tbuckley/cabot-search huggingface dataset:
<i>N-Ras</i>–Induced Growth Suppression of Myeloid Cells Is Mediated by<i>IRF-1</i>
Authors: Toby Passioura, Alla Dolnikov, Sylvie Shen, Geoff Symonds
Journal: Cancer Research (2005)

Abstract Activating mutations in ras oncogenes occur at high frequency in human malignancies and expression of activated ras in immortalized cells lines is generally transforming. However, somewhat paradoxically, ectopic expression of ras in some myeloid cell lines has been shown to induce growth suppression associated with up-regulation of the cyclin-dependent kinase inhibitor p21CIP1/WAF1 in a p16INK4a, p15INK4b, and p53 independent fashion. We have used cDNA array technology to compare the expression profile induced by activated N-ras (N-rasG13R) in growth-suppressed myeloid cells with that induced in myeloid cells, which are transformed by N-rasG13R. The expression profile induced in growth suppressed cells was consistent with differentiation and included the up-regulation of the transcription factor IFN regulatory factor-1 (IRF-1), a known transcriptional activator of p21CIP/WAF1 expression and a target of oncogenic mutations associated with myeloid leukemia. Antisense suppression of IRF-1 prevented N-rasG13R–associated growth arrest and up-regulation of p21CIP1/WAF1. These results define a novel tumor suppressive response to oncogenic signaling and provide a mechanistic link between growth suppression and differentiation in myeloid cells.
The Association Between Continuity of Care and the Overuse of Medical Procedures
Authors: Max J. Romano, Jodi B. Segal, Craig Evan Pollack
Journal: JAMA Internal Medicine (2015)

Both the overuse of unnecessary medical procedures and poor continuity of care are thought to contribute to high health care spending and poor patient outcomes.To investigate the association between care continuity and use of potentially unnecessary procedures.Observational retrospective cohort (n = 1,208,250 patients > 65 years) using 5% Medicare fee-for-service claims from 2008.We evaluated continuity using the Bice-Boxerman continuity of care index. We measured overuse using a previously validated set of 19 potentially overused procedures.Altogether, 14.7% of patients received at least 1 potentially overused procedure during the calendar year. For each 0.1 increase in the continuity score (0.4 SDs), patients had 0.93 times the odds of receiving overused procedures than those with lower scores (95% CI, 0.93-0.94). Higher continuity was significantly associated with lower odds of 9 procedures (Holm-Bonferroni corrected P < .02 was significant: 6 of 13 diagnostic tests [with ORs, 0.84-0.99; P < .001] and 3 therapeutic procedures [with ORs 0.81-0.87; P <.001]). Conversely, higher continuity was significantly associated with increased overuse for 3 procedures (1 diagnostic test [OR, 1.06; P < .001], 1 of 2 screening tests [OR, 1.05; P < .001], and the single monitoring test [OR, 1.03; P < .01]).Increased continuity was associated with an overall decrease in overuse, suggesting a potential benefit of high-continuity care; however, the strength and direction of the association varied according to the specific procedure.
Dysfunctional CD39<sup>POS</sup>regulatory T cells and aberrant control of T-helper type 17 cells in autoimmune hepatitis
Authors: Charlotte R. Grant, Rodrigo Liberal, Beth S. Holder, John Cardone, Yun Ma, Simon C. Robson, Giorgina Mieli-Vergani, Diego Vergani, Maria Serena Longhi
Journal: Hepatology (2013)

Autoimmune hepatitis (AIH) is an important cause of severe liver disease and is associated with both quantitative and qualitative regulatory T-cell (Treg) impairments. Tregs express CD39, an ectonucleotidase responsible for extracellular nucleotide hydrolysis, culminating in the production of immunosuppressive adenosine. Here, we describe multiple CD39pos Treg defects that potentially contribute to the impaired immunoregulation that is characteristic of AIH. We have examined the frequency and phenotype of CD39pos Tregs by flow cytometry and measured their ectonucleotidase activity. The capacity of CD4posCD25high, CD4posCD25highCD39pos, and CD4posCD25highCD39neg subsets to suppress both proliferation of effector T cells and interleukin (IL)-17 production was evaluated. In AIH, CD39pos Tregs are decreased in frequency, exhibit limited adenosine triphosphate/adenosine diphosphate hydrolysis activity, and fail to suppress IL-17 production by effector CD4 T cells. Moreover, these CD39pos Tregs display a more proinflammatory profile in AIH, which is characterized by elevated CD127 positivity, and a greater propensity to produce interferon-gamma or IL-17 upon challenge with proinflammatory stimuli. Conclusions: In AIH, CD39pos Tregs are decreased in number, fail to adequately hydrolyze proinflammatory nucleotides and do not efficiently suppress IL-17 production by effector CD4 T cells. CD39pos Tregs show plasticity and are unstable upon proinflammatory challenge, suggesting that defective immunoregulation in AIH might result not only from reduced Treg number and function, but also from increased conversion of Tregs into effector cells. (Hepatology 2014;59:1007–1015)
Rheumatic and Metabolic Bone Diseases in the Elderly.
Authors: David F. Giansiracusa, Fred G. Kantrowitz
Journal: Annals of Internal Medicine (1982)

For the busy physician later in life, confident in his craft and perhaps a little bored by it, literature has special virtues.It takes him from the grinding reality of the clinic into realms of imagination, lyricism and drama; it provides those moments of delectation without which the soul shrivels.Literature refreshes the physician's view of the men and women he sees as 'patients' and restores them to their real roles in the human drama.... Whatever enriches the doctor's sensibilities must make him a better physician.""Medicine and Literature" instructs.The book is not just for the medical reader with a dilettante's interest in literature.It is a thoughtful, scholarly, readable book; a book to browse over by the fire, to learn from, to refer to, to enjoy andrarely -to lend.
Abstract 12662: Differences in Journal Impact Factor(IF) Between Initial and Subsequent Publication of Cardiovascular Clinical Trials-An Analysis From the ClinicalTrials.gov Repository
Authors: Jasjit Bhinder, Saurav Chatterjee, Franz H Messerli
Journal: Circulation (2014)

Introduction: After publication of the primary outcome of a clinical trial additional data of interest continue to be published -.To achieve high visibility of their findings most authors tend to select journals with a high IF. The IF is often viewed as a measure of journal quality as a whole. Hypothesis: We compared IF of journals where the primary outcomes from a clinical trial were published to IF of journals where subsequent papers were published. Methods: This was a cross sectional analysis design. We analyzed cardiovascular clinical trials from Clinicaltrials.gov. We did not limit our search by date. We chose clinical trials which had 2 or more published manuscripts in journals with indexed IFs. We queried the Thomson Reuters’ Web of Knowledge to determine the individual IF. Results: Our search returned 72 cardiovascular clinical trials from a query of the Clinicaltrials.gov database. The mean IF of the primary index publication from the trials were 27.01 (95% confidence interval-CI 21.96-32.06); while that from subsequent publications from the same trials were 11.72 (95% CI 8.97-14.47). The mean difference in IF of journals publishing the index and subsequent results was 15.28 (95% 2.11-17.96). There was a strong correlation between the initial publication IF and the IF difference with the subsequent manuscript (p&lt;0.001). Conclusions: The initial publications of cardiovascular trials consistently occur in journals with an IF higher than in subsequent publications. The higher the journal IF of the initial publication the greater the difference in journal IF between initial and subsequent publications.
Abstract 20662: Variations in Local Calcium Signaling in Adjacent Cardiomyocytes of the Intact Mouse Heart Detected With Two-Dimensional Confocal Microscopy
Authors: Karin P Hammer, Burkert M Pieske, Frank R Heinzel
Journal: Circulation (2014)

Coordinated Ca release in the heart ensures efficient myocardial contraction and electrical stability. Dyssynchronous Ca release within individual cardiomyocytes has been linked to cellular contractile dysfunction. Differences in Ca kinetics in adjacent cells may also provide a substrate for inefficient contraction and arrhythmias. We present an approach to quantify local Ca signals related to the geometry of adjacent cardiomyocytes within the intact heart using 2D confocal microscopy. We observe significant differences in Ca kinetics between adjacent cardiomyocytes. Methods: Ca transients (CaT, Fluo-8 AM) and cell membranes (Di-4 ANEPPS) were visualized in an epicardial area of 465 μm by 315 μm (12 to 20 cells) in Langendorff-perfused mouse hearts. Images (55/second) from a series of CaT at steady state stimulation (250 ms cycle length) were registered to their relative timepoint in the cardiac cycle to restore local CaT with a temporal resolution of 2 ms. Variation of local CaT within a cardiomyocyte (INTRA) and between adjacent cardiomyocytes (INTER) were compared with regard to amplitude, time to peak (TTP) and time constant of decay (TAU). Results: Temporal registration of images from successive CaT yielded local signals with good signal/noise ratio (N= 4 hearts, n= 8 regions). Along the long axis but not along the short axis of cardiomyocyte orientation the variation of CaT amplitude was significantly larger between that within cells (INTER 51.49 ±23.57% vs. INTRA &lt;0.01 ±0.001% of global Ca amplitude). Variation in TTP Ca was comparable in all directions, but TAU also tended to vary more along the long axis (INTER 68.50 ±27.03% vs. INTRA 37.74 ±13.17%). Isoproterenol (10 μM) significantly increased the differences in TAU between adjacent cardiomyocytes along the short axis but not along the long axis. Summary: We present an approach to detect and analyze local Ca signals in Langendorff-perfused intact mouse hearts with high temporal and spatial resolution, taking into account 2D orientation of the cells. We observed significant differences in the synchrony of Ca signals along the long and short axis of adjacent cardioymyocytes. Alterations in synchrony of Ca signals in neighboring cells may contribute to the substrate in cardiac remodeling.
Involvement of the high-affinity receptor for IgG (Fc gamma RI; CD64) in enhanced tumor cell cytotoxicity of neutrophils during granulocyte colony-stimulating factor therapy
Authors: T Valerius, R Repp, TP de Wit, S Berthold, E Platzer, JR Kalden, M Gramatzki, JG van de Winkel
Journal: Blood (1993)
Impaired Hematopoiesis in Paroxysmal Nocturnal Hemoglobinuria/Aplastic Anemia Is Not Associated With a Selective Proliferative Defect in the Glycosylphosphatidylinositol-Anchored Protein-Deficient Clone
Authors: Jaroslaw P. Maciejewski, Elaine M. Sloand, Tadatsugu Sato, Stacie Anderson, Neal S. Young
Journal: Blood (1997)
THE TREATMENT OF SUBACUTE BACTERIAL ENDOCARDITIS WITH PENICILLIN AND SODIUM PARA-AMINOHIPPURATE BY CONTINUOUS INTRAVENOUS DRIP
Authors: R WALL, O BRUNDAGE
Journal: Annals of Internal Medicine (1949)

Case Reports1 June 1949THE TREATMENT OF SUBACUTE BACTERIAL ENDOCARDITIS WITH PENICILLIN AND SODIUM PARA-AMINOHIPPURATE BY CONTINUOUS INTRAVENOUS DRIPROBERT WALL, M.D., OLIVER BRUNDAGE, M.D.ROBERT WALL, M.D.Search for more papers by this author, OLIVER BRUNDAGE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-30-6-1295 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe use of penicillin with and without heparin in the treatment of subacute bacterial endocarditis has justified the hope for temporary or permanent arrest of this disease. The addition of sodium para-aminohippurate as an enhancing agent may increase the effectiveness of penicillin therapy. Its use with penicillin in the treatment of subacute bacterial endocarditis has been reported by Loewe1 and others with evident success.Our patient was thought worthy of report because of: (1) the finding of a relatively resistant organism identified asStreptococcus viridans, (2) the large quantities of penicillin and para-aminohippurate administered, and (3) the apparent success of...Bibliography1. LOEWEROSENBLATTGREENERUSSELL LPHM: Combined penicillin and heparin therapy of subacute bacterial endocarditis, report of seven consecutive successfully treated patients, Jr. Am. Med. Assoc., 1944, cxxiv, 144-149. CrossrefGoogle Scholar2. LOEWEROSENBLATTRUSSELLALTURE-WERBER LPME: The superiority of the continuous drip for the maintenance of effectual serum levels of penicillin: comparative studies with particular reference to fractional and continuous intramuscular administration, Jr. Lab. and Clin. Med., 1945, xxx, 730-735. Google Scholar3. LOEWEROSENBLATTALTURE-WERBERKOZAK LPEM: The prolonging action of penicillin by para-aminohippuric acid, Proc. Soc. Exper. Biol. and Med., 1945, lviii, 298-300. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication July 21, 1947. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byErkrankungen des EndokardTreatment of Bacterial EndocarditisDie Therapie der Endocarditis lenta und ihre Grundlagen 1 June 1949Volume 30, Issue 6Page: 1295-1300KeywordsBacterial diseasesEndocarditisHeparinPenicillinSodiumStreptococcus ePublished: 1 December 2008 Issue Published: 1 June 1949 PDF downloadLoading ...
Abstract #4437: BRCA1 expression is downregulated in uterine leiomyosarcomas
Authors: Yevgeniya Ioffe, Xuan Xu, Deyin Xing, Esther Oliva, Beth Karlan, Sandra Orsulic
Journal: Cancer Research (2009)

Objectives:  Uterine leiomyosarcoma (ULMS) is a rare tumor that accounts for approximately one percent of all uterine malignancies. More than 80% of patients experience tumor recurrence after initial treatment, in large part responsible for ULMS\#8217; high mortality. Germline BRCA1 mutations have not been associated with a predisposition to developing ULMS, indicating that genomic alterations of BRCA1 are unlikely to play a role in the development of this disease. It is possible, however, that genetic or epigenetic somatic inactivation of BRCA1 contributes to the progression of ULMS. In a murine model of ULMS, our laboratory has previously shown that the loss of BRCA1 function accelerates tumor formation. This finding prompted us to hypothesize that BRCA1 expression may be altered in human ULMS. To address this question, we evaluated BRCA1 protein expression in a cohort of ULMS and benign uterine leiomyoma human tissue specimens.    Methods:  Paraffin-embedded sections from sixty-seven ULMS and twenty-eight benign leiomyomas were obtained from the institutional pathology departments under an IRB-approved protocol. Immunohistochemical staining with BRCA1 antibody (Calbiochem, 1:100 dilution) was performed on the sections using the avidin-biotin immunoperoxidase method. Nuclear positivity was scored by two independent observers using microscopy and was quantified as either present or absent. Results were analyzed using a two-tailed Fisher\#8217;s exact test.    Results:  By IHC analysis, BRCA1 protein expression was absent in twenty-four out of sixty-seven ULMS samples. In contrast, BRCA1 expression was absent in zero out of twenty-eight benign leiomyoma samples. This difference in BRCA1 expression was statistically significant with  p    Conclusion:  Our results indicate a significant difference in BRCA1 expression between ULMS and benign uterine leiomyoma. This observation suggests that BRCA1 silencing might play a role in the development or progression of ULMS. Our findings provide a rationale for investigation of targeted therapies tailored to take advantage of the absence of BRCA1 expression.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4437.
Tat-immunoconjugates specifically inhibit the function of nuclear p21WAF-1/CIP-1 and differentially sensitize human breast cancer cells to antiproliferative agents
Authors: Meiduo Hu, Judy Wang, Paul Chen, Katherine Vallis, Raymond Reilly
Journal: Cancer Research (2006)

4869  p21WAF-1/CIP-1 is a central downstream effector of the p53-mediated response of breast cancer (BC) cells to DNA-damaging treatments. We have designed specific HIV-1 transactivator peptide (tat) immunoconjugates (IC’s) that penetrate the membrane of BC cells and translocate to the nucleus where they inhibit the ability of p21WAF-1/CIP-1 to cause G1/S-phase arrest. Our objective in this study was to determine if these tat-anti-p21WAF-1/CIP-1 IC’s would sensitize BC cells to antiproliferative agents that mediate their effects through p21WAF-1/CIP-1. MDA-468 [high epidermal growth factor receptor (EGFR), mutant p53] and MCF-7 (low EGFR, wild type p53) were treated with camptothecin (CPT; 0.1-4 μM) or EGF (0.5-10 nM), respectively, or with γ-radiation (2-20 Gy) for 0-24 h. Treatments were given alone or combined with tat-anti-p21WAF-1/CIP-1 IC’s (5 μM). Response was evaluated at early times (24 h) after EGF or CPT exposure or γ-radiation (8 h) by studying p21WAF-1/CIP-1 induction (Western blot), cell cycle distribution (flow cytometry) and proliferation (WST-1 assay). Treatment of MDA-468 cells with EGF or CPT increased p21WAF-1/CIP-1 expression 2-5-fold and caused G1/S-phase arrest. Cell growth was inhibited 27.5 ± 0.6% or 31.8 ± 2.5% by 10 nM EGF or 1 μM CPT, respectively. Growth inhibition was significantly increased by 11.6 ± 0.4% or 29.2 ± 1.1% for EGF-treated (p=0.0001) or CPT-treated (p=0.0004) cells, respectively, when co-treated with tat-anti-p21WAF-1/CIP-1 IC’s. γ-radiation did not induce p21WAF-1/CIP-1 in MDA-468 cells but growth was inhibited 31.8 ± 1.9% at 8 h post-treatment; tat-anti-p21WAF-1/CIP-1 IC’s did not increase cell growth inhibition in these cells (26.8 ± 3.9%, p=0.311). MCF-7 cells exposed to γ-radiation or CPT had a 3-5-fold induction of p21WAF-1/CIP-1 associated with G2/M-arrest (γ-radiation) or prolonged S-phase (CPT). Cell growth was inhibited 15.4 ± 4.3% or 21.0 ± 2.5 % by 10 Gy γ-radiation at 8 h post-exposure or 1 μM CPT at 24 h post-treatment, respectively. Co-treatment with tat-anti-p21WAF-1/CIP-1 IC’s significantly increased growth inhibition by 28.9 ± 4.9% or 11.3 ± 0.9%, respectively for γ-radiation (p=0.011) or CPT (p=0.013). EGF was growth-stimulatory to MCF-7 cells; there was no effect on p21WAF-1/CIP-1 induction and tat-anti-p21WAF-1/CIP-1 IC’s did not increase growth inhibition. We conclude that tat-anti-p21WAF-1/CIP-1 IC’s differentially sensitized BC cells to antiproliferative agents that mediate their effects through p21WAF-1/CIP-1. To our knowledge, this is the first report of the use of specific tat-immunoconjugates for blocking the function of key nuclear cell cycle checkpoint proteins. This new approach provides opportunities to enhance the response to treatment in BC by interfering with protective mechanisms that rely on cell cycle arrest.
Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure
Authors: Ralf Birkenhäger, Edgar Otto, Maria J. Schürmann, Martin Vollmer, Eva-Maria Ruf, Irina Maier-Lutz, Frank Beekmann, Andrea Fekete, Heymut Omran, Delphine Feldmann, David V. Milford, Nicola Jeck, Martin Konrad, Daniel Landau, Nine V.A.M. Knoers, Corinne Antignac, Ralf Sudbrak, Andreas Kispert, Friedhelm Hildebrandt
Journal: Nature Genetics (2001)
Treatment of severe pemphigus with protein A immunoadsorption, rituximab and intravenous immunoglobulins
Authors: I. Shimanovich, M. Nitschke, C. Rose, J. Grabbe, D. Zillikens
Journal: British Journal of Dermatology (2007)

Pemphigus is a life-threatening autoimmune blistering disease usually treated with high-dose corticosteroids and other immunosuppressants. However, this regimen may prove inadequate in severe cases and cause dangerous side-effects. While protein A immunoadsorption (PAIA) induces a rapid remission in severe pemphigus, the disease usually recurs once the treatment is stopped. In contrast, anti-CD20 antibody rituximab has a delayed onset of action but may lead to a long-term remission of pemphigus.To develop a treatment protocol combining the rapid remission induced by PAIA with the positive long-term effects of rituximab.Five patients with pemphigus vulgaris and two patients with pemphigus foliaceus were treated with a combination of PAIA, rituximab and conventional immunosuppressants. Patients who failed to respond to this therapy subsequently received intravenous immunoglobulins (IVIg).All seven patients showed a sharp decline of circulating autoantibody levels and rapid improvement of cutaneous and mucosal lesions within 4 weeks of therapy. Long-term remission was induced in three patients and one further patient showed a partial improvement of his disease. The three remaining patients who could not be weaned off PAIA and remained resistant to rituximab treatment showed a good response to IVIg therapy.The combination of PAIA and rituximab induces a rapid and durable remission in a subset of patients with severe pemphigus. IVIg therapy appears to be a good treatment option for rituximab nonresponders.
460. Immunogenicity of E2b-Deleted Adenoviral Vectors Compared with First Generation Vectors
Authors: Catherine Hsu, Megan M. Boysen, Phyllis D. Frosst, Dan J. Von Seggern
Journal: Molecular Therapy (2004)

Numerous studies have shown that adenovirus (Ad)-mediated delivery of a gene encoding a tumor antigen to dendritic cells (DC) can lead to a T cell response directed against tumor antigens, but the vectors generally used in gene therapy are based on an viral serotype (Ad5) that infects DC very inefficiently. The inefficiency of infection generally requires that cells be manipulated ex vivo, infected, and re-infused. This is complicated, expensive, and involves generation of patient-specific reagents. Ad tropism is largely determined by binding of the viral fiber protein to cells, and DC have been shown to lack the fiber receptor (CAR) used by Ad5. We hypothesized that Ad vectors that more efficiently infected DC would allow vector administration directly to patients and eliminate ex vivo cell culture.