tbuckley/cabot-search huggingface dataset:
Dipeptidyl peptidase IV expression in a cellular and human model of intestinal inflammation
Authors: G. Moran, C. O'Neill, P. Padfield, J. McLaughlin
Journal: Gut (2011)

<h3>Introduction</h3> Dipeptidyl peptidase IV (DP IV) is a serine protease. It modulates the physiological activity of satiety inducing hormones such as glucagon like peptide 1 (GLP-1) and polypeptide YY (PYY). It also inactivates GLP-2, an enteroendocrine hormone with cytoprotective and reparative properties. By cleaving chemokines essential for the Th-2 inflammatory pathway, DP IV enhances the Th-1 pathway. Reduced serum DP IV activity has been observed in patients with inflammatory bowel disease (IBD) including Crohn9s disease (CD). Plasma levels and tissue expression have never been described together. The latter is of particular clinical significance since this is the local site of action of trophic GLP-2 and GLP-1 mediated vagal afferent stimulation. <h3>Methods</h3> Experiments were also carried out on a Caco-2 cell line model of intestinal inflammation with TNFα incubation in a graded concentration/time course. DP IV expression was studied at the mRNA level through quantitative PCR (qPCR) and protein level by tissue western blotting and plasma ELISA. DP IV expression was also studied in active small (n=18) and large bowel CD (n=5). A subgroup of patients were restudied when inactive (n=6) and all results were compared to healthy controls (n=17). <h3>Results</h3> In Caco-2 cells an ∼ 18-fold increase (p&lt;0.0001) in DP IV protein expression was seen after incubation with TNFα at a concentration of 25 ng/μl for 48 h, as compared to untreated cells. This change is mirrored at the mRNA level with a twofold increase in DP IV expression at similar TNFα concentration and time course. Similar changes were noted in human tissue with a significant 4.5-fold DP IV upregulation (p=0.02) in CD compared to normal controls. However, results at the protein level in human tissue showed an opposite trend, with a ∼2.7-fold decrease in DP IV expression in CD tissue compared to controls (p=0.05). The highest DP IV fasting plasma levels were noted in the control group (558.5±39.98 ng/ml). Levels in CD were significantly less (p=0.0028) both in large bowel CD (406.2±48.10 ng/ml) and more so in the small bowel CD group (361.3±38.83 ng/ml; p&lt;0.01). There was no significant difference in plasma DP IV between active and inactive disease. <h3>Conclusion</h3> Results in the reductionist cellular model of intestinal inflammation support an increase in DP IV in an inflammatory milieu. However, in the complex, chronic human disease DP IV expression is decreased, as observed in other inflammatory states such human inflammatory arthritis and systemic lupus erythematosus. It is possible that a decrease in DP IV would preserve more biologically active GLP-2, enhancing trophic activity and promoting repair. DP IV may present a potential therapeutic target in IBD.
Scientific Program
Journal: JAMA (1967)

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
NO FEAR OF CHOLERA.
Journal: JAMA (1893)

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
Correction: Discovery and validation of a prognostic proteomic signature for tuberculosis progression: A prospective cohort study
Authors: Adam Penn-Nicholson, Thomas Hraha, Ethan G. Thompson, David Sterling, Stanley Kimbung Mbandi, Kirsten M. Wall, Michelle Fisher, Sara Suliman, Smitha Shankar, Willem A. Hanekom, Nebojsa Janjic, Mark Hatherill, Stefan H. E. Kaufmann, Jayne Sutherland, Gerhard Walzl, Mary Ann De Groote, Urs Ochsner, Daniel E. Zak, Thomas J. Scriba
Journal: PLoS Medicine (2019)

[This corrects the article DOI: 10.1371/journal.pmed.1002781.].
Periodontal Disease May Pose One Risk for Premature Birth
Authors: C. Marwick
Journal: JAMA (2000)

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
Error in Figure
Authors: Charles Brown Iv, Charles Hogue
Journal: JAMA Surgery (2020)

Patients: A Nested Randomized Clinical Trial." 1 We recognize that this is a small single-center study with limitations.The methods used to characterize autoregulation in this particular study can be labor intensive and the data subject to interpretation.There were some differences between groups in perioperative characteristics, including obstructive sleep apnea and temperature management.For all of these reasons and more, we tried to be tempered in our conclusions, in particular stating that "these results should be considered preliminary and need to be confirmed in a broad population." 1 We do point out that the study was randomized, and the outcome assessment was rigorous, each of which limits important sources of bias.Clinicians were generally masked and so the autoregulation methods should not have affected postoperative care and/or sedation protocols.Although delirium is multifactorial, cerebrovascular contributions may be important after cardiac surgery.We did collect information on Bispectral index and cerebral oximetry in many patients and plan to examine associations with delirium in future studies.We did not systematically vary mean arterial pressure to characterize autoregulation (because we thought this would not be ethical in a high-risk group), but rather relied on spontaneous fluctuations in a range of blood pressures observed prior to cardiopulmonary bypass.An experienced investigator interpreted the data for all patients, thus ensuring consistency across the study.Our results suggest that prebypass data have physiologic relevance during bypass, although characterization of the factors that may affect autoregulation during bypass remains an important research question.The results of this study, coupled with the comments discussed in these letters, support the need for a large multicentered study, using autoregulation monitoring based on cerebral oximetry (ie, less labor-intensive methods), with the study design primarily focused on delirium as a primary outcome.Such a study would provide important, robust, and generalizable information on whether cerebral autoregulation monitoring could be used to reduce the incidence of a common and important complication after cardiac surgery.
A post-mortem study of gastric and duodenal peptic lesions: Part II Correlations with other pathological conditions
Journal: Gut (1963)

1949 the Rotterdam laboratory had the same Director, and the same necropsy technique was used.An increased use of steroids, salicylates, or other anti-inflammatory drugs has been advanced to explain this rise but in fact no sudden increase in the requests for these drugs at that time could be demonstrated by Dr. Lenstra in the Pharmacy of the Rotterdam Municipal Hospitals. SUMMARYThe frequency of peptic lesions of the stomach and the duodenum in post-mortem material of the Central Pathological Laboratory of the Municipal Hospitals of Rotterdam, Netherlands, has been investigated.From May 1940 to January 1959 11,125 necropsies were performed on persons of 20 years and older.
VACCINATION IN PORTO RICO.
Journal: JAMA (1901)

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
Findings May Lead to New Strategies for GVHD
Journal: Cancer Discovery (2017)

A new study in mice demonstrates that activating the RIG-I and STING signaling pathways, normally associated with antiviral immunity, can help protect the intestinal epithelium from damage caused by chemotherapy and radiation following stem cell transplantation. The findings may help in developing strategies to prevent graft-versus-host disease in patients with leukemia and other blood disorders.
Neurohumoral Blood Pressure Regulation in Lead Exposure
Authors: Paolo Boscolo, Marco Carmignani
Journal: Environmental Health Perspectives (1988)

Previous human studies demonstrated that lead exposure may modify the metabolism of catecholamines and of hormones controlled by the hypothalamo-pituitary axis and may affect the kallikrein-kinin system. This paper reports unpublished data on the plasma renin activity of lead-exposed workers; these results are in agreement with those of previous human and experimental studies suggesting that the synthesis or release of renin is increased after short and moderate exposure to inorganic lead and reduced whenever the exposure is prolonged. Previous experimental investigations demonstrated that lead may act on the cardiovascular system, with effects on the renin-angiotensin system, on the reactivity to stimulation of peripheral catecholaminergic receptors, on sympathetic and vagal tone, and on reactivity to the stimulation of baroreceptors. This paper reports the results of a study on male Sprague-Dawley rats that received 0, 15, 30, and 60 micrograms/mL of lead in drinking water for 18 months. Blood pressure was increased in the rats receiving 30 and 60 ppm of lead; cardiac inotropism was augmented only in those receiving the higher dose of the metal, and heart rate was not modified. Cardiovascular responses to agonists indicated that lead exposure affects the renin-angiotensin system and induces sympathetic hyperactivity by acting on central and peripheral sympathetic junctions increasing the responsiveness to stimulation of alpha 2-adrenoreceptors and by increasing the reactivity to stimulation of cardiac and vascular beta-adrenergic and dopaminergic receptors. The cAMP-dependent availability of Ca2+ for contractile mechanisms of the cardiovascular muscle cells was affected by lead.
Animal Model for AIDS Dementia?
Journal: JAMA (1992)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A penicillin shot without culturing the child's throat
Authors: L. W. Wannamaker
Journal: JAMA (1976)

ENTHUSIASM for throat cultures varies widely among physicians in practice. Some rely solely and precariously on their clinical acumen. Although clinical findings are important in diagnosing streptococcal sore throat, they are not sufficiently distinctive to provide the basis for a foolproof diagnosis.<sup>1,2</sup>The batting average among experienced physicians in predicting which sore throats will be culture-positive for β-hemolytic streptococci is poor (only slightly better than 50% without cultures, about 75% if they have the advantage of culture results from other patients). Red throats are nonspecific. Exudate occurs frequently in streptococcal pharyngitis, but it may not appear until the second day and may also be found in viral infections. In infants, exudative pharyngitis is rarely streptococcal in cause. Anterior cervical nodes that are tender to palpation are one of the most reliable clinical indicators of streptococcal infection,<sup>3</sup>but they are not present in all patients. The rash we associate
Undescended testis
Authors: L. R. King
Journal: JAMA (1996)

Q Left-sided inguinal exploratory surgery in a 5-year-old boy for a unilateral undescended testis demonstrated a normal vas deferens just beneath the external oblique fascia. The vas terminated in a 1.2-cm fibrous nodule located just outside the external ring. The nodule was excised, and histologic study showed portions of the vas deferens and hyalinized tissue with dystrophic calcification and without definable organoid structures. Now, 25 years later, the patient is healthy and has a normal testis palpable in the opposite side of the scrotum. Can it be assumed that the structure at the end of the vas was a maldeveloped testis? Is it possible that the actual testis remains undetected in the retroperitoneum, and therefore poses an increased risk for the development of a malignancy? If so, would imaging studies be helpful in searching for an undescended testis? <b>A</b>It has become unusual in the United States for boys with
ABSTRACTS
Authors: Joseph Ross, Helen Balding, N Maier, Sheila Callender, Maws Nm, George Cartwright, Jean Soulier, Roger Crafts, M Suarez, San Juan, Puerto Rico, Charles Emerson, Wm Valentine, Solomon Estren, Philip Wagley, F Hampton, H Mayerson, F Roofe, H Latirner, M Madison, M Maffet, F Wilkinson
Journal: Blood (1950)
A phase I trial of the human double minute 2 (HDM2) inhibitor MK-8242 in patients (pts) with advanced solid tumors.
Authors: Andrew J. Wagner, Udai Banerji, Amit Mahipal, Neeta Somaiah, Heather Anne Hirsch, Craig Fancourt, Amy Levonas, Raymond Lam, Amy Meister, Ramon Karmel Kemp, Clayton Knox, Shelonitda Rose, David S. Hong
Journal: Journal of Clinical Oncology (2015)

10564 Background: HDM2 binds and inhibits wild-type (WT) p53 thereby promoting oncogenesis. MK-8242 is a potent, orally bio-available, small-molecule inhibitor of the HDM2:p53 protein-protein interaction under development as a novel cancer therapy. Methods: A multi-center, 2-part (dose escalation/Part I and confirmation/Part 2; using modified TPI design) Phase I study of MK-8242, administered p.o. BID on days 1-7 in 21 day cycles, was performed to determine the safety, tolerability, and recommended Phase 2 dose (RP2D) in pts with advanced solid tumors with WT p53. RP2D was based on tolerability, plasma pharmacokinetics (PK), and pharmacodynamics (PD) in tumor/blood, including expression of the p53 target PHLDA3. Other objectives were characterizing PK/PD relationship, correlation of biomarkers with response, and assessment of tumor response (RECIST v1.1). Results: 47 pts received MK-8242 across 8 dose levels ranging from 60 mg to 500 mg. Initially, 6 pts developed DLTs (G2 nausea at 120 mg; G3 fatigue at 250 mg; G2 nausea and G4 thrombocytopenia at 350 mg; G3 vomiting and G3 diarrhea at 500 mg). DLT criteria were revised to permit management of GI toxicity, and 4 additional DLTs were observed (G4 neutropenia and G4 thrombocytopenia at 400 mg; G4 thrombocytopenia [2 pts] at 500 mg). Other drug-related G3-4 events included anemia, leukopenia, pancytopenia, nausea, hyperbilirubinemia, hypophosphatemia, and anorexia. The RP2D was established at 400 mg as tolerability (i.e., 2 DLTs in 14 evaluable pts), PK, and PD targets were achieved at this dose level. Plasma PK analysis of 400 mg on Day 7 found AUC0-12hr of 16.7 µM*hr, Cmax 3.1 µM, Tmax 2-6 hr, and T1/2 6.5 hr. Blood concentration of PHLDA3 correlated with drug exposure (R2 = 0.69, p < .0010). In 41 pts who had post-baseline scans, 31 showed SD, 2 achieved PR (both with liposarcoma [LPS], at 250 mg and 400 mg), 8 had PD. 7 pts with LPS remain on study. In total, 27 pts had LPS and their median time-to-progression was > 300 days. Conclusions: At the RP2D of 400 mg BID, MK-8242 activates the p53 pathway with an acceptable tolerability profile. Preliminary evidence of clinical activity with PR and prolonged PFS was seen providing impetus for further study of HDM2 inhibitors in LPS pts. Clinical trial information: NCT01463696.
Seeking Forgiveness
Authors: Michael A. LaCombe
Journal: Annals of Internal Medicine (1999)

Editorials2 March 1999Seeking ForgivenessMichael A. LaCombe, MDMichael A. LaCombe, MDHarrison, ME 04040 (LaCombe)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-5-199903020-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail If there is a common theme running through the submissions to the On Being a Doctor section of Annals of Internal Medicine, it is the story of the physician suddenly confronted by his own humanity. In form, this most commonly centers upon a dying patient, the physician overwhelmed by emotion, all at once aware of the depth of his or her caring. Much of the poetry submitted to the Ad Libitum section takes this form as well, such that together, we, the editorial staff, have come to refer to these submissions collectively as the “death-and-dying” pieces.Far less common, but ...Reference1. Costigan DJ. Trying to let go. Ann Intern Med. 1999;130:446. LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Michael A. LaCombe, MDAffiliations: Harrison, ME 04040 (LaCombe)Corresponding Author: Michael A. LaCombe, MD, 1303 Naples Road, Harrison, ME 04040. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTrying To Let Go David J. Costigan Metrics Cited byMedical Students' Experience of Academic Review and Promotions CommitteesAt wit’s end 2 March 1999Volume 130, Issue 5Page: 444-445KeywordsEmergency medical techniciansEmotionsImmunityIntubationJewish peoplePostural controlRunningSafetyShouldersThorax ePublished: 15 August 2000 Issue Published: 2 March 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Drug May Counteract Depression Caused by Ethanol Intoxication
Journal: JAMA (1964)

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