tbuckley/cabot-search huggingface dataset:
NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant
Authors: A.-G. Besnard, N. Guillou, J. Tschopp, F. Erard, I. Couillin, Y. Iwakura, V. Quesniaux, B. Ryffel, D. Togbe
Journal: Allergy (2011)

To cite this article: Besnard A-G, Guillou N, Tschopp J, Erard F, Couillin I, Iwakura Y, Quesniaux V, Ryffel B, Togbe D. NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant. Allergy 2011; 66: 1047–1057. Background: Inflammasome activation with the production of IL-1β received substantial attention recently in inflammatory diseases. However, the role of inflammasome in the pathogenesis of asthma is not clear. Using an adjuvant-free model of allergic lung inflammation induced by ovalbumin (OVA), we investigated the role of NLRP3 inflammasome and related it to IL-1R1 signaling pathway. Methods: Allergic lung inflammation induced by OVA was evaluated in vivo in mice deficient in NLRP3 inflammasome, IL-1R1, IL-1β or IL-1α. Eosinophil recruitment, Th2 cytokine, and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates, and mediastinal lymph node cells ex vivo. Results: Allergic airway inflammation depends on NLRP3 inflammasome activation. Dendritic cell recruitment into lymph nodes, Th2 lymphocyte activation in the lung and secretion of Th2 cytokines and chemokines are reduced in the absence of NLRP3. Absence of NLRP3 and IL-1β is associated with reduced expression of other proinflammatory cytokines such as IL-5, IL-13, IL-33, and thymic stromal lymphopoietin. Furthermore, the critical role of IL-1R1 signaling in allergic inflammation is confirmed in IL-1R1-, IL-1β-, and IL-1α-deficient mice. Conclusion: NLRP3 inflammasome activation leading to IL-1 production is critical for the induction of a Th2 inflammatory allergic response.
Analysis of regional heterogeneity of myocardial velocities by tissue Doppler echocardiography in patients with ischemic and dilated cardiomyopathy
Authors: M. Plewka, J. Drozdz, J.D. Kasprzak, M. Ciesielczyk, M. Borkowski, J.Z. Peruga, M. Krzeminska‐Pakula
Journal: European Journal of Heart Failure (2000)
258 HIGH FREE AND GLYCOCONJUGATED AND LOW TAUROCONJUGATED BA LEVELS IN SERUM ARE THE MIRROR OF INTESTINAL EVENTS AND HEPATIC UPTAKE
Authors: F. Buonfiglioli, F. Azzaroli, M. Montagnani, P. Simoni, M. Locatelli, M.E. Raspanti, A. Lisotti, F. Lodato, F. Alessandrelli, A. Colecchia, D. Festi, A. Roda, E. Roda, G. Mazzella
Journal: Journal of Hepatology (2009)
Review: High-calorie supplements increase weight in persons with dementia and feeding problems; no evidence exists for other outcomes
Authors: Lionel S. Lim
Journal: Annals of Internal Medicine (2011)

ACP Journal Club16 August 2011Review: High-calorie supplements increase weight in persons with dementia and feeding problems; no evidence exists for other outcomesLionel S. Lim, MD, MPH, FACP, FACPMLionel S. Lim, MD, MPH, FACP, FACPMGriffin Hospital, Derby, Connecticut, USA (L.S.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-4-201108160-02005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHanson LC, Ersek M, Gilliam R, Carey TS. Oral feeding options for people with dementia: a systematic review. J Am Geriatr Soc. 2011;59:463-72. https://pubmed.ncbi.nlm.nih.gov/21391936Clinical Impact RatingsGIM/FP/GP: Hospitalists: Geriatrics: References1 Milne AC, Potter J, Vivanti A, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev. 2009;(2):CD003288. [PMID: 19370584] Google Scholar2 Avenell A, Handoll HH. Nutritional supplementation for hip fracture aftercare in older people. Cochrane Database Syst Rev. 2010;(1):CD001880. [PMID: 20091525] Google Scholar3 Langer G, Schloemer G, Knerr A, Kuss O, Behrens J. Nutritional interventions for preventing and treating pressure ulcers. Cochrane Database Syst Rev. 2003;(4):CD003216. [PMID: 14583961] Google Scholar Author, Article, and Disclosure InformationAffiliations: Griffin Hospital, Derby, Connecticut, USA (L.S.L.)This article was published at Annals.org on 2 August 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 August 2011Volume 155, Issue 4Page: JC2-5KeywordsChocolateDementiaFoodNursing homesNutritionPneumoniaPressure ulcersSystematic reviewsWeight gain ePublished: 16 August 2011 Issue Published: 16 August 2011 CopyrightCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Prostate Cancer DNA Ploidy and Response to Salvage Hormone Therapy After Radiotherapy With or Without Short-Term Total Androgen Blockade: An Analysis of RTOG 8610
Authors: A. Pollack, D.J. Grignon, K.H. Heydon, E.H. Hammond, C.A. Lawton, J.B. Mesic, K.K. Fu, A.T. Porter, R.A. Abrams, W.U. Shipley
Journal: Journal of Clinical Oncology (2003)

Purpose: DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus short-course (∼4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB). Patients and Methods: The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival. Results: DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation. Conclusions: Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.
Differences in the Mechanism of In Vitro Immune Hemolysis Related to Antibody Specificity*
Authors: David A. Sears, Robert I. Weed, Scott N. Swisher
Journal: Journal of Clinical Investigation (1964)

This investigation of the mechanism of immune hemolysis was undertaken to define qualitatively and quantitatively the processes involved in the breakdown of the human red cell membrane pro- duced by the action of complement (C') and hemolytic antibodies of differing specificity.Recent investigations in man and animals have provided insight into patterns of immune hemo- lysis occurring in the intact organism (1-4).At the cellular level, the kinetics of antibody dependent hemolysis and of C' action have been studied extensively by many investigators, uti- lizing the classical sheep erythrocyte-rabbit anti- body-guinea pig C' system (5).Ponder (6) has described the kinetics of hemolysis produced by a wide variety of chemical and physical agents.Little is known, however, about the nature of the injury to the human red cell membrane induced by antibody and C' and the mechanism by which that injury ultimately leads to hemolysis.Although the normal intact red blood cell is isotonic with its plasma environment, as recently demonstrated by Williams, Fordham, Hollander, and Welt (7), this is possible only because of an effective or net impermeability to cations that,
Ultrastructural studies of hepatocyte cytoskeletons of phalloidin-treated rats by quick-freezing and deep-etching method
Authors: Atsuhiko Naramoto, Shinichi Ohno, Kiyoshi Furuta, Nobuo Itoh, Koh Nakazawa, Masayuki Nakano, Hidekazu Shigematsu
Journal: Hepatology (1991)

We observed hepatocyte cytoskeletons in phalloidin-treated rats by the quick-freezing and deep-etching method in three dimensions and compared them with the ultrastructural findings on conventional ultrathin sections. The numbers of microvilli in dilated bile canaliculi were decreased in the rats treated with phalloidin for 1 wk. In hepatocytes the cytoplasm around bile canaliculi could be divided into three layers, increased microfilament layer, cell organelle layer of secretory system and increased smooth surface endoplasmic reticulum layer. In the rats treated with phalloidin for 4 wk, microfilaments were extended into the cytoplasm near the nucleus in addition to the increased number of large lysosomes and microtubules. In both groups, three-dimensional structures of microfilaments could be visualized around bile canaliculi and along cell borders by the quick-freezing and deep-etching method. The branching microfilaments with the diameters of 7 to 10 nm were directly attached to other filaments, cell organelles or cytoplasmic sides of cell membranes. Moreover, bundled intermediate filaments were increased around peribiliary microfilaments associated with long-term cholestasis. It is suggested that excessive accumulation of peribiliary microfilaments disturb the secretion of bile components into bile canaliculi. The cytoskeletal reorganizations of intermediate filaments seem to alter the arrangements of various cell organelles.
Social Activists and Social Change: The Chicago Demonstrators
Authors: PAUL R. MILLER
Journal: American Journal of Psychiatry (1970)

A representative sample of 107 social activists who were arrested during the Chicago protest demonstrations in 1968 completed a self-administered questionnaire, providing the data for this study. The demonstrators were likely to be of upper middle class background, college educated, and aiming at a career in the professions. Their protest focused upon three areas: racism and poverty, war and the military-industrial complex, and unrepresentative government. The author suggests that activists may be best understood in terms of their youth, their life style of explicit congruity, and the growing youth culture.
Treatment of Physicians Who Are Psychologically Vulnerable
Authors: Stanley H. King
Journal: New England Journal of Medicine (1972)

There is a theme in the article by Vaillant, Sobowale, and McArthur (page 372) that deserves further amplification — a theme that relates to the interpretation of the data rather than to the data themselves. The authors show that a sample of physicians were vulnerable in specific ways and indicate that their doctors had differing personality characteristics from control subjects. However, Vaillant and his colleagues chose to emphasize the coping or adaptive aspects of the personalities of physicians rather than the defensive or neurotic aspects. This emphasis illustrates the fact that the same items of behavior can be interpreted in . . .
Structure-induction versus structure-toxicity relationships for polychlorinated biphenyls and related aromatic hydrocarbons.
Authors: J D McKinney, K Chae, E E McConnell, L S Birnbaum
Journal: Environmental Health Perspectives (1985)

A comparison of the structure-induction (involving rat and mouse Ah receptor binding) and structure-toxicity (in vivo guinea pig toxicity) relationships suggests that two receptors with structurally distinct binding properties may be involved. This is supported by demonstration of potentiated toxicity through a mechanism believed to involve the Ah receptor as a site of loss with respect to toxicity. Theoretical and working models are proposed for these separate receptors to aid in the search for other relevant binding proteins. The findings suggest that polychlorinated biphenyls that are relatively low in toxicity may have modulating properties on the action of highly toxic compounds with which they are normally found in the environment.
Abstract 4527: Sensitization of cancer cells to cisplatin by curcumin: mlecular mechanism and drug delivery.
Authors: Natalie Daurio, Stephen Tuttle, Nimil Sood, Daniel Hammer, Constantinos Koumenis
Journal: Cancer Research (2013)

Abstract Curcumin, the major active component of the spice Turmeric, is known to sensitize cancer cells to treatment with cisplatin. However, the exact mechanism by which this occurs is unresolved. We hypothesize that sensitization is dependent on curcumin-mediated inhibition of thioredoxin reductase 1, a major antioxidant enzyme. We have shown that a knock down of TxnRd1 expression ameliorates sensitization by curcumin and that over-expression of TxnRd1 in cells with low endogenous levels enhances cisplatin sensitivity. The use of curcumin clinically has been limited by is its low bioavailability outside the GI tract. Therefore, we have also encapsulated curcumin into polymersome nanoparticles composed of poly(ethylene oxide)-block-polycaprolactone co-polymer to improve drug delivery. These vesicles have the unique advantage of being completely biodegradable and can be dual loaded with individual drugs in the membrane and aqueous core allowing for simultaneous delivery of curcumin and cisplatin. Preliminary studies have demonstrated that these polymersomes encapsulate both curcumin in the hydrophobic membrane and cisplatin in the aqueous core and can deliver them to tumor cells. Future studies will determine whether these bifunctional polymersomes demonstrate enhanced cytotoxicity to animal models of solid tumors. Citation Format: Natalie Daurio, Stephen Tuttle, Nimil Sood, Daniel Hammer, Constantinos Koumenis. Sensitization of cancer cells to cisplatin by curcumin: mlecular mechanism and drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4527. doi:10.1158/1538-7445.AM2013-4527
Letter: Drugs and candy
Authors: A. Navarrete
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The response to my painting,<i>Pitkin County</i>, on the cover of the Sept 23 issue was a pleasant surprise. The many inquiries and compliments I received from physicians who saw the cover are both encouraging and rewarding. I thank the staff ofThe Journalfor its fine presentation of my painting.
Building on Experience — The Development of Clinical Reasoning
Authors: Geoffrey Norman
Journal: New England Journal of Medicine (2006)

As medical students become physicians, they need to learn to diagnose and manage clinical problems — a process often referred to as developing clinical reasoning skills. Researchers have been exploring the nature of clinical diagnostic reasoning for more than three decades. The initial interest was sparked by a new generation of medical schools, such as those at McMaster University and Michigan State University, whose curricula were explicitly directed toward teaching and learning about "clinical problem-solving." Little was known about the process, but the belief was that if it were better understood, we could teach it more effectively. In this issue . . .
Nova et Vetera
Authors: C. Lillingston
Journal: BMJ (1956)

EDICJOURN 1041The available vaccine will be distributed as evenly as possible throughout all the age groups.To achieve this children are being chosen for vaccination according to their month of birth.Details of those children to be vaccinated first will be found on p. 1055.The Medical Research Council is carrying out the selection, after first analysing all the registrations.
Fetal Loss and Caffeine Intake-Reply
Authors: Claire Infante-Rivard
Journal: JAMA (1994)

<h3>In Reply.</h3> —Dr Wei is surprised that smoking and alcohol consumption were not strongly related to fetal loss in our study; however, this has also been observed in at least two previous studies.<sup>1,2</sup>It is suggested that this could be because of a selection bias in our study. It seems unlikely that being a coffee drinker, a smoker, or an alcohol drinker would be related to day or night discharge. The analysis suggested for the odds of fetal loss before and during pregnancy is inadequate, since women did not necessarily shift in the lower intake category, and ours is a 3:1 matched analysis. Finally, we cannot see the appropriateness of controlling for caffeine intake during pregnancy when analyzing the effect of intake before pregnancy. Dr Kline and colleagues give a clear explanation of the results of their study in which cases were karyotyped. Although studying karyotypes is advantageous, it
Simultaneous Immunization with B.C.G., Diphtheria-tetanus, and Oral Poliomyelitis Vaccines in Children Aged 13-14
Authors: N. S. Galbraith, G. Crosby, J. M. Barnes, R. Fernandes
Journal: BMJ (1971)

The simultaneous administration of B.C.G. vaccine, diphtheria-tetanus toxoid aluminium hydroxide adsorbed vaccine, and oral poliovaccine was studied in 628 children aged 13-14 years between 1966 and 1969 in Newham, London. The efficacy of these vaccines was unaffected by administering them at the same time; routine simultaneous administration is considered justified when organizational difficulties prevent the attainment of high immunization rates with the vaccines given separately. No adverse reactions to B.C.G. or oral poliomyelitis vaccines took place, but 8% of children had moderately severe local reactions after diphtheria-tetanus aluminium hydroxide adsorbed vaccine, which were attributed to diphtheria toxoid. Serological studies showed the need for immunization against diphtheria, tetanus, and poliomyelitis at 13-14 years of age. Because of the adverse reactions to diphtheria toxoid, however, simultaneous administration of tetanus toxoid aluminium hydroxide adsorbed, oral poliomyelitis, and B.C.G. vaccines only is recommended at present. An “adult type” diphtheria-tetanus toxoid might overcome the problem of reactions, though in two to three years9 time most children aged 13-14 years will have received diphtheria-tetanus-pertussis vaccine in infancy and reinforcement might then be accomplished by a small intradermal dose of the currently available fluid diphtheria-tetanus vaccine. Continued serological studies of diphtheria and tetanus antitoxins and polio antibody are necessary to determine the future need for reinforcement of immunity; such studies should become an essential part of the surveillance of the community immunization programme.
Broad Functional Correction of Molecular Impairments by Systemic Delivery of scAAVrh74-hSGSH Gene Delivery in MPS IIIA Mice
Authors: F Jason Duncan, Bartholomew J Naughton, Kimberly Zaraspe, Darren A Murrey, Aaron S Meadows, Kelly Reed Clark, David E Newsom, Peter White, Haiyan Fu, Douglas M McCarty
Journal: Molecular Therapy (2015)

Mucopolysaccharidosis (MPS) IIIA is a neuropathic lysosomal storage disease caused by deficiency in N-sulfoglucosamine sulfohydrolase (SGSH). Genome-wide gene expression microarrays in MPS IIIA mice detected broad molecular abnormalities (greater than or equal to twofold, false discovery rate ≤10) in numerous transcripts (314) in the brain and blood (397). Importantly, 22 dysregulated blood transcripts are known to be enriched in the brain and linked to broad neuronal functions. To target the root cause, we used a self-complementary AAVrh74 vector to deliver the human SGSH gene into 4-6 weeks old MPS IIIA mice by an intravenous injection. The treatment resulted in global central nervous system (CNS) and widespread somatic restoration of SGSH activity, clearance of CNS and somatic glycosaminoglycan storage, improved behavior performance, and significantly extended survival. The scAAVrh74-hSGSH treatment also led to the correction of the majority of the transcriptional abnormalities in the brain (95.9%) and blood (97.7%), of which 182 and 290 transcripts were normalized in the brain and blood, respectively. These results demonstrate that a single systemic scAAVrh74-hSGSH delivery mediated efficient restoration of SGSH activity and resulted in a near complete correction of MPS IIIA molecular pathology. This study also demonstrates that blood transcriptional profiles reflect the biopathological status of MPS IIIA, and also respond well to effective treatments.
Divergent regulation of the Glut 1 and Glut 4 glucose transporters in isolated adipocytes from Zucker rats.
Authors: O Pedersen, C R Kahn, B B Kahn
Journal: Journal of Clinical Investigation (1992)

We have studied the relationship between glucose uptake rate and Glut 1 and Glut 4 protein and mRNA levels per fat cell in lean (FA/FA) and obese (fa/fa) Zucker rats at 5, 10, and 20 wk of age, and after induction of acute diabetes with streptozotocin. 5 wk obese rats exhibit insulin hyperresponsive glucose uptake, whereas 20 wk obese rats show insulin resistant glucose uptake. The relative abundance of Glut 1 and Glut 4 mRNA and protein per equal amount of total RNA and total membrane protein, respectively, is lower in adipocytes from obese rats. However, at all ages the enlargement of fat cells from obese rats is accompanied by a severalfold increase in total RNA and total membrane protein per cell. Thus, on a cellular basis, mRNA and protein levels of Glut 4 increases in young obese rats and gradually declines as a function of age. Basal glucose uptake is increased severalfold in fat cells from obese rats, and in parallel Glut 1 expression per cell in obese rats is two- to threefold increased over lean rats at all ages. Acute diabetes in 20 wk obese rats causes a profound downregulation of glucose uptake and a concomitant reduction of both Glut 1 and Glut 4 protein levels. Thus, changes in Glut 4 expression are a major cause of alteration in insulin-stimulated glucose uptake of adipocytes during evolution of obesity and diabetes in Zucker rats.
Skin Involvement in Generalized Amyloidosis
Authors: ALAN RUBINOW
Journal: Annals of Internal Medicine (1978)

A punch or excisional biopsy of the skin was done in 50 patients with generalized amyloidosis: In 46, clinically normal skin, usually the forearm, was biopsied and in four, only cutaneous lesions. Amyloid was seen in the skin of 21 of 38 patients with primary and multiple myeloma-associated amyloidosis. Sixteen of 34 biopsies from clinically uninvolved skin were positive. Five of 12 patients with secondary amyloidosis had amyloid deposits in clinically normal skin. Overall, amyloidosis was definitively diagnosed on skin biopsy examination in 26 patients. A punch biopsy of clinically involved or uninvolved skin is an innocuous, simple procedure with a high diagnostic yield and can be done in an office setting.
THE MUTUAL INTEREST OF THE MEDICAL PROFESSION AND INSURANCE COMPANIES IN THE PROLONGATION OF LIFE.Read before the Section of Medicine at the Forty-fourth Annual Meeting of the American Medical Association, held in Milwaukee, Wis., June, 1893.
Authors: CHARLES DENISON
Journal: JAMA (1893)

This is a new inquiry, seeking to bring into better harmony and successful coöoperation two great institutions,<i>i. e.</i>, scientific medicine and life insurance business. Those satisfied with what is already the rule will oppose with the argument, cui bonof the two callings are wholly distinct and entirely sufficient as they are. The argument is both fallacious and deceptive, besides being useless. We, the medical profession, are not and do not pretend to be perfect. We are simply on the road to perfection, constantly passing many things by the, way with regretted and unregretted, if unknown, ignorance of their real nature. If Lawson Tait had any reason to make the statement attributed to him, that "that man would be rash who would make a positive diagnosis of any given condition within the abdominal cavity," then certainly every physician must appreciate the equal necessity of the largest possible array of evidence