tbuckley/cabot-search huggingface dataset:
Mutated calreticulin retains structurally disordered C terminus that cannot bind Ca2+: some mechanistic and therapeutic implications
Authors: V Shivarov, M Ivanova, R V Tiu
Journal: Blood Cancer Journal (2014)

Two very recent reports1, 2 made a tremendous breakthrough in our understanding of the molecular basis of myeloproliferative neoplasms (MPNs) without mutations in Janus kinase 2 (JAK2) and myeloproliferative leukemia (MPL) virus oncogene genes. Klampfl et al.1 and Nangalia et al.2 independently identified recurrent somatic mutation in the calreticulin (CALR) gene exclusively in patients with JAK2 and MPL mutation-negative MPNs. Strikingly, all these mutations were small deletions and insertions in exon 9 of the gene leading to a shift in the open reading frame and expression of peptides in which the wild-type C terminus was substituted for a novel identical in all mutants C terminus and a small mutant-specific portion of variable length. This specific feature of CALR mutations necessitates further elucidation of the mechanisms through which they promote neoplastic transformation and might be particularly challenging to dissect as CALR is involved in a plethora of intra- and extra-endoplasmic reticulum (ER) cellular processes.3
Practical Obstetrics and Gynecology: Manual of Selected Procedures and Treatments
Authors: Alex S. Tulsky
Journal: JAMA (1979)

When I was a youth in medical school we used abbreviated booklets in various courses called compendiums. This volume is such a booklet, updated of course, in obstetrics and gynecology. It is in a loose-leaf format with glossy paper and, as the authors indicate, is geared to the house staff level. They refer to it as a manual that they evidently intend to flesh out, but their primary selection has been rather odd. It consists basically of complications of pregnancy, labor, and delivery, a gratuitous chapter on obstetrical regional anesthesia, a few chapters on uterine and ovarian carcinoma, management of postmenopausal bleeding, and a finale on evaluation of female infertility, which includes organization of a fertility clinic. If the book addresses itself to the house staff, it would appear to me that chapters on proper conduct of normal pregnancy, labor, and delivery are equally important as their aberration. They have
Review: Oral phosphodiesterase 4 inhibitors reduce exacerbations but increase adverse events in COPD
Authors: Felix S.F. Ram
Journal: Annals of Internal Medicine (2011)

ACP Journal Club20 September 2011Review: Oral phosphodiesterase 4 inhibitors reduce exacerbations but increase adverse events in COPDFelix S.F. Ram, PhD, Clinical PharmacologistFelix S.F. Ram, PhD, Clinical PharmacologistMassey University, Auckland, New Zealand (F.S.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-6-201109200-02002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationChong J, Poole P, Leung B, Black PN. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;(5):CD002309. https://pubmed.ncbi.nlm.nih.gov/21563134Clinical Impact RatingsGIM/FP/GP: Pulmonology: References1 Jones PW. St. George's Respiratory Questionnaire: MCID. COPD. 2005;2:75-9. [PMID: 17136966] Google Scholar2 Robichaud A, Stamatiou PB, Jin SL, et al. Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis. J Clin Invest. 2002;110:1045-52. [PMID: 12370283] Google Scholar Author, Article, and Disclosure InformationAffiliations: Massey University, Auckland, New Zealand (F.S.R.)This article was published at Annals.org on 6 September 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 September 2011Volume 155, Issue 6Page: JC3-2KeywordsAbdominal painAdverse eventsChronic obstructive pulmonary diseaseDiarrheaLungsNauseaPhosphodiesterasesVomitingWeight loss ePublished: 20 September 2011 Issue Published: 20 September 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Economics of Genomic Medicine
Authors: W. Gregory Feero, Catherine Wicklund, David L. Veenstra
Journal: JAMA (2013)

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
Results of surveillance for infections with Shiga toxin-producing Escherichia coli (STEC) of serotype O104:H4 after the large outbreak in Germany, July to December 2011
Authors: C Frank, A Milde-Busch, D Werber
Journal: Eurosurveillance (2014)

After the massive outbreak of infections with Shiga toxin-producing Escherichia coli (STEC) of serotype O104:H4 in Germany in the summer of 2011, post-outbreak surveillance for further infections with this type of STEC was maintained until the end of 2011. This surveillance was based on national mandatory reporting of STEC infections and the associated complication of haemolytic uraemic syndrome (HUS), as well as on data obtained from a questionnaire. Between the outbreak’s end (5 July) and 31 December 2011, a total of 33 post-outbreak cases were recorded. Post-outbreak cases occurred with diminishing frequency towards the year’s end and resembled the outbreak cases in many respects, however the proportion of HUS among all post-outbreak cases was smaller than during the outbreak. Two thirds of the post-outbreak cases were likely infected by contact with known outbreak cases. Both laboratory and nosocomial spread was noted in this period. No post-outbreak case recalled sprout consumption as a potential source of infection. The scarcity of information conveyed by the nonculture tests routinely used in Germany to diagnose STEC made linkage of post-outbreak cases to the outbreak difficult. Though post-outbreak surveillance demonstrated the outbreak strain’s potential for lengthy chains of transmission aided by prolonged shedding, our results and continued routine surveillance until the end of 2013 do not support the notion, that the outbreak strain has been able to establish itself in the German environment.
Tolerance to Organic Nitrates: Evidence, Mechanisms, Clinical Relevance, and Strategies for Prevention
Authors: Uri Elkayam
Journal: Annals of Internal Medicine (1991)

Objective: To review the available information about nitrate tolerance, its potential mechanisms, clinical implications, and strategies for prevention. Data Identification: A survey of the National Library of Medicine MEDLINE database and bibliographies of the reviewed articles. Study Selection and Data Extraction: Studies were selected from the English language literature with an emphasis on recent studies and, when available, randomized placebo-controlled studies. Old studies were selected on the basis of their historical value and originality. A total of 134 retrieved articles were considered relevant and were reviewed in depth. Results: The available information about the experimental as well as the clinical evidence for tolerance to organic nitrates has been summarized. In addition, information related to potential mechanisms, clinical implications, and possible methods for prevention have been reviewed. Conclusions: Evidence indicates that prolonged in-vitro exposure to organic nitrates, continuous intravenous or topical administration of nitrates, and frequent in-vivo oral dosing result in the rapid development of tolerance to the peripheral as well as to the coronary vasodilatory effects of the drugs. This phenomenon leads to the rapid attenuation of the hemodynamic and anti-ischemic effects of nitrates in patients with ischemic heart disease or congestive heart failure, or both. Tolerance development seems to be dose- and time-dependent, and its main mechanism seems to be a depletion of sulfhydryl groups at the vascular cell. Although the repletion of sulfhydryl groups with the use of sulfhydryl-containing drugs may help to prevent tolerance, the efficacy and safety of this approach requires further evaluation. Intermittent therapy allowing a sufficiently long, daily nitrate-washout interval seems to be the most effective and the most safe strategy currently available for the prevention of nitrate tolerance.
The swelling-activated chloride channel ClC-2, the chloride channel ClC-3, and ClC-5, a chloride channel mutated in kidney stone disease, are expressed in distinct subpopulations of renal epithelial cells.
Authors: N Obermüller, N Gretz, W Kriz, R F Reilly, R Witzgall
Journal: Journal of Clinical Investigation (1998)

The mammalian genome encodes at least nine different members of the ClC family of chloride channels. So far only two of them could be localized on a cellular level in the kidney. We now report on the precise intrarenal localization of the mRNAs coding for the chloride channels ClC-2, ClC-3 and ClC-5. Expression of ClC-2 mRNA, encoding a swelling-activated chloride channel, could be demonstrated in the S3 segment of the proximal tubule. The chloride channel ClC-3 mRNA and ClC-5 mRNA, coding for a chloride channel mutated in kidney stone disease, were both expressed in intercalated cells of the connecting tubule and collecting duct. Whereas ClC-3 mRNA expression was most prominent in the cortex of rat kidneys, ClC-5 mRNA was expressed from the cortex through the upper portion of the inner medulla. A detailed analysis revealed that ClC-3 was expressed by type B intercalated cells, whereas ClC-5 was expressed by type A intercalated cells. These findings have important implications for the pathogenesis of hereditary kidney stone disease caused by mutations in the CLCN5 gene.
PEG shielded MMP sensitive CPPs for efficient and tumor specific gene delivery in vivo
Authors: Kadi-Liis Veiman, Kadri Künnapuu, Tõnis Lehto, Kristina Kiisholts, Kalle Pärn, Ülo Langel, Kaido Kurrikoff
Journal: Journal of Controlled Release (2015)

Gene therapy has great potential to treat a range of different diseases, such as cancer. For that therapeutic gene can be inserted into a plasmid vector and delivered specifically to tumor cells. The most frequently used applications utilize lipoplex and polyplex approaches where DNA is non-covalently condensed into nanoparticles. However, lack of in vivo efficacy is the major concern that hinders translation of such gene therapeutic applications into clinics. In this work we introduce a novel method for in vivo delivery of plasmid DNA (pDNA) and efficient tumor-specific gene induction using intravenous (i.v) administration route. To achieve this, we utilize a cell penetrating peptide (CPP), PepFect14 (PF14), double functionalized with polyethylene glycol (PEG) and a matrix metalloprotease (MMP) substrate. We show that this delivery vector effectively forms nanoparticles, where the condensed CPP and pDNA are shielded by the PEG, in an MMP-reversible manner. Administration of the complexes results in efficient induction of gene expression specifically in tumors, avoiding normal tissues. This strategy is a potent gene delivery platform that can be used for tumor-specific induction of a therapeutic gene.
Btk is a positive regulator in the TREM-1/DAP12 signaling pathway
Authors: Tereza Ormsby, Eva Schlecker, Janina Ferdin, Anja Sibylle Tessarz, Pavla Angelisová, Afitap Derya Köprülü, Michael Borte, Klaus Warnatz, Ilka Schulze, Wilfried Ellmeier, Václav Hořejší, Adelheid Cerwenka
Journal: Blood (2011)
PREVALENCE AND CLINICAL OUTCOMES OF STENT FRACTURE AND RECOIL AFTER DRUG-ELUTING STENT IMPLANTATION
Authors: Naoki Saito, Kazushige Kadota, Mitsuru Yoshino, Koshi Miyake, Haruki Eguchi, Suguru Otsuru, Yuki Hayakawa, Daiji Hasegawa, Yoshikazu Shigemoto, Seiji Habara, Hiroyuki Tanaka, Shingo Hosogi, Tsuyoshi Tada, Naoki Oka, Harumi Kato, Yasushi Fuku, Hiroyuki Yamamoto, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2011)
Dexamethasone selectively attenuates prostanoid-induced vasoconstrictor responses in vitro.
Authors: W C Sessa, A Nasjletti
Journal: Circulation Research (1990)

Glucocorticoids bind to specific vascular receptors resulting in a variety of functional consequences that may affect vascular smooth muscle behavior. We, therefore, examined in rabbits the effect of treatment with dexamethasone (2.5 mg/kg) for 6 days on vascular responses to pressor prostanoids in aortic and carotid arterial rings and in the isolated perfused kidney. Isometric tension development to prostaglandin F2 alpha and U46619, a thromboxane/prostaglandin endoperoxide mimetic, was markedly reduced in vessels from dexamethasone-treated rabbits. The inhibitory effect of dexamethasone on vascular reactivity was manifested by an increase in the concentration of agonist for threshold tension development and a reduction in the maximal response to prostaglandin F2 alpha and U46619. In contrast, reactivity to phenylephrine, potassium, histamine, or endothelin was not affected by dexamethasone treatment. In addition, pressor responses to prostaglandin F2 alpha and U46619 in Krebs'-perfused kidneys from dexamethasone-treated rabbits were also diminished. These data suggest that dexamethasone selectively interferes with the expression of receptor-mediated contractile responses to eicosanoids.
Alcohol Consumption and Risk of Cardiovascular Disease and Death in Women
Authors: Luc Djoussé, I-Min Lee, Julie E. Buring, J. Michael Gaziano
Journal: Circulation (2009)

Background— Although an association between moderate alcohol consumption and decreased cardiovascular disease (CVD) and death has been reported, limited data are available on potential mediating mechanisms. We examined the association between alcohol and CVD and death in 26 399 women and estimated the proportion of reduced risk of CVD/death explained by a series of intermediate factors. Methods and Results— Alcohol consumption was self-reported at baseline, and CVD events and deaths were ascertained via follow-up questionnaires and medical records. Baseline levels of hemoglobin A1c, inflammatory markers, hemostatic factors, and lipids were measured. Blood pressure and hypercholesterolemia and treatment for lipids were self-reported. During a mean follow up of 12.2 years, 1039 CVD events and 785 deaths (153 CVD deaths) occurred. There was a J-shaped relation between alcohol consumption and incident CVD and total and CVD deaths in a multivariable model. Compared with abstainers, alcohol intake of 5 to 14.9 g/d was associated with 26%, 35%, and 51% lower risk of CVD, total death, and CVD death, respectively, in a multivariable model. For CVD risk reduction, lipids made the largest contribution to the lower risk of CVD (28.7%), followed by hemoglobin A1c/diabetes (25.3%), inflammatory/hemostatic factors (5%), and blood pressure factors (4.6%). All these mediating factors together explained 86.3%, 18.7%, and 21.8% of the observed lower risk of CVD, total death, and CVD death, respectively. Conclusions— These data suggest that alcohol effects on lipids and insulin sensitivity may account for a large proportion of the lower risk of CVD/death observed with moderate drinking under the assumption that the alcohol-CVD association is causal.
Penicillin allergy and the heterogenous immune responses of man to benzylpenicillin.
Authors: B B Levine, A P Redmond, M J Fellner, H E Voss, V Levytska
Journal: Journal of Clinical Investigation (1966)

The administration of benzylpenicillin (penicil- lin) to man has been shown to induce the synthesis of antibodies of several distinct haptenic speci- ficities and of several molecular classes (1-13).Specifically, skin-sensitizing antibodies of benzyl- penicilloyl (BPO) haptenic specificity (1-7, 11) and of the minor determinant specificities (6, 7, 11) have been demonstrated.Also, BPO-specific antibodies of IgM and IgG classes have been iden- tified in serum by passive hemagglutination (3-5, 8-10, 12, 13).We now report the results of as- says for BPO-specific IgM, IgG, and skin-sensitizing antibodies, and minor determinant specific skin-sensitizing antibodies in various groups of pa- tients with and without recent allergic reactions to penicillin.The data obtained describe the hetero- geneous immune responses to penicillin made by human beings and permit initial inferences as to the nature of the immunological mechanisms that mediate allergic reactions to penicillin.'
Nasal polyp inflammation. Effect of topical nasal steroid.
Authors: N Kanai, J Denburg, M Jordana, J Dolovich
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Topical nasal corticosteroid therapy produces clinical improvement in patients with nasal polyposis. To examine the mechanisms of steroid effect, we quantified the number of inflammatory cell types as well as the expression of relevant cell markers in nasal polyps from steroid treated patients (n = 11) and polyps from untreated patients (n = 10) judged to require polypectomy for symptomatic relief. We found that the majority of eosinophils in these tissues were in the stromal layers, and that the proportion of activated eosinophils (EG2+ versus total eosinophil count) was significantly lower in polyps from patients treated with the topical nasal steroid budesonide, 200 to 400 micrograms/d for 1 mo, than in polyps from untreated patients. We also found that in polyps from treated patients, the superficial stromal layer (SSL) and deep stromal layer (DSL) both contained a significantly lower tissue density of lymphocytes of CD3, CD4, and CD8 subsets. Treatment was also associated with a lower, albeit nonsignificant, expression of ICAM-1 and HLA-DR in the epithelium. The tissue density of CD14+ cells (monocyte/macrophage) and of tryptase+ cells (mast cells) was the same in the two groups. These findings demonstrate tissue effects of topical corticosteroid treatment which may point to the mechanisms of therapeutic benefit. In addition, these observations illustrate the value of markers that indicate cell functional activity rather than just cell numbers.
Paradoxical Results of Infundibular Resection in Tetralogy of Fallot
Authors: E. M. M. BESTERMAN, T. V. O'DONNELL, WALTER SOMERVILLE
Journal: Circulation (1959)

The ultimate aim of surgical treatment of Fallot's tetralogy is complete anatomic repair by removal of the obstruction to pulmonary blood flow and closure of the ventricular septal defect. This ideal has been achieved by a small number of surgeons using a pump oxygenator and cardiac arrest. Until it can be realized by all, less complete operations will be performed that will improve the condition without correcting it. Considerable clinical improvement follows infundibular resection by open cardiotomy with or without pulmonary valvotomy. Paradoxically some of these patients may develop a syndrome of heart failure due to the development of a left-to-right shunt through the ventricular septal defect.
A New Sulphonamide (Sulphonamide E.O.S.): Its Pharmacology, Chemotherapy, and Curative Value in Meningococcal Meningitis
Authors: N. Mutch
Journal: BMJ (1941)

MEDICAL oURNAL 503 previous day.Both of these specimens on the tellurite- iron-rosolic acid medium showed hundreds of colonies of Flexner's bacillus and absolutely no B. coli, whereas the same emulsion on MacConkey's plates yielded a profuse growth of B. coli and no recognizable colonies of B. dysenteriae.Summary Lactose nutrient agar containing, per 100 c.cm., 0.5 c.cm. of a 1 % alcoholic solution of rosolic acid, 0.5 c.cm. of a 1 % solution of potassium tellurite, and 1 c.cm. of a 4% solution of iron alum provides a medium on which Flexner's B. dysenteriae grows profusely, whereas there is great in- hibition of most strains of B. coli and B. lactis aerogenes.The growth of Salmonella food-poisoning organisms, typhoid and paratyphoid bacilli, Sonne's bacillus, and cholera vibrios is suppressed.
Alcohol Consumption and Mortality among Women
Authors: Charles S. Fuchs, Meir J. Stampfer, Graham A. Colditz, Edward L. Giovannucci, JoAnn E. Manson, Ichiro Kawachi, David J. Hunter, Susan E. Hankinson, Charles H. Hennekens, Bernard Rosner, Frank E. Speizer, Walter C. Willett
Journal: New England Journal of Medicine (1995)

Studies in men suggest that light-to-moderate alcohol intake is associated with a reduction in overall mortality, due primarily to a reduced risk of coronary heart disease. Among women with similar levels of alcohol consumption, an increased risk of breast cancer has been noted that complicates the balance of risks and benefits.
Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting
Authors: Youfei Guan, Yahua Zhang, Jing Wu, Zhonghua Qi, Guangrui Yang, Dou Dou, Yuansheng Gao, Lihong Chen, Xiaoyan Zhang, Linda S. Davis, Mingfeng Wei, Xuefeng Fan, Monica Carmosino, Chuanming Hao, John D. Imig, Richard M. Breyer, Matthew D. Breyer
Journal: Journal of Clinical Investigation (2007)

Clinical use of prostaglandin synthase-inhibiting NSAIDs is associated with the development of hypertension; however, the cardiovascular effects of antagonists for individual prostaglandin receptors remain uncharacterized. The present studies were aimed at elucidating the role of prostaglandin E2 (PGE2) E-prostanoid receptor subtype 1 (EP1) in regulating blood pressure. Oral administration of the EP1 receptor antagonist SC51322 reduced blood pressure in spontaneously hypertensive rats. To define whether this antihypertensive effect was caused by EP1 receptor inhibition, an EP1-null mouse was generated using a "hit-and-run" strategy that disrupted the gene encoding EP1 but spared expression of protein kinase N (PKN) encoded at the EP1 locus on the antiparallel DNA strand. Selective genetic disruption of the EP1 receptor blunted the acute pressor response to Ang II and reduced chronic Ang II-driven hypertension. SC51322 blunted the constricting effect of Ang II on in vitro-perfused preglomerular renal arterioles and mesenteric arteriolar rings. Similarly, the pressor response to EP1-selective agonists sulprostone and 17-phenyltrinor PGE2 were blunted by SC51322 and in EP1-null mice. These data support the possibility of targeting the EP1 receptor for antihypertensive therapy.
Myeloid Suppressors Decrease Melanoma Survival by Abating Tumor-Fighting T Cells
Authors: Rolf Kiessling, Yumeng Mao, Yago Pico de Coaña
Journal: Clinical Cancer Research (2014)

Abstract Disseminated malignant melanoma has a poor prognosis. Immunotherapy based on cytokines or checkpoint inhibitors has a protracted beneficial effect in a select group of patients. Understanding the mechanisms that inhibit tumor-specific T cells will help the development of biomarkers to formulate therapy for this disease. Clin Cancer Res; 20(6); 1401–3. ©2014 AACR.