tbuckley/cabot-search huggingface dataset:
Abstract 2972: Pharmacological reactivation of epigenetically regulated genes in prostate cancer.
Authors: Hans Krause, Odiljon Ikromov, Imad Al Kamal, Ahmed Magheli, Carsten Kempkensteffen, Kurt Miller
Journal: Cancer Research (2013)

Abstract Transcriptional silencing caused by promoter hypermethylation is a widespread mechanism for inactivation of known and putative tumor suppressor genes in many types of cancers. GSTP1, CDKN2A, CDH1, APC, and RASSF1A among others are known to be downregulated in prostate cancer. The aim of this study was to search for hitherto unknown genes that are upregulated after treatment by demethylating agents (i.e. DMNT inhibitors) thereby marking them as potential new therapeutic targets and putative biomarkers in prostate carcinogenesis. Prostate cancer cell lines DU-145 and LNCaP were treated in three independent biological experiments with 100μM zebularine for ten days and monitored for cytotoxic and apoptotic side effects. Efficacy of the treatment was verified on the RNA expression level of known epigenetically regulated genes. Expression changes of total RNA from treated and untreated cells were compared using whole genome expression microarrays (Affymetrix Human Gene 1.0 ST). A number of conspicuously upregulated genes (&amp;gt;15.0-fold, presence of CpG islands, higher expression in normal prostate) were further evaluated by Q-PCR in 50 cases of paired normal and tumor tissue samples of prostate cancer patients who underwent radical prostatectomy in our clinic between 2002 and 2004. The seryl-tRNA synthetase gene SARS was discovered by us for the first time to be downregulated in 34/50 cases (66%; p = 0,04) in prostate cancer. The DNA-damage-inducible transcript 1 (DDIT1), also known as GADD45A and was downregulated in 42/50 cases (84%; p = 0,0004). The discovery of a downregulated GADD45A in our independent experiments supports the already known fact of a methylation-mediated repression of GADD45A in prostate cancer (Ramachandran et al., 2009) and its suitability as a potential therapeutic target. In addition, we found a statistically significant inverse correlation of SARS expression and raising patient Gleason scores. Based on our estimated “upregulation-rate” of the promoter hypermethylation gold standard gene for prostate cancer GSTP1 in 98% of our patient samples (48/50; p = 0,0001) we present a robust workflow for the discovery of methylation-mediated transcriptionally inactivated genes. Citation Format: Hans Krause, Odiljon Ikromov, Imad Al Kamal, Ahmed Magheli, Carsten Kempkensteffen, Kurt Miller. Pharmacological reactivation of epigenetically regulated genes in prostate cancer. [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 2972. doi:10.1158/1538-7445.AM2013-2972
Controlled Trial of Megestrol Acetate for the Treatment of Cancer Anorexia and Cachexia
Authors: C. L. Loprinzi, N. M. Ellison, D. J. Schaid, J. E. Krook, L. M. Athmann, A. M. Dose, J. A. Mailliard, P. S. Johnson, L. P. Ebbert, L. H. Geeraerts
Journal: JNCI Journal of the National Cancer Institute (1990)

Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite ( P = .003) and food intake ( P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo ( P = .003). Patients receiving megestrol acetate reported significantly less nausea (13 % vs. 38 %; P = .001) and emesis (8 % vs. 25 %, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients.
Function of the Minor Duodenal Papilla in Humans as Determined under Duodenoscopy Using Indigo Carmine Dye and a pH Sensor
Authors: H. Nakagawa, Y. Tsukamoto, Y. Naitoe
Journal: Endoscopy (1991)

The function of the minor duodenal papilla in humans was studied by duodenoscopy using indigo carmine dye and a pH sensor. By this method it was possible to classify the function of the minor papilla into three types: Type I: pancreatic juice excretion without secretin administration; Type II: pancreatic juice excretion following secretin administration; Type III: no pancreatic juice excretion despite secretin administration. To determine the relative numbers of each type, the findings in 23 normal subjects were compared with those in 26 patients with benign papillary stenosis. In normal individuals, there were 11 Type I, 4 Type II and 8 Type III, while in patients with papillary stenosis we observed 20 Type I, 4 Type II and 2 Type III function, indicating that in patients with papillary stenosis, the incidence of Type I minor papilla was significantly high. From this it can be inferred that a minor papilla that does not excrete pancreatic juice spontaneously may begin such excretion, if pancreatic duct pressure persistently increases.
SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status
Authors: L López-Corral, M E Sarasquete, S Beà, R García-Sanz, M V Mateos, L A Corchete, J M Sayagués, E M García, J Bladé, A Oriol, M T Hernández-García, P Giraldo, J Hernández, M González, J M Hernández-Rivas, J F San Miguel, N C Gutiérrez
Journal: Leukemia (2012)
CXCR3 &lt;-&gt; ligand–mediated skin inflammation in cutaneous lichenoid graft-versus-host disease
Authors: Joerg Wenzel, Svenja Lucas, Sabine Zahn, Sandra Mikus, Dieter Metze, Sonja Ständer, Esther von Stebut, Uwe Hillen, Thomas Bieber, Thomas Tüting
Journal: Journal of the American Academy of Dermatology (2008)
Variations in budgets of fundholding practices.
Authors: P Day, R Klein
Journal: BMJ (1991)

process (waiting times in clinics, liaison at discharge, quality of explanation to patients, etc), but we hope to extend our approach to include both our performance and health outcomes.The information generated by monitoring services complements the canvassing of general practitioners' opinions of services advocated by Hicks and Baker.'It will provide a measure ofquality in service agreements, without which price will tend to dominate the purchase of care.
Importance of left atrial function in patients with myocardial infarction.
Authors: Y Matsuda, Y Toma, H Ogawa, M Matsuzaki, K Katayama, T Fujii, F Yoshino, K Moritani, T Kumada, R Kusukawa
Journal: Circulation (1983)

Left atrial function was evaluated in patients with and without remote myocardial infarction. The simultaneous left atrial pressure recording and left atrial and left ventricular cineangiograms were obtained with a catheter-tip micromanometer. The pressure-volume curve of the left atrium was composed of an A-loop and a V-loop. The ratio of active atrial emptying to left ventricular stroke volume in patients with myocardial infarction was significantly larger than that in normal subjects (42 +/- 12% vs 29 +/- 10%, p less than 0.05). The left atrial work was also significantly greater in patients with myocardial infarction (1690 +/- 717 mm Hg X ml) than in normal subjects (940 +/- 426 mm Hg X ml, p less than 0.05). The ratio of active atrial emptying to left ventricular stroke volume and left atrial work were significantly related in both normal subjects and patients with myocardial infarction (gamma = 0.72, p less than 0.01). The left ventricular ejection fraction correlated inversely with left atrial work (gamma = -0.5, p less than 0.05). Left atrial work also showed a significant linear correlation with left atrial volume before active atrial emptying (gamma = 0.82, p less than 0.01). We conclude that the left atrial contribution to left ventricular function is increased in patients with remote myocardial infarction. This left atrial contribution to the left ventricle is attributed to the Frank-Starling mechanism in the left atrium.
Diabetes and Portacaval Anastomosis
Authors: A. H. Hunt
Journal: BMJ (1963)

BmxsBi site.It is curious, though, that it should be the one particular parasite every time.Urinary protein electrophoresis has not suggested a preferential leak of any particular protein; though in our cases (adults) as much gamma-globulin is lost as is albumin.We are conscious of the limitations of plain paper electrophoresis in work of this kind and it is still possible that a loss occurs.An interesting observation is an in- creased incidence of P. malariae parasitaemia in our peculiar "big spleen disease."A possibility exists that this syndrome is a manifestation of reticulo- endothelial hypertrophy occurring under the action of some stimulus.Quartan malaria is known to persist the longest.
Orders to Limit Emergency Treatment for an Ambulance Service in a Large Metropolitan Area
Authors: Steven H. Miles, Timothy J. Crimmins
Journal: JAMA (1985)

We describe a policy allowing paramedics and emergency physicians to honor orders from nursing home records not to perform resuscitation or endotracheal intubation. The policy was adopted by the regional body coordinating emergency medical care and endorsed by the county medical society. The policy establishes community-wide definitions for "do not resuscitate" and "do not intubate" orders. It requires physicians to write such directives in patient's medical records and to update them every two years. It urges long-term care facilities to adopt policies to help ensure good decision-making practices in the formulation of these directives. The policy intends to partially address the unnecessary loss of patient autonomy that occurs when emergency care is administered according to routine orders. (<i>JAMA</i>1985;254:525-527)
Commentary: NICE—setting clinical standards
Authors: Gillian Leng, Michael Rawlins, Mercia Page
Journal: BMJ (2007)

The clinical guidelines programme of the National Institute for Health and Clinical Excellence (NICE) is arguably the largest in the world and is unique in considering both cost effectiveness as well as clinical effectiveness. This article by Hill and Treasure is the first in a series to be published in the BMJ : each article will give a short account of key features of newly published NICE guidelines. The articles will particularly focus on areas where changes in current practice are recommended.

NICE guidelines are produced by an independent guideline development group. Its members include relevant clinicians, experts in areas such as systematic reviews and health economics, as well as at least two patients or carers. The development process is based on an internationally agreed methodology (box),1 2 and NICE has now published almost 50 clinical guidelines. In …
INDIVIDUALIZING THE CARE OF THE AGING
Authors: HOLLIS E. CLOW
Journal: American Journal of Psychiatry (1953)

Fear of losing independence and individual identity precipitates emotional difficulties in aging people. These disturbances often occur long before actual incapacity. The time and degree of aging is individual. Our cultural attitude generally and artificially places it at retirement after the age of 65. Many problems of aging are now imposed rather than inevitable. Such problems require individual attention to prevent personality disorganization and to stimulate the best level of functioning in those with different degrees of organic physical or mental incapacity. Social recognition of the value and usefulness of aging people with opportunities for employment and security consistent with their capacities and desires are necessary to solve the problems of a tremendously increasing aging population. Such advantages must be related to individual needs. Families need to understand their aging members. The physician, often a psychiatrist, must be completely familiar with the facilities of community services to meet individual needs for employment, financing, housing, religion, adult education, nursing homes, hospitals and medical attention. Individualized care supports the morale and personality integration of those in their own homes, homes for the aging, or in hospitals including those for mental disorders. An environment without too much change or too many new people often enables confused patients to maintain a relatively clear sensorium. The aging should not be submerged in routine but should be encouraged, when capable, in hobbies or productive chores. They should be allowed some cherished possessions of their own for stability and reassurance offered by continuity with memories of the past. Personal relationships are a great support. Short walks, sitting outdoors, and recreation evoke interest. Maintenance of health habits and personal appearance are essential. The cases of 2 aged hospital patients are presented.
PALLIATIVES FOR HAY FEVER.
Authors: SOLOMON SOLIS-COHEN
Journal: JAMA (1906)

Since 1898, when I made the first announcement of the value of preparations of the suprarenal gland in the treatment of hay fever,<sup>1</sup>I have made many observations on myself and others with a view to determine the best of these preparations and the best method of application and administration. I have also made observations with other promising palliatives, especially pollantin. The results may be summed briefly. <h3>I. SUPRARENAL PREPARATIONS SYSTEMICALLY.</h3> For some individuals, and in certain seasons, the systemic action of suprarenal preparations suffices to induce and preserve comparative comfort. The stomach, however, as I have previously pointed out, is not an eligible channel of administration. The medicinal substance must be absorbed from some other mucous membrane, where it can escape exposure to the digestive juices and the action of the liver. The eye, the tongue, the nose, the pharynx may be utilized. It was, and still is,
Sudden cardiac death. Support for a role of triggering in causation.
Authors: S N Willich, M Maclure, M Mittleman, H R Arntz, J E Muller
Journal: Circulation (1993)

Epidemiological studies have identified associations between time of day and risk of sudden cardiac death. The marked peak in the occurrence of sudden cardiac death after awakening suggests that the disease is triggered by changes that occur during this time period. Increased sympathetic stimulation is a likely cause of such triggering. In the light of the circadian variation of sudden cardiac death and the evidence linking physical activity or mental stress (both associated with activation of the sympathetic nervous system) to the disease, the role of potential triggering events should be investigated. Controlled studies are needed to determine the relative risk of activities that may trigger sudden cardiac death. Since such studies must rely on witnesses (or resuscitated patients), data quality must be closely scrutinized, and studies using case-control and case-crossover designs are needed. The epidemiological and pathophysiological data reviewed in the present article suggest a number of pathways through which activities may trigger sudden cardiac death. Different extrinsic stimuli may cause similar physiological changes that subsequently lead to acute pathological events, a decrease in the ventricular fibrillation threshold through a direct myocardial effect, or a harmful effect on the conduction system. Myocardial ischemia induced by plaque rupture and thrombosis may lead directly to myocardial electric instability. The presence of chronic structural abnormalities of the myocardial tissue or the conduction system may further lower the threshold for electric instability and ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)
IL-12–induced IFN-γ is dependent on caspase-1 processing of the IL-18 precursor
Authors: Giamila Fantuzzi, David A. Reed, Charles A. Dinarello
Journal: Journal of Clinical Investigation (1999)

IL-12 and IL-18 are IFN-gamma-inducing cytokines. In the present study, the role of endogenous IL-18 in the induction of IFN-gamma by IL-12 was investigated in mice. In the presence of a specific inhibitor of caspase-1 (also known as IL-1beta-converting enzyme, or ICE) IL-12-induced IFN-gamma from splenocytes was reduced by 85%. Using splenocytes from ICE-deficient mice, IL-12-induced IFN-gamma was reduced by 80%. However, the role of ICE was not through processing and release of IL-1beta. Neutralizing anti-IL-18 IgG reduced IL-12-induced IFN-gamma in splenocytes by 85%. Splenocytes cultured in vitro spontaneously released IL-18 into the extracellular compartment over time. Extracellular levels of IL-18 significantly correlated with IL-12-induced IFN-gamma and were reduced in cells obtained from ICE-deficient mice. In vivo, IL-12 administration increased circulating levels of IL-18 in wild-type mice but not in ICE-deficient mice. Both neutralization of IL-18 and ICE deficiency significantly reduced induction of circulating IFN-gamma in mice receiving IL-12. The IL-18 precursor was constitutively expressed in the livers and spleens of untreated mice. Furthermore, administration of IL-12 significantly increased liver-associated IL-18 levels. These data demonstrate that endogenous, ICE-cleaved IL-18 significantly contributes to induction of IFN-gamma by IL-12.
Causes of Peripheral Embolism and Their Significance
Authors: Edward A. Edwards
Journal: JAMA (1966)

A review was made of 82 consecutive patients undergoing peripheral arterial embolectomy in the 15-year period 1948 to 1963 at the Peter Bent Brigham Hospital, with emphasis on the etiology and histology of the embolism. Rheumatic and arteriosclerotic heart disease comprised the most common causes. In-hospital mortality for patients with rheumatic heart disease was 25% (12 of 45), while that of patients with arteriosclerosis was 75% (23 of 31). Long-term mortality trends showed similar patterns. Aortoiliac arteriosclerosis is the most common cause of embolism of unusual origin. Careful gross and microscopic examination of an embolus may be most helpful in elucidating etiology.
Is journalism the drug industry's new dance partner?
Authors: R. Moynihan
Journal: BMJ (2011)

Exploring the new frontier in influence peddling



Just as many doctors contemplate an end to their dance with drug company marketers, a fresh new crew is stepping lively onto the floor: journalists and media organisations looking for easy ways to fund their reporting, travel, and education.

The BMJ reported last week that the Murdoch empire’s flagship newspaper in Australia has accepted an undisclosed amount of sponsorship money from the drug industry for a series of articles on health policy—and that the idea arose from a meeting between advertising agents.1

Defending the deal, the Australian ’s editor said that independence and integrity were maintained; but as others pointed out, this new form of financial closeness between journalists and the companies they scrutinise raises real concerns.

A few years ago the industry body Medicines Australia started sponsoring annual journalism awards, with the prize for the health journalist of the year award including $A1000 cash (£660; €760; $US1060) and an international study tour. Presumably all recipients will swear that the award and the world trip had no undesirable effects on their future coverage, and they may well be right. But what we’re witnessing …
Doctors are one of the "linchpins" in closing the UK health inequalities gap
Authors: J. Wise
Journal: BMJ (2010)

All doctors should do more to tackle social inequalities in health, and place more emphasis on the promotion of good health and the prevention of ill health, says a report from the Royal College of Physicians.

The health inequalities that persist in the United Kingdom are not inevitable, says the report. All sectors have a part to play in reducing the gap, with doctors one of the “linchpins in this endeavour.”

The report, written in conjunction with the Royal College of General Practitioners, Royal College of Psychiatrists, Faculty of Public Health, National Heart Forum, and the NHS Sustainable Development Unit, calls on doctors to ensure they encourage people from disadvantaged backgrounds to access health information, screening, and health promotion services.

Professor Ian Gilmore, president of …
Effect of mineral particles containing iron on primary cultures of rabbit tracheal epithelial cells: possible implication of oxidative stress.
Authors: C Guilianelli, A Baeza-Squiban, E Boisvieux-Ulrich, O Houcine, R Zalma, C Guennou, H Pezerat, F Marano
Journal: Environmental Health Perspectives (1993)

Environmental mineral particles such as asbestos are responsible for numerous respiratory diseases. In addition to effects related to their geometry, particles are now assumed to act by triggering an oxidative stress process. Iron-containing particles, in particular, can produce oxygen-activated species by oxidizing their iron. To evaluate the involvement of iron-containing particles in respiratory diseases, three mineral particles (chrysotile, nemalite, and hematite) were tested in primary cultures of tracheal epithelium. Because of the ciliary beat, the three mineral particles were quickly concentrated at the periphery of the mucociliary epithelium, reconstituted in vitro where they induced cellular lesions. Endocytosis of the three types of particles was observed. Cytotoxicity studies have indicated that among the tested particles, the most cytostatic after 24 hr of treatment was the one that contained more Fe2+ available on the surface, nemalite. Moreover, the effect of nemalite was reduced by pretreatment with desferrioxamine. As mineral particles, especially asbestos, are suspected to induce squamous metaplasia, we chose to study two specific transformations of the epithelium: the expression of cytokeratin-13 and the formation of cross-linked envelopes. Under our culture conditions, nemalite and chrysotile increased the expression of the cytokeratin-13, a specific marker of squamous metaplasia, whereas nemalite was the only particle able to strongly induce the formation of cross-linked envelopes. Nemalite was the most cytostatic particle and the most efficient at inducing squamous metaplasia. Measures of oxidizing power by electron-spin resonance revealed that nemalite produced the most oxygen-activated species.(ABSTRACT TRUNCATED AT 250 WORDS)