tbuckley/cabot-search huggingface dataset:
Meeting Report: The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases
Authors: Richard G. Stevens, David E. Blask, George C. Brainard, Johnni Hansen, Steven W. Lockley, Ignacio Provencio, Mark S. Rea, Leslie Reinlib
Journal: Environmental Health Perspectives (2007)

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge.
Effects of an Arteriovenous Fistula on the Devascularized Limb
Authors: Harlan D. Root
Journal: JAMA (1965)

To reverse the tendency for thrombosis in small prosthetic grafts and sutured or otherwise damaged vessels, the advantages of maintaining a high rate of blood flow through these vessels by small caudad arteriovenous fistulae have been demonstrated previously in our laboratory. Neointimaformation was found in these damaged vessels. This principle could be used to maintain vessel patency until collateral flow could develop, particularly in patients with ischemic limbs in which standard femoropopliteal-artery reconstruction is unsuitable. The effects of arteriovenous fistulae have been said to be harmful. Four groups of dogs were used for study in order to avoid imposing further damage on ischemic limbs of patients. We sought thus to duplicate experimentally the clinical situation of obstructed or obliterated popliteal arteries. <h3>Materials and Methods</h3> Dogs of either sex weighing 25 to 35 lb were anesthetized with intravenous pentobarbital sodium. Through low midline abdominal and ventral thigh incisions, all branches of
Lung Cancer: A Combined Modality Approach to Staging and Therapy
Authors: H. M. Golomb, T. R. DeMeester
Journal: CA A Cancer Journal for Clinicians (1979)

To develop treatment strategies for lung cancer, one must know the histology as well as the extent of the disease.This paper emphasizes the importance of the histological diagnosis, the value of care ful clinical and pathological staging, and the development of treatment strategies based on this knowledge.The signs and symptoms of lung cancer,1 the radio graphic findings, and the means of ob taining a tissue diagnosis2 are well-known to all practicing physicians and will only be mentioned as they pertain to the de velopment of treatment strategies. HistologyAlthough lung cancers include a wide spectrum of neoplasms that may be of entodermal, mesodermal, or possibly neuroectodermal derivation, carcinomas contribute 90 to 95 percent of these Ui mors.The four major cell types include
A 2 year old girl with fever, cough, and tachypnoea
Authors: M. Tebruegge, N. Ritz, T. Connell, N. Curtis
Journal: BMJ (2009)

A 2 year old girl presented to the accident and emergency department with high grade fever (temperature 39.2oC), cough, tachypnoea (respiratory rate 45 breaths/min), and lethargy. She had been unwell for six weeks with general malaise and intermittent fever. She had also been anorexic for three weeks and had lost about 7% of her body weight. She was born in Australia to parents from the South Pacific Islands. Her routine immunisations were up to date and her past medical history was unremarkable. The patient underwent chest radiography (fig 1⇓). Fig 1 Chest radiograph of a 2 year old girl with high grade fever, cough, and tachypnoea ### Short answers Fig 2 Chest radiograph showing bilateral miliary infiltrates and outlining the cavitating pulmonary lesion in the left lower lobe (arrows)
PREVALENCE AND LONG TERM PROGNOSIS OF PATIENTS WITH COMPLETE LEFT BUNDLE BRANCH BLOCK AND WITHOUT A PRIOR HISTORY OF HEART DISEASE REFERRED FOR NUCLEAR STRESS SPECT
Authors: Azhar Supariwala, Seth Uretsky, Sonal Kamalia, Narasimhanaidu Guriginjakunta, Madhusudhan Ponnala, Lakshmi Prasad Ravipati, Dinesh Gaddam, Alan Rozanski
Journal: Journal of the American College of Cardiology (2012)
Evaluation of Drugs Used in Pregnancy and Pediatric Age Groups
Authors: DONALD S. ROBINSON
Journal: Annals of Internal Medicine (1975)

Editorial NotesJune 1, 1975Evaluation of Drugs Used in Pregnancy and Pediatric Age GroupsDONALD S. ROBINSON, M.D.DONALD S. ROBINSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-6-841 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe clinical investigation of new drugs has come under increasing scrutiny and control, mainly as a result of two factors. One is passage of the 1962 Kefauver Amendment to the Food and Drug Act, an aftermath of the thalidomide catastrophe. The other is a growing national concern about protection of human subjects and ethical controls, which have come about in part from adverse publicity over clinical research involving prisoners, mentally retarded persons, and impaired patients. This concern has led the National Institutes of Health to develop recommended policies (1) for research involving children, prisoners, and the institutionalized mentally infirmed. The...References1. Fed Regist, vol. 38, no. 221, part 2, 16 November 1973 Google Scholar2. : General Guidelines for the Evaluation of Drugs to be Approved for Use During Pregnancy and for Treatment of Infants and Children, 1974 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Clinical Pharmacology Unit University of Vermont College of Medicine Burlington, Vermont PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 1, 1975Volume 82, Issue 6Page: 841-842KeywordsAge groupsDrugs Issue Published: June 1, 1975 PDF DownloadLoading ...
Measurement methods for human exposure analysis.
Authors: P J Lioy
Journal: Environmental Health Perspectives (1995)

The general methods used to complete measurements of human exposures are identified and illustrations are provided for the cases of indirect and direct methods used for exposure analysis. The application of the techniques for external measurements of exposure, microenvironmental and personal monitors, are placed in the context of the need to test hypotheses concerning the biological effects of concern. The linkage of external measurements to measurements made in biological fluids is explored for a suite of contaminants. This information is placed in the context of the scientific framework used to conduct exposure assessment. Examples are taken from research on volatile organics and for a large scale problem: hazardous waste sites.
Midlife Risk Factors and Healthy Survival in Men
Authors: Bradley J. Willcox, Qimei He, Randi Chen, Katsuhiko Yano, Kamal H. Masaki, John S. Grove, Timothy A. Donlon, D. Craig Willcox, J. David Curb
Journal: JAMA (2006)

ContextHealthy survival has no clear phenotypic definition, and little is known about its attributes, particularly in men.ObjectiveTo test whether midlife biological, lifestyle, and sociodemographic risk factors are associated with overall survival and exceptional survival (free of a set of major diseases and impairments).Design, Setting, and ParticipantsProspective cohort study within the Honolulu Heart Program/Honolulu Asia Aging Study. A total of 5820 Japanese American middle-aged men (mean age, 54 [range, 45-68] years) free of morbidity and functional impairments were followed for up to 40 years (1965-2005) to assess overall and exceptional survival. Exceptional survival was defined as survival to a specified age (75, 80, 85, or 90 years) without incidence of 6 major chronic diseases and without physical and cognitive impairment.Main Outcome MeasureOverall survival and exceptional survival.ResultsOf 5820 original participants, 2451 participants (42%) survived to age 85 years and 655 participants (11%) met the criteria for exceptional survival to age 85 years. High grip strength and avoidance of overweight, hyperglycemia, hypertension, smoking, and excessive alcohol consumption were associated with both overall and exceptional survival. In addition, high education and avoidance of hypertriglyceridemia were associated with exceptional survival, and lack of a marital partner was associated with mortality before age 85 years. Risk factor models based on cumulative risk factors (survival risk score) suggest that the probability of survival to oldest age is as high as 69% with no risk factors and as low as 22% with 6 or more risk factors. The probability of exceptional survival to age 85 years was 55% with no risk factors but decreased to 9% with 6 or more risk factors.ConclusionThese data suggest that avoidance of certain risk factors in midlife is associated with the probability of a long and healthy life among men.
Noninvasive assessment of coronary vasodilation using magnetic resonance angiography
Authors: Masahiro Terashima, Craig H. Meyer, Brian G. Keeffe, Eric J. Putz, Erasmo de la Pena-Almaguer, Phillip C. Yang, Bob S. Hu, Dwight G. Nishimura, Michael V. McConnell
Journal: Journal of the American College of Cardiology (2004)
Effect of Nasopharyngeal Carcinoma-Derived Exosomes on Human Regulatory T Cells
Authors: Dhafer Mrizak, Nathalie Martin, Clément Barjon, Anne-Sophie Jimenez-Pailhes, Rami Mustapha, Toshiro Niki, Joël Guigay, Véronique Pancré, Yvan de Launoit, Pierre Busson, Olivier Moralès, Nadira Delhem
Journal: JNCI Journal of the National Cancer Institute (2014)

Regulatory T cells (Treg) and tumor-exosomes are thought to play a role in preventing the rejection of malignant cells in patients bearing nasopharyngeal carcinoma (NPC). Treg recruitment by exosomes derived from NPC cell lines (C15/C17-Exo), exosomes isolated from NPC patients' plasma (Patient-Exo), and CCL20 were tested in vitro using Boyden chamber assays and in vivo using a xenograft SCID mouse model (n = 5), both in the presence and absence of anti-CCL20 monoclonal antibodies (mAb). Impact of these NPC exosomes (NPC-Exo) on Treg phenotype and function was determined using adapted assays (FACS, Q-PCR, ELISA, and MLR). Experiments were performed in comparison with exosomes derived from plasma of healthy donors (HD-Exo). The Student's t test was used for group comparisons. All statistical tests were two-sided. CCL20 allowed the intratumoral recruitment of human Treg. NPC-Exo also facilitated Treg recruitment (3.30±0.34 fold increase, P < .001), which was statistically significantly inhibited (P < .001) by an anti-CCL20 blocking mAb. NPC-Exo also recruited conventional CD4+CD25- T cells and mediated their conversion into inhibitory CD4+CD25high cells. Moreover, NPC-Exo enhanced (P = .0048) the expansion of human Treg, inducing the generation of Tim3Low Treg with increased expression of CD25 and FOXP3. Finally, NPC-Exo induced an overexpression of cell markers associated with Treg phenotype, properties and recruitment capacity. For example, GZMB mean fold change was 21.45±1.75 (P < .001). These results were consistent with a stronger suppression of responder cells' proliferation and the secretion of immunosuppressive cytokines (IL10, TGFB1). Interactions between NPC-Exo and Treg represent a newly defined mechanism that may be involved in regulating peripheral tolerance by tumors and in supporting immune evasion in human NPC.
A critical function for CD200 in lung immune homeostasis and the severity of influenza infection
Authors: Robert J Snelgrove, John Goulding, Arnaud M Didierlaurent, Daphne Lyonga, Seema Vekaria, Lorna Edwards, Emily Gwyer, Jonathon D Sedgwick, A Neil Barclay, Tracy Hussell
Journal: Nature Immunology (2008)
Chromosome 17 polysomy (Ch17) as a predictor of anthracycline response: emerging evidence from the UK <i>NEAT</i> adjuvant breast cancer trial.
Authors: J Bartlett, A Munro, J Dunn, L Hiller, S Jordan, C Twelves, D Cameron, J Thomas, F Campbell, D Rea, E Provenzano, P Pharoah, C Caldas, H Earl, C Poole
Journal: Cancer Research (2009)

Abstract Abstract #45 Background: The role of HER2 and Topoisomerase IIα (TOPO2α) as predictors of anthracycline sensitivity remains controversial. To address this we conducted an analysis of HER2, Topoisomerase IIα amplification (TOPO2α-amp) and deletion (TOPO2α-del), chromosome 17 polysomy (C17) and Ki67 as prognostic and predictive markers in the UK National Epirubicin Adjuvant Trial (NEAT) which compared classical CMF with Epirubicin followed by CMF (NEJM 2006;355:1851-62).&amp;#x2028; Methods: TMAs constructed with 1638/2021 tumors from patients in the NEAT study were analysed for HER2/TopoIIα gene alterations, C17 polysomy, and Ki67. Log-rank analyses explored the prognostic value of markers on relapse-free survival (RFS) and overall survival (OS). Cox-regression models tested independent prognostic value on RFS and OS in the presence of treatment, age, type of surgery, tumor size, nodal status, ER status and grade, and marker x treatment interactions for RFS and OS.&amp;#x2028; Results: Of 1625 NEAT samples analysed, 806(50%) received anthracycline-containing treatment; 985(61%) were ≤50 years old; 1114(69%) had nodal involvement; 791 (49%) were ER+ve; 961(59%) had G3 tumours; and 893 (56%) had tumour size &amp;gt;2cm. 19% were HER2-amp, 9% were TOPO2α-amp, 9% were TOPO2α-del, 18% were polysomic for C17 and 62% had high Ki67 (&amp;gt;13.0%). HER2-amp and TOPO2α-del were significant poor prognostic factors (P&amp;lt;0.001) for RFS and OS, and were independent variables in multivariate analyses. Other factors did not reach significance at the 1% level. No significant treatment interaction with anthracyclines was seen for HER2-amp (OS p=0.25, RFS p=0.51). Polysomy C17 was not prognostic but exhibited a significant treatment interaction with anthracyclines (RFS p=0.02, HRs 0.96 95%CI 0.73-1.26 vs 0.56 95%CI 0.33-0.97, OS p=0.06, HRs 0.97 95%CI 0.72-1.30 vs 0.60 95%CI 0.33-1.08). Patients with C17 polysomic tumours had significantly greater benefit from anthracyclines.&amp;#x2028; Conclusions: Analysis of samples from the NEAT trial, which for the first time included HER2, TOPO2α, Ki67 and C17, strongly suggest that the most powerful predictor of benefit from adjuvant anthracyclines is chromosome 17 polysomy, perhaps as a marker of chromosomal instability, with a weak effect for HER2-amp. No effect was observed for differing TOPO2α status. Given the lack of consistency seen in previous studies with respect to HER2 and TOPO2α, we suggest that polysomy C17 could be the unifying predictive marker of anthracycline sensitivity, particularly as these data are confirmed by data from a separate meta-analysis of MA5 and BR9601 trials (SABCS2008). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 45.
Renal Performance in Patients Undergoing Replacement of the Aortic Valve
Authors: JOHN E. MIELKE, FRANK T. MAHER, JAMES C. HUNT, JOHN W. KIRKLIN
Journal: Circulation (1965)

Renal performance of seven patients undergoing replacement of the aortic valve was investigated. The initial portion of cardiopulmonary bypass was characterized by low arterial blood pressure and anuria. With a subsequent rise in arterial pressure during bypass, urine flow suddenly increased in five patients. In two patients urine flow did not resume until immediately after cardiopulmonary bypass. The high rate of urine flow at these times is thought to be partially due to a glucose-induced osmotic diuresis. The glomerular filtration rate (inulin clearance) and the effective renal plasma flow (PAH clearance) fell with induction of anesthesia and opening of the chest, but there was no further drop in these functions as a result of total body perfusion. Urine osmolality fell significantly during and immediately after cardiopulmonary bypass. The changes in urine osmolality are thought to be due in part to the osmotic diuresis and in part to a temporary reduction in the renal medullary hyperosmolality secondary to hemodynamic changes. All of the alterations in renal function were reversible in the patients studied.
Instantaneous and Sudden Deaths
Authors: R. Edward Dodge
Journal: JAMA (1973)

To the Editor.—  I was surprised at the suggestion of the authors that moderate or severe physical activity should not be indulged in. The authors do not make clear whether they believe such restriction of activity should be limited to known coronary patients or to the public at large. Certainly their data do not support such a generalization.  The classification of activity used by the authors is not very informative. There is a gross classification of intensity of exercise, but no indication of frequency or average duration of exercise, both of which are rather important factors. A person who plays handball or tennis once a week may think of himself as being accustomed to that level of activity, whereas substantial data indicate that a higher frequency of exercise is necessary to maintain fitness.  Therefore, if one is going to examine exercise in relation to heart disease in any meaningful way,
Spliced Leader RNA–Mediated trans-Splicing in Phylum Rotifera
Authors: Natalia N. Pouchkina-Stantcheva, Alan Tunnacliffe
Journal: Molecular Biology and Evolution (2005)

In kinetoplastids, Euglena, and four metazoan phyla, trans-splicing has been described as a mechanism for the generation of mature messenger RNAs (mRNAs): 5′-ends of precursor mRNAs are replaced by a short spliced leader (SL) exon from a small SL RNA. Although the full phylogenetic range is unknown, trans-splicing has not been found in vertebrates, insects, plants, or yeast. In animal groups where it does occur, i.e., nematodes, cnidarians, platyhelminths, and primitive chordates, SL RNAs do not show sequence relatedness across phyla. The apparently sporadic phylogenetic distribution and the lack of SL RNA homology have led to opposing hypotheses on its evolution, involving either an ancient origin followed by loss in multiple lineages or independent acquisition in several taxa. Here we present evidence for the occurrence of trans-splicing in bdelloid rotifers (Bdelloidea, Rotifera). A common 23-nt sequence, representing the SL exon—diagnostic of SL RNA–mediated trans-splicing—was found at the 5′-end of at least 50%–65% of mRNAs from Adineta ricciae and Philodina sp. The trans-splicing pattern in bdelloid rotifers can be unusually complex, as observed in transcripts from a heat shock protein gene, hsp82-1, where the SL exon was spliced to three alternative positions. Bdelloid rotifer SL RNAs were found to be 105 or 106 nt long and comprised the SL sequence, a conserved splice donor site and an intron containing a putative spliceosome–binding motif. Intriguingly, some similarity of rotifer SL RNA sequence and predicted secondary structure was seen to that of the predominant SL1 RNA of nematodes, although it is unlikely that this demonstrates homology. In addition, sequence corresponding to the rotifer SL exon was found at the 5′-end of a number of full-length complementary DNA (cDNA) clones in a rice (Oryza sativa) database. None of these cDNAs gave a close match with homologous plant genes, suggesting that a small but significant portion of the rice expressed sequence tag database represents sequences derived from rotifers. In summary, the description of SL-mediated trans-splicing in Rotifera extends its representation to at least five metazoan phyla, making it increasingly probable that this is a phylogenetically widespread and therefore ancient phenomenon.
GMC lays out charges against headache doctor in research misconduct case
Authors: C. Dyer
Journal: BMJ (2014)

A lead investigator in a clinical trial that led to a renowned libel case that helped to change English defamation law now faces allegations of research misconduct in a hearing that opens this month.

Andrew Dowson, a headache specialist who co-led the MIST (Migraine Intervention with STARFlex Technology) trial with a cardiologist, Peter Wilmshurst, is due to appear at the Medical Practitioners Tribunal Service in Manchester for an eight week hearing starting on 29 October.

The case is seen as the most important to feature allegations by the General Medical Council regarding research misconduct since that of Andrew Wakefield, …
Renin and kallikrein in connecting tubule of mouse
Authors: Andreas Rohrwasser, Tomoaki Ishigami, Barbu Gociman, Pierre Lantelme, Terry Morgan, Tong Cheng, Elaine Hillas, Shuhua Zhang, Kenneth Ward, M.A.Y. Bloch-Faure, Pierre Meneton, J.M. Lalouel
Journal: Kidney International (2003)
Playing with words, working with concepts, testing ideas
Authors: J. M. Zanker
Journal: Behavioral and Brain Sciences (1999)

Gold &amp; Stoljar's attempt to disentangle the body-mind problem in time for the end of the decade of the brain deserves praise for its diligence and courage in moving onto the treacherous ground of interdisciplinary discourse. In making their point, they should not have stopped half-way: a more clearly defined experimental paradigm seems necessary to solve this exciting and substantial problem.
Mental Health and Productivity in the Workplace: A Handbook for Organizations and Clinicians
Authors: P. Hymel
Journal: JAMA (2003)

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