tbuckley/cabot-search huggingface dataset:
Abstract 1641: Structure-based design and development of pyrazolopyridine-based inhibitors of Mcl-1
Authors: Fardokht A. Abulwerdi, Ahmed S.A. Mady, Andrej Perdih, Jeanne A. Stuckey, Hollis D. Showalter, Zaneta Nikolovska-Coleska
Journal: Cancer Research (2014)

Abstract The anti-apoptotic myeloid cell leukemia protein Mcl-1, a member of the Bcl-2 family proteins, has emerged as a promising therapeutic target. Mcl-1 is overexpressed in many human cancers which has been associated with inferior survival, poor prognosis and resistance to chemotherapies. Disruption of Mcl-1 interaction with its pro-apoptotic partners through small molecules is a viable strategy to overcome Mcl-1 mediated resistance to apoptosis. Targeting Mcl-1 protein represents a promising strategy either alone or in combination with other therapies. Applying an integrated screening approach through combining high throughput and virtual screenings, several novel chemical classes were identified as Mcl-1 inhibitors. Compound 38 with a pyrazolopyridine scaffold was selected as a promising high throughput lead for medicinal chemistry efforts. Using reported chemistry a focused library of analogs of 38 was generated. Through HSQC protein-observed NMR studies and chemical shift mapping, the binding of the lead compound 38 was characterized and confirmed to be the BH3 binding pocket of Mcl-1. Computational modeling guided by NMR studies was applied in lead optimization and rational design of more potent analogs. Structure-activity relationship was established utilizing two different competitive platforms of fluorescent polarization and surface plasmon resonance, and confirmed by HSQC NMR spectroscopy. The binding affinity of this class of compounds was improved more than twenty fold in comparison with the lead compound 38. In vitro binding, functional and cell-based assays were performed in order to determine selectivity profile against five members of Bcl-2 family, mechanism of action and cellular activity of analogs with improved potency. The obtained results show promise for further chemical modification and development of pyrazolopyridine-based inhibitors of Mcl-1. Citation Format: Fardokht A. Abulwerdi, Ahmed S.A. Mady, Andrej Perdih, Jeanne A. Stuckey, Hollis D. Showalter, Zaneta Nikolovska-Coleska. Structure-based design and development of pyrazolopyridine-based inhibitors of Mcl-1. [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 1641. doi:10.1158/1538-7445.AM2014-1641
Coffee Consumption and Development of Type 2 Diabetes
Authors: Celia M Ross
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
ULTRASTRUCTURAL DIFFERENCES IN HUMAN MALIGNANT MELANOMATA.
Authors: HERBERT KLUG, WOLFGANG GuNTHER
Journal: British Journal of Dermatology (1972)

Journal Article ULTRASTRUCTURAL DIFFERENCES IN HUMAN MALIGNANT MELANOMATA: AN ELECTRON MICROSCOPICAL STUDY Get access HERBERT KLUG, HERBERT KLUG Department of Dermatology, University Hospital (Charite), Berlin, DDR Search for other works by this author on: Oxford Academic Google Scholar WOLFGANG GüNTHER WOLFGANG GüNTHER Department of Dermatology, University Hospital (Charite), Berlin, DDR Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 4, 1 April 1972, Pages 395–407, https://doi.org/10.1111/j.1365-2133.1972.tb05053.x Published: 01 April 1972 Article history Accepted: 11 November 1971 Published: 01 April 1972
Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain
Authors: Imane Allali, Susana Delgado, Pablo Isidro Marron, Aurora Astudillo, Jen Jen Yeh, Hassan Ghazal, Saaïd Amzazi, Temitope Keku, M Andrea Azcarate-Peril
Journal: Gut Microbes (2015)

Colorectal cancer (CRC) is the third most common cancer in the world and the second leading cause of cancer deaths in the US and Spain. The molecular mechanisms involved in the etiology of CRC are not yet elucidated due in part to the complexity of the human gut microbiota. In this study, we compared the microbiome composition of 90 tumor and matching adjacent tissue (adjacent) from cohorts from the US and Spain by 16S rRNA amplicon sequencing in order to determine the impact of the geographic origin on the CRC microbiome. Data showed a significantly (P < 0.05) higher Phylogenetic Diversity (PD) for the US (PD Adjacent = 26.3 ± 5.3, PD Tumor = 23.3 ± 6.2) compared to the Spanish cohort (PD Adjacent = 18.9 ± 5.9, PD Tumor = 18.7 ± 6.6) while no significant differences in bacterial diversity were observed between tumor and adjacent tissues for individuals from the same country. Adjacent tissues from the Spanish cohort were enriched in Firmicutes (SP = 43.9% and US = 22.2%, P = 0.0001) and Actinobacteria (SP = 1.6% and US = 0.5%, P = 0.0018) compared to US adjacent tissues, while adjacent tissues from the US had significantly higher abundances of Fusobacteria (US = 8.1% and SP = 1.5%, P = 0.0023) and Sinergistetes (US = 0.3% and SP = 0.1%, P = 0.0097). Comparisons between tumor and adjacent tissues in each cohort identified the genus Eikenella significantly over represented in US tumors (T = 0.024% and A = 0%, P = 0.03), and the genera Fusobacterium (T = 10.4% and A = 1.5%, P = <0.0001), Bulleida (T = 0.36% and A = 0.09%, P = 0.02), Gemella (T = 1.46% and A = 0.19%, P = 0.03), Parvimonas (T = 3.14% and A = 0.86%, P = 0.03), Campylobacter (T = 0.15% and A = 0.008%, P = 0.047), and Streptococcus (T = 2.84% and A = 2.19%, P = 0.05) significantly over represented in Spanish tumors. Predicted metagenome functional content from 16S rRNA surveys showed that bacterial motility proteins and proteins involved in flagellar assembly were over represented in adjacent tissues of both cohorts, while pathways involved in fatty acid biosynthesis, the MAPK signaling pathway, and bacterial toxins were over represented in tumors. Our study suggests that microbiome compositional and functional dissimilarities by geographic location should be taken in consideration when approaching CRC therapeutic options.
AZD3199: A fast acting β2-receptor agonist with a long duration of action
Authors: Alan Young, Roger Bonnert, Elaine Cadogan, Stephen Connolly, Philip Gardiner, Stephen Jordan, David Nicholls, Stuart Paine, Gary Pairaudeau, Michael Stocks
Journal: European Respiratory Journal (2011)

Background:  AZD3199 is a novel, ultra long acting β 2  -agonist (uLABA) designed to combine 24 hour duration of action with a fast onset of action similar to formoterol, as well as low systemic exposure. Its  in vivo  profile was evaluated in the guinea pig.   Methods:  Bronchoconstriction was elicited in anesthetized guinea pigs by histamine administration. Dose-response curves for AZD3199 given via the inhaled and intra-tracheal (i.t.) routes were constructed and sub-maximal doses used to define duration of action from 2–72 hours. The b-antagonist propranolol was administered after histamine-challenge to show the level of β 2  efficacy at each dose and time point. Blood samples were taken throughout and plasma K +  concentrations used as a marker of systemic β 2  effects. Satellite groups were used to monitor lung and plasma AZD3199 levels. The pharmacodynamic and pharmacokinetic profiles of AZD3199 were compared to formoterol and salmeterol.   Results:  Sub-maximal doses of AZD3199 given i.t. inhibited bronchoconstriction for 24 hours; equi-effective doses of formoterol and salmeterol had significant effects for 12 hours. AZD3199 had the longest lung PK half-life. Inhalation of sub-maximal doses of nebulized AZD3199 gave bronchoprotection lasting 24 hours, with no significant effects on blood K +  levels. An equi-effective inhaled dose of formoterol bronchoprotected for 8 hours with decreases in blood K +  seen at 2 hours. The reduced systemic effects for AZD3199 relative to formoterol are consistent with its high lung to plasma concentration ratio.   Conclusion:  AZD3199 is a novel uLABA with a fast onset of action and a longer duration of action than conventional LABAs, and also has a low potential for systemic effects.
Abstract 17966: First In Man Transendocardial Injection of Autologous AdiPose-deRived StEm Cells in Patients with Non RevaScularizable IschEmic Myocardium (PRECISE)
Authors: Emerson C Perin, Pedro L Sanchez, Ricardo S Ruiz, Rosa Perez-Cano, Jose Lasso, Juan Carlos Alonso-Farto, Lucia Fernandez-Pina, Patrick W Serruys, H.J. (Eric) Duckers, Jens Kastrup, Steven Chameleau, Yi Zheng, Guilherme V Silva, Alexander M Milstein, Michael T Martin, James T Willerson, Francisco F Aviles
Journal: Circulation (2010)

Background: Stem cells from various origins have been tested in patients with IHD ranging from AMI to ischemic heart failure, including those from bone marrow, skeletal muscle, and blood. We present the first-in-man study to assess the safety and feasibility of autologous adipose-derived regenerative cells (ADRCs) delivered transendocardialy in patients with non revascularizable ischemic myocardium. Methods: 27 patients with no option for revascularization were randomized (3:1) to receive 44±17 × 106 of ADRCs or placebo. Up to 540 mL of subcutaneous adipose tissue was harvested from the abdomen using minimally invasive liposuction procedures, and ADRCs were obtained by Cytori's proprietary extraction, washing and concentration methods (the CelutionTM system). Feasibility endpoints (infarct size measured by MRI as percent of LV infracted and peak VO2) were evaluated at baseline and 6 months. Post-hoc comparisons were made using Student's t-test or repeated measures ANOVA. Results: There were no adverse eve...
Screening for Chlamydia trachomatis
Authors: F. Boag, F. Kelly
Journal: BMJ (1998)

News p 1479 

This month the chief medical officer of England published the report of an expert advisory group on Chlamydia trachomatis , which highlighted the need for immediate action to reduce the prevalence of chlamydia infection and the morbidity associated with it.1 Chlamydia is the most prevalent, treatable sexually transmitted infection in the United Kingdom and has serious sequelae, including pelvic inflammatory disease, infertility, ectopic pregnancy, and neonatal infections. All these conditions, except for infertility, have been shown to be preventable if chlamydia trachomatis is treated in its asymptomatic phase. The expert group is proposing an education campaign to increase awareness of chlamydia infection coupled with opportunistic screening of asymptomatic sexually active young women.

The advisory group's main recommendations are to offer testing to all men and women with symptoms of infection, all attenders at genitourinary medicine clinics, and women seeking terminations of pregnancy and to screen opportunistically sexually active women aged under 25 and those over 25 with …
T cell-specific overexpression of interleukin-27 receptor α subunit (WSX-1) prevents spontaneous skin inflammation in MRL/lpr mice
Authors: M. Kido, S. Takeuchi, N. Sugiyama, H. Esaki, H. Nakashima, H. Yoshida, M. Furue
Journal: British Journal of Dermatology (2011)

Interleukin (IL)-27 and WSX-1, the receptor α-specific subunit, have been shown to play important roles in initiating Th1 responses and in inducing immune modulation, and the immunosuppressive effect of IL-27 appears to be exerted via suppression of IL-10 and IL-17, which may participate in the pathogenesis of human systemic lupus erythematosus (SLE).To examine the significance of IL-27/WSX-1 signalling in spontaneous skin inflammation of MRL/lpr mice, a model for SLE.The severity and development of skin lesions, dermal inflammatory cells and epidermal-dermal depositions in the skin lesions of MRL/lpr mice with CD2-promoted WSX-1 overexpression (WSX-1 Tg mice) and those with globally disrupted WSX-1 (WSX-1 KO mice) were examined and compared with those of MRL/lpr mice.By 4 months of age, both WSX-1 KO mice and control MRL/lpr mice developed predominantly similar skin inflammation, while WSX-1 Tg mice hardly did so, demonstrating that intensifying IL-27/WSX-1 signalling on T cells prevents the spontaneous skin inflammation. WSX-1 KO mice showed Th2-type skin inflammation as evidenced by the Th2-prone dermal infiltrating cells and an absence of cutaneous Th1-type IgG deposition. Interestingly, there were significant IL-17+ dermal infiltrating cells in both WSX-1 KO and control MRL/lpr mice, which might potentially contribute to the formation of skin inflammation in these mice.These data indicate that IL-27/WSX-1 signalling may play a protective role in the development of SLE-like skin inflammation, and modulating IL-27/WSX-1 signalling might be an interesting therapeutic strategy in the treatment of SLE.
Abstract 668: Lipoprotein Particle Size Effects of Colesevelam HCl in Combination with Ezetimibe and Simvastatin
Authors: Harold Bays, James Rhyne, Stacey Abby, Yu-Ling Lai, Michael Jones
Journal: Circulation (2006)

Lipid-lowering combination therapy is often required to achieve low density lipoprotein cholesterol (LDL-C) goals and to favorably affect other lipid parameters. This is the first double-blind, par...
Human Immunodeficiency Virus Infection among Men with Sexually Transmitted Diseases
Authors: J. Neil Simonsen, D. William Cameron, Michael N. Gakinya, Jackoniah O. Ndinya-Achola, Lourdes J. D'Costa, Peter Karasira, Mary Cheang, Allan R. Ronald, Peter Piot, Francis A. Plummer
Journal: New England Journal of Medicine (1988)

Heterosexual transmission of the human immunodeficiency virus (HIV) appears to occur readily in Africa but less commonly in North America and Europe. We conducted a case-control study among men attending a clinic for sexually transmitted diseases in Nairobi to determine the prevalence of HIV infection and the risk factors involved. HIV antibody was detected in 11.2 percent of 340 men who enrolled in the study. Reports of nonvaginal heterosexual intercourse and homosexuality were notably rare. Recent injections and blood transfusions were not associated with HIV infection. Travel and frequent contact with prostitutes were associated with HIV seropositivity. Men who were uncircumcised were more likely to have HIV infection (odds ratio, 2.7; P = 0.003), as were those who reported a history of genital ulcers (odds ratio, 7.2; P<0.001). A current diagnosis of genital ulcers was also associated with HIV seropositivity (odds ratio, 2.0; P = 0.028). Multivariate analysis revealed an independent association of genital ulcers with HIV infection in both circumcised and uncircumcised men. Uncircumcised men were more frequently infected with HIV, regardless of a history of genital ulcers. Our study finds that genital ulcers and an intact foreskin are associated with HIV infection in men with a sexually transmitted disease. Genital ulcers may increase men's susceptibility to HIV, or they may increase the infectivity of women infected with HIV. The intact foreskin may operate to increase the susceptibility to HIV. (N Engl J Med 1988; 319:274–8.)
Abstract 13555: Impact of Public-Access Defibrillation at School on the Outcome After Out-of-Hospital Cardiac Arrest of Cardiac Origin in Elementary and Middle School Students: A Japanese Nationwide Survey
Authors: Yoshihide Mitani, Kunio Ohta, Fukiko Ichida, Masaki Nii, Yoshio Arakaki, Hiroya Ushinohama, Hiroyuki Ohashi, Noriko Yodoya, Shigeru Tateno, Seiichi Sato, Tsugutoshi Suzuki, Takashi Higaki, Mari Iwamoto, Masao Yoshinaga, Naokata Sumitomo
Journal: Circulation (2010)

Background: Since the lay use of automatic external defibrillator (AED) was legally approved in Japan in July 2004, the percentage of AED placement increased up to 72.0 and 89.8% in elementary and ...
Preparing for Flu Season
Authors: Mike Mitka
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
Prevalence and Significance of Periduodenal Venous Collaterals in Patients Evaluated for Pancreaticobiliary Disorders by Endosonography
Authors: M. Eloubeidi, D. Iseman, V. Chen, S. Vickers, C. Wilcox
Journal: Endoscopy (2003)

The prevalence of periduodenal venous collaterals detected by endoscopic ultrasonography (EUS) in patients undergoing evaluation for pancreaticobiliary disorders, and their influence on the success of transduodenal fine-needle aspiration (FNA) of solid pancreatic masses is not known.Records for all consecutive patients who underwent EUS for pancreaticobiliary disorders over a 14-month period were reviewed. EUS was carried out by a single endosonographer using a radial echo endoscope. When FNA was attempted, a curvilinear-array echo endoscope was used in conjunction with color flow Doppler. Periduodenal and perigastric collaterals were defined as multiple anechoic serpiginous structures imaged from the duodenal bulb, the second portion of duodenum, or the stomach. Established criteria were used to assess the presence of chronic pancreatitis.Over the study period, 338 patients (mean age 58.9 +/- 14.5 years; 52 % women) underwent EUS for pancreaticobiliary disorders. Periduodenal collaterals were detected in 22 patients (6.5 %), 21 of whom (19 %) had pancreatic cancer. Patients with pancreatic cancer were significantly more likely to have periduodenal collaterals in comparison with those without pancreatic cancer (OR 25; 95 %CI, 5.75 - 109; P = 0.001). Computed tomography detected collaterals in only two of the 22 patients (9.1 %). Periduodenal collaterals made transduodenal FNA impossible in nine of the 22 patients (41 %). However, in these patients a cancer diagnosis was obtained using EUS-FNA from liver lesions in two cases; using a transgastric approach in two (pancreatic neck lesions); and atypical cells were obtained in two. A safe window could not be achieved in three patients (13.6 %). Transduodenal FNA was performed by avoiding the collaterals and was successful in 13 of the 22 patients, with no bleeding complications.Periduodenal collateral vessels are infrequent in patients with suspected pancreaticobiliary disease, but are relatively common in patients with pancreatic cancer. Transduodenal EUS-FNA can be carried out safely in the majority of cases in the presence of periduodenal collaterals, but collaterals may occasionally hamper successful transduodenal pancreatic FNA.
Abstract 4176: Identifying analytes associated with poor prognosis in CRC
Authors: Christi Lynn French, Alissa Weaver
Journal: Cancer Research (2014)

Abstract Cancer patients with undetectable micrometastases at the time of diagnosis are in danger of subsequent metastatic growth that worsens their outcome. Therefore, identification of these patients with latent metastases could reduce morbidity and mortality by helping physicians to choose whether to treat with an adjuvant therapy. In colorectal carcinoma (CRC), 20-30% of stage II patients will have a recurrence at a distant site after removal of the primary tumor. In order for cancer cells to metastasize, they must switch to an “invasive phenotype”. To identify molecular changes in cancer that drive invasion, our laboratory previously built a molecular network model of invasive subcellular structures termed invadopodia. Centrality and random walk analyses identified candidate signaling hubs that may control invadopodia formation or activity. To identify which of these hubs control invasion in specific cancers, we are mining reverse phase protein array (RPPA) data from publicly available human tumor datasets. In this study, we focused on analysis of RPPA data from TCGA in CRC patients, segregated by poor prognosis and good prognosis. We tested three different definitions of poor prognosis: recurrence, survival, and TNM status at diagnosis. We found several promising analytes that were significantly associated with each poor prognosis definition, and recurrence provided the best separation of good vs. poor prognosis. Interestingly, many of the analytes significantly associated with survival are involved in apoptosis. Additionally, we refined the analysis by using a subset of patients (stage I-II), which resulted in even better separation of good vs. poor prognosis. We identified several analytes that are already significantly associated with the invadopodia network (src kinase and PI 3-kinase). We also identified some potential new invadopodia regulators, such as Cox2. This method has potential both to improve CRC survival by identifying patients that need adjuvant therapy as well as identify novel drivers of invadopodia. Citation Format: Christi Lynn French, Alissa Weaver. Identifying analytes associated with poor prognosis in CRC. [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 4176. doi:10.1158/1538-7445.AM2014-4176