tbuckley/cabot-search huggingface dataset:
AFG3L2 supports mitochondrial protein synthesis and Purkinje cell survival
Authors: Eva R. Almajan, Ricarda Richter, Lars Paeger, Paola Martinelli, Esther Barth, Thorsten Decker, Nils-Göran Larsson, Peter Kloppenburg, Thomas Langer, Elena I. Rugarli
Journal: Journal of Clinical Investigation (2012)

Mutations in the AFG3L2 gene have been linked to spinocerebellar ataxia type 28 and spastic ataxia-neuropathy syndrome in humans; however, the pathogenic mechanism is still unclear. AFG3L2 encodes a subunit of the mitochondrial m-AAA protease, previously implicated in quality control of misfolded inner mitochondrial membrane proteins and in regulatory functions via processing of specific substrates. Here, we used a conditional Afg3l2 mouse model that allows restricted deletion of the gene in Purkinje cells (PCs) to shed light on the pathogenic cascade in the neurons mainly affected in the human diseases. We demonstrate a cell-autonomous requirement of AFG3L2 for survival of PCs. Examination of PCs prior to neurodegeneration revealed fragmentation and altered distribution of mitochondria in the dendritic tree, indicating that abnormal mitochondrial dynamics is an early event in the pathogenic process. Moreover, PCs displayed features pointing to defects in mitochondrially encoded respiratory chain subunits at early stages. To unravel the underlying mechanism, we examined a constitutive knockout of Afg3l2, which revealed a decreased rate of mitochondrial protein synthesis associated with impaired mitochondrial ribosome assembly. We therefore propose that defective mitochondrial protein synthesis, leading to early-onset fragmentation of the mitochondrial network, is a central causative factor in AFG3L2-related neurodegeneration.
Alterations of Factors Predisposing to Coronary Heart Disease
Authors: LEON D. OSTRANDER
Journal: Annals of Internal Medicine (1968)

Habits, Physical and psychological factors, and biochemical abnormalities associated with an increased risk of coronary heart disease are discussed. There is no conclusive proof that correction of such factors prevents or delays the development of overt coronary heart disease, but the inferential evidence is impressive. Physicians and all persons interested in public health should enthusiastically advocate cessation of smoking, the maintenance of a lean body weight, and regular physical exercise. Compliance is safe, cheap, and noncontroversial. Beyond alterations in habits, the physician should strive for the early identification and correction of hypertension, hyperlipemia, and diabetes mellitus among his patients. The principles of treatment are discussed, but rigid and dogmatic recommendations are purposely avoided. Treatment must be flexible enough to fulfill the needs of patients with a variety of abnormalities that in some instances do not respond as expected to an apparently appropriate regimen.
Correction: Atenolol for Migraine
Authors: Kusum L. Kumar
Journal: Annals of Internal Medicine (1990)

Letters and Corrections1 August 1990Correction: Atenolol for MigraineKusum L. Kumar, MDKusum L. Kumar, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-3-257_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:There was an error in our letter (1), "Visual Symptoms after Atenolol Therapy for Migraine," in the 1 May issue. In the fourth paragraph, the second sentence should read "However, no patients in this study were reported to have symptoms of aura without a headache." The word "no" was omitted by error, and we feel it is important to correct this mistake.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Kusum L. Kumar, MDAffiliations: Veterans Affairs Medical Center Oregon Health Sciences University Portland, OR 97207 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1990Volume 113, Issue 3Page: 257-257KeywordsEpilepsyHeadachesMigraine ePublished: 1 December 2008 Issue Published: 1 August 1990 PDF downloadLoading ...
Interpretation of aortic root angiography in dogs and in humans
Authors: M. THUBRIKAR, B. A CARABELLO, J. AOUAD, S. P NOLAN
Journal: Cardiovascular Research (1982)

Journal Article Interpretation of aortic root angiography in dogs and in humans Get access MANO THUBRIKAR, MANO THUBRIKAR § ** From the Department of Surgery, University of Virginia Medical Center, Charlottesville, Virginia §Address for reprint requests: Mano Thubrikar, PhD, Box 263, Department of Surgery, University of Virginia Medical Center, Charlottesville, Virginia 22908, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar BLASE A CARABELLO, BLASE A CARABELLO † From the Department of Internal Medicine, University of Virginia Medical Center, Charlottesville, Virginia Search for other works by this author on: Oxford Academic PubMed Google Scholar JAAFAR AOUAD, JAAFAR AOUAD ‡ From the Department of Comparative Medicine, University of Virginia Medical Center, Charlottesville, Virginia Search for other works by this author on: Oxford Academic PubMed Google Scholar STANTON P NOLAN STANTON P NOLAN ** From the Department of Surgery, University of Virginia Medical Center, Charlottesville, Virginia Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 1, January 1982, Pages 16–21, https://doi.org/10.1093/cvr/16.1.16 Published: 01 January 1982
MEDICO-PHARMACEUTICAL ETHICS
Authors: A. S. MUSANTE
Journal: JAMA (1910)

Parogenum sulphuris-sulphur parogen.Sulphur subi. 3,linseed oil 37; dissolve by aid of heat; then mix with parogen to 100.Parogenum sulphuris compositum-compd.sulphur parogen.Sulphur parogen 10, oil of cade 10, thymol 0.3.eucalyptol 3, oil of turpentine 30, parogen to 100.Dissolve the thymol and eucalyptol in the oil, mix with the parogen.Parogenum terebinth inn-turpentine paraffin.Venice turpentine fact. 20,parogen to 100; mix them.Parogenum spissum-thick parogen.Hard paraffin 12, liquid paraffin 48, oleic acid 30.alcohol ammon.(5 per cent.) 10.Melt the hard paraffin; add the liquid paraffin, then the oleic acid und the alcohol und continue the heat on a water-bath until the product weighs 90.The following single generic names are suggested for the same reasons as was the parogenum for petrolatum saponatum.If physicians are expected to use these preparations, the generic titles must be composed of single words otherwise when the specific name is added they become too cumbersome.LANOLIMENTA-LANOI.IMENTS Lanolinientiim mentholis-menthol hinoliment.Menthol 5, hydrous wool-fat to 100; mix.Lanolimentum mentholis salicylatum-salicylated menthol lanoliment.Menthol 5, methyl salieylate 10, hydrous wool-fat to 100; mix.I'urullinoleum mentholis-menthol paraffinol-liquid petro¬ latum and menthol.Menthol 2, liquid petrolatum to 100.Mix and strain if necessary.ParaHinoloum eucalypti-eucalyptus paraffinol.Oil eucalyptus 5, liquid petrolatum to 100; mix.Paraffinoleum thymolis-thymol paraffinol.Thymol 1, liquid petrolatum to 100.Dissolve by tritura¬ tion in a warm mortar.Paraffinol phenolis-phenol paraffinol.Phenol cryst. 1,liquid petrolatum to 100.Dissolve by trituration in a warm mortar.74 East Twelfth Street.
759–5 Use of an Interactive Electronic Whiteboard to Teach Clinical Cardiology Decision Analysis to Medical Students
Authors: John F. Murphy, Nilesh L. Jain, S. Andrew Spooner, Scott W. Hassan, John L. Schnase, Edward S. Metcalfe, Paul A. Schoening, Edward L. Cunnius, Mark E. Frisse
Journal: Journal of the American College of Cardiology (1995)
A multi-modal, emergent view of the development of syllables in early phonology
Authors: Lise Menn
Journal: Behavioral and Brain Sciences (1998)

A narrow focus on the jaw (or on motor generators) does not account for individual and language-specific differences in babbling and early speech. Furthermore, data from Yoshinaga-Itano's laboratory support earlier findings that show glottal rather than oral stops in deaf infants' babbling: audition is crucial for developing normal syllables.
Real-time Raman Spectroscopy for <i>In Vivo</i> Skin Cancer Diagnosis
Authors: Harvey Lui, Jianhua Zhao, David McLean, Haishan Zeng
Journal: Cancer Research (2012)

Abstract Raman spectroscopy is a noninvasive optical technique capable of measuring vibrational modes of biomolecules within viable tissues. In this study, we evaluated the application of an integrated real-time system of Raman spectroscopy for in vivo skin cancer diagnosis. Benign and malignant skin lesions (n = 518) from 453 patients were measured within 1 second each, including melanomas, basal cell carcinomas, squamous cell carcinomas, actinic keratoses, atypical nevi, melanocytic nevi, blue nevi, and seborrheic keratoses. Lesion classification was made using a principal component with general discriminant analysis and partial least-squares in three distinct discrimination tasks: skin cancers and precancers from benign skin lesions [receiver operating characteristic (ROC) = 0.879]; melanomas from nonmelanoma pigmented lesions (ROC = 0.823); and melanomas from seborrheic keratoses (ROC = 0.898). For sensitivities between 95% and 99%, the specificities ranged between 15% and 54%. Our findings establish that real-time Raman spectroscopy can be used to distinguish malignant from benign skin lesions with good diagnostic accuracy comparable with clinical examination and other optical-based methods. Cancer Res; 72(10); 2491–500. ©2012 AACR.
Excessive FMS-like tyrosine kinase3-ligand heralds lymphoma in primary sjogren's syndrome
Authors: J.-O. Pers, G. J. Tobon, J.-E. Gottenberg, R. Seror, V. Devauchelle-Pensec, J. Morel, S. Rist, X. Mariette, A. Saraux, P. Youinou
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> To determine if the FMS-like tyrosine kinase 3 ligand (FL), a cytokine implicated not only in B cell ontogenesis and proliferation, but also in haematological malignancies, contributes to increases in the blood Bm2 and Bm29 B cell subsets and heralds lymphoma in patients with primary Sjögren9s syndrome (pSS). <h3>Patients and methods</h3> Serum levels of FL were measured in 64 pSS patients and 20 matched healthy controls (HCs). The densities of FL and its receptor Flt3 were determined in blood B cells and salivary gland (SG) samples by immunofluorescence. The effect of FL on B lymphocytes was then investigated by coculture with human SG (HSG) cell line cells. Finally, FL serum levels were measured in 334 patients from the French cohort of primary SS patients (‘Assessment of Systemic Signs and Evolution of Sjögren9s Syndrome’, ASSESS). We evaluated the association between FL levels and lymphoma development (past or present), and disease activity according to the EULAR SS Disease Activity Index (ESSDAI). <h3>Results</h3> Serum levels of FL were increased in patients with pSS, compared to HCs (135.8 ± 5.5 vs 64.4 ± 4.5 pg/ml, p&lt;0.001). These levels of FL correlated with the numbers of Bm2 and Bm29 (r=0.459, p&lt;0.0006) in pSS patients, and Flt3 was selectively expressed in Bm2 and Bm29 cells. B cell culture experiments showed that FL potentiates the proliferative effect of anti-IgM stimulation. SGs-infiltrating B cells expressed Flt3, and epithelial cells produced FL. Thus, excesses FL appeared to be associated with high ESSDAI (p&lt;0.05) and lymphoma (p&lt;0.0001) in the 334 patients of the ASSESS cohort. ROC analysis showed that 175 pg/ml was the ideal cut-off to detect the association with lymphoma with the sensitivity 44% and the specificity 97.5%. <h3>Conclusions</h3> Serum levels of FL are elevated in pSS, accompanied by abnormal B cell distribution, and associated with history of lymphoma. Flt3 is mainly express by Bm2 and Bm29 cells. Serum levels of FL might explain the clinical evolution of pSS to B cell lymphoma, thus opening new avenues for therapy.
Peripheral functional organisation of vagally evoked gastric motor responses in the ferret.
Authors: P L Andrews, I N Lawes, A J Bower
Journal: Gut (1980)

The aims of the present study were to determine the relative amplitudes of intragastric motor responses evoked by different vagal branches and to establish whether the effects of acute or chronic vagotomy could be predicted from these data. Intragastric pressure responses to electrical stimulation of the vagus were measured in urethane-anaesthetised ferrets and acute or chronic vagotomies were performed. The results show that the left and right cervical vagi were equipotential and fully overlaped each other. Their contributions to the dorsal trunk were equipotential and fully overlapping and so were their contributions to the ventral trunk. The dorsal trunk was more effective than the ventral trunk and there was total functional overlap between these two trunks. Vagal evoked gastric motor responses of the ferret are apparently organised in a different way from vagally induced acid secretion or hormone release in the cat. Acute removal of a trunk led to a reduction in evoked responses that was not linear function of the effect of stimulation of that trunk. In contrast, chronic removal caused a relative increase in evoked responses that ws inversely related to the decrease caused by acute removal. The implications of total functional overlap and neuromuscular reorganisation after chronic vagotomy are discussed.
New answers raise new questions in pulmonary arterial hypertension
Authors: S.M. Kawut, H.I. Palevsky
Journal: European Respiratory Journal (2004)

Research and treatment of pulmonary vascular diseases pose distinct challenges. Despite these hurdles (or perhaps because of them), a cadre of basic scientists, geneticists, physiologists, clinical researchers and clinicians have dedicated themselves to the study and care of patients with pulmonary vascular disease. The European Respiratory Journal ( ERJ ) series “Advances in Pathobiology, Diagnosis, and Treatment of Pulmonary Hypertension” 1–10 comprehensively categorises the achievements of these individuals and concludes this month with a fitting finale. Peacock et al. 11 (this issue of the ERJ ) and Hoeper et al. 12 have written statements from recent conferences focused on the methodology of randomised controlled trials (RCTs) in pulmonary arterial hypertension (PAH); until recently, a seemingly quixotic discussion. As with all important research, these documents potentially raise more questions than they answer.

The availability of bosentan (an endothelin‐1 receptor antagonist) and other safe, effective therapies for PAH led the working groups to re­evaluate the ethical and scientific merit of using untreated placebo­control arms in RCTs 2, 13–15. This is a very controversial area faced by researchers in other conditions with pre­existing effective therapies, such as congestive heart failure (CHF) 16–19. In general, it is considered to be ethical to perform such trials if: 1) the patient is fully informed about the alternatives; and 2) there is minimal risk of irreversible or severe morbidity, or mortality, posed by withholding effective therapy.

While the former concern is relatively straightforward, the working groups recognised the difficulty in defining the boundaries of the latter. As the success of future placebo­controlled trials in this rare disease will depend on patients' and physicians' willingness to enrol in such trials, future study designs will have to be acceptable to both groups. Such acceptability may be important to investigate before initiating …
DIFFERENCES OF EFFECT BY VALVULAR SURGERY ON LEFT VENTRICULAR SYSTOLIC FUNCTION ASSESSED BY 2-DIMENSIONAL SPECKLE-TRACKING ECHOCARDIOGRAPHY BETWEEN AORTIC REGURGITATION AND AORTIC STENOSIS
Authors: Hisao Yoshikawa, Makoto Suzuki, Takako Tsuchida, Tsukasa Osaki, Takenori Otsuka, Takayoshi Matsuyama, Hiromasa Yamashita, Makoto Uchida, Norio Uchimura, Shigeyuki Ozaki, Kaoru Sugi
Journal: Journal of the American College of Cardiology (2010)
Comprehensive Geriatric Assessment in the Decision-Making Process in Elderly Patients With Cancer: ELCAPA Study
Authors: Philippe Caillet, Florence Canoui-Poitrine, Johanna Vouriot, Muriel Berle, Nicoleta Reinald, Sebastien Krypciak, Sylvie Bastuji-Garin, Stephane Culine, Elena Paillaud
Journal: Journal of Clinical Oncology (2011)

To identify Comprehensive Geriatric Assessment (CGA) components independently associated with changes in planned cancer treatment.We prospectively included 375 consecutive elderly patients with cancer (ELCAPA01 study) assessed by geriatricians using the CGA. Multivariate analysis was used to identify factors associated with changes in the cancer treatment (intensification, decrease, or delayed > 2 weeks). Change was defined as a difference between the initial treatment proposal and the final treatment selected in a multidisciplinary meeting.Mean age was 79.6 years (standard deviation [SD], 5.6 years), and 197 (52.5%) were women. The most common tumor location was the digestive system (58.7%). The mean number of comorbidities was 4.2 (SD, 2.7) per patient, and the mean Cumulative Illness Rating Scale for Geriatrics score was 11.8 (SD, 5.3). After the CGA, the initial cancer treatment plan was modified for 78 (20.8%) of 375 patients (95% CI, 16.8 to 25.3), usually to decrease treatment intensity (63 [80.8%] of 78 patients). By univariate analysis, cancer treatment changes were associated with Eastern Cooperative Oncology Group performance status ≥ 2 (73.3% in the group with changes v 41.1% in the in the group without changes; P < .001), dependency for one or more activities of daily living (ADL; 59.0% v 24.2%; P < .001), malnutrition (81.8% v 51.2%; P < .001), cognitive impairment (38.5% v 24.9%; P = .023), depression (52.6% v 21.7%; P < .001), and greater number of comorbidities (mean, 4.8 [SD, 2.9] v 4.0 [SD, 2.6]; P = .02). By multivariate analysis, factors independently associated with cancer treatment changes were a lower ADL score (odds ratio [OR], 1.25 per 0.5-point decrease; CI, 1.04 to 1.49; P = .016) and malnutrition (OR, 2.99; CI, 1.36 to 6.58; P = .007).Functional status assessed by the ADL score and malnutrition were independently associated with changes in cancer treatment.
Nasal Staphylococci and Sepsis in Newborn Babies
Authors: P. A. Manfield, R. A. Shooter, O. M. Lidwell
Journal: BMJ (1960)

In Rat-1 fibroblasts, endothelin-1 and a protein kinase C-stimulating phorbol ester stimulated extracellular signal-regulated kinase (ERK), whereas phenylephrine, acting at stably transfected human α<sub>1A</sub>-adrenoceptors, inhibited basal and endothelin-1- and phorbol ester-stimulated ERK. On the other hand, phenylephrine stimulated p38 mitogen-activated protein kinase (MAPK). Anisomycin caused p38 activation and ERK inhibition quantitatively similar to those produced by phenylephrine. SB 203,580, an inhibitor of p38, significantly attenuated phenylephrine- and anisomycin-induced ERK inhibition. The ERK inhibition by phenylephrine was not affected by the cytosolic phospholipase A<sub>2</sub> inhibitor arachidonyltrifluoromethyl ketone or the cyclooxygenase inhibitor indomethacin but was significantly attenuated by a combination of the phosphatase inhibitors Na<sub>3</sub>VO<sub>4</sub> and okadaic acid. Neither SB 203,580 nor the phosphatase inhibitors significantly affected ERK inhibition by the adenylyl cyclase activator forskolin. We conclude that there is a previously unrecognized interaction between ERK and p38 MAPK, in which activation of p38 causes inhibition of ERK; this may at least partly involve MAPK phosphatases that inactivate ERK.
Narcotic Usage
Authors: Norman E. Zinberg, David C. Lewis
Journal: New England Journal of Medicine (1964)

JOE S. is a twenty-four-year-old man who says he is a narcotic addict. He also has hemophilia and has spent twelve of the last thirty-six months in a general hospital. Joe personifies the highly unpleasant elements of a complex and seemingly insoluble social problem. During the same period he spent six months in jail for possession of narcotics and a syringe and two weeks at the narcotic center at Lexington, Kentucky. He has been examined by dozens of doctors, who have spent uncounted hours discussing their findings. His unstable family background, his inability to cope with a crippling disease and . . .
Triple-Reassortant Swine Influenza A (H1) in Humans in the United States, 2005–2009
Authors: Vivek Shinde, Carolyn B. Bridges, Timothy M. Uyeki, Bo Shu, Amanda Balish, Xiyan Xu, Stephen Lindstrom, Larisa V. Gubareva, Varough Deyde, Rebecca J. Garten, Meghan Harris, Susan Gerber, Susan Vagasky, Forrest Smith, Neal Pascoe, Karen Martin, Deborah Dufficy, Kathy Ritger, Craig Conover, Patricia Quinlisk, Alexander Klimov, Joseph S. Bresee, Lyn Finelli
Journal: New England Journal of Medicine (2009)

Triple-reassortant swine influenza A (H1) viruses--containing genes from avian, human, and swine influenza viruses--emerged and became enzootic among pig herds in North America during the late 1990s.We report the clinical features of the first 11 sporadic cases of infection of humans with triple-reassortant swine influenza A (H1) viruses reported to the Centers for Disease Control and Prevention, occurring from December 2005 through February 2009, until just before the current epidemic of swine-origin influenza A (H1N1) among humans. These data were obtained from routine national influenza surveillance reports and from joint case investigations by public and animal health agencies.The median age of the 11 patients was 10 years (range, 16 months to 48 years), and 4 had underlying health conditions. Nine of the patients had had exposure to pigs, five through direct contact and four through visits to a location where pigs were present but without contact. In another patient, human-to-human transmission was suspected. The range of the incubation period, from the last known exposure to the onset of symptoms, was 3 to 9 days. Among the 10 patients with known clinical symptoms, symptoms included fever (in 90%), cough (in 100%), headache (in 60%), and diarrhea (in 30%). Complete blood counts were available for four patients, revealing leukopenia in two, lymphopenia in one, and thrombocytopenia in another. Four patients were hospitalized, two of whom underwent invasive mechanical ventilation. Four patients received oseltamivir, and all 11 recovered from their illness.From December 2005 until just before the current human epidemic of swine-origin influenza viruses, there was sporadic infection with triple-reassortant swine influenza A (H1) viruses in persons with exposure to pigs in the United States. Although all the patients recovered, severe illness of the lower respiratory tract and unusual influenza signs such as diarrhea were observed in some patients, including those who had been previously healthy.
46 INHIBITION OF HGF/C-MET AND NEMO-DEPENDENT SIGNALLINGS PATHWAYS ARE CRUCIAL FOR ENGRAFTMENT AND POSITIVE CELL SELECTION AFTER HEPATOCYTE TRANSPLANTATION
Authors: M. Kaldenbach, D.F. Tschaharganeh, S. Erschfeld, A. Giebeler, K. Chaudhary, C. Birchmeier, C. Liedtke, C. Trautwein, K.L. Streetz
Journal: Journal of Hepatology (2011)