tbuckley/cabot-search huggingface dataset:
How alum works
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

For more than 70 years, alum has been used as a trusty aide to improve antibody responses to vaccines. But how this aluminum-containing compound boosts the response to vaccines has been a mystery. On page 869, Kool et al. expose its mysterious mechanism; they find that alum causes cells to produce a stimulator of dendritic cells (DCs).






Figure 1

Mice injected with antigens mixed with alum produce uric acid that then attracts monocytes.




DCs were once the favored hypothetical link between alum and B cells, as they activate CD4+ T cells, which can then enhance B cell activation and antibody production. But DCs were later dismissed when it was found that they were not stimulated by alum in vitro.

These in vitro results are now shown to be a red herring by Kool et al., who find that alum activates DCs in vivo by provoking the secretion of uric acid—a molecule that is triggered by tissue and cell trauma. The injection of alum, the group found, induced an influx of neutrophils and inflammatory cytokines and chemokines—a combination that was previously seen in response to the injection of uric acid into mice.

In mice injected with antigens mixed with alum, uric acid levels increased within hours. The uric acid might be released by the cells' lining the body's cavities that turn necrotic after contacting the alum. The absence of these uric acid sources in in vitro assays might have led to the previous misleading results.

In response to the uric acid, inflammatory monocytes flocked to the injection site, took up the antigens, and broke them down into T cell–stimulating epitopes. The monocytes then migrated to lymph nodes, where they matured into DCs and activated CD4+ T cells.

Without alum, the antigens were not taken up at the injection site. Still, they eventually reached lymph nodes via the flowing lymph. The resident node DCs, however, did not process the alum-free antigens efficiently or express T cell costimulating receptors. The resulting subdued immunity was similar to that seen in mice that were depleted of inflammatory monocytes or those injected with enzymes that degrade uric acid.
American Melancholy: Constructions of Depression in the Twentieth Century
Authors: Mark H. Fleisher
Journal: JAMA (2010)

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
ON INFLAMMATIONS OF THE SCLEROTICA
Authors: W. Cooper
Journal: BMJ (1853)

chievous constitution of our hospitals and dispensares has a still more momentous bearing: it detrop orprevens the formation of provideant habits among thepoorer d8.The man who knows that a charity is open to him whenever he wants a dose of medicine, is not likely to save money ; with him, sufficient for the day is the evil thereof; and thus when his family are laid aside by sickness, the dispensary doctor is struck with the poverty of the den or garret, which, had not indiscriminate charity existed, might have been a com-
Doppler echocardiography. Use of a graphical display system.
Authors: G Lorch, S Rubenstein, D Baker, T Dooley, H Dodge
Journal: Circulation (1977)

Pulsed Doppler echocardiography (PDE) is a technique for evaluating blood flow characteristics at specific locations within the heart and great vessels. Because this method assesses blood flow rather than cardiac structures, PDE complements the findings of M-mode echocardiography. A new on-line graphical method for displaying pulsed Doppler information provides 1) a printed, permanent record of flow information, 2) precise timing of blood flow events, and 3) information on the direction of flow in the heart and great vessels.
T Cell-Independent Antigens Type 2
Authors: James J. Mond, Andrew Lees, Clifford M. Snapper
Journal: Annual Review of Immunology (1995)

In this review we have attempted to define the characteristics of TI-2 antigens that enable them to stimulate antibody production in the absence of T cell help. One of the most critical properties of this group of antigens is their ability to deliver prolonged and persistent signaling to the B cell. This by itself is not however sufficient to stimulate Ig synthesis, and they must therefore stimulate non-T cells to interact with the B cells either directly or indirectly via cytokine production. There is evidence implicating the NK cell and T cell as playing this important role in response to TI antigens. Furthermore, we discuss the importance of cytokines such as IL-3, GMCSF, and IFN-gamma, which significantly enhance antibody production by these antigens. Finally, we present evidence demonstrating that B cell activation via TI stimuli does not play merely a permissive role in allowing for cell cycle entry and enhanced responsiveness to other stimuli. Rather, the nature of the B cell activating signal is critical in determining the quantitative and qualitative profile of Ig isotype production.
Metastatic malignant clear cell hidradenoma associated with bullous pemphigoid
Authors: ALEXANDRA KAZAKIS, C. WOOD, REGINA ANDERSON
Journal: British Journal of Dermatology (1988)

The clinicopathological features of a case of mctastatic malignant clear cell hidradenoma (MCCH) occurring in a 72‐year‐old black male are reported. Unusual features of the case included the location of the tumour on the posterior trunk, the probable origination of the tumour from a benign appendageal tumour, and the occurrence of a bullous eruption immediately after surgical removal of the tumour. Clinicopathological aspects of MCCH are reviewed and treatment modalities, including chemotherapy, are discussed.
ERYTHROPOIETIC PROTOPORPHYRIA: SUBMICROSCOPIC EVENTS DURING THE ACUTE PHOTOSENSITIVITY FLARE
Authors: T. J. RYAN
Journal: British Journal of Dermatology (1975)

Journal Article ERYTHROPOIETIC PROTOPORPHYRIA: SUBMICROSCOPIC EVENTS DURING THE ACUTE PHOTOSENSITIVITY FLARE Get access T. J. RYAN T. J. RYAN Department of Dermatology, The Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 93, Issue 5, 1 November 1975, Page 605, https://doi.org/10.1111/j.1365-2133.1975.tb02259.x Published: 01 November 1975
Follicular lymphoma without t(14;18) and with BCL-6 rearrangement: a lymphoma subtype with distinct pathological, molecular and clinical characteristics
Authors: F Jardin, P Gaulard, G Buchonnet, N Contentin, S Leprêtre, P Lenain, A Stamatoullas, JM Picquenot, C Duval, F Parmentier, H Tilly, C Bastard
Journal: Leukemia (2002)
Incident reporting and patient safety
Authors: Charles Vincent
Journal: BMJ (2007)

Incident reporting should ideally communicate all information relevant to patient safety.Local incident reporting systems in hospitals typically use an incident form that comprises basic clinical details and a brief description of the incident.Such systems are ideally used as part of an overall safety and quality improvement strategy, but in practice they may be dominated by managing claims and complaints. 1 Specialty reporting systems 2 and large scale systems, such as that of the UK National Patient Safety Agency (www.npsa.nhs.uk/),allow wider dissemina-
GABAB Receptor Activation Inhibits Neuronal Excitability and Spatial Learning in the Entorhinal Cortex by Activating TREK-2 K+ Channels
Authors: Pan-Yue Deng, Zhaoyang Xiao, Chuanxiu Yang, Lalida Rojanathammanee, Laurel Grisanti, John Watt, Jonathan D. Geiger, Rugao Liu, James E. Porter, Saobo Lei
Journal: Neuron (2009)
Abstract 3483: A centrifugal ultrafiltration-based method for rapid purification of exosomes from biological samples
Authors: Amedeo Cappione, Sara Gutierrez, Masaharu Mabuchi, Janet Smith, Ivona Strug, Timothy Nadler
Journal: Cancer Research (2014)

Abstract Exosomes represent a subset of small particles secreted by many types of cells under both normal and pathological conditions. The release of microvesicles has demonstrated biological relevance; these particles act as mediators of intercellular communication both within the local microenvironment of the release site as well as systemically. Moreover, since exosomes contain RNA (messenger and miRNA) and protein (membrane-bound and cytosolic) from their cells of origin, and given that this content can be influenced by cell state, they also potentially represent a burgeoning target for biomarker discovery. Critical to understanding the physiological significance of these particles is the development of preparative techniques permitting reliable isolation of purified fractions. While numerous methods of exosome purification exist, including ultracentrifugation, immunoaffinity-based isolation using magnetic beads, precipitation, and ultrafiltration, most are plagued by sample limitations or require long and tedious workflows to achieve success. Here we present a rapid alternative method for the selective fractionation of exosomes from biological samples using an ultrafiltration device. Since the method is spin-based and dependent on size exclusion, the device has broad applications with regards to sample volume and/or type. Optimization of the protocol was aided through use of a mid infrared (MIR)-based spectroscopy platform that permits simultaneous monitoring of lysis conditions, protein quantitation, and analysis of total lipid content during exosome fractionation. Given the ultrafiltration device's capacity for buffer exchange and sample concentration, purified fractions can be easily formatted to meet the requirements of any downstream analysis platform. To demonstrate this, resulting fractions were assayed by numerous techniques including flow cytometry, western blotting, ELISA-based assays, and electron microscopy. Citation Format: Amedeo Cappione, Sara Gutierrez, Masaharu Mabuchi, Janet Smith, Ivona Strug, Timothy Nadler. A centrifugal ultrafiltration-based method for rapid purification of exosomes from biological samples. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3483. doi:10.1158/1538-7445.AM2014-3483
Cytotoxic T cell responses to human telomerase reverse transcriptase in patients with hepatocellular carcinoma
Authors: Eishiro Mizukoshi, Yasunari Nakamoto, Yohei Marukawa, Kuniaki Arai, Tatsuya Yamashita, Hirokazu Tsuji, Kiyotaka Kuzushima, Masafumi Takiguchi, Shuichi Kaneko
Journal: Hepatology (2006)

Human telomerase reverse transcriptase, hTERT, has been identified as the catalytic enzyme required for telomere elongation. hTERT is expressed in most tumor cells but seldom expressed in most human adult cells. It has been reported that 80% to 90% of hepatocellular carcinomas (HCCs) express hTERT, making the enzyme a potential target in immunotherapy for HCC. In the current study, we identified hTERT-derived, HLA-A*2402-restricted cytotoxic T cell (CTL) epitopes and analyzed hTERT-specific CTL responses in patients with HCC. Peptides containing the epitopes showed high affinity to bind HLA-A*2402 in a major histocompatibility complex binding assay and were able to induce hTERT-specific CTLs in both hTERT cDNA-immunized HLA-A*2402/Kb transgenic mice and patients with HCC. The CTLs were able to kill hepatoma cell lines depending on hTERT expression levels in an HLA-A*2402-restricted manner and induced irrespective of hepatitis viral infection. The number of single hTERT epitope-specific T cells detected by ELISPOT assay was 10 to 100 specific cells per 3 x 10(5) PBMCs, and positive T cell responses were observed in 6.9% to 12.5% of HCC patients. hTERT-specific T cell responses were observed even in the patients with early stages of HCC. The frequency of hTERT/tetramer+ CD8+ T cells in the tumor tissue of patients with HCC was quite high, and they were functional. In conclusion, these results suggest that hTERT is an attractive target for T-cell-based immunotherapy for HCC, and the identified hTERT epitopes may be valuable both for immunotherapy and for analyzing host immune responses to HCC.
Clinical and Biochemical Manifestations of Hyaluronidase Deficiency
Authors: Marvin R. Natowicz, M. Priscilla Short, Yu Wang, G. Richard Dickersin, Mark C. Gebhardt, Daniel I. Rosenthal, Katherine B. Sims, Andrew E. Rosenberg
Journal: New England Journal of Medicine (1996)

The mucopolysaccharidoses are lysosomal storage disorders caused by a genetic deficiency of enzymes that catalyze the degradation of glycosaminoglycans (mucopolysaccharides). These disorders are clinically variable and commonly associated with mental retardation, short stature, coarse facial features, organomegaly, and an accumulation of glycosaminoglycans in tissues. Hyaluronan (hyaluronic acid) is one of the major glycosaminoglycans and has a vital role in many physiologic processes.1–4 Genetic deficiencies of most of the lysosomal enzymes that catalyze the degradation of glycosaminoglycans have been identified, with the exception of hyaluronidase, a lysosomal endoglycosidase that catalyzes the degradation of hyaluronan.5–7 We describe the clinical, pathological, . . .
Erythrocyte glutathione synthetase deficiency leads not only to glutathione but also to glutathione-S-transferase deficiency.
Authors: E Beutler, T Gelbart, C Pegelow
Journal: Journal of Clinical Investigation (1986)

Glutathione synthetase (GSH-S) is one of the two known hereditary causes of glutathione deficiency. We describe a family whose two children have hemolytic anemia. The children's erythrocytes lack GSH and are severely deficient in GSH-S activity. No neurologic findings or 5-oxoprolinuria were present. A concurrent deficiency of glutathione-S-transferase (GST) was also detected in the erythrocytes. Residual glutathione could be detected in the erythrocytes using a sensitive cycling assay. The deficiency was found to be most severe in reticulocyte-depleted preparations. The GSH-S activity of the erythrocytes of the parents was one-half normal, while the glutathione S-transferase activity was normal. We conclude that the primary defect is one of GSH-S. Glutathione stabilizes GST in vitro, and it is assumed that the deficiency of GST in the erythrocytes of the patients is due to the instability of this enzyme in the absence of adequate intracellular GSH levels.
Calculating Body Mass Index
Authors: Robert Matz
Journal: Annals of Internal Medicine (1993)

Letters1 February 1993Calculating Body Mass IndexRobert Matz, MDRobert Matz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-3-199302010-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I took note of the Equation for calculating body mass index (BMI) using pounds and inches proposed by Frankel and Staeheli [1]. A simpler one is:BMI = weight (in pounds)/height (in inches)2 × 703.REFERENCE1. Frankel MH, Staeheli JC. Calculating body mass index. Ann Intern Med. 1992; 117:698-9. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe height importance of male athletes for the classification in the world handball championshipsThe Relationship of the Anthropometric Variables to the Infusion Rate of Rocuronium in the ElderlyMedical nutrition therapy for the treatment of obesityREFERENCE LIST 1 February 1993Volume 118, Issue 3Page: 232KeywordsBody mass index ePublished: 15 August 2000 Issue Published: 1 February 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comparison of emergent endoscopy and upper gastrointestinal series radiography in acute upper gastrointestinal haemorrhage.
Authors: R T Keller, G M Logan
Journal: Gut (1976)

A prospective study of early diagnostic procedures in acute upper gastrointestinal haemorrhage was conducted in a series of 76 patients. The diagnostic procedures included upper gastrointestinal series radiography (UGIS) and endoscopy (ENDO). The clinicians9 diagnosis and management improved in a statistically significant way as a result of the findings of endoscopy. The findings of UGIS did not significantly improve diagnostic accuracy and resulted in a statistically significant adverse effect on patient management. The results suggest that endoscopy is more effective in promoting early accurate diagnosis and management in patients with acute upper gastrointestinal haemorrhage.
Effect of Oestrogen Therapy on Plasma and Urinary Levels of Uric Acid
Authors: A. Nicholls, M. L. Snaith, J. T. Scott
Journal: BMJ (1973)

Uric acid clearance studies were carried out on a low-purine diet in 22 trans-sexual men before and during oestrogen therapy for this condition (stilboestrol in 21 cases, ethinyloestradiol in one). Plasma uric acid fell in 15 of the subjects and urinary uric acid rose in 17 of 20 subjects in whom satisfactory collections were obtained. These changes are significant and it is suggested that hormonal influences are responsible for the known age and sex differences in plasma uric acid.
Yellow Fever
Authors: Susan E. Robertson
Journal: JAMA (1996)

Since the 1980s, yellow fever has reemerged across Africa and in South America. The total of 18 735 yellow fever cases and 4522 deaths reported from 1987 to 1991 represents the greatest amount of yellow fever activity reported to the World Health Organization (WHO) for any 5-year period since 1948. There is an excellent vaccine against yellow fever. At present, a high proportion of travelers to at-risk areas are reported to be immunized, reflecting widespread knowledge about the International Health Regulations. In South America, yellow fever remains an occupational hazard for forest workers, who should be immunized. However, Aedes aegypti mosquitoes are now present in urban areas in the Americas (including southern parts of the United States), and there is concern that yellow fever could erupt in explosive outbreaks. In Africa, a large proportion of cases have occurred in children. The WHO, the United Nations Children's Fund (UNICEF), and the World Bank have recommended that 33 African countries at risk for yellow fever add the vaccine to the routine Expanded Programme on Immunization; studies show that this would be highly cost-effective. To date, financing yellow fever vaccine has been a major problem for these countries, which are among the poorest in the world. For this reason, WHO has launched an appeal to raise $70 million for yellow fever control in Africa.
520 Significance of HBV DNA, core promoter/precore mutations, genotypes, specific sequences of polymerase gene on three-year lamivudine treatment: A predictive model for antiviral therapy
Authors: M.E Yuen, E. Sablon, E. Libbrecht, H. Van de Velde, D.K.H. Wong, J. Fung, B.C.Y. Wong, C.L. Lai
Journal: Journal of Hepatology (2006)
Abstract 5074: Identification of Ras compartment-specific interacting proteins
Authors: Ze-Yi Zheng, Chiang-min Cheng, Xin-Rong Fu, Zhou Songyang, Eric C. Chang
Journal: Cancer Research (2010)

Abstract Ras proteins are powerful molecular switches that control a wide range of functions, including cell growth, differentiation, apoptosis, cytoskeleton remodeling, etc. In humans, there are three RAS genes encode structurally highly similar Ras proteins that appear to have different functions in the cell. We have previously reported that a given Ras protein can signal from different cell compartments to control distinct functions in yeast. This present project aims to identify proteins that bind Ras in a cell compartment-specific manner in human cells to define how compartmentalized Ras signaling impacts tumor formation. We used the biomolecular fluorescence complementation (BiFC) method to screen a human cDNA library. Sixty two proteins were thus identified that bound the constitutively activated H-Ras (H-RasG12V), but not the GST control. These proteins also bound weakly to H-RasG12V whose effector binding motif has been mutated. To determine if these proteins can alter Ras functions, we first overexpressed them and then tested for their impacts on Ras-induced cell transformation and transcription. Only 25 of the isolated proteins could alter Ras signaling in these assays. Many of these 25 proteins are known to either associate with cellular membrane and/or regulate protein transportation, suggesting that as a group they highlight the importance of regulating Ras trafficking in the control of cell transformation. In particular, a number of isolated proteins may regulate endosome sorting, and we thus focused on two such proteins, CHMP6/VPS20 and VPS4A, for further investigation. We first validated the Ras binding by co-immunoprecipitation; furthermore the microscopy data showed that the binding is readily detectable in endosomes. Moreover, up- or down-regulating of level of either CHMP6/VPS20 or VPS4A dramatically inhibited Ras-induced transformation of NIH-3T3 cells. To determine how these molecules regulate Ras activities, we first examined whether they modulate Ras protein intracellular transport. Cell fractionation using sucrose gradients has shown that VPS4A knock-down could alter both wide-type and constitutively activated Ras membrane localization. In summary, we indentified Ras compartment-specific binding proteins by a cell-based approach. Many of the proteins are trafficking regulating proteins. In particular, two endosome sorting proteins CHMP6/VPS20 and VPS4A have been shown to regulate the oncogenic effects of Ras, possibly by localizing Ras proteins into proper cell compartments. We believe that the study of compartment-specific Ras interacting proteins is indispensable for better understanding the complex roles of Ras in oncogenesis of breast cancer as well as many other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5074.