tbuckley/cabot-search huggingface dataset:
The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality
Authors: Caroline S. Fox, Lisa Sullivan, Ralph B. D’Agostino, Peter W.F. Wilson
Journal: Diabetes Care (2004)

OBJECTIVE—The risk of coronary heart disease (CHD) in type 2 diabetes is two- to threefold higher than in the general population, but the effect of diabetes duration on CHD risk has not been well characterized. We hypothesized that duration of diabetes is an important predictor of incident CHD among people with diabetes. RESEARCH DESIGN AND METHODS—The duration of diabetes (fasting glucose ≥126 mg/dl, random glucose ≥200 mg/dl, or use of an oral hypoglycemic agent or insulin) was assessed in participants with diabetes in the original and offspring cohorts of the Framingham Heart Study. Only subjects with diabetes diagnosed between the ages of 30 and 74 years, without a history of ketoacidosis, and free of cardiovascular disease at the baseline evaluation were included. Cox proportional hazards models were used to estimate the hazard ratio of incident CHD events and mortality over a 12-year follow-up period; models were adjusted for known CHD risk factors. RESULTS—Among 588 person-exams with diabetes (mean age 58 ± 9 years, 56% men), there were 86 CHD events, including 36 deaths. After adjustment for age, sex, and CHD risk factors, the risk of CHD was 1.38 times higher for each 10-year increase in duration of diabetes (95% CI 0.99–1.92), and the risk for CHD death was 1.86 times higher (1.17–2.93) for the same increase in duration of diabetes. CONCLUSIONS—Duration of diabetes increases the risk of CHD death independent of coexisting risk factors. Further research is necessary to understand the pathophysiology of this increased risk.
The wealth of distinguished doctors: retrospective survey
Authors: I C McManus
Journal: BMJ (2005)

To assess changes in the wealth of distinguished doctors in the United Kingdom between 1860 and 2001.Retrospective survey.The UK.980 doctors of sufficient distinction to be included in the Oxford Dictionary of National Biography and who died between 1860 and 2001.Wealth at death, based on probate records and adjusted relative to average earnings in 2002.The wealth of distinguished doctors declined substantially between 1860 and 2001, and paralleled a decline in the relative income of doctors in general. The wealth of distinguished doctors also declined relative to other groups of distinguished individuals.In the 19th century, distinction in doctors was accompanied by substantial wealth, whereas by the end of the 20th century, the most distinguished doctors were less wealthy than their contemporaries who had achieved national distinction in other areas.
Modified Glomerular Filtration Rate Estimating Equation for Chinese Patients with Chronic Kidney Disease
Authors: Ying-Chun Ma, Li Zuo, Jiang-Hua Chen, Qiong Luo, Xue-Qing Yu, Ying Li, Jin-Sheng Xu, Song-Min Huang, Li-Ning Wang, Wen Huang, Mei Wang, Guo-Bin Xu, Hai-Yan Wang
Journal: Journal of the American Society of Nephrology (2006)

The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method of assessing GFR in patients with chronic kidney disease (CKD). However, previous research indicated that modification of these equations is necessary for application in Chinese patients with CKD. The objective of this study was to modify MDRD equations on the basis of the data from the Chinese CKD population and compare the diagnostic performance of the modified MDRD equations with that of the original MDRD equations across CKD stages in a multicenter, cross-sectional study of GFR estimation from plasma creatinine, demographic data, and clinical characteristics. A total of 684 adult patients with CKD, from nine geographic regions of China were selected. A random sample of 454 of these patients were included in the training sample set, and the remaining 230 patients were included in the testing sample set. With the use of the dual plasma sampling (99m)Tc-DTPA plasma clearance method as a reference for GFR measurement, the original MDRD equations were modified by two methods: First, by adding a racial factor for Chinese in the original MDRD equations, and, second, by applying multiple linear regression to the training sample and modifying the coefficient that is associated with each variable in the original MDRD equations and then validating in the testing sample and comparing it with the original MDRD equations. All modified MDRD equations showed significant performance improvement in bias, precision, and accuracy compared with the original MDRD equations, and the percentage of estimated GFR that did not deviate >30% from the reference GFR was >75%. The modified MDRD equations that were based on the Chinese patients with CKD offered significant advantages in different CKD stages and could be applied in clinical practice, at least in Chinese patients with CKD.
Molecular cloning and identification of the human interleukin 13 alpha 2 receptor (IL-13Ra2) promoter
Authors: An-hua Wu, Walter C. Low
Journal: Neuro-Oncology (2003)

The interleukin 13 alpha 2 receptor (IL-13Ra2) has been shown to be expressed in most malignant glioblastoma cells. Recent studies suggest that IL-13Ra2 serves as a dominant negative inhibitor or a decoy receptor for IL-13. To investigate the transcriptional regulation of this receptor, we cloned and characterized the promoter for the human IL-13Ra2 gene. Our results demonstrate that this promoter contains three TATA boxes and one CCAAT site. Several putative transcriptional factor binding sites for nuclear factor of activated T cells 1, AP1 (c-JUN and c-FOS), AP2, GABP, OCT1, GATA3, PRE, and C-ETS1 were predicted in the promoter region. Using the secreted alkaline phosphate reporter gene assay, we investigated the functional activity of the human IL-13Ra2 promoter by transient transfection in glioma cell lines U118, U87, and T98, which differ in their expression of the human IL-13Ra2 protein. The different secreted alkaline phosphate activities among these 3 cell lines suggest that the expression of human IL-13Ra2 is regulated at the transcriptional level. Methylation analysis showed that expression of IL-13Ra2 may not be the result of methylation of the CpG dinucleotides in the promoter region of the gene. Deletion analysis identified a 64 base pair (bp) region that is necessary for human IL-13Ra2 promoter activity. This 64-bp sequence contains cis-elements for AP1, nuclear factor of activated T cells, and AP2. The possible role of AP1 in the regulation of human IL-13Ra2 promoter activity was suggested by in vitro mutagenesis and c-JUN N-terminal kinase inhibition analysis.
Glutamine Deprivation Enhances Antitumor Activity of 3-Bromopyruvate through the Stabilization of Monocarboxylate Transporter-1
Authors: Simone Cardaci, Salvatore Rizza, Giuseppe Filomeni, Roberta Bernardini, Fabio Bertocchi, Maurizio Mattei, Maurizio Paci, Giuseppe Rotilio, Maria Rosa Ciriolo
Journal: Cancer Research (2012)

Anticancer drug efficacy might be leveraged by strategies to target certain biochemical adaptations of tumors. Here we show how depriving cancer cells of glutamine can enhance the anticancer properties of 3-bromopyruvate, a halogenated analog of pyruvic acid. Glutamine deprival potentiated 3-bromopyruvate chemotherapy by increasing the stability of the monocarboxylate transporter-1, an effect that sensitized cells to metabolic oxidative stress and autophagic cell death. We further elucidated mechanisms through which resistance to chemopotentiation by glutamine deprival could be circumvented. Overall, our findings offer a preclinical proof-of-concept for how to employ 3-bromopyruvate or other monocarboxylic-based drugs to sensitize tumors to chemotherapy.
ENDOCRINE FACTORS TN ACNE VULGARTS.
Authors: E. LIPMAN COHEN
Journal: British Journal of Dermatology (1941)

Journal Article ENDOCRINE FACTORS TN ACNE VULGARTS. Get access E. LIPMAN COHEN, M.B., B.Chir.Cantab. E. LIPMAN COHEN, M.B., B.Chir.Cantab. Physician to Western Skin Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 53, Issue 8-9, 1 August 1941, Pages 231–254, https://doi.org/10.1111/j.1365-2133.1941.tb10924.x Published: 01 August 1941
Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis
Authors: Robert Lindsay, Jeri Nieves, Carmelo Formica, Emily Henneman, Lillian Woelfert, Victor Shen, David Dempster, Felicia Cosman
Journal: The Lancet (1997)

BackgroundSmall increases in bone mass are commonly seen with existing treatments for osteoporosis, which reduce bone remodelling and primarily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed.MethodsWe did a 3-year randomised controlled trial to find out the effects of 1–34 human parathyroid hormone (hPTH [1–34], 400 U/25 μg daily subcutaneously) in postmenopausal women with osteoporosis taking hormone-replacement therapy (n=17). The controls were women taking hormone-replacement therapy only (n=17). The primary outcome was bone-mineral density of the lumbar vertebrae, with bone-mineral density at other sites and vertebral fractures as secondary endpoints.FindingsPatients taking hormone-replacement therapy and PTH (1–34) had continuous increase in vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in vertebral bone-mineral density was 13·0% (p<0·001); 2·7% at the hip (p=0·05); and 8·0% in total-body bone mineral (p=0·002). No loss of bone mass was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was significant when fractures were taken as a 15% reduction in vertebral height (p=0·04). During the first 6 months of treatment, serum osteocalcin concentration, which reflects bone formation, increased by more than 55%, whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of bone formation and resorption. By 6 months, there were similar increases in both markers, which gradually returned towards baseline as the study progressed. Vertebral bone-mineral density increased most during the first year of PTH treatment.InterpretationWe found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy. PTH also increases total-body bone mineral, with no detrimental effects at any skeletal site. The increased vertebral mass was associated with a reduced rate of vertebral fracture, despite increased bone turnover. Bone-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important implications for the treatment of postmenopausal osteoporosis.
Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers
Authors: Alayne L Brunner, Andrew H Beck, Badreddin Edris, Robert T Sweeney, Shirley X Zhu, Rui Li, Kelli Montgomery, Sushama Varma, Thea Gilks, Xiangqian Guo, Joseph W Foley, Daniela M Witten, Craig P Giacomini, Ryan A Flynn, Jonathan R Pollack, Robert Tibshirani, Howard Y Chang, Matt van de Rijn, Robert B West
Journal: Genome biology (2012)

Abstract Background Molecular characterization of tumors has been critical for identifying important genes in cancer biology and for improving tumor classification and diagnosis. Long non-coding RNAs, as a new, relatively unstudied class of transcripts, provide a rich opportunity to identify both functional drivers and cancer-type-specific biomarkers. However, despite the potential importance of long non-coding RNAs to the cancer field, no comprehensive survey of long non-coding RNA expression across various cancers has been reported. Results We performed a sequencing-based transcriptional survey of both known long non-coding RNAs and novel intergenic transcripts across a panel of 64 archival tumor samples comprising 17 diagnostic subtypes of adenocarcinomas, squamous cell carcinomas and sarcomas. We identified hundreds of transcripts from among the known 1,065 long non-coding RNAs surveyed that showed variability in transcript levels between the tumor types and are therefore potential biomarker candidates. We discovered 1,071 novel intergenic transcribed regions and demonstrate that these show similar patterns of variability between tumor types. We found that many of these differentially expressed cancer transcripts are also expressed in normal tissues. One such novel transcript specifically expressed in breast tissue was further evaluated using RNA in situ hybridization on a panel of breast tumors. It was shown to correlate with low tumor grade and estrogen receptor expression, thereby representing a potentially important new breast cancer biomarker. Conclusions This study provides the first large survey of long non-coding RNA expression within a panel of solid cancers and also identifies a number of novel transcribed regions differentially expressed across distinct cancer types that represent candidate biomarkers for future research.
Individual Mindfulness-Based Cognitive Therapy and Cognitive Behavior Therapy for Treating Depressive Symptoms in Patients With Diabetes: Results of a Randomized Controlled Trial
Authors: K. Annika Tovote, Joke Fleer, Evelien Snippe, Anita C.T.M. Peeters, Paul M.G. Emmelkamp, Robbert Sanderman, Thera P. Links, Maya J. Schroevers
Journal: Diabetes Care (2014)

OBJECTIVE Depression is a common comorbidity of diabetes, undesirably affecting patients’ physical and mental functioning. Psychological interventions are effective treatments for depression in the general population as well as in patients with a chronic disease. The aim of this study was to assess the efficacy of individual mindfulness-based cognitive therapy (MBCT) and individual cognitive behavior therapy (CBT) in comparison with a waiting-list control condition for treating depressive symptoms in adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled trial, 94 outpatients with diabetes and comorbid depressive symptoms (i.e., Beck Depression Inventory-II [BDI-II] ≥14) were randomized to MBCT (n = 31), CBT (n = 32), or waiting list (n = 31). All participants completed written questionnaires and interviews at pre- and postmeasurement (3 months later). Primary outcome measure was severity of depressive symptoms (BDI-II and Toronto Hamilton Depression Rating Scale). Anxiety (Generalized Anxiety Disorder 7), well-being (Well-Being Index), diabetes-related distress (Problem Areas In Diabetes), and HbA1c levels were assessed as secondary outcomes. RESULTS Results showed that participants receiving MBCT and CBT reported significantly greater reductions in depressive symptoms compared with patients in the waiting-list control condition (respectively, P = 0.004 and P &amp;lt; 0.001; d = 0.80 and 1.00; clinically relevant improvement 26% and 29% vs. 4%). Both interventions also had significant positive effects on anxiety, well-being, and diabetes-related distress. No significant effect was found on HbA1c values. CONCLUSIONS Both individual MBCT and CBT are effective in improving a range of psychological symptoms in individuals with type 1 and type 2 diabetes.
Finishing the finished human chromosome 22 sequence
Authors: Charlotte G Cole, Owen T McCann, John E Collins, Karen Oliver, David Willey, Susan M Gribble, Fengtang Yang, Karen McLaren, Jane Rogers, Zemin Ning, David M Beare, Ian Dunham
Journal: Genome biology (2008)

Abstract Background Although the human genome sequence was declared complete in 2004, the sequence was interrupted by 341 gaps of which 308 lay in an estimated approximately 28 Mb of euchromatin. While these gaps constitute only approximately 1% of the sequence, knowledge of the full complement of human genes and regulatory elements is incomplete without their sequences. Results We have used a combination of conventional chromosome walking (aided by the availability of end sequences) in fosmid and bacterial artificial chromosome (BAC) libraries, whole chromosome shotgun sequencing, comparative genome analysis and long PCR to finish 8 of the 11 gaps in the initial chromosome 22 sequence. In addition, we have patched four regions of the initial sequence where the original clones were found to be deleted, or contained a deletion allele of a known gene, with a further 126 kb of new sequence. Over 1.018 Mb of new sequence has been generated to extend into and close the gaps, and we have annotated 16 new or extended gene structures and one pseudogene. Conclusion Thus, we have made significant progress to completing the sequence of the euchromatic regions of human chromosome 22 using a combination of detailed approaches. Our experience suggests that substantial work remains to close the outstanding gaps in the human genome sequence.
The Opitz Syndrome Gene Mid1 Is Transcribed from a Human Endogenous Retroviral Promoter
Authors: Josette-Renée Landry, Arefeh Rouhi, Patrik Medstrand, Dixie L. Mager
Journal: Molecular Biology and Evolution (2002)

Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-containing elements comprise a significant portion (8%) of the human genome and are likely vestiges of retroviral infections during primate evolution. Many of the HERVs present in human DNA have retained functional promoter, enhancer, and polyadenylation signals, and these regulatory sequences have the potential to modify the expression of nearby genes. To identify retroviral elements that contribute to the transcription of human genes, we screened sequence databases for chimeric (viral-cellular) transcripts. These searches revealed a fusion transcript containing the LTR of an HERV-E element linked to the Opitz syndrome gene Mid1. We confirmed the authenticity of the chimeric transcript by 5' rapid amplification of cDNA ends (RACE) and established that the Mid1 mRNA isoform was transcribed from a retroviral LTR. The identification of a retroviral first exon suggested the existence of alternative promoters for Mid1 because nonretroviral (native) 5' untranslated regions (UTRs) had been reported previously for this gene. Although Mid1 transcripts could be detected in all tissues tested, quantitative real-time reverse transcription-polymerase chain reaction indicated that the retroviral promoter contributes significantly to the level of Mid1 transcripts in placenta and embryonic kidney, where chimeric mRNAs were found to represent 25% and 22% of overall Mid1 mRNAs, respectively. Transient transfection studies supported a role for the LTR as a strong tissue-specific promoter in placental and embryonic kidney cell lines and suggested a function for the LTR as an enhancer. These findings provide further evidence that some endogenous retroviruses have evolved a biological function by contributing transcriptional regulatory elements to cellular genes.
A shot in the back
Authors: B. Inman
Journal: BMJ (1995)

Most of us suffer from back pain at some time in our lives. When analgesic tablets, physiotherapists, osteopaths, and faith healers have failed us we may turn to the anaesthetist, who will try injecting lignocaine or steroids into the extradural space at the bottom of the spine. All forms of treatment carry some risk, and occasionally something will go wrong. The question is, who is to blame?

World in Action set out to investigate claims that a multinational drug company had pressured doctors into giving steroids by an unauthorised route—into the epidural space. …
Acetylcholinesterase containing nerve fibres in coronary circulation
Authors: F. AMENTA, F. FERRANTE, C. CAVALLOTTI
Journal: Cardiovascular Research (1981)

Journal Article Acetylcholinesterase containing nerve fibres in coronary circulation Get access FRANCESCO AMENTA, FRANCESCO AMENTA * From the Laboratorio di Neurobiologia, Istituto di Anatomia Umana Normale Università di Roma, Italy *Please address correspondence and reprint requests to: Dr Francesco Amenta, Laboratorio di Neurobiologia, Istituto di Anatomia Umana Normale, V le Regina Elena n 289-1 00161 Roma (Italy). Search for other works by this author on: Oxford Academic PubMed Google Scholar FABIO FERRANTE, FABIO FERRANTE From the Laboratorio di Neurobiologia, Istituto di Anatomia Umana Normale Università di Roma, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar CARLO CAVALLOTTI CARLO CAVALLOTTI From the Laboratorio di Neurobiologia, Istituto di Anatomia Umana Normale Università di Roma, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 15, Issue 3, March 1981, Pages 171–174, https://doi.org/10.1093/cvr/15.3.171 Published: 01 March 1981
Relation between hepatic expression of ATP-binding cassette transporters G5 and G8 and biliary cholesterol secretion in mice
Authors: Astrid Kosters, Raoul J.J.M. Frijters, Frank G. Schaap, Edwin Vink, Torsten Plösch, Roelof Ottenhoff, Milan Jirsa, Iris M. De Cuyper, Folkert Kuipers, Albert K. Groen
Journal: Journal of Hepatology (2003)
Diabetes and Coronary Heart Disease in Filipino-American Women
Authors: Claudia Langenberg, Maria Rosario G. Araneta, Jaclyn Bergstrom, Michael Marmot, Elizabeth Barrett-Connor
Journal: Diabetes Care (2007)

OBJECTIVE—To investigate associations between adult markers of childhood growth and the prevalence of diabetes and coronary heart disease (CHD) in Filipino-American women and to determine the role of social and educational differences, including the influence of social mobility between childhood and adulthood. RESEARCH DESIGN AND METHODS—Socioeconomic disadvantage and poor infant growth, resulting in short leg length, may contribute to the dramatically increased risk of diabetes and CHD in Filipino-American women, but this has not been investigated. This study is a cross-sectional study of 389 Filipino-American women (age 58.7 ± 9.4 years [mean ± SD]). Diabetes was defined by 1999 World Health Organization criteria and CHD by ischemic electrocardiogram changes, Rose angina, a history of myocardial infarction, or revascularization surgery. A score of social mobility (0–4) was calculated by summarizing childhood and adult financial circumstances. RESULTS—Diabetes prevalence (31.4%) was not associated with measures of growth but was significantly lower in women with greater education, childhood and adult income, or social mobility score. Compared with Filipinas who were poorest in childhood and adulthood, respective odds ratios (95% CI) for diabetes were 0.55 (0.18–1.68), 0.19 (0.06–0.62), and 0.11 (0.03–0.42), down to 0.07 (0.01–0.51) in the most advantaged women (P &amp;lt; 0.0001). Family history of diabetes [5.14 (2.72–9.70)] and larger waist [1.07 per cm (1.03–1.10)] were also significant predictors in multiple adjusted models. In contrast, CHD prevalence (22.4%) was most strongly associated with leg length, but not trunk length; compared with individuals with the shortest legs, respective odds ratios (95% CI) for CHD were 0.60 (0.31–1.19), 0.53 (0.26–1.05), and 0.44 (0.22–0.91) in the tallest group, in age- (Ptrend = 0.02) and multiple-adjusted models (Ptrend = 0.01). CONCLUSIONS—Socioeconomic disadvantage contributes to the high prevalence of diabetes in Filipinas. Factors limiting early growth of the legs may increase the risk of CHD in this comparatively short population.