tbuckley/cabot-search huggingface dataset:
Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation
Authors: Yi Luo, Brad Bolon, Steve Kahn, Brian D. Bennett, Safura Babu-Khan, Paul Denis, Wei Fan, Hue Kha, Jianhua Zhang, Yunhua Gong, Laura Martin, Jean-Claude Louis, Qiao Yan, William G. Richards, Martin Citron, Robert Vassar
Journal: Nature Neuroscience (2001)
Abstract 18255: Atrial Fibrillation in RyR2-R2474S Mice
Authors: Wenjun Xie, Jian Shan, Steven Reiken, Bi-Xing Chen, Andrew Marks
Journal: Circulation (2011)

Background: Atrial fibrillation (AF) is one of the most common arrhythmias. Despite a wealth of information on the electrical abnormalities present in the working atrial muscle, a detailed understanding of the cellular events that underlie AF is lacking. Methods: To explore the role of ryanodine receptor (RyR2) in triggering AF, we executed in vivo intra-esophageal burst pacing induced AF and in vitro atrial myocyte SR Ca2+ leak measurements in WT and RyR2-R2474S+/- mice. Results: With the in vivo stimulation protocol, 70% of RyR2-R2474S+/- mice could be stimulated into AF whereas WT mice showed no AF (WT: n = 33, R2474S: n = 10, P &lt; 0.05). Confocal Ca2+ imaging in isolated atrial myocytes from these mice showed that atrial myocytes from RyR2-R2474S+/- mice exhibited a 152% increase in SR Ca2+ leak compared to WT (WT: n = 25, R2474S: n=20, P &lt; 0.01). Further, pretreatment of RyR2-R2474S+/- atrial myocytes for 2 hours with 10 µM S107, a 1,4-benzothiazepine derivative that stabilizes RyR2 by inhibiting depletion of the stabilizing subunit calstabin2 (FKBP12.6) from the RyR2 channel (thereby reducing SR Ca2+ leak), resulted in a 68% decrease in diastolic SR Ca2+ leak AF (n = 23, P &lt; 0.05). Administration of S107 treatment via drinking water (20mg/kg/day) for two weeks in RyR2-R2474S+/- mice prevented burst pacing induced-AF (from 70% to 0%) (n = 10 in both groups, P &lt; 0.05). Conclusions: Thus, SR Ca2+ leak via RyR2 plays a critical role in the pathogenesis of AF and may be a novel therapeutic target for AF in humans.
Abstract 16724: Evidence of Associations Between Genetic Ancestry and Measures of Subclinical Atherosclerosis in African Americans: The Jackson Heart Study
Authors: Samson Y Gebreab, Sharon K Davis, Pia Riestra, Khan Rumana, Ruihua Xu, Fasil Tekola-Ayele, Solomon Musani, James Wilson, Correa Adolfo, Charles N Rotimi
Journal: Circulation (2014)

Background:  Substantial disparities in subclinical atherosclerosis between African Americans and European Americans are well documented. However, it is unclear whether genetic or non-genetic risk factors or a combination contribute to these disparities. This study examines the associations between percent of European ancestry (PEA) and various subclinical atherosclerosis measures among African Americans of the Jackson Heart Study (JHS).   Methods:  We examined the associations of PEA with peripheral arterial disease (PAD, Ankle-brachial index  0) and aortic calcification (AAC >0) among 1139 JHS participants measured in visit 2. PEA was estimated based on 1747 ancestry informative markers (AIMs) from the Illumina custom ITMAT-Broad-CARe (IBC) array using HAPMIX software. Multivariable regression models with restricted cubic splines were used to assess potential nonlinear associations.   Results:  There was an inverse significant linear association of PEA with PAD (p=0.0066). The prevalence of PAD decreased with one standard deviation increases in PEA [prevalence ratio (PR) = 0.89 (95% CI: 0.81, 0.97)], adjusting for age and gender. PEA was also associated with CAC (p =0.0192) and cCIMT (p = 0.0340) but in non-linear fashion. Participants with low PEA (≤7%) had lower CAC prevalence [PR = 0.50 (95% CI: 0.31, 0.80)] and those with high PEA (≥ 30%) had lower cCIMT [mean difference = -0.035 (95% CI:-0.06, -0.01)] compared to those with the median PEA. Adjusting for cardiovascular disease (CVD) risk factors, socioeconomic status and psychosocial factors attenuated the associations of PEA with PAD [PR = 0.91(95% CI: 0.83, 1.01)], but the association between lower PEA and CAC remained significant [PR = 0.55 (95% CI: 0.32, 0.96)]. A similar pattern of associations was found between PEA and AAC, but PEA was not significantly associated with iCIMT.   Conclusion:  Our findings support the hypothesis that genetic factors in combination with CVD risk factors may contribute to differences in subclinical atherosclerosis between African and European ancestry.
Healthy living centres
Authors: C. Salisbury
Journal: BMJ (1999)

The United Kingdom government has set aside £300m from the National Lottery to establish a network of “healthy living centres” around the country.1 Its aim is to improve health through community action and particularly to reduce inequalities in health in deprived areas. The support for healthy living centres therefore complements other strategies such as health action zones and local health improvement programmes. The initiative involves a considerable commitment of money and energy. How can we tell if this investment is worthwhile? The criteria for assessing applications for lottery funding rightly emphasise the importance of evaluation,1 but the difficulties should not be underestimated.

Healthy living centres will take various forms and may exist as partnerships and networks rather than as new buildings. They are based on a recognition that determinants of poor health in deprived areas include economic, social, and environmental factors which are outside the influence of conventional health services.2 Any attempt to address these wider issues requires a coordinated approach from several agencies in the statutory and voluntary sectors …
Metalloproteinases Are Involved in Lipopolysaccharide– and Tumor Necrosis Factor-–Mediated Regulation of CXCR1 and CXCR2 Chemokine Receptor Expression
Authors: Masud H. Khandaker, Gordon Mitchell, Luoling Xu, Joseph D. Andrews, Rajkumari Singh, Harry Leung, Joaquı́n Madrenas, Stephen S.G. Ferguson, Ross D. Feldman, David J. Kelvin
Journal: Blood (1999)
Deri yaralarında mikrobiyolojik inceleme:1 yıllık süreçde dermatoloji kliniğinde yatan hastalarda antibiyotik direncine doğru uyarıcı bir akım
Authors: Isabel C. Valencia, Robert S. Kirsner, veFrancisco A. Kerdel, Florida
Journal: Journal of the American Academy of Dermatology (2004)
Retinal Vascular Changes in Hypertension
Authors: Henry P. Wagener
Journal: Annals of Internal Medicine (1930)

Article1 September 1930Retinal Vascular Changes in HypertensionHENRY P. WAGENER, M.D.HENRY P. WAGENER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-3-222 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA mere catalogue of the changes observed in the retina of patients with hypertension offers little of interest to the internist. The presence of arteriosclerosis or of arteriolosclerosis and its complications, and of retinitis, is universally recognized. From the standpoints of differential diagnosis and prognosis, retinal changes are of definite value. But the most alluring possibilities offered by the retina seem to me to lie in the field of interpretation of the basic pathologic and the pathologicophysiologic changes concerned in the production of hypertensive disease, or, at least, of some of its more serious manifestations.In my opinion, all of the...Bibliography1 HASELHORSTMYLIUS GK: Zur Frage de Grefàsskrampfe bei Eklampsie. Zentralbl. f. Gynäk. 52: 1180-1189 (May) 1928. Google Scholar2 KEITHWAGENERKERNOHAN NMHPJW The syndrome of malignant hypertension. Arch. Int. Med. 41: 141-188 (Feb.) 1928. CrossrefGoogle Scholar3 O'HAREWALKER JPWG: Arteriosclerosis and hypertension. Arch. Int. Med. 33: 343-349 (March) 1924. CrossrefGoogle Scholar4 VOLHARD F: Die Pathogenese der Retinitis albuminurica. Zentralbl. f. d. ges. Ophth. u. i. Grenzgeb. 21: 129-136 (March) 1929. Google Scholar5 YATERWAGENER WMHP: Ophthalmoscopic signs in diseases of the heart. A study of one hundred thirty-seven cases verified by necropsy. Am. Jour. Med. Sc. 178: 105-115 (July) 1929. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Read before the American College of Physicians, Minneapolis, Minnesota, February 11, 1930. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA case of complete AV block produced by guanethidineDie Sympathektomie beim Hochdruck und ihre Ergebnisse 1 September 1930Volume 4, Issue 3Page: 222-226KeywordsHypertensionRetinaRetinitis ePublished: 1 December 2008 Issue Published: 1 September 1930 PDF downloadLoading ...
Causes of Hypouricemia
Authors: Herbert J. Van Peenen
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 June 1973Causes of HypouricemiaHERBERT J. VAN PEENEN, M.D.HERBERT J. VAN PEENEN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-6-977 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The data on hypouricemia presented by Drs. Ramsdell and Kelley in the February issue (1) is welcome and valid; however, their population was largely drawn from a Veteran's Administration Hospital and is not representative. The following data from a large community hospital amplifies theirs.Data from SMA 12-60* analyses on 5000 patients were reviewed; 56% of them were women and all were admitted between 1 January and 1 April 1972. Thirty-six patients had a serum uric acid level of less than 2.0 mg/100 ml on one or more occasions. Only 4 of the 36 were male.Group...Reference1. RAMSDELLKELLEY CW: The clinical significance of hypouricemia. Ann Intern Med 78:239-242, 1973 LinkGoogle Scholar1. MATZCHRISTODOULOUVIANNA RJN: Renal tubular dysfunction associated with alcoholism and liver disease. NY State J Med 69:1312-1314, 1969 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Texas Medical School at Houston and Hermann Hospital Texas Medical Center Houston, Texas*Trademark of the Technicon Corp., Ardsley, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypouricemia and Urate TransportersDepletion of Uric Acid Due to SLC22A12 (URAT1) Loss-of-Function Mutation Causes Endothelial Dysfunction in HypouricemiaClinical Aspects of Gout and Associated Disease StatesA case of acute renal failure after exercise with renal hypouricemia demonstrated compound heterozygous mutations of uric acid transporter 1A Case of Exercise-induced Acute Renal Failure with G774A Mutation in SCL22A12 Causing Renal HypouricemiaMutational analysis of idiopathic renal hypouricemia in KoreaRecurrent URAT1 gene mutations and prevalence of renal hypouricemia in JapaneseMutations in Human Urate Transporter 1 Gene in Presecretory Reabsorption Defect Type of Familial Renal HypouricemiaHypouricemia in individuals admitted to an inpatient hospital-based facilityRenal hypouricemia: Prevention of exercise-induced acute renal failure and a review of the literatureEpidemiology of HyperuricaemiaUric acid levels in southern Germany in 1989HypourikämieHypo-uricémie paranéoplasique (à propos de deux cas)Limited Value of Uric Acid to Creatinine Ratios in Estimating Uric Acid ExcretionROBERT L. WORTMANN, M.D., IRVING H. FOX, M.D.A Case of Uric Acid Renal Stone with Hypouricemia Caused by Tubular Reabsorptive Defect of Uric AcidHypouricemia 1 June 1973Volume 78, Issue 6Page: 977-978KeywordsUric acid ePublished: 1 December 2008 Issue Published: 1 June 1973 PDF downloadLoading ...
Epigenetic factors that control estrogen receptor alpha (ERα) binding site utilization and specificity in the MCF-7 human breast cancer cell line
Authors: Roy Joseph, Jane Thomsen, Vega Vinsensius, Kandhadayar Srinivasan, Patrick Ng, Radha Karuturi, Yew Kok Lee, Wei Chia-Lin, Yijun Ruan, Edison Liu
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C62 

ChIP-chip and DITAG sequencing experiments on MCF-7 cells showed that sequences with high predicted affinity for estrogen receptor alpha (ERα) occur far more often than actual protein-DNA interactions in vivo . Using only the classical canonical ER binding motif, there is more than one million putative binding sites present in the genome. Our previous work identified an extended palindrome that dramatically enhances the ability to predict ER binding. Still, out of a total 38,000 predicted high affinity binding sites, only a mere fraction (estimated 14%) of them are true binding sites. The most widely cited mechanism by which differential binding-site utilization could occur is by controlling transcription factor access to DNA through variations in local chromatin composition and/or through cofactor interaction. Regulation of gene expression is also profoundly influenced by nucleosome position. We have pursued a multipronged genome wide approach to assess the epigenetic control of ERα binding to DNA. Our fundamental goal is to determine the rules by which ERα selects the precise binding sites. We constructed a genome-wide ER specific binding chip that includes all validated binding sites from two genome wide studies, and most of the computationally predicted sites using our hERE algorithm. In addition, we have also conducted a chromatin immunoprecipitation sequencing analysis of DNA bound to specific histone marks. Our preliminary data show that the chromatin is altered towards an activated format around the selected upregulated ERα target genes promoters and associated with histone markers that are characteristic to euchromatic regions. Repressed genes appear to have different patterns of regulation. Our work more accurately defines the relationship between local chromatin environment and ERα mediated transcription regulation.
Abstract #5608: Synthetic lethal interaction between oncogenic KRAS dependency and suppression of STK33 in human cancer cells
Authors: Claudia Scholl, Stefan Fröhling, Ian Dunn, Anna Schinzel, David Barbie, So Kim, Serena Silver, Pablo Tamayo, Raymond Wadlow, Sridhar Ramaswamy, Konstanze Döhner, Lars Bullinger, Peter Sandy, Jesse Boehm, David Root, Tyler Jacks, William Hahn, D. Gilliland
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Activating KRAS mutations are among the most common pathogenetic events in a broad spectrum of hematologic malignancies and epithelial tumors. However, oncogenic KRAS has thus far not proven to be a tractable target for therapeutic intervention. An alternative to direct targeting of known oncogenes is to perform \#8220;synthetic lethality\#8221; screens to identify genes that are selectively required for cell viability in the context of specific cancer-causing mutations. Using this approach, we have discovered a synthetic lethal interaction between mutant KRAS, the most frequently mutated oncogene in human cancer, and inactivation of the gene encoding the STK33 serine/threonine protein kinase. To identify genes that are essential for cell viability in the context of mutant KRAS, we performed high-throughput loss-of-function RNA interference (RNAi) screens in eight human cancer cell lines (mutant KRAS, n=4; wildtype KRAS, n=4), representing five different tumor types (acute myeloid leukemia, colon cancer, breast cancer, prostate cancer, glioblastoma), as well as normal human fibroblasts and mammary epithelial cells. We screened each cell line with a subset of the short hairpin RNA (shRNA) library developed by the RNAi Consortium that consists of 5,024 individual shRNA constructs targeting 1,011 human genes, including the majority of known and putative protein kinase genes and a selection of protein phosphatase genes and known cancer-related genes. In these cell lines, suppression of STK33 preferentially inhibited the viability and proliferation of cells that were dependent on mutant KRAS. The differential requirement for STK33 based on oncogenic KRAS dependency was confirmed in 17 additional cell lines using in vitro transformation assays and human tumor xenograft models. Biochemical analyses support the hypothesis that STK33 promotes cell growth and survival in a kinase activity-dependent manner by regulating the activity of S6K1 selectively in mutant KRAS-dependent cells. Notably, molecular genetic characterization of cancer cell lines and analysis of patient-derived genomic data sets indicated that STK33 is not frequently mutated or overexpressed in human tumors. These observations identify STK33 as a potential target for the treatment of mutant KRAS-driven cancers that may have a broad therapeutic index in normal versus malignant cells, and illustrate the potential of RNAi for discovering critical functional dependencies created by oncogenic mutations that cannot be identified using other genomic technologies.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5608.
Anti-inflammatory Intervention in Depression
Authors: Harris A. Eyre, Bernhard T. Baune
Journal: JAMA Psychiatry (2015)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
Recurrent chromosomal translocation regions in gastric cancer encode dysregulated microRNAs
Authors: Siew Hong Leong, Cheryl Lee, Oi Lian Kon
Journal: Clinical Cancer Research (2007)

C65   MicroRNAs (miRNAs) are a class of small non-protein coding transcripts that are postulated to have important roles in the initiation and progression of oncogenesis. Aberrant patterns of global miRNA expression, relative to normal tissues, have been reported in solid cancers, lymphomas and leukemias. Genomic abnormalities e.g. amplifications, deletions, translocations and epigenetic modifications have been implicated, directly or indirectly, as causes of dysregulated miRNA expression. We have globally profiled miRNA expression in 17 human gastric cancer cell lines and have mapped commonly dysregulated miRNAs to recurrent chromosomal rearrangements present in same panel of cell lines. There is to date no published report of a similar study in gastric cancer. Global miRNA expression profiling was performed on oligonucleotide microarrays, each having 283 miRNAs printed in duplicate (Ambion, Inc.). Small RNAs ( o C water bath. Hybridization signal intensities were obtained using a GenePix 4000B scanner (Axon Instruments, Inc.). Solution hybridization validated differential expression of selected miRNAs. Spectral karyotypes (ASI, GmbH) of the same gastric cancer cell lines were documented by examining 6 - 20 metaphases from each cell line (ISCN nomenclature). This revealed several specific and recurrent chromosomal rearrangements that we deem to be nonrandom. We found 32 miRNAs to be at least 2-fold differentially expressed compared to a pooled normal stomach reference. miR-21, a putative oncomir with postulated anti-apoptotic and pro-survival functions which modulates PTEN expression, was up regulated in 14 of 17 cell lines (82%). Eight cell lines (47%) showed increased expression of miR-122a. Down regulation of miR-26a occurred in 12 cell lines (71%). Let-7 family members (let-7-a,b,c) showed either low or no expression in nearly all cell lines compared to normal stomach. Forty-five recurrent breakpoints were identified from composite karyotypes of all cell lines. The most frequently rearranged cytobands (in 6 of 17 cell lines) were 1q12, 2p22, 13q22, 18q21 and 22q12. Fifteen miRNAs were mapped to 9 recurrent breakpoint cytobands e.g. miR-122a mapped to 18q21, a recurrent breakpoint in 6 cell lines.We have identified at least 32 miRNAs whose expressions are dysregulated in human gastric cancer. Our data suggest functional associations between specific nonrandom chromosomal rearrangements and miRNA expression profiles. These findings implicate a subset of miRNAs as mediators of genome level aberrations that alter downstream transcriptional and translational processes. Elucidating these processes should be helpful in developing robustly validated molecular pathways of gastric oncogenesis.
Abstract 4069: Capn4 contributes to tumor growth and metastasis of hepatocellular carcinoma by activation of FAK-Src signaling pathways
Authors: Zhi Dai, Jian Zhou, Jia Fan
Journal: Cancer Research (2014)

Abstract Calpain small subunit 1 (Capn4) has been identified as a major gene that promotes metastasis of hepatocellular carcinoma (HCC). However, the mechanism by which Capn4 promotes progression of HCC is not understood. In this study, we found that Capn4 expression was increased in highly metastatic HCC cell lines and in tumor tissue from HCC patients compared to healthy patient tissue. Overexpression of Capn4 in HCC cells enhanced tumor cell growth in vitro and increased invasiveness, tumorigenicity, and lung metastasis in vivo. Protein microarray analyses in HCC cells with altered Capn4 levels (through Capn4 silencing or overexpression) showed that expression of multiple proteins was regulated by Capn4 and that the activation of focal adhesion kinase (FAK) signaling pathways might play a key role in Capn4-enhanced tumor development. Immunoprecipitation and western blotting verified that Capn4 was physically associated with FAK and promoted hyperactivity of the FAK-Src signaling pathway via increased phosphorylation of specific tyrosine residues of FAK, Src, and p130Cas. Knockdown of Capn4 expression suppressed the malignant behavior of HCC cells and inhibited the FAK-Src signaling pathway. Furthermore, Capn4-mediated invasion and metastasis of HCC cells required up-regulation of matrix metalloproteinase-2 (MMP2) through activation of this signaling pathway. Our clinical data revealed that Capn4 expression correlated well with the levels of phospho-FAK, and overexpression of both Capn4 and phospho-FAK correlates with the poorest survival outcomes in HCC. These results suggest that Capn4 can contribute to HCC growth and metastasis via activation of the FAK-Src Signaling pathway and MMP2. Capn4 could be a therapeutic target for HCC. Citation Format: Zhi Dai, Jian Zhou, Jia Fan. Capn4 contributes to tumor growth and metastasis of hepatocellular carcinoma by activation of FAK-Src signaling pathways. [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 4069. doi:10.1158/1538-7445.AM2014-4069
Potent amyloidogenicity and pathogenicity of Aβ43
Authors: Takashi Saito, Takahiro Suemoto, Nathalie Brouwers, Kristel Sleegers, Satoru Funamoto, Naomi Mihira, Yukio Matsuba, Kazuyuki Yamada, Per Nilsson, Jiro Takano, Masaki Nishimura, Nobuhisa Iwata, Christine Van Broeckhoven, Yasuo Ihara, Takaomi C Saido
Journal: Nature Neuroscience (2011)