tbuckley/cabot-search huggingface dataset:
Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction
Authors: Jingying Wang, Chao Tong, Xiaoyan Yan, Eddie Yeung, Sunilkumar Gandavadi, Alissa A. Hare, Xin Du, Yibang Chen, Huabao Xiong, Changxing Ma, Lin Leng, Lawrence H. Young, William L. Jorgensen, Ji Li, Richard Bucala
Journal: Circulation (2013)

Background— Macrophage migration inhibitory factor (MIF) exerts a protective effect on ischemic myocardium by activating AMP-activated protein kinase (AMPK). Small molecules that increase the affinity of MIF for its receptor have been recently designed, and we hypothesized that such agonists may enhance AMPK activation and limit ischemic tissue injury. Methods and Results— Treatment of cardiomyocytes with the candidate MIF agonist, MIF20, augmented AMPK phosphorylation, increased by 50% the surface localization of glucose transporter, and enhanced by 25% cellular glucose uptake in comparison with MIF alone. In mouse hearts perfused with MIF20 before no-flow ischemia and reperfusion, postischemic left ventricular function improved commensurately with an increase in cardiac MIF-AMPK activation and an augmentation in myocardial glucose uptake. By contrast, small-molecule MIF agonism was not effective in cells or tissues genetically deficient in MIF or the MIF receptor, verifying the specificity of MIF20 for MIF-dependent AMPK signaling. The protective effect of MIF20 also was evident in an in vivo regional ischemia model. Mice treated with MIF20 followed by left coronary artery occlusion and reperfusion showed a significant reduction in infarcted myocardium. Conclusions— These data support the pharmacological utility of small-molecule MIF agonists in enhancing AMPK activation and reducing cardiac ischemic injury.
ABC's of Interpretive Laboratory Data
Authors: B. Bergeron
Journal: JAMA (2003)

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
Failure of clonal deletion in neonatally thymectomized mice: tolerance is preserved through clonal anergy.
Authors: L A Jones, L T Chin, G R Merriam, L M Nelson, A M Kruisbeck
Journal: The Journal of Experimental Medicine (1990)

Self-tolerance is achieved in part through intrathymic deletion of self-reactive T cells. The necessity of the thymus for this process is suggested by the development of autoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure of clonal deletion in nude mice. Indeed, the present study demonstrates that neonatal thymectomy on day 3 after birth results in the failure of clonal deletion of V beta 11+ T cells in BALB/c mice and V beta 5+ and V beta 6+ T cells in DBA/2 mice. However, these potentially autoreactive cells are nonfunctional as measured by proliferation and lymphokine production after stimulation with appropriate anti-V beta mAbs or stimulator cells. It appears that this induction of nonresponsiveness may have occurred extrathymically: the early neonatal thymus (presumably the source of the peripheral T cells observed in neoTx mice) also contains T cells with self-reactive receptors, but these cells are fully functional. Therefore, neonatal thymectomy aborts deletion of self-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones.
Rapid Alteration of MicroRNA Levels by Histone Deacetylase Inhibition
Authors: Gary K. Scott, Michael D. Mattie, Crystal E. Berger, Stephen C. Benz, Christopher C. Benz
Journal: Cancer Research (2006)

Abstract Improved understanding of the molecular mechanisms by which small-molecule inhibitors of histone deacetylases (HDAC) induce programs, such as cellular differentiation and apoptosis, would undoubtedly assist their clinical development as anticancer agents. As modulators of gene transcript levels, HDAC inhibitors (HDACi) typically affect only 5% to 10% of actively transcribed genes with approximately as many mRNA transcripts being up-regulated as down-regulated. Using microRNA (miRNA) array analysis, we report rapid alteration of miRNA levels in response to the potent hydroxamic acid HDACi LAQ824 in the breast cancer cell line SKBr3. Within 5 hours of exposure to a proapoptotic dose of LAQ824, significant changes were measured in 40% of the &amp;gt;60 different miRNA species expressed in SKBr3 cells with 22 miRNA species down-regulated and 5 miRNAs up-regulated. To explore a potential functional link between HDACi induced mRNA up-regulation and miRNA down-regulation, antisense experiments were done against miR-27a and miR-27b, both abundantly expressed and down-regulated in SKBr3 cells by LAQ824. Correlating a set of genes previously determined by cDNA array analysis to be rapidly up-regulated by LAQ824 in SKBr3 with a database of potential 3′ untranslated region miRNA binding elements, two genes containing putative miR-27 anchor elements were identified as transcriptionally up-regulated following miR-27 antisense transfection, ZBTB10/RINZF, a Sp1 repressor, and RYBP/DEDAF, an apoptotic facilitator. These findings emphasize the importance of post-transcriptional mRNA regulation by HDACi in addition to their established effects on promoter-driven gene expression. (Cancer Res 2006; 66(3): 1277-81)
Gastric metaplasia and Helicobacter pylori infection.
Authors: L A Noach, T M Rolf, N B Bosma, M P Schwartz, J Oosting, E A Rauws, G N Tytgat
Journal: Gut (1993)

Duodenal and antral mucosal biopsy specimens were obtained from 139 patients with dyspeptic complaints to study the prevalence and extent of gastric metaplasia in the duodenal bulb in relation to Helicobacter pylori (H pylori) infection and duodenal ulcer disease. On logistic regression, the presence and extent of gastric metaplasia was not significantly associated with H pylori infection. The prevalence of gastric metaplasia, however, was found to be higher in patients with current or past evidence of duodenal ulcer disease in comparison with subjects with functional dyspepsia (p = 0.01). A follow up study on 22 patients before and at least one year after eradication of H pylori showed that the mean extent of gastric metaplasia did not change significantly after eradication and did not differ when compared with 21 patients with persisting infection. It is concluded that the unchanged gastric acid output after eradication of H pylori is a more important factor in the development of gastric metaplasia than the H pylori related inflammatory process.
Endoscopic mucosal resection of early esophageal squamous cell cancer using the Duette mucosectomy kit
Authors: S. Seewald, T. Ang, S. Omar, S. Groth, F. Dy, Y. Zhong, U. Seitz, F. Thonke, E. Yekebas, J. Izbicki, N. Soehendra
Journal: Endoscopy (2006)

Background and study aim: Endoscopic mucosal resection (EMR) is a less invasive alternative treatment strategy to surgery for intramucosal esophageal squamous cell carcinoma (SCC). This study described our initial experience with the newly introduced Duette Multiband Mucosectomy Kit (Cook Ireland Ltd, Limerick, Ireland) for the treatment of extensive early esophageal SCC. Patients and methods: Five patients with extensive early esophageal SCC, covering at least half of the circumference of the esophageal wall and measuring a mean of 2.8 cm longitudinally, underwent EMR after EUS staging. Results: EMR was successfully completed in one session in five patients. Post-EMR stricture occurred in four patients but was successfully treated with bougienage. One patient did not return for follow-up after bougienage and died from ischemic heart disease 3 months later. For the remaining four patients, there was no recurrence over a mean follow up of 14.7 months. Conclusion: This new device obviates the need for repeated insertion of the endoscope during the process of ligation and resection and thus facilitates EMR of extensive SCC.
Polydipsia Associated with Occult Hydrocephalus
Authors: Patrick A. Hogan, Robert M. Woolsey
Journal: New England Journal of Medicine (1967)

OCCULT hydrocephalus is usually accompanied by symptoms of headache, dementia or gait disturbance that may occur individually or in any possible combination.1 The patient reported below showed hyperdipsia as the first manifestation of the hydrocephalic process.Case ReportR.G., a 10-year-old boy, was admitted to Cardinal Glennon Memorial Children's Hospital on February 8, 1964, because of daily bitemporal headaches and staggering gait for 4 months. Three years previously he had been evaluated for excessive water drinking, reportedly requiring a glass of water every half hour and voiding equally often during his waking hours only. Physical examination and laboratory tests, including . . .
Who are tomorrow's generalists?
Authors: J. Smith
Journal: BMJ (2012)

People have been lamenting the decline of the general physician for decades—so it’s good to see that the tide may now be turning.

In their Analysis article Robert M Wachter and Derek Bell describe the renaissance of hospital generalists on both sides of the Atlantic (doi:10.1136/bmj.e652). The reasons—growing numbers of older patients with complex multiple illnesses and curtailed hours for trainee doctors—are similar in the UK and the United States, but generalists have taken different forms in each country. In America hospitalists are responsible for the general medical care of patients during their entire stay in hospital, working alongside specialists. In the UK, physicians in acute medicine manage patients in the first …
Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia
Authors: Chen Shochat, Noa Tal, Vitalina Gryshkova, Yehudit Birger, Obul R. Bandapalli, Giovanni Cazzaniga, Nava Gershman, Andreas E. Kulozik, Andrea Biondi, Marc R. Mansour, Jean-Claude Twizere, Martina U. Muckenthaler, Nir Ben-Tal, Stefan N. Constantinescu, Dani Bercovich, Shai Izraeli
Journal: Blood (2014)
Case 44-1962
Authors: Warren Point, Austin L. Vickery
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A fifty-eight-year-old man was admitted to the hospital because of abdominal pain.One year previously the patient had a protracted episode of vomiting that was attributed to a viral infection. Subsequently, he began to experience episodic periumbilical pain accompanied by nonradiating pain in the back at the level of the first lumbar vertebra. The pain was constant, severe and aching and usually occurred a half to one hour after eating, frequently with intermittent vomiting. The pain and vomiting often lasted for one or two days and then regressed to a constant dull ache in . . .
Results of routine preoperative coronary angiography in tetralogy of Fallot.
Authors: K E Fellows, M D Freed, J F Keane, R Praagh, W F Bernhard, A C Castaneda
Journal: Circulation (1975)

In the surgical repair of tetralogy of Fallot, morvidity and mortality are increased by certain coronary anomalies, in particular, an anterior descending branch originating from the right coronary artery or a single coronary artery in which a large coronary branch runs across the pulmonary outflow tract. In series of 94 patients with tetralogy of Fallot who underwent cardiac catheterization, coronary artery visualization was attempted routinely, most often by flush aortography using a venous catheter. Diagnostic coronary visualization was obtained in 84 patients (89%). In these, the incidence of recognized coronary anomalies was 5%; anterior decending from the right coronary artery in four patients (4%), and singly left coronary in one patient (1%). In 195 autopsied cases of tetralogy, the incidence of coronary anomalies was also 5%. Routine preoperative demonstration of the coronary artery anatomy in tetralogy patients usually can be accomplished satisfactorily and conveniently by transvenous flush aortography.
High-Intensity Signals in Coronary Plaques on Noncontrast T1-Weighted Magnetic Resonance Imaging as a Novel Determinant of Coronary Events
Authors: Teruo Noguchi, Tomohiro Kawasaki, Atsushi Tanaka, Satoshi Yasuda, Yoichi Goto, Masaharu Ishihara, Kunihiro Nishimura, Yoshihiro Miyamoto, Koichi Node, Nobuhiko Koga
Journal: Journal of the American College of Cardiology (2013)
Phenobarbital-induced Alterations in the Metabolism of [3H]Vitamin D3 by the Perfused Rachitic Rat Liver In Vitro
Authors: Daniel T. Baran, Aurora C. Fausto, Marilyn L. Roberts, Irene Karl, Louis V. Avioli
Journal: Journal of Clinical Investigation (1979)

Anticonvulsant therapy of seizure disorders in man is associated with the development of complications involving bone and mineral metabolism including hypocalcemia, elevated serum immunoreactive parathyroid hormone levels, and increased amounts of unmineralized bone or osteoid. The latter has been attributed to a reduction in serum-25-hydroxycholecalciferol levels resulting from increased hepatic metabolism of vitamin D. Using an in vitro recycling hepatic perfusion system, we have demonstrated that 5 d of phenobarbital treatment increases the hepatic production of [(3)H]25-hydroxyvitamin D(3) (4.3+/-0.3 vs. 3.3+/-0.2%/h, P <0.025) without affecting the biliary excretion of radioactivity. Furthermore, rachitic livers perfused with blood obtained from animals treated with phenobarbital for 5 d also manifested an increase in [(3)H]25-hydroxyvitamin D(3) production (4.6+/-0.5 vs. 3.3+/-0.2%/h, P < 0.02). Addition of phenobarbital or its major metabolite, p-hydroxyphenobarbital, directly to the perfusion apparatus had no effect on [(3)H]25-hydroxyvitamin D(3) production. Phenobarbital treatment was also attended by a decrease in the intrahepatic content of [(3)H]vitamin D(3) (11.7+/-0.4 vs. 17.5+/-0.7 dpm/mg liver protein, P < 0.001) without alterations in the content of [(3)H]25-hydroxyvitamin D(3). The data collectively suggest that the increased hepatic conversion of [(3)H]vitamin D(3) to [(3)H]25-hydroxyvitamin D(3) attending phenobarbital treatment is secondary to stimulation of the hepatic 25-hydroxylation system(s) by a metabolite of phenobarbital other than p-hydroxyphenobarbital and/or by metabolic alterations resulting from phenobarbital therapy.
Cord Serum Concentrations of Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoate (PFOA) in Relation to Weight and Size at Birth
Authors: Benjamin J. Apelberg, Frank R. Witter, Julie B. Herbstman, Antonia M. Calafat, Rolf U. Halden, Larry L. Needham, Lynn R. Goldman
Journal: Environmental Health Perspectives (2007)

BackgroundRecent studies have reported developmental toxicity among rodents dosed with perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA).ObjectivesWe examined the relationship between concentrations of PFOS and PFOA in cord serum (surrogates for in utero exposures) and gestational age, birth weight, and birth size in humans.MethodsWe conducted a hospital-based cross-sectional epidemiologic study of singleton deliveries in Baltimore, Maryland. Cord serum samples (n = 293) were analyzed for PFOS and PFOA by online solid-phase extraction, coupled with reversed-phase high-performance liquid chromatography–isotope dilution tandem mass spectrometry. Maternal characteristics and anthropometric measures were obtained from medical charts.ResultsAfter adjusting for potential confounders, both PFOS and PFOA were negatively associated with birth weight [per ln-unit: β = −69 g, 95% confidence interval (CI), −149 to 10 for PFOS; β = −104 g, 95% CI, −213 to 5 for PFOA], ponderal index (per ln-unit: β = −0.074 g/cm3 × 100, 95% CI, −0.123 to −0.025 for PFOS; β = −0.070 g/cm3 × 100, 95% CI, −0.138 to −0.001 for PFOA), and head circumference (per ln-unit: β = −0.32 cm, 95% CI, −0.56 to −0.07 for PFOS; β = −0.41 cm, 95% CI, −0.76 to −0.07 for PFOA). No associations were observed between either PFOS or PFOA concentrations and newborn length or gestational age. All associations were independent of cord serum lipid concentrations.ConclusionsDespite relatively low cord serum concentrations, we observed small negative associations between both PFOS and PFOA concentrations and birth weight and size. Future studies should attempt to replicate these findings in other populations.
Monitoring for Side Effects of NSAIDs
Authors: Garth K. Graham
Journal: JAMA (1991)

To the Editor.—  In his editorial comment 1 concerning nonsteroidal anti-inflammatory drug (NSAID) side effects, Dr Gay has placed an important safety issue in excellent perspective and noted a rare but morbidly important outcome to the use of a group of drugs that have a favorable effect on patients' quality of life. In his concluding remarks, however, he states that, We would be well advised, then, to monitor liver functions (especially the transaminases) carefully and serially [emphasis added] in any patient undergoing long-term NSAID therapy.  Like it or not, the terms carefully and serially may well be presented for definition to a jury of lay persons in our litigious environment. Advice so worded places an unnecessary burden on prescribing physicians since their carefulness and the appropriate frequency of their serial testing will probably be judged retrospectively. In fact, the case reports of Helfgott et al 2 neither support nor negate
Inhibition of mammalian target of rapamycin aggravates the respiratory burst defect of neutrophils from decompensated patients with cirrhosis
Authors: Loïc Rolas, Nesrine Makhezer, Soumeya Hadjoudj, Jamel El-Benna, Bahia Djerdjouri, Laure Elkrief, Richard Moreau, Axel Périanin
Journal: Hepatology (2012)

Cirrhosis is commonly accompanied by impaired defense functions of polymorphonuclear leucocytes (PMNs), increased patient susceptibility to infections, and hepatocellular carcinoma (HCC). PMN antimicrobial activity is dependent on a massive production of reactive oxygen species (ROS) by nicotinamide adenine dinucleotide phosphate (NADPH) 2 (NADPH oxidase 2; NOX2), termed respiratory burst (RB). Rapamycin, an antagonist of mammalian target of rapamycin (mTOR), may be used in the treatment of HCC and in transplanted patients. However, the effect of mTOR inhibition on the PMN RB of patients with cirrhosis remains unexplored and was studied here using the bacterial peptide, formyl-Met-Leu-Phe (fMLP), as an RB inducer. fMLP-induced RB of PMN from patients with decompensated alcoholic cirrhosis was strongly impaired (30%-35% of control) as a result of intracellular signaling alterations. Blocking mTOR activation (phospho-S2448-mTOR) with rapamycin further aggravated the RB defect. Rapamycin also inhibited the RB of healthy PMNs, which was associated with impaired phosphorylation of the NOX2 component, p47 phox (phox: phagocyte oxidase), on its mitogen-activated protein kinase (MAPK) site (S345) as well as a preferential inhibition of p38-MAPK relative to p44/42-MAPK. However, rapamycin did not alter the fMLP-induced membrane association of p47 phox and p38-MAPK in patients' PMNs, but did prevent their phosphorylation at the membranes. The mTOR contribution to fMLP-induced RB, phosphorylation of p47 phox and p38-MAPK was further confirmed by mTOR knockdown in HL-60 cells. Finally, rapamycin impaired PMN bactericidal activity, but not bacterial uptake. Conclusion : mTOR significantly up-regulates the PMN RB of patients with cirrhosis by p38-MAPK activation. Consequently, mTOR inhibition by rapamycin dramatically aggravates their PMN RB defect, which may increase patients' susceptibility to infection. Thus, concerns should be raised about the use of rapamycin in immuno-depressed patients. (Hepatology 2013)
Why specific design is not the mark of the adaptational
Authors: Jerome C. Wakefield
Journal: Behavioral and Brain Sciences (2002)

Andrews et al.'s analysis suffers from a series of conceptual confusions they inherit from Gould's work. Their proposal that adaptations can be distinguished from exaptations essentially by specific design criteria fails because exaptations are often maintained and secondarily adapted by natural selection and therefore, over evolutionary time, can come to have similar levels of design specificity to adaptations.
Patient vs Physician Follow-up for Melanoma: A Clarification
Authors: Wen Jen Poo
Journal: JAMA (1996)

<h3>To the Editor.</h3> —In 1995, our group<sup>1</sup>wrote an abstract that was presented at the annual meeting of American Society of Clinical Oncology (ASCO) describing a series of melanoma patients whose recurrences were detected much more frequently (94%) by patient self-examination than at follow-up physician visits (6%). Weiss et al<sup>2</sup>have cited our abstract in recommending that carefully educated patients may not need frequent follow-up examinations. When we were preparing our study for full publication, we found a critical flaw in our data collection mechanism. In fact, of the 66 recurrences, 29 patients (44%) had symptoms that signaled recurrence that they called to the attention of their physicians, and the other 37 recurrences (56%) were diagnosed solely by frequent physician surveillance. Although many recurrences were recognized by informed patients, half in our series might not have been found early without frequent and thorough follow-up examinations. The revised data
Defective Neutrophil Chemotaxis and Cellular Immunity in a Child with Recurrent Infections
Authors: ROBERT A. CLARK
Journal: Annals of Internal Medicine (1973)

Studies of leukocyte function and cell-mediated immunity were done in an 11-year-old girl with a lifelong history of recurrent pyogenic and mucocutaneous candida infections. An intrinsic cellular defect in neutrophil chemotaxis was found with the Boyden chamber method. Family members had normal chemotaxis, and the patient's serum was capable of generating normal amounts of chemotactic factors. This in vitro defect correlated with a reduction in leukocyte migration in vivo by the skin window method, but all other aspects of neutrophil function, including phagocytosis, bactericidal activity, metabolic activity, and passive motility, were normal. Studies of cellular immunity disclosed negative delayed cutaneous reactions to antigens from Candida albicans and failure of in vitro production of migration inhibitory factor. The cellular defect in leukocyte chemotaxis and the abnormalities in cellular immunity in this child may be important factors in her marked susceptibility to infections.