tbuckley/cabot-search huggingface dataset:
Spontaneous abrogation of the G2 DNA damage checkpoint has clinical benefits but promotes leukemogenesis in Fanconi anemia patients
Authors: Raphael Ceccaldi, Delphine Briot, Jérôme Larghero, Nadia Vasquez, Catherine Dubois d’Enghien, Delphine Chamousset, Maria-Elena Noguera, Quinten Waisfisz, Olivier Hermine, Corinne Pondarre, Thierry Leblanc, Eliane Gluckman, Hans Joenje, Dominique Stoppa-Lyonnet, Gérard Socié, Jean Soulier
Journal: Journal of Clinical Investigation (2010)

DNA damage checkpoints in the cell cycle may be important barriers against cancer progression in human cells. Fanconi anemia (FA) is an inherited DNA instability disorder that is associated with bone marrow failure and a strong predisposition to cancer. Although FA cells experience constitutive chromosomal breaks, cell cycle arrest at the G2 DNA damage checkpoint, and an excess of cell death, some patients do become clinically stable, and the mechanisms underlying this, other than spontaneous reversion of the disease-causing mutation, are not well understood. Here we have defined a clonal phenotype, termed attenuation, in which FA patients acquire an abrogation of the G2 checkpoint arrest. Attenuated cells expressed lower levels of CHK1 (also known as CHEK1) and p53. The attenuation could be recapitulated by modulating the ATR/CHK1 pathway, and CHK1 inhibition protected FA cells from cell death. FA patients who expressed the attenuated phenotype had mild bone marrow deficiency and reached adulthood, but several of them eventually developed myelodysplasia or leukemia. Better understanding of attenuation might help predict a patient's clinical course and guide choice of treatment. Our results also highlight the importance of evaluating the cellular DNA damage checkpoint and repair pathways in cancer therapies in general.
P261 Does the provision of a rescue pack keep patients with chronic obstructive pulmonary disease (COPD) at home?
Authors: L. E. E. Schomberg, J. L. Garner, J. W. Porter, K. Bahadur, L. Ross, C. A. Kosky, A. C. Davidson
Journal: Thorax (2011)

<h3>Introduction</h3> COPD accounts for one in eight hospital admissions, 1 million bed days and costs £870–930 m a year.1 Early treatment of exacerbations with steroids reduces severity and may reduce the need for hospital admission.2 We evaluated the acceptance and use of a rescue pack provided on discharge from hospital. <h3>Methods</h3> 38 patients, discharged between 1 February and 30 June 2011, were supplied a 7 day rescue pack comprising Prednisolone 25 mg and Doxycycline 100 mg (total cost of £7) with education and a self-management plan. A telephone questionnaire was conducted in July: Do you remember being given a rescue pack on discharge from hospital? Have you had a flare-up of your COPD since discharge? Did you use your rescue pack? Did you take both antibiotic and steroid? Did you complete the course? Do you think it helped keep you at home? Have you got a replacement rescue pack? <h3>Results</h3> 25 out of 38 (66%) patients were contactable. 11 (44%) were male and 14 (56%) female. The median age was 77 (range 53–89) years. The median time from discharge to telephone contact was 110 (range 21–168) days. 24 (96%) patients acknowledged receipt of the rescue pack. 14 out of 15 (93%) patients who had experienced an exacerbation of COPD had used the rescue pack. Of these 14 patients, 13 (93%) were confident of the benefit and 10 (71%) had obtained a replacement pack. Six of the 38 (16%) patients supplied with a rescue pack were re-admitted with an exacerbation. <h3>Conclusions</h3> The results of this service evaluation suggest a cost-effective initiative that may reduce hospital re-admission by promoting earlier treatment. Rescue packs should be supported by education and a self-management plan.
Cerebral Protection With Filter Devices During Carotid Artery Stenting
Authors: Bernhard Reimers, Nicola Corvaja, Sharam Moshiri, Salvatore Saccà, Remo Albiero, Carlo Di Mario, Pietro Pascotto, Antonio Colombo
Journal: Circulation (2001)

Distal embolization of debris during percutaneous carotid artery stenting may result in neurological deficit. Filter devices for cerebral protection potentially reduce the risk of embolization.Elective carotid stent implantation using 3 different types of distal filter protection devices was attempted in 88 consecutive lesions (84 patients) in the internal carotid artery that had >70% diameter stenosis (mean, 78.7+/-10.7%). Procedures were performed in 3 different centers. The mean age of the patients was 69+/-8 years, 75% were men, and 35.7% had neurological symptoms. In 86 lesions, a stent was successfully implanted (97.7%). In 83 of these 86 procedures (96.5%), it was possible to position a filter device. In 53% of filters, there was macroscopic evidence of debris. Collected material consisted of lipid-rich macrophages, fibrin material, and cholesterol clefts. Neurological complications during the procedure, in the hospital, and at 30 days of clinical follow-up occurred in only one patient (1.2%). This patient suffered a minor stroke that resolved within 1 week. Two major adverse cardiac events (2.3%) occurred during the 30 days of follow-up.Filter protection during carotid artery stenting seems feasible and safe. In the present series, the incidence of neurological complications was low.
Abstract A32: RET fusion gene: Translation to personalized lung cancer therapy.
Authors: Takashi Kohno, Koji Tsuta, Katsuya Tsuchihara, Tatsuji Mizukami, Kiyotaka Yoh, Koichi Goto
Journal: Clinical Cancer Research (2014)

Abstract Oncogenic RET fusion gene, occurring in 1–2% of LADCs, was recently identified by us and others as a new targetable driver gene in lung adenocarcinoma. Existing FDA-approved inhibitors of RET tyrosine kinase, such as vandetanib, show promising therapeutic effects both in vitro and in vivo, as well as in a few patients. A phase II clinical trial, investigating the therapeutic effects of vandetanib, has been started in Japan (UMIN00001009) in Q1 of 2013. The RET fusion screening is being conducted in &amp;gt; 120 hospitals throughout Japan by a consortium designated “LC-SCRUM (Lung Cancer Genomic Screening Project for Individualized Medicine in Japan)”. Approximately 4% of &amp;gt;300 EGFR-mutation negative NSCLC patients screened have been diagnosed as being positive for RET fusion, and the therapy of several patients has started. Positive responses to vandetanib have been observed as expected. In addition, the structure of breakpoints of RET fusion in lung adenocarcinoma indicates that the different molecular processes generate oncogenic RET fusions between lung adenocarcinoma and papillary thyroid carcinoma. Etiology and therapeutic significance of RET fusion in lung adenocarcinoma will be discussed. Citation Format: Takashi Kohno, Koji Tsuta, Katsuya Tsuchihara, Tatsuji Mizukami, Kiyotaka Yoh, Koichi Goto. RET fusion gene: Translation to personalized lung cancer therapy. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A32.
Disinfection with glutaraldehyde.
Authors: G Ayliffe, B J Collins, J R Babb
Journal: BMJ (1979)

ing.Medical journals in particular should stop immediately the implicit advertising of alcohol which often appears in their pages concerned with eating out and such recreations.It is not long since in Birmingham the BMA itself arranged a whisky tasting evening.On the other hand, with heroin we have created a "pushers' market," and our methods for handling this problem are those which have proved disastrous in America in respect of the prohibition of alcohol.In the case of alcohol
CD19-Regulated Signaling Thresholds Control Peripheral Tolerance and Autoantibody Production in B Lymphocytes
Authors: Makoto Inaoki, Shinichi Sato, Bennett C. Weintraub, Christopher C. Goodnow, Thomas F. Tedder
Journal: The Journal of Experimental Medicine (1997)

The CD19 cell surface molecule regulates signal transduction events critical for B lymphocyte development and humoral immunity. Increasing the density of CD19 expression renders B lymphocytes hyper-responsive to transmembrane signals, and transgenic mice that overexpress CD19 have increased levels of autoantibodies. The role of CD19 in tolerance regulation and autoantibody generation was therefore examined by crossing mice that overexpress a human CD19 transgene with transgenic mice expressing a model autoantigen (soluble hen egg lysozyme, sHEL) and high-affinity HEL-specific IgMa and IgDa (IgHEL) antigen receptors. In this model of peripheral tolerance, B cells in sHEL/IgHEL double-transgenic mice are functionally anergic and do not produce autoantibodies. However, it was found that overexpression of CD19 in sHEL/IgHEL double-transgenic mice resulted in a breakdown of peripheral tolerance and the production of anti-HEL antibodies at levels similar to those observed in IgHEL mice lacking the sHEL autoantigen. Therefore, altered signaling thresholds due to CD19 overexpression resulted in the breakdown of peripheral tolerance. Thus, CD19 overexpression shifts the balance between tolerance and immunity to autoimmunity by augmenting antigen receptor signaling.
THE ETIOLOGY, PATHOLOGY AND DIAGNOSIS OF INTESTINAL TUBERCULOSIS.
Authors: N. SENN
Journal: JAMA (1898)

Renewed interest has been awakened in the subject of intestinal tuberculosis since recent experience in modern aggressive surgery has taught the profession that some of the cases in which the disease occurs as a primary affection are amenable to successful surgical intervention. Intestinal tuberculosis appears under so many different pathologic forms and presents such various clinical aspects, that it becomes necessary to inquire carefully into its etiology and pathology, in order to enable the surgeon to exercise the necessary care in the selection of cases for operative treatment. The field of abdominal surgery is rapidly increasing in extent and usefulness, and one of its most recent acquisitions is the successful treatment of certain forms of intestinal tuberculosis. It is my intention on this occasion to discuss as briefly as possible the etiology, pathology, symptoms and diagnosis of this affection of the intestinal canal, with special reference to the indications which
Retreat from openness
Authors: A. Cartwright
Journal: BMJ (1988)

<h3>Abstract</h3> Spike (S) protein is the primary antigenic target for neutralization and vaccine development for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It decorates the virus surface and undergoes large conformational changes of its receptor binding domain (RBD) to enter the host cell, as the abundant structural studies suggest. Here, we observe Down, one-Up, one-Open, and two-Up-like structures in enhanced molecular dynamics simulations without pre-defined reaction coordinates. The RBD<sub>A</sub> transition from Down to one-Up is supported by transient salt-bridges between RBD<sub>A</sub> and RBD<sub>C</sub> and by the glycan at N343<sub>B</sub>. Reduced interactions between RBD<sub>A</sub> and RBD<sub>B</sub> induce the RBD<sub>B</sub> motions toward two-Up. Glycan shielding for neutralizing antibodies is the weakest in one-Open. Cryptic pockets are revealed at the RBD interfaces in intermediate structures between Down and one-Up. The inherent flexibility in S-protein is, thus, essential for the structure transition and shall be considered for antiviral drug rational design or vaccine development.
Insertion of a 5' truncated L1 element into the 3' end of exon 44 of the dystrophin gene resulted in skipping of the exon during splicing in a case of Duchenne muscular dystrophy.
Authors: N Narita, H Nishio, Y Kitoh, Y Ishikawa, Y Ishikawa, R Minami, H Nakamura, M Matsuo
Journal: Journal of Clinical Investigation (1993)

We report here the second evidence of retrotransposition of L1, which was found inserted into the dystrophin gene of a patient, causing Duchenne muscular dystrophy (DMD).When the PCR was used to amplify a region of the dystrophin gene en- compassing exon 44 from genomic DNA of two Japanese brothers with DMD, it was found to be -600 bp larger than expected.Both the normal and the abnormally large products were amplified from the DNA of their mother.However, the maternal grandparents did not have the abnormal allele, and the mutation must therefore have occurred in the mother.Anal- ysis of nucleotide sequence of the amplified product from a patient disclosed that the insertion was present zero to two bases upstream from the 3' end of exon 44 and that two to four bases of the exon sequence were deleted from the insertion site.The insertion sequence was found to be composed of 606-608 bp and to be almost identical to the inverse complement of 3' portion of the Li retrotransposon consensus sequence.The dystrophin gene transcript from peripheral lymphocytes of one of the patients was analyzed by using reverse transcription/ semi-nested PCR.The size of the amplified product encom- passing exon 42 to 46 was smaller than expected.Sequencing of the amplified product disclosed that the sequence of exon 43 was directly joined to that of exon 45.Exon 44 of the transcript was thus shown to be skipped during splicing.This novel muta- tion of the dystrophin gene has important implications regard- ing retrotransposition of an active Ll element and provides a new insight into the origins of mutations in the dystrophin gene.
Psychosis is also common in users of "normal" cannabis
Authors: A. J McBride, H. Thomas
Journal: BMJ (1995)

EDITOR,--A S Wylie and colleagues report that three of eight patients on a methadone programme experienced psychotic symptoms after using modest amounts of “skunk” cannabis.1 The tetrahydrocannabinol content of cannabis resin seized in 1984-9 varied widely among batches, years, and countries of origin,2 the average content being …
Abstract 2383: Clinical significance of intratumoral HER2 heterogeneity in gastric cancer.
Authors: Hye Seung Seung Lee, Hee Eun Lee, Kyoung Un Park, Soo Kyung Nam, Do Joong Park, Hyung-Ho Kim
Journal: Cancer Research (2013)

Abstract Aim: To evaluate the clinical significance of intratumoral HER2 heterogeneity in gastric cancer (GC). Methods: A total of 322 GC tissues were evaluated by HER2 immunohistochemistry (IHC), of which 73 with IHC 2+ or 3+ were subjected to fluorescence in situ hybridization (FISH). Also, 3-5 distinct spots in each case showing different HER2 staining intensity were evaluated individually for comparing IHC staining intensity with gene copy number (GCN). Minimum, average, and maximum FISH scores were generated for each case. Results: Intratumoral heterogeneity of HER2 overexpression and gene amplification were 54 and 30 of 73 cases with IHC 2+ or 3+, respectively. These cases were characterised by diffuse or mixed Lauren type, HER2 IHC 2+, and low-level amplification. Kaplan-Meier survival analysis revealed that the heterogeneous overexpression was significantly associated with longer disease-free survival times than the homogeneous, and the high average GCN was most associated with poor outcome. Also, there was a strong correlation between the IHC and FISH results for each spot. Quantitative PCR analysis of the cancer tissues and the cell-free plasma showed that HER2 gene copy by quantitative PCR on tissue correlated well with those by FISH, but plasma HER2 level was not.Conclusions: Considering the high incidence of intratumoral HER2 heterogeneity in GC, accurate HER2 assessment would require larger tissues and more detailed guidelines. The guidelines should include the recommendation that FISH-scoring areas be selected with reference to a corresponding IHC slide. Also, the definition of HER2-positive tumours should be reassessed considering the intratumoral heterogeneity. Citation Format: Hye Seung Seung Lee, Hee Eun Lee, Kyoung Un Park, Soo Kyung Nam, Do Joong Park, Hyung-Ho Kim. Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2383. doi:10.1158/1538-7445.AM2013-2383
Study Examines Effects of Advance Access to Emergency Contraception
Authors: Tracy Hampton
Journal: JAMA (2007)

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
Dynamics of Langerhans cells in genetically defined murine epidermal cell culture
Authors: RHONNA L. COHEN, D.A. CHAMBERS
Journal: British Journal of Dermatology (1984)

Unlike keratinocytes, Langerhans cells express both surface ATPase activity and Ia (HLA-DR) antigens. A well-characterized in vitro system containing Langerhans cells would be of great use in elucidating their functions. Thus, epidermal cell cultures derived from neonatal Balb/c mice were examined for the presence of Langerhans cells. Twenty-four hours after initiation of culture, ATPase- and Ia-positive cells were seen to be associated with cell aggregates. By day 3, Langerhans cells migrated on to the substratum and, as the cultures matured and stratified, were seen both in groups and as single cells for the duration of the cultures (day 14). During culture, although the total number of cells increased, the percentage of cells expressing Ia antigen and ATPase activity remained constant, suggesting that Langerhans cells increase in number during cell culture. Such a situation could arise from actual division of Langerhans cells during culture or from latent expression of Ia antigen and ATPase activity by pre-existing cells. This is the first study of the dynamics of Langerhans cells in a cell culture system and shows that Langerhans cells are present throughout the lifespan of the cultures.
Of Genes and Men: The Alternative View of Sex Differences in Cystic Fibrosis
Authors: Carlos E. Milla, Joanne Billings, Antoinette Moran
Journal: Diabetes Care (2006)

Creus et al. (1) offer an intriguing hypothesis, namely that protective genes on the Y chromosome confer a survival advantage to men with cystic fibrosis. While there are aspects of this theory that are attractive, its does not explain the fact that …
Relevance of duration of transient ischaemic attacks in carotid territory.
Authors: G W Duncan, M Pessin, J P Mohr
Journal: BMJ (1978)

heart size decreased after discontinuation of digoxin, contrary to expectations.These observations underline the inherent dangers of digitalis therapy, especially in coronary heart disease and respiratory in- sufficiency.It seems important to make sure that the only patients who are allowed to go on taking digoxin are those who otherwise would deteriorate clinically.At the moment the only way to achieve this goal is to discontinue the drug under conditions enabling close observation of the patients.
Fulminant Hyperthermia During Anesthesia and Surgery
Authors: Charles R. Stephen
Journal: JAMA (1967)

Rapid, progressive hyperpyrexia is becoming a cause for concern. It occurred in 12 patients, ten of whom failed to survive the acute episode. Conventional anesthetic drugs, including thiopental sodium, succinylcholine chloride, nitrous oxide, and halothane, were employed in most of the patients. No specific signs or symptoms heralded the onset of the hyperthermia. Usually the first observation was that the skin of the patient felt very hot; cardiovascular collapse developed shortly thereafter. At the moment, the primary treatment is prophylactic: continual monitoring of body temperature will detect beginning increases in body heat and permit efforts to reverse the situation before it becomes irreversible. When the syndrome develops, drastic measures must be instituted at once to reduce body temperature, provide high concentrations of oxygen with hyperventilation, and combat metabolic acidosis.
Diuretics and Nonocclusive Infarcts
Authors: Sarko M. Tilkian
Journal: JAMA (1975)

To the Editor.—  The article, Diuretic Agents: Inciting Factor in Nonocclusive Mesenteric Infarction? (229: 1451, 1974), by John B. Sharefkin, MD, and William Silen, MD, describes three cases of nonocclusive mesenteric infarctions following diuretic and digitalis therapy and suggests hypovolemia, diuretic-induced, together with vasospasm, possibly digitalis-induced, as the mechanism for the infarction. Although some hypovolemia seems to have occurred, the slight elevation in blood urea nitrogen level of two of the patients renders the hypovolemia theory not too impressive.  Another more likely explanation may be the hypothesis forwarded by Alexander Leaf, MD, 1,2 suggesting cell swelling as the possible cause of nonocclusive infarcts. The cell swelling is caused by potassium efflux coupled with sodium chloride and water influx across the cellular semipermeable membrane, and thus interference with cell metabolism and possibly impingement on micro-circulation. The current knowledge of the mechanisms of adenosine triphosphate (ATP)-dependent active sodium-potassium transport involving the specific
Segmental allergen challenge in patients with atopic asthma leads to increased IL-9 expression in bronchoalveolar lavage fluid lymphocytes
Authors: Veit J. Erpenbeck, Jens M. Hohlfeld, Brunhild Volkmann, Andreas Hagenberg, Henning Geldmacher, Armin Braun, Norbert Krug
Journal: Journal of Allergy and Clinical Immunology (2003)
Intestinal permeability to 51Cr-EDTA in rats with experimentally induced enteropathy.
Authors: I Bjarnason, P Smethurst, A J Levi, T J Peters
Journal: Gut (1985)

Intestinal permeability has been investigated in the normal rat by measuring the five hour urine excretion of 51Cr-EDTA after intragastric administration. Twelve control animals excreted 2.06% +/- 0.22 (mean +/- SE) of the administered dose. Prolonged intestinal transit times with atropine had no significant effect on the apparent permeability with a urine excretion 2.31% +/- 0.36. The concomitant administration of a hypertonic, but rapidly absorbed glycerol solution, was accompanied by increased urinary excretion (3.05% +/- 0.33) while the administration of a poorly absorbed sugar, lactulose, significantly decreased the apparent permeability (urine excretion 0.61% +/- 0.14) showing that passive intestinal permeability estimations are affected by test dose composition. Enteropathy was induced by ethanol, cetrimide, or methotrexate and each was associated with increased permeability, with urine excretions of 4.19% +/- 0.47, 4.20% +/- 0.66 and 3.97% +/- 0.49 respectively. It is thus suggested that the normal rat mucosa is maximally resistant to the absorption of foreign compounds such as 51Cr-EDTA and intestinal damage will disrupt this barrier.