. These older methods not infrequently did much harm by additional trauma to the soft parts, including laceration of the capsular ligament sufficient to impair greatly its aid in maintaining reduction. A patient in whom fracture of the hip is suspected should be transported as quickly as possible to a suitable hospital. This can be done without risk of additional trauma in most cases, if care is taken to apply a Thomas leg splint properly or a long side splint extending from the axilla to the foot. This side splint may be reinforced by placing a pillow between the legs, the uninjured as well
478 KINETICS OF SERUM HEPATITIS B SURFACE ANTIGEN LEVEL IN GENOTYPE C HBS AG SEROCLEARED CARRIERS
Authors: S. Nagaoka, H. Yatsuhashi, Y. Kugiytama, K. Ogihara, S. Bekki, S. Hashimoto, M. Ohtani, S.K. Bae, A. Saeki, S. Abiru, A. Komori, H. Ishibashi
Journal: Journal of Hepatology (2012)
Sex Education: How Should It Be Offered?
Authors: James S. Marks
Journal: JAMA (1986)

Sexual messages pervade our lives—at home, in schools, in media, in shopping centers, on airplanes, and even in physicians' offices. Rightly so, since being sexual is part of being human. Using public health values, sex can be a conduit for either good (enjoyment, planned pregnancy) or unfortunate (unplanned pregnancy, sexually transmitted diseases [STD]) outcomes. To avoid the adverse consequences, individuals need both factual information and decision-making skills to make informed choices to reduce their risks of these unfortunate outcomes. Teenagers are especially vulnerable, not only to sexual messages but also to sexual misfortunes.<sup>1,2</sup>Adolescent pregnancy and childbearing, as well as STDs in adolescents, continue to be major public health problems in the United States. In 1981, an estimated 1.3 million adolescents became pregnant, and of these over 500,000 had live births.<sup>3,4</sup>Over 80% of these pregnancies were unintended. Between 1971 and 1982, the proportion of metropolitan-area, never-married 15- to
Immunologic Mechanisms in Intestinal Diseases
Authors: STEPHAN R. TARGAN
Journal: Annals of Internal Medicine (1987)

The intestine is a unique immunologic organ that comprises an afferent and efferent compartment and provides the host with the ability to respond through several different effector mechanisms against environmental factors. We discuss mechanisms in three intestinal diseases in this overview of the mucosal immune system. Genetic and immunologic factors are important in the pathogenesis of celiac disease, which is characterized by damage to the mucosa of the small intestine with resultant malabsorption. Pathogenic microbes are important environmental agents that interact with the intestinal mucosa and initiate local immune responses. Advances in the understanding of the mucosal immune response to these pathogenic microbes have produced a clear picture of the way in which this specialized immune system works in concert with systemic immunity. As to the autoimmune nature of inflammatory bowel disease, no specific antigen has been shown to incite the inflammatory reactions and neither the target cells nor the effector mechanism involved have been identified. Several factors exist, however, to suggest an autoimmune mechanism and the role of mucosal immunologic factors in this disease.
Prevention of Deep Vein Thrombosis after Elective Hip Surgery
Authors: Mark N. Levine, Jack Hirsh, Michael Gent, Alexander G. Turpie, Jacques Leclerc, Peter J. Powers, Richard M. Jay, Jean Neemeh
Journal: Annals of Internal Medicine (1991)

To determine the relative efficacy and safety of low molecular weight (LMW) heparin (Enoxaparin) compared with standard calcium heparin for the prevention of postoperative deep vein thrombosis in patients undergoing elective hip surgery.A double-blind, randomized, controlled trial.Six hundred sixty-five consecutive patients undergoing hip replacement at five participating hospitals.Patients received either fixed-dose LMW heparin, 30 mg subcutaneously twice daily, or fixed-dose standard calcium heparin, 7500 units subcutaneously twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge if sooner.All patients had postoperative I-125-fibrinogen leg scanning and impedance plethysmography. If results of one or both tests were positive, then venography was done. Otherwise, venography was done between day 10 and day 14, or sooner if the patient was ready for discharge.Evaluable venograms were obtained in 258 of the 333 patients randomly assigned to receive LMW heparin and in 263 of the 332 patients assigned to receive calcium heparin. For patients with evaluable venograms, thrombosis was detected in 50 patients (19.4%) who received LMW heparin compared with 61 patients (23.2%) who received standard heparin (difference, -3.8%; 95% CI, -11.1% to 3.6%) (P greater than 0.2). Proximal deep vein thrombosis was detected in 5.4% of the patients receiving LMW heparin and in 6.5% of the patients receiving standard heparin (difference, -1.1%; CI, - 5.2% to 3.3%) (P greater than 0.2). For the entire group of 665 patients, venous thrombosis occurred in 17.1% given LMW heparin and in 19.0% given standard heparin. Hemorrhagic complications occurred in 31 patients (9.3%) given standard heparin and in 17 patients (5.1%) given LMW heparin (difference, 4.2%; CI, 0.3% to 8.2%) (P = 0.035). The relative risk reduction was 45%. The rate of major bleeding in the standard heparin group was 5.7% compared with 3.3% in the LMW heparin group (difference, 2.4%; CI, -1.0% to 5.4%) (P = 0.13). The relative risk reduction was 42%.Low molecular weight heparin is significantly less hemorrhagic than standard unfractionated heparin; the difference in the rate of deep vein thrombosis, although not statistically significant (P greater than 0.2), favors the use of LMW heparin.
Redesigning Surgical Decision Making for High-Risk Patients
Authors: Laurent G. Glance, Turner M. Osler, Mark D. Neuman
Journal: New England Journal of Medicine (2014)

Shared decision making in surgical care requires a culture shift. For patients at high risk for adverse events after surgery, or in cases with an equivocal risk–benefit balance, evidence-based decision making may require input from a multidisciplinary group of experts.