tbuckley/cabot-search huggingface dataset:
Jab1 regulates Schwann cell proliferation and axonal sorting through p27
Authors: Emanuela Porrello, Cristina Rivellini, Giorgia Dina, Daniela Triolo, Ubaldo Del Carro, Daniela Ungaro, Martina Panattoni, Maria Laura Feltri, Lawrence Wrabetz, Ruggero Pardi, Angelo Quattrini, Stefano Carlo Previtali
Journal: The Journal of Experimental Medicine (2013)

Axonal sorting is a crucial event in nerve formation and requires proper Schwann cell proliferation, differentiation, and contact with axons. Any defect in axonal sorting results in dysmyelinating peripheral neuropathies. Evidence from mouse models shows that axonal sorting is regulated by laminin211- and, possibly, neuregulin 1 (Nrg1)-derived signals. However, how these signals are integrated in Schwann cells is largely unknown. We now report that the nuclear Jun activation domain-binding protein 1 (Jab1) may transduce laminin211 signals to regulate Schwann cell number and differentiation during axonal sorting. Mice with inactivation of Jab1 in Schwann cells develop a dysmyelinating neuropathy with axonal sorting defects. Loss of Jab1 increases p27 levels in Schwann cells, which causes defective cell cycle progression and aberrant differentiation. Genetic down-regulation of p27 levels in Jab1-null mice restores Schwann cell number, differentiation, and axonal sorting and rescues the dysmyelinating neuropathy. Thus, Jab1 constitutes a regulatory molecule that integrates laminin211 signals in Schwann cells to govern cell cycle, cell number, and differentiation. Finally, Jab1 may constitute a key molecule in the pathogenesis of dysmyelinating neuropathies.
Clearing of cells bearing the bcl-2 [t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy
Authors: M.S. Czuczman, A.J. Grillo-López, P. McLaughlin, C.A. White, M. Saleh, L. Gordon, A.F. LoBuglio, J. Rosenberg, B. Alkuzweny, D. Maloney
Journal: Annals of Oncology (2001)
THE RELATION OF HOUSING TO BEHAVIOR DISORDER
Authors: E. A. GROOTENBOER
Journal: American Journal of Psychiatry (1962)

Clinical experience has left the impression that housing situation of the nuclear family is related to the behavioral health of the children. Cases of varying degrees of typicalness are briefly presented to illustrate this situation. It remains to be seen how important and separable a factor this may be and to what extent it is important as an etiological factor. It is hoped that having called the situation to attention more may be done to see that the child is protected from any ill effects.
OCT in bronchoscopic diagnosis and treatment of preinvasive endobronchial lesions
Authors: Carlos Disdier Vicente, Dagoberto Bejarano Ugalde, Hipólito Gutiérrez García, María Henar Borrego Pintado, Jose María Matilla González, Rafael López Castro
Journal: European Respiratory Journal (2013)

Introduction: Optical coherence tomography (OCT) is an imaging technique that can offer high resolution and real-time axial images of cellular microstructure at and below tissue surface. The objective of the study was to determine the usefulness of this technique in the bronchoscopic study of carcinoma in situ and severe dysplasia and its role in deciding endoscopic treatment with curative intent in early central bronchogenic carcinoma (Stage 0 or IA).  Methods: In all patients with suspected early lung cancer was performed an usual study that included a chest CT scan, PET/CT and autofluorescence bronchoscopy (AFB). Upon inspection by AFB, an OCT was performed by inserting a probe into the working channel of the bronchoscope. Were recorded lesion characteristics, the wall thickness and length. After OCT, a biopsy with forceps or cryo probe was taken in the same procedure.  Results: We studied 7 patients with 11 endobronchial preinvasive lesions. Initial indication for bronchoscopy was pneumonia (2), pulmonary nodule or mass (2), periodic review after lung cancer surgery (2) and hemoptysis (1). In nine lesions were detected structural changes and thickening of the mucosa between 0.28 to 0.73 mm for carcinoma in situ and 0.36 to 0.59 mm for moderate or severe dysplasia. Two carcinomas in situ were not detected by OCT; one of those previously treated with cryotherapy without visible lesions after previous biopsy.  Conclusions: OCT combined with AFB is a useful technique to select candidates for endoscopic treatment with curative intent and evaluating degree of depth invasion into the mucosa. Suspecting preinvasive endobronchial lesion should be performed an OCT before biopsy or endoscopic treatment.
Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial
Authors: Masashi Mizokami, Osamu Yokosuka, Tetsuo Takehara, Naoya Sakamoto, Masaaki Korenaga, Hitoshi Mochizuki, Kunio Nakane, Hirayuki Enomoto, Fusao Ikeda, Mikio Yanase, Hidenori Toyoda, Takuya Genda, Takeji Umemura, Hiroshi Yatsuhashi, Tatsuya Ide, Nobuo Toda, Kazushige Nirei, Yoshiyuki Ueno, Yoichi Nishigaki, Juan Betular, Bing Gao, Akinobu Ishizaki, Masa Omote, Hongmei Mo, Kim Garrison, Phillip S Pang, Steven J Knox, William T Symonds, John G McHutchison, Namiki Izumi, Masao Omata
Journal: The Lancet Infectious Diseases (2015)
Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma
Authors: Steven G. DuBois, Susan Groshen, Julie R. Park, Daphne A. Haas-Kogan, Xiaodong Yang, Ethan Geier, Eugene Chen, Kathy Giacomini, Brian Weiss, Susan L. Cohn, M. Meaghan Granger, Gregory A. Yanik, Randall Hawkins, Jesse Courtier, Hollie Jackson, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, Denice Tsao-Wei, Judith G. Villablanca, Araz Marachelian, Katherine K. Matthay
Journal: Clinical Cancer Research (2015)

(131)I-metaiodobenzylguanidine (MIBG) is a radiopharmaceutical with activity in neuroblastoma. Vorinostat is a histone deacetylase inhibitor that has radiosensitizing properties. The goal of this phase I study was to determine the MTDs of vorinostat and MIBG in combination.Patients ≤ 30 years with relapsed/refractory MIBG-avid neuroblastoma were eligible. Patients received oral vorinostat (dose levels 180 and 230 mg/m(2)) daily days 1 to 14. MIBG (dose levels 8, 12, 15, and 18 mCi/kg) was given on day 3 and peripheral blood stem cells on day 17. Alternating dose escalation of vorinostat and MIBG was performed using a 3+3 design.Twenty-seven patients enrolled to six dose levels, with 23 evaluable for dose escalation. No dose-limiting toxicities (DLT) were seen in the first three dose levels. At dose level 4 (15 mCi/kg MIBG/230 mg/m(2) vorinostat), 1 of 6 patients had DLT with grade 4 hypokalemia. At dose level 5 (18 mCi/kg MIBG/230 mg/m(2) vorinostat), 2 patients had dose-limiting bleeding (one grade 3 and one grade 5). At dose level 5a (18 mCi/kg MIBG/180 mg/m(2) vorinostat), 0 of 6 patients had DLT. The most common toxicities were neutropenia and thrombocytopenia. The response rate was 12% across all dose levels and 17% at dose level 5a. Histone acetylation increased from baseline in peripheral blood mononuclear cells collected on days 3 and 12 to 14.Vorinostat at 180 mg/m(2)/dose is tolerable with 18 mCi/kg MIBG. A phase II trial comparing this regimen to single-agent MIBG is ongoing.
Boxing and the brain
Authors: P McCrory
Journal: British Journal of Sports Medicine (2002)

Revisiting chronic traumatic encephalopathy

Chronic traumatic brain injury or chronic traumatic encephalopathy (CTE) is considered by some authorities to be the most serious health problem in modern day boxing.1 The condition is often referred to by a number of names in the medical and non-medical literature including dementia pugilistica and “punch drunk” syndrome.

Whilst there exists great controversy regarding the ethics of boxing, one of the key medical issues is the risk of a boxer developing CTE either during or after his boxing career. Recent evidence suggests that exposure to boxing alone is insufficient to cause this condition.

It is believed that CTE represents the cumulative long term neurological consequences of repetitive concussive and sub concussive blows to the head.1–4 CTE is more common in professional rather than amateur boxers, however, CTE has been documented in other sports such as American Football, ice …
Effects of chest compression on secretion removal, lung mechanics, and gas exchange in mechanically ventilated patients: a crossover, randomized study
Authors: Elaine Cristina Gonçalves, Hugo C. D. Souza, Joana Tambascio, Marcelo Barros Almeida, Anibal Basile Filho, Ada Clarice Gastaldi
Journal: Intensive Care Medicine (2015)
Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance
Authors: K L Winthrop, S A Novosad, J W Baddley, L Calabrese, T Chiller, P Polgreen, F Bartalesi, M Lipman, X Mariette, O Lortholary, M E Weinblatt, M Saag, J Smolen
Journal: Annals of the Rheumatic Diseases (2015)

No consensus has previously been formed regarding the types and presentations of infectious pathogens to be considered as 'opportunistic infections' (OIs) within the setting of biologic therapy. We systematically reviewed published literature reporting OIs in the setting of biologic therapy for inflammatory diseases. The review sought to describe the OI definitions used within these studies and the types of OIs reported. These findings informed a consensus committee (infectious diseases and rheumatology specialists) in deliberations regarding the development of a candidate list of infections that should be considered as OIs in the setting of biologic therapy. We reviewed 368 clinical trials (randomised controlled/long-term extension), 195 observational studies and numerous case reports/series. Only 11 observational studies defined OIs within their methods; no consistent OI definition was identified across studies. Across all study formats, the most numerous OIs reported were granulomatous infections. The consensus group developed a working definition for OIs as 'indicator' infections, defined as specific pathogens or presentations of pathogens that 'indicate' the likelihood of an alteration in host immunity in the setting of biologic therapy. Using this framework, consensus was reached upon a list of OIs and case-definitions for their reporting during clinical trials and other studies. Prior studies of OIs in the setting of biologic therapy have used inconsistent definitions. The consensus committee reached agreement upon an OI definition, developed case definitions for reporting of each pathogen, and recommended these be used in future studies to facilitate comparison of infection risk between biologic therapies.
The contractile state of cat and dog heart in relation to the interval between beats.
Authors: J Pidgeon, M Lab, A Seed, G Elzinga, D Papadoyannis, M I Noble
Journal: Circulation Research (1980)

We induced atrioventricular dissociation and initiated ventricular pacing in intact dogs and isolated cat hearts. Left ventricular pressure, its time derivative (dP/t), and action potentials were recorded. When a test pulse was introduced at varying intervals after a period of steady pacing, an optimum contractile response was obtained at an average interval of 720 msec. A similar optimum interval was obtained after pacing at various frequencies and after paired pulse stimulation but was shortened to 560 msec after infusion of epinephrine. The magnitude of the optimum contractile response increased with an increase in the frequency of prior pacing which was accompanied by an increase in the time the cell membrane was depolarized. The optimum contractile response following paired pulse stimulation was greater than that following regular pacing, with the same number of stimuli per minute and the same time of membrane depolarization. The results are explicable in terms of intracellular calcium ion recirculation with separate compartments for release to and uptake from the contractile proteins. A negative feedback control of Ca2+ inflow to the cell by intracellular Ca2+ content is postulated to explain the effect of paired pulse stimulation and shortening of action potential duration following an increase in regular pacing frequency.
Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Philip L. Molyneaux, Patrick Mallia, Michael J. Cox, Joseph Footitt, Saffron A. G. Willis-Owen, Daniel Homola, Maria-Belen Trujillo-Torralbo, Sarah Elkin, Onn Min Kon, William O. C. Cookson, Miriam F. Moffatt, Sebastian L. Johnston
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rhinovirus infection is followed by significantly increased frequencies of positive, potentially pathogenic sputum cultures in chronic obstructive pulmonary disease (COPD). However, it remains unclear whether these represent de novo infections or an increased load of organisms from the complex microbial communities (microbiome) in the lower airways.To investigate the effect of rhinovirus infection on the airway bacterial microbiome.Subjects with COPD (n = 14) and healthy control subjects with normal lung function (n = 17) were infected with rhinovirus. Induced sputum was collected at baseline before rhinovirus inoculation and again on Days 5, 15, and 42 after rhinovirus infection and DNA was extracted. The V3-V5 region of the bacterial 16S ribosomal RNA gene was amplified and pyrosequenced, resulting in 370,849 high-quality reads from 112 of the possible 124 time points.At 15 days after rhinovirus infection, there was a sixfold increase in 16S copy number (P = 0.007) and a 16% rise in numbers of proteobacterial sequences, most notably in potentially pathogenic Haemophilus influenzae (P = 2.7 × 10(-20)), from a preexisting community. These changes occurred only in the sputum microbiome of subjects with COPD and were still evident 42 days after infection. This was in contrast to the temporal stability demonstrated in the microbiome of healthy smokers and nonsmokers.After rhinovirus infection, there is a rise in bacterial burden and a significant outgrowth of Haemophilus influenzae from the existing microbiota of subjects with COPD. This is not observed in healthy individuals. Our findings suggest that rhinovirus infection in COPD alters the respiratory microbiome and may precipitate secondary bacterial infections.
A Life of Adventure in Immunobiology
Authors: Max D. Cooper
Journal: Annual Review of Immunology (2009)

This article outlines my early start in medicine, a late start in immunology research, and my efforts to integrate the two activities. I first describe some of the background information, excitement, and implications of the recognition of T and B cells as separate but functionally intertwined arms of the adaptive immune system. The article continues with a brief account of my colleagues' and my efforts to use the model of hematopoietic stem cell differentiation along T and B cell lines to gain a better understanding of immunodeficiency diseases and lymphoid malignancies. It concludes with the discovery of a more ancient adaptive immune system in which T-like and B-like cells in jawless vertebrates use variable lymphocyte receptors constructed with leucine-rich-repeat sequences to recognize antigens.
One Year After Discharge: Community Adjustment of Schizophrenic Patients
Authors: NINA R. SCHOOLER, SOLOMON C. GOLDBERG, HELVI BOOTHE, JONATHAN O. COLE
Journal: American Journal of Psychiatry (1967)

From a group of 299 schizophrenic patients discharged after a study of short-term drug action, 254 were living in the community a year following initial discharge from the hospital. These expatients were evaluated to assess their community adjustment and to determine the relationship between aspects of each individual's premorbid history and course of illness with subsequent community adjustment. While most of the expatients were functioning at a social level comparable to their own "best former" level, only 11 percent could be described as functioning as well as the average person in the community. A number of background, psychiatric history, and environmental factors were found to be related to community adjustment; of these, the characteristics of the environment to which the patient was discharged seemed especially significant.
Level of chronic life stress predicts clinical outcome in irritable bowel syndrome
Authors: E J Bennett, C C Tennant, C Piesse, C-A Badcock, J E Kellow
Journal: Gut (1998)

Life stress contributes to symptom onset and exacerbation in the majority of patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD); research evidence is conflicting, however, as to the strength of these effects.To test prospectively the relation of chronic life stress threat to subsequent symptom intensity over time.One hundred and seventeen consecutive outpatients satisfying the modified Rome criteria for IBS (66% with one or more concurrent FD syndromes) participated.The life stress and symptom intensity measures were determined from interview data collected independently at entry, and at six and 16 months; these measures assessed the potency of chronic life stress threat during the prior six months or more, and the severity and frequency of IBS and FD symptoms during the following two weeks.Chronic life stress threat was a powerful predictor of subsequent symptom intensity, explaining 97% of the variance on this measure over 16 months. No patient exposed to even one chronic highly threatening stressor improved clinically (by 50%) over the 16 months; all patients who improved did so in the absence of such a stressor.The level of chronic life stress threat predicts the clinical outcome in most patients with IBS/FD.
Interferon gamma receptor 2 gene variants are associated with liver fibrosis in the general population: the Rotterdam Study
Authors: Elisabeth P C Plompen, Bettina E Hansen, Jeoffrey N L Schouten, Sarwa Darwish Murad, Daan W Loth, Willem Pieter Brouwer, Aaron Isaacs, Pavel Taimr, Albert Hofman, Cornelia M van Duijn, André G Uitterlinden, Bruno H C Stricker, Frank W G Leebeek, Harry L A Janssen
Journal: Gut (2014)

Dear Editor,

Increasing evidence suggests that genetic factors play a role in the multifactorial aetiology of liver fibrosis. In their recent paper, Zhao et al 1 support this by describing the role of the Jnk1 gene in liver fibrogenesis. Previously, the role of other inflammatory-related genes in the development of liver fibrosis has been described in patients with chronic liver diseases. In patients with chronic hepatitis C, Nalpas et al 2 demonstrated a strong association between single nucleotide polymorphisms (SNP) in the interferon gamma receptor 2 ( IFNGR2 ) gene and progression of liver fibrosis. The role of interferon gamma in liver fibrogenesis has been reported before, but the precise mechanism of this effect has not yet been fully elucidated.3 ,4 Currently, it is not known whether the genetic variants in the IFNGR2 gene also influence liver fibrogenesis in individuals without liver disease. Therefore, we aimed to study the association between the IFNGR2 SNPs and liver fibrosis in the general population.

For this purpose, we assessed the extent of liver fibrosis non-invasively by measuring liver stiffness (LS) using transient elastography (TE) (Fibroscan, Echosens) in 1059 participants of the Rotterdam study. Genotyping in these, almost exclusively Caucasian (99.6%) participants was performed with the Infinium II HumanHap 550K Genotyping Bead-Chip V.3 (Illumina, San Diego, California, USA). The Rotterdam Study is a large, ongoing, prospective population-based cohort study in subjects aged ≥55 years in …
THE EVEREST II REALISM CONTINUED ACCESS STUDY: EFFECTIVENESS OF TRANSCATHETER REDUCTION OF SIGNIFICANT MITRAL REGURGITATION IN SURGICAL CANDIDATES
Authors: Saibal Kar, D. Lim, Richard Smalling, Brian Whisenant, Chidambaram Rammohan, Peter Fail, Michael Rinaldi, James Hermiller, Howard Herrmann, Robert Kipperman, John Williams, Carlos Ruiz, William Gray, James Slater, Neil Weissman, Elyse Foster, Ted Feldman
Journal: Journal of the American College of Cardiology (2013)
Bone marrow engraftment in a rodent model of chemical carcinogenesis but no role in the histogenesis of hepatocellular carcinoma
Authors: H Ishikawa
Journal: Gut (2004)

Recent studies indicated that hepatic stem cells in the bone marrow could differentiate into mature hepatocytes, suggesting that bone marrow cells could be used for replacement of damaged hepatocytes in a variety of liver diseases. Hepatocellular carcinoma (HCC) is thought to arise from hepatic stem cells. In this study, we investigated the malignant potential of hepatic stem cells derived from the bone marrow in a mouse model of chemical hepatocarcinogenesis.Bone marrow cells were obtained from the male beta-galactosidase (beta-gal) transgenic mouse and transplanted into female recipient mice. Hepatocarcinogenesis was induced by a year of treatment with diethylnitrosamine and phenobarbital (NDEA/PB). One year later, the liver was removed from each treated mouse and evaluated by x-gal staining, immunohistochemistry, and fluorescence in situ hybridisation (FISH).Forty per cent of recipient mice survived and developed multiple HCC. Clusters of beta-gal positive mature hepatocytes were detected sporadically in the entire liver of NDEA/PB treated mice who underwent bone marrow transplantation (BMT) with while no such hepatocytes were identified in the liver of BMT mice that were not treated with NDEA/PB. The Y chromosome was detected with the same frequency as the donor male liver in clusters of beta-gal positive mature hepatocytes by FISH. However, no HCC was positive for beta-gal or the Y chromosome. Immunohistochemically, beta-gal positive mature hepatocytes did not express CD34 or alpha-fetoprotein.Our results suggest that hepatic stem cells derived from the bone marrow have low malignant potential, at least in our model.
A Case of Pneumonia, Occurring at a Cold High Altitude
Authors: A. T. Wise
Journal: BMJ (1886)

r"Ni "M i4w.t; lee of tkenipplo .nfIotU,;ad,tulpwsr Of *,~piuJehiud.with flA-4 eit ion.Therws lvidity o the fq,S,.iIpp.-Tape~at¢r?i pulse 8.re tns 8.O1 Zn X aIteVrnwon,them w rz tte ehae, and the av hured epu tIps wera most ontirely b hil Blood to the extent of eight or t qo. was take from the arm.This was foUowed by marked iiiproveat in the puse ; the respirations fell -to 62 ; and the patient flt V0. essler, ani slot a little.The temperature remaed at 10L.8'.SeptembR 4th The patie,t d rested well during the n$ght.Toepratwr 9&.4', pulse 98, repirations 40..The physiaml sigus re- mained the same as those of the previous day.In the evening, the pu2ae was 88, temperature 98,4', irations 32..There were dulIes and bronchial breathing, with a few loaud rdla and friction-sund on the left side; small crepitation, with bronchial breathing, on the right The sputum continued rusty and tenacious.September 6th.Morning: pulse 92, temperature 98.40, respirations 40.Dulness was not diiniihed.Crepitatio redux was heard.Evening: pulse 88, temperature, 98.4', respirations 26.September 7th.Pulse 80, re- spirtions 32, temperature 98.4'.Evening: pulse 76, temperature 98.4, respirtions 32.September 8th