tbuckley/cabot-search huggingface dataset:
Economic globalisation and its effect on health
Authors: N. Unwin, G. Alberti, T. Aspray, R. Edwards, J.-C. Mbanya, E. Sobngwi, F. Mugusi, S. Rashid, P. Setel, D. Whiting
Journal: BMJ (1998)

Letters p 1456 

According to World Bank figures Tanzania ranks as one of the world's poorest countries,1 yet its commercial centre, Dar es Salaam, is one of the most expensive cities in the world in which to live2—because expatriates on developed world salaries have helped to fuel living costs. An even greater irony is that for Tanzania and many developing nations net flows of wealth remain, as in colonial days, from poor to rich.3 Far more is spent on servicing national debt than on services such as health or education.4 These are perhaps some of the less expected features of globalisation of the world economy.

At the eighth congress of the World Federation of Public Health Associations last October in Arusha, Tanzania, a recurring theme was the advance of globalisation and its adverse effects on health.5 Professor Kris …
Revisiting the role of cladribine in acute myeloid leukemia: An improvement on past accomplishments or more old news?
Authors: Craig W. Freyer, Neha Gupta, Meir Wetzler, Eunice S. Wang
Journal: American Journal of Hematology (2014)

Originally studied in lymphoid diseases, cladribine (CdA) is an adenosine deaminase resistant analog of adenosine that was later discovered to induce myeloid cell apoptosis. The activity of CdA in myeloid malignancies was first reported in relapsed/refractory (RR) pediatric acute myeloid leukemia (AML) with complete response (CR) rates of up to 47%. Consequently, several studies have confirmed the efficacy of single agent CdA or CdA combination regimens in AML. Established CR rates for combination regimens in RR adults are approximately 50%, while CR rates for newly diagnosed (ND) adults are approximately 70% and show similar toxicity profiles to previously used regimens. Despite these promising data, many centers have yet to adopt CdA combination regimens for these difficult to treat populations. We review the pharmacology, pharmacokinetics, clinical data, and safety of CdA monotherapy and combination regimens for the management of pediatric and adult ND and RR-AML.
Abstract 061: Long-chain monounsaturated fatty acids and congestive heart failure incidence: the Atherosclerosis Risk in Communities Study
Authors: Fumiaki Imamura, Rozenn N Lemaitre, Lyn M Steffen, Aaron R Folsom, David S Siscovick, Dariush Mozaffarian
Journal: Circulation (2012)

Background: Animal experiments in 1970s demonstrated direct cardiotoxicity of long-chain monounsaturated fatty acid (LCMUFA, 22:1 and 24:1 fatty acids) consumption. We recently found plasma phospholipid 22:1 and 24:1 to be associated with 34% and 75% higher risk (quintiles 5 vs. 1), respectively, of congestive heart failure (CHF) among older adults in the Cardiovascular Health Study. We wished to validate these results in a second independent cohort of middle-aged adults. Methods: We evaluated 3,577 adults free of CHF at baseline (age=54.1±5.8) in the Minnesota subcohort of the Atherosclerosis Risk in Communities Study (ARIC) in whom plasma phospholipid LCMUFA were measured. Incident CHF was ascertained from 1988 to 2008 by annual phone contacts, hospitalization discharge codes, and death certificates. Using multivariate Cox models, we evaluated prospective association of each LCMUFA with incident CHF, and potential mediation via CHF risk factors, including ECG left ventricular hypertrophy, and incident coronary heart disease (CHD). As a negative control, we also evaluated incident stroke, given its many shared risk factors for CHF but no link to potentially direct cardiotoxicity. Results: Mean±SD plasma phospholipid levels (% of total fatty acids) of 22:1 and 24:1 were 0.01±0.03 and 0.58±0.17. Over the 64,438 person-years of follow-up, 330 CHF events occurred. After multivariable adjustment, higher levels of 22:1 and 24:1 were associated with higher risk of CHF (Figure). Hazard ratios (95%CI) for quintiles 5 vs. 1 of 22:1 and 24:1 levels were 1.57 (1.11–2.23) and 1.92 (1.22–3.03) (p trend=0.03 and 0.002), respectively. These associations were only partly attenuated by potential mediators, including incident CHD. Neither LCMUFA was associated with incident stroke (not shown). Conclusions: Higher 22:1 and 24:1 LCMUFA levels were associated with CHF risk in middle-aged adults, consistent with our prior findings in older adults. These findings support the possibility of clinical cardiotoxicity of LCMUFA in humans.
Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens
Authors: Arancha Rodríguez-Caballero, Andrés C. García-Montero, Paloma Bárcena, Julia Almeida, Francisco Ruiz-Cabello, Maria Dolores Tabernero, Pilar Garrido, Santiago Muñoz-Criado, Yorick Sandberg, Anton W. Langerak, Marcos González, Ana Balanzategui, Alberto Orfao
Journal: Blood (2008)
Abstract 425: Methylation, copy number, and LOH analysis of Chr1q21.3 for discovery of ovarian and breast cancer biomarkers
Authors: Matthew L. Poulin, Ann Meyer, Jessica Alexander, Jessica Xu, Liying Yan
Journal: Cancer Research (2014)

Abstract The association of genetic abnormalities and specific cancers is leading to an increasing number of biomarkers that can be used for early detection of cancers, determination of treatment protocols and predicted prognoses. Additionally, the methylation state of an increasing number of genes is also producing possible predictive biomarkers for specific cancers and stages of cancer as well. To this end, we have analyzed both breast and ovarian cancers and their normal adjacent tissue using both DNA methylation analysis and genome wide array screening for LOH and copy number variations. The combination of these two methods has yielded several groupings of markers that are cancer specific as well as showing specificity for the specific tumor type. Specifically, there are increased copies in the chr1q21.3 region in both ovarian and breast tumor DNA and differences in the methylation when one compares breast tumor to ovarian tumor DNA's. Interestingly, in ovarian tumor samples where there is no amplification of the region, the hypomethylation is greater than in tumor samples in which there is amplification in the region. This suggests that a greater degree of demethylation is needed to potentially activate this region of the genome, where this may not be necessary in regions where an increase in gene copy number may cause increased expression. Citation Format: Matthew L. Poulin, Ann Meyer, Jessica Alexander, Jessica Xu, Liying Yan. Methylation, copy number, and LOH analysis of Chr1q21.3 for discovery of ovarian and breast cancer biomarkers. [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 425. doi:10.1158/1538-7445.AM2014-425
METABOLISM OF CREATINE AND CREATININE IN MUSCLE DISEASE
Authors: A. T. Milhorat, H. G. Wolff
Journal: Annals of Internal Medicine (1936)

Article1 January 1936METABOLISM OF CREATINE AND CREATININE IN MUSCLE DISEASEA. T. MILHORAT, H. G. WOLFF, F.A.C.P.A. T. MILHORATSearch for more papers by this author, H. G. WOLFF, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-7-834 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Excerpt1. Patients with diseases which affect the skeletal muscle commonly have a creatinuria even when they are maintained on a creatine-free diet. Accompanying the creatinuria, there is usually a diminution in the excretion of creatinine and in the ability of the body to retain ingested creatine (a low creatine tolerance).2. In progressive muscular dystrophy, often large amounts of creatine are excreted. The level of the creatinuria and the impairment of the creatine tolerance are usually related to the amount of muscle disability. In advanced stages of the disease the creatine tolerance may be impaired to the extent that all... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Read at the Philadelphia meeting of the American College of Physicians, April 29, 1935.From the New York Hospital and the Department of Medicine, Cornell University Medical College, and the Russell Sage Institute of Pathology, New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Biochemistry of Myasthenia GravisBiochemie der progressiven MuskeldystrophieCreatinuria in Patients with palpable muscle affections (Myosis)THE EFFECT OF PARENTERAL INJECTION OF AMINO ACIDS AND RELATED SUBSTANCES UPON CREATINE FORMATION AND STORAGE IN THE RAT 1 January 1936Volume 9, Issue 7Page: 834-837KeywordsCreatineCreatinineDietDisabilitiesExcretionHospital medicineMusclesMuscular dystrophiesSkeletal muscles ePublished: 1 December 2008 Issue Published: 1 January 1936 PDF downloadLoading ...
Effects of bosentan on nondigital ulcers in patients with systemic sclerosis
Authors: T. Taniguchi, Y. Asano, M. Hatano, Z. Tamaki, M. Tomita, T. Kawashima, M. Miyazaki, H. Sumida, K. Akamata, T. Takahashi, Y. Ichimura, T. Toyama, M. Sugita, S. Noda, A. Yao, K. Kinugawa, S. Sato
Journal: British Journal of Dermatology (2011)

Bosentan is an oral dual endothelin receptor antagonist, which has been shown to be efficacious for preventing new digital ulcers in patients with systemic sclerosis (SSc) in two high-quality randomized controlled trials. However, its efficacy for nondigital ulcers in SSc remains unknown.To evaluate the efficacy of bosentan on nondigital ulcers in patients with SSc.Bosentan was administered to five patients with SSc with pulmonary arterial hypertension, who also had nondigital ulcers refractory to conventional treatments. The efficacy of bosentan on nondigital ulcers and its association with clinical features of ulcers were analysed.The nondigital ulcers refractory to conventional treatments were significantly improved by the administration of bosentan in cases surrounded with severe cyanosis. In contrast, nondigital ulcers without cyanosis were still refractory to bosentan therapy.Bosentan may be efficacious for accelerating the healing of nondigital ulcers with severe cyanosis, suggesting that nondigital ulcers caused by severely impaired peripheral circulation are highly responsive to this treatment.
Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications
Authors: Amedeo Sciarra, Luca Di Tommaso, Masayuki Nakano, Annarita Destro, Guido Torzilli, Matteo Donadon, Marco Maggioni, Silvano Bosari, Gaetano Bulfamante, Masanori Matsuda, Hideki Fujii, Tomoaki Ichikawa, Hiroyuki Morisaka, Katsuhiro Sano, Shintaro Ichikawa, Massimo Roncalli
Journal: Journal of Hepatology (2015)
T cells are the critical source of IL-4/IL-13 in a mouse model of allergic asthma
Authors: K. Oeser, J. Maxeiner, C. Symowski, M. Stassen, D. Voehringer
Journal: Allergy (2015)

IL-4 and IL-13 play a crucial role during allergic asthma. Both cytokines can be produced by T cells and a variety of cell types of the innate immune system. The relative contribution of T-cell-derived vs innate IL-4/IL-13 for allergic inflammation and airway hyperreactivity remains unclear. We compared the severity of OVA/alum-induced allergic lung inflammation in WT BALB/c mice to mice that lack expression of IL-4/IL-13 only in T cells (4-13Tko) or in all cell types (4-13ko). T-cell-derived IL-4/IL-13 was required for IgG1 and IgE production, recruitment of eosinophils and basophils to the lung, goblet cell hyperplasia, expression of Muc5ac, Clca3, and RELMβ, differentiation of alternatively activated macrophages, and airway hyperreactivity. Interestingly, ILC2 recruitment to the lung occurred independently of T-cell-derived IL-4/IL-13 but was diminished in the absence of IL-4/IL-13 from all cell types. Thus, the number of IL-4/IL-13-competent ILC2s did not correlate with the severity of lung pathology. Th2 cells appear to be the critical IL-4/IL-13-expressing cell type for the induction of allergic airway inflammation and airway hyperreactivity. The translational perspective of our results indicates that inhibition or reprogramming of Th2 cells may be very effective for the treatment of allergic asthma.
Abstract 87: Targeting androgen receptor acetylation as a treatment for castrate-resistant prostate cancer
Authors: Erin Heine, Diane E. Merry, Scott Dehm, Karen E. Knudsen, Heather L. Montie
Journal: Cancer Research (2015)

Abstract The goal of our studies is to determine the potential of targeting androgen receptor (AR) acetylation as a means to counter androgen-independent prostate cancer (PCa). AR lysine residues 630/632/633 are acetylated in response to androgen-binding. This AR modification has been shown to enhance the transcriptional function of AR and to contribute to prostate tumorigenesis. These observations are supported by the discovery of an AR mutation that mimics this modification in a subset of prostate cancer patients (K630T), as well as increased levels of AR acetyltransferases in some advanced cases. We are specifically interested in the role of this modification in castrate-resistant prostate cancer, and we hypothesize that acetylation contributes to aberrant AR activation in castrate-resistant prostate cancer and possibly in androgen receptor antagonist resistant disease. We are utilizing genetic and pharmacological approaches to determine the function of AR acetylation in PCa, both in cell culture and in in vivo models. We have generated C4-2 cell lines within which we have stably knocked down endogenous AR (shRNA) and replaced it with acetylation-mutant AR (acetylation-null, acetylation-mimic, or lysine-intact controls). We have been performing growth and transcription assays to assess the effect of AR acetylation on these attributes of castrate-resistant PCa. Cells expressing acetylation-mimic AR have increased expression of select AR target gene transcripts, compared to cells expressing AR, null for acetylation. Enhanced AR transcriptional activity corresponds with a growth advantage of acetylation-mimic AR-expressing cells, whereas acetylation-null AR expressing cells undergo a substantial growth inhibition. Studies in mouse xenografts will further clarify whether AR acetylation is a driver of castrate-resistant disease and whether targeting AR acetylation is a rational strategy to treat this advanced disease state. Continued studies will also validate the potential of targeting AR acetylation as a means to combat AR antagonist resistant disease. The growth inhibition of cells expressing acetylation-null AR suggests that reducing AR acetylation may be a means to treat castrate-resistant PCa. Citation Format: Erin Heine, Diane E. Merry, Scott Dehm, Karen E. Knudsen, Heather L. Montie. Targeting androgen receptor acetylation as a treatment for castrate-resistant prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 87. doi:10.1158/1538-7445.AM2015-87
Random signature testing procedure: A new method to verify the prognostic performance of gene signatures
Authors: Maud Starmans, Glenn Fung, Harald Steck, Philippe Lambin, Bradly Wouters
Journal: Clinical Cancer Research (2008)

A14  Highly parallel analysis of gene expression has recently been used to identify gene sets or 9signatures9 to improve patient diagnosis and risk stratification. These signatures are usually identified by way of traditional statistical testing procedures that, due to the dimensionality of microarrays, lead to a high number of false prognostic signatures.  A method was developed to test batches of a user-specified number of randomly chosen signatures in patient microarray datasets. The percentage of random generated signatures yielding prognostic value was assessed using ROC analysis by calculating the area under the curve (AUC) in six publically available cancer patient microarray datasets.  Within these datasets, we found that a signature consisting of randomly selected genes has an average 10% chance of being called prognostic when assessed in a single dataset, but can range from 1% to ~40% depending on the dataset in question. Increasing the number of validation datasets markedly reduced this number.  We further show that the use of an arbitrary cut-off value for evaluation of signature significance is not suitable for this type of research, but should be defined for each dataset separately. Our method can be used to establish and evaluate signature performance of any derived signature within single or multiple datasets by comparing its performance to thousands of randomly generated signatures.
Patterns of bone mineral acquisition in children with epidermolysis bullosa: a longitudinal study
Authors: T. Fu, B. Lingala, K. Kent, L.K. Bachrach, A.L. Bruckner
Journal: British Journal of Dermatology (2011)

Reduced bone mass and fractures are known complications of generalized forms of epidermolysis bullosa (EB). However, the aetiology - inadequate bone acquisition, premature bone loss, or a combination - is unclear.To determine patterns of bone mineral acquisition in children with EB and to identify clinical and laboratory correlates of change in areal bone mineral density (aBMD).Seventeen subjects ≥ 6 years of age with generalized EB were studied at two visits at least 12 months apart with clinical and laboratory evaluations and dual energy X-ray absorptiometry scans of the lumbar spine. Wilcoxon signed-rank tests were used to determine if changes from baseline to follow-up were significant. Wilcoxon rank-sum tests were used to compare subjects with gains in aBMD Z-score with those who experienced no change or decreases to determine if baseline laboratory or clinical characteristics differed between the two groups.Subjects gained height and weight at follow-up, but there was no significant improvement in mean Z-scores for height, weight or body mass index. Laboratory values did not change significantly. Mean bone mineral content and aBMD of the lumbar spine increased significantly at follow-up, but mean aBMD Z-scores remained static. No differences in clinical characteristics or laboratory values were seen between subjects with increased aBMD Z-scores vs. those whose scores decreased or did not change.Low bone mass in children with generalized EB is due primarily to inadequate gains in aBMD. Interventions to improve overall health and to help build bone mass in this patient population are warranted.
Abstract 4071: SAH-p53-mediated inhibition of cell migration via alteration of actin dynamics
Authors: Bethanie L. Morrison, Amanda L. Whiting, Federico Bernal
Journal: Cancer Research (2014)

Abstract The mutation of p53 is critical for the increased metastatic potential of cancer cells. As such, it is essential not only to understand the mechanisms underlying the functional implications of p53 mutation, but also to identify ways to regulate their impact on cancer cell physiology. I have found that a hydrocarbon-stapled p53 transactivation domain peptide (SAH-p53) designed to disrupt the interaction of p53 with its negative regulators HDM2 and HDMX retains its function in cells harboring a mutant TP53. A common gain-of-function activity of the mutant p53 protein (mtp53) is the enhancement of cell migration and invasion; however, I found that SAH-p53 has the ability to inhibit the migration and invasion of HS578T and MDA-MB-231 breast cancer cells (mtp53), while exhibiting no change in proliferative ability at the same dose. This effect was accompanied by sustained alterations in actin stress fiber dynamics and inhibition of focal adhesion assembly and signaling. Furthermore, treatment of MDA-MB-231 cells with various growth factors (EGF, TGF-β, PDGF, HGF) was unable to rescue the migratory ability of cells in the presence of SAH-p53. The combination of SAH-p53 and TGF-β resulted in a decrease in the total expression levels of both EGFR and FAK. Moreover, it was shown that the combined treatment of SAH-p53 and TGF-β enhanced the localization of EGFR to early endosomes and eventually to lysosomes, prompting the use of fluorophore-capped SAH-p53 to track the localization of the peptide in relation to EGFR. It was determined that over time SAH-53 localizes to vesicles containing EGFR, but not other RTKs (ie. PDGFRβ). SAH-p53 was able to retain its ability to inhibit migration in the absence of functional HDMX/HDM2 or mutant p53, suggesting the possibility of an alternative target. We are currently using a photoactivatable and capped SAH-p53 that can cross-link to a target protein in the presence of UV in order to determine the identity of the target of SAH-p53 responsible for the anti-migratory effects seen in mutant p53- or p53-null cells. These data show that the use of a stapled peptide provides a novel avenue to study the molecular interactions that drive metastatic behavior in cancer cells. Citation Format: Bethanie L. Morrison, Amanda L. Whiting, Federico Bernal. SAH-p53-mediated inhibition of cell migration via alteration of actin dynamics. [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 4071. doi:10.1158/1538-7445.AM2014-4071
Combination therapy may be beneficial for the treatment of lymphangioleiomyomatosis
Authors: Lyn Moir, Ho Yin Ng, Brian Oliver, Janette Burgess, Vera Krymskaya, Judith Black
Journal: European Respiratory Journal (2013)

Dysfunction of the tuberous sclerosis genes (TSC), in particular TSC2, results in enhanced cell proliferation and migration associated with lymphangioleiomyomatosis (LAM). Although rapamycin has shown some clinical benefit cessation of treatment causes a decline in lung function. Rapamycin inhibits cell proliferation but has little effect on migration. Thus, targeting multiple processes may be beneficial for LAM treatment. We examined the combined effect of doxycycline and rapamycin on cell proliferation and migration and investigated the signalling pathways involved.  Methods: Proliferation and migration of TSC2+/+ and TSC2-/- mouse embryonic fibroblasts (MEF) were assessed by manual cell counts, transwell and wound closure assays. Phosphorylated p70S6K (p-p70S6K) was assessed by immunoblotting and RhoA activity by ELISA.  Results: Doxycycline inhibited both RhoA activity and migration of TSC2-/- MEF (n=4, p 0.05) or proliferation (n=4, p>0.05). Rapamycin inhibited p-p70S6K and proliferation (n=5, p 0.05). However, combination treatment reduced the rate of wound closure by TSC2-/- MEF compared to individual drugs (n=4, p  Conclusion: Doxycycline inhibits the enhanced cell migration associated with TSC2-dysfunction through the RhoA GTPase pathway. LAM is a multifactorial disease, utilising multiple signalling pathways, thus combination therapy that targets these pathways may be beneficial.