tbuckley/cabot-search huggingface dataset:
Immunization with aspartate-β-hydroxylase-loaded dendritic cells produces antitumor effects in a rat model of intrahepatic cholangiocarcinoma
Authors: Takehiro Noda, Masafumi Shimoda, Vivian Ortiz, Alphonse E. Sirica, Jack R. Wands
Journal: Hepatology (2011)

Dendritic cells (DCs) capture and process proteins and present peptides on the cell surface in the context of major histocompatibility complex I and II molecules to induce antigen–specific T cell immune responses. The aims of this study were to (1) employ an expanded and purified DC population and load them with aspartate–β–hydroxylase (ASPH), a highly expressed tumor–associated cell surface protein, and (2) to determine if immunization induced antitumor effects in an orthotopic rat model of intrahepatic cholangiocarcinoma. Splenocytes were incubated with ASPH–coated beads and passed through a magnetic field to yield an 80% pure DC OX62+ population. This DC subset was stimulated with granulocyte–macrophage colony–stimulating factor, interleukin–4, CD40L, and interferon–γ, resulting in a 40–fold increase in interleukin–12A messenger RNA expression to subsequently generate a T helper 1–type immune response. After incubation with the cytokine cocktail, DCs were found to have matured, as demonstrated by increased expression of CD40, CD80, and CD86 costimulatory molecules. Immunization with ASPH–loaded DCs induced antigen–specific immunity. A clone of the parental tumorigenic rat BDEneu cholangiocyte cell line, designated BDEneu–CL24, was found to have the highest number of cells expressing this surface protein (97%); it maintained the same phenotypic characteristics of the parental cell line and was used to produce intrahepatic tumors in immunocompetent syngeneic Fisher–344 rats. Immunization with ASPH–loaded DCs generated cytotoxicity against cholangiocarcinoma cells in vitro and significantly suppressed intrahepatic tumor growth and metastasis, and was associated with increased CD3+ lymphocyte infiltration into the tumors. Conclusion : These findings suggest that immunization with ASPH–loaded DCs may constitute a novel therapeutic approach for intrahepatic cholangiocarcinoma, because this protein also appears to be highly conserved and expressed on human hepatobiliary tumors. (Hepatology 2012;55:86–97)
Drugs and Adverse Drug Reactions
Authors: David W. Bates
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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
Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in mice
Authors: Julien Bricambert, Jonatan Miranda, Fadila Benhamed, Jean Girard, Catherine Postic, Renaud Dentin
Journal: Journal of Clinical Investigation (2010)

Obesity and type 2 diabetes are associated with increased lipogenesis in the liver. This results in fat accumulation in hepatocytes, a condition known as hepatic steatosis, which is a form of nonalcoholic fatty liver disease (NAFLD), the most common cause of liver dysfunction in the United States. Carbohydrate-responsive element-binding protein (ChREBP), a transcriptional activator of glycolytic and lipogenic genes, has emerged as a major player in the development of hepatic steatosis in mice. However, the molecular mechanisms enhancing its transcriptional activity remain largely unknown. In this study, we have identified the histone acetyltransferase (HAT) coactivator p300 and serine/threonine kinase salt-inducible kinase 2 (SIK2) as key upstream regulators of ChREBP activity. In cultured mouse hepatocytes, we showed that glucose-activated p300 acetylated ChREBP on Lys672 and increased its transcriptional activity by enhancing its recruitment to its target gene promoters. SIK2 inhibited p300 HAT activity by direct phosphorylation on Ser89, which in turn decreased ChREBP-mediated lipogenesis in hepatocytes and mice overexpressing SIK2. Moreover, both liver-specific SIK2 knockdown and p300 overexpression resulted in hepatic steatosis, insulin resistance, and inflammation, phenotypes reversed by SIK2/p300 co-overexpression. Finally, in mouse models of type 2 diabetes and obesity, low SIK2 activity was associated with increased p300 HAT activity, ChREBP hyperacetylation, and hepatic steatosis. Our findings suggest that inhibition of hepatic p300 activity may be beneficial for treating hepatic steatosis in obesity and type 2 diabetes and identify SIK2 activators and specific p300 inhibitors as potential targets for pharmaceutical intervention.
Risk stratification for arrhythmic events in patients with nonischemic dilated cardiomyopathy and nonsustained ventricular tachycardia: Role of programmed ventricular stimulation and the signal-averaged electrocardiogram
Authors: Gioia Turitto, Ratan K. Ahuja, Edward B. Caref, Nabil El-Sherif
Journal: Journal of the American College of Cardiology (1994)
Colonoscopic Surveillance after Polypectomy: Considerations of Cost Effectiveness
Authors: David F. Ransohoff, Christopher A. Lang, H. Sung Kuo
Journal: Annals of Internal Medicine (1991)

Objective: To assess the cost effectiveness of the current recommendation that persons who have had an adenomatous colon polyp removed have periodic colonoscopic surveillance at fixed and regular intervals. Design: Cost-effectiveness analysis using data from the medical literature in a simulation model to estimate the costs of and the risk for perforation associated with periodic colonoscopic surveillance for a 50-year-old man followed for 30 years. Main Results: A program of colonoscopy every 3 years would incur cumulatively a 1.4% risk for colon perforation, a 0.11% risk for perforation-related death, and direct physician costs of $2071 for colonoscopy (discounted at 5%). If a 50-year-old man's cumulative remaining risk for death from cancer is 2.5% after the removal of a single small adenoma and if effectiveness of colonoscopic surveillance every 3 years is 100%, then one death from cancer could be prevented by doing 283 colonoscopies, incurring 0.6 perforations, 0.04 perforation-related deaths, and direct physician costs of $82 000. If surveillance were 50% effective and the cumulative remaining risk for death from cancer were 1.25%—a plausible scenario—1131 colonoscopies would be required to prevent one death from cancer, incurring 2.3 perforations, 0.17 perforation-related deaths, and physician costs of $331 000. Conclusions: The cost effectiveness of colonoscopic surveillance is very sensitive to estimates of the cumulative remaining risk for death from cancer after polypectomy as well as to surveillance efficacy. For persons whose remaining risk for death from cancer may be low, such as persons with a single small adenoma, recommendations for colonoscopic surveillance at fixed and regular intervals may be excessively costly.
Bile-duct destruction and collagen deposition: A prominent ultrastructural feature of the liver in cystic fibrosis
Authors: Anders Lindblad, Rolf Hultcrantz, Birgitta Strandvik
Journal: Hepatology (1992)

To study the liver disease of patients with cystic fibrosis, percutaneous liver biopsies were performed in 10 patients with cystic fibrosis aged 6 to 22 yr. Nine of 10 patients had high Shwachman scores, eight had normal serum levels of transaminases. Light-microscopical examination showed steatosis in seven cases and in five slight or moderate inflammatory infiltration. Eight patients showed varying degrees of fibrosis and even cirrhosis. Six patients had bile-duct proliferation and, in one case a bile plug was found. Other signs of cholestasis were not seen. Electron-microscopical investigation showed no specific signs of cholestasis such as ductal plugs or intracellular bile pigments. The canaliculi were not dilated, except in one case. Most patients had bile-duct cells with irregular shapes, protruding into the lumen, and some cases even had necrotic cells. Around the bile ducts and ductules, collagen was deposited and fat-storing cells were a common finding. Our findings do not support the view that cholestasis is the pathogenetic factor in liver disease in cystic fibrosis. A cytotoxic influence on the biliary cells, stimulating collagen deposition, seems more likely.
Leon Creaney responds to Des Spence
Authors: L. Creaney
Journal: BMJ (2011)

Throughout his article entitled “Bad medicine: sports medicine,” Spence criticises global corporations making footwear and sports drinks, sports scientists, athletes and coaches, physiotherapists, podiatrists, and sports surgeons, but nowhere does he consider sports medicine itself.1 To label sports medicine as bad medicine is wildly inaccurate when much of current sports medicine practice has been ignored.

Sport and exercise medicine was established as the newest medical specialty in the UK in 2005 by parliament, has a faculty in the Royal College of Physicians of London, as well as a curriculum approved by the Joint Royal Colleges of Physicians’ Training Board and General Medical Council, with 64 specialist trainees in training …
Umbilical cord blood gas analysis
Authors: J. P. Neilson
Journal: BMJ (2010)

Paired samples should be analysed in selected circumstances

The umbilical cord, discarded without thought from labour wards for so long, has recently generated interest on several fronts. Cord blood is a source of stem cells and some parents want cord blood collected for banking by commercial enterprises in case it can help their child’s future health needs. However, the Human Tissue Authority in the United Kingdom has recently expressed concerns about the safety of collection mechanisms.1 It is also increasingly recognised that obstetricians and midwives often clamp the cord too soon after birth, thereby depriving the baby of substantial amounts of blood—this is particularly important in parts of the world where infant anaemia is prevalent.2 And now we have biochemical analysis of cord blood. In the linked systematic review (doi:10.1136/bmj.c1471), Malin and colleagues assess the association between umbilical cord pH at birth and outcomes.3 

Umbilical cord blood gases could be of value in auditing the outcomes of labour, predicting future …
Don't throw the baby out with the math water: Why discounting the developmental foundations of early numeracy is premature and unnecessary
Authors: Kevin Muldoon, Charlie Lewis, Norman Freeman
Journal: Behavioral and Brain Sciences (2008)

Abstract We see no grounds for insisting that, because the concept natural number is abstract, its foundations must be innate. It is possible to specify domain general learning processes that feed into more abstract concepts of numerical infinity. By neglecting the messiness of children's slow acquisition of arithmetical concepts, Rips et al. present an idealized, unnecessarily insular, view of number development.
Characterization of angiotensin II receptor subtypes in rat heart.
Authors: L A Sechi, C A Griffin, E F Grady, J E Kalinyak, M Schambelan
Journal: Circulation Research (1992)

Angiotensin II exerts positive inotropic and chronotropic effects on the mammalian heart by binding to specific membrane receptors. Recently, two subtypes of angiotensin II receptors (AT1 and AT2) have been distinguished by using the nonpeptide antagonists losartan (previously known as DuP 753) and PD123177. To evaluate the tissue distribution and subtypes of angiotensin II receptors in rat heart, we performed a 125I-[Sar1,Ile8]angiotensin II in situ binding assay on tissue sections obtained from adult Sprague-Dawley rats (10 and 14 weeks old). Binding specificity was verified by competition with unlabeled [Sar1]angiotensin II. Distribution of AT1 and AT2 receptors was determined by competition with losartan and PD123177, respectively, and the density of the receptors was quantified by emulsion autoradiography. Angiotensin II receptors were widely distributed throughout the heart, with each receptor subtype accounting for approximately 50% of the specific binding. Binding density was comparable in the atria, right and left ventricles, intraventricular septum, and sinoatrial node, whereas it was significantly greater in the atrioventricular node. The AT1 receptor appears to interact with guanidine nucleotide regulatory proteins, because GTP-gamma-S causes dissociation of the radioligand from this receptor. In contrast, the AT2 receptor does not appear to directly interact with guanine nucleotide regulatory proteins, inasmuch as radioligand dissociation from this receptor subtype is not affected by GTP-gamma-S. Because angiotensin II has been reported to have growth-potentiating effects in several tissues, we examined angiotensin II receptors in fetal (embryonic days 16 and 19) and neonatal (1-, 2-, 3-, and 10-day-old) rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Golf-Course Dermatitis Due to Thiram Fungicide
Authors: Walter B. Shelley
Journal: JAMA (1964)

Contact dermatitis developed in a golfer who had allergic sensitization to a thiram fungicide used on the golf greens. Thiram and related compounds are components of numerous fungicides, insecticides, seed disinfectants, larvacides, germicidal soaps, lotions, ointments, rubber goods, and disulfiram (Antabuse). Ethanol-sensitization reactions also occur; in contrast to the reported eczematous contact sensitivity, these are nonallergic in nature. They include erythema, urticaria, and pruritus developing shortly after alcohol is taken by persons who ingest disulfiram or have topical exposure to thiram.
Edema and Diuresis from Peritoneal Biopsy
Authors: WILLIS C. MADDREY
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 June 1972Edema and Diuresis from Peritoneal BiopsyWILLIS C. MADDREY, M.D., HARRY F. KLINEFELTER, M.D.WILLIS C. MADDREY, M.D.Search for more papers by this author, HARRY F. KLINEFELTER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-6-1044_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The rapid appearance of scrotal and peripheral edema after abdominal paracentesis, as described by Conn in the ANNALS OF INTERNAL MEDICINE (1), was seen in a patient after percutaneous peritoneal biopsy. Of particular interest was the concomitant occurrence of an impressive diuresis, beginning within hours of the biopsy.The patient, a 37-year-old man—a laborer, chronic alcoholic, and heroin user— was studied for persistent massive ascites, which was treated unsuccessfully for 2 months with salt and water restriction, spironolastone (Aldactone®; up to 150 mg/day), and furosenide (Lasix®; up to 240 mg/day). The elevated ascitic-fluid protein (2.5 to 3.4...References1. CONN H: Sudden scrotal edema in cirrhosis: a postparacentesis syndrome. Ann Intern Med 74:943-945, 1971 LinkGoogle Scholar2. SHEAR S, CHING S, and GABUZDA G: Compartmentalization of ascites and edema in patients with hepatic cirrhosis. N Engl J Med 282:1391-1396, 1970 CrossrefMedlineGoogle Scholar1. CROSBY R and COONEY E: Surgical treatment of ascites. N Engl J Med 235:581-585, 1946 CrossrefMedlineGoogle Scholar2. PEARLMAN D and DUREMDES G: Treatment of intractable ascites by reinfusion of unmodified autogenous ascitic fluid. Surgery 62:248-254, 1967 Google Scholar3. HYDE G and MOOSNICK F: Treatment of intractable ascites by peritoneal atrial shunt. JAMA 201:264-266, 1967 CrossrefMedlineGoogle Scholar4. DUMONT A and MULHOLLAND J: Hepatic lymph in cirrhosis, in Progress in Liver Disease II, edited by POPPER H, SCHAFFNER F. New York, Grune and Stratton, Inc., 1965, pp. 427-441 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: WILLIS C. MADDREY, M.D.; HARRY F. KLINEFELTER, M.D.Affiliations: Department of Medicine The Johns Hopkins Hospital Baltimore, Md. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byUnilateral Edema and Jaundice, and PopeROBERT M. ROSA, M.D. 1 June 1972Volume 76, Issue 6 Page: 1044-1044 Keywords Alcoholics Ascites Biopsy Edema Heroin Proteins Salts ePublished: 1 December 2008 Issue Published: 1 June 1972 PDF downloadLoading ...
Impaired nuclear responsiveness to cytoplasmic signals in lymphocytes from elderly humans with depressed proliferative responses.
Authors: J K Gutowski, J B Innes, M E Weksler, S Cohen
Journal: Journal of Clinical Investigation (1986)

Lymphocytes from many elderly individuals exhibit depressed proliferative responses to the plant phytohemagglutinin (PHA). We have previously reported that this proliferative defect is not due to a failure to generate a cytoplasmic activator of DNA replication (ADR). In the present study, we tested the DNA synthetic response of nuclei derived from aged cells to an exogenous source of ADR. We found that nuclei from aged lymphocytes exhibiting low PHA responses were impaired in their ability to synthesize DNA in responses to ADR, compared with nuclei from younger adult donors. In contrast, those aged cells maintaining intact PHA responses provided nuclei that were also unimpaired in their response to ADR. The relationship between PHA responsiveness of the intact cells and ADR responsiveness of nuclei derived from these was a linear one. These results suggest that the depressed cellular reactivity of aged lymphocytes to PHA (when seen) may be due to a failure of these nuclei to respond to cytoplasmic stimulatory signals induced by the mitogen.
Type I Interferon Inhibits Antibody Responses Induced by a Chimpanzee Adenovirus Vector
Authors: Scott E Hensley, Ann S Cun, Wynetta Giles-Davis, Yan Li, Zhiquan Xiang, Marcio O Lasaro, Bryan R G Williams, Robert H Silverman, Hildegund C J Ertl
Journal: Molecular Therapy (2007)
"SURGICAL TREATMENT OF HYPERTENSION"
Authors: Geza de Takats
Journal: JAMA (1941)

To the Editor:—  In their article on the surgical treatment of hypertension (The Journal, Nov. 30, 1940, p. 1875) Peet, Woods and Braden state that bilateral supradiaphragmatic splanchnic nerve section and lower dorsal sympathetic ganglionectomy were first introduced into this country by Peet in 1933. Publications by Fenn and myself in the Annals of Internal Medicine ( 7: 422 [Oct.] 1933 and 7: 1201 [April] 1934) may easily have been overlooked by the authors. Later this operation was reported and illustrated in the Annals of Surgery ( 102: 22 [July] 1935). Our first operation, as can be seen from the first publication, was done Oct. 22, 1932.  There is, of course, no question of priority in the matter, as Pieri adequately described and illustrated this approach in 1930 (La cura chirurgica delle nevrosi gastriche, Belluno, Tipografia Editrice La Cartolibraria). Since these early operations, which were done for juvenile diabetes, we have used
Functional Outcomes After Lower Extremity Revascularization in Nursing Home Residents
Authors: Lawrence Oresanya, Shoujun Zhao, Siqi Gan, Brant E. Fries, Philip P. Goodney, Kenneth E. Covinsky, Michael S. Conte, Emily Finlayson
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Lower extremity revascularization often seeks to allow patients with peripheral arterial disease to maintain the ability to walk, a key aspect of functional independence. Surgical outcomes in patients with high levels of functional dependence are poorly understood. <h3>Objective</h3> To determine functional status trajectories, changes in ambulatory status, and survival after lower extremity revascularization in nursing home residents. <h3>Design</h3> Using full Medicare claims data for 2005 to 2009, we identified nursing home residents who underwent lower extremity revascularization. With the Minimum Data Set for Nursing Homes activities of daily living summary score, we examined changes in their ambulatory and functional status after surgery. We identified patient and surgery characteristics associated with a composite measure of clinical and functional failure—death or nonambulatory status 1 year after surgery. <h3>Setting</h3> All nursing homes in the United States participating in Medicare or Medicaid. <h3>Participants</h3> Nursing home residents who underwent lower extremity revascularization. <h3>Main Outcomes and Measures</h3> Functional status, ambulatory status, and death. <h3>Results</h3> During the study period, 10 784 long-term nursing home residents underwent lower extremity revascularization. Prior to surgery, 75% of the residents were not walking; 40% had experienced functional decline. One year after surgery, 51% of patients had died, 28% were nonambulatory, and 32% had sustained functional decline. Among 1672 residents who were ambulatory before surgery, 63% had died or were nonambulatory at 1 year; among 7188 who were nonambulatory, 89% had died or were nonambulatory. After multivariate adjustment, factors independently associated with death or nonambulatory status were 80 years or older (adjusted hazard ratio [AHR], 1.28; 95% CI, 1.16-1.40), cognitive impairment (AHR, 1.23; 95% CI, 1.18-1.29), congestive heart failure (AHR, 1.16; 95% CI, 1.11-1.22), renal failure (AHR, 1.09; 95% CI, 1.04-1.14), emergent surgery (AHR, 1.29; 95% CI, 1.23-1.35), nonambulatory status before surgery (AHR, 1.88; 95% CI, 1.78-1.99), and decline in activities of daily living before surgery (AHR, 1.23; 95% CI, 1.18-1.28). <h3>Conclusions and Relevance</h3> Of nursing home residents in the United States who undergo lower extremity revascularization, few are alive and ambulatory 1 year after surgery. Most who were still alive had gained little, if any, function.
Be Your Own Philosopher
Authors: Samuel Vaisrub
Journal: JAMA (2014)

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 2022 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