tbuckley/cabot-search huggingface dataset:
High throughput sequencing (HTS) provides full repertoire analysis of the B and T cell receptors in humans and mice, both in blood and synovial tissue
Authors: P. L. Klarenbeek, P. P. Tak, M. E. Doorenspleet, B. D. C. van Schaik, F. M. Wensveen, L. Gottschal, M. E. Jakobs, I. A. M. Derks, E. Eldering, A. H. C. van Kampen, F. Baas, N. de Vries
Journal: Annals of the Rheumatic Diseases (2010)

The adaptive immune system protects the body from invading pathogens. However, adaptive responses have also been implicated in autoimmune diseases such as rheumatoid arthritis. During these immune responses, activated T and B cells can undergo clonal expansion. Identification and monitoring of expanded clones has proved difficult owing to the extremely high diversity of T and B cell receptor (TCR/ BCR) repertoires. Current techniques are unable to rapidly and quantitatively analyse these vast repertoires with sufficient resolution; furthermore, they are vulnerable to artefacts. Here the authors …
Thorax in focus: chronic obstructive pulmonary disease
Authors: David B Hodgson, Gauri Saini, Charlotte E Bolton, Michael C Steiner
Journal: Thorax (2011)

Keeping up to date with scientific developments in any field of medicine is challenging, and chronic obstructive pulmonary disease (COPD) is no exception. <i>Thorax</i> has played an important part in the communication of key developments to its readership. In this article we review original research published in the journal over the last 2-3 years. We consider scientific and clinical developments in the epidemiology, mechanisms and treatment of COPD, placing these articles in the context of other relevant literature in COPD.
The “von Meyenburg complex”
Authors: Michael Quentin, Axel Scherer
Journal: Hepatology (2010)

A 67-year-old woman was admitted to our hospital with weakness, fatigue, fever, and persistent vomiting for 2 days. Physical examination showed reduced general condition and adiposity, but no abdominal tenderness. Laboratory tests revealed elevated levels of serum gamma glutamyltransferase (50 U/L [normal < 28 U/L]) and C-reactive protein (16 mg/dL [normal < 1 mg/dL]). Serum levels of total bilirubin and direct bilirubin were normal. Blood cultures were negative. Ultrasound examination of the abdomen showed multiple hyperechoic and hypoechoic liver lesions accentuated in the right liver lobe. The further diagnostic workup included a magnetic resonance cholangiopancreatography (MRCP) which showed multiple hyperintense liver lesions. There was no visible communication between the cystic lesions and the normal biliary system (Fig. AB). In some parts of the liver, the lesions were surrounded by fibrosis. Due to persisting uncertainty of the pathology, the patient underwent ultrasound-guided fine-needle biopsy, which showed chronic portal and periportal inflammation. In addition, septal fibrosis with bile duct proliferation and metaplasia could be observed. There was no evidence of malignancy. The histological findings were compatible with bile duct hamartomas embedded in a fibrous stroma (Fig. C). MRCP, magnetic resonance cholangiopancreatography; VMC, von Meyenburg complex. The numerous, disseminated cystic lesions in MRCP, smaller than 10 mm in size and without communication to the normal biliary system, is a highly suggestive imaging feature of multiple biliary hamartomas.1 The entity of multiple biliary hamartomas was first described by von Meyenburg in 1918 and is hence also known as the "von Meyenburg complex" (VMC).2 Although VMC is a rare clinical diagnosis, the prevalence of VMC is up to 5.6% in large autopsy series.3 Because VMC often lacks clinical symptoms, it is typically an incidental finding. On the other hand, there are single case reports of VMC associated with clinical symptoms of jaundice, epigastric pain, cholangitis, and fever.4 Thus, it can be easily confused with a variety of multifocal liver lesions, e.g., Caroli syndrome, cysts, or metastases.5 Differential diagnosis of VMC in MRCP depends on the number of lesions and their uniformity and dissemination. In addition, a normal-sized biliary tree and accompanying fibrosis are main diagnostic criteria. In asymptomatic patients with VMC, no treatment or follow-up examinations are required. Therefore, the knowledge of this distinctive imaging feature is important and can help physicians avoid unnecessary examinations and biopsies.
Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type
Authors: K.-F. Foo, E.-H. Tan, S.-S. Leong, J.T.S. Wee, T. Tan, K.-W. Fong, L. Koh, B.-C. Tai, L.-G. Lian, D. Machin
Journal: Annals of Oncology (2002)
The Relationship Between Cost and Quality
Authors: Karen E. Joynt, Ashish K. Jha
Journal: JAMA (2012)

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
Microcomplexes: The basic unit of the cerebellar role in adaptive motor control
Authors: Michael A. Arbib, Jacob Spoelstra
Journal: Behavioral and Brain Sciences (1997)

We offer a critique of the role of the parallel fiber beam as the unit of cerebellar computation, with the “tidal wave” as its mode of operation. Instead we see the microcomplex linking cerebellar cortex and nuclei as the unit, with parallel fibers providing the means to coordinate the effects of microcomplexes in modulating various motor pattern generators (MPGs).
The long non-coding RNA PCGEM1 is regulated by androgen receptor activity in vivo
Authors: Abhijit Parolia, Francesco Crea, Hui Xue, Yuwei Wang, Fan Mo, Varune Rohan Ramnarine, Hui Hsuan Liu, Dong Lin, Nur Ridzwan Nur Saidy, Pier-Luc Clermont, Hongwei Cheng, Colin Collins, Yuzhuo Wang, Cheryl D Helgason
Journal: Molecular Cancer (2015)

Long non-coding RNAs (lncRNAs) can orchestrate oncogenic or tumor-suppressive functions in cancer biology. Accordingly, PCGEM1 and PRNCR1 were implicated in progression of prostate cancer (PCa) as transcriptional co-regulators of the androgen receptor (AR). However, these findings were recently refuted asserting that neither gene physically binds to the AR. Despite evidence for differing AR transcriptional programs in vivo and in vitro, studies investigating AR-regulation of these genes hitherto have only been conducted in vitro. Here, we further examine the relevance of PCGEM1 and PRNCR1 in PCa, and their relationship with AR signaling, using patient-derived xenograft models. RNA sequencing of two distinct androgen-dependent models shows PCGEM1 to be considerably expressed, while PRNCR1 showed scant basal expression. PCGEM1 was sharply down-regulated following castration and up-regulated upon AR activation in vivo. However, we found no parallel evidence following AR stimulation in vitro. A PCGEM1-associated gene expression signature (PES) was significantly repressed in response to androgen ablation therapy and in hormone-refractory versus hormone-naïve PCa patients. Furthermore, we found PCGEM1 was uniformly distributed in PCa cell nucleus and cytoplasm which remained unaltered upon AR transcriptional activation. PCGEM1 was up-regulated in primary PCa but not in metastasized PCa. Accordingly, the PES was significantly down-regulated in advanced and higher grade PCa patients from multiple independent studies. Our results demonstrate PCGEM1 as an in vivo androgen-regulated transcript with potential nuclear and/or cytoplasmic function(s). Importantly, the clinical expression profile of PCGEM1 implicates it in the early stages of PCa warranting further research in this direction.
Performance of<i>BRCA1/2</i>Mutation Prediction Models in Asian Americans
Authors: Allison W. Kurian, Gail D. Gong, Nicolette M. Chun, Meredith A. Mills, Ashley D. Staton, Kerry E. Kingham, Beth B. Crawford, Robin Lee, Salina Chan, Susan S. Donlon, Yolanda Ridge, Karen Panabaker, Dee W. West, Alice S. Whittemore, James M. Ford
Journal: Journal of Clinical Oncology (2008)

Purpose There are established differences in breast cancer epidemiology between Asian and white individuals, but little is known about hereditary breast cancer in Asian populations. Although increasing numbers of Asian individuals are clinically tested for BRCA1/2 mutations, it is not known whether computer models that predict mutations work accurately in Asian individuals. We compared the performance in Asian and white individuals of two widely used BRCA1/2 mutation prediction models, BRCAPRO and Myriad II. Patients and Methods We evaluated BRCAPRO and Myriad II in 200 Asian individuals and a matched control group of 200 white individuals who were tested for BRCA1/2 mutations at four cancer genetics clinics, by comparing numbers of observed versus predicted mutation carriers and by evaluating area under the receiver operating characteristic curve (AUC) for each model. Results BRCAPRO and Myriad II accurately predicted the number of white BRCA1/2 mutation carriers (25 observed v 24 predicted by BRCAPRO; 25 predicted by Myriad II, P ≥ .69), but underpredicted Asian carriers by two-fold (49 observed v 25 predicted by BRCAPRO; 26 predicted by Myriad II; P ≤ 3 × 10 −7 ). For BRCAPRO, this racial difference reflects substantial underprediction of Asian BRCA2 mutation carriers (26 observed v 4 predicted; P = 1 × 10 −30 ); for Myriad II, separate mutation predictions were not available. For both models, AUCs were nonsignificantly lower in Asian than white individuals, suggesting less accurate discrimination between Asian carriers and noncarriers. Conclusion Both BRCAPRO and Myriad II underestimated the proportion of BRCA1/2 mutation carriers, and discriminated carriers from noncarriers less well, in Asian compared with white individuals.
Hedgehog Signaling Inhibition Blocks Growth of Resistant Tumors through Effects on Tumor Microenvironment
Authors: Emanuela Heller, Michelle A. Hurchla, Jingyu Xiang, Xinming Su, Sara Chen, Jochen Schneider, Kyu-Sang Joeng, Marcos Vidal, Leah Goldberg, Hongju Deng, Mary C. Hornick, Julie L. Prior, David Piwnica-Worms, Fanxin Long, Ross Cagan, Katherine N. Weilbaecher
Journal: Cancer Research (2011)

Hedgehog (Hh) signaling is implicated in bone development and cellular transformation. Here we show that inhibition of Hh pathway activity inhibits tumor growth through effects on the microenvironment. Pharmacologic inhibition of the Hh effector Smoothened (Smo) increased trabecular bone in vivo and inhibited osteoclastogenesis in vitro. In addition, enhanced Hh signaling due to heterozygosity of the Hh inhibitory receptor Patched (Ptch1(+/-)) increased bone resorption, suggesting direct regulation of osteoclast (OC) activity by the Hh pathway. Ptch1(+/-) mice had increased bone metastatic and subcutaneous tumor growth, suggesting that increased Hh activation in host cells promoted tumor growth. Subcutaneous growth of Hh-resistant tumor cells was inhibited by LDE225, a novel orally bioavailable SMO antagonist, consistent with effects on tumor microenvironment. Knockdown of the Hh ligand Sonic Hh (SHH) in these cells decreased subcutaneous tumor growth and decreased stromal cell production of interleukin-6, indicating that tumor-derived Hh ligands stimulated tumor growth in a paracrine fashion. Together our findings show that inhibition of the Hh pathway can reduce tumor burden, regardless of tumor Hh responsiveness, through effects on tumor cells, OCs, and stromal cells within the tumor microenvironment. Hh may be a promising therapeutic target for solid cancers and bone metastases.
Trichuris suis therapy in Crohn's disease
Authors: R W Summers
Journal: Gut (2004)

Crohn's disease is common in highly industrialised Western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Thus exposure to helminths may help prevent or even ameliorate Crohn's disease.The aim of the study was to determine the safety and possible efficacy of the intestinal helminth Trichuris suis in the treatment of patients with active Crohn's disease.Twenty nine patients with active Crohn's disease, defined by a Crohn's disease activity index (CDAI) > or =220 were enrolled in this open label study.All patients ingested 2500 live T suis ova every three weeks for 24 weeks, and disease activity was monitored by CDAI. Remission was defined as a decrease in CDAI to less than 150 while a response was defined as a decrease in CDAI of greater than 100.At week 24, 23 patients (79.3%) responded (decrease in CDAI >100 points or CDAI <150) and 21/29 (72.4%) remitted (CDAI <150). Mean CDAI of responders decreased 177.1 points below baseline. Analysis at week 12 yielded similar results. There were no adverse events.This new therapy may offer a unique, safe, and efficacious alternative for Crohn's disease management. These findings also support the premise that natural exposure to helminths such as T suis affords protection from immunological diseases like Crohn's disease.
Modulation of Age- and Cancer-Associated DNA Methylation Change in the Healthy Colon by Aspirin and Lifestyle
Authors: Faiza Noreen, Martin Röösli, Pawel Gaj, Jakub Pietrzak, Stefan Weis, Patric Urfer, Jaroslaw Regula, Primo Schär, Kaspar Truninger
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundAberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa.
Severe airflow obstruction and eosinophilic lung disease after Stevens-Johnson syndrome
Authors: A. P. Shah, H. Xu, P. J. Sime, D. R. Trawick
Journal: European Respiratory Journal (2006)

Respiratory involvement is a frequent complication of Stevens–Johnson syndrome (SJS). However, there are very few convincing reports of persistent pulmonary sequelae, as demonstrated by spirometry, radiology and pathology. The current study presents a case of a 13-yr-old female with T-cell acute lymphocytic leukaemia who developed persistent, severe, obstructive lung disease following an episode of SJS. A lung biopsy demonstrated bronchiolar submucosal fibrosis consistent with constrictive bronchiolitis, as well as eosinophilic micro-abscesses, which, to the current authors’ knowledge, has not been previously described. The present study illustrates specific histopathological features that highlight a possible association between Stevens–Johnson syndrome, constrictive bronchiolitis and eosinophilic micro-abscesses. The eosinophils may be associated with permanent mucosal damage, as seen in the present case, by releasing mediators that have a pro-fibrogenetic role. However, further investigation is warranted.
Synovial tissue macrophages and joint erosion in rheumatoid arthritis.
Authors: G Yanni, A Whelan, C Feighery, B Bresnihan
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To analyse the mononuclear cell populations in synovial membrane biopsies obtained before treatment from patients with rheumatoid arthritis (RA) and to correlate the findings with the degree of joint damage occurring over one year. METHODS--Multiple needle biopsy specimens were obtained from inflamed knee joints on entry to the study. The tissue samples were examined using immunohistochemical techniques. The degree of joint damage was estimated using the Larsen radiological index. RESULTS--Twelve patients were studied. It was observed that there was a significant correlation between the number of synovial tissue macrophages and the degree of joint erosion over one year (r = 0.66; p = 0.04). The synovial lining layer contained large numbers of macrophages and the cellularity of the lining layer correlated significantly with the number of macrophages infiltrating the sublining areas (r = 0.65; p = 0.01). Finally, the cellularity of the lining layer correlated with the synovial fluid levels of interleukin-6 (r = 0.66; p = 0.04). The radiological course did not correlate with infiltrating T or B lymphocyte populations, but did correlate with other previously identified indicators of the clinical course, including a high index of disease activity and IgA rheumatoid factors levels. CONCLUSION--This study suggests that synovial tissue macrophages play a critical role in the pathogenesis of joint erosion in RA.
Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study
Authors: Simon P L Travis, Silvio Danese, Limas Kupcinskas, Olga Alexeeva, Geert D'Haens, Peter R Gibson, Luigi Moro, Richard Jones, E David Ballard, Johan Masure, Matteo Rossini, William J Sandborn
Journal: Gut (2013)

<h3>Objective</h3> Budesonide MMX is a novel oral formulation of budesonide that uses Multi-Matrix System (MMX) technology to extend release to the colon. This study compared the efficacy of budesonide MMX with placebo in patients with active, mild-to-moderate ulcerative colitis (UC). <h3>Design</h3> Patients were randomised 1:1:1:1 to receive budesonide MMX 9 mg or 6 mg, or Entocort EC 9 mg (budesonide controlled ileal-release capsules; reference arm) or placebo once daily for 8 weeks. The primary endpoint was combined clinical and endoscopic remission, defined as UC Disease Activity Index score ≤1 with a score of 0 for rectal bleeding and stool frequency, no mucosal friability on colonoscopy, and a ≥1-point reduction in endoscopic index score from baseline. <h3>Results</h3> 410 patients were evaluated for efficacy. Combined clinical and endoscopic remission rates with budesonide MMX 9 mg or 6 mg, Entocort EC and placebo were 17.4%, 8.3%, 12.6% and 4.5%, respectively. The difference between budesonide MMX 9 mg and placebo was significant (OR 4.49; 95% CI 1.47 to 13.72; p=0.0047). Budesonide MMX 9 mg was associated with numerically higher rates of clinical (42.2% vs 33.7%) and endoscopic improvement (42.2% vs 31.5%) versus placebo. The rate of histological healing (16.5% vs 6.7%; p=0.0361) and proportion of patients with symptom resolution (23.9% vs 11.2%; p=0.0220) were significantly higher for budesonide MMX 9 mg than placebo. Adverse event profiles were similar across groups. <h3>Conclusion</h3> Budesonide MMX 9 mg was safe and more effective than placebo at inducing combined clinical and endoscopic remission in patients with active, mild-to-moderate UC.
Determination of the specific activity of CDK1 and CDK2 as a novel prognostic indicator for early breast cancer
Authors: S.J. Kim, S. Nakayama, Y. Miyoshi, T. Taguchi, Y. Tamaki, T. Matsushima, Y. Torikoshi, S. Tanaka, T. Yoshida, H. Ishihara, S. Noguchi
Journal: Annals of Oncology (2007)
Animal Models of Obesity: Genetic Aspects
Authors: P R Johnson, M R C Greenwood, B A Horwitz, J S Stern
Journal: Annual Review of Nutrition (1991)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation
Authors: Scott R. Solomon, Stephan Mielke, Bipin N. Savani, Aldemar Montero, Laura Wisch, Richard Childs, Nancy Hensel, John Schindler, Victor Ghetie, Susan F. Leitman, Thao Mai, Charles S. Carter, Roger Kurlander, Elizabeth J. Read, Ellen S. Vitetta, A. John Barrett
Journal: Blood (2005)
Production of the second component of complement by human monocytes: stimulation by antigen-activated lymphocytes or lymphokines.
Authors: B H Littman, S Ruddy
Journal: The Journal of Experimental Medicine (1977)

Human peripheral blood mononuclear cells cultured in the presence of antigen produced hemolytically active second complement component earlier and in larger amounts than did control cultures of the same cells without antigen. The increased amount of C2 in culture supernates came primarily from the adherent cell population and was due to increased synthesis as demonstrated by inhibition with 10(-4) M cycloheximide. Purified adherent monocytes produced more C2 when exposed to lymphokine-rich supernates from antigen-stimulated lymphocytes than when exposed to control supernates from unstimulated lymphocyte cultures. The increased synthesis of C2, which appeared to be mediated by a lymphokine, was partially inhibited specifically by 0.025 M alpha-L(-) fucose, a sugar which has previously been shown in inhibit the response of macrophages to migration inhibitory factor.
THE DOUBTFUL NATURE OF “LUXUSKONSUMPTION” 1
Authors: F. H. Wiley, L. H. Newburgh
Journal: Journal of Clinical Investigation (1931)

In 1911, and several times thereafter, Grafe and his associates (1) stated that the fasting, resting metabolism of an individual is not pro- portional to the surface area, but is significantly affected by the calorific value of the food previously ingested.They also postulated that the total metabolism is influenced in the same way by the total intake of energy.According to them, normal animals, including man, maintain a constant weight, almost without regard to the energy intake, and obesity is often nothing more than the failure of this alleged mechanism to respond normally to the stimulus of food.Finally, leanness is an over-response to a normal stimulus.They supported these views by the following type of experiments: A dog was starved for a long time, and its resting, fasting metabolism was then determined.This value was used as the basis for comparison.The dog was now offered an abundance of food, and gained weight rapidly.The metabolism was repeatedly determined in the fasting, resting state.The metabolic rate thus determined showed a progressive increase out of proportion to the increase in body surface.Table I sets forth their data in detail, rearranged by us.This increase in metabolic rate of the overfed animal beyond that of the starved animal was accepted by them as proof that the resting, fasting metabolism of the normal animal is increased by previous over- feeding.But the metabolic rate obtained after prolonged starvation should not have been accepted as a proper basis for comparison, since Schondorff (2) had previously shown that starvation caused a decrease I The expenses of this investigation were defrayed in part by a fund for the study of nutrition, created by