tbuckley/cabot-search huggingface dataset:
NF-κB2 is required for the establishment of central tolerance through an Aire-dependent pathway
Authors: Mingzhao Zhu, Robert K. Chin, Peter A. Christiansen, James C. Lo, Xiaojuan Liu, Carl Ware, Ulrich Siebenlist, Yang-Xin Fu
Journal: Journal of Clinical Investigation (2006)

NF-kappaB2-deficient mice have impaired T and B cell responses. We found, however, that in these mice there was severe infiltration of lymphocytes into multiple organs and increased activity of autoantibodies to peripheral tissue antigens in a manner similar to that of autoimmune regulator-deficient (Aire-deficient) mice. We further demonstrated that NF-kappaB2 was required for thymic Aire gene transcriptional regulation. The Nfkb2(-/-) thymus had distinct cortical and medullar structures, but reduced Aire and target gene expression of peripheral tissue antigens. Engraftment of Nfkb2(-/-) thymic stroma to nude mice recapitulated the autoimmune phenotype of the native Nfkb2(-/-) mice, confirming a key defect in central tolerance. Lymphotoxin beta receptor (LTbetaR) ligation-induced Aire gene expression was also largely abolished in the absence of NF-kappaB2. Thus NF-kappaB2 downstream of LTbetaR plays an important role in the regulation of central tolerance in an Aire-dependent manner.
Chemoprevention of Familial Adenomatous Polyposis by Low Doses of Atorvastatin and Celecoxib Given Individually and in Combination to APCMin Mice
Authors: Malisetty V. Swamy, Jagan M.R. Patlolla, Vernon E. Steele, Levy Kopelovich, Bandaru S. Reddy, Chinthalapally V. Rao
Journal: Cancer Research (2006)

Abstract Preclinical and clinical studies have established evidence that cyclooxygenase-2 (COX-2) inhibitors and statins [hydroxy-3-methylglutaryl CoA reductase (HMGR) inhibitors] inhibit colon carcinogenesis. Chronic use of high doses of COX-2 inhibitors may induce side effects, and combining the low doses of agents may be an effective way to increase their efficacy and minimize the side effects. We assessed the chemopreventive efficacy of atorvastatin (Lipitor) and celecoxib individually or in combination in an animal model of familial adenomatous polyposis. Six-week-old male C57BL/6J-APCmin/+ mice were either fed diets containing 0 or 100 ppm atorvastatin or 300 ppm celecoxib, or a combination of both for ∼80 days. Mice were sacrificed, and their intestines were scored for tumors. Normal-seeming mucosa and intestinal tumors were harvested and assayed for apoptosis (terminal deoxynucleotidyl transferase–mediated nick-end labeling) and HMGR and COX-2 protein expression and activity. We observed that 100 ppm atorvastatin significantly (P &amp;lt; 0.002) suppressed intestinal polyp formation. As anticipated, 300 ppm celecoxib decreased the rate of formation of intestinal polyps by ∼70% (P &amp;lt; 0.0001). Importantly, the combination of 100 ppm atorvastatin and 300 ppm celecoxib in the diet suppressed the colon polyps completely and small intestinal polyps by &amp;gt;86% (P &amp;lt; 0.0001) compared with the control group. The inhibition of tumor formation by the atorvastatin and celecoxib combination was significant (P &amp;lt; 0.005) when compared with tumor inhibition by celecoxib alone. In addition, increased rates of apoptosis in intestinal tumors (P &amp;lt; 0.01-0.0001) were observed in animals fed with atorvastatin and celecoxib and more so with the combinations. Tumors of animals fed atorvastatin showed a significant decrease in HMGR-R activity. Similarly, tumors of mice exposed to celecoxib showed significantly lower levels of COX-2 activity. These observations show that atorvastatin inhibits intestinal tumorigenesis and that, importantly, when given together with low doses of celecoxib, it significantly increases the chemopreventive efficacy in an APCmin mice. (Cancer Res 2006; 66(14): 7370-7)
An Index for the Evaluation of Arteriosclerotic Lesions in the Abdominal Aorta
Authors: RUSSELL L. HOLMAN, B. W. BROWN, IRA GORE, GARDNER C. MCMILLAN, JAMES C. PATERSON, O. J. POLLAK, JAMES C. ROBERTS, ROBERT W. WISSLER
Journal: Circulation (1960)

An index for the evaluation of arteriosclerotic lesions based on visual observation of selected and unselected specimens of the abdominal aorta was derived from a statistical analysis of simple grading and ranking studies. This index, I = 1/2P T + 1/4P F + 1/2P C , takes cognizance of most of the grossly visible quantitative and qualitative features of human arteriosclerotic lesions. In it P T , P F , and P C are the quantitative estimates of the per cent of total area diseased (T) and the per cent lesion area with fibrous plaques (F) and complicated lesions (C), respectively. The index is subjective but relatively reproducible by the same or different observers. It does not carry any implications of etiology or pathogenesis. The work of the Committee is continuing, and it is hoped that indices based on such methods may prove useful when applied to other parts of the arterial system or in studying several parts simultaneously, thus facilitating basic studies on arteriosclerosis both in man and in animals.
Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage
Authors: Deepak Darshan, Liviu Vanoaica, Larry Richman, Friedrich Beermann, Lukas C. Kühn
Journal: Hepatology (2009)

Ferritin plays a central role in iron metabolism by acting both as iron storage and a detoxifying protein. We generated a ferritin H allele with loxP sites and studied the conditional ferritin H deletion in adult mice. Ten days after Mx-Cre induced deletion, ferritin H messenger RNA (mRNA) was below 5% in the liver, spleen, and bone marrow of deleted mice compared to control littermates. Mice lost their cellular iron stores indicating the requirement of ferritin H in iron deposition. Serum iron and transferrin saturation were slightly increased and correlated with a two-fold increased liver hepcidin 1 mRNA and a reduced duodenal DcytB mRNA level. Under a normal iron regimen, deleted mice survived for 2 years without visible disadvantage. Mice fed on a high iron diet prior to ferritin H deletion suffered from severe liver damage. Similarly, ferritin H deleted mouse embryonic fibroblasts showed rapid cell death after exposure to iron salt in the medium. This was reversed by wild-type ferritin H but not by a ferritin H mutant lacking ferroxidase activity. Cell death was preceded by an increase in cytoplasmic free iron, reactive oxygen species, and mitochondrial depolarization.Our results provide evidence that the iron storage function of ferritin plays a major role in preventing iron-mediated cell and tissue damage.
ASYMPTOMATIC HEART BLOCK OF LONG DURATION
Authors: Harold Thomas Hyman
Journal: JAMA (1930)

The accompanying electrocardiogram shows a complete dissociation between auricle and ventricle. Each auricular beat occurs at an interval of 0.72 second (82 a minute) and each ventricular beat at 1.4 seconds (42 a minute). The tracing in itself is not unusual, but the history of the patient from whom it was made is remarkable for its negativity. The man is now 57 years old and has had an equally slow heart rate since he was 12 years old, if not before. He remembers distinctly that he was always able to obtain sick leave from school by having his pulse rate counted. At the age of 2 and again at 10 he had some protracted fever, both of which attacks were called typhoid and the details of which are no longer obtainable, but they did not resemble diphtheria. Since his school days he has worked in all corners of the world
Critique on the Concept of Vesical Neck Obstruction in Children
Authors: Donald R. Smith
Journal: JAMA (1969)

It is doubtful that vesical neck obstruction in children is the common cause of urinary infection, reflux, and enuresis. Routine revision of the bladder neck, in association with ureterovesicoplasty, does not improve the cure rate of the antireflux operation. Most agree that it is difficult, if not impossible, to diagnose such obstruction with endoscopy or cystourethrography. Outlet obstruction, through trigonal hypertrophy, tends to further protect the ureterovesical "valve" from incompetency. Voiding pressure studies reveal no significant gradient on either side of the vesical neck. Recent investigations show that the area of increased resistance in young girls is not at the vesical neck but in the midurethra and is caused by involuntary spasm of the periurethral striated muscle. Treatment of the accompanying distal urethral stenosis usually relieves this spasm.
An Occidental Case of Cardiomyopathy and Selenium Deficiency
Authors: Robert Arnold Johnson, Susan S. Baker, John T. Fallon, Edwin P. Maynard, Jeremy N. Ruskin, Zhimei Wen, Keyou Ge, Harvey J. Cohen
Journal: New England Journal of Medicine (1981)

SELENIUM is a trace element that until recently has been considered unimportant in human nutrition, except when ingested in excessive amounts.1 During the past decade, Chinese investigators have shown that selenium deficiency is one of the principal factors responsible for Keshan disease, a "dilated" (congestive) cardiomyopathy that affects persons (mainly children and young women) living in rural areas of a selenium-deficient zone in China.2 3 4 This report describes an Occidental patient in whom selenium deficiency became associated with dilated cardiomyopathy.Case ReportA 43-year-old man had been receiving parenteral alimentation for two years (one liter of FreAmine 11 [an amino acid . . .
Genetic inference of immune responsiveness of melanoma cancer patients to TIL therapy
Authors: Michele Sommariva, Foo Cheung, Jinguo Chen, Rongye Shi, Ling Zhang, Richard Morgan, Davide Bedognetti, Valeria De Giorgi, Maria L Ascierto, Steven A Rosenberg, Francesco M Marincola, Ena Wang
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Adoptive cell transfer therapy (ACT) holds a highly promising treatment for metastatic melanoma patients. ACT involves the ex vivo expansion of autologous antitumor reactive tumor infiltrating lymphocytes and their reinfusion into lymphodepleted patients, accompanied by IL-2
Reviews: Organ Transplantation: Meanings and Realities
Authors: Patricia A. Marshall
Journal: Annals of Internal Medicine (1997)

Medical Writings15 January 1997Reviews: Organ Transplantation: Meanings and RealitiesPatricia A. MarshallPatricia A. MarshallSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-2-199701150-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Youngner SJ, Fox RC, O'Connell LJ; eds. 290 pages. Madison, WI: Univ of Wisconsin Pr; 1996. $22.95. ISBN 0299149641. Order phone 608-262-8782.Field of medicine: Ethics.Format: Softcover book.Audience: Health care providers, organ transplantation specialists, bioethicists, philosophers, theologians, social scientists, and scholars in the medical humanities.Content: Sponsored by the Chicago-based Park Ridge Center for the Study of Health, Faith, and Ethics, this book is the result of ongoing discussions among an interdisciplinary group of experts from diverse fields. It addresses the existential crises raised by the sophisticated science and technology of organ transplantation.Highlights: This book explores the ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1997Volume 126, Issue 2Page: 175KeywordsBioethicsHealth care providersMedical ethics, humanities, and educationOrgan transplantationScientistsTransplantation ePublished: 15 August 2000 Issue Published: 15 January 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Measurement of de novo hepatic lipogenesis in humans using stable isotopes.
Authors: M K Hellerstein, M Christiansen, S Kaempfer, C Kletke, K Wu, J S Reid, K Mulligan, N S Hellerstein, C H Shackleton
Journal: Journal of Clinical Investigation (1991)

Direct measurement of de novo lipogenesis has not previously been possible in humans. We measured de novo hepatic lipogenesis in normal men by means of stable isotopes and by combining the acetylated-xenobiotic probe technique with mass isotopomer analysis of secreted very low density lipoprotein-fatty acids (VLDL-FA). Sulfamethoxazole (SMX) was administered with [13C]acetate during an overnight fast followed by refeeding with intravenous glucose (7-10 mg/kg of weight per min), oral Ensure (7-10 mg of carbohydrate/kg of weight per min), or a high-carbohydrate mixed-meal breakfast (3.5 g of carbohydrate/kg of weight). Respiratory quotients remained less than 1.0. High-performance liquid chromatography/mass spectrometry-determined enrichments in SMX-acetate attained stable plateau values, and hepatic acetyl-coenzyme A (CoA) dilution rate did not increase with refeeding (approximately 0.024 mmol/kg per min). The fraction of VLDL-palmitate derived from de novo lipogenesis was only 0.91 +/- 0.27% (fasted) and 1.64-1.97% (fed). For stearate, this was 0.37 +/- 0.08% and 0.47-0.64%. Precursor enrichments predicted from isotopomer ratios were close to measured SMX-acetate enrichments, indicating that SMX-acetate samples the true lipogenic acetyl-CoA pool. Stearate synthesis was less than palmitate and the two did not move in parallel. Estimated total VLDL-FA synthesis is less than 500 mg/day. Thus, de novo hepatic lipogenesis is a quantitatively minor pathway, consistent with gas exchange estimates; fatty acid futile cycling (oxidation/resynthesis) is not thermogenically significant; and synthesis rates of different nonessential fatty acids by human liver are not identical in nonoverfed normal men. The contribution and regulation of de novo lipogenesis in other settings can be studied using this technique.
The truth and value of theories of associative learning
Authors: Tom Beckers, Bram Vervliet
Journal: Behavioral and Brain Sciences (2009)

Abstract In this commentary, we assess the propositional approach to associative learning not only in terms of veridicality and falsifiability, but also in heuristic value. We remark that it has furthered our knowledge and understanding of human, as well as animal, associative learning. At the same time, we maintain that models developed from the association formation tradition continue to bear great heuristic value as well.
Defensiveness, Cynical Hostility and Cardiovascular Reactivity: A Moderator Analysis
Authors: Randall S. Jorgensen, Kenneth Abdul-Karim, Todd A. Kahan, James J. Frankowski
Journal: Psychotherapy and Psychosomatics (1995)

We examined the interaction of a defensive need for approval with cynical hostility, in the prediction of pressor and heart rate reactivity to a stressful mental arithmetic task. For both systolic blood pressure and heart rate, analyses revealed the predicted interaction between defensiveness and cynical hostility; subsequent analyses showed significant correlations of defensiveness with systolic blood pressure and heart rate reactivity only among the high cynical hostility subjects. These analyses support the theory and empirical findings linking the conflicting traits of cynical hostility and defensiveness to cardiovascular reactivity and, quite possibly, to stress-related coronary disease.
Sca-1 <sup>+</sup> Stem Cell Survival and Engraftment in the Infarcted Heart
Authors: Gang Lu, Husnain K. Haider, Shujia Jiang, Muhammad Ashraf
Journal: Circulation (2009)

Background— We report that elevated connexin-43 (Cx-43) in stem cells preconditioned with insulin-like growth factor-1 (IGF-1) is cytoprotective and reprograms the cells for cardiomyogenic differentiation. Methods and Results— Sca-1 + cells were preconditioned with 100 nmol/L IGF-1 for 30 minutes followed by 8 hours of oxygen glucose deprivation to assess the cytoprotective effects of preconditioning. LDH release assay, cytochrome c release, and mitochondrial membrane potential assay showed improved survival of preconditioned Sca-1 + cells under oxygen glucose deprivation compared with nonpreconditioned Sca-1 + cells via PI3K/Akt-dependent caspase-3 downregulation. We observed PI3K/Akt-dependent upregulation of cardiac-specific markers including MEF-2c (2.5-fold), GATA4 (3.1-fold), and Cx-43 (3.5-fold). Cx-43 inhibition with specific RNA interference reduced cell survival under oxygen glucose deprivation and after transplantation. In vivo studies were performed in a female rat model of acute myocardial infarction (n=78). Animals were grouped to receive intramyocardially 70 μL Dulbecco modified Eagles medium without cells (group 1) or containing male 1×10 6 nonpreconditioned Sca-1 + cells (group 2) or preconditioned Sca-1 + (group 3) cells labeled with PKH26. Survival of the preconditioned Sca-1 + cells was 5.5-fold higher in group 3 compared with group 2 at 7 days after transplantation. Confocal imaging after actinin and Cx-43 specific immunostaining showed extensive engraftment and myogenic differentiation of preconditioned Sca-1 + cells. Compared with group 2, group 3 showed increased blood vessel density (22.3±1.7 per microscopic field; P &lt;0.0001) and attenuated infarction size (23.3±3.6%; P =0.002). Heart function indices including ejection fraction (56.2±3.5; P =0.029) and fractional shortening (24.3±2.1; P =0.03) were improved in group 3 compared with group 2. Conclusions— Preconditioning with IGF-1 reprograms Sca-1 + for prosurvival signaling and cardiomyogenic differentiation with an important role for Cx-43 in this process.
Hematopoietic support and cytokine expression of murine-stable hepatocyte cell lines (MMH)
Authors: Alessandro Aiuti, Carla Cicchini, Silvia Bernardini, Giorgio Fedele, Laura Amicone, Antonio Fantoni, Marco Tripodi
Journal: Hepatology (1998)

It was recently reported that transgenic expression in the liver of truncated human Met renders hepatocytes constitutively resistant to apoptosis and reproducibly permits their immortalization. The derived stable cell lines (MMH from Met murine hepatocyte) are highly differentiated and nontransformed. In this report, the capacity of MMHs to support in vitro hematopoiesis is characterized. By reverse–transcription polymerase chain reaction, the expression by MMHs of cytokines involved in the survival and self–renewal of early progenitor cells (stem cell factor and FLT3 ligand) as well as those acting at different stages of progenitor differentiation (interleukin [IL] 1β, IL–3, leukemia inhibitory factor, IL–6, granulocyte–macrophage colony-stimulating factor, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and thrombopoietin) was shown. A ribonuclease protection assay further substantiated the presence of at least six cytokine transcripts in MMH lines. Cocultures between MMH layers and progenitor–enriched fetal liver hematopoietic cells resulted in a 40–fold to 80–fold expansion of total hematopoietic cells and in a 2.5–fold expansion of clonogenic progenitors after 1 to 2 weeks. Hematopoiesis was maintained for up to 6 weeks with formation of typical cobblestone cell areas and continuous differentiation of precursor into cells at various degrees of maturation. At 5 weeks of coculture, clonogenic progenitors were maintained at 20% of the input level in coculture with embryonic–derived hepatocytes, showing the ability of hepatocyte feeder layer to support survival and possibly self–renewal of clonogenic progenitors. Therefore, the data emphasize a direct role of the hepatocyte in sustaining hematopoietic cell proliferation and differentiation.
Fluorinated per-acetylated GalNAc metabolically alters glycan structures on leukocyte PSGL-1 and reduces cell binding to selectins
Authors: Dhananjay D. Marathe, Alexander Buffone, E. V. Chandrasekaran, Jun Xue, Robert D. Locke, Mehrab Nasirikenari, Joseph T. Y. Lau, Khushi L. Matta, Sriram Neelamegham
Journal: Blood (2009)
A prospective randomized trial of cannulation technique in ERCP: effects on technical success and post-ERCP pancreatitis
Authors: A. Bailey, M. Bourke, S. Williams, P. Walsh, M. Murray, E. Lee, V. Kwan, P. Lynch
Journal: Endoscopy (2008)

See also: Commentaire de travail de A. A. Bailey et al., pp. 296Endoscopy 2008; 40(04): 452-452DOI: 10.1055/s-0032-1306825
Labor: Clinical Evaluation and Management
Authors: Larry McGowan
Journal: JAMA (1967)

The text is the culmination of Dr. Friedman's interest in labor, and it brings together in an orderly manner the results of his graphic and statistical analytic methods of study. The monograph has five parts. The first deals with normal labor, the development of the methods of study and demonstration of their value and limitations, and review of known physiologic material. The second part analyzes the varieties of abnormal labor with particular regard to definition, etiology, therapy, and prognosis. The effects of endogenous and exogenous factors on the course of labor are covered in the third and fourth sections, respectively. The concluding portion presents programs of management of labor aberrations based on material presented earlier. The author aims to present objectively the phenomenon of labor from the standpoint of its dynamic changes, and he has accomplished his purpose. He uses graphic expressions of cervical dilatation as a function of time
Innovative leads for antineoplastic drugs suggested by a more intimate familiarity with structural motifs of oncoproteins
Authors: Maria Pia Pescarolo, Luca Bagnasco, Davide Malacarne, Antonella Melchiori, Piera Valente, Enrico Millo, Silvia Bruno, Stefania Basso, Silvio Parodi
Journal: Nature Genetics (2001)
Captopril-Induced Acute Pancreatitis
Authors: N Jeandidier, M Klewansky, M Plnget
Journal: Diabetes Care (1995)

OBJECTIVE To increase awareness concerning abdominal pain asociated with the use of captopril, which is a molecule frequently used in diabetic patients. CASE:— One case of acute pancreatitis associated with captopril, confirmed by a reintroduction, is described in a type II diabetes patient. CONCLUSIONS Captopril and other angiotensin-converting enzyme inhibitors are very frequently prescribed in diabetic patients. Therefore, it is important to be aware of the possibility of pancreatitis linked to these molecules and to withdraw the treatment in case of severe unexplained abdominal pain.
Pneumococcal Vaccination in Diabetes-Reply
Authors: James M. Moss
Journal: JAMA (1981)

<h3>In Reply.—</h3> The comments of Dr Beam are appreciated. He has drawn different conclusions from the literature, but he does admit "the incidence of pneumococcus disease in this country is unknown." Before anyone advocates a vaccination program, he should have good data about the incidence of the disease and the costeffectiveness of the program. The swine flu fiasco is an example of the hazards of a massive campaign against a nonexistent disease. The benefits of a vaccination program must be weighed against the danger and the cost of the vaccine. The hazard of polyvalent pneumococcal polysaccharide vaccine is small. However, the cost is too large for the entire population to be immunized. The effort to select high-risk groups is based on old literature and not on modern clinical studies. Infectious diseases specialists who work in teaching hospitals commonly see diabetic derelicts with chronic malnutrition, hyperglycemia, and ketosis. They have no