tbuckley/cabot-search huggingface dataset:
Localization of the cystic fibrosis transmembrane conductance regulator in airway secretory glands
Authors: J Jacquot, E Puchelle, J Hinnrasky, C Fuchey, C Bettinger, C Spilmont, N Bonnet, A Dieterle, D Dreyer, A Pavirani, al. et
Journal: European Respiratory Journal (1993)

Cystic fibrosis (CF) is caused by mutations in the gene coding for the CF transmembrane conductance regulator (CFTR). From human normal tracheal submucosal gland cells in culture, we identified endogenous CFTR as a 170 kDa protein, consistent with that of fully glycosylated, mature CFTR molecule. This observation led to the hypothesis that airway secretory glands could be an important site for the CFTR expression. Using anti-human CFTR polyclonal and monoclonal antibodies, we examined the cellular and subcellular localization of the CFTR protein in airway submucosal glands from human and bovine tracheal tissues as well as in tracheal gland cell cultures. In human tracheal tissue, CFTR immunolabelling was present along both the apical and basolateral plasma membranes of glandular mucous cells. In contrast, CFTR was associated with the secretory granules of glandular serous cells. Using immunogold electron microscopy, we demonstrated that CFTR protein was more specifically associated with the membrane of serous cell secretory granules. In bovine tracheal tissue CFTR labelling was also identified in the secretory granules of glandular serous cells. In contrast, when bovine and human tracheal gland cells were cultured, no mature secretory granules were present, but a predominantly intracytoplasmic distribution of CFTR was observed. Our data thus suggest that in airway tissues, CFTR could be involved in intracellular processes of the mucus exocytosis in submucosal secretory glands.
Glutethimide Dependence: Phenobarbital Treatment
Authors: Robert E. Vestal, Barry H. Rumack
Journal: Annals of Internal Medicine (1974)

Letters1 May 1974Glutethimide Dependence: Phenobarbital TreatmentROBERT E. VESTAL, M.D., BARRY H. RUMACK, M.D.ROBERT E. VESTAL, M.D., BARRY H. RUMACK, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-5-670_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Glutethimide (Doriden®*) may produce physical dependence and addiction, with the associated abstinence syndrome on withdrawal (1). Smith and Wesson (2) proposed using phenobarbital, a long-acting barbiturate, as a substitute for the primary addicting agent, when treating withdrawal from various nonopiate drugs. In this case we used phenobarbital to treat the glutethimide abstinence syndrome.A 28-year-old man was admitted to the hospital because of chronic glutethimide abuse. His average daily dose for about 2½ years was 5 g/day, but he had used doses of 13.5 g/day. During the preceding 5 weeks the patient had gradually reduced his daily...References1. JOHNSONVAN BUREN FH: Abstinence syndrome following glutethimide intoxication. JAMA 180:1024-1027, 1962 CrossrefGoogle Scholar2. SMITHWESSON DD: A new method for treatment of barbiturate dependence. JAMA 213:294-295, 1970 CrossrefMedlineGoogle Scholar3. ESSIGCARTER CW: Failure of diphenylhydantoin in preventing barbiturate withdrawal convulsions in a dog. Neurology (Minneap) 12:481-484, 1962 CrossrefMedlineGoogle Scholar4. ESSIGFRASER CH: Failure of chlorpromazine to prevent barbiturate withdrawal convulsions. Clin Pharmacol Ther 7:466-469, 1966 CrossrefMedlineGoogle Scholar5. CHAZANGAREILLA JS: Glutethimide intoxication: a perspective study of 70 patients treated conservatively without hemodialysis. Arch Intern Med 128:215-219, 1971 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Clinical Pharmacology Departments of Pediatrics and Medicine University of Colorado Medical Center Denver, Colorado 80220*USV Pharmaceuticals Corp., Tuckahoe, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTin 1 May 1974Volume 80, Issue 5Page: 670-670KeywordsDrugs ePublished: 1 December 2008 Issue Published: 1 May 1974 PDF downloadLoading ...
Paternity in men with stage I testis tumors on surveillance.
Authors: H W Herr, N Bar-Chama, M O'Sullivan, P C Sogani
Journal: Journal of Clinical Oncology (1998)

We report long-term paternity in men with stage I testis tumors who were managed initially by surveillance.One hundred five patients with clinical stage I nonseminomatous germ cell tumors of the testis were entered on a surveillance protocol and followed up for more than 10 years. Actual fertility potential was assessed by pregnancy.Of the 105 patients, 41 (39%) have fathered children, which includes 36 of 78 (46%) patients while on active surveillance and five of 27 (19%) patients after treatment for relapse. Of 63 couples who attempted a pregnancy on surveillance or were presumed capable of impregnation (whether they tried or not), 41 (65%) were successful.These results show that the majority of men with stage I testis tumor who are on surveillance after orchiectomy, have a suitable partner, and attempt impregnation achieve a successful pregnancy. Pregnancy rates appear to be less than reported in men who have a nerve-sparing retroperitoneal lymph node dissection (RPLND) because more patients on surveillance require treatment for relapse, which reduces their chances for pregnancy.
Immune Complex-Associated Deafness: Preliminary Communication
Authors: Gerald B Brookes
Journal: Journal of the Royal Society of Medicine (1985)

During the last year patients presenting with progressive bilateral or sudden sensorineural deafness of unknown aetiology have been investigated for possible abnormal immune activity. Twenty-six cases are reported in which significantly raised circulating immune complexes were present, together with 2 cases of clinical autoimmune deafness where the complexes were normal. Thirty-six control subjects were also studied. Following a review of the clinical features, the pathogenesis of this new association with sensorineural deafness is discussed. In some cases the aetiology is probably autoimmune, and in others related to infection. In certain patients the deafness has been partly reversed by medical treatment with systemic steroids or plasma exchange. It is hypothesized that circulating immune complexes may reflect a previously unrecognized final common pathophysiological pathway in a variety of cochleovestibular disorders.
Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages
Authors: T Lyberg, B Nakstad, O Hetland, NP Boye
Journal: European Respiratory Journal (1990)

Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.
Different modes of allergen – Rhinovirus interaction control chemokine production
Authors: Nathan Bartlett, Nicholas Glanville, Ross Walton, Sebastian Johnston
Journal: European Respiratory Journal (2011)

Interacting immune responses to rhinovirus (RV) and allergen in asthma are thought to increase the risk of asthma exacerbations. To investigate this we used a mouse model of RV-induced asthma exacerbation and assessed expression of eosinophil, Th1 and Th2 recruiting chemokine protein in BAL fluid. Experimental groups: allergen (OVA)-challenged, RV-infected (RV-OVA); OVA challenged, mock infected with UV-inactivated RV (UV-OVA), RV-infected mock allergen challenged with PBS (RV-PBS) and double negative control (UV-PBS).   Results:  CCL11 and CCL24 (eotaxin 1 and 2) in RV-OVA were significantly increased (P
How Many Days of Bed Rest for Acute Low Back Pain?
Authors: Richard A. Deyo, Andrew K. Diehl, Marc Rosenthal
Journal: New England Journal of Medicine (1986)

Abstract Bed rest is usually recommended for acute low back pain. Although the optimal duration of bed rest is uncertain, a given prescription may directly affect the number of days lost from work or other activities. In a randomized trial, we compared the consequences of recommending two days of bed rest (Group I) with those of recommending seven days (Group II). The subjects were 203 walk-in patients with mechanical low back pain; 78 percent had acute pain (≤30 days), and none had marked neurologic deficits. Follow-up data were obtained at three weeks (93 percent) and three months (88 percent). Although compliance with the recommendation of bed rest was variable, patients randomly assigned to Group I missed 45 percent fewer days of work than those assigned to Group II (3.1 vs. 5.6 days, P = 0.01), and no differences were observed in other functional, physiologic, or perceived outcomes. For many patients without neuromotor deficits, clinicians may be able to recommend two days of bed rest rather than longer periods, without any perceptible difference in clinical outcome. If widely applied, this policy might substantially reduce absenteeism from work and the resulting indirect costs of low back pain for both patients and employers. (N Engl J Med 1986; 315:1064–70.)
Herpes simplex virus type 1 and respiratory disease in critically-ill patients: real pathogen or innocent bystander?
Authors: A.M. Simoons-Smit, E.M. Kraan, A. Beishuizen, R.J. Strack van Schijndel, C.M. Vandenbroucke-Grauls
Journal: Clinical Microbiology and Infection (2006)
Properties of Mouse Embryo Fibroblasts Transformed In Vitro by Infectious Bovine Rhinotracheitis Virus&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: L Geder, K J Lee, M S Dawson, R W Hyman, R M Maliniak, F Rapp
Journal: JNCI Journal of the National Cancer Institute (1980)

Infection of CD-1 mouse embryo fibroblast(s) (MEF) with infectious bovine rhinotracheitis virus (IBRV) strain HMC resulted in persistent infection and subsequent transformation of these cells. IBRV-transformed MEF cultures consisted of short fibroblastoid cells, and IBRV-specific membrane and intracellular antigens were detectable in early in vitro passages by indirect imunofluorescence (IF) techniques. The presence of IBRV genetic information was confirmed in IF-positive and IF-negative cells by in situ hybridization. IBRV-transformed MEF induced fibrosarcomas in athymic nude mice given sc transplants. Infectious virus could not be rescued from the transformed cells or from tumor cells by cocultivation with rabbit kidney cells, by treatment with 5-iodo-2'-deoxyuridine, or by UV irradiation. Nontransformed control cells did not survive more than 10 in vitro passages and did not induce tumors when transplanted to athymic nude mice. These observations represent new data concerning the mouse cell-transforming potential of IBRV and confirm the presence of at least part of the virus genome in the transformants.
Abstract 3522: A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid and pancreatic cancers
Authors: Gregory T. Gallanis, Kathleen A. Heller, Eleni-Marina Melas, Stephen B. Gruber
Journal: Cancer Research (2014)

Abstract BRCA1 associated protein-1 (BAP1) functions as a tumor suppressor gene by modulating fundamental cellular mechanisms such as cell cycle progression and cell growth. Inactivating germline mutations of BAP1 predispose to multiple cancers including uveal and cutaneous melanoma as well as malignant mesothelioma. In the present study we document a family with a novel germline mutation of BAP1 (g.1777C&amp;gt;T) that results in expression of a truncated BAP1 protein. Family members with this mutation demonstrated a primary clinical phenotype of autosomal dominant, early-onset melanocytic neoplasms with immunohistochemistry (IHC) of these tumors demonstrating lack of BAP1 protein expression. In addition, family members harboring the BAP1 germline mutation developed other neoplastic disease such as thyroid cancer and pancreatic cancer. IHC analysis of these cancers also demonstrated loss of BAP1 protein expression. Our investigation identifies a new BAP1 mutation, further underscores the relevance of BAP1 as a clinically important tumor suppressor gene and broadens the range of cancers associated with BAP1 inactivation. Further study will be required to understand the full scope of BAP1-associated neoplastic disease. Citation Format: Gregory T. Gallanis, Kathleen A. Heller, Eleni-Marina Melas, Stephen B. Gruber. A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid and pancreatic cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3522. doi:10.1158/1538-7445.AM2014-3522
Molecular and cytological features of the mouse B-cell lymphoma line iMycEμ-1
Authors: Seong Su Han, Arthur L Shaffer, Liangping Peng, Seung Tae Chung, Jae Hwan Lim, Sungho Maeng, Joong Su Kim, Nicole McNeil, Thomas Ried, Louis M Staudt, Siegfried Janz
Journal: Molecular Cancer (2005)

Abstract Background Myc -induced lymphoblastic B-cell lymphoma (LBL) in iMyc Eμ mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings. We have recently shown that gene-targeted iMyc Eμ mice that carry a His 6 -tagged mouse Myc cDNA, Myc His , just 5' of the immunoglobulin heavy-chain enhancer, Eμ, are prone to B cell and plasma cell tumors. The predominant tumor (~50%) that arose in the iMyc Eμ mice on the mixed genetic background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of this study was to establish and characterize a cell line, designated iMyc Eμ -1, for the in-depth evaluation of LBL in vitro . Methods The morphological features and the surface marker expression profile of the iMyc Eμ -1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMyc Eμ -1 cells was assessed by spectral karyotyping (SKY). The expression of the inserted Myc His gene was determined using RT-PCR and qPCR. Clonotypic immunoglobulin gene arrangements were detected by Southern blotting. The global gene expression program of the iMyc Eμ -1 cells and the expression of 768 "pathway" genes were determined with the help of the Mouse Lymphochip © and Superarray © cDNA micro- and macroarrays, respectively. Array results were verified, in part, by RT-PCR and qPCR. Results Consistent with their derivation from LBL, the iMyc Eμ -1 cells were found to be neoplastic IgM high IgD low lymphoblasts that expressed typical B-cell surface markers including CD40, CD54 (ICAM-1), CD80 (B7-1) and CD86 (B7-2). The iMyc Eμ -1 cells harbored a reciprocal T(9;11) and three non-reciprocal chromosomal translocations, over-expressed Myc His at the expense of normal Myc , and exhibited gene expression changes on Mouse Lymphochip © microarrays that were consistent with Myc His -driven B-cell neoplasia. Upon comparison to normal B cells using eight different Superarray © cDNA macroarrays, the iMyc Eμ -1 cells showed the highest number of changes on the NFκB array. Conclusion The iMyc Eμ -1 cells may provide a uniquely useful model system to study the growth and survival requirements of Myc -driven mouse LBL in vitro .
The importance of manganese superoxide dismutase in delayed preconditioning Involvement of reactive oxygen species and cytokines
Authors: S Hoshida
Journal: Cardiovascular Research (2002)

It is clinically important to elucidate the mechanism underlying the delayed preconditioning against ischemia-reperfusion injury observed 24-72 h after sublethal stress such as brief ischemia, hyperthermia and exercise. The time course of induction of myocardial manganese-superoxide dismutase (Mn-SOD) and appearance of the ischemic tolerance coincide well, and the percent increase in Mn-SOD activity and percent reduction of infarct size are correlated well under various stresses. Furthermore, treatments with antisense oligodeoxynucleotides to Mn-SOD completely abolished the delayed preconditioning and any increase in Mn-SOD content. These results indicate that Mn-SOD induction plays a pivotal role in the late phase preconditioning afforded with brief ischemia, hyperthermia and exercise. We also showed that cytokines, e.g., tumor necrosis factor-alpha and interleukin-1beta, and reactive oxygen species are involved in the process of signal transduction for the Mn-SOD induction.
Targeted therapies: detrimental treatment for nonsmall cell lung cancer without driver mutations
Authors: Thierry Berghmans, Anne-Pascale Meert, Elisabeth Quoix
Journal: European Respiratory Journal (2015)

The search for oncogenic driver mutations is currently a standard in the management of advanced nonsquamous nonsmall cell lung cancer (NSCLC) [1], at least for epidermal growth factor receptor ( EGFR ) activating mutations and anaplastic lymphoma kinase ( ALK ) rearrangement. At the beginning of the 21st century, two small orally available molecules with EGFR tyrosine kinase inhibitor (TKI) activity, erlotinib and gefitinib, have been developed and tested mainly in unselected Caucasian populations, concomitantly or sequentially with chemotherapy. Five randomised phase III trials did not demonstrate any supplemental activity by adding the TKI to a conventional platinum-based chemotherapy [2–6]. After these disappointing data, additional research showed that these small molecules had a major activity in the presence of EGFR -activating mutations [7, 8]. Multiple randomised trials have now confirmed that first-generation (erlotinib, gefitinib) or second-generation (afatinib) TKIs are more active than platinum-based chemotherapy in terms of response rate and progression-free survival, while their impact on overall survival remains debatable, probably because of the large crossover noted in those trials [9–14]. Targeted therapies are detrimental in patients with wild-type tumours fit for conventional chemotherapy <http://ow.ly/MTgy8>
A Quest for the Mechanism of “Spontaneous” Malignant Transformation in Culture With Associated Advances in Culture Technology&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K K Sanford, V J Evans
Journal: JNCI Journal of the National Cancer Institute (1982)

The discovery of “spontaneous” malignant transformation of mouse cells in culture raised questions answerable only by obtaining a better control of culture conditions through technologic advances. One of these advances was the introduction of cellophane and later glass as a substrate to replace the plasma clot matrix, widely used in tissue culture at that time. Removal of cells from plasma clot and culture under cellophane or on glass not only increased cell yield but also allowed the manipulation of individual cells in suspension. Other advances included the design and technology of three-dimensional substrate cultures, the establishment for the first time of clonal cell populations from single isolated cells, the development of instrumentation and quantitative techniques for measuring cell proliferation, the introduction of the suspension culture of cells of “fixed tissue” origin, and the formulation of serum-free, antibiotic-free, chemically characterized culture media that could support the continuous proliferation of numerous cell lines from different tissues and species. These technologic advances promoted the application of microbial techniques to vertebrate tissue cells, marked the beginning of modern quantitative cell culture, and provided the tools for recent developments in virology, vaccine production, genetics, molecular biology, and other areas of biomedical research. These technologic advances were associated with a quest for an explanation of spontaneous malignant transformation. In this quest it was found that normal tissue cells of various rodent species after prolonged culture in the absence of added carcinogens or viruses and even in serum-free, chemically defined medium undergo malignant transformation. Certain differences between the normal cell and its malignant derivative were identified, and their reliability as in vitro criteria of malignancy was shown. Certain observations support the hypothesis that aberrant methylation of nucleic acids may be a chemical event in carcinogenesis, and methyltransferases were discovered in all RNA retroviruses examined. Three environmental agents were found to enhance or induce malignant transformation: the type of serum used, molecular oxygen, and repeated exposure to low-intensity fluorescent light. All three agents produce chromosomal DNA damage. Experimental results indicate that the DNA damage produced by light results directly or indirectly from the intracellular generation of hydrogen peroxide and/or the derivative free hydroxyl radical. Thus the malignant transformation of rodent cells is not spontaneous but is induced by specific environmental agents that produce chromosomal DNA damage. The progression to malignancy in mouse cells and the susceptibility of human cells to malignant transformation appear to be associated with an impaired capacity to repair the DNA damage produced by these environmental agents.
Ceruloplasmin Assays In Diagnosis and Treatment of Human Lung, Breast, and Gastrointestinal Cancers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Maria C. Linder, Joan R. Moor, Kristine Wright
Journal: JNCI Journal of the National Cancer Institute (1981)

Ceruloplasmin was assayed as enzyme activity, as antigen, and as total copper in serum samples from 150 male lung cancer patients and comparable numbers of male controls. By all three assays, ceruloplasmin was significantly increased above the normal before treatment, and the degree of elevation was related to TNM stage [i.e., the International Union Against Cancer classification system based on extent of primary tumor (T), condition of lymph nodes (N), and absence of presence of metastases (M)]. Surgery had no immediate effects, but in patients who evidence of disease for longer periods, ceruloplasmin returned to nearly normal values. High levels of ceruloplasmin was elevated in 6 of 9 patients before tumor recurrence; 2 of 3 smokers (in the first panel of sera) with elevated ceruloplasmin levels subsequently developed lung cancer. The relative merits of the three assays were compared. Some sex- and age-related differences among normal controls were apparent. The results of pilot studies on men with gastrointestinal cancer and women with breast cancer are presented. It is concluded that only in limited situations will assays of ceruloplasmin aid in diagnosis, prognosis, and long-term monitoring of cancer patients.