tbuckley/cabot-search huggingface dataset:
Influence of acid sphingomyelinase deficiency in a murine model of allergen-induced asthma
Authors: Eva Verjans, Dieter Adam, Christian Martin, Stefan Uhlig
Journal: European Respiratory Journal (2011)

Introduction:  Acid sphingomyelinase (ASM) deficency causes lipid storage diseases, called Niemann-Pick-disease (NPD) type A (neuronopathic) and B (non-neuronopathic). Previous studies demonstrated an association of NPD type B with respiratory failure and lung infections. We investigated the role of ASM deficiency in a murine model of allergic asthma.   Method:  Male C57BL/6 (WT) and ASM knockout mice (ASM-KO) were intraperitoneally sensitized with ovalbumin (OVA)/Alum (10μg/1.5mg) on days 0, 14 and 21. Repeated aerosol challenges (1% OVA) followed for five weeks on two consecutive days every week. Bronchoalveolar lavage (BAL), serum and lung tissue were taken for cell counts, cytokine measurements, histology slides and calculation of wet/dry-ratio. Precision-cut lung slices (PCLS) were prepared to investigate early asthmatic response (EAR).   Results:  Edema formation was less in ASM-KO (73.6±7.6%) compared to WT. In addition, sensitized ASM-KO showed significantly higher cell numbers in BAL and lung tissue primarily consisting of neutrophils and enlarged macrophages, whereas numbers of eosinophils were similar. The ratio of eosinophils and neutrophils was characteristic of a typical Th1-pattern. Differences in cytokine and IgE-levels in BAL and serum were not found. OVA stimulation of PCLS from both mouse strains resulted in a weak bronchoconstriction.   Conclusion:  ASM-KO showed the typical characteristics of NPD, but their allergic inflammation was similar to that of WT mice, except for an increased neutrophil/eosinophil ratio. The major observation was reduced edema formation in ASM-KO mice. We conclude that ASM contributes to allergic edema formation, a key feature of asthma.
Prevalence of Intraepithelial Carcinoma of the Cervix in the Early Years of Marriage&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Frank E. Lundin, Cyrus C. Erickson
Journal: JNCI Journal of the National Cancer Institute (1965)

There was a deficiency of intraepithelial carcinoma of the cervix in the early years of marriage among a group of white women who participated in a large cytologie survey. This finding, which may indicate the presence of an induction period in intraepithelial carcinoma, is consistent with other studies suggesting that cervical cancer is etiologically related to sexual activity. The nature of the postulated causal factor(s) is unknown.
Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study
Authors: Elias Jabbour, Hagop Kantarjian, Farhad Ravandi, Deborah Thomas, Xuelin Huang, Stefan Faderl, Naveen Pemmaraju, Naval Daver, Guillermo Garcia-Manero, Koji Sasaki, Jorge Cortes, Rebecca Garris, C Cameron Yin, Joseph D Khoury, Jeffrey Jorgensen, Zeev Estrov, Zachary Bohannan, Marina Konopleva, Tapan Kadia, Nitin Jain, Courtney DiNardo, William Wierda, Vicky Jeanis, Susan O'Brien
Journal: The Lancet Oncology (2015)
Easing Cancer Chemotherapy Effects
Authors: Rebecca Voelker
Journal: JAMA (2015)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Abstract 1459: Connexin 43 Hemi Channels are Permeable to Exogenously Added NAD: Implications in Protection of Cardiomyocytes against PARP-mediated Cell Death
Authors: Vinodkumar B Pillai, Jyothish B Pillai, Senthilkumar Rajamohan, Madhu Gupta, Jai Raman, Mahesh P Gupta
Journal: Circulation (2007)

Robust activation of poly (ADP ribose) polymerase-1 (PARP) following oxidative stress and DNA damage is a major cause of caspase independent cardiomyocyte cell death. PARP-mediated cell-death is associated with cellular NAD depletion. Connexin 43 (Cx43) is a major gap junction protein which forms hemi channels in cardiomyocytes. This study was designed to investigate whether exogenously added NAD can enter into cardiomyocytes via Cx43 hemi channels, and protect cells from PARP-mediated cell death. Primary cultures of neonatal rat heart myocytes were treated at various time points with a free-radical generating mixture of H 2 O 2 and FeSO4 (0.1mM each). To examine permeability of cells to NAD, myocytes were treated with FITC-tagged-NAD (NAD-FITC) and intracellular localization of NAD was determined by confocal microscopy. We found that following oxidative stress myocyte cell death was proportionally related to intensity of PARP activation and NAD depletion. In these cells with PARP activation, exogenously added NAD-FITC (green) readily entered into the cell interior. This NAD transport was abolished when myocytes were treated with gap junction blockers such as carbenoxolone or 18β-glycyrrhetinic acid. To further confirm a role of Cx43 in NAD transport, we utilized HeLa cells in which Cx43 was either epigenetically silenced or constitutively over expressed. We found that HeLa cells lacking Cx43 had no NAD transport activity, while cells over expressing Cx43 showed abundant entry of NAD into the cells, thus validating a role of Cx43 in cellular NAD transport. Addition of NAD into culture media prior to PARP activation also rescued cells from PARP-mediated cell death. Cellular NAD levels are known to control the activity of the longevity factor SIRT1 deacetylase. To test if SIRT1 could be involved in mediating the beneficial effects of NAD, we did an identical cell death experiment with myocytes in which SIRT1 levels were reduced 50% by siRNA silencing. In these cells we found no beneficial effect of NAD following oxidative stress, thus indicating that SIRT1 is taking part in cell survival effects of NAD. These results demonstrate that exogenously added NAD can enter into cardiomyocytes via Cx43 hemi channels and protect cells against PARP-mediated cell death.
The profile of dendritic cell and T cell response is related to the viral trigger in children with severe asthma exacerbation
Authors: Clémence Mordacq, Antoine Deschildre, Isabelle Tillie-Leblond, Anny Dewilde, Muriel Pichavant, Caroline Thumerelle, David Romero, Philippe Gosset
Journal: European Respiratory Journal (2012)

Viral infection are associated with asthma exacerbations (AE). Activation of dendritic cells (DC) plays a key role in the response to virus and drives the activation and polarization of T cells. Mobilization of Pattern Recognition Receptor (PRR): Toll Like Receptor (TLR3), RNA helicases (RIG-I, MDA-5) are involved. Our purpose was to analyze expression and function of the PRR in DC and to corroborate this with the presence of virus and the T cell response.   Methods:  54 allergic asthmatic children (6-15 y) included during hospitalization for severe AE. Virus identified on nasal secretions by RT-PCR. T cell response determined in blood and induced sputum at the inclusion and in the stable state, 8 weeks later. Mononuclear cells (MNC) stimulated  in vitro  with poly(IC) and liposomes containing poly(IC) and levels of IL-4, IFN-g, IL-17A measured. Expression of markers of maturation (CD80, CD86) and PRR studied in circulating DC by flow cytometry.   Results:  Virus were indentified in 60 % (Rhinovirus: 82 %). A Th1 and Th17 (IFNg, IL17A) response was observed in the airways and the blood from the infected patients (V+) during exacerbation whereas a Th2 (IL-4) response prevailed in non-infected patients (V-). The stimulation of MNC induced a Th2 and Th17 response for V+ at inclusion, but Th1 in V-. A defect in RNA helicases expression by blood DC was observed in V+ at inclusion, while the expression of the markers of maturation did not differ among both groups.   Conclusion:  Viral infection modifies the T cell response during AE and is associated with a defect of RNA-helicase expression in DC. This could contribute to describe new mechanisms in the virus induced AE.
CT and lung function patterns in bronchopulmonary dysplasia (BPD) in the post-surfactant era
Authors: A Krishnan
Journal: Thorax (2008)

Advances in neonatal management, particularly the use of surfactant, have been associated with the emergence of a new form of bronchopulmonary dysplasia (BPD). This is thought to be a result of arrested lung development and is characterised by abnormalities of alveolar septation and microvascular maturation. This retrospective review …
Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series Commentary: Larger trials are needed
Authors: M. A Taylor
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. <b>Design:</b> Randomised, double blind, placebo controlled, parallel group, multicentre study. <b>Setting:</b> Four general practices and a hospital ear, nose, and throat outpatient department. <b>Participants:</b> 51 patients with perennial allergic rhinitis. <b>Intervention:</b> Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. <b>Main outcome measures:</b> Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. <b>Results:</b> Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) <i>v</i> 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). <b>Conclusion:</b> The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.
A randomized trial of melphalan and prednisone versus melphalan, prednisone, cyclophosphamide, MeCCNU, and vincristine in untreated multiple myeloma.
Authors: S Pavlovsky, J Saslavsky, M Tezanos Pinto, L Palmer, M Curuchet, J M Lein, G Garay, M Dragosky, E Quiroga-Micheo, A B Huberman
Journal: Journal of Clinical Oncology (1984)

In a randomized study with 234 previously untreated patients with multiple myeloma, 129 were treated with melphalan (8 mg/m2 perorally for four days) and prednisone (40 mg/m2 perorally for seven days, both every four weeks) and 105 with melphalan and prednisone at the same doses plus cyclophosphamide (600 mg/m2 intravenously every four weeks), MeCCNU (100 mg/m2 PO every eight weeks), and vincristine (MPCCV, 0.6 mg/m2 IV every four weeks). A total of 49 (38%) of the 129 patients treated with melphalan and prednisone (MP) and 48 (46%) of the 105 patients treated with MPCCV showed good response (GR) (P not significant); the overall response rates were 58% and 70%, respectively. Thirty-seven percent of the MP group and 39% of the MPCCV group remain alive at 48 months from first treatment (P not significant). The estimated 48-month survival from first treatment, according to different prognostic factors at diagnosis, in both groups was as follows: stage 1,56%; stage II, 46%, and stage III, 23% (I and II v III P less than .001). Survival at 48 months according to response was GR, 68%; partial response (PR), 33%; and null, 16% (GR v null, P less than .0005; GR v PR, P less than .0005). Survival according to renal function was 43% for a creatinine level less than 2 mg/100 mL and 27% for a creatine level greater than or equal to 2 mg/100 mL (P less than .0005). No significant difference has been found between the two treatment schedules in terms of response rate and survival time, in any stage of disease.
Patients with severe allergic rhinitis are more often affected by sleep disorders.
Authors: Anilkumar Pillai
Journal: Thorax (2007)

▴Allergic rhinitis and its consequences on quality of sleep: an unexplored area. Leger D, Annesi-Maesano I, Carat F, et al . Arch Intern Med2006;166:1744–8.

[OpenUrl][1][CrossRef][2][PubMed][3]



Allergic rhinitis is common in the general population and impairs sleep and social life. This French study seems to be the first attempt to assess the impact of duration and severity of allergic rhinitis on the quality of sleep and consequently on everyday living.

From a nationwide controlled cross …

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Abstract 3563: Postconditioning Inhibits Mitochondrial Permeability Transition Pore Opening Independently of any Modification of the Oxidative Phosphorylation and of the Inner Membrane Potential at Reperfusion
Authors: Mélanie Paillard, Ludovic Gomez, Lionel Augeul, Joseph Loufouat, Michel Ovize
Journal: Circulation (2008)

Mitochondrial permeability transition pore (mPTP) inhibition plays a crucial role in postconditioning (PostC). We sought to determine whether oxidative phosphorylation and mitochondrial membrane potential (ΔΨ m ), which both modulate mPTP opening, are involved in the inhibition of mPTP opening in the postconditioned heart. Anesthetized rabbits underwent 30 minutes of ischemia followed by 10 minutes of reperfusion. At the onset of reperfusion, they received either no intervention (Control, C), 4 cycles of 1 min ischemia followed by 1 min reperfusion (PostC), or an IV injection of 5mg/kg of the powerful inhibitor of mPTP opening, i.e. cyclosporine A (CsA). Sham rabbits underwent no ischemic insult throughout the 40 minute experiment. At the end of the 10 minute reperfusion period, the myocardial area at risk was excised, and mitochondria were isolated by differential centrifugations. Calcium retention capacity, an index of mPTP inhibition (CRC: nmol Ca 2+ /mg prot) and ΔΨ m (at state 4: % of FCCP-evoked maximum) were assessed by spectrofluorimetry in isolated subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria. Oxidative phosphorylation (at states 3 and 4: nmol O 2 /min/mg) was assessed using a Clark-type electrode (RCR: state 3 / state 4). As expected, PostC and CsA treatments improved CRC when compared to the C group. Control, PostC and CsA mitochondria exhibited a comparable significant dissipation of ΔΨ m , together with a comparable significant decrease of RCR in both SSM and IFM. In all three groups, this latter effect was related to a concomitant significant decrease in state 3 and to an increase in state 4 respiration. These data suggest that during the early minutes of reperfusion, postconditioning inhibits mPTP opening, independent of any specific modification of the oxidative phosphorylation or of ΔΨ m . Summarized data:
Sevoflurane improves lung function impairment induced by cardiopulmonary bypass in cardiac surgery patients
Authors: Zsofia Csorba, Ferenc Petak, Gabor Bogats, Barna Babik
Journal: European Respiratory Journal (2013)

Rationale: Although the relaxation properties of sevoflurane (SEV) against exogenous constrictor agonists have been established, the potential of SEV to reverse the compromised lung mechanics and gas exchange following cardiopulmonary bypass (CPB) has not been studied.  Methods: Pulmonary input impedance (ZL) and the expiratory capnogram were measured in two groups of anaesthetized mechanically ventilated patients undergoing CPB. Measurements were made 5 min after weaning from CPB, and 5 min after SEV administrations at 1 MAC (Group S, n=56). A matched control group including patients with maintenance of iv anaesthesia (Group C, n=32) was also studied accordingly. The airway resistance (Raw), and tissue damping (G) and elastance (H) were obtained from the ZL spectra by model fitting. The third phase slope of the capnogram (S III ) and the arterial partial pressure of oxygen (PaO 2 ) were also determined.  Results: CPB induced marked increases in Raw in both groups (274±40[SE]% and 308±52% in Groups S and C, respectively, p III  (18±6%, p 2 /FiO 2 ) increased (15±3%, p  Conclusions: SEV reverses deteriorations in lung mechanics and oxygenation subsequent to CPB. Considering the cardioprotective properties of SEV, this additional beneficial pulmonary profile further advocates its use in patient with cardiac surgery involving CPB.  Grant support: OTKA K81179, TAMOP 4.2.2.A-11/1/KONV-2012-0052.
Molecular Pathways: Targeting IDO1 and Other Tryptophan Dioxygenases for Cancer Immunotherapy
Authors: Lijie Zhai, Stefani Spranger, David C. Binder, Galina Gritsina, Kristen L. Lauing, Francis J. Giles, Derek A. Wainwright
Journal: Clinical Cancer Research (2015)

Indoleamine 2, 3-dioxygenase 1 (IDO1), IDO2, and tryptophan 2, 3-dioxygenase (TDO) comprise a family of enzymes that catalyze the first- and rate-limiting step associated with the catabolic conversion of tryptophan (Trp) into kynurenine (Kyn). Through subsequent enzymatic and spontaneous reactions, Kyn is further converted into the energetic substrates, NAD(+) and ATP, to fuel cellular metabolic functions. Coincidently, the depletion of Trp and accumulation of Kyn has been demonstrated to induce effector T-cell apoptosis/dysfunction and immunosuppressive regulatory T-cell induction, respectively. Similar to other immune checkpoints, IDO1 and TDO are suggested to be important targets for immunotherapeutic intervention. This is represented by the recent growth of efforts to inhibit the Trp-to-Kyn pathway as a means to control immunosuppression. Inhibitors currently in clinical trials, INCB024360, GDC-0919, indoximod, and an IDO1 peptide-based vaccine, are being evaluated for their efficacy against a wide range of cancers including melanoma, glioblastoma, non-small cell lung, pancreatic, and/or breast cancer, as well as metastatic disease. Despite the rapid development of potent clinical grade inhibitors, strategic questions remain. Here, we review the state of the literature with respect to current therapeutic inhibitors of tryptophan catabolism, evaluation of those efforts preclinically and clinically, compensatory changes that occur with therapeutic targeting, as well as newly recognized signaling features that raise critical questions to the field. Given the rapidly evolving interest in determining how IDO1/TDO, and to an unknown extent, IDO2, can be targeted for increasing cancer immunotherapeutic efficacy, we present a brief but comprehensive analysis that addresses critical questions, while highlighting the mechanics that remain to be explored.
The Management of Pain in Patients With Cancer
Authors: Robert A. Swarm
Journal: Journal of the National Comprehensive Cancer Network (2013)

More than 30% of patients with cancer report chronic pain, which is an indication of both the frequency of cancer-related pain and the failure to optimally manage it. Although access to opioid analgesics has greatly improved over the past 25 years, much remains to be done for patients experiencing severe pain. Opioids are far from ideal analgesics, noted Dr. Robert A. Swarm at the recent NCCN 18th Annual Conference. Universal screening for cancer pain is part of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain. This is not a one-time effort but should be part of management throughout the cancer care continuum.
Kidney growth and hypertrophy: the role of mTOR and vesicle trafficking
Authors: Qais Al-Awqati
Journal: Journal of Clinical Investigation (2015)

The kidney, like other organs, grows in constant proportion to the rest of the body. When one kidney is removed, the remaining one hypertrophies. In a comprehensive series of studies, Chen et al. show that growth during maturation is mediated by the mTORC1 signaling pathway, which is induced by EGF-like peptides, and requires PI3K, PDK, AKT, mTORC2, and activation of mTORC1 through the combined effects of TSC and RHEB as part of a multiprotein complex localized on lysosomes. However, compensatory growth is mediated by amino acids, which act on mTORC1 independently of the previous pathway, and requires a class III PI3K (VPS34) that is known to be involved in vesicle trafficking to the lysosomes.
Differential effects of GLP-1 receptor agonist on foam cell formation in monocytes between non-obese and obese subjects
Authors: Masashi Tanaka, Yoshiyuki Matsuo, Hajime Yamakage, Shinya Masuda, Yuko Terada, Kazuya Muranaka, Hiromichi Wada, Koji Hasegawa, Akira Shimatsu, Noriko Satoh-Asahara
Journal: Metabolism (2015)