tbuckley/cabot-search huggingface dataset:
Forced myocardin expression primes cardiac and smooth muscle transcription patterning in human mesenchymal stem cells
Authors: C VENTURA
Journal: Cardiovascular Research (2005)

See article by van Tuyn et al.  [7]  (pages 245–255) in this issue. 

Loss of cardiomyocytes during myocardial infarction or hereditary cardiomyopathies may represent a major determinant in the progression toward heart failure. The reported ability of haematopoietic bone marrow cells to afford myocardial regeneration after direct injection in experimental animals [1] has triggered a number of clinical trials in humans. Nevertheless, the initial observations and the scientific underpinning of the human trials have been challenged by a number of studies using a foreign gene, LacZ or GFP, to track the fate of haematopoietic stem cells after transplant into normal and/or injured mouse hearts [2,3]. In these studies, no transdifferentiation into cardiomyocytes was detectable, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, raising a cautionary note for clinical studies of infarct repair.

These controversial results emphasize the need to assess whether cardiac lineage-committable cells may be comprised within the bone marrow, and prompt further studies to dissect the signals … 

*Present address: S. Orsola-Malpighi Hospital, Institute of Cardiology, Via Massarenti N.g, 40138 Bologna, Italy. Tel.: +39 051 6363605; fax: +39 051 344859. Email address: cvent{at}libero.it
Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial
Authors: M.R. Alidaee, A. Taheri, P. Mansoori, S.Z. Ghodsi
Journal: British Journal of Dermatology (2005)

Background Aphthous stomatitis is a painful, recurrent disease of the oral mucous membrane. Silver nitrate sticks have been used for a long time to provide pain relief for the duration of an aphthous ulceration, with only one application. Silver nitrate causes chemical cauterization and increases the depth of injury. Objectives To study the effect of chemical cautery with silver nitrate in reducing pain of aphthous ulceration and to determine if this treatment shortens or prolongs healing. Methods In a randomized, patient-blinded, placebo-controlled study, 97 patients with painful minor oral aphthous ulceration were randomized to receive silver nitrate cautery or placebo. The severity of pain was rated on a three-category scale (severe, mild, none) and was recorded each day until the seventh day after the procedure. The lesion size was recorded at the time of the procedure and on the seventh day afterwards. In the treatment group, the ulcer was gently painted with a silver nitrate stick until it turned white. In the placebo group, the ulcer was gently painted with a placebo stick. Results In the treatment group, 33 of 47 patients (70%) evaluated and in the placebo group, four of 38 patients (11%) evaluated had reduction in severity of pain 1 day after the procedure. The difference was statistically significant (P < 0·001). On the seventh day after the procedure, the ulcers were completely re-epithelialized in 39 patients (83%) in the treatment group and in 34 patients (89%) in the placebo group. The difference was not statistically significant (P = 0·39). Conclusions The results of our study showed that one application of silver nitrate can decrease the severity of pain in aphthous ulceration without significantly shortening or prolonging healing time. We did not observe any side-effects in our study. The effect is rapid and lasts for the duration of the lesion. The treatment is simple and cost-effective in patients with infrequent recurrences.
Transcriptional and post-translational regulation of Flip, an inhibitor of Fas-mediated apoptosis, in human gut inflammation
Authors: F Caprioli, C Stolfi, R Caruso, D Fina, G Sica, L Biancone, F Pallone, G Monteleone
Journal: Gut (2008)

<h3>Objective:</h3> Defects in Fas-mediated apoptosis are supposed to contribute to the accumulation of T lymphocytes in the gut of patients with Crohn’s disease (CD). This phenomenon has been functionally linked with the elevated expression of Flip, an inhibitor of Fas-mediated apoptosis. In this study, the molecular mechanisms that control Flip in CD were examined. <h3>Methods:</h3> Paired colonic biopsies of patients with CD, patients with ulcerative colitis (UC) and normal controls were analysed for Flip by real-time PCR and western blotting. Flip was also evaluated in CD3<sup>+</sup> lamina propria lymphocytes (T-LPLs) cultured with tosyl phenylalanyl chloromethyl ketone (TPCK; a nuclear factor-κB (NF-κB) inhibitor), AG490 (a Janus kinase 2 (Jak2)/signal transducer and activator of transcription (Stat) inhibitor) or 17-desmethoxy-17-<i>N</i>,<i>N</i>-dimethylamino-geldanamycin (DMAG; an inhibitor of heat shock protein 90). The rate of apoptosis was examined by flow cytometry. <h3>Results:</h3> In CD, upregulation of Flip occurred at both the RNA and protein level. Treatment of CD CD3<sup>+</sup> T-LPLs with TPCK or AG490 markedly reduced Flip RNA, suggesting a role for NF-κB and Jak/Stat pathways in the transcriptional control of Flip in this condition. Consistently, both TPCK and AG490 sensitised CD T-LPLs to Fas-mediated apoptosis. Flip protein in cells from normal gut was rapidly degraded by the proteasome pathway. In contrast, in inflamed gut of both CD and UC patients, there was a reduced degradation of Flip via the ubiquitin–proteasome-dependent pathway, but Flip expression can be decreased by DMAG. <h3>Conclusions:</h3> The data demonstrate that Flip is regulated at both the transcriptional and post-translational level in CD, and indicate that in the normal but not inflamed gut Flip is degraded via the ubiquitin–proteasome-dependent pathway.
Selective inhibition by des-1-Asp-8-lle-angiotensin ii of the steroidogenic response to restricted sodium intake in the rat.
Authors: C A Sarstedt, E D Vaughan, M J Peach
Journal: Circulation Research (1975)

Angiotensin III (des-1-Asp-angiotensin II) is a potent steriodogenic agent in many species. The effects of the heptapeptide in the adrenal zona glomerulosa are resistant to blockade by C-terminally substituted analogues of angiotensin II (1-Sar-8-Ile- or 1-Sar-8-Ala-octapeptides). For this reason, the effects of 7-Ile-angiotensin III, a C-terminally substituted analogue of the heptapeptide, and 1-Sar-8-Ile-angiotensin II on aldosterone biosynthesis in rabbit adrenal cortical cell suspensions and on urinary aldosterone excretion in sodium-deprived rats were studied. In the vitro studies, 7-Ile-angiotensin III was a better antagonist of angiotensin II- or angiotensin III-induced steroidogenesis than was 1-Sar-8-Ile-angiotensin II. In the rats, subcutaneously administered 1-Sar-8-Ile-angiotensin II (0.9 mumoles/kg) produced prolonged blockade of the pressor responses to exogenous angiotensin II. 70Ile-angiotensin III (0.9 mumoles/kg) had no effect on resting blood pressure or on blood pressure responses to angiotensin II infusions. At the doses studied, however, 7-Ile-angiotensin III caused a marked decrease (50%) in aldosterone excretion in sodium-deprived rats, but 1-Sar-8-Ile-angiotensin II had no effect on aldosterone excretion. In the sodium-deprived rats, the administration of 7-Ile-angiotensin Ile was not associated with an acute increase in plasma renin activity, but treatment with 1-Sar-8-Ile-angiotensin II resulted in a sixfold increase in plasma renin activity, but otensin III was not associated with an acute increase in plasma renin activity, but treatment with 1-Sar-8-Ile-angiotensin II resulted in a sixfold increase in plasma renin activity. These results are consistent with a role for angiotensin III in the control of aldosterone biosynthesis.
The effect of fasting, diet, and actinomycin D on insulin secretion in the rat
Authors: N. J. Grey, S. Goldring, D. M. Kipnis
Journal: Journal of Clinical Investigation (1970)

The present studies were performed to elucidate the mechanisms responsible for the impairment of glucose-stimulated insulin secretion observed in fasting. Rats fasted for 48 hr displayed marked impairment in their insulin secretory response to both oral and intravenous glucose. Glucose-stimulated insulin secretion was restored within 24 hr by refeeding; actinomycin D given before refeeding blocked the expected return of normal glucose-stimulated insulin secretion despite adequate food intake. Fasted rats refed a diet devoid of carbohydrate failed to display a return of normal insulin secretory responsiveness to oral glucose in contrast to rats fed isocalorically a high carbohydrate diet. Differences in insulin secretion in fed, fasted, and fasted-refed rats could not be attributed to changes in pancreatic insulin content. There was no significant difference in the insulin secretory response to aminophylline of fed, fasted, or fasted-refed rats. The intermittent pulsing of fasted rats with hyperglycemic episodes by the injection of small amounts of glucose (500 mg) intraperitoneally every 8 hr ameliorated the impairment of glucose-stimulated insulin secretion characteristic of the fasting state. These results suggest that the impairment of glucose-stimulated insulin secretion during fasting and its restoration by refeeding are regulated by changes in a glucose-inducible enzyme system in the pancreatic beta cell.
Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins
Authors: J Kim, H A Reber, S M Dry, D Elashoff, S L Chen, N Umetani, M Kitago, O J Hines, K K Kazanjian, S Hiramatsu, A J Bilchik, S Yong, M Shoup, D S B Hoon
Journal: Gut (2006)

Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer.To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised disease.Seventy patients who underwent curative resection for pancreatic ductal adenocarcinoma were evaluated.All patients had surgical resection margins (pancreatic transection and retroperitoneal) that were histologically free of invasive cancer. DNA was extracted from these paraffin embedded surgical margins and assessed by quantitative real time polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors.K-ras mutation was detected in histologically negative surgical margins of 37 of 70 (53%) patients. A significant difference in overall survival was demonstrated between patients with margins that were K-ras mutation positive compared with negative (median 15 v 55 months, respectively; p = 0.0008). By univariate and multivariate analyses, detection of K-ras mutation in the margins was a significant prognostic factor for poor survival (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95% CI 1.4-5.5), p = 0.004, respectively).Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.
Year in review in Intensive Care Medicine 2010: III. ARDS and ALI, mechanical ventilation, noninvasive ventilation, weaning, endotracheal intubation, lung ultrasound and paediatrics
Authors: Massimo Antonelli, Elie Azoulay, Marc Bonten, Jean Chastre, Giuseppe Citerio, Giorgio Conti, Daniel De Backer, Herwig Gerlach, Goran Hedenstierna, Michael Joannidis, Duncan Macrae, Jordi Mancebo, Salvatore M. Maggiore, Alexandre Mebazaa, Jean-Charles Preiser, Jerôme Pugin, Jan Wernerman, Haibo Zhang
Journal: Intensive Care Medicine (2011)

Year in review in Intensive Care Medicine 2010 : III. ARDS and ALI, mechanical ventilation, noninvasive ventilation, weaning, endotracheal intubation, lung ultrasound and paediatrics
Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during Fas-mediated apoptosis.
Authors: Q Tian, J Taupin, S Elledge, M Robertson, P Anderson
Journal: The Journal of Experimental Medicine (1995)

We have identified a serine/threonine kinase that is rapidly activated during Fas-mediated apoptosis. Fas-activated serine/threonine kinase (FAST) is phosphorylated on serine and threonine residues in Jurkat cells. In response to Fas ligation, it is rapidly dephosphorylated and concomitantly activated to phosphorylate TIA-1, a nuclear RNA-binding protein that has been implicated as an effector of apoptosis. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation, suggesting a role in signaling downstream events in the apoptotic program. Our results introduce Fast and TIA-1 as components of a molecular cascade involved in signaling Fas-mediated apoptosis.
Ring-like elevations in the large bowel: endoscopic signs to distinguish the artefact from true neoplastic lesions Reply
Authors: M MATSUSHITA
Journal: Gut (2000)

Editor,—We read with great interest the article by Martin et al ( Gut 1999; 45 :147) on normal histological findings in small depressed lesions of the large bowel. They described three patients with 7–8 mm depressed rectal lesions, similar to small flat or depressed neoplastic lesions, during sigmoidoscopy (two cases) and total colonoscopy (one case). Specimens taken by extensive biopsy or removed by endoscopic mucosectomy were histologically normal with no evidence of neoplasia. Two weeks later, colonoscopy with chromoscopy in one patient failed to locate the lesion. In contrast to true flat adenomas characterised by rough, reddened central mucosa and an irregular outline, the lesions had normal central mucosa and a regular circular elevation. The authors therefore concluded that flat … Dr J Martin (email:jplmartin{at}aol.com) Dr J Martin (email:jplmartin{at}aol.com)
Neural Correlates of Stress- and Food Cue–Induced Food Craving in Obesity
Authors: Ania M. Jastreboff, Rajita Sinha, Cheryl Lacadie, Dana M. Small, Robert S. Sherwin, Marc N. Potenza
Journal: Diabetes Care (2012)

Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR.Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI.Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus.These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.
Scrutiny phase brings chance of change to NHS reform bill
Authors: A. O'Dowd
Journal: BMJ (2011)

Interested parties are hopeful that important changes to the government’s planned reforms of the NHS can be achieved now that the Health and Social Care Bill enters its next parliamentary phase before becoming law.

After a comfortable vote supporting it in the House of Commons on 31 January ( BMJ 2011;342:d711, doi:10.1136/bmj.d711) the bill is due to be scrutinised by a newly appointed committee of 26 MPs.

The committee is made up of 11 Conservatives, three Liberal Democrats, 11 Labour MPs, and one Democratic Unionist Party MP. Members include Kevin Barron, the Labour MP for Rother Valley and former chairman of the health select committee, the current health ministers Simon Burns and Paul Burstow, and Daniel Poulter, the Conservative MP for Central Suffolk and North Ipswich and an NHS doctor.

The committee stage is crucial as it allows all interested parties to submit written and oral evidence before the end of March and to propose amendments to the bill before it is debated again in the House of Commons in its third reading. The bill may become law as early as July this year or as late as spring 2012.

Several witnesses are due to appear before the committee on Tuesday 8 and Thursday 10 February. These include the NHS chief executive, David Nicholson; the BMA’s chairman of council, Hamish Meldrum; the chief executive of the healthcare think tank the King’s Fund, Chris Ham; and witnesses from the NHS Confederation, the representative body for most NHS organisations, the public sector unions Unison and Unite, the health think tank the Nuffield Trust, and the NHS Alliance, which represents primary …
The ‘McArdle paradox’: exercise is a good advice for the exercise intolerant
Authors: Alejandro Lucia, Ros Quinlivan, Andrew Wakelin, Miguel A Martín, Antoni L Andreu
Journal: British Journal of Sports Medicine (2012)

McArdle disease (glycogen storage disease type V, OMIM database number 232600) may provide the ultimate model of exercise intolerance in humans, and thus is of great interest in the sports medicine setting. The condition is an autosomal recessive disorder of muscle glycogen metabolism originally described in 1951 by Brian McArdle.1 Patients have pathogenic mutations in both alleles of the PYGM gene, which encodes myophosphorylase , the skeletal muscle isoform of glycogen phosphorylase.2 As a result, myophosphorylase activity is totally absent. Because this enzyme initiates the breakdown of muscle glycogen leading to liberation of glucose-1-phosphate, patients are unable to obtain energy from their muscle glycogen stores. Hence this disease is arguably the paradigm of exercise intolerance in humans.2 Exercise is the trigger for symptom occurrence in McArdle patients; as such, they tend to be averse to exercise and have often been advised by clinicians to refrain from exercise.

Men and women are equally affected and symptoms usually begin during childhood, typically in the school playground or physical education classes.3 The clinical presentation is dominated by exercise intolerance in the form of acute crises of early fatigue and contractures, which are often accompanied by exertional rhabdomyolysis, as indicated by marked increases in serum levels of creatine kinase (CK) activity and myoglobinuria.3 Rhabdomyolysis can sometimes be so severe as to cause acute renal failure. A typical feature of the disease is the so-called ‘second wind’ phenomenon, that is, marked improvement in the tolerance of aerobic, dynamic, large muscle mass exercise (walking …
Effect of fibroblasts on epidermal regeneration
Authors: A. El-Ghalbzouri, S. Gibbs, E. Lamme, C.A. Van Blitterswijk, M. Ponec
Journal: British Journal of Dermatology (2002)

There is little information on specific interactions between dermal fibroblasts and epidermal keratinocytes. The use of engineered skin equivalents consisting of organotypic cocultures of keratinocytes and fibroblasts offers an attractive approach for such studies.To examine the role fibroblasts play in generation and maintenance of reconstructed epidermis.Human keratinocytes were seeded on collagen matrices populated with increasing numbers of fibroblasts and cultured for 2 weeks at the air-liquid interface.In the absence of fibroblasts, stratified epidermis with only three or four viable cell layers was formed. In the presence of fibroblasts, keratinocyte proliferation was stimulated and epidermal morphology was improved. Epidermal morphogenesis was also markedly improved in epidermis generated in organotypic keratinocyte monocultures grown in medium derived from dermal equivalents or from organotypic keratinocyte-fibroblast cocultures. These observations clearly indicate the proliferation-stimulating activity of soluble factors released from fibroblasts. Under all experimental conditions, onset of keratinocyte differentiation was shown by the expression of keratin 10 in all suprabasal cell layers. With increasing numbers of fibroblasts incorporated into the collagen matrix, the expression of markers associated with keratinocyte activation, e.g. keratins 6, 16 and 17 and the cornified envelope precursor SKALP decreased, and involucrin localization shifted toward the granulosum layer. This fibroblast-mediated effect was even more pronounced when the fibroblasts were precultured in the collagen matrices for 1 week instead of overnight. The basement membrane proteins collagen VII and laminin 5 were present at the epithelial-matrix border. The expression of integrin alpha 6 beta 4 and of E-cadherin was comparable with that seen in native skin and was not significantly modulated by fibroblasts. Under all experimental conditions the expression of integrin subunits alpha 2, alpha 3 and beta 1 was upregulated, indicating keratinocyte activation.Our results illustrate that numbers of fibroblasts in the collagen matrix and their functional state is a critical factor for establishment of normal epidermal morphogenesis.
KIT oncogene inhibition drives intratumoral macrophage M2 polarization
Authors: Michael J. Cavnar, Shan Zeng, Teresa S. Kim, Eric C. Sorenson, Lee M. Ocuin, Vinod P. Balachandran, Adrian M. Seifert, Jonathan B. Greer, Rachel Popow, Megan H. Crawley, Noah A. Cohen, Benjamin L. Green, Ferdinand Rossi, Peter Besmer, Cristina R. Antonescu, Ronald P. DeMatteo
Journal: The Journal of Experimental Medicine (2013)

Tumor-associated macrophages (TAMs) are a major component of the cancer microenvironment. Modulation of TAMs is under intense investigation because they are thought to be nearly always of the M2 subtype, which supports tumor growth. Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and typically results from an activating mutation in the KIT oncogene. Using a spontaneous mouse model of GIST and 57 freshly procured human GISTs, we discovered that TAMs displayed an M1-like phenotype and function at baseline. In both mice and humans, the KIT oncoprotein inhibitor imatinib polarized TAMs to become M2-like, a process which involved TAM interaction with apoptotic tumor cells leading to the induction of CCAAT/enhancer binding protein (C/EBP) transcription factors. In human GISTs that eventually developed resistance to imatinib, TAMs reverted to an M1-like phenotype and had a similar gene expression profile as TAMs from untreated human GISTs. Therefore, TAM polarization depends on tumor cell oncogene activity and has important implications for immunotherapeutic strategies in human cancers.