tbuckley/cabot-search huggingface dataset:
Functional Epigenomics Identifies Genes Frequently Silenced in Prostate Cancer
Authors: Dimitri Lodygin, Alexey Epanchintsev, Antje Menssen, Joachim Diebold, Heiko Hermeking
Journal: Cancer Research (2005)

Abstract In many cases, silencing of gene expression by CpG methylation is causally involved in carcinogenesis. Furthermore, cancer-specific CpG methylation may serve as a tumor marker. In order to identify candidate genes for inactivation by CpG methylation in prostate cancer, the prostate cancer cell lines LNCaP, PC3, and Du-145 were treated with 5-aza-2′ deoxycytidine and trichostatin A, which leads to reversion of epigenetic silencing. By microarray analysis of 18,400 individual transcripts, several hundred genes were found to be induced when compared with cells treated with trichostatin A. Fifty re-expressed genes were selected for further analysis based on their known function, which implied a possible involvement in tumor suppression. Twelve of these genes showed a significant degree of CpG methylation in their promoters. Six genes were silenced by CpG methylation in the majority of five analyzed prostate cancer cell lines, although they displayed robust mRNA expression in normal prostate epithelial cells obtained from four different donors. In primary prostate cancer samples derived from 41 patients, the frequencies of CpG methylation detected in the promoter regions of these genes were: GPX3, 93%; SFRP1, 83%; COX2, 78%; DKK3, 68%; GSTM1, 58%; and KIP2/p57, 56%. Ectopic expression of SFRP1 or DKK3 resulted in decreased proliferation. The expression of DKK3 was accompanied by attenuation of the mitogen-activated protein kinase pathway. The high frequency of CpG methylation detected in the promoters of the identified genes suggests a potential causal involvement in prostate cancer and may prove useful for diagnostic purposes.
Differential effects of insulin-like growth factor I and growth hormone on developmental stages of rat growth plate chondrocytes in vivo.
Authors: E B Hunziker, J Wagner, J Zapf
Journal: Journal of Clinical Investigation (1994)

Skeletal growth depends upon enchondral ossification in growth plate cartilage, within which chondrocytes undergo well defined stages of maturation. We infused IGF-I or growth hormone (GH), two key regulators of skeletal growth, into hypophysectomized rats and compared their effects on growth plate chondrocyte differentiation using qualitative and quantitative autoradiography, stereology, and incident light fluorescence microscopy. Stem cell cycle time was shortened from 50 to 15 and 8 d after treatment with IGF-I and GH, respectively. Proliferating cell cycle time decreased from 11 to 4.5 and 3 d, and duration of the hypertrophic phase decreased from 6 to 4 and 2.8 d. Average matrix volume per cell at each differentiation stage was similar for normal, hormone-treated, and untreated hypophysectomized groups. Mean cell volume and cell height were significantly reduced by hypophysectomy at the proliferative and hypertrophic stages, but were restored to physiological values by IGF-I and GH. In contrast, cell productivity, i.e., increases in cell volume, height, and matrix production per unit of time, did not reach normal values with either IGF-I or GH, and this parameter was inversely proportional to cell cycle time or phase duration. IGF-I and GH are thus capable of stimulating growth plate chondrocytes at all stages of differentiation, albeit to variable degrees with respect to individual cell activities. Although it is generally accepted that GH acts at both the stem and proliferating phases of chondrocyte differentiation, our data represent the first evidence in vivo that IGF-I is also capable of stimulating stem cells.
MANAGEMENT OF CATARRHAL PNEUMONIA IN INFANTS.
Authors: CHARLES GILMORE KERLEY
Journal: JAMA (1903)

Catarrhal pneumonia, on account of its large mortality and because of its frequent appearance as a complication in almost every disease of infancy, is one of the most formidable ailments which we are called on to treat. The disease is usually described as primary and secondary. Among the several hundred cases which have come under the writer's observation comparatively few were primary, not 5 per cent. Those described as primary usually follow a bronchitis, often a neglected bronchitis. The disease varies considerably as regards its severity, depending on the age and condition of the child, the nature of the infection and the amount of lung involved. It occurs with its greatest fatality when associated with diphtheria and measles. Catarrhal pneumonia demands the best attention we can give it, not only on account of the delicate organ attacked, enclosed in weak thoracic walls, but because, unlike lobar pneumonia, scarlet fever
Artificial reduction in transepidermal water loss improves skin barrier function
Authors: I. Buraczewska, U. Broström, M. Lodén
Journal: British Journal of Dermatology (2007)

Artificial reduction of abnormal transepidermal water loss (TEWL) is considered to improve skin diseases associated with a defective barrier function. Treatment of the skin with moisturizers is also known to influence skin barrier function. Whether or not differences in occlusion between creams contribute to their effects on the skin barrier function is unknown.To investigate the long-term effects of a semipermeable membrane on the skin barrier function in normal skin. In addition, the occlusive properties of two creams were studied.The study was randomized, controlled and evaluator-blind using measurement of TEWL and skin susceptibility to sodium lauryl sulphate as indicators of skin barrier function.Coating of the skin with a silicone membrane for 23 h per day for 3 weeks improved skin barrier function, whereas no significant changes were found after using the membrane for 8 h per day.Differences between creams in terms of their effect on skin barrier function cannot be solely explained by their occlusive properties.
The hydration and electrolyte maintenance properties of an experimental sports drink.
Authors: J. White, M. A. Ford
Journal: British Journal of Sports Medicine (1983)

Seven highly trained subjects underwent exercise dehydration without fluid replacement (X), resulting in approximately 1.9% and approximately 3.5% body weight (fluid) losses at one and two hours, respectively. Subsequently, subjects underwent two identical exercise trials with isovolumetric fluid replacement of water (W) and an experimental formulation (Q). An anti-dehydration schedule was initiated prior to, and continued throughout the exercise, with W and Q supplied every 15 minutes at 16 degrees C in volumes related to each subject's fluid loss estimate derived from trial X. A rehydration schedule was maintained for two hours of recovery, with total fluid replacement equivalent to the body weight decrement due to fluid losses. In both W and Q trials, selected physiological indices of work performance were maintained closer to homeostatic levels during exercise, with a more rapid return to pre-exercise resting levels during recovery than during that trial X. Furthermore, W and Q were equally effective in preventing plasma volume changes during exercise and restoration to pre-exercise levels during recovery, as well as in preventing plasma osmolality disturbances during exercise and recovery, although minimal plasma electrolyte changes were associated with Q.
Molecular Interaction of CD1b with Lipoglycan Antigens
Authors: William A Ernst, Juli Maher, Sungae Cho, Kayvan R Niazi, Delphi Chatterjee, D.Branch Moody, Gurdyal S Besra, Yutaka Watanabe, Peter E Jensen, Steven A Porcelli, Mitchell Kronenberg, Robert L Modlin
Journal: Immunity (1998)
Positive Phentolamine Test in Hypertension Induced by a Nasal Decongestant
Authors: Wolfgang F. C. Duvernoy
Journal: New England Journal of Medicine (1969)

HYPERTENSIVE episodes after ingestion of nasal decongestants containing phenylpropanolamine have been sporadically reported in the past,1 2 3 4 occurring with normal doses,4 as well as after an overdose of 400 mg.3 This report describes a patient with phenylpropanolamine-induced hypertension, who had a positive response to the phentolamine test.Case ReportA 21-year-old Negro corpsman was taken to the local dispensary after the sudden onset of diffuse abdominal pain, severe right-sided throbbing headaches and nausea. Initially, a blood pressure of 240/120 was recorded. After 330 mg of phenobarbital given intramuscularly and 32 mg of codeine the blood pressure decreased to 170/120. He was . . .
Zonal distribution of chondroitin-4-sulphate/dermatan sulphate and chondroitin-6-sulphate in normal and diseased human synovium.
Authors: J G Worrall, L S Wilkinson, M T Bayliss, J C Edwards
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--Chondroitin sulphate is the major sulphated glycosaminoglycan present in the extracellular matrix of soft connective tissues and the aim of this study was to investigate the distribution of chondroitin sulphate species in normal and diseased synovium. METHODS--Distribution of chondroitin-4-sulphate/dermatan sulphate (Ch4S/DS) and chondroitin-6-sulphate in normal (n = 6), osteoarthritic (n = 4) and rheumatoid (n = 10) synovium was determined using an immunoperoxidase technique and specific monoclonal antibodies to chondroitinase ABC-digested preparations. RESULTS--Ch4S/DS was expressed throughout the interstitium of all tissues and was also present on blood vessels in rheumatoid samples only. Ch6S was expressed in the lining layer of normal synovium but was absent from this site in osteoarthritic and rheumatoid tissues. Ch6S was also present on all blood vessels in all tissues. CONCLUSIONS--The distinct zonal distributions of Ch4S/DS and Ch6S and their alteration in disease suggest these molecules have different and specific functions in normal and diseased synovium.
Combinatorial Antiangiogenic Gene Therapy by Nonviral Gene Transfer Using the Sleeping Beauty Transposon Causes Tumor Regression and Improves Survival in Mice Bearing Intracranial Human Glioblastoma
Authors: John R. Ohlfest, Zachary L. Demorest, Yasuhiko Motooka, Isabelita Vengco, Seunguk Oh, Eleanor Chen, Frank A. Scappaticci, Rachel J. Saplis, Stephen C. Ekker, Walter C. Low, Andrew B. Freese, David A. Largaespada
Journal: Molecular Therapy (2005)

Glioblastoma is a fatal brain tumor that becomes highly vascularized by secreting proangiogenic factors and depends on continued angiogenesis to increase in size. Consequently, a successful antiangiogenic therapy should provide long-term inhibition of tumor-induced angiogenesis, suggesting long-term gene transfer as a therapeutic strategy. In this study a soluble vascular endothelial growth factor receptor (sFlt-1) and an angiostatin-endostatin fusion gene (statin-AE) were codelivered to human glioblastoma xenografts by nonviral gene transfer using the Sleeping Beauty (SB) transposon. In subcutaneously implanted xenografts, co-injection of both transgenes showed marked anti-tumor activity as demonstrated by reduction of tumor vessel density, inhibition or abolition of glioma growth, and increase in animal survival (P = 0.003). Using luciferase-stable engrafted intracranial gliomas, the anti-tumor effect of convection-enhanced delivery of plasmid DNA into the tumor was assessed by luciferase in vivo imaging. Sustained tumor regression of intracranial gliomas was achieved only when statin-AE and sFlt-1 transposons were coadministered with SB-transposase-encoding DNA to facilitate long-term expression. We show that SB can be used to increase animal survival significantly (P = 0.008) by combinatorial antiangiogenic gene transfer in an intracranial glioma model.
Abstract 5038: AZD8055 is an effective inhibitor of mTOR kinase signaling and breast cancer growth while relieving feedback inhibition of HER-kinase signaling
Authors: Vanessa S. Rodrik-Outmezguine, Nen Cao, Sarat Chandarlapaty, Qing-Bai She, Qing Ye, Paul Smith, Sylvie Guichard, Neal Rosen
Journal: Cancer Research (2010)

Abstract The PI3K signaling pathway is often dysregulated in human cancer. mTOR kinase is a component of this pathway that mediates activation of cap-dependent translation, other AGC-kinases and feedback inhibition of upstream components of the pathway. The natural product rapamycin binds to and inhibits the mTOR-containing TORC1, but not the TORC2 complex. Rapamycin-like TORC1 inhibitors have modest clinical activity in renal cell and other cancers, but only marginal activity in glioblastoma, prostate and breast cancers in which PI3K/AKT signaling is often activated. The limited antitumor activity of rapamycin may be due to inefficient inhibition of TORC1, induction of TORC1-dependent feedback, or lack of inhibition of TORC2. Potent mTOR kinase inhibitors could obviate these issues by inhibiting both TORC1 and TORC2 and by preventing induction of phosphorylation of AKT at Serine 473. We have now compared the effects of the specific mTOR kinase inhibitor AZD8055 and rapamycin in breast cancer models with amplified HER2 or mutant p110alpha PI3K. As expected, AZD8055 and rapamycin both inhibit S6K and S6 phosphorylation, but only the former inhibits AKT phosphorylation at Serine 473, which is, instead, induced by rapamycin. Moreover, AZD8055 is a more potent inhibitor of 4EBP-1 phosphorylation, CAP-dependent translation, and D-cyclin expression. Thus, the mTOR kinase inhibitor inhibits mTOR functions more effectively than rapamycin. Whereas both drugs cause tumor cells to undergo autophagy and G1 arrest, only AZD8055 induces significant apoptotic cell death. The more effective inhibition of 4EBP1 phosphorylation, cap-dependent translation and enhancement of apoptosis compared to that caused by rapamycin may be due to more complete inhibition of TORC1 function or to abolition of feedback activation of AKT by AZD8055. As previously established with rapamycin, we now show that AZD8055 causes relief of feedback inhibition of HER kinase signaling in these tumors, resulting in marked induction of both ERK and PI3K signaling. These results suggest that mTOR kinase inhibition with drugs such as AZD8055 can more effectively inhibit TOR activity than rapamycin. They therefore have the potential for increased antitumor activity, but relief of TOR kinase-dependent negative feedback could create a rationale for combination therapy. 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 5038.
Nonsurgical Management of Obesity in Adults
Authors: Robert H. Eckel
Journal: New England Journal of Medicine (2008)

A 44-year-old woman desires weight reduction. She has a history of hypertension, daytime somnolence, and osteoarthritis. Her weight is 215 lb (98 kg), her waist circumference is 40 in. (102 cm), and her body-mass index is 32.7. Her blood pressure is 140/92 mm Hg. What would you advise?
Mental health services need more talking therapy and care after hours
Authors: Toby Reynolds
Journal: BMJ (2006)

England's community mental health services should widen patients' access to talking therapies and information and provide better out of hours care, the Healthcare Commission said after a national review.

A survey conducted by the commission found that users were mostly satisfied with the service, with 77% rating their care as good, very good, or excellent and more than 80% saying that their psychiatrist and community psychiatric nurse had treated them with respect and dignity.

But less than half said they had a telephone number of someone from their local mental health service who could be contacted out of hours.

“The majority of people who suffer from mental illness receive their treatment in their …
Ovarian Tumor Domain-Containing Viral Proteases Evade Ubiquitin- and ISG15-Dependent Innate Immune Responses
Authors: Natalia Frias-Staheli, Nadia V. Giannakopoulos, Marjolein Kikkert, Shannon L. Taylor, Anne Bridgen, Jason Paragas, Juergen A. Richt, Raymond R. Rowland, Connie S. Schmaljohn, Deborah J. Lenschow, Eric J. Snijder, Adolfo García-Sastre, Herbert Whiting Virgin
Journal: Cell Host & Microbe (2007)
Durability of lamivudine-induced HBeAg seroconversion for chronic hepatitis B patients with acute exacerbation
Authors: Chuan-Mo Lee, Guan-Yeow Ong, Sheng-Nan Lu, Jing-Houng Wang, Chun-Ann Liao, Hung-Da Tung, Tsung-Ming Chen, Chi-Sin Changchien
Journal: Journal of Hepatology (2002)
Re: Niels M. Graafland, Joost A.P. Leijte, Renato A. Valdés Olmos, et al. Scanning with 18F-FDG-PET/CT for Detection of Pelvic Nodal Involvement in Inguinal Node-Positive Penile Carcinoma. Eur Urol 2009;56:339–45
Authors: Oliver W. Hakenberg, Chris Protzel
Journal: European Urology (2009)
Computerization Can Create Safety Hazards: A Bar-Coding Near Miss
Authors: Clement J. McDonald
Journal: Annals of Internal Medicine (2006)

Increasing numbers of hospitals are implementing bar-coding systems to prevent errors in patient identification. In the present case, a diabetic patient admitted to a teaching hospital was mistakenly given the bar-coded identification wristband of another patient who was admitted at the same time. When a laboratory result that documented the diabetic patient's severe hyperglycemia was entered into the other patient's electronic medical record, the latter patient seemed to have a very high glucose level and was almost given what could have been a fatal dose of insulin. This near miss shows that computer systems, although having the potential to improve safety, may create new kinds of errors if not accompanied by well-designed, well-implemented cross-check processes and a culture of safety. Moreover, computer systems may have the pernicious effect of weakening human vigilance, removing an important safety protection. Researchers should continue to study real-world implementation of computerized systems to understand their benefits and potential harms, and administrators and providers should seek ways to anticipate these harms and mitigate them.
No effect of acenocoumarol therapy on levels of endothelial activation markers in sickle cell disease
Authors: J.B. Schnog, M.R. Mac Gillavry, R.A. Rojer, J.C.M. Meijers, R. Fijnheer, H. ten Cate, D.P.M. Brandjes, A.J. Duits
Journal: American Journal of Hematology (2002)

Sickle cell patients are characterized by a chronic inflammatory and hypercoagulable state, depicted by elevated levels of pro-inflammatory cytokines, endothelial adhesion molecules, and elevated markers of thrombin generation. We set out to determine whether anticoagulation with a coumadin derivative reduces inflammation in sickle cell disease. Therefore, serum levels of NFkappaB-regulated endothelial adhesion molecule soluble vascular cell adhesion molecule-1 and serum levels of non-NFkappaB-dependent markers of endothelial activation (soluble cellular fibronectin and von Willebrand factor antigen) were compared during treatment with acenocoumarol (INR 1.6-2.0) and placebo. No effect on circulating levels of the measured parameters was observed during treatment with acenocoumarol as compared to placebo. In the targeted INR range, anticoagulation of sickle cell patients with acenocoumarol does not seem to reduce endothelial activation.
Bacillary angiomatosis on a region of burned skin in a immunocompetent patient
Authors: M. Karakaş, M. Baba, V.L. Aksungur, S. Homan, H.R. Memİsoğlu, A. Uğuz
Journal: British Journal of Dermatology (2000)

Bacillary angiomatosis usually develops in immunodeficient patients with a history of contact with cats. We report a 21-year-old immunocompetent woman with facial angiomatous lesions following a second-degree burn and without a history of direct contact with cats. The diagnosis of bacillary angiomatosis was based on the demonstration of bacilli in histological sections stained by the Warthin–Starry method. The lesions resolved 2 months after treatment with oral erythromycin for 8 weeks. This case emphasizes that bacillary angiomatosis may be seen in immunocompetent individuals and may be transmitted in other ways than cat scratches, e.g. by arthropods.
The Effects of Air Pollution on Hospitalizations for Cardiovascular Diseasein Elderly People in Australian and New Zealand Cities
Authors: Adrian G. Barnett, Gail M. Williams, Joel Schwartz, Trudi L. Best, Anne H. Neller, Anna L. Petroeschevsky, Rod W. Simpson
Journal: Environmental Health Perspectives (2006)

The goal of this study was to estimate the associations between outdoor air pollution and cardiovascular hospital admissions for the elderly.Associations were assessed using the case-crossover method for seven cities: Auckland and Christchurch, New Zealand; and Brisbane, Canberra, Melbourne, Perth, and Sydney Australia. Results were combined across cities using a random-effects meta-analysis and stratified for two adult age groups: 15-64 years and >/= 65 years of age (elderly). Pollutants considered were nitrogen dioxide, carbon monoxide, daily measures of particulate matter (PM) and ozone. Where multiple pollutant associations were found, a matched case-control analysis was used to identify the most consistent association.In the elderly, all pollutants except O3 were significantly associated with five categories of cardiovascular disease admissions. No associations were found for arrhythmia and stroke. For a 0.9-ppm increase in CO, there were significant increases in elderly hospital admissions for total cardiovascular disease (2.2%) , all cardiac disease (2.8%), cardiac failure (6.0%), ischemic heart disease (2.3%), and myocardial infarction (2.9%). There was some heterogeneity between cities, possibly due to differences in humidity and the percentage of elderly people. In matched analyses, CO had the most consistent association.The results suggest that air pollution arising from common emission sources for CO, NO2, and PM (e.g., motor vehicle exhausts) has significant associations with adult cardiovascular hospital admissions, especially in the elderly, at air pollution concentrations below normal health guidelines. Relevance to clinical and professional practice: Elderly populations in Australia need to be protected from air pollution arising from outdoor sources to reduce cardiovascular disease.