tbuckley/cabot-search huggingface dataset:
Telomere Dysfunction Drives Aberrant Hematopoietic Differentiation and Myelodysplastic Syndrome
Authors: Simona Colla, Derrick Sek Tong Ong, Yamini Ogoti, Matteo Marchesini, Nipun A. Mistry, Karen Clise-Dwyer, Sonny A. Ang, Paola Storti, Andrea Viale, Nicola Giuliani, Kathryn Ruisaard, Irene Ganan Gomez, Christopher A. Bristow, Marcos Estecio, David C. Weksberg, Yan Wing Ho, Baoli Hu, Giannicola Genovese, Piergiorgio Pettazzoni, Asha S. Multani, Shan Jiang, Sujun Hua, Michael C. Ryan, Alessandro Carugo, Luigi Nezi, Yue Wei, Hui Yang, Marianna D’Anca, Li Zhang, Sarah Gaddis, Ting Gong, James W. Horner, Timothy P. Heffernan, Philip Jones, Laurence J.N. Cooper, Han Liang, Hagop Kantarjian, Y. Alan Wang, Lynda Chin, Carlos Bueso-Ramos, Guillermo Garcia-Manero, Ronald A. DePinho
Journal: Cancer Cell (2015)
No Sign of Proliferative Retinopathy in 15 Patients With Permanent Neonatal Diabetes With a Median Diabetes Duration of 24 Years
Authors: Dario Iafusco, Silvana Salardi, Giovanni Chiari, Sonia Toni, Ivana Rabbone, Roberta Pesavento, Bruno Pasquino, Antonella de Benedictis, Giulio Maltoni, Carlo Colombo, Lucia Russo, Ornella Massa, Maurizio Sudano, Francesco Cadario, Massimo Porta, Fabrizio Barbetti
Journal: Diabetes Care (2014)

The knowledge about the long-term consequences of diabetes with onset in the neonatal period is scanty. We investigated the impact of long-standing diabetes (>15 years) on the retina of 10 patients with permanent neonatal diabetes mellitus (PNDM) (diabetes diagnosis within 6 months of birth) associated with mutations of GCK , KCNJ11 , INS , or ABCC8 genes and of two parents carrying an INS gene mutation diagnosed with diabetes in their childhood (1,2) (Table 1, patients 1–12). Eye complications were also evaluated in three patients with diabetes onset within 1 year of age and negative for type 1A diabetes autoantibodies (2) (Table 1, patients 13–15).

View this table:

Table 1 
Clinical and genetic features of PNDM patients with a median diabetes duration of 24 years



The mean age at diagnosis of diabetes of patients with …
Genistein reduces androgen dependent and independent prostate cancer in TRAMP mice.
Authors: Jun Wang, Isam-Eldin Eltoum, Coral A. Lamartiniere
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5584 

Epidemiological studies suggest an inverse association between soy intake and prostate cancer risk. Genistein, the predominant phytoestrogen in soy food, has been proposed as a potential chemopreventive agent mainly due to its estrogen/anti-estrogen and tyrosine kinase inhibitory properties. We used the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) model to test the hypothesis that dietary genistein would prevent prostate cancer progression. To determine the most effective period for genistein chemoprevention, we treated TRAMP mice (30/group) with a) AIN-76A control diet only, or 250 mg genistein/kg AIN-76A diet during the following periods b) prepubertal only, c) as adults only and d) for lifetime. At 28 weeks of age, histopathological evaluations performed by a certified pathologist revealed the following incidence of poorly differentiated adenocarcinomas, controls: 34.4%; genistein from 1–35 days: 32.3%; genistein from 84–196 days: 24.1%; genistein from 1–196 days: 16.7%. The most significant effect was seen in the TRAMP mice exposed to genistein throughout life (1–196 days) with a 51% decrease in poorly-differentiated cancerous lesions compared to controls. To investigate the effect of adult genistein treatment on androgen-independent prostate cancer development, TRAMP mice were castrated at 12 weeks of age and monitored until sacrifice at 28 weeks. After castration, controls were provided with AIN-76A diet only (n=47) or 250 mg genistein/kg AIN-76A diet from 12 to 28 weeks (n=39). Castrated TRAMP mice fed control diet had 23% poorly-differentiated prostate cancerous lesions while castrated TRAMP mice fed genistein had 15% incidence poorly-differentiated cancerous lesions. Hence, dietary genistein suppressed poorly-differentiated cancerous lesions by a 35% decrease compared with control group in castrated TRAMP mice. Associated with this suppressive effect on androgen-independent prostate cancer is down-regulation of SV40 T-antigen protein levels and cell proliferation as measured by immunohistochemistry for proliferating cell nuclear antigen, respectively. Castration of TRAMP mice resulted in decreased androgen receptor and increased phospho-extracellular regulated kinases 1 and 2 protein expression in prostate tumors. Our data obtained in intact and castrated transgenic mice that spontaneously develop prostate tumors suggest that genistein may be a promising chemopreventive agent against prostate cancer. Supported by NIH/NIEHS 1 R01 ES-11743.
A phase 2, randomized, double‐blind, placebo‐controlled study of siltuximab (anti‐IL‐6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma
Authors: Robert Z. Orlowski, Liana Gercheva, Cathy Williams, Heather Sutherland, Tadeusz Robak, Tamás Masszi, Vesselina Goranova‐Marinova, Meletios A. Dimopoulos, James D. Cavenagh, Ivan Špička, Angelo Maiolino, Alexander Suvorov, Joan Bladé, Olga Samoylova, Thomas A. Puchalski, Manjula Reddy, Rajesh Bandekar, Helgi van de Velde, Hong Xie, Jean‐Franςois Rossi
Journal: American Journal of Hematology (2014)

We compared the safety and efficacy of siltuximab (S), an anti‐interleukin‐6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. Siltuximab was given by 6 mg/kg IV every 2 weeks. On progression, B was discontinued and high‐dose dexamethasone could be added to S/plc. Response and progression‐free survival (PFS) were analyzed pre‐dexamethasone by European Group for Blood and Marrow Transplantation (EBMT) criteria. For the 281 randomized patients, median PFS for S + B and plc + B was 8.0 and 7.6 months (HR 0.869, P = 0.345), overall response rate was 55 versus 47% ( P = 0.213), complete response rate was 11 versus 7%, and median overall survival (OS) was 30.8 versus 36.8 months (HR 1.353, P = 0.103). Sustained suppression of C‐reactive protein, a marker reflective of inhibition of interleukin‐6 activity, was seen with S + B. Siltuximab did not affect B pharmacokinetics. Siltuximab/placebo discontinuation (75 versus 66%), grade ≥3 neutropenia (49 versus 29%), thrombocytopenia (48 versus 34%), and all‐grade infections (62 versus 49%) occurred more frequently with S + B. The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or refractory multiple myeloma. © 2014 Wiley Periodicals, Inc. Am. J. Hematol. 90:42–49, 2015. © 2014 Wiley Periodicals, Inc.
Abstract 4081: Id4 (inhibitor of dna binding 4) crosstalk with pten-akt pathway
Authors: Shravan Kumar Komaragiri
Journal: Cancer Research (2014)

Abstract Introduction: Inhibitor of DNA binding/differentiation protein 4 (Id4), acts as a dominant negative regulator of basic helix loop helix (bHLH) family of transcription factors. Id4 shares the homology of HLH domain with other Ids and lack the basic DNA binding region. Previous studies from our lab had shown that unlike Id1, Id2 and Id3, Id4 acts as a tumor suppressor in prostate cancer by attenuating cell proliferation and promoting apoptosis. In this study we investigated whether Id4 acts as a tumor suppressor by regulating the AKT pathway. Experimental procedures: Id4 protein expression was analyzed on human prostate adenocarcinoma samples by Immunohistochemistry. We also performed Immunohistochemistry to determine AKT, pAKT, PTEN protein expression in Id4 knockout mouse prostates. In addition we determined the expression levels of the above mentioned proteins in prostate cancer cell lines with or without Id4 (LNCaP, LNCaP-Id4, DU145, DU145+Id4, PC3). Results: IHC demonstrated decreased Id4 protein expression in human prostate tissue samples whereas higher nuclear Id4 expression was found in normal human and mouse prostate tissues. IHC on Id4 knockout (Id4-/-) mouse prostates demonstrated an increase in pAKT expression, whereas AKT expression did not change significantly when compared to normal mouse prostate. PTEN expression levels decreased ignificantly in Id4 knockout mouse prostates. Similar pattern was observed in prostate cancer cell lines: DU145 cells lacking Id4 had low PTEN as compared to Id4 over-expressing DU145 cells. Id4 expression was also associated with PI3 kinase activity in LNCaP and PC3 cells. These results suggest Id4 regulates AKT-PI3K pathway by attenuating PTEN. Conclusions: Id4 appears as a potential tumor suppressor gene that exerts its tumor suppressor activity by promoting PTEN expression. PTEN in turn regulates AKT phosphorylation that stabilizes p53, AR and NKX3.1 expression in the normal prostate. Acknowledgement: The research was supported by NIH/NCI-RO1CA128914 and in part by NIH/NCRR/RCMI G12RR03062 Citation Format: Shravan Kumar Komaragiri. Id4 (inhibitor of dna binding 4) crosstalk with pten-akt pathway. [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 4081. doi:10.1158/1538-7445.AM2014-4081
Fasting and Medical Issues During Ramadan
Authors: Sondra S Crosby, Elizabeth J Rourke, Mohamed A Warfa
Journal: JAMA (2005)

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
OBSERVATIONS ON THE TREATMENT OF LIPOID NEPHROSIS
Authors: Ralph H. Major
Journal: Annals of Internal Medicine (1939)

Article1 April 1939OBSERVATIONS ON THE TREATMENT OF LIPOID NEPHROSISRALPH H. MAJOR, M.D.RALPH H. MAJOR, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-10-1555 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe disease known as chronic nephrosis or lipoid nephrosis has been the subject of continued dispute since the initial publications of Munk and of Epstein. Opinion still seems to be divided as to whether it is a type of glomerulonephritis or a distinct clinical and pathological entity. There is apparently an increasing amount of opinion favoring the latter view.In a series of 14 patients, who have been carefully followed since their dismissal from the hospital, all are alive and consider themselves well. All of the 14 show at the present time a normal blood chemistry and are entirely free...Bibliography1. BESTHUNTSMAN CHME: The effects of the components of lecithine upon deposition of fat in the liver, Jr. Physiol., 1932, lxxv, 405. CrossrefGoogle Scholar2. COLLIP JB: Chemistry and physiology of anterior pituitary hormones, Trans. Congr. Am. Phys. and Surg., Fifteenth Session, 47. Google Scholar3. MAJOR RH: The after-history of lipoid nephrosis, Trans. Assoc. Am. Phys., 1935, l, 128. Google Scholar4. THADDEAFASSHAUER SW: Nebennierenrinde und Cholesterinstoffwechsel, Arch. f. exper. Path. u. Pharmakol., 1936, clxxxii, 477. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Kansas City, Kansas*Received for publication March 4, 1938.From the Department of Internal Medicine, University of Kansas School of Medicine. Kansas City, Kansas. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDegenerative Nierenerkrankungen 1 April 1939Volume 12, Issue 10Page: 1555-1559KeywordsBlood chemistryGlomerulonephritis ePublished: 1 December 2008 Issue Published: 1 April 1939 Copyright & PermissionsCopyright, 1939, by The American College of PhysiciansPDF downloadLoading ...
144. In Vivo Studies on the Toxicity of Adenovirus Vectors for Kupffer Cells
Authors: Elanchezhiyan Manickan, Jeffrey S. Smith, Jie Tian, Andrew P. Byrnes
Journal: Molecular Therapy (2005)

When adenovirus type 5 vectors (AdVs) are injected into the bloodstream, the liver macrophages known as Kupffer cells (KCs) take up the vast majority of the virions, preventing the vector from reaching other more desirable targets, and contributing to the innate immune response. It has also been reported that AdVs cause a large decrease in the number of KCs in the liver (Schiedner et al 2003, Human Gene Ther 14:1631). In the current study, we provide evidence that AdVs are rapidly cytotoxic for KCs in vivo, and we describe an anatomical pathway for the depletion of KCs.
Abstract 1966: A unique cross-talk between HER2 and sonic hedgehog signaling promotes anoikis resistance in breast cancer cells
Authors: Parul Gupta, Sanjay K. Srivastava
Journal: Cancer Research (2014)

Abstract Metastatic cancer cells possess a unique capacity to survive without appropriate signaling from the extracellular matrix (ECM). The epithelial cells surrounded by proper ECM within tissues are designed to grow and differentiate whereas epithelial cells lacking suitable EMC are destined to anoikis, a form of apoptosis. The metastatic cancer cells resist anoikis to survive under the absence of ECM. Current study identifies a novel interplay between HER2 and sonic hedgehog signaling in promoting anoikis resistance. MDA-MB-231 cells exhibited an up-regulation of HER2 expression in cells cultured under anchorage- independent conditions as compared to adherent cells. Similar phenomenon was also observed in 4T-1 cells. The survival of MDA-MB-231 cells with stable HER2 overexpression (HH) was significantly enhanced when cultured under anchorage-independent conditions. However, the enhanced survival of MDA-MB-231 (HH) was reduced when HER2 was silenced using shRNA. These observations indicate the obligatory role of HER2 in anoikis resistance. Furthermore cells grown under anchorage-independent conditions induced the expression of sonic hedgehog (SHH). Increase in SHH was accompanied with enhanced expressions of PTCH2 and GLI2, the receptor and subsequent transcription factors of the sonic hedgehog signaling. Our results further showed that the induction of SHH was significantly higher in MDA-MB-231 (HH) cells relative to parent cells when cultured under anchorage-independent conditions, suggesting a correlation between HER2 and SHH signaling. Treatment of MDA-MB-231 and 4T-1 cells with cyclopamine (SHH signaling inhibitor) reduced the survival of cells under anchorage-independent conditions. Interestingly, cyclopamine treatment also inhibited the induction of HER2 during anchorage-independent culture conditions. Taken together, our study suggests a SHH-mediated induction of HER2 to promote anoikis resistance in breast cancer cells. Further mechanistic and in vivo studies are under progress. [Supported in part by R01 grant CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: Parul Gupta, Sanjay K. Srivastava. A unique cross-talk between HER2 and sonic hedgehog signaling promotes anoikis resistance in breast cancer cells. [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 1966. doi:10.1158/1538-7445.AM2014-1966
Sirt1 Limits Endothelial Notch Signaling During Blood Vessel Growth Through NICD Deacetylation
Authors: Michael Potente
Journal: Circulation (2009)

Abstract #3056 Michael Potente, Virginia Guarani, Inst for Cardiovascular Regeneration, Frankfurt, Germany; Gianluca Deflorian, IFOM, the FIRC Inst of Molecular Oncology, Milan, Italy; Raul Mostoslavsky, The MGH Cancer Ctr-Harvard Medical Sch, Boston, MA; Ralf Brandes, Inst for Cardiovascular Physiology, Frankfurt, Germany; Marina Mione, IFOM, the FIRC Inst of Molecular Oncology, Milan, Italy; Holger Gerhardt, Vascular Biology Lab, London, United Kingdom; Andreas M Zeiher, Dept of Cardiology, Frankfurt, Germany; Stefanie Dimmeler, Inst for Cardiovascular Regeneration, Frankfurt, Germany Michael Potente, 2009 Finalist and Presenting Author
Abstract 15469: Depressive Symptoms are Associated with Arterial Stiffness in Premenopausal Women with Type 1 Diabetes
Authors: Shideh Majidi, Sandra Ruland, Lindsey Duca, Rachel Sippl, Janet Snell-Bergeon
Journal: Circulation (2014)

Cardiovascular disease (CVD) is the primary cause of mortality in people with diabetes. Arterial stiffness is increased in type 1 diabetes (T1D) even in young adulthood. Depression rates are higher in T1D versus non-diabetic (non-DM) people, and in the general population, depressive symptoms correlate with subclinical atherosclerosis. However, little is known about associations between depression and earlier markers of CVD in young adults with T1D. This study evaluated the association between depressive symptoms and arterial stiffness in premenopausal women with and without T1D. The study included 132 women (44 with T1D, 88 non-DM) between 18-45 years of age (mean age ± SD = 33 ± 8 years in T1D, and 30 ± 6 years in non-DM, p=0.03). Women with T1D had a mean diabetes duration ± SD of 21 ± 9 years. Depressive symptoms were assessed using the Beck Depression Inventory II depression scale (BDI II) and BDI II subscales (somatic, affective, and cognitive). Arterial stiffness was assessed by measuring carotid-fe...
60. Site-Specific Integration in Human Somatic Cell DNA by Adeno/AAV Hybrid Vectors
Authors: Alessandra Recchia, Laura Perani, Daniela Sartori, Clelia Olgiati, Fulvio Mavilio
Journal: Molecular Therapy (2004)

Non-random integration of complex genes into the human genome cannot be achieved by the currently available retroviral vector technology. The wild-type adeno-associated virus (AAV) can insert its genome at a specific site of the human chromosome 19 (AAVS1) through the activity of a specific replicase/integrase protein (Rep) binding both the AAVS1 and the viral inverted terminal repeats (ITRs). AAV-derived vectors, however, do not carry the rep gene and cannot maintain the property of site-specific integration. We report the construction of novel hybrid vectors carrying an integration cassette flanked by AAV ITRs and a tightly regulated, drug-inducible Rep expression cassette in the framework of a helper-dependent, fully deleted adenoviral (Ad) vector. The hybrid Ad/AAV vectors were successfully packaged and purified at a titer of >109 transducing units/ml. Upon infection at low multiplicity of susceptible human primary cells (amniocytes, keratinocytes) and cell lines (HeLa, HepG2), Rep-dependent, AAVS1-specific integration of the ITR-flanked cassette was obtained with an efficiency comparable to that of wild-type AAV (1–16%) without cell selection and in the absence of toxicity. Southern blot analysis and sequencing of the integration junctions showed integration of single or tandem copies of the expression cassette of intact size and function within the AAVS1. Site-specific integration was studied also in vivo, in a transgenic mice carrying one copy of a 3.5 Kb fragment of the AAVS1 in the chromosome X. Upon a single, tail vein administration of a non-toxic dose of Ad/AAV vectors, AAVS1-specific integration were mapped and sequenced in DNA obtained from liver of animals where activation of Rep expression was induced by drug treatment. These data indicate that site-specific integration of double-stranded DNA into the human genome can be obtained ex vivo and in vivo by the use of a replication-defective, hybrid Ad/AAV vectors with an efficiency compatible with many gene therapy application.
Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis
Authors: Melody C. Carter, Sarah T. Clayton, Hirsh D. Komarow, Erica H. Brittain, Linda M. Scott, Daly Cantave, Donna M. Gaskins, Irina Maric, Dean D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 13765: Impact of Atrial Fibrillation on Clinical Outcomes After Transcatheter Aortic Valve Implantation. Study From the FRANCE 2 Registry
Authors: Romain Chopard, Nicolas Meneveau, Sidney Chocron, Martine Gilard, Marc Laskar, Helene Eltchaninoff, Bernard Iung, Pascal Leprince, Emmanuel Teiger, Karine Chevreul, Alain Prat, Michel Lievre, Alain Leguerrier, Patrick Donzeau-Gouge, Jean Fajadet, Francois Schiele
Journal: Circulation (2014)

Introduction: Atrial fibrillation (AF) is well-known to be associated with mortality and morbidity after conventional cardiac surgery. In the present sub-analysis of the FRANCE 2 registry, we investigated the impact of AF on VARC-defined outcomes in patients with severe aortic stenosis undergoing transcatether aortic valve implantation (TAVI). Methods: The FRANCE 2 registry included all TAVI performed in France between January 2010 and December 2011. Analyses were performed at 2 different time points: (1) AF vs no AF, before valve implantation, and (2) AF vs no AF, after the procedure, among the survivors at day 2. Comparisons of clinical outcomes at 30 days and 1 year, between patients with and without AF, were adjusted for baseline (all analysis) and procedural (analysis 2) characteristics by multivariate analysis. Results: In total, 3875 patients whose pre-TAVI ECG was reported were included (25.8% with AF) (study population for analysis 1). Procedural success was 94% in the non-AF group and 94.5% in the AF group. Three hundred thirteen patients (8.1%) died during the first 24 hours (non-AF: 7.8%, AF: 9.2%; P=0.13); 3377 were alive at day 2 with an ECG (study population for analysis 2); 827 (24.5%) were in AF, including 164 patients with new onset AF (4.8%). The main findings concerning the clinical outcomes of the study populations are displayed in the table. The higher rate of VARC-defined combined efficacy endpoint observed in patients with AF vs those without, in both analysis, is driven by cardiovascular deaths, worsening congestive heart failure and NYHA functional status class III or IV. Conclusion: AF, before and after TAVI, is associated with a higher rate of one-year mortality and morbidity.