tbuckley/cabot-search huggingface dataset:
Light chain (AL) amyloidosis: update on diagnosis and management
Authors: Michael Rosenzweig, Heather Landau
Journal: Journal of Hematology & Oncology (2011)

Light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (SCT) or oral melphalan with dexamethasone (MDex). The use of novel agents (thalidomide, lenalidomide and bortezomib) alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk adapted approach to SCT followed by novel agents as consolidation reduces treatment related mortality with promising outcomes. Immunotherapeutic approaches targeting pathologic plasma cells and amyloid precursor proteins or fibrils are being developed. Referral of patients to specialized centers focusing on AL amyloidosis and conducting clinical trials is essential to improving patient outcomes.
Wheezing in preschool children is associated with increased levels of cytokines/chemokines in exhaled breath condensate
Authors: Kim D.G. van de Kant, Ester M.M. Klaassen, Quirijn Jöbsis, Karlijn Koers, Ger T. Rijkers, Chris P. van der Grinten, Onno C.P. van Schayck, Valéria Lima Passos, Edward Dompeling
Journal: Journal of Allergy and Clinical Immunology (2010)
Identification of crystals in synovial fluid
Authors: P. DIEPPE, A. SWAN
Journal: Annals of the Rheumatic Diseases (1999)

<h3>Abstract</h3> <h3>Background</h3> Severe Covid19 is characterised by a hyperactive immune response. Carnitine, an essential nutrient, and it’s derivative acetyl-carnitine can downregulate proinflammatory cytokines and has been suggested as a potential treatment for the disease. <h3>Methods</h3> We carried out Mendelian randomization analyses using publicly available data from a large genome wide association study (GWAS) of metabolites and a collaborative genome wide study of Covid19 to investigate the nature of the relationship between carnitine and acetyl-carnitine and Covid19 infection, hospitalisation with Covid19 and very severe Covid19. We used the same methodology to determine whether carnitine was associated with co-morbidities commonly found among those with severe Covid19. <h3>Results</h3> We found evidence of a protective effect against very severe Covid19 for both carnitine and acetyl-carnitine, with around a 40% reduction in risk associated with a doubling of carnitine or acetyl-carnitine (carnitine odds ratio (OR) = 0.56, 95% confidence intervals (CI) 0.33 to 0.95, p=0.03 and acetyl-carnitine OR=0.60, 95% CI 0.35 to 1.02, p=0.06), and evidence of protective effects on hopitalisation with Covid19. For acetyl-carnitine the largest protective effect was seen in the comparison between those hospitalised with Covid19 and those infected but not hospitalised (OR=0.34, 95%CI 0.18 to 0.62, p=0.0005). <h3>Conclusion</h3> Carnitine and acetyl-carnitine merit further investigation in respect to the prevention of severe Covid19.
Osteoarticular manifestations of pustulosis palmaris et plantaris and of psoriasis: two distinct entities.
Authors: O Mejjad, A Daragon, J P Louvel, L F Da Silva, E Thomine, P Lauret, X Le Loet
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To test the hypothesis that pustulosis palmaris et plantaris and psoriatic arthritis (PsA) are two distinct diseases, and that the associated dermatoses are therefore also distinct diseases. METHODS: We prospectively performed clinical, radiological, biological, and bone scan investigations in 23 outpatients with pustolotic arthritis and 23 outpatients with PsA, matched by gender, age (+/- one year) and duration of arthritis (+/- two years). RESULTS: The anterior chest wall, especially the sternocostoclavicular joints, was more frequently involved in pustulotic arthritis than in PsA, both clinically (82% v 43%; p &lt; 0.001) and radiologically (47% v 17%; p &lt; 0.05). Sternocostoclavicular joints generally presented with erosive lesions in PsA, and with large ossifications in pustulotic arthritis. Peripheral joint involvement was mono- or oligoarticular, affecting proximal joints, in pustulotic arthritis (74% v 21%; p &lt; 0.01), and polyarticular, involving small distal joints, in PsA (60% v 0%; p &lt; 10(-4)), in which condition it was also more often erosive (43% v 8%; p &lt; 0.01). The frequency of sacroiliitis and of spine involvement was similar in pustulotic arthritis and PsA. Biology and bone scan did not help distinguish between the two groups. CONCLUSIONS: Pustulotic arthritis and PsA are clinically and radiologically different, therefore pustulosis palmaris et plantaris and psoriasis are most probably distinct dermatological diseases.
Peutz-Jeghers syndrome: a systematic review and recommendations for management
Authors: A. D. Beggs, A. R. Latchford, H. F. A. Vasen, G. Moslein, A. Alonso, S. Aretz, L. Bertario, I. Blanco, S. Bulow, J. Burn, G. Capella, C. Colas, W. Friedl, P. Moller, F. J. Hes, H. Jarvinen, J.-P. Mecklin, F. M. Nagengast, Y. Parc, R. K. S. Phillips, W. Hyer, M. Ponz de Leon, L. Renkonen-Sinisalo, J. R. Sampson, A. Stormorken, S. Tejpar, H. J. W. Thomas, J. T. Wijnen, S. K. Clark, S. V. Hodgson
Journal: Gut (2010)

Peutz–Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the S<i>TK11</i> gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype–phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.
Attention-Deficit/Hyperactivity Disorder in Adults
Authors: Timothy E Wilens, Stephen V Faraone, Joseph Biederman
Journal: JAMA (2004)

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
Presence of sorbin in human digestive tract and endocrine digestive tumours
Authors: F A. El Fadil-Nicol
Journal: Gut (2000)

<h3>BACKGROUND</h3> Sorbin, a 153 amino acid peptide isolated from porcine intestine, was localised by immunohistochemistry in endocrine cells of the intestinal mucosa and pancreas and in the enteric nervous system in the pig. <h3>AIMS</h3> To identify sorbin cells in normal human digestive tissues and to explore the expression of sorbin in 37 digestive endocrine tumours: 14 intestinal carcinoid tumours and 23 endocrine pancreatic tumours including six insulinomas. <h3>METHODS</h3> Two polyclonal antibodies against the C-terminal and the N-terminal sequences of porcine sorbin raised in rabbit were used to evaluate sorbin expression by immunohistochemistry. <h3>RESULTS</h3> In the human digestive tract, sorbin, characterised by both C-terminal and N-terminal immunoreactivity, was found in enterochromaffin cells of the gastric and intestinal epithelium from the pyloric junction to the descending colon. C-Terminal sorbin immunoreactivity alone was found in plexii from the enteric nervous system and in some insulin-containing cells of normal pancreas. C-Terminal and N-terminal antibodies disclosed sorbin in five of 14 intestinal carcinoid tumours; C-terminal antibody alone disclosed a C-terminal sorbin peptide in two of six insulinomas and three of 17 endocrine pancreatic tumours. The presence of sorbin was not associated with a specific clinical syndrome. <h3>CONCLUSIONS</h3> Sorbin is present in the digestive tract in several forms. It is expressed in some intestinal and pancreatic endocrine tumours.
Association of Exposure to Cow's Milk Protein and β-Cell Autoimmunity
Authors: H. Michael Dosch
Journal: JAMA (1996)

To the Editor.  —In another retrospective epidemiologic study of possible links between insulin-dependent diabetes mellitus (IDDM) and early infant-feeding history, Dr Norris and colleagues 1 have used a novel approach in analyzing not diabetic children, but 18 probands considered to be at risk for diabetes development as defined by the presence of 1 (n=14) or more (n=4) antibodies to insulin (78%), glutamic acid decarboxylase (GAD 65 ), or islet cell autoantigen (ICA) 512 combined with insulinoma-associated islet tyrosine phosphatases autoantibody (IA-2). The authors compared retrospective questionnaires to obtain early infant-feeding histories and found no differences between the probands and 153 unrelated comtrols. They conclude that diabetes risk is not linked to any nutritional antigens derived from either plant or animal sources. Based on the analysis of their very small cohort of children that may (or may not) develop diabetes, the authors reject similar studies that collectively analyzed more than 1000 diabetic
Hepatic differentiation of amniotic epithelial cells
Authors: Fabio Marongiu, Roberto Gramignoli, Kenneth Dorko, Toshio Miki, Aarati R. Ranade, Maria Paola Serra, Silvia Doratiotto, Marcella Sini, Shringi Sharma, Keitaro Mitamura, Tiffany L. Sellaro, Veysel Tahan, Kristen J. Skvorak, Ewa C. S. Ellis, Stephen F. Badylak, Julio C. Davila, Ronald Hines, Ezio Laconi, Stephen C. Strom
Journal: Hepatology (2011)

Abstract Hepatocyte transplantation to treat liver disease is largely limited by the availability of useful cells. Human amniotic epithelial cells (hAECs) from term placenta express surface markers and gene characteristics of embryonic stem cells and have the ability to differentiate into all three germ layers, including tissues of endodermal origin (i.e., liver). Thus, hAECs could provide a source of stem cell–derived hepatocytes for transplantation. We investigated the differentiation of hAECs in vitro and after transplantation into the livers of severe combined immunodeficient (SCID)/beige mice. Moreover, we tested the ability of rat amniotic epithelial cells (rAECs) to replicate and differentiate upon transplantation into a syngenic model of liver repopulation. In vitro results indicate that the presence of extracellular matrix proteins together with a mixture of growth factors, cytokines, and hormones are required for differentiation of hAECs into hepatocyte-like cells. Differentiated hAECs expressed hepatocyte markers at levels comparable to those of fetal hepatocytes. They were able to metabolize ammonia, testosterone, and 17α-hydroxyprogesterone caproate, and expressed inducible fetal cytochromes. After transplantation into the liver of retrorsine (RS)-treated SCID/beige mice, naïve hAECs differentiated into hepatocyte-like cells that expressed mature liver genes such as cytochromes, plasma proteins, transporters, and other hepatic enzymes at levels equal to adult liver tissue. When transplanted in a syngenic animal pretreated with RS, rAECs were able to engraft and generate a progeny of cells with morphology and protein expression typical of mature hepatocytes. Conclusion: Amniotic epithelial cells possess the ability to differentiate into cells with characteristics of functional hepatocytes both in vitro and in vivo , thus representing a useful and noncontroversial source of cells for transplantation. (Hepatology 2011;)
Predicting Human Tumor Drug Concentrations from a Preclinical Pharmacokinetic Model of Temozolomide Brain Disposition
Authors: Qingyu Zhou, Ping Guo, Gary D. Kruh, Paolo Vicini, Xiaomin Wang, James M. Gallo
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Knowledge of drug concentrations in tumors is critical for understanding the determinants of drug accumulation in tumors. Because significant obstacles prevent making these measurements in humans, development of a predictive pharmacokinetic model would be of great value to the translation of preclinical data to the clinic. Our goal was to show how the latter could be achieved for temozolomide, an agent used in the treatment of brain tumors, using an orthotopic brain tumor model in rats. Experimental Design: Rats bearing i.c. tumors received 20 mg/kg i.v. of temozolomide followed by the subsequent measurement of serial plasma, cerebrospinal fluid (CSF), normal brain, and brain tumor temozolomide concentrations. The resultant data provided the framework to develop a hybrid physiologically based pharmacokinetic model for temozolomide in brain. The preclinical pharmacokinetic model was scaled to predict temozolomide concentrations in human CSF, normal brain, and brain tumor, and through a series of Monte Carlo simulations, the accumulation of temozolomide in brain tumors under conditions of altered blood-brain barrier permeability, fractional blood volume, and clinical dosing schedules was evaluated. Results: The developed physiologically based pharmacokinetic model afforded a mechanistic and accurate prediction of temozolomide brain disposition in rats, which through model scale-up procedures accurately predicted the CSF/plasma area under the drug concentration-time curve ratios of 0.2 reported in patients. Through a series of model simulations, it was shown that the brain tumor accumulation of temozolomide varied substantially based on changes in blood-brain barrier permeability and fractional tumor blood volume but minimally based on clinical dosing regimens. Conclusions: A physiologically based pharmacokinetic modeling approach offers a means to translate preclinical to clinical characteristics of drug disposition in target tissues and, thus, a means to select appropriate drug dosing regimens for achieving optimal target tissue drug concentrations.
Gene Expression Profiles in Paraffin-Embedded Core Biopsy Tissue Predict Response to Chemotherapy in Women With Locally Advanced Breast Cancer
Authors: Luca Gianni, Milvia Zambetti, Kim Clark, Joffre Baker, Maureen Cronin, Jenny Wu, Gabriella Mariani, Jaime Rodriguez, Marialuisa Carcangiu, Drew Watson, Pinuccia Valagussa, Roman Rouzier, W. Fraser Symmans, Jeffrey S. Ross, Gabriel N. Hortobagyi, Lajos Pusztai, Steven Shak
Journal: Journal of Clinical Oncology (2005)

Purpose We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Methods Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Results Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P &lt; .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) –related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P &lt; .05 (false discovery, four genes) and 32 genes showed correlation with P &lt; .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit. Conclusion Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.
Congenital Duodenal Obstruction and Double-Bubble Sign
Authors: Jorge Correia-Pinto, Andreia Ribeiro
Journal: New England Journal of Medicine (2014)

A 1080-g girl was born at a gestational age of 29 weeks because of premature rupture of membranes. Enteral feeding was not tolerated. The infant's condition deteriorated, with nonbilious vomiting and a lack of stools. Abdominal radiography showed the double-bubble sign.
Abstract 2227: Aptamer selection for cancer markers: High-throughput, quantitative selection and characterization of nucleic acid aptamers for human angiopoietin-2.
Authors: Minseon Cho, Seung Soo Oh, Jeff Nie, Ron Stewart, Michael Eisenstein, James Chambers, Jamey D. Marth, James A. Thomson, Tom H. Soh
Journal: Cancer Research (2013)

Abstract Abstract Nucleic acid-based aptamers represent a promising class of affinity reagents, as they can be chemically synthesized and modified, undergo reversible folding and exhibit excellent stability. Thus, the identification of aptamers that bind to specific cancer markers may serve as a powerful tool for early diagnosis and treatments of cancers. Unfortunately, conventional methods of aptamer generation remain inherently low-throughput in nature, and there is a pressing need for alternative technologies that can generate high quality aptamers in a high-throughput and economical manner. Towards the goal of accelerating aptamer discovery, we have developed the Quantitative Parallel Aptamer Selection System (QPASS) - an integrated platform that combines microfluidic selection, next-generation sequencing and in situ-synthesized aptamer arrays for parallel binding measurements. As a model, we used QPASS to select aptamers that specifically bind to human angiopoietin-2, an important mediator of angiogenesis and a biomarker of colon, prostate and breast cancers; after microfluidic selection and sequencing, we fabricated a custom aptamer array containing 120,000 sequences representing the most enriched aptamer candidates. Using this array, we simultaneously obtained equilibrium dissociation constants (Kd) and binding specificity data for these candidate aptamers in a massively parallel manner. Furthermore, we show that our array can operate directly in undiluted serum, enabling rapid identification of aptamers that perform optimally in complex mixtures. By exploiting the scalability and commercial availability of high-throughput sequencing and nucleic acid arrays, the QPASS platform offers the capability to simultaneously analyze and characterize unprecedented numbers of aptamer candidates—either against a common cancer marker, or for screening in parallel against multiple different biomarkers. Citation Format: Minseon Cho, Seung Soo Oh, Jeff Nie, Ron Stewart, Michael Eisenstein, James Chambers, Jamey D. Marth, James A. Thomson, Tom H. Soh. Aptamer selection for cancer markers: High-throughput, quantitative selection and characterization of nucleic acid aptamers for human angiopoietin-2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2227. doi:10.1158/1538-7445.AM2013-2227
Renal Tubular Acidosis
Authors: F J Gennari, J J Cohen
Journal: Annual Review of Medicine (1969)

Renal tubular acidosis (RTA) is recognized to occur in several forms. Primary proximal RTA presents in infancy, almost exclusively in males, and is the only form of primary RTA that is transient. Distal RTA is encountered in familial and sporadic forms, the latter predominantly in females. A severe form of distal RTA in infancy, recently recognized, may represent still another type of the disease.
Therapeutic Targeting of the Interleukin-6 Receptor
Authors: Toshio Tanaka, Masashi Narazaki, Tadamitsu Kishimoto
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Interleukin (IL)-6 is a typical cytokine featuring redundancy and pleiotropic activity. It contributes to host defense against pathogens, but dysregulation of IL-6 production plays a significant pathological role in various autoimmune and inflammatory diseases. Because IL-6 blockade was expected to constitute a novel strategy for the treatment of such diseases, tocilizumab, a humanized anti-IL-6 receptor antibody (anti-IL-6RAb), was developed. Clinical trials have demonstrated the efficacy of anti-IL-6RAb for patients with rheumatoid arthritis, Castleman's disease, and juvenile idiopathic arthritis, resulting in approval of this innovative biologic for the treatment of these diseases, and it can be expected to become a novel drug for various other autoimmune and inflammatory diseases. In murine models of autoimmune diseases, anti-IL-6RAb induces Treg and inhibits Th17 and/or Th1 differentiation, indicating that anti-IL-6RAb may be able to repair Th17/Treg imbalance in human diseases as well.