tbuckley/cabot-search huggingface dataset:
Chlorambucil as a steroid-sparing agent in bullous pemphigoid
Authors: T.A. Chave, N.J. Mortimer, D.S. Shah, P.E. Hutchinson
Journal: British Journal of Dermatology (2004)

Journal Article Chlorambucil as a steroid‐sparing agent in bullous pemphigoid Get access T.A. Chave, T.A. Chave Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail:toby@chave.fsbusiness.co.uk Search for other works by this author on: Oxford Academic Google Scholar N.J. Mortimer, N.J. Mortimer Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail:toby@chave.fsbusiness.co.uk Search for other works by this author on: Oxford Academic Google Scholar D.S. Shah, D.S. Shah Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail:toby@chave.fsbusiness.co.uk Search for other works by this author on: Oxford Academic Google Scholar P.E. Hutchinson P.E. Hutchinson Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail:toby@chave.fsbusiness.co.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 5, 1 November 2004, Pages 1107–1108, https://doi.org/10.1111/j.1365-2133.2004.06241.x Published: 01 November 2004
Effective Targeting of Quiescent Chronic Myelogenous Leukemia Stem Cells by Histone Deacetylase Inhibitors in Combination with Imatinib Mesylate
Authors: Bin Zhang, Adam C. Strauss, Su Chu, Min Li, Yinwei Ho, Keh-Dong Shiang, David S. Snyder, Claudia S. Huettner, Leonard Shultz, Tessa Holyoake, Ravi Bhatia
Journal: Cancer Cell (2010)
Biomarkers of Phenethyl Isothiocyanate-Mediated Mammary Cancer Chemoprevention in a Clinically Relevant Mouse Model
Authors: S. V. Singh, S.-H. Kim, A. Sehrawat, J. A. Arlotti, E.-R. Hahm, K. Sakao, J. H. Beumer, R. C. Jankowitz, K. Chandra-Kuntal, J. Lee, A. A. Powolny, R. Dhir
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundPhenethyl isothiocyanate (PEITC) is a natural plant compound with chemopreventative potential against some cancers and the ability to induce apoptosis in breast cancer cells.
Increased peroxisome proliferator-activated receptor gamma (PPAR) expression in atherectomy specimens from patients with restenosis after percutaneous transluminal coronary angioplasty
Authors: Seiji Hokimoto, Taro Saito, Shuichi Oshima, Katsuo Noda, Yasushi Moriyama, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2002)
An Unusual Form of Purifying Selection in a Sperm Protein
Authors: Alejandro P. Rooney, Jianzhi Zhang, Masatoshi Nei
Journal: Molecular Biology and Evolution (2000)

Protamines are small, highly basic DNA-binding proteins found in the sperm of animals. Interestingly, the proportion of arginine residues in one type of protamine, protamine P1, is about 50% in mammals. Upon closer examination, it was found that both the total number of amino acids and the positions of arginine residues have changed considerably during the course of mammalian evolution. This evolutionary pattern suggests that protamine P1 is under an unusual form of purifying selection, in which the high proportion of arginine residues is maintained but the positions may vary. In this case, we would expect that the rate of nonsynonymous substitution is not particularly low compared with that of synonymous substitution, despite purifying selection. We would also expect that the selection for a high arginine content results in a high frequency of the nucleotide G in the coding region of this gene, because all six arginine codons contain at least one G. These expectations were confirmed in our study of mammalian protamine genes. Analysis of nonmammalian vertebrate genes also showed essentially the same patterns of evolutionary changes, suggesting that this unusual form of purifying selection has been active since the origin of bony vertebrates. The protamine gene of an insect species shows similar patterns, although its purifying selection is less intense. These observations suggest that arginine-rich selection is a general feature of protamine evolution. The driving force for arginine-rich selection appears to be the DNA-binding function of protamine P1 and an interaction with a protein kinase in the fertilized egg.
Textbook of Internal Medicine
Authors: Frank D. Gray
Journal: JAMA (1989)

When perusing a new textbook of medicine, the slow but inexorable progress of medical science stands out in relief as it influences important changes in the practice of medicine. These changes are continuous and pervasive, and they constitute the most important justification for the seemingly endless production of new textbooks striving to keep us in the forefront of our profession. The enormous volume of publications creates a competitive market obliging editors to provide a broad perspective, and if an editor has a large number of diversified authors he can usually assure the reader of a broad perspective, as Kelley does with 529 contributors. I was concerned, however, to observe that several authors have contributed chapters to one or more other current textbooks presumed to be competitors. Are we gestating a new professional class of textbook writers? If it were a trend that might lead to rigid mainstream pronouncements I would
Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes
Authors: David Z.I. Cherney, Vesta Lai, James W. Scholey, Judith A. Miller, Bernard Zinman, Heather N. Reich
Journal: Diabetes Care (2009)

Blockade of the renin-angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes. The recent development of direct renin inhibitors (DRIs) provides a new approach to block the RAS, but the effects of DRIs on renal and systemic vascular function in uncomplicated type 1 diabetes have not been elucidated.Renal hemodynamic function (inulin and paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (flow-mediated dilation [FMD]), and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after administration of aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 diabetes during clamped euglycemia (4-6 mmol/l) and hyperglycemia (9-11 mmol/l).In response to the DRI, plasma renin activity decreased (from 0.40 to 0.13 ng . ml(-1) . h(-1), P < 0.05) and plasma renin increased (from 5.2 to 75.0 ng/l, P < 0.05). Peripheral and central blood pressures decreased, and effective renal plasma flow and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (P < 0.05). The carotid augmentation index during clamped euglycemia decreased (from 26 +/- 6 to 20 +/- 5%, P < 0.05) as did pulse wave velocity during clamped hyperglycemia (from 7.8 +/- 0.6 to 6.8 +/- 0.5 m/s, P < 0.05). In response to the DRI, FMD increased during both clamped euglycemia (from 1.92 +/- 1.13 to 5.55 +/- 0.81%) and hyperglycemia (from 1.86 +/- 0.98 to 5.63 +/- 0.62) as did the vasodilatory response to sublingual nitroglycerin.DRIs exert a renal vasodilatory effect and improve parameters of systemic vascular function, suggesting that blockade of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type 1 diabetes.
Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice
Authors: Hajime Ishii, Yasuo Horie, Shigetoshi Ohshima, Yumiko Anezaki, Nobukatsu Kinoshita, Takahiro Dohmen, Ei Kataoka, Wataru Sato, Takashi Goto, Junko Sasaki, Takehiko Sasaki, Sumio Watanabe, Akira Suzuki, Hirohide Ohnishi
Journal: Journal of Hepatology (2008)
Academic staff frustrated with research assessment exercise
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

Academic staff are deeply dissatisfied with the research assessment exercise, the mechanism that is used to allocate funding in higher education. This is the finding of a survey of clinical academic and research staff in the United Kingdom.

Although a minority (21%) of the 756 academics who returned the BMA's questionnaire said that the assessment exercise had had a positive impact on their career, twice as many (40%) said that it had affected them in a negative way. Two fifths (39%) said that it had not influenced their career.

One respondent wrote, “As [the research assessment exercise] is the only ‘quality’ measure linked to funding, then career progression depends entirely on research …
Temporal synchrony, dynamic bindings, and Shruti: A representational but nonclassical model of reflexive reasoning
Authors: Lokendra Shastri
Journal: Behavioral and Brain Sciences (1996)

Abstract Lange &amp; Dyer misunderstand what is meant by an “entity” and confuse a medium of representation (synchrony) with the content being represented. This leads them to the erroneous conclusion that SHRUTI will run out of phases and that its representation of bindings lacks semantic content. It is argued that (1) the limit on the number of phases suffices, and (2) SHRUTI can be interpreted as using “dynamic signatures” that offer significant advantages over fixed preexisting signatures. Bonatti refers to three levels of commitment to a representational theory of the mind (RTM) and states that SHRUTI is committed to RTM at levels 1 and 2. He acknowledges that SHRUTI is not committed at level 3, but argues that an extended SHRUTI would have to make such a commitment. We agree that SHRUTI is committed to RTM at level 1 and, in a sense, also at level 2. SHRUTI, however, is not committed to RTM at level 3 and, even though it has been extended in several ways, it has retained its original representational character.
Pip5 Transduction Peptides Direct High Efficiency Oligonucleotide-mediated Dystrophin Exon Skipping in Heart and Phenotypic Correction in mdx Mice
Authors: HaiFang Yin, Amer F Saleh, Corinne Betts, Patrizia Camelliti, Yiqi Seow, Shirin Ashraf, Andrey Arzumanov, Suzan Hammond, Thomas Merritt, Michael J Gait, Matthew JA Wood
Journal: Molecular Therapy (2011)

Induced splice modulation of pre-mRNAs shows promise to correct aberrant disease transcripts and restore functional protein and thus has therapeutic potential. Duchenne muscular dystrophy (DMD) results from mutations that disrupt the DMD gene open reading frame causing an absence of dystrophin protein. Antisense oligonucleotide (AO)-mediated exon skipping has been shown to restore functional dystrophin in mdx mice and DMD patients treated intramuscularly in two recent phase 1 clinical trials. Critical to the therapeutic success of AO-based treatment will be the ability to deliver AOs systemically to all affected tissues including the heart. Here, we report identification of a series of transduction peptides (Pip5) as AO conjugates for enhanced systemic and particularly cardiac delivery. One of the lead peptide-AO conjugates, Pip5e-AO, showed highly efficient exon skipping and dystrophin production in mdx mice with complete correction of the aberrant DMD transcript in heart, leading to >50% of the normal level of dystrophin in heart. Mechanistic studies indicated that the enhanced activity of Pip5e-phosphorodiamidate morpholino (PMO) is partly explained by more efficient nuclear delivery. Pip5 series derivatives therefore have significant potential for advancing the development of exon skipping therapies for DMD and may have application for enhanced cardiac delivery of other biotherapeutics. Induced splice modulation of pre-mRNAs shows promise to correct aberrant disease transcripts and restore functional protein and thus has therapeutic potential. Duchenne muscular dystrophy (DMD) results from mutations that disrupt the DMD gene open reading frame causing an absence of dystrophin protein. Antisense oligonucleotide (AO)-mediated exon skipping has been shown to restore functional dystrophin in mdx mice and DMD patients treated intramuscularly in two recent phase 1 clinical trials. Critical to the therapeutic success of AO-based treatment will be the ability to deliver AOs systemically to all affected tissues including the heart. Here, we report identification of a series of transduction peptides (Pip5) as AO conjugates for enhanced systemic and particularly cardiac delivery. One of the lead peptide-AO conjugates, Pip5e-AO, showed highly efficient exon skipping and dystrophin production in mdx mice with complete correction of the aberrant DMD transcript in heart, leading to >50% of the normal level of dystrophin in heart. Mechanistic studies indicated that the enhanced activity of Pip5e-phosphorodiamidate morpholino (PMO) is partly explained by more efficient nuclear delivery. Pip5 series derivatives therefore have significant potential for advancing the development of exon skipping therapies for DMD and may have application for enhanced cardiac delivery of other biotherapeutics.
Antibodies to adalimumab are associated with future inflammation in Crohn's patients receiving maintenance adalimumab therapy: a post hoc analysis of the Karmiris trial
Authors: Filip Baert, Venkateswarlu Kondragunta, Steven Lockton, Niels Vande Casteele, Scott Hauenstein, Sharat Singh, Konstantinos Karmiris, Marc Ferrante, Ann Gils, Séverine Vermeire
Journal: Gut (2015)

<h3>Introduction</h3> Data on immunogenicity to adalimumab (ADL) therapy in patients with IBD is limited. We performed additional analyses on the Karmiris cohort using the homogeneous mobility shift assay (HMSA) focusing on the inter-relationship of serum ADL concentration, antibodies-to-adalimumab (ATA), inflammatory markers and sustained response. <h3>Methods</h3> 536 prospectively collected serum samples were available for analysis of ADL concentration and ATA using HMSA. We studied the role of week 4 serum ADL concentration and immunomodulator (IMM) use on ATA formation with a Cox proportional hazards model. Mixed model repeated measures analysis was performed to assess the independent effects of serum ADL concentration and ATA on C-reactive protein (CRP) and response. <h3>Results</h3> ATA was detected in 20% of patients after a median of 34 (12.4–60.5) weeks. ATA-positive samples correlated with lower serum ADL concentration (p&lt;0.001). Cox regression modelling showed that week 4 ADL concentration of &lt;5 µg/mL significantly increased the future risk of ATA formation (HR=25.1; 95% CI 5.6 to 111.9; p=0.0002) and that IMM co-treatment prevented ATA formation (HR=0.23; 95% CI 0.06 to 0.86; p=0.0293). Regression modelling showed a negative correlation between CRP and ADL concentration (p=0.0001) and a positive one with ATA (p=0.0186). The model revealed that both lower serum ADL concentration and ATA were independently associated with future CRP (p=0.0213 and p=0.0013 respectively). ATA positivity was associated with discontinuation of ADL because of loss or response (OR=3.04; 95% CI 1.039 to 9.093; p=0.034). <h3>Conclusions</h3> ATA were detected in 20% of patients. Risk of ATA formation increased with lower early serum ADL concentration and in patients not on IMM. ATA and ADL were strongly associated with higher future CRP level and discontinuation of ADL.
Arterial haemodynamics and coronary artery calcification in adult patients with juvenile idiopathic arthritis
Authors: Hanne A Aulie, Anne M Selvaag, Anne Günther, Vibke Lilleby, Øyvind Molberg, Anders Hartmann, Hallvard Holdaas, Berit Flatø
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To compare arterial haemodynamics in adults with long-term juvenile idiopathic arthritis (JIA) to that of healthy controls, and explore the influence of traditional cardiovascular risk factors and disease characteristics on arterial haemodynamics plus coronary artery calcification. <h3>Methods</h3> 87 JIA patients (median age 38.4 years) with persistently active disease at least 15 years after disease onset (registered by longitudinal follow-up), were re-examined after median 29 years and compared with 87 matched controls. Arterial haemodynamics were characterised by arterial stiffness and blood pressure. Sphygmocor was used to measure the arterial stiffness markers pulse wave velocity (PWV) and augmentation index (AIx). Coronary calcification was assessed by CT. <h3>Results</h3> Compared to controls, patients had significantly higher PWV (7.2 vs 6.9 m/s, p=0.035), and systolic and diastolic blood pressure (SBP, p=0.050 and DBP, p=0.029). AIx was numerically higher in the patients compared to the controls, but no statistically significant difference was found. Coronary calcification was present in 22 (26%) of the patients. Daily smoking was more frequent (p=0.043), and insulin resistance was higher (p=0.034) in patients than controls. In patients, DBP, but no disease variables were determinants of PWV. Disease variables as well as traditional cardiovascular risk factors were associated with higher AIx, DBP and the presence of coronary calcification. <h3>Conclusions</h3> JIA patients with long-term active disease had altered arterial haemodynamics compared with controls in our study. PWV was mainly determined by increased DBP, a parameter that again was associated with JIA disease and treatment variables.
Hyperhomocysteinemia from trimethylation of hepatic phosphatidylethanolamine during cholesterol cholelithogenesis in inbred mice
Authors: Ji Zhang, Diane E. Handy, Yufang Wang, Guylaine Bouchard, Jacob Selhub, Joseph Loscalzo, Martin C. Carey
Journal: Hepatology (2011)

Because hyperhomocysteinemia can occur in cholesterol gallstone disease, we hypothesized that this may result from trimethylation of phosphatidylethanolamine (PE), which partakes in biliary phosphatidylcholine (PC) hypersecretion during cholesterol cholelithogenesis. We fed murine strains C57L/J, C57BL/6J, SWR/J, AKR/J, PE N -methyltransferase (PEMT) knockout (KO), PEMT heterozygous (HET), and wildtype (WT) mice a cholesterol/cholic acid lithogenic diet (LD) for up to 56 days and documented biliary lipid phase transitions and secretion rates. We quantified plasma total homocysteine (tHcy), folate, and vitamin B12 in plasma and liver, as well as biliary tHcy and cysteine secretion rates. Rate-limiting enzyme activities of PC synthesis, PEMT and cytidine triphosphate: phosphocholine cytidylyltransferase (PCT), S -adenosylmethionine (SAM), and S -adenosylhomocysteine (SAH) were measured in liver homogenates. Other potential sources of plasma tHcy, glycine N -methyltransferase (GNMT) and guanidinoacetate N -methyltransferase (GAMT), were assayed by gene expression. Plasma tHcy and PEMT activities became elevated during cholelithogenesis in gallstone-susceptible C57L, C57BL/6, and SWR mice but not in the gallstone-resistant AKR mice. Persisting in C57L mice, which exhibit the greatest Lith gene burden, these increases were accompanied by elevated hepatic SAM/SAH ratios and augmented biliary tHcy secretion rates. Counter-regulation included remethylation of Hcy to methionine concurrent with decreased folate and vitamin B12 levels and Hcy transsulfuration to cysteine. Concomitantly, methylenetetrahydrofolate reductase ( Mthfr ), betaine-homocysteine methyltransferase ( Bhmt ), and cystathionine-β-synthase ( Cbs ) were up-regulated, but Gnmt and Gamt genes were down-regulated. PEMT KO and HET mice displayed biliary lipid secretion rates and high gallstone prevalence rates similar to WT mice without any elevation in plasma tHcy levels. Conclusion: This work implicates up-regulation of PC synthesis by the PEMT pathway as a source of elevated plasma and bile tHcy during cholesterol cholelithogenesis. (Hepatology 2011;)
Health information for all by 2015?
Authors: Richard Smith
Journal: BMJ (2004)

In my increasingly desperate search for originality in editor's choice I've come up with something devilishly simple: choose something from the Lancet . I urge you to read “Can we achieve health information for all by 2015?” by Fiona Godlee and others, which was posted on the Lancet website on 9 July (http://image.thelancet.com/extras/04art6112web.pdf). This move isn't quite as crazy as it seems as the article is free, hugely important, written in part by a BMJ employee, and coincides with a meeting held this week in BMA House.

The meeting marked the tenth anniversary of our first meeting …
IMPAIRMENT OF PLATELET FUNCTION BY GROWTH-HORMONE RELEASE- INHIBITING HORMONE
Authors: G.M. Besser, A.M. Paxton, S.A.N. Johnson, E.J. Moody, C.H. Mortimer, R. Hall, A. Gomez-Pan, A.V. Schally, A.J. Kastin, D.H. Coy
Journal: The Lancet (1975)
Effects of appendicectomy on the course of ulcerative colitis
Authors: J Cosnes
Journal: Gut (2002)

<b>Background:</b> Appendicectomy reduces the risk of having ulcerative colitis. However, its effect on the natural history of ulcerative colitis remains uncertain. <b>Aim:</b> To determine whether appendicectomy reduces the overall severity of ulcerative colitis. <b>Patients and methods:</b> Appendicectomy status and smoking habits were specified by direct interview in 638 patients seen consecutively between 1997 and 2000. Severity of ulcerative colitis was assessed by reviewing therapeutic needs from the onset of colitis. Additionally, the annual incidence of flare up was assessed prospectively between 1997 and 2000 in patients who had not been colectomised. <b>Results:</b> The 10 year risk of colectomy was 16 (7)% in previously appendicectomised patients (n=49) compared with 33 (2)% in non-appendicectomised patients (n=589, p=0.05). Cox regression showed that previous appendicectomy and current smoking were independent factors protecting against colectomy (adjusted hazard ratio and 95% confidence intervals: 0.40 (0.20–0.78) and 0.60 (0.40–0.95), respectively). The respective proportions of appendicectomised and non-appendicectomised patients who required oral steroids and immunosuppressive therapy were not significantly different (67% <i>v</i> 70% and 27% <i>v</i> 19%, respectively). Between 1997 and 2000, ulcerative colitis was active for 48% of the time in appendicectomised patients (47 of 98 patient years) and for 62% of the time in non-appendicectomised patients (631 of 1024 patient years; p&lt;0.01). <b>Conclusion:</b> Previous appendicectomy is associated with a less severe course of ulcerative colitis. The beneficial effect of appendicectomy on the risk of colectomy is additive to that of current smoking.
Detecting abnormalities in left ventricular function during exercise by respiratory measurement.
Authors: A Koike, H Itoh, K Taniguchi, M Hiroe
Journal: Circulation (1989)

The degree of exercise-induced cardiac dysfunction and its relation to the anaerobic threshold were evaluated in 23 patients with chronic heart disease. A symptom-limited exercise test was performed with a cycle ergometer with work rate increased by 1 W every 6 seconds. Left ventricular function, as reflected by ejection fraction, was continuously monitored with a computerized cadmium telluride detector after the intravenous injection of technetium-labeled red blood cells. The anaerobic threshold (mean, 727 +/- 166 ml/min) was determined by the noninvasive measurement of respiratory gas exchange. As work rate rose, the left ventricular ejection fraction increased but reached a peak value at the anaerobic threshold and then fell below resting levels. Ejection fraction at rest, anaerobic threshold, and peak exercise were 41.4 +/- 11.3%, 46.5 +/- 12.0%, and 37.2 +/- 11.0%, respectively. Stroke volume also increased from rest (54.6 +/- 17.0 ml/beat) to the point of the anaerobic threshold (65.0 +/- 21.2 ml/beat) and then decreased at peak exercise (52.4 +/- 18.7 ml/beat). The slope of the plot of cardiac output versus work rate decreased above the anaerobic threshold. The anaerobic threshold occurred at the work rate above which left ventricular function decreased during exercise. Accurate determination of the anaerobic threshold provides an objective, noninvasive measure of the oxygen uptake above which exercise-induced deterioration in left ventricular function occurs in patients with chronic heart disease.