tbuckley/cabot-search huggingface dataset:
Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1 gene and protein in human endothelial cells in culture.
Authors: M Phelan, S P Perrine, M Brauer, D V Faller
Journal: Journal of Clinical Investigation (1995)

The molecular defect in sickle cell disease resides in the beta globin gene, with consequent defects in erythrocytes only, suggesting that the vascular occlusion and vasomotor instability which characterize this disease are the result of interactions between abnormal sickle erythrocytes and cells of the blood vessel wall. We explored whether sickle erythrocytes may have effects on vascular tone, exclusive of adhesion events. Exposure of human endothelial cells in culture to previously sickled sickle erythrocytes resulted in a four to eight-fold transcriptional induction of the gene encoding the potent vasoconstrictor endothelin-1 (ET-1). Unsickled sickle erythrocytes or normal erythrocytes exposed to "sickling" conditions had no effect on ET-1 gene induction. Contact of the sickled erythrocytes with the endothelium was not required. Elevations in the ET-1 transcript peaked at 3 h after exposure and persisted for up to 24 h. Four to sixfold increases in the amount of ET-1 peptide was released into the medium surrounding the endothelial cells after exposure to sickled sickle erythrocytes. This is the first demonstration of the regulation of gene expression in endothelial cells as a result of interaction with sickle cells, with induction of genes encoding vasoconstrictors. Furthermore, these findings suggest that sickle erythrocytes may have the capacity to affect local vasomotor tone directly.
Spread of bloodborne viruses among Australian prison entrants
Authors: N. Crofts, T. Stewart, P. Hearne, X. Y. Ping, A. M Breschkin, S. A Locarnini
Journal: BMJ (1995)

To assess spread of bloodborne viruses among prison entrants in Victoria, Australia.Voluntary confidential testing of all prison entrants for markers of exposure to bloodborne viruses with collection of minimal data on demography and risk factors over 12 months.Her Majesty's Prisons, Pentridge and Fairlea, Victoria, Australia.3429 male and 198 female prison entrants (> 99% of all prison entrants); 344 entered prison and were tested more than once.Prevalence and incidence of antibodies to HIV, hepatitis B, and hepatitis C viruses, and minimal data on risk factors.1562 (46%) gave a history of use of injected drugs, 1171 (33%) had antibody to hepatitis B core antigen, 1418 (39%) were anti-hepatitis C positive including 914 (64%) of the men who injected drugs, 91 (2.5%) were positive for hepatitis B surface antigen, and 17 (0.47%) were positive for antibody to HIV. Incidence rates for infection with hepatitis B and C virus were 12.6 and 18.3 per 100 person years, respectively; in men who injected drugs and were aged less than 30 years (29% of all prison entrants) these were 21 and 41 per 100 person years. Seroconversion to hepatitis B or C was associated with young age and shorter stay in prison. Only 5% of those who were not immune to hepatitis B reported hepatitis B immunisation.Hepatitis B and C are spreading rapidly through some populations of injecting drug users in Victoria, particularly among men aged less than 30 years at risk of imprisonment in whom rates of spread are extreme; this group constitutes a sizeable at risk population for spread of HIV. This spread is occurring in a context of integrated harm reduction measures outside prisons for prevention of viral spread but few programmes within or on transition from prisons; it poses an urgent challenge to these programmes.
Promotion of Good Health
Authors: Stephen S. Rinsler
Journal: JAMA (1984)

<h3>To the Editor.—</h3> In their commentary entitled "Why Not Share the Secrets of Good Health?" Drs Dismuke and Miller<sup>1</sup>focus on "health promotion by physicians." However, they offer no clear definition of health and, from my vantage point, do not seem to be discussing health but rather reduction and avoidance of disease, dysfunction, and premature decay. I believe that "health" promotion is an important function of primary medical practitioners and that it includes the promotion of (1) physical fitness, (2) satisfaction with self, and (3) the pursuit of reasonable self-chosen goals. The "tools" required for such efforts are primary care medical skills for disease detection and "health" hazard appraisal, adequate listening skills (or an affiliation with a counselor), and the ability to facilitate life-style modification, especially with regard to diet, exercise, and the management of stress. Although these comments are unquantitated, a recent study published in<i>JAMA</i><sup>2,3</sup>seems
LIPOPROTEIN(A) AS AN INDEPENDENT RISK FACTOR FOR CORONARY ARTERY DISEASE
Authors: Sung Woo Kwon, Hyuck Moon Kwon, Dae-Won Ma, Yoo-Mi Park, Hye-Moon Chung, Jong-Youn Kim, Pil-Ki Min, Byoung Kwon Lee, Bum-Kee Hong, Se-Joong Rim
Journal: Journal of the American College of Cardiology (2011)
Visceral fat: A key mediator of steatohepatitis in metabolic liver disease
Authors: David van der Poorten, Kerry‐Lee Milner, Jason Hui, Alexander Hodge, Michael I. Trenell, James G. Kench, Roslyn London, Tony Peduto, Donald J. Chisholm, Jacob George
Journal: Hepatology (2008)

Visceral obesity is intimately associated with metabolic disease and adverse health outcomes. However, a direct association between increasing amounts of visceral fat and end-organ inflammation and scarring has not been demonstrated. We examined the association between visceral fat and liver inflammation in patients with nonalcoholic fatty liver disease (NAFLD) to delineate the importance of visceral fat to progressive steatohepatitis and hence the inflammatory pathogenesis of the metabolic syndrome. We undertook a cross-sectional, proof of concept study in 38 consecutive adults with NAFLD at a tertiary liver clinic. All subjects had a complete physical examination, anthropometric assessment, and fasting blood tests on the day of liver biopsy. Abdominal fat volumes were assessed by magnetic resonance imaging within 2 weeks of liver biopsy. The extent of hepatic inflammation and fibrosis augmented incrementally with increases in visceral fat (P < 0.01). For each 1% increase in visceral fat, the odds ratio for increasing liver inflammation and fibrosis was 2.4 (confidence interval [CI]: 1.3-4.2) and 3.5 (CI: 1.7-7.1), respectively. Visceral fat remained an independent predictor of advanced steatohepatitis (odds ratio [OR] 2.1, CI: 1.1-4.2, P = 0.05) and fibrosis (OR 2.9, CI: 1.4-6.3, P = 0.006) even when controlled for insulin resistance and hepatic steatosis. Interleukin-6 (IL-6) levels, which correlated with visceral fat, also independently predicted increasing liver inflammation. Visceral fat was associated with all components of the metabolic syndrome. Conclusion: Visceral fat is directly associated with liver inflammation and fibrosis independent of insulin resistance and hepatic steatosis. Visceral fat should therefore be a central target for future interventions in nonalcoholic steatohepatitis and indeed all metabolic disease. (HEPATOLOGY 2008.)
Congenital Heart Disease: A Plea for an Experimental Approach
Authors: Robert L. DeHaan
Journal: New England Journal of Medicine (1968)

During the process whereby a fertilized egg cleaves into two cells, and then four — and forms eventually a fetus, and infant — the genetic information carried initially on its chromosomes is copied many times over. If the original genome contains major defects, or if the copying mechanisms function inaccurately, the developing embryo dies or becomes malformed. Among the more common groups of congenital defects, cardiac anomalies have been closely related to genetic load. Syndromes that include congenital cardiovascular anomalies result from at least four different chromosomal aberrations. Genetic strains of chickens1 and of dogs2 that exhibit high incidences of . . .
Model Contracts for Hospital Medical and Dental Staff
Authors: S. Harrison
Journal: BMJ (1970)

Representative Meeting the B.M.A. will debate the annual retention fee for registra- tion on the Medical Register.The B.M.A. has already aired the prob- lem of a minority of doctors who wish to retire temporarily from medicine and who mav consider it unnecessary to remain on the Register-or who do not wish to pay the annual retention fee.Most of these will be young married women doctors with domestic commitments.The B.M.A. considered that the G.M.C. might feel able to include these
NICE may fail to stop "postcode prescribing," MPs told
Authors: K. Burke
Journal: BMJ (2002)

Official efforts to reduce “postcode prescribing” could backfire, because health authorities are being made to fund certain treatments at the expense of others, a parliamentary inquiry has heard.

Medical and legal experts told the Commons health select committee last week that the National Institute for Clinical Excellence (NICE) could—contrary to its aims—make prescribing more inconsistent by skewing healthcare priorities.

Ike Iheanacho, representing the Drug and Therapeutics Bulletin , warned that cash strapped health authorities may have to downgrade care in important areas to channel money into interventions approved by NICE.

“Health authorities will have to cut their cloth to fit,” said Mr Iheanacho, the journal's deputy editor. “If the cost of implementing a whole batch of NICE guidance means they don't have enough money left and if …
RIFT VALLEY FEVER IN MAN
Authors: Francis F. Schwentker, Thomas M. Rivers
Journal: The Journal of Experimental Medicine (1934)

A case of Rift Valley fever following an accidental laboratory infection, and believed to be the first instance of the disease in the Western hemisphere, is reported. Although the course of illness was otherwise quite typical, it was complicated by thrombophlebitis-a condition not previously described in association with this disease in man. Death was caused by a pulmonary embolus.
Abstract LB-317: Interactive pipeline for reproducible genomics analyses
Authors: Michael Considine, Hilary S. Parker, Yingying Wei, Xiao X. Xia, Leslie Cope, Michael F. Ochs, Elana J. Fertig
Journal: Cancer Research (2014)

Abstract Automated Genomics Analysis (AGA) is a program to analyze high-throughput genomic data sets, such as Affymetrix gene expression arrays. The software implements an easy to use, point and click, guided pipeline to combine, define and compare datasets, and customize their outputs. Batch correction techniques are implemented to combine data sets. Options to save plots, tables and data are available throughout the analysis, and log files containing the R script run are also generated to facilitate reproducible analyses. The software has been applied to gene expression measurements from head and neck squamous cell carcinoma (HNSCC). It has batch corrected several public domain microarray HNSCC datasets, facilitating accurate comparison of subtypes such as HPV status. Moreover, current extensions enable users to interactively perform reproducible genomics analysis using clinical covariates in RNA sequencing data from TCGA. Citation Format: Michael Considine, Hilary S. Parker, Yingying Wei, Xiao X. Xia, Leslie Cope, Michael F. Ochs, Elana J. Fertig. Interactive pipeline for reproducible genomics analyses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-317. doi:10.1158/1538-7445.AM2014-LB-317
A new paradigm for African American breast cancer involving stem cell differentiation.
Authors: JJ Latimer, NA Lalanne, NT Myers, AB Courtney, L Mock, SG Grant
Journal: Cancer Research (2009)

Abstract Abstract #5051 Background: African American (AA) women have a higher incidence of breast cancer (BC) than white women before age 40, and are more likely to die from BC at every age. These differences are often attributed to socio-economic factors, however, there may be intrinsic biological differences in the breast tissue of AA and white women. For example, triple negative breast tumors are more prevalent in AA women than in non-Hispanic white women, although neither population is monolithic in its breast cancer phenotypes. We hypothesis that intrinsic biological differences between women of AA and European-white ancestry might be revealed by differences in growth and differentiation in vitro, reflecting underlying differences in the proportions and/or potency of breast epithelial stem cells.&amp;#x2028; Methods: Our laboratory has developed a novel tissue engineering system for Human Mammary Epithelial Cells (HMEC), both normal and malignant. This system allows for long-term establishment of non-diseased primary cultures that begin as 3-dimensional attached “epispheres”, that are structures made up of 40-100 epithelial cells. These non-diseased epispheres subsequently differentiate into functional, organotypic branching ducts and lobules that demonstrate ESA and CK -18,-19 staining, lumen, polarized nuclei, desmosomes, microvilli on apical surfaces and casein secretion.&amp;#x2028; Results: We have established primary HMEC cultures from 36/36 breast reduction mammoplasty tissues, including 9 AA donors matched in socioeconomic status. We have found: 1) The more children a woman had, the less likely her breast tissue was to form ductal structures in vitro. This finding is consistent with the idea that lactational differentiation decreases the number of pluripotent stem cells in the breast. 2) Pre-menopausal breast tissue was more likely to form ductal structures than post-menopausal tissue. 3) Race was a modifying factor in the ability to form ductal architecture in culture, significantly affecting the rate of differentiation. Putative mammary stem cells were analyzed by flow cytometry (CD44+, CD24-, MUC1-, α6 integrin+) and cloning. Stem cell proportions varied widely (range 0.5-15%), with no obvious association with race.&amp;#x2028; Discussion: One interpretation of the hormonal risk factors for BC involves the susceptibility of undifferentiated breast tissue to transformation. In other systems, especially the gonads, interference with terminal differentiation is also associated with susceptibility to transformation. If AA breast tissue has more robust differentiation potential than that of white women, it may also contain stem cells more likely to transform into an aggressive tumor type. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5051.
Successful treatment of diffuse lipoid pneumonitis with whole lung lavage.
Authors: H Y Chang, C W Chen, C Y Chen, T R Hsuie, C R Chen, W W Lei, M H Wu, Y T Jin
Journal: Thorax (1993)

Diffuse lipoid pneumonitis is rare. Prednisolone can be beneficial, but no other method of treatment has been tried. The first case of diffuse lipoid pneumonitis successfully managed with whole lung lavage is described.
Why did my colleagues turn to crime?
Authors: Jorma Palo
Journal: BMJ (2004)

The news reached me in 2000 while I was on a German autobahn, driving to France for my summer holiday. My son called to say that Professor Urpo Rinne had been arrested and was under police investigation for transferring 10 million Finnish marks (£1m; $2m; €1.7m) of research money into his own bank account.

Not again, I thought. Just a year before, Professor Paavo Riekkinen was arrested because he had placed large sums of research money, given for the development of new drugs against epilepsy and dementia, in high interest savings accounts and had kept the income, about two million Finnish marks. He was sent to prison for two years. Soon afterwards his younger son, Paavo Riekkinen Junior, was found guilty of 23 different crimes also involving research money. His sentence was two years, three months. Both have already been released.

> Under no circumstances should money be given directly to researchers 

What had happened to my fellow neurologists? Rinne …
The Childhood Emotional Pattern and Corey Jones: A Psychoanalytical Biography
Authors: George E. Gifford
Journal: JAMA (1978)

This book, a thinly veiled autobiography, is labeled "unique in that it deals with a healthy rather than an abnormal subject... the<i>first</i>to trace its subject from infancy to old age. It clearly demonstrates the profound impact of childhood emotional patterns on marriage, career, and other aspects of adult life." The author, Leon J. Saul, has had a life strictly comparable with that of the fictitious Corey Jones. He was born in 1901 in New York City, graduated from Harvard Medical School in 1928, and, after a medical internship, had his psychiatric training at the Boston Psychopathic Hospital. He then held a Commonwealth Fellowship, studied with Dr Franz Alexander, married a graduate of Radcliffe, and had three daughters and nine grandchildren. In 18 of the book's 31 chapters, the opening sentence reads, "said Corey Jones." Most likely, the book's Dr Camp is Macfie Campbell, who was professor of psychiatry
The Stroke Prevention Policy Model: Linking Evidence and Clinical Decisions
Authors: David B. Matchar
Journal: Annals of Internal Medicine (1997)

Simulation models that support decision and cost-effectiveness analysis can further the goals of evidence-based medicine by facilitating the synthesis of information from several sources into a single comprehensive structure. The Stroke Prevention Policy Model (SPPM) performs this function for the clinical and policy questions that surround stroke prevention. This paper first describes the basic structure and functions of the SPPM, concentrating on the role of large databases (broadly defined as any database that contains many patients, regardless of study design) in providing the SPPM inputs. Next, recognizing that the use of modeling continues to be a source of some controversy in the medical community, it discusses the philosophical underpinnings of the SPPM. Finally, it discusses conclusions in the context of both stroke prevention and other complex medical decisions. We conclude that despite the difficulties in developing comprehensive models (for example, the length and complexity of model development and validation processes, the proprietary nature of data sources, and the necessity for developing new software), the benefits of such models exceed the costs of continuing to rely on more conventional methods. Although they should not replace the clinician in decision making, comprehensive models based on the best available evidence from large databases can support decision making in medicine.
The lipoprotein abnormality in Tangier disease: quantitation of A apoproteins.
Authors: G Assmann, E Smootz, K Adler, A Capurso, K Oette
Journal: Journal of Clinical Investigation (1977)

In this study we have determined by radioimmunoassay and double immunoelectrophoresis the total quantities and distributions of A apoproteins in three adult patients affected with Tangier disease (hereditary alpha-lipoprotein deficiency). Compared with normal plasma, the total quantities of apoproteins A-I and A-II in Tangier plasma were determined to be less than 1% and 5-7%, respectively. In Tangier patients, approximately 90% of the apoprotein A-I sedimented when ultracentrifugations of plasma were carried out at density 1.21 g/ml KBr. By contrast, more than 95% of the apoprotein A-II floated under those conditions. In normal plasma, approximately 90% of both apoproteins A-I and A-II is found in the 1.063-1.21-g/ml KBr density fraction. These findings suggest that complete dissociation of A apoproteins occurs in Tangier plasma. This dissociation of apoproteins was confirmed by double immunoelectrophoresis with monospecific antisera. Immunochemical and electrophoretic experiments did not provide evidence for a structural abnormality of apoprotein A-I in these patients, The results taken together strongly suggest that normal high-density lipoproteins are absent from Tangier plasma.
Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus
Authors: Kari Otterdal, Jeshina Janardhanan, Elisabeth Astrup, Thor Ueland, John A.J. Prakash, Tove Lekva, O.C. Abraham, Kurien Thomas, Jan Kristian Damås, Prasad Mathews, Dilip Mathai, Pål Aukrust, George M. Varghese
Journal: Journal of Infection (2014)
... as does policy on antibiotics
Authors: G. Barlow, P. Moss
Journal: BMJ (2009)

Activation of protein kinase C (PKC), by the phorbol ester PMA, or the membrane-permeable diacylglycerol 1-oleoyl 2-acetylglycerol (OAG), had different effects on the proliferation-associated responses of a more than 99% pure population of human T cells. Treatment with PMA or OAG caused down-regulation of the TCR-CD3 complex, but only PMA, in combination with ionomycin, was capable of stimulating IL-2R expression and proliferation. Immunocytochemical staining with antisera specific for the PKC subspecies alpha, beta I, beta II, and gamma showed that untreated resting T cells normally coexpress alpha, beta I, and beta II PKC subspecies, which are distributed diffusely throughout the cell, with some localization around the periphery of the nucleus. There was no difference between the responses of these PKC subspecies to OAG and PMA, redistributing, after 10 min of treatment, to a discrete focal area within the cell. Treatment with OAG resulted in transient redistribution of PKC, maximal at 10 min, while in PMA-stimulated cells, the PKC redistribution was prolonged, persisting for at least 24 h. The results suggest that the difference in cellular response to treatment with PMA and OAG is not a consequence of differential activation of various PKC subspecies.
Defence ministry denies ignoring Gulf war syndrome in pension award
Authors: Owen Dyer
Journal: BMJ (2006)

The UK Ministry of Defence has denied trying to change the terms of an award made by a pensions tribunal to a former soldier who was granted a disability pension for Gulf war syndrome. Changes made by the ministry's Veterans' Agency to the wording of the award that seemed to ignore the finding of Gulf war syndrome were attributable to “a poor choice of words by a policy official,” a ministry spokesman said.

Harcourt Concannon, president of the Pensions Appeal Tribunals, which adjudicate appeals from servicemen and women who have been denied war pensions, accused the ministry of “tampering” with the terms of a ruling made in November last year ( BMJ 2005;331:1103).

In that decision, …
Another View on Overviews
Authors: Patrick McBride
Journal: JAMA (1995)

To  Editor.  —I enjoy your Users' Guide to  Medical Literature series and find these review articles useful for medical education. The article by Dr Oxman and colleagues 1 addressing how to use an overview was well organized, but  clinical example and overviews used were incomplete, and  results will mislead readers.  The patient described in  clinical scenario has a cholesterol level of 7.9 mmol/L (305 mg/dL) with no other risk factors described. A lipoprotein breakdown or personal history of coronary heart disease is not provided. In  Resolution of  Scenario section  authors state (apparently derived from their overview research) that the patient described in  scenario has a risk of dying of approximately 1.0% over  next decade. 1 According to many cohort studies and clinical trials,  patient has a much higher risk of death from coronary heart disease than stated, approximately 10%