tbuckley/cabot-search huggingface dataset:
Vascular Lipid Accumulation, Lipoprotein Oxidation, and Macrophage Lipid Uptake in Hypercholesterolemic Zebrafish
Authors: Konstantin Stoletov, Longhou Fang, Soo-Ho Choi, Karsten Hartvigsen, Lotte F. Hansen, Chris Hall, Jennifer Pattison, Joseph Juliano, Elizabeth R. Miller, Felicidad Almazan, Phil Crosier, Joseph L. Witztum, Richard L. Klemke, Yury I. Miller
Journal: Circulation Research (2009)

Lipid accumulation in arteries induces vascular inflammation and atherosclerosis, the major cause of heart attack and stroke in humans. Extreme hyperlipidemia induced in mice and rabbits enables modeling many aspects of human atherosclerosis, but microscopic examination of plaques is possible only postmortem. Here we report that feeding adult zebrafish ( Danio rerio ) a high-cholesterol diet (HCD) resulted in hypercholesterolemia, remarkable lipoprotein oxidation, and fatty streak formation in the arteries. Feeding an HCD supplemented with a fluorescent cholesteryl ester to optically transparent fli1:EGFP zebrafish larvae in which endothelial cells express green fluorescent protein (GFP), and using confocal microscopy enabled monitoring vascular lipid accumulation and the endothelial cell layer disorganization and thickening in a live animal. The HCD feeding also increased leakage of a fluorescent dextran from the blood vessels. Administering ezetimibe significantly diminished the HCD-induced endothelial cell layer thickening and improved its barrier function. Feeding HCD to lyz:DsRed2 larvae in which macrophages and granulocytes express DsRed resulted in the accumulation of fluorescent myeloid cells in the vascular wall. Using a fluorogenic substrate for phospholipase A 2 (PLA 2 ), we observed an increased vascular PLA 2 activity in live HCD-fed larvae compared to control larvae. Furthermore, by transplanting genetically modified murine cells into HCD-fed larvae, we demonstrated that toll-like receptor-4 was required for efficient in vivo lipid uptake by macrophages. These results suggest that the novel zebrafish model is suitable for studying temporal characteristics of certain inflammatory processes of early atherogenesis and the in vivo function of vascular cells.
Abstract 2596: Correlation of TGF beta receptor II and pSmad2 expression with clinico-pathological factors in human breast cancer: An immunohistochemical observation from the Shanghai Breast Cancer Study
Authors: Qingchao Qiu, Yinghao Su, Wei Lu, Hui Cai, Ying Zheng, Xiao Ou Shu, Wei Zheng, Qiuyin Cai
Journal: Cancer Research (2012)

Abstract Loss of transforming growth factor (TGF)-α expression occurs in the early stages of breast carcinogenesis, which contributes to tumor progression. The loss of TGF-β responsiveness frequently occurs at the level of the TGF- ≤ receptor II (TGF-βRII) in breast cancer. Smad2 is a major receptor-activated Smad downstream of TGF-β signaling. Phosphorylated Smad2 (pSmad2) is translocated into the nucleus to modulate transcription of target genes involved in many cell functions. We evaluated the correlation of TGF-βRII and pSmad2 protein expression with clinico-pathological factors in human breast cancer tissue from 435 breast cancer cases from the Shanghai Breast Cancer Study, a population-based, case-control study. Expression of the TGF-βRII and pSmad2 proteins was detected using a double immunofluorescence staining method, which was validated with standard single immunostains. Lab-constructed tissue microarray samples were used as positive and negative controls. The immunofluorescence signals were designated as negative, positive, or strong-positive based on a modified Allred scoring system. Staining patterns of TGF-βRII were classified into membranous or cytoplasmic predominant. TGF-βRII expression intensity was significantly higher in normal and early-stage breast cancers (in situ carcinoma) than that in later stages (in situ carcinoma adjacent to invasive carcinoma, and invasive carcinoma) (P&amp;lt;0.001). The cytoplasmic predominant expression pattern of TGF-βRII was more frequently observed in breast cancer than that in normal breast epithelium on the same tissue section (P&amp;lt;0.001). pSmad2 expression was significantly increased in breast cancer compared with adjacent normal breast epithelium. In addition, the increased pSmad2 expression was significantly associated with higher breast cancer grade (P=0.004). No significant correlations between TGF-βRII/pSmad2 protein expression and other prognostic factors, such as age at diagnosis, menopause status, history of breast cancer, TNM stage, and ER/PR/HER2 status, was found. The results of this study suggest that reduced TGF-βRII expression and its cytoplasmic predominant expression pattern may be associated with the progression of breast cancer, and increased pSmad2 expression may be associated with carcinogenesis and poor differentiation of breast cancer cells. Additional samples are being analyzed to validate these findings and to evaluate the expression of TGF-βRII and pSmad2 in relation to breast cancer survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2596. doi:1538-7445.AM2012-2596
Abstract 264: Mesenchymal stem cells mediate epithelial-to-mesenchymal transition (EMT) and stemness regulation in pancreatic cancer via Notch signal.
Authors: Ayano Kabashima-Niibe, Hajime Higuchi, Yumi Matsuzaki, Yo Mabuchi, Shinsuke Funakoshi, Masayuki Adachi, Yasuo Hamamoto, Hiromasa Takaishi, Toshifumi Hibi
Journal: Cancer Research (2013)

Abstract Cancer associate fibroblasts (CAFs), one of the major components of the cancer stroma, are prominently involved in tumor progression including epithelial to mesenchymal transition (EMT). Recently, bone marrow derived mesenchymal stem cells (MSCs) have been suggested as candidate for the source of tumor-promoting CAFs. We previously demonstrated that side population (SP) cells, which are enriched with so-called tumor initiating stem cell like cells (TISCs), play a pivotal role of local invasion and liver metastasis in pancreatic cancer (Int-J-Cancer 124:2771, 2009). Therefore, we formulated the hypothesis that MSCs regulate SP cells EMT and TISC-like properties such as tumor formation/progression. The AIM of the present study was to examine whether bone marrow-derived MSCs have ability to mediate EMT and/or tumor progression in pancreatic cancer SP cells. METHODS: MSCs were pre-treated with TGF-beta for 3 days. SP or non-SP cells were co-cultured in the presence or absence of TGF-beta-pretreated MSCs (Tb-MSCs) for 3 days. Real-time PCR experiments were performed to quantitate mRNA levels of EMT associated genes as well as so-called stemness related genes. PANC-1 derived SP or non-SP cells were co-injected with Tb-MSCs into NOD/SCID mice, and their tumorigenesity was evaluated. RESULTS: Co-culturing with Tb-MSCs dramatically induced EMT-associated mRNA alterations including suppression of E-cadherin and induction of slug in PANC-1 SP cells. In SP cells but not in non-SP cells, levels of stemness genes including CD133, Oct4, LGR5, were enhanced by co-culturing with Tb-MSCs. Tb-MSCs enhanced in vitro sphere forming activity as well as in vivo tumor formation in SP cells. These alterations including EMT-associated gene modifications and enhanced sphere formation were suppressed by Notch signal inhibition, suggested MSCs-associated regulation of EMT and TISC-like properties are mediated by Notch-signaling. In CONCLUSION, MSCs regulate EMT and they maintain TISC-like properties in pancreatic cancer SP cells via Notch signal-dependent mechanisms. Targeting Notch signaling would appear to be attractive to prevent MSCs and/or stromal cell-associated cancer progression. Citation Format: Ayano Kabashima-Niibe, Hajime Higuchi, Yumi Matsuzaki, Yo Mabuchi, Shinsuke Funakoshi, Masayuki Adachi, Yasuo Hamamoto, Hiromasa Takaishi, Toshifumi Hibi. Mesenchymal stem cells mediate epithelial-to-mesenchymal transition (EMT) and stemness regulation in pancreatic cancer via Notch signal. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 264. doi:10.1158/1538-7445.AM2013-264
Is NOS uncoupling the missing link between atrial fibrillation and chronic non-ischaemic cardiomyopathy? Reply
Authors: Y. Nishijima, A. Sridhar, J. L. Zweier, A. J. Cardounel, C. A. Carnes
Journal: Cardiovascular Research (2011)

We thank Crijns et al. for their positive comments regarding the importance of our recent study in Cardiovascular Research .1 We also appreciate the detailed attention of Crijns et al. to the methodologies presented in our study. We welcome the opportunity to provide additional information that we hope will clarify our approach and conclusions for the readers of Cardiovascular Research . The two issues raised by Crijns et al. generally address nitric oxide synthase (NOS) biochemistry, related analytical methodology, and acquisition and interpretation of findings related to the electrophysiological data.

It is important to note that the presence of NOS monomer is not direct evidence of NOS uncoupling and that changes in the dimer/monomer ratio are not directly related to the functional uncoupling of the enzyme. Moreover, only the dimeric form has been shown to be biochemically active and able to generate NO and superoxide.2–4 Several lines of evidence in our manuscript are consistent with iNOS oxidase activity in the atria of heart failure (HF) dogs, including (i) decreased tetrahydrobiopterin (BH4) levels, (ii) reduced NO production, and (iii) increased superoxide production. These alterations occurred in the face …
Ethics as Practiced.
Authors: Herbert A. Russell
Journal: JAMA (1898)

Brooklyn, July 7, 1898. <h3>To whom it may concern:</h3> —This is to certify that I am acquainted with the methods of the International Fidelity Rupture Cure Co., and am satisfied that it is a work which any doctor, whom this Co. may consider competent and reliable, can take up in connection with his regular practice, with great advantage to himself, and at the same time keep within the bounds of Professional Ethics. Yours respectfully, Demonstrator of Anatomy at Long Island College Hospital. P. S.—The above is a verbatim letter from Dr. Russell, who is using this treatment in connection with his practice.
Connective Tissue Diseases
Authors: J. T. Scott
Journal: Annals of the Rheumatic Diseases (1978)

Local measures of neurotransmitters provide crucial insights into neurobiological changes underlying altered functional connectivity in psychiatric disorders. However, noninvasive neuroimaging techniques such as magnetic resonance spectroscopy (MRS) may cover anatomically and functionally distinct areas, such as <i>p32</i> and <i>p24</i> of the pregenual anterior cingulate cortex (pgACC). Here, we aimed to overcome this low spatial specificity of MRS by predicting local glutamate and GABA based on functional characteristics and neuroanatomy in a sample of 88 human participants (35 females), using complementary machine learning approaches. Functional connectivity profiles of pgACC area <i>p32</i> predicted pgACC glutamate better than chance (<i>R</i><sup>2</sup> = 0.324) and explained more variance compared with area <i>p24</i> using both elastic net and partial least-squares regression. In contrast, GABA could not be robustly predicted. To summarize, machine learning helps exploit the high resolution of fMRI to improve the interpretation of local neurometabolism. Our augmented multimodal imaging analysis can deliver novel insights into neurobiology by using complementary information. <b>SIGNIFICANCE STATEMENT</b> Magnetic resonance spectroscopy (MRS) measures local glutamate and GABA noninvasively. However, conventional MRS requires large voxels compared with fMRI, because of its inherently low signal-to-noise ratio. Consequently, a single MRS voxel may cover areas with distinct cytoarchitecture. In the largest multimodal 7 tesla machine learning study to date, we overcome this limitation by capitalizing on the spatial resolution of fMRI to predict local neurotransmitters in the PFC. Critically, we found that prefrontal glutamate could be robustly and exclusively predicted from the functional connectivity fingerprint of one of two anatomically and functionally defined areas that form the pregenual anterior cingulate cortex. Our approach provides greater spatial specificity on neurotransmitter levels, potentially improving the understanding of altered functional connectivity in mental disorders.
Histochemical staining of sunburn cells for sulphhydryl and disulphide groups: a time course study
Authors: KIICHIRO DANNO, TAKESHI HORIO
Journal: British Journal of Dermatology (1980)

SUMMARY Ultraviolet light (UV)-exposed rabbit skin was stained with a fluorescent thiol reagent or haematoxylin and eosin to investigate a time relationship between histochemical stainings for sulphhydryl (-SH) and disulphide (S-S) groups and sunburn cell (SBC) production. SBCs appeared by 8 h after irradiation, increased and showed a peak at 48 h, then declined to zero by 96 h. SBCs showing -SH staining increased to a maximum of 41–59% at 24–48 h and declined to 26–45% by 72 h, whereas S-S-stained SBCs were only a few at 8–24 h and then increased up to 65–85% by 72 h. The results seem to indicate that S-S linkage may occur in the process of SBC production.
Aortic Valve Replacement in Patients With Severe Aortic Regurgitation and Reduced Left Ventricular Ejection Fraction
Authors: Shahbudin H. Rahimtoola
Journal: Circulation (2003)

To the Editor:Chaliki et al 1 have presented data in patients with severe aortic regurgitation (AR) with normal left ventricular (LV) ejection fraction (LVEF Ն50%; nϭՆ73)."Mild" LVEF reduction (35% to 50%; nϭ134) and "markedly" low LVEF (Ͻ35%; nϭ43) who were operated on between 1980 and 1995.In February of 1980, 2 we documented (in a study not cited by the authors) the outcome of 17 patients with severe AR and LVEF of 0.25 to 0.49 who had aortic valve replacement (AVR) between January 1973 and July 1977.There were no operative deaths.There were 5 late deaths, and of the remaining 12 patients, 5 and 6 were in New York Heart Association functional classes II and I, respectively.We concluded that all patients with severe AR and moderately severe impairment of LV function should be offered AVR with or without coronary artery bypass graft unless there is a specific contraindication to surgery because of the low operative mortality and the improvement in symptoms and in various parameters of LV size and function after AVR.Of interest, the conclusion of Chaliki and coworkers 1 in 2002 that such patients "should not be denied the benefits of AVR" is not different from ours in 1980.The findings of Chaliki et al 1 would be more valuable clinically if the following were provided:(1) The number and percentage of patients in each of the 3 subgroups who had preoperative coronary arteriography, and of these, the number and percentage who had significantly obstructive coronary artery disease.(2) The numbers of patients with LVEF 20% to Ͻ25% and 15% to Ͻ20%, and their operative mortality and survival (meanϮSE) at 3, 5, 10, and 20 years.(3) Actuarial event-free survival (including operative mortality and all complications including those related to the prosthesis and to cardiac and noncardiac comorbid conditions) at 5 and 10 years (mean Ϯ SE) in the subgroup of markedly low LVEF; the authors state that "a notable period of event-free survival can be achieved in most patients after correction of AR despite their very low preoperative EF," but actuarial event-free survival data were not presented.Their finding of the higher than "expected" late mortality (Figure 2 1 ) is problematic because operative mortality was excluded, and the comparison to the population is inappropriate in this instance.
Orf Skin Ulcer
Authors: P Roingeard, L Machet
Journal: New England Journal of Medicine (1997)

Figure 1. A painful finger ulcer (Panel A) developed in a 58-year-old man who was also found to have a palpable olecranal lymph node. The rest of his examination was unremarkable. A biopsy specimen of the lesion, fixed and sectioned thinly for transmission electron microscopy, revealed numerous parapoxvirus particles. At a low magnification, extreme swelling of infected cells can be seen, resulting in degeneration (Panel B, ×6000). Higher magnification of a section of Panel B (see box) clearly shows characteristic oval virions consisting of a core (c) surrounded by an envelope (e) (Panel C, × 60,000). When questioned about risk . . .
Salmonella Dublin Osteomyelitis of the Spine
Authors: A. A. Miller
Journal: BMJ (1954)

CHRONIC BRONCHITISWe must also explain the differences in mortality rates from chronic bronchitis in the different countries of the world.Why should our mortality rate from this condition be almost 30 times greater than in the U.S.A. ?And why should it be more than twice as much as that of Belgium ?Obviously there is a great need for further research and inquiry into the causation of and variation in the disease.This research should be carried out at a number of levels, one of which should be in general practice, for it is here that the true incidence and course can be observed.That this is possible has been proved, and perhaps it should be the first step in a national and possibly world-wide investi- gation and effort.It is.considered by many to be a pre- ventable disease (Lewis-Faning, 1940; Pemberton, 1952; Joules, 1953a, 1953b).If this is borne out then vigorous steps at the highest levels should be taken to implement the findings. SummaryThe toll from chronic bronchitis includes 30,000 deaths and 161 million lost days from work annually.In the G.P.O.15% of all medical retirements are due to this cause.Around 10% of all attendances in general prac-
Ethical Debate: Providing treatment against a patient's wishes
Authors: D W Yates
Journal: BMJ (1995)

A patient who presents voluntarily at an emergency department should be assumed to want treatment. If relatives or friends bring in a patient we can again assume that they want the person in their care to receive attention. The situation is more difficult if a patient is brought in by the police or by a carer from an institution. However, in the two cases reported here the casualty officer would have known that friends or relatives were responsible for each patient's presentation. In such cases the doctor must therefore take into account the broader perspectives of each case rather than the short term demands of a patient.

Decisions must be taken on the basis of previously agreed, evidence based protocols and should …
Quantification of myocardial infarction by computer-assisted positron emission tomography
Authors: A. B NICHOLS, R. H MOORE, S. COCHAVI, G. M POHOST, W. H STRAUSS
Journal: Cardiovascular Research (1980)

The accuracy of three-dimensional transverse section positron emission imaging for quantification of myocardial infarction size was validated and compared with the accuracy of two-dimensional planar positron imaging. After induction of acute anterior myocardial infarction in anaesthetised dogs, gallium-68 albumin microspheres were injected into the left atrium. Planar and transverse section images of the thorax were obtained with a multicrystal positron camera. After staining with tetrazolium tetrachloride injected intravenously, the hearts were excised, sectioned manually, and planar imaging repeated. Each myocardial infarction was clearly delineated by transverse section imaging with high contrast ratios (mean 0.68 ± 0.02 SEM); planar imaging identified seven of nine infarcts but with lower contrast ratios (0.24 ± 0.04; P <0.001). The volume of infarcted myocardium determined from transverse section images correlated well with true infarct volume (r = 0.94); whereas planar images poorly predicted infarct size (r = 0.63). Thus, computer-assisted transverse section positron imaging provides in vivo localisation of microsphere distribution for improved radioisotopic quantification of myocardial infarction.
Influence of interleukin-6 gene polymorphisms in epicardial adipose tissue and coronary artery calcification in patients with psoriasis
Authors: T. Torres, N. Bettencourt, J. Ferreira, C. Carvalho, D. Mendonça, P. Pinho-Costa, C. Vasconcelos, M. Selores, B. Silva
Journal: British Journal of Dermatology (2014)

Journal Article Influence of interleukin‐6 gene polymorphisms in epicardial adipose tissue and coronary artery calcification in patients with psoriasis Get access T. Torres, T. Torres Department of Dermatology Centro Hospitalar do Porto Porto PortugalUnit for Multidisciplinary Investigation in Biomedicine Instituto Ciências Biomédicas Abel Salazar University of Porto Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar N. Bettencourt, N. Bettencourt Department of Cardiology Centro Hospitalar Gaia/Espinho Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar J. Ferreira, J. Ferreira Immunogenetics Laboratory Instituto Ciências Biomédicas Abel Salazar University of Porto Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar C. Carvalho, C. Carvalho Immunogenetics Laboratory Instituto Ciências Biomédicas Abel Salazar University of Porto Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar D. Mendonça, D. Mendonça Department of Population Studies Instituto Ciências Biomédicas Abel Salazar University of Porto Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar P. Pinho‐Costa, P. Pinho‐Costa Unit for Multidisciplinary Investigation in Biomedicine Instituto Ciências Biomédicas Abel Salazar University of Porto Porto PortugalImmunogenetics Laboratory Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA) Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar C. Vasconcelos, C. Vasconcelos Unit for Multidisciplinary Investigation in Biomedicine Instituto Ciências Biomédicas Abel Salazar University of Porto Porto PortugalDepartment of Clinical Immunology Centro Hospitalar do Porto Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar M. Selores, M. Selores Department of Dermatology Centro Hospitalar do Porto Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar B. Silva B. Silva Unit for Multidisciplinary Investigation in Biomedicine Instituto Ciências Biomédicas Abel Salazar University of Porto Porto PortugalImmunogenetics Laboratory Instituto Ciências Biomédicas Abel Salazar University of Porto Porto Portugal Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 2, 1 February 2015, Pages 534–536, https://doi.org/10.1111/bjd.13271 Published: 01 February 2015