tbuckley/cabot-search huggingface dataset:
Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension<i>in vivo</i>
Authors: Jonathan A. Fallowfield, Annette L. Hayden, Victoria K. Snowdon, Rebecca L. Aucott, Ben M. Stutchfield, Damian J. Mole, Antonella Pellicoro, Timothy T. Gordon-Walker, Alexander Henke, Joerg Schrader, Palak J. Trivedi, Marc Princivalle, Stuart J. Forbes, Jane E. Collins, John P. Iredale
Journal: Hepatology (2013)

Active myofibroblast (MF) contraction contributes significantly to the increased intrahepatic vascular resistance that is the primary cause of portal hypertension (PHT) in cirrhosis. We sought proof of concept for direct therapeutic targeting of the dynamic component of PHT and markers of MF activation using short-term administration of the peptide hormone relaxin (RLN). We defined the portal hypotensive effect in rat models of sinusoidal PHT and the expression, activity, and function of the RLN-receptor signaling axis in human liver MFs. The effects of RLN were studied after 8 and 16 weeks carbon tetrachloride intoxication, following bile duct ligation, and in tissue culture models. Hemodynamic changes were analyzed by direct cannulation, perivascular flowprobe, indocyanine green imaging, and functional magnetic resonance imaging. Serum and hepatic nitric oxide (NO) levels were determined by immunoassay. Hepatic inflammation was assessed by histology and serum markers and fibrosis by collagen proportionate area. Gene expression was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting and hepatic stellate cell (HSC)-MF contractility by gel contraction assay. Increased expression of RLN receptor (RXFP1) was shown in HSC-MFs and fibrotic liver diseases in both rats and humans. RLN induced a selective and significant reduction in portal pressure in pathologically distinct PHT models, through augmentation of intrahepatic NO signaling and a dramatic reduction in contractile filament expression in HSC-MFs. Critical for translation, RLN did not induce systemic hypotension even in advanced cirrhosis models. Portal blood flow and hepatic oxygenation were increased by RLN in early cirrhosis. Treatment of human HSC-MFs with RLN inhibited contractility and induced an antifibrogenic phenotype in an RXFP1-dependent manner. We identified RXFP1 as a potential new therapeutic target for PHT and MF activation status.
Abstract 2977: Clinical Outcomes of Aortic Valve Repair in Asymptomatic Patients With Chronic Severe Aortic Valve Regurgitation
Authors: Khalil Fattouch, Roberta Sampognaro, Marco Caruso, Emiliano Navarra, Marco Moscarelli, Giuseppe Speziale, Giuseppina Novo, Salvatore Novo, Giovanni Ruvolo
Journal: Circulation (2009)
Vaccination Compliance and the US Measles Epidemic
Authors: Raymond Leung, Maya Munoz
Journal: JAMA Pediatrics (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Detoxification and Treating Opioid Dependence
Authors: Jose A Contreras
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Lesson of the week: Childhood Cushing's syndrome induced by betamethasone nose drops, and repeat prescriptions
Authors: C A Findlay, J F Macdonald, A M Wallace, N Geddes, M D C Donaldson
Journal: BMJ (1998)

Children should have betamethasone nose drops prescribed for only short periods 

Iatrogenic Cushing's syndrome secondary to oral corticosteroid treatment is well documented, as is systemic absorption of topical steroid preparations that are potent or used for a long time. However, frank Cushing's syndrome as a result of inhaled or intranasal corticosteroids is not well recognised. We present two cases of childhood Cushing's syndrome secondary to prolonged use of intranasal betamethasone.

### Case 1

>A boy aged 7 years was referred to the endocrine clinic with a history of growth failure associated with obesity. Over the past two years his weight had increased from the 50th to the 97th centile with height falling from the 10th to the 3rd centile. He had no history of note apart from mild atopy and chronic catarrh, for which he had been prescribed 0.1% betamethasone nasal drops.

On examination he was cushingoid with normal prepubertal genitalia. His blood pressure was 165/75 mm Hg (>95th centile for age). Pituitary Cushing's syndrome was diagnosed clinically and he was admitted for endocrine assessment. We expected to find high serum cortisol concentrations, but cortisol was undetectable (<24 nmol/l) and he did not respond to stimulation by insulin hypoglycaemia. Adrenocorticotrophic hormone was also undetectable. A 24 hour urine sample showed extremely low adrenal steroid metabolite concentrations, indicating severely impaired adrenal function. Computed tomography of the brain and adrenal glands showed …
Rate-limiting steps in steady-state intestinal absorption of trioctanoin-l-14C
Authors: Susanne Bennett Clark, Peter R. Holt
Journal: Journal of Clinical Investigation (1968)

During continuous intraduodenal infusion of emulsified fat in rats, a steady state of intestinal absorption is achieved. Maximal steady-state absorption of trioctanoin, a medium-chain triglyceride (MCT), by unanesthetized, restrained rats was found to be the same after total bile diversion as in controls (1560 mumoles of fatty acid per hr).After pancreatic and bile diversion, absorption of MCT was still one-third as rapid as in controls, and mucosal uptake apparently occurred in the form of unhydrolyzed triglyceride. Returning bile to the intestinal lumen during pancreatic diversion did not increase the absorption rate.From intestinal tissue lipid-(14)C concentrations measured during steady-state maximal absorption it was possible to calculate turnover times for labeled lipid passing through the mucosal cells. Mucosal turnover times of about 4 min for control and bile-diverted rats, and about 20 min for animals with pancreatic diversion were obtained. The rate-limiting step in octanoic acid absorption in control and bile-diverted rats was probably mucosal penetration. During absorption of unhydrolyzed triglyceride by pancreatic flow-diverted rats, both passage from the lumen into the mucosal cell and intracellular lipolysis were rate-controlling factors.
Novel mutations in the inverted formin 2 gene of Chinese families contribute to focal segmental glomerulosclerosis
Authors: Jingyuan Xie, Xu Hao, Evren U. Azeloglu, Hong Ren, Zhaohui Wang, Jun Ma, Jian Liu, Xiaodan Ma, Weiming Wang, Xiaoxia Pan, Wen Zhang, Fang Zhong, Yifu Li, Guoyu Meng, Krzysztof Kiryluk, John Cijiang He, Ali G. Gharavi, Nan Chen
Journal: Kidney International (2015)
Abstract MP51: Evaluating the Effectiveness of a Web-Based Intervention to Prevent Unhealthy Weight Gain in College Students
Authors: Leslie A Lytle, Melissa Laska, Marilyn Nanney, Jennifer Linde, Stacey Moe
Journal: Circulation (2015)

CHOICES was a randomized control trial evaluating a one-credit college course and a social-network website to reduce unhealthy weight gain in young adults. The primary outcome was relative change in BMI and weight status between conditions at the end of the 24-month intervention. The study sample was 441 young adults attending 3 2-year colleges in the Twin Cities of Minnesota. At baseline the mean age of the sample was 22.8 and the sample was approximately 68% female, 73% white, and 71% lower income (income less than $12,000). At baseline 47% of the sample was overweight or obese with a mean BMI of 25.4. Students were randomized after baseline data were collected into one of two conditions. Students in the intervention condition took a one credit class focusing on weight gain prevention behaviors and were invited to participate in a social networking website designed to help individuals track and learn about weight related health behaviors and network with each other for support. The retention rate of participants at the final data collection period (24 months) was 83.4%. Adjusting for age, gender, race and education, there were no statistically significant differences in BMI between study conditions at 24 months (26.13: intervention and 26.09: control). However, the proportion of students that were overweight and obese was significantly smaller in the intervention condition (47%) as compared to the control condition (55%) at the 24-month period. Analyses also examined the extent to which participants maintained, gained and lost weight over the course of the trial. More that half (54%) of the sample gained weight (more than 3% of baseline weight) during the 24 months of the trial. There were no treatment differences between categories of weight stability. CHOICES is one of the first web-based weight gain prevention intervention trials to be conducted in 2-year or technical colleges and the results suggest that a primarily web-based intervention may be useful in helping young adults avoid transitioning from a healthy weight to overweight or obese weight status.
TRK-Fused Gene (TFG) Is a New Partner of ALK in Anaplastic Large Cell Lymphoma Producing Two Structurally DifferentTFG-ALK Translocations
Authors: Luis Hernández, Magda Pinyol, Silvia Hernández, Silvia Beà, Karen Pulford, Andreas Rosenwald, Laurence Lamant, Brunangelo Falini, German Ott, David Y. Mason, Georges Delsol, Elias Campo
Journal: Blood (1999)
Abstract 15236: The Histone Demethylase Jumonji D3 Regulates Angiogenesis
Authors: Tina Lucas, Cong Zhao, Kisho Ohtani, Ariane Fischer, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2014)

Vascular development is tightly controlled by epigenetic regulators. Histone modifications control specific gene expression, whereby trimethylation of histone H3 at lysine 27 (H3K27me3) represses expression. H3K27me3 can be erased e.g. by the demethylase Jumonji D3 (Jmjd3) to activate expression of target genes. The role of Jmjd3 in the regulation of vascular differentiation and angiogenesis is unclear. Using Jmjd3-depleted mouse embryonic stem cells, we demonstrate that Jmjd3 is required for mesoderm differentiation and vascular lineage commitment in vitro. Jmjd3 reduces H3K27me3 marks at the promoter of the mesoderm gene brachyury and facilitates recruitment of beta-catenin, which is critical for canonical Wnt signal-induced mesoderm differentiation. To investigate the importance of Jmjd3 function in endothelial cells (EC) in vivo, we generated global and EC-specific Jmjd3 knockout mice. Overall deletion of Jmjd3 is reflected in early embryonic lethality before E6.5 (n=17). In contrast, Tie2-Cre-specifi...
Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma
Authors: N. Scichilone, S. Battaglia, C. Sorino, G. Paglino, L. Martino, A. Paternò, R. Santagata, M. Spatafora, G. Nicolini, V. Bellia
Journal: Allergy (2010)

Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways.To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function.After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 microg daily or fluticasone propionate/salmeterol (FP/S) 500/100 microg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed.Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV(1)) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV(1) in both BDP/F and FP/S groups (0.37 +/- 0.13 l and 0.36 +/- 0.12 l, respectively). PD(20)FEV(1) Mch improved significantly from 90.42 (+/-30.08) microg to 432.41 (+/-122.71) microg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN(2) test parameters.The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN(2) tests.
Abstract #5499: Overcoming TRAIL resistance by dipyridamole: A new role for an old drug
Authors: Ahmed Goda, Tatsushi Yoshida, Mano Horinaka, Takashi Yasuda, Takumi Shiraishi, Miki Wakada, Toshiyuki Sakai
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The development of resistance to T umor necrosis factor- R elated A poptosis- I nducing L igand (TRAIL) undermines its merits of efficacy against p53-mutant cancers and in vivo tolerability. Therefore, the current study was undertaken to investigate the potential of combined treatment with TRAIL and the well-known antiplatelet drug; dipyridamole to overcome such resistance in a number of human cancer cell lines. Flow cytometry and immunoblotting showed that TRAIL-induced apoptosis in SW480, MG63 and DU145 cells was significantly increased upon combined treatment with dipyridamole. Systematic analysis of apoptosis signal-regulating molecules along TRAIL signaling pathway via immunoblotting and immunocytometry revealed an increased expression of TRAIL death receptors and downregulation of survivin in response to dipyridamole treatment. Target validation via RNA interference emphasized the preferential contribution of dipyridamole-induced DR5 upregulation and the importance of survivin downregulation, especially the improved TRAIL-induced processing of caspases-8 and -10 following survivin siRNA. Mechanistically, dipyridamole induced a transcriptional shutdown of survivin expression accompanying re-activation of RB pathway and G1 arrest that was triggered by downregulation of D-type cyclins and cdk6. Moreover, RNA interference confirmed the cause-effect relationship of CHOP and DR5 induction by dipyridamole. Although protein kinase-A and -G are known downstream targets of dipyridamole, their specific activation however failed to enhance TRAIL antitumor activity. Additionally, inhibitors of protein kinase-A and -G could not revert dipyridamole-induced enhancement of TRAIL efficacy or alterations of protein expression. In conclusion, the present study described novel mechanisms of dipyridamole action which explained, at least in part, its potential to amplify TRAIL-triggered apoptotic signals.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5499.
Live and Learn
Authors: M J Fisher
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Spectroscope and Its Uses in General Analytical Chemistry.
Authors: T. Thorne Baker
Journal: JAMA (1923)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Circulating endothelial cells as a therapeutic marker for docetaxel treatment and combination therapy of docetaxel and thalidomide in a human prostate cancer model
Authors: Haiqing Li, Valentina Raia, Francesco Bertolini, William D. Figg
Journal: Clinical Cancer Research (2006)

PR-10   The field of anti-angiogenic therapy has developed rapidly in last decade and the pace has been accelerated when the FDA approved bevacizumab in 2004, the first selective anti-angiogenesis therapy approved for treatment of human cancer. Because anti-angiogenic agents do not target tumor cells directly, the efficacy of these drugs often are difficult to be detected by the traditional therapeutic endpoints utilized for cytotoxic regimens. Hence, a good therapeutic biomarker for anti-angiognic drugs is urgently needed.Circulating endothelial cells (CEC) has been tested for this purpose and has shown good promise. An increased level of circulating endothelial cells were found in patients with a wide range of cancers, compared to healthy controls. However, there are conflicted publications about the effects of drug treatment on CEC levels. Some drugs have been shown to decrease CEC levels in patients with cancer, while other anti-angiogenic drugs have increased CEC levels. Furthermore, it has become clear that a combination regimen of an anti-angiogenic agents and chemotherapies will be needed to treat patients with cancer. While chemotherapy itself has been shown to affect CEC levels in patients, it is still unclear whether CEC serve a good therapeutic marker to detect the efficacy of an anti-angiogenic drug when it is used in combination with chemotherapy drugs.We tested CEC as a therapeutic marker in a human prostate cancer model. We treated PC3 xenograft tumors with either docetaxel alone or docetaxel/thalidomide combination therapy and tested the CEC levels at the different time points before or during treatments. The results showed that shortly after the treatment, docetaxel dramatically increased dead CEC level to 2.6 fold and the combination of docetaxel and thalidomide further augmented it to 4.3 fold, suggesting that anti-angiogenic drugs may enhance the cytotoxicity of chemotherapy drugs against vascular endothelial cells. At a later time point, Thalidomide reduced viable CEC level by 18% while docetaxel decreased it by 61%. The combination treatment further diminished the viable CEC level by 75%, indicating that anti-angiogenic drugs may inhibit the proliferation and differentiation of bone marrow derived endothelial progenitor cells.
New Guidelines on Managing Chronic Pain in Older Persons
Authors: L Lamberg
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains
Authors: Christelle Peyron, Juliette Faraco, William Rogers, Beth Ripley, Sebastiaan Overeem, Yves Charnay, Sona Nevsimalova, Michael Aldrich, David Reynolds, Roger Albin, Robin Li, Marcel Hungs, Mario Pedrazzoli, Muralidhara Padigaru, Melanie Kucherlapati, Jun Fan, Richard Maki, Gert Jan Lammers, Constantin Bouras, Raju Kucherlapati, Seiji Nishino, Emmanuel Mignot
Journal: Nature Medicine (2000)