tbuckley/cabot-search huggingface dataset:
Comparative Teratogenic Activity of Cancer Chemopreventive Retinoidal Benzoic Acid Congeners (Arotinoids)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1987)

The benzoic acid derivatives of retinoic acid, often referred to as arotinoids, are synthetic retinoids that possess some of the properties of vitamin A. In general, these retinoids have more favorable therapeutic ratios, based on acute toxicity in adults, than all-trans-retinoic acid in cancer chemoprevention. In the present study, a single dose of (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthalenyl)-1-propen-1-yl]benzoic acid (Ro 13-7410; arotinoic acid), ethyl-(E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8- tetramethyl-2-naphthalenyl)-1-propen-1-yl]benzoate (Ro 13-6298; arotinoid ethyl ester), (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthalenyl)-1-propen-1-yl]phenylmethanol (Ro 13-8320; arotinoic methanol), or (E)-1,2,3,4-tetrahydro-1,1,4, 4-tetramethyl-6-[1-(4-methylphenyl)-1-propen-2-yl]naphthalene (Ro 13-9272; methyl arotinoid) was administered to pregnant Syrian golden hamsters during the early primitive streak stage of gestation. A significant increase in the numbers of litters containing one or more malformed offspring occurred at all doses of each retinoid studied. The types of malformations induced by oral arotinoid treatment were essentially identical to those found after maternal treatment with all-trans-retinoic acid or other teratogenic retinoids during the same gestational age. The results indicate that the alcohol congener was approximately 400 times more potent on a milligram per kilogram basis than all-trans-retinoic acid as a teratogen, and it was 70 times as embryolethal as all-trans-retinoic acid. The ethyl ester congener was 132 times, and the free acid 123 times, as embryolethal as all-trans-retinoic acid. On a molar basis, the arotinoic acid was at least 375 times as teratogenic as all-trans-retinoic acid and at least 140 times as teratogenic as etretinate in hamsters. Because the dose-response curves for arotinoids were significantly parallel to that for all-trans-retinoic acid, and because the spectrum of congenital defects induced by arotinoids was identical to that induced by all-trans-retinoic acid and other teratogenic retinoids, the mechanism of embryopathic action of these conformationally restricted retinoids was concluded to be similar to that of all-trans-retinoic acid.
Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.
Authors: E Canalis, M Centrella, W Burch, T L McCarthy
Journal: Journal of Clinical Investigation (1989)

PTH was studied for its effects on bone formation in cultured rat calvariae. 0.01-10 nM PTH stimulated [3H]thymidine incorporation into DNA by up to 4.8-fold. Although continuous treatment with PTH for 24-72 h inhibited [3H]proline incorporation into collagen, transient (24 h) treatment enhanced [3H]proline incorporation into collagen 24-48 h after the hormone was removed. The collagen stimulated by PTH was type I and the effect was observed in the periosteum-free bone and was not blocked by hydroxyurea. Furthermore, treatment with 1-100 nM PTH for 24 h increased insulin-like growth factor (IGF) I concentrations by two to fourfold, and an IGF I antibody prevented the PTH stimulation of collagen synthesis, but not its mitogenic effect. In conclusion, continuous treatment with PTH inhibits calvarial collagen, whereas transient treatment stimulates collagen synthesis, and the stimulatory effect is mediated by local production of IGF I.
Development of radiological knee osteoarthritis in patients with knee complaints
Authors: B M de Klerk, S Willemsen, D Schiphof, J B J van Meurs, B W Koes, A Hofman, S M A Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2011)

Objectives It is currently impossible to identify which patients with knee complaints presenting to the general practitioner will develop knee osteoarthritis (OA) pathology at a later stage. This study examines the determinants for developing OA pathology on x-ray in patients with knee complaints but no radiological OA at baseline in the painful knee. Methods Data from the prospective Rotterdam cohort study (including subjects aged ≥55 years) were used. Analysis was performed on 623 subjects with knee complaints at baseline and their data at 6-year follow-up (T1; n=607) and at 11-year follow-up (T2; n=457). At baseline, none had radiological OA (rOA=Kellgren and Lawrence (KL) grade ≥2) in the painful joint. At follow-up, predictors for rOA were determined using multivariate ordinal logistic regression analysis. Results At T1, 8.5% of the group had developed knee rOA and, by T2, this had increased to 23%. Determinants remaining significant in the multivariate analysis were female gender (OR 1.95, 95% CI 1.15 to 3.36), other joint complaints (OR 2.22, 95% CI 1.12 to 4.35) and KL grade 1 at baseline in the painful knee joint (OR 7.14, 95% CI 4.55 to 11.1). All outcomes are adjusted for all included determinants. Conclusion The best predictors of development of knee rOA are a combination of female gender, other joint complaints and KL grade 1 in the painful joint. KL grade 1 in combination with knee pain should be considered as early OA in patient management.
Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis
Authors: Cristina Ripoll, Roberto J. Groszmann, Guadalupe Garcia-Tsao, Jaime Bosch, Norman Grace, Andrew Burroughs, Ramon Planas, Angels Escorsell, Juan Carlos Garcia-Pagan, Robert Makuch, David Patch, Daniel S. Matloff
Journal: Journal of Hepatology (2009)
Challenges and opportunities for new medical schools in Africa
Authors: Quentin Eichbaum, Peter Nyarango, Jorge Ferrao, Nonkosi Tlale, Marius Hedimbi, Celso Belo, Kasonde Bowa, Olli Vainio, Johnstone Kumwenda
Journal: The Lancet Global Health (2014)

www.thelancet.com/lancetgh Vol 2 December 2014 e689 schools have “a nervousness about not being seen to conform to Western educational imperatives”. This unease impels these schools to use accreditation systems from developed countries (a trend that has proven lucrative for some American educational organisations). Disfavouring this model, CONSAMS has instead innovated networks of external examiners who monitor assessment and evaluation standards at partner schools and are also developing context-appropriate accreditation standards. The CONSAMS schools have sought to promote health-worker capacitybuilding through interprofessional and transprofessional training programmes. The University of Oulu in Finland has for several years been doing interprofessional programmes with the University of Namibia School of Medicine and the Lurio University Medical School that involves students in medicine, nursing, pharmacology, and optometry working in teams within local communities. The OneStudent-One-Family programme at Lurio also includes community workers in the health-care team and is thus an example of what The Lancet report terms “transprofessional learning”. In conclusion, new medical schools that have decided to work together in consortia such as CONSAMS have strengthened their ability to face challenges and succeeded at educational innovation. The creation of networks, alliances, and consortia between medical schools should be supported as an effective strategy for health-care strengthening and capacity-building in Africa.
Tumors: Too sweet to remember?
Authors: H Peter Vollmers, Stephanie Brändlein
Journal: Molecular Cancer (2007)

Immunity, based on a natural and an educated system, is responsible for recognition and elimination of infectious particles, cellular waste, modified self and transformed cells. This dual system guarantees that dangerous particles are removed immediately after appearance and that a memory with maturated weapons exists, if the organism is re-infected by the same particle. For malignant cells, however, the immune response seems to be restricted to innate immunity, because at least for the humoral response, all so far detected tumor-specific antibodies belong to the natural immunity. In this review we try to explain why malignant cells might be "too sweet" to induce a memory.
Neurological Features and Enzyme Therapy in Patients With Endocrine and Exocrine Pancreas Dysfunction Due to <i>CEL</i> Mutations
Authors: Mette Vesterhus, Helge Ræder, Harald Aurlien, Clara G. Gjesdal, Cecilie Bredrup, Pål I. Holm, Anders Molven, Laurence Bindoff, Arnold Berstad, Pål R. Njølstad
Journal: Diabetes Care (2008)

OBJECTIVE—To further define clinical features associated with the syndrome of diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene and to assess the effects of pancreatic enzyme substitution therapy. RESEARCH DESIGN AND METHODS—Nine patients with CEL gene mutation, exocrine deficiency, and diabetes were treated and followed for 30 months. RESULTS—Treatment improved symptoms in seven of nine patients. Exocrine and endocrine function assessed by fecal elastase and A1C were not affected, although fecal lipid excretion was reduced. Vitamin E was low in all patients but increased with treatment (P &amp;lt; 0.001 at 30 months) and improved in five subjects. A predominantly demyelinating neuropathy was seen in a majority of patients, and carpal tunnel syndrome was common. CONCLUSIONS—Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. Glycemic control was not significantly affected. The CEL syndrome seems associated with a demyelinating neuropathology.
Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients
Authors: C. Johansson, M.H. Sandstrom, J. Bartosik, T. Sarnhult, J. Christiansen, A. Zargari, O. Back, C.F. Wahlgren, J. Faergemann, A. Scheynius, M. Tengvall Linder
Journal: British Journal of Dermatology (2003)

Summary Background The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). Objectives To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. Methods In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). Results Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. Conclusions These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.
Clinical Features of the Initial Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in China
Authors: Bin Cao, Xing-Wang Li, Yu Mao, Jian Wang, Hong-Zhou Lu, Yu-Sheng Chen, Zong-An Liang, Lirong Liang, Su-Juan Zhang, Bin Zhang, Li Gu, Lian-He Lu, Da-Yan Wang, Chen Wang
Journal: New England Journal of Medicine (2009)

The first case of 2009 pandemic influenza A (H1N1) virus infection in China was documented on May 10. Subsequently, persons with suspected cases of infection and contacts of those with suspected infection were tested. Persons in whom infection was confirmed were hospitalized and quarantined, and some of them were closely observed for the purpose of investigating the nature and duration of the disease.During May and June 2009, we observed 426 persons infected with the 2009 pandemic influenza A (H1N1) virus who were quarantined in 61 hospitals in 20 provinces. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection, the clinical features of the disease were closely monitored, and 254 patients were treated with oseltamivir within 48 hours after the onset of disease.The mean age of the 426 patients was 23.4 years, and 53.8% were male. The diagnosis was made at ports of entry (in 32.9% of the patients), during quarantine (20.2%), and in the hospital (46.9%). The median incubation period of the virus was 2 days (range, 1 to 7). The most common symptoms were fever (in 67.4% of the patients) and cough (69.5%). The incidence of diarrhea was 2.8%, and the incidence of nausea and vomiting was 1.9%. Lymphopenia, which was common in both adults (68.1%) and children (92.3%), typically occurred on day 2 (range, 1 to 3) and resolved by day 7 (range, 6 to 9). Hypokalemia was observed in 25.4% of the patients. Duration of fever was typically 3 days (range, 1 to 11). The median length of time during which patients had positive real-time RT-PCR test results was 6 days (range, 1 to 17). Independent risk factors for prolonged real-time RT-PCR positivity included an age of less than 14 years, male sex, and a delay from the onset of symptoms to treatment with oseltamivir of more than 48 hours.Surveillance of the 2009 H1N1 virus in China shows that the majority of those infected have a mild illness. The typical period during which the virus can be detected with the use of real-time RT-PCR is 6 days (whether or not fever is present). The duration of infection may be shortened if oseltamivir is administered.
Three cases of idiopathic pleuroparenchymal fibroelastosis associated with amyotrophic lateral sclerosis
Authors: Shinobu Akagawa, Ryota Sato, Kennichi Okuda, Kazuya Koyama, Masahiro Shimada, Kimihiko Masuda, Hirotosi Matsui, Ken Ohta
Journal: European Respiratory Journal (2014)

Introduction:  In Japanese cases of idiopathic pleuroparenchymal fibroelastosis (IPPFE), radiological abnormalities are mostly localized in the bilateral upper lobes. With disease progression, patients may complain severe dyspnea and lose much weight like neuromuscular diseases. We reported and discussed about the clinical features of 3 patients clinically diagnosed as IPPFE associated with amyotrophic lateral sclerosis (ALS).   Report:  At the time of diagnosis of IPPFE, patients were 49-yr-old (male, Case 1), 53-yr-old (female, Case 2), and 63-yr-old (male, Case 3). Symptoms including severe dyspnea, tachypnea, severe atrophy around upper chest wall, dysphagia, articulation disorder appeared 2 years after the diagnosis in Case 1, 4 years in Case 2, and 7 years in Case 3. As they had no muscular dysfunctions in extremities at the time, diagnosis of ALS was denied in consultation with neurologists then in spite of the bulbar palsy. Diagnosis of ALS was confirmed when their symptoms and signs progressed 6 months after in Case 1, 2 years in Case 2, and 6 months in Case 3. At the onset of ALS, PaCO 2  / PaO 2  were 50 torr / 92 torr in Case 1, 48/ 82 in Case 2, and 50 / 98 in Case 3. Body mass indices at the onset of IPPFE were 14.4 in Case 1, 17.2 in Case 2, and 18.8 in Case 3, and they were further decreased at the onset of ALS.   Discussion:  All 3 patients of IPPFE associated with ALS presented initial symptoms caused from weakness of respiratory muscles and bulbar palsy which are not typical in the early stage of ALS. A patient of IPPFE who exhibits bulbar palsy and severe dyspneic sensation inappropriate for pulmonary lesion should be suspected of the association with ALS.
miRNA-17 and -144 regulate cAMP-responsive element binding protein (CREB1) signaling in murine ovalbumin-induced asthma and in human bronchial epithelial cells
Authors: Sabine Bartel, Francesca Alessandrini, Oliver Eickelberg, Susanne Krauss-Etschmann
Journal: European Respiratory Journal (2012)

Background: MicroRNAs (miRs) are small non-coding RNAs that are essential for immune function and lung development. They are influenced by environmental exposures such as smoke or nutrition, both of which are also known to affect asthma risk development. Previously, we reported increased pulmonary expression of miR-17 and -144 in mice with OVA-induced asthma. This correlated with decreased mRNA and protein levels of CREB1, a validated target of both miRs. In addition, the cAMP-regulated transcriptional co-activators, CRTC-1 and -3, have been described to enhance CREB1-mediated gene transcription (Altarejos et al. , Nat Rev Mol Cell Biol., 2011, 12) and are also predicted targets of miR-17 and -144. Thus,we hypothesized that miR-17 and -144 regulate CREB1/CRTC-mediated gene transcription in experimental asthma and sought to elucidate this interdependency in vitro .

Methods: Human bronchial epithelial cells (16HBE) were transfected with precursor miRs or antagomiRs for miR-17 and miR-144. The expression of miR and endogenous CREB1, CRTC-1, -2, and -3 was assessed by RT-qPCR and Western blot analysis.

Results: The mRNA levels of CRTC-1 and -3, but not CRTC-2 in the lung were decreased in OVA-induced murine asthma. In 16HBE cells, the mRNA and protein levels of CREB1 and the mRNA levels of its co-activators CRTC-1,-2, and -3 were significantly decreased after transfection with precursor miR-17 and -144. Vice versa, their expression increased after inhibition of miRs by antagomiRs.

Conclusion: These findings suggest a role for microRNA-17 and -144 in the regulation of CREB1/CRTC signaling of potential relevance in asthma.
Lower Respiratory Viral Illnesses
Authors: Jorge Garbino, Margaret W. Gerbase, Werner Wunderli, Christelle Deffernez, Yves Thomas, Thierry Rochat, Beatrice Ninet, Jacques Schrenzel, Sabine Yerly, Luc Perrin, Paola M. Soccal, Laurent Nicod, Laurent Kaiser
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We assessed the frequency and the potential role of respiratory viruses on disease outcomes in hospitalized patients and lung transplant recipients who underwent a bronchoalveolar lavage (BAL) for an acute respiratory infection. BAL specimens (148) were analyzed by reverse transcription-polymerase chain reaction for the presence of 11 different viruses, as well as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Respiratory viruses were identified in 34 of 117 BAL specimens (29%) obtained in patients with a suspected respiratory infection and in only 2 of 31 control subjects (7%) (p < 0.01). M. pneumoniae was identified in five additional cases. Only 30% of cases that were virus positive by molecular methods were also positive by cell culture analysis. Rhinovirus was the most frequently identified virus (56% of cases) followed by respiratory syncytial virus (27%). In lung transplant recipients, the rate of viral infections was 55% in cases with respiratory symptoms compared with only 4% in control subjects (p < 0.001). In these cases, respiratory viral infections were associated with significant lung function abnormalities. By using reverse transcription-polymerase chain reaction assays, we frequently identified respiratory viruses in BAL specimens of patients hospitalized with lower respiratory tract infections. These viruses were associated with high morbidity, particularly in lung transplant recipients.
Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial
Authors: William J Marks, Raymond T Bartus, Joao Siffert, Charles S Davis, Andres Lozano, Nicholas Boulis, Jerrold Vitek, Mark Stacy, Dennis Turner, Leonard Verhagen, Roy Bakay, Raymond Watts, Barton Guthrie, Joseph Jankovic, Richard Simpson, Michele Tagliati, Ron Alterman, Matthew Stern, Gordon Baltuch, Philip A Starr, Paul S Larson, Jill L Ostrem, John Nutt, Karl Kieburtz, Jeffrey H Kordower, C Warren Olanow
Journal: The Lancet Neurology (2010)
Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary β2-adrenergic receptor gene delivery
Authors: John P. Maurice, Jonathan A. Hata, Ashish S. Shah, David C. White, Patricia H. McDonald, Paul C. Dolber, Katrina H. Wilson, Robert J. Lefkowitz, Donald D. Glower, Walter J. Koch
Journal: Journal of Clinical Investigation (1999)

Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function can be realized, efficient and reproducible in vivo gene techniques must be established to efficiently transfer transgenes globally to the myocardium. We have been testing the hypothesis that genetic manipulation of the myocardial β-adrenergic receptor (β-AR) system, which is impaired in HF, can enhance cardiac function. We have delivered adenoviral transgenes, including the human β2-AR (Adeno-β2AR), to the myocardium of rabbits using an intracoronary approach. Catheter-mediated Adeno-β2AR delivery produced diffuse multichamber myocardial expression, peaking 1 week after gene transfer. A total of 5 × 1011 viral particles of Adeno-β2AR reproducibly produced 5- to 10-fold β-AR overexpression in the heart, which, at 7 and 21 days after delivery, resulted in increased in vivo hemodynamic function compared with control rabbits that received an empty adenovirus. Several physiological parameters, including dP/dtmax as a measure of contractility, were significantly enhanced basally and showed increased responsiveness to the β-agonist isoproterenol. Our results demonstrate that global myocardial in vivo gene delivery is possible and that genetic manipulation of β-AR density can result in enhanced cardiac performance. Thus, replacement of lost receptors seen in HF may represent novel inotropic therapy.
Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin–paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002)
Authors: A. Inoue, K. Kobayashi, M. Maemondo, S. Sugawara, S. Oizumi, H. Isobe, A. Gemma, M. Harada, H. Yoshizawa, I. Kinoshita, Y. Fujita, S. Okinaga, H. Hirano, K. Yoshimori, T. Harada, Y. Saijo, K. Hagiwara, S. Morita, T. Nukiwa
Journal: Annals of Oncology (2012)
Growth hormone increases the proliferation of existing cardiac myocytes and the total number of cardiac myocytes in the rat heart
Authors: A BRUEL, T CHRISTOFFERSEN, J NYENGAARD
Journal: Cardiovascular Research (2007)

Objective Growth hormone (GH) is known to induce growth of the normal rat heart. Whether this growth is due solely to hypertrophy of the cardiac myocytes or whether a concomitant hyperplasia of the cardiac myocytes also takes place is currently not known. Therefore, the aim of the present study was to investigate whether GH induces hyperplasia in the left ventricle (LV) of sexually mature rats.