tbuckley/cabot-search huggingface dataset:
A comparison of psychiatric symptoms in vascular dementia and Alzheimer's disease
Authors: D L Sultzer, H S Levin, M E Mahler, W M High, J L Cummings
Journal: American Journal of Psychiatry (1993)

Psychiatric symptoms account for much of the morbidity of vascular dementia and Alzheimer's disease. The goals of this study were to extend previous observations of the psychopathology and behavioral problems associated with vascular dementia and to compare the profile of symptoms in patients with vascular dementia to that in patients with Alzheimer's disease.Twenty-eight pairs of patients (one with vascular dementia and one with Alzheimer's disease) were matched with respect to education, age, and severity of dementia. Their psychiatric symptoms were assessed with the Neurobehavioral Rating Scale, a 28-item observer-rated instrument, and the Hamilton Depression Rating Scale, and the symptoms in the two diagnostic groups were compared.Blunted affect, depressed mood, emotional withdrawal, motor retardation, low motivation, anxiety, unusual thoughts, and somatic concerns occurred in more than one-third of the patients with vascular dementia. There was no significant relation between severity of cognitive impairment and severity of these noncognitive symptoms. The patients with vascular dementia had more impairment than the patients with Alzheimer's disease, as indicated by the Neurobehavioral Rating Scale total scores and scores on the behavioral retardation, anxiety/depression, and verbal output disturbance factors. They also had a higher total score on the Hamilton depression scale and higher scores on 14 of the 17 Hamilton depression items.Patients with vascular dementia have more severe behavioral retardation, depression, and anxiety than those with Alzheimer's disease when the groups have similar levels of cognitive impairment. This probably reflects the contrasting brain regions typically involved in the two disorders.
New methylation profile and high microsatellite instability in African-American colon cancer
Authors: Hassan Brim, Krisahm Kumar, Kevin Belgrave, Kamla Al-Mawaly, Francis Giardiello, Edward Lee, Mitra Hafezi, Camela Sahebi, Duane Smoot, Mehdi Nouraie, Hassan Ashktorab
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2649 

Background: Colorectal cancer (CRC) incidence and mortality are higher in African Americans (AAs), than in the general population. Whether or not there are any molecular particularities or preferential pathways in colon carcinogenesis in AAs need to be investigated at the genetic and epigenetic levels. We chose four prominent markers for epigenetic silencing including APC2. This new marker is a homologue of the adenomatous polyposis coli tumor suppressor which plays overlapping roles in wingless signaling and proliferation in CRC. In addition, we analyzed BRAF mutation, MSI status and MLH1 and MSH2 expression.    Material and Methods: A total number of 223 cases of primary CRC were selected from Howard University and John Hopkins Hospitals. DNA was extracted from microdissected tumor and matched normal MSI were studies using five sets of primers (BAT25, BAT26, NR21, NR22 and NR24). P16, MLH1, APC, APC2 methylation and BRAF V600E mutation were determined by MSP and/or pyrosequencing. MLH1 and MSH2 expression was determined by immunohistochemistry. Demographic and clinical data were extracted from patients charts. Difference of MSI by dependent factors were assessed by computing OR (95%CI).    Results: The mean (SD) age of cases was 66 (14) years and 42% were males. Fifty two percent (52%) of tumors were right sided, and 84% were moderately differentiated. The frequency of MSI was 20%. There was no statistically significant difference between age groups, gender, tumor location for MSI-H. The frequency of p16, MLH1, APC and APC2 methylation in the MSI-H group were 32%, 68%, 70% and 80%, respectively. Frequency of BRAF mutation was 23% among MSI-H group. MLH1 and MSH2 expression were 18% and 21% in MSI-H samples respectively.    Conclusion:    The MSI-H rate is higher (20%) than in the general population. At least 1/5 of MSI-H tumors (23%) are BRAF related. APC2, APC and MLH1 are frequent targets of epigenetic silencing and may be part of the colorectal cancer hypermethylome.
Abstract 3191: Experimental Validation Using Radiolabeled Microspheres of Absolute Quantitation of Regional Myocardial Blood Flow (MBF) Using Dynamic Rb-82 Positron Emission Tomography (PET)
Authors: Georges El Fakhri, Choukri Mekkaoui, Arkadiusz Sitek, Donald P Dione, Richard E Carson, Matthew Brennan, Marcelo F Di Carli, Albert J Sinusas
Journal: Circulation (2007)

Absolute quantitation of MBF with dynamic Rb-82 PET has great potential in the assessment of the extent and severity of ischemia in patients with suspected coronary artery disease, particularly at centers that lack access to a cyclotron, but requires validation of MBF estimation. METHODS: In order to validate our automated Rb-82 PET MBF quantitation based on generalized factor and compartment analyses (GFADS), we compared rest/stress regional Rb-82 MBF to reference MBF measured with radiolabeled microspheres (MS) in 6 dogs before and after creation of a critical LAD stenosis. High resolution dynamic Rb-82 PET acquisitions were performed on a Siemens HRRT in 3D listmode at rest and during adenosine stress in conjunction with injection of MS. Studies were rebinned into 24 5-sec, 6 10-sec, and 4 20-sec frames, and reconstructed using OSEM, compensating for scatter, randoms, attenuation and resolution. Hearts were cut into 5 mm slices (8 radial segments per slice). Myocardial segments were re-mapped to match the 17 segments of the standard polar map. Left and right ventricle input functions were automatically computed using GFADS. LV input was validated with on-line measurements of arterial activity. Polar maps of MBF (K1, ml/g/min) and coronary flow reserve (CFR) were computed using a 2-compartment kinetic model yielding 34 segments at rest and stress for each dog, that were remapped into apical, mid and basal ischemic and non-ischemic territories. RESULTS: MBF (uncorrected by RPP) derived from dynamic PET were in reasonable agreement with MS values at rest: MBF (PET) = 0.38 x MS + 0.39, r= 0.70, and in good agreement with MS values at stress: MBF(PET) = 0.48 x MS + 0.22; r=0.86. Regional CFR derived from dynamic PET was also in good agreement with MS values in the normal LCX territory (PET:1.44Â±0.17 vs MS:1.53Â±0.14) as well as in the LAD territory where a stenosis was created (1.07Â±0.18 vs. 1.17Â±0.16). PET and MS CFR values correlated well over the range of 0.51–2.37: CFR(PET) = 0.796 x MS + 0.421; r=0.940. CONCLUSION: Absolute quantification of MBF and CFR can be obtained from dynamic rest/stress Rb-82 PET using a fully automated GFADS approach which was validated in experimental animals using MS flow and should permit rapid determination of absolute MBF in patients.
Activity Of a JAK1/JAK2 Inhibitor In a Patient With KIT-Mutated Systemic Mastocytosis (SM) Associated With Myelofibrosis
Authors: Fabio P S Santos, Ricardo Helman, Welbert O Pereira, Renato D Puga, Sandra S Nakashima, Isabel C Bello, Michelli S Diniz, Nelson Hamerschlak, Paulo Vidal Campregher
Journal: Blood (2013)
Role of VEGF, PDGF and FGF in glioblastoma progression as determined by soluble decoy receptor expression in preclinical models
Authors: Thomas Harding, Minh Nguyen, Satya Yendluri, Gaung-Huan Tu, Melissa Gonzalez-Edick, Karin Jooss
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

3030 

A number of anti-angiogenic therapies that are currently in clinical development target the vascular endothelial growth factor (VEGF) family of ligands and receptors. The VEGF family has a demonstrated role in a wide range of malignancies, particularly highly vascularized tumors such as glioblastoma (GBM), although recent research has indicated that additional growth factor pathways may also be involved. Of these factors, members of the fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) family have been implicated. Inhibition of these additional pathways, either alone or in addition to VEGF, may result in potent anti-cancer responses that may lead to tumor dormancy or regression in cancer types that are unresponsive to VEGF treatment alone. We wished to examine the relative contribution of the VEGF, PDGF and FGF growth factors in glioblastoma angiogenesis and growth using soluble decoy receptors to specifically inhibit these individual growth factor pathways for therapeutic development. Soluble decoy receptors were constructed from VEGF receptor 1 and 2 (VEGFR1 and R2), PDGF receptor α and β (PDGFRα and β) and FGF receptor 1 and 2 (FGFR1 and R2) by fusion of the extracellular Ig-like domains of the receptor to an Fc segment of human IgG1. Ligand binding affinity and in vivo bioavailability was examined on multiple variants of each growth factor receptor to determine an optimal soluble inhibitor for the VEGF, PDGF and FGF pathways. Recombinant adeno-associated virus (rAAV) gene delivery was then employed to express the optimized receptors systemically in mice. Following a single intravenous or intramusclar injection of rAAV, the soluble receptors were expressed long-term (>3 months) and at a high-level (200-2000 μg/ml depending on receptor), providing sustained inhibition of their respective growth factor signaling pathways. Preclinical efficacy was examined for each soluble receptor in the subcutaneous C6 rat glioma, 4C8 murine glioma and the human U-87 and U-251 MG glioblastoma models, allowing the relative impact of VEGF, PDGF and FGF inhibition to be assessed side-by-side. Inhibition of VEGF provided therapeutic efficacy irrespective of the glioma model examined, however, the anti-tumor efficacy of PDGF and FGF inhibition was model-dependent. Following examination of anti-tumor efficacy as a monotherapy, growth factor inhibitors were combined to examine potential synergy by targeting multiple pathways in GBM models. The development of these optimized soluble decoy receptors allows the effect of specific inhibition of growth factor pathways to be individually investigated in tumor progression and may aid in the identification of signaling pathways to inhibit in combination for the next generation of angiogenic inhibitors.
Stakeholder health insurance
Authors: D. G Green, A. C Enthoven, J. Dixon, J. Appleby
Journal: BMJ (2001)

Editor—In their commentary to my article Dixon and Appleby seem to have been deeply taken aback by my claim that the NHS fails the poorest people in society and responded with a personal attack, asserting: “Green's aims are disingenuous at best.”1 The ordinary meaning of disingenuous is to be insincere or to have secret motives.

The essence of my argument is this: the rich can always take care of themselves and it is the government's responsibility to ensure that the poorest people have access to a reasonable standard of health care. But what should that standard be? Should it be perceived as a minimum or core standard, in which case it will always be possible to claim that it is too low? Or should it be seen as comprehensive, in which case it will be unachievable, as the BMA's recent inquiry acknowledged.

My proposed scheme tries to deal with this conundrum by removing the decision about the appropriate standard from the political domain. Instead, the standard guaranteed by the government should be linked to the choices made on their own behalf by people with middle incomes. I propose that the government should guarantee this standard for everyone. Yes, the rich will be able to afford more, but they can do so now under the NHS. That will not change, but the deeper reality is that all healthcare systems must be affordable, whether they are paid for by taxes on earnings or by private payments made from earnings.

My claim is that, compared with the standard currently provided by the NHS, such a guarantee would be a substantial improvement for the poorest people in the United Kingdom. In addition, the guaranteed standard will rise with growing incomes because it is linked to the personal market choices of middle income earners. It will not be a residual or second class standard.

The evidence for this claim is that the social insurance systems of France, Germany, and the Netherlands already work in a similar manner and it should be possible to put this case in a learned journal without being accused of bad faith. The King's Fund has been very keen to encourage the practice of evidence based medicine by doctors. How about some evidence based public policy analysis from Dixon and Appleby?
Defective WNT Signaling and Genetic Profile Of Endothelial Cells In Patients With Low Risk Myelodysplastic Syndromes Suggest a Contribution Of Vascular Niches To Myelodysplasia
Authors: Luciana Teofili, Maurizio Martini, Eugenia Rosa Nuzzolo, Sara Capodimonti, Alessandra Cocomazzi, Maria Grazia Iachininoto, Maria Teresa Voso, Gina Zini, Luigi M. Larocca
Journal: Blood (2013)
Abstract 260: Impact of Viewing an Ultrabrief Chest Compression--Only Video or Teaching a Chest Compression--Only Class on Lay Bystander CPR Performance in a High School
Authors: Daniel Beskind, Rebecca Thiede, Riley Hoyer, Melissa Ludgate, Devin McMorrow, Tim Tiutan, Romy Shane, Jeffrey Brown, Ann Smith, Mike Smith, Michael Pleasants, Ashish Panchal, Whitney E Burns, Uwe Stoltz
Journal: Circulation (2014)

Introduction: Cardiac arrest is responsible for 300,000 deaths in the United States. Bystander CPR has been shown to improve survival, but is only performed 30-50% of the time. Objectives: To determine if a chest compression-only (CCO) ultra-brief video (UBV) and a CCO-CPR class are effective at teaching CCO-CPR to high school students. Methods: This was a prospective cluster-randomized controlled trial with three arms: 1) CCO- UBV, 2) CCO-Class, 3) a control group (college recruiting video). High school students enrolled in a health course were randomized by class into of the 3 study arms. CPR performance was assessed with Laerdal Skillreporter mannequins after presentation of a scenario (sudden witnessed collapse) before (Pre), after (Post), and at 2 months following each intervention. CPR performance measures included the following: calling 911/starting compressions within 2 minutes, mean rate and depth of compressions. Results: 168/206 students 14-18 years of age, representing 5 classes, participated in this study. Results are shown in the Table. The proportion of participants that called 911 and/or started compressions within 2 minutes, as well as chest compression rate, significantly improved following the UBV and CCO-Class Post and at 2 months. Chest compression depth significantly improved following the CCO-Class both Post and at 2 months. No performance measure improved Pre to Post for the control arm. Limitations: More than one model of mannequin was used, observers and participants were not blinded to the intervention, and the study population represented a single public high school. Conclusions: A CCO-UBV and a brief CCO-CPR Class were effective at increasing the likelihood of calling 911, initiating CCO-CPR within 2 minutes and improving chest compression rate up to 2 months after the video or class in a population of high school students. The CCO-CPR class also significantly improved chest compression depth up to 2 months after the class.
Detailed molecular characterization of the 19q13 amplicon in pancreatic cancer
Authors: Riina Kuuselo, Eija Mahlamäki, Ritva Karhu, Anne H. Kallioniemi
Journal: Cancer Research (2006)

4191   Pancreatic cancer is a devastating disease with high mortality. This is mainly due to the lack of effective treatment regimens and tools to identify tumors at early stage of development. To improve the poor prognosis of this disease, we need to identify new molecular markers for earlier diagnosis as well as new therapeutic targets. Microarray-based technologies have provided us better tools to identify putative novel cancer genes. Previously, we performed a genome-wide copy number survey in pancreatic cancer cell lines using comparative genomic hybridization (CGH) on cDNA microarrays and identified 24 independent amplified regions. Here, we aimed to characterize more precisely one of the amplified regions, the 19q13 locus, to identify genes that might be of importance in pancreatic carcinogenesis. Public genome databases (http://www.ncbi.nlm.nih.gov/ and http://www.genome.ucsc.edu/) were used to select 15 BAC clones evenly distributed over this 2.9 Mb amplicon. Fluorescence  in situ  hybridization (FISH) with labeled BAC probes was performed in 16 pancreatic cell lines to define copy number alterations. FISH analyses confirmed the array CGH results and revealed extremely high level amplification (up to 20-fold) in PANC-1 cell line as well as lower level amplification in SU.86.86 and HPAC cell lines. FISH analysis also allowed us to narrow down the amplicon core to 1.1 Mb. The cell line copy number data was further validated in primary pancreatic tumors using FISH to a tissue microarray containing 33 indi vidual pancreatic cancer samples. High-level copy number increase of the 19q13 region was observed in three cases (9%). The 1.1 Mb core region of amplification contains 40 genes, including 24 known genes and 16 hypothetical proteins. expression levels of these transcripts were evaluated in the same set of cell lines using quantitative real-time RT-PCR. Interestingly, PANC-1 cells showed highly elevated expression levels of all genes located within the amplified region, thus suggesting that the high level amplification observed in this cell line overrules general transcription regulation mechanisms. In contrast, the SU.86.86 and HPAC cell lines with low level amplification showed a more specific expression pattern with a subset of genes having elevated expression levels. Taken together, a detailed characterization of the 19q13 amplicon in pancreatic cancer cell lines delineated a minimal region of amplification to 1.1 Mb. The presence of this amplicon was validated also in primary pancreatic tumors. expression profiling revealed a small set of biologically interesting genes that were more strongly expressed in the amplified cell lines than in the non-amplified group. In addition, a unique pattern of overexpression throughout the amplicon was observed in PANC-1 cells.
P1196 : Autoimmune hepatitis with T-regulatory cell deficiency in the context of GATA-2 dysfunction: A novel single gene association
Authors: G.J. Webb, A.G. Richter, M. Blahova, S.M. Curbishley, K.-K. Li, D.A.H. Neil, Y.H. Oo, D.H. Adams, V.H. Bigley, M.P. Collin, G.M. Hirschfield
Journal: Journal of Hepatology (2015)
Abstract #245: Metallothionein is up-regulated under hypoxia and promotes the survival of human prostate cancer cells
Authors: Mutsushi Yamasaki, Takeo Nomura, Takanori Matsubara, Kenichi Hirai, Fuminori Sato, Hiromitsu Mimata
Journal: Cancer Research (2009)

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

Tumor hypoxia is a common feature of several cancers, including prostate cancer, and is associated with tumor progression, acquisition of anti-apoptotic potential and therapeutic resistance. We explored hypoxia-inducible genes and examined the effect of knockdown of a target molecule with small interference RNA (siRNA) on the proliferation of human prostate cancer cells. Human prostate cancer cell lines (LNCaP and PC-3) were cultured in normoxia (21% O2) or hypoxia (0.5% O2). Hypoxia-inducible genes were identified by cDNA microarray analysis. Metallothionein (MT) expression was assessed by real time RT-PCR, Western blot analysis and immunohistochemical staining. siRNA was transfected to knock down MT expression, and the cell cycle and apoptosis were evaluated by flow cytometry analysis. In cDNA microarray analysis, 22 genes (including MT) were up-regulated under hypoxia. MT-1X and MT-2A were up-regulated in real time RT-PCR. In particular, MT-2A was increased 3-fold in LNCaP and 8-fold in PC-3. The siRNA-MT-2A treatment resulted in a 20% inhibition of cell growth and induced apoptosis in both LNCaP and PC-3. In human prostate tissue, intense staining of MT was observed in cancer cells and residual cancer cells after androgen ablation therapy, while normal tissue was only stained in patches. In conclusion, MT was up-regulated under hypoxia in prostate cancer cells and overexpressed in prostate cancer tissue and residual cancer cells after androgen ablation therapy. As down-regulation of MT by siRNA inhibited cell growth and induced cell death, MT may be a new molecular target for the treatment of human prostate cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 245.
Longitudinal Gene Expression Profiling Reveals Down-Regulation Of BCR Signaling-Related Genes In Chronic Lymphocytic Leukemia (CLL) Patients Treated With Ibrutinib Plus Rituximab
Authors: Julia Hoellenriegel, Elena Hartmann, Andreas Rosenwald, Susan O'Brien, Michael Keating, William G. Wierda, Joseph J. Buggy, Jan A. Burger
Journal: Blood (2013)
Abstract 16845: Peroxiredoxin 1 Protects DDAH Activity During Oxidative Stress
Authors: Ping Zhang, Xin Xu, Xinli Hu, John Fassett, Yingjie Chen, Robert J Bache
Journal: Circulation (2011)

Peroxiredoxins (Prdxs) are a family of small nonseleno peroxidases that catalyze the reduction of H 2 O 2 , organic hydroperoxides and peroxynitrite. Prx 1 is the most abundant and ubiquitously distributed member of mammalian Prx. In macrophages, nitric oxide (NO) increases Prx1 expression, inhibits Prx overoxidation, and increases Sulfiredoxin (SRX) expression (SRX is the major macrophage sulfinyl reductase that regenerates oxidized 2-cys Prxs to the active form). DDAH1 is the major enzyme that degrades the endogenous NOS inhibitor ADMA and thereby plays an important role in maintaining normal endothelial function. Using co-immunoprecipitation and mass spectrometry we found that Prx1 binds to DDAH1. On the basis of this finding, we hypothesized that as a result of degrading ADMA, increasing NOS activity and NO production, DDAH1 causes increased SRX expression and regenerates active Prx; the association of Prx1 and DDAH1 could thus protect DDAH1 from loss of activity caused by oxidative stress. In HUVEC, the NO donor DETA-NO (100μM) increased SRX expression and decreased Prx overoxidation (Prx-SO2). Comparing aortic endothelial cells from DDAH1 global KO (KO cells) and wild type control mice (wt cells), we found higher Prx-SO2 levels in KO cells. Furthermore, treatment with ADMA (100 μM) inhibited SRX expression in KO cells but not in wt cells. These results suggest that DDAH1 increases SRX expression, and facilitates regeneration of the Prx active form. Since DDAH1 activity can be inhibited by oxidative stress, we studied the effect of hydroperoxide on the Prx1 and DDAH1 interaction. When we treated HUVEC overexpressing DDAH1 with tert-Butyl hydroperoxide (t-BH 50 μM, 30 min), DDAH activity decreased 15% ± 2.9% (p&lt;0.05), while the level of Prx1 and DDAH1 interaction increased as shown by DDAH1 immunoprecipitation and Prx1 western blot. The findings suggest that under conditions of oxidative stress, increased Prx1 binding to DDAH1 acts to protect DDAH activity.