tbuckley/cabot-search huggingface dataset:
CD36-Dependent 7-Ketocholesterol Accumulation in Macrophages Mediates Progression of Atherosclerosis in Response to Chronic Air Pollution Exposure
Authors: Xiaoquan Rao, Jixin Zhong, Andrei Maiseyeu, Bhavani Gopalakrishnan, Frederick A. Villamena, Lung-Chi Chen, Jack R. Harkema, Qinghua Sun, Sanjay Rajagopalan
Journal: Circulation Research (2014)

Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood.To investigate the mechanisms by which particulate matter <2.5 μm (PM2.5) induces progression of atherosclerosis.Atherosclerosis-prone ApoE(-/-) or LDLR(-/-) mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis.Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh, in air pollution-induced atherosclerosis progression.
Exercise in Individuals With IDDM
Authors: David H Wasserman, Bernard Zinman
Journal: Diabetes Care (1994)

The greater energy requirements that accompany exercise necessitate an increase in fuel mobilization from sites of storage and a subsequent increase in the oxidation of thesefuels within the working muscle. A precise endocrine response controls the needed increment in fuel metabolism. The importance of the endocrine system is readily apparent in individuals with insulin-dependent diabetes mellitus (IDDM) in whom the normal endocrine response to exercise is lost. When a person with IDDM exercises with too little insulin in the circulation, an excessive counterregulatory hormone response may ensue, and the alreadyelevated blood glucose and ketone body levels can become even greater. On the other hand,if too much insulin is present, the exercise-induced increase in substrate mobilization can be attenuated or completely blocked and, as a result, hypoglycemia may ensue. Insulin therapy must be modified in anticipation of exercise to avoid states of under- or overinsulinization, and/or carbohydrate ingestion must be adjusted to compensate for the potential glycemic effects of inappropriate insulin levels. The presence of advanced diabetic complications can further accentuate the difficulty of exercise for those with IDDM. The purpose of this review is to provide the scientific information necessary to assess therationale for recommending regular exercise to individuals with IDDM and to develop guidelines for integrating daily exercise with insulin treatment and dietary management.
Abstract 3767: Detection biomarkers for squamous cell bladder carcinoma in a global setting
Authors: Wael Al-Delaimy, Ahmed Shokeir
Journal: Cancer Research (2010)

Abstract Bladder cancer is the fifth common malignancy in the US, and internationally it is the second most common cause of mortality from genitourinary malignancies after prostate cancer. Current clinical practice and recommendations do not include early screening for prevention. The use of cystoscopy cannot become a routine screening method of early detection due to limitations, including cost, while cytology is specific but not sensitive. Biomarkers that screen for bladder cancer before it becomes invasive are an alternative viable solution if validated and made cost-effective. Studies have mostly looked at translational cell bladder cancer and not squamous cell bladder cancer that is much more common in many parts of Africa, including Egypt and related to Schistomiasis parasitic infection. The aim in this study was to validate the use of three FDA approved biomarkers of early detection of translational baldder cancer on squamous bladder cancer in Egypt. The NMP22, Telomerase, and CD44 test kits were used for urine sample from 60 squamous bladder cancer patients and 60 non-cancer population controls. The cases and the controls were recruited from the Urology and Nephrology Center at Mansora University in Mansora, Egypt. Patients were diagnosed by cytoscopy and cytology. There was a significant difference in mean NMP22, CD44 and Telomerase levels among cases compared to controls. However, when adjusting for age and sex, only NMP22 and Telomerase remained significant. There was no significant difference among bladder cancer patients for presence or absence of a mass or schistomiases infection. CD44 and NMP22 mean levels were higher among patients if they were with stages 3 or 4 of bladder cancer compared to stages 1or 2 but this did not reach statistical significance. NMP22 and Telomerase biomarkers had better specificity and sensitivity than CD44 in predicting bladder cancer as shown by the Receiver Operating Characteristics (ROC) curves. In Conclusion, these biomarkers are satisfactory for detection of squamous cell bladder cancer, especially NMP22 and telomerase, and can become routinely used in the clinical setting in developing countries with high percentage of squamous cell bladder cancer. The next phase of biomarker validation for these assays among high-risk populations is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3767.
Gambogic acid and celastrol are two powerful anti-inflammatory drugs in arthritis
Authors: R. Cascao, B. Vidal, J. E. Fonseca, L. F. Moita
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease where the excessive secretion of pro-inflammatory cytokines plays an important role. The authors have previously reported an increase in circulating interleukin 1β (IL-1β) levels in very recent onset arthritis and in the synovial fluid of established RA patients. This observation may be explained by the continuous activation of caspase-1 that the authors observed both in early polyarthritis and in established RA patients. Therefore, pathways that regulate IL-1β, such as caspase-1 and nuclear factor-κB (NF-κB) activation, might play a relevant role in arthritis onset and drugs that target these pathways could potentially constitute promising therapeutic agents in RA. The authors have thus used a THP1 macrophage-like cell line to screen among several Food and Drug Administration approved drugs those which downregulate IL-1β and caspase-1 activation. Gambogic acid and celastrol were two of the most promising therapeutic candidates obtained by this screening. <h3>Objectives</h3> The study main goal was to investigate whether gambogic acid and celastrol administration is able to attenuate inflammation in a rat model of antigen-induced arthritis (wistar AIA rat). <h3>Materials and methods</h3> Drugs and vehicle control were administrated to arthritic wistar AIA rats after 4 days of disease induction for a period of 15 days. The inflammatory score, paw diameter and body weight were evaluated during the time of treatment. Rats were killed after 19 days of disease evolution and paw samples were collected for histology observation of erosions, pannus formation and cellular infiltration. <h3>Results</h3> The authors found that both gambogic acid and celastrol significantly suppressed inflammation in the joints in comparison with arthritic rats treated with vehicle only. Moreover, the rats treated with these drugs did not show differences in body weight or other evident side effects. The histology results revealed that gambogic acid and celastrol treated rats showed a normal joint structure with a complete abrogation of the inflammatory infiltrate. <h3>Conclusions</h3> This results suggest that both drugs have significant anti-inflammatory properties, in agreement with their reported ability to suppress NF-κB activation. Gambogic acid and celastrol might therefore constitute putative anti-inflammatory drugs with therapeutic efficacy in the treatment of inflammatory diseases, such as RA.
Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb
Authors: Tiziana Bruno, Roberta De Angelis, Francesca De Nicola, Christian Barbato, Monica Di Padova, Nicoletta Corbi, Valentina Libri, Barbara Benassi, Elisabetta Mattei, Alberto Chersi, Silvia Soddu, Aristide Floridi, Claudio Passananti, Maurizio Fanciulli
Journal: Cancer Cell (2002)
THE ORIENTAL EUNUCHS.
Authors: EDMUND ANDREWS
Journal: JAMA (1898)

The word eunuch is Greek and derived from [unk] and [unk], literally having charge of the bedchamber, i. e., a chamberlain. In Hebrew it was<i>Saris</i>, meaning mutilated; probably because the first royal chamberlains were castrated men. However, men officially called eunuchs soon began to be employed in all sorts of offices, though many of them were really not such in the surgical sense, and the word became merely equivalent to the term officer. A figure of speech also crept into use in which certain persons for religious reasons are said to have "eunuchized" themselves, who, in the opinion of commentators, underwent no mutilation, but merely lived in total celibacy, like eunuchs, as in the third class mentioned in Matthew, 19, 12. This habit of broadening the definition of words at the expense of their precision is a linguistic trait of oriental countries. The people were very fond of this
V. The Proposed Indiana Family Practice Program
Authors: John B. Hickam
Journal: JAMA (1961)

WITH the encouragement of representatives of the American Medical Association Council on Medical Education and Hospitals, the Indiana University School of Medicine late in 1959 outlined a 2-year training program to prepare students for family practice. This program followed generally the recommendations made in June, 1959, by the Committee on Preparation for General Practice, with respect to division of time among different subjects and made provision for experience in comprehensive patient care. The program is not yet in operation, but planning it has shown us some problems which can attend the introduction of family practice training into a university medical center. This presentation will outline the program we have conceived and some of the problems which we expect. <h3>Proposed Program</h3> The 2-year program is planned to accommodate 6 trainees, 3 in each year of the program. <h3>Introductory Period.—</h3> The first 9 months will be spent in a rotation which includes the
The spatial association between community air pollution and mortality: a new method of analyzing correlated geographic cohort data.
Authors: R Burnett, R Ma, M Jerrett, M S Goldberg, S Cakmak, C A Pope, D Krewski
Journal: Environmental Health Perspectives (2001)

We present a new statistical model for linking spatial variation in ambient air pollution to mortality. The model incorporates risk factors measured at the individual level, such as smoking, and at the spatial level, such as air pollution. We demonstrate that the spatial autocorrelation in community mortality rates, an indication of not fully characterizing potentially confounding risk factors to the air pollution-mortality association, can be accounted for through the inclusion of location in the model assessing the effects of air pollution on mortality. Our methods are illustrated with an analysis of the American Cancer Society cohort to determine whether all cause mortality is associated with concentrations of sulfate particles. The relative risk associated with a 4.2 microg/m(3) interquartile range of sulfate distribution for all causes of death was 1.051 (95% confidence interval 1.036-1.066) based on the Cox proportional hazards survival model, assuming subjects were statistically independent. Inclusion of community-based random effects yielded a relative risk of 1.055 (1.033, 1.077), which represented a doubling in the residual variance compared to that estimated by the Cox model. Residuals from the random-effects model displayed strong evidence of spatial autocorrelation (p = 0.0052). Further inclusion of a location surface reduced the sulfate relative risk and the evidence for autocorrelation as the complexity of the location surface increased, with a range in relative risks of 1.055-1.035. We conclude that these data display both extravariation and spatial autocorrelation, characteristics not captured by the Cox survival model. Failure to account for extravariation and spatial autocorrelation can lead to an understatement of the uncertainty of the air pollution association with mortality.
Patrick Alan Adam
Authors: J. ROBBINS
Journal: BMJ (2003)

Former general practitioner Plymstock, Plymouth (b Folkestone 1918; q Edinburgh 1942; DPM), died 30 March 2003.

Shortly after qualifying Pat joined the Royal Naval Volunteer Reserve and served as a medical officer on the Russian convoys bound for Murmansk. After the second world war he trained in psychiatry, working for a time at St Andrew's Hospital, Northampton. In 1954 he started in general practice in Plymstock, where he stayed until retirement in 1983. Humorous and urbane he would host, with his wife, Isobel, the most magnificent dinner parties. Pat was a prizewinning gardener and an accomplished sailor, skier, and golfer. He leaves Isobel, three children, and seven grandchildren.
SNOMED International (systematized nomenclature of human and veterinary medicine). 3rd ed. Edited by R.A. Cote, D.J. Rothwell, J.L. Palotay and R.S. Beckett. Vol. I (868 pp) and Vol. II (1160 pp), Numeric indices, Vol. III (1,004 pp) and Vol. IV (1,260 pp), Alphabetical Indices. Chicago: College of American Pathologists, 1993. $300 ($225 for members of College of American Pathologists)
Authors: J. Ludwig
Journal: Hepatology (1994)
ET-40 * ONCOLYTIC VIRUS INDUCED HMGB1 SECRETION AND ITS IMPACT ON TUMOR ANGIOGENESIS
Authors: K. Muili, C. Bolyard, C. Jaime-Ramirez, J. Y. Yoo, B. Kaur
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is a difficult-to-treat, and the most aggressive of primary brain tumors. Survival is less than 2 years despite aggressive therapy. Oncolytic virus (OV) therapy has shown tremendous benefits in the treatment of GBM and other tumors. This benefit is limited by host antiviral immune responses that enhance OV clearance and tumor progression. In this study, using both in-vivo and in-vitro models of GBM, we have tested the role of High mobility group box 1 (HMGB1) in OV therapy. HMGB1 is a nuclear protein that binds and regulates transcription factors. Extracellular HMGB1 functions as damage associated molecular pattern (DAMP), it mediates the inflammatory response upon binding to inflammation mediators, such as receptor of advanced glycated end product (RAGE), toll-like receptors (TLRs) 2, 4, and 9. Here, we report that; 1) HSV1716 infection induced significant secretion of HMGB1 in human glioma cell lines and glioma neurosphere cells alone or when co-cultured with microglia. 2) Measurement of HMGB1 in serum of mice with intracranial tumors revealed an increase in serum HMGB1 levels after virus treatment. 3) HSV1716 infection enhanced human brain microvascular endothelial cells (HBMEC) migration towards infected cells, which was blocked by HMGB1 blocking antibodies. 4) HMGB1 both directly enhanced HBMEC migration and induced production of VEGF by microglia cells co-cultured with glioma cells. 5) Pharmacologic inhibitor of HMGB1 (Garbexate (100uM)), and anti-HMGB1 polyclonal blocking antibody blocked HSV1716 induced HMGB1 secretion of VEGF in vitro and in vivo. Our findings suggest that OV therapy with HSV1716 activates proangiogenic pathway by induction of HMGB1, and that tumor microenvironment contributes to it proangiogenic property. Thus we conclude that OV therapy that target HMGB1 secretion and angiogenic axis may improve virotherapy of HSV1716, and other oncolytic herpes simplex virus in tumors.
Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci
Authors: Manuel F. Rosado, Gerald E. Byrne, Feying Ding, Kenneth A. Fields, Phillip Ruiz, Sander R. Dubovy, Gale R. Walker, Arnold Markoe, Izidore S. Lossos
Journal: Blood (2005)
The Costs, Clinical Benefits, and Cost-Effectiveness of Screening for Cervical Cancer in HIV-Infected Women
Authors: Sue J. Goldie
Journal: Annals of Internal Medicine (1999)

Background: Women with HIV infection have a higher risk for cervical squamous intraepithelial lesions than do women without HIV infection, and the optimal regimen for cervical cancer screening in these women is uncertain. Objective: To assess the net health consequences, costs, and cost-effectiveness of various screening strategies for cervical neoplasia and cancer in HIV-infected women. Design: A cost-effectiveness analysis from a societal perspective done by using a state-transition Markov model. Values for incidence, progression, and regression of cervical neoplasia; efficacy of screening and treatment; progression of HIV disease; mortality from HIV infection and cancer; quality of life; and costs were obtained from the literature. Setting: Simulated clinical practice in the United States. Patients: HIV-infected women representative of the U.S. population. Intervention: Six main screening strategies—no screening, annual Papanicolaou smears, annual Papanicolaou smears after two negative smears obtained 6 months apart (recommended by the Centers for Disease Control and Prevention), semiannual Papanicolaou smears, annual colposcopy, and semiannual colposcopy—were considered. Measurements: Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness. Results: Annual Papanicolaou smear screening resulted in a 2.1-month gain in quality-adjusted life expectancy for an incremental cost of $12 800 per QALY saved. Annual Papanicolaou smear screening after two negative smears obtained 6 months apart provided an additional 0.04 QALYs at a cost of $14 800 per QALY saved. Semiannual Papanicolaou smear screening provided a further 0.17 QALYs at a cost of $27 600 per QALY saved. Annual colposcopy cost more but provided no additional benefit compared with that given by semiannual Papanicolaou smear screening, and semiannual colposcopy exceeded $375 000 per QALY saved. Results were most sensitive to the rate of progression of neoplasia to invasive cancer. Conclusions: In HIV-infected women, cervical cancer screening with annual Papanicolaou smears after two negative smears obtained 6 months apart offers quality-adjusted life expectancy benefits at a cost comparable to that of other clinical preventive interventions.
New guidance will ease revalidation process for doctors, says academy
Authors: M. Limb
Journal: BMJ (2012)

Doctors in the United Kingdom are being provided with final guidance to help them prepare supporting information for their annual appraisals under the new revalidation scheme.

Fourteen specialty guidance frameworks were published on 28 June by the Academy of Medical Royal Colleges and its member colleges and faculties.

Neil Douglas, chairman of the academy, said that the guidance was consistent with the General Medical Council’s own supporting information guidance and was welcomed by the GMC.

He said that it would be “key to making the process of appraisal and revalidation more straightforward and consistent for all doctors, irrespective of their medical specialty.”

Revalidation, …
A soluble acidic protein of the cell nucleus which reacts with serum from patients with systemic lupus erythermatosus and Sjögren's syndrome.
Authors: M Akizuki, R Powers, H R Holman
Journal: Journal of Clinical Investigation (1977)

A soluble nuclear antigen that reacts with sera obtained from patients with systemic lupus erythematosus and Sjögren's syndrome has been described. The antigen, tentatively named the Ha antigen after the prototype serum, was shown to react with specific antibodies by precipitin, complement fixation, and immunofluorescence techniques. The Ha antigen prepared from isolated nuclei of calf thymus glands, calf liver, and rat liver showed identical immunological reactivities; a wide distribution among different species and tissues is presumed. The Ha antigen was destroyed by trypsin and relatively mild heat or pH variation from neutrality, but was resistant to DNase or RNase. Many of these characteristics are similar to those of the "B" antigen to which antibodies have recently been described in Sjögren's syndrome. The nuclear origin of the Ha antigen was confirmed by the speckled nuclear immunofluorescence staining pattern given by purified antibody to Ha obtained from a specific immune precipitate. Preliminary results showed approximately 13% of patients with systemic lupus erythematosus and 30% of patients with Sjögren's syndrome had precipitating antibodies to the Ha antigen.
MENTAL ABERRATIONS.Read before the Southeast Missouri Medical Association, at Charleston, Mo., May, 1893.
Authors: L. T. HALL
Journal: JAMA (1893)

"Man is a harp, whose chords elude the sight, Each yielding harmony, disposed aright. The screws reversed (a task which, if He please, God in a moment executes with ease), Ten thousand thousand strings at once go loose, Lost, till He tune them, all their power and use." Thus sadly sang one of England's purest, sweetest poets, out of the sad experience of a life of alternating light and shadow, harmony and discord, now reveling in the loftiest flights of poetic fancy, the profoundest depths of spiritual, experience; now groveling in darkness and despair, driving him to a desperate attempt upon his life, the light of reason finally going out behind a cloud of impenetrable gloom. This comparison of the human mind to a musical instrument, susceptible when attuned aright of the most delightful harmonies, but with "the screws reversed" its "ten thousand thousand strings" giving forth only jarring discord,
Steroid Receptor Coactivator-3/AIB1 Promotes Cell Migration and Invasiveness through Focal Adhesion Turnover and Matrix Metalloproteinase Expression
Authors: Jun Yan, Halime Erdem, Rile Li, Yi Cai, Gustavo Ayala, Michael Ittmann, Li-yuan Yu-Lee, Sophia Y. Tsai, Ming-Jer Tsai
Journal: Cancer Research (2008)

Abstract Steroid receptor coactivator-3 (SRC-3)/AIB1 is a member of the p160 nuclear receptor coactivator family involved in development and cell cycle progression. We previously showed that SRC-3/AIB1 is required for prostate cancer cell proliferation and survival. Here, we reported that the elevated SRC-3/AIB1 expression is significantly correlated with human prostate cancer seminal vesicle invasion and lymph node metastasis. Furthermore, SRC-3/AIB1 is associated with increased prostate cancer cell migration and invasion. SRC-3/AIB1 is required for focal adhesion turnover and focal adhesion kinase activation. In addition, SRC-3/AIB1 directly regulates transcription of matrix metalloproteinase (MMP)-2 and MMP-13 through its coactivation of AP-1 and PEA3. Taken together, these data suggest that SRC-3/AIB1 plays an essential role in prostate cancer cell invasion and metastasis. [Cancer Res 2008;68(13):5460–8]