tbuckley/cabot-search huggingface dataset:
Defective major histocompatibility complex class I expression on lymphoid cells in autoimmunity.
Authors: Y Fu, D M Nathan, F Li, X Li, D L Faustman
Journal: Journal of Clinical Investigation (1993)

Lymphocytes from patients with insulin-dependent diabetes mellitus (IDDM), a chronic autoimmune disease, have recently been shown to have decreased surface expression of MHC class I antigens. Since IDDM and other autoimmune diseases share a strong genetic association with MHC class II genes, which may in turn be linked to genes that affect MHC class I expression, we studied other autoimmune diseases to determine whether MHC class I expression is abnormal. Fresh PBLs were isolated from patients with IDDM, Hashimoto's thyroiditis, Graves' disease, systemic lupus erythematosis, rheumatoid arthritis, and Sjogren's syndrome. Nondiabetic and non-insulin-dependent diabetes mellitus patients served as controls. MHC class I expression was measured with a conformationally dependent monoclonal antibody, W6/32. Freshly prepared PBLs from the autoimmune diseases studied and the corresponding fresh EBV-transformed B cell lines had decreased MHC class I expression compared with PBLs from normal volunteers and non-insulin-dependent (nonautoimmune) diabetic patients. Only 3 of more than 180 donors without IDDM or other clinically recognized autoimmune disease had persistently decreased MHC class I expression; one patient was treated with immunosuppressive drugs, and subsequent screening of the other two patients revealed high titers of autoantibodies, revealing clinically occult autoimmunity. Patients with nonautoimmune inflammation (osteomyelitis or tuberculosis) had normal MHC class I expression. Autoimmune diseases are characterized by decreased expression of MHC class I on lymphocytes. MHC class I expression may be necessary for self-tolerance, and abnormalities in such expression may lead to autoimmunity.
No conspiracy regarding recommendation for a group B meningococcus vaccine
Authors: A. J. Pollard, A. Riordan, M. Ramsay
Journal: BMJ (2014)

Isaacs and McVernon highlight the importance and complexity of policy decision making for a group B meningococcal vaccine based on cost effectiveness.1

The health economic analysis for a group B meningococcal vaccine is difficult because of uncertainties about critical parameters that determine whether the vaccine meets the required threshold for cost effectiveness. Indeed, the first health economic model made available to the independent scientific committee that advises the UK Departments of Health—the Joint Committee on Vaccination and …
Basophil Suppression in Peanut Allergic Patients Undergoing Sublingual Immunotherapy (SLIT)
Authors: S.J. Chin, E.H. Kim, J.A. Bird, M.D. Kulis, S.S. Laubach, L. Pons, W.G. Shreffler, P. Steele, J.S. Kamilaris, B.P. Vickery
Journal: Journal of Allergy and Clinical Immunology (2011)
Progress in Angiography
Authors: Richard E. Buenger
Journal: JAMA (1965)

<b>Vascular Roentgenology: Arteriography, Phlebography, Lymphography.</b>Edited by Robert A. Schobinger and Francis F. Ruzicka, Jr. 747 pp, with illus. $35. The Macmillan Co., 60 Fifth Ave, New York 11, 1964 <i>Progress in Angiography</i>very neatly conveys the atmosphere of the refresher course which it records. The text is divided into sections on technique, angiocardiography, coronary arteriography, renal angiography, abdominal angiography, neuroangiography, venography, and lymphangioadenography. Each section has several subspecialist authors and each concludes with a refreshing panel discussion in which experts and audience both participate. It is here that the practical questions are answered and the valleys between the superspecialized heights of the formal presentations are filled with a leveling amount of clinical application to routine problems. Since the scope of angiography is so wide, a selected bibliography by each expert enables us to utilize this text as a complete reference book. The reproductions, mainly demonstrating pathological states commonly encountered,
Significance of Cross-Linking of α2-Plasmin Inhibitor to Fibrin in Inhibition of Fibrinolysis and in Hemostasis
Authors: Yoichi Sakata, Nobuo Aoki
Journal: Journal of Clinical Investigation (1982)

When blood is clotted, α2-plasmin inhibitor (α2PI) is cross-linked to fibrin by activated fibrin-stabilizing factor (activated coagulation Factor XIII, plasma transglutaminase). The amount of cross-linked α2-PI is proportional to the amount of α2PI present at the time of clotting. Plasma from a patient with congenital deficiency of α2PI was supplemented with various amounts of purified α2PI. Clots were prepared from these plasmas and were suspended in plasma containing a normal concentration of α2PI, and spontaneous clot lysis was observed. When the clot was formed in the presence of calcium ions and thereby allowing cross-linking to occur, the rate and extent of fibrinolysis were found to be inversely proportional to the concentrations of α2PI present in the clot at the time of clotting. When the clot was formed in the absence of calcium ions so that no cross-linking occurred, the clot underwent fibrinolysis at similar rates, regardless of the concentrations of α2PI in the clot. When the clot formed in the presence of calcium ions was squeezed and washed to remove unbound proteins before being suspended in plasma, the extent of fibrinolysis was also inversely proportional to the amount of α2PI cross-linked to fibrin. Similar results were obtained when the clot was suspended in buffered saline instead of plasma. These observations suggest that spontaneous fibrinolysis is mainly carried out by plasminogen/plasminogen activator bound to fibrin, and this fibrinolysis caused by fibrin-associated activation of plasminogen was mainly inhibited by α2PI cross-linked to fibrin. To further support this concept, α2PI treated with activated fibrin-stabilizing factor and that had lost most of its cross-linking capacity was used in similar experiments. This modified α2PI had the same inhibitory activity on plasmin as the native inhibitor, but gave significantly less inhibition of fibrinolysis in every experiment, particularly when the clot was compacted by platelet-mediated clot retraction or by squeezing. Thus, it was concluded that α2PI cross-linked to fibrin plays a significant role in inhibition of physiologically occurring fibrinolysis. It is further suggested that the absence of cross-linked α2PI contributes to accelerated fibrinolysis and hemorrhagic tendency in patients with congenital deficiency of fibrin-stabilizing factor.
Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase
Authors: Madhav D. Sharma, Babak Baban, Phillip Chandler, De-Yan Hou, Nagendra Singh, Hideo Yagita, Miyuki Azuma, Bruce R. Blazar, Andrew L. Mellor, David H. Munn
Journal: Journal of Clinical Investigation (2007)

A small population of plasmacytoid DCs (pDCs) in mouse tumor-draining LNs can express the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO). We show that these IDO+ pDCs directly activate resting CD4+CD25+Foxp3+ Tregs for potent suppressor activity. In vivo, Tregs isolated from tumor-draining LNs were constitutively activated and suppressed antigen-specific T cells immediately ex vivo. In vitro, IDO+ pDCs from tumor-draining LNs rapidly activated resting Tregs from non-tumor-bearing hosts without the need for mitogen or exogenous anti-CD3 crosslinking. Treg activation by IDO+ pDCs was MHC restricted, required an intact amino acid-responsive GCN2 pathway in the Tregs, and was prevented by CTLA4 blockade. Tregs activated by IDO markedly upregulated programmed cell death 1 ligand 1 (PD-L1) and PD-L2 expression on target DCs, and the ability of Tregs to suppress target T cell proliferation was abrogated by antibodies against the programmed cell death 1/PD-L (PD-1/PD-L) pathway. In contrast, Tregs activated by anti-CD3 crosslinking did not cause upregulation of PD-Ls, and suppression by these cells was unaffected by blocking the PD-1/PD-L pathway. Tregs isolated from tumor-draining LNs in vivo showed potent PD-1/PD-L-mediated suppression, which was selectively lost when tumors were grown in IDO-deficient hosts. We hypothesize that IDO+ pDCs create a profoundly suppressive microenvironment within tumor-draining LNs via constitutive activation of Tregs.
Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease
Authors: Katie Lunnon, Rebecca Smith, Eilis Hannon, Philip L De Jager, Gyan Srivastava, Manuela Volta, Claire Troakes, Safa Al-Sarraj, Joe Burrage, Ruby Macdonald, Daniel Condliffe, Lorna W Harries, Pavel Katsel, Vahram Haroutunian, Zachary Kaminsky, Catharine Joachim, John Powell, Simon Lovestone, David A Bennett, Leonard C Schalkwyk, Jonathan Mill
Journal: Nature Neuroscience (2014)
A Six-Year-Old Girl with Tick Paralysis
Authors: Michael W. Felz, Carrie Davis Smith, Thomas R. Swift
Journal: New England Journal of Medicine (2000)

Tick paralysis is a neurologic syndrome that is frequently confused with other acute disorders. In this syndrome, ascending paralysis is caused by a potent neurotoxin produced by an attached, engorged tick. Removal of the tick leads to prompt recovery. Although cases of tick paralysis were clearly described almost 90 years ago in the United States,1 Canada,2 and Australia,3 the syndrome is unfamiliar to many clinicians today. Since a delay in the diagnosis can have devastating consequences, physicians must be aware of the salient features of this syndrome. If the diagnosis of tick paralysis is being considered, detection is possible with . . .
Abstract 1122: Tetrandrine induces expression of growth/differentiation factor-15 and promoted terminal differentiation of PCa cells
Authors: Sweaty Koul, Hari K. Koul
Journal: Cancer Research (2014)

Abstract Tetrandrine (Tet) is a naturally derived bis-benzylisoquinoline alkaloid, from S tenrandra, a herb that has been used in Chinese medicine for its anti-inflammatory, immunologic and antiallergenic effects. Results from our laboratory show that Tetrandarine blocks prostate cancer growth, promotes cell cycle arrest and induces apoptosis in a time and concentration dependent manner. In the present study we performed un-biased gene expression analysis of LNCaP cells following treatment with Tet. Analysis of gene expression revealed that GDF-15 was one of the most highly expressed cytokines following treatment of LNCaP cells with Tet. The gene expression results were further confirmed in relative quantitative PCR and Real time PCR assays, as was protein expression of GDF-15 confirmed by Western blot analysis. Our results, in light of the role of GDF-15 as a macrophage inhibitory factor as well as prostate epithelial differentiating factor, suggest that Tet may serve as a useful agent to promote prostate epithelial differentiation and inhibit tumor macrophage infiltration. Additional studies revealed that Treatment of PCa cells with Tet inhibited cell migration and invasion and suppressed EMT. Taken together we conclude that Tet by regulating GDF-15 expression may serve as an inhibitor of Prostate cancer cell progression and metastasis. (Financial Support: Supported in part by NIH/NCI R01CA161880 (PI:H.Koul); VA Merit Award 01BX001258 (PI:H.Koul); Carroll W. Feist endowed Cahir and LSUHSC Chair Commitment Funds) Citation Format: Sweaty Koul, Hari K. Koul. Tetrandrine induces expression of growth/differentiation factor-15 and promoted terminal differentiation of PCa cells. [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 1122. doi:10.1158/1538-7445.AM2014-1122
From Medical Student to Intern: Where Are the Role Models?
Authors: Judy L. Paukert, George Hsieh
Journal: JAMA (2001)

THE OPPORTUNITY TO GAIN exposure to the various fields of medicine en route to selecting a specialty.Each spring, the residency match process lights a fire under senior medical students.Interviewing applicants and residencies evaluate and rank each other prior to final placement by the National Residency Matching Program (NRMP).At many schools, the culminating event is a Match Day ceremony, where seniors gather to learn whether their efforts have merited entry into their program of choice.The agony and ecstasy of medical school crystallize into a single moment as the seal is broken on the envelope holding each graduate's match outcome.The result is met with elation and relief for many, disappointment for some.Most feel satisfaction at advancing closer to a career, perhaps mingled with regret at leaving other options behind.Even amid the jubilation, an undercurrent of anticipation and trepidation is palpable at the prospect of assuming real responsibilities.In 2001, 93.7% of graduating allopathic US medical students matched into residency, accounting for 73.8% of the 18354 positions filled by the NRMP. 1 An additional 4215 positions were filled by US osteopathic applicants, US international medical graduates (IMGs) and non-US IMGs.Overall, available positions in primary and specialty care both showed an 89% fill rate, although entry into primary care was down 3.6% compared to 2000. 1 Residency training is a relatively new development in medical education. 2 In the early 1900s, medical school was considered adequate preparation for general practice.Expansion of information by the 1920s necessitated a "rounding out" year of internship.Specialty training (a privilege reserved for only the most promising candidates) was also launched around this time.Required to live on hospital grounds, these intrepid and typically unpaid souls were aptly dubbed "residents."Although much of their time was spent caring for patients, resident physicians also languished in laboratory and custodial work.The process could take many years, advancement was arbitrary, and attrition was high.Some physicians eschewed this pathway and sought specialty training abroad; others proclaimed themselves specialists after brief, unregulated study.The quality of postgraduate education varied widely.The lack of standardization was addressed in the 1930s with the establishment of many specialty boards.By the 1950s, residents exceeded medical students in number and specialist physicians exceeded generalists.A match plan (similar to today's) was established in 1951.Further refinements included salaries for residents and relaxation of rules pertaining to personal life.The 1970s saw merging of internship and residency as well as proliferation of subspecialty and fellowship training.Electronic application was recently introduced.How will the residency selection process continue to evolve?jms060601f1scan
MEDICAL PHASES OF DENTAL DISORDERS.
Authors: SAMUEL A. HOPKINS
Journal: JAMA (1906)

Under this head we have two classes of cases which present themselves for consideration. On the one hand, there are those which, while presenting medical symptoms, are directly due to some disturbance in the teeth or the surrounding tissues; on the other hand, we may have a large number of reflex disorders, the origin of which is not always apparent, but which ultimately we find to be located in a diseased tooth. Whatever the medical phases of dental disorders may be, or wherever they may be located, in the ears, eyes, throat, nose, in the cervical or the salivary glands or even in more remote organs, it is an unfortunate fact that very many of the cases reported as having their origin in diseased teeth bear with them the confession of failure on the part of the physician to make an early and successful diagnosis. In going over the meager
Cholesterol kinetics in subjects with bile fistula. Positive relationship between size of the bile acid precursor pool and bile acid synthetic rate.
Authors: C C Schwartz, L A Zech, J M VandenBroek, P S Cooper
Journal: Journal of Clinical Investigation (1993)

Our aim was to identify and quantitate cholesterol pools and transport pathways in blood and liver. By studying bile fistula subjects, using several types of isotopic preparations, simultaneous labeling of separate cholesterol pools and sampling all components of blood and bile at frequent intervals, we developed a comprehensive multicompartmental model for cholesterol within the rapidly miscible pool. Data in six components (bile acids, esterified cholesterol in whole plasma, and free cholesterol in blood cells, bile, alpha lipoproteins, and beta lipoproteins) were modeled simultaneously with the SAAM program. The analysis revealed extensive exchange of free cholesterol between HDL and liver, blood cells, and other tissues. There was net free cholesterol transport from HDL to the liver in most subjects. The major organ that removed esterified cholesterol from blood was the liver. A large portion (4,211 mumol) of total hepatic cholesterol comprised a pool that turned over rapidly (t1/2 of 72 min) by exchanging mainly with plasma HDL and was the major source of bile acids and biliary cholesterol. Only 6% of hepatic newly synthesized cholesterol was used directly for bile acid synthesis: the analysis showed that 94% of newly synthesized cholesterol was partitioned into the large hepatic pool (putative plasma membrane free cholesterol) which exchanged rapidly with plasma lipoproteins. Bile acid synthetic rate correlated directly with the size of the large hepatic pool. In conclusion, hepatic and blood cholesterol pools and transports have been quantitated. HDL plays a central role in free cholesterol exchange/transport between all tissues and plasma. In humans, the metabolically active pool comprises a large portion of total hepatic cholesterol that, in part, regulates bile acid synthesis.
The Shigella flexneri Type Three Secretion System Effector IpgD Inhibits T Cell Migration by Manipulating Host Phosphoinositide Metabolism
Authors: Christoph Konradt, Elisabetta Frigimelica, Katharina Nothelfer, Andrea Puhar, Wilmara Salgado-Pabon, Vincenzo di Bartolo, Daniel Scott-Algara, Cristina D. Rodrigues, Philippe J. Sansonetti, Armelle Phalipon
Journal: Cell Host & Microbe (2011)
Different electrophysiological responses of canine endocardium and epicardium to combined hyperkalemia, hypoxia, and acidosis.
Authors: R F Gilmour, D P Zipes
Journal: Circulation Research (1980)

To determine whether canine epicardium and endocardium show intrinsically different electrophysiological responses to metabolic alterations that occur during acute myocardial ischemia in vivo, endocardial, epicardial, papillary muscle tip, and Purkinje fibers (PF) were superfused in vitro with Tyrode's solution containing 8.0 DM KC1 at a pH of 6.85 and a Po 2 < 50 mm Hg.During the initial 10 minutes of superfusion with altered Tyrode's solution, reduction of action potential (AP) amplitude and dV/dtmax and prolongation of activation times were greater in epicardium than in endocardium or in PF, despite similar changes in resting membrane potential.After superfusion for 15 minutes, only 3 of 18 epicardial and 5 of 16 papillary muscle cells were excitable, whereas 14 of 16 endocardial muscle cells and 13 of 13 PF still were responsive.Membrane responsiveness at takeoff potentials < -65mV was lower in epicardium and papillary muscle than in endocardium during superfusion with normal or altered Tyrode's solution.The effects produced by the initial 15 minutes of superfusion with altered Tyrode's solution were partially reversed in endocardium and PF but not in epicardium or papillary muscle, during a subsequent 20-to 60-minute period of continued superfusion.Tetrodotoxin (1'1'X, 5 x 10" 6 M) depressed AP amplitude and dV/dtm., more in epicardium than in endocardium.TTX had only a small effect on the upstroke of PF AP, but shortened AP duration by 30-40%.Verapamil (2 x 10~6 M) had equivalent effects on endocardium and epicardium.These data indicate that excitability is more easily depressed by a combination of hyperkalemia, hypoxia, and acidosis, and by TTX, in epicardium and papillary muscle tip than in endocardium and PF.Responsiveness of endocardial muscle during exposure to altered Tyrode's solution or TTX may be enhanced by contact with PF. drc Res 46: 814-825, 1980IT IS well established that conduction in the subendocardium remains relatively preserved during acute myocardial ischemia in vivo at a time when conduction in the subepicardium has undergone progressive delay and fractionation (Boineau and Cox, 1973;Williams et al, 1974;Scherlag et al., 1974;Elharrar et al., 1977;Ruffy et al., 1979).This difference between the electrophysiological response of endocardium and epicardium is particularly puzzling, considering the established susceptibility of the subendocardium to the necrotizing effects of coronary artery occlusion (Jennings et al., 1957; Rivas.etal., 1976).Various explanations have been offered, including effects of cavity blood (Friedman
Slow-growing lung cancer as an emerging entity: from screening to clinical management
Authors: Maurizio Infante, Thierry Berghmans, Marjolein A. Heuvelmans, Gunnar Hillerdal, Matthijs Oudkerk
Journal: European Respiratory Journal (2013)

The current paradigm is that untreated lung cancer is invariably and rapidly fatal, therefore the medical community normally dismisses the idea that a patient could live with such a disease for years without any therapy. Yet evidence from lung cancer screening research and from recent clinical series suggests that, although rarely recognised in routine practice, slow-growing lung cancers do exist and are more common than previously thought. Here, current evidence is reviewed and clinical cases are illustrated to show that slow-growing lung cancer is a real clinical entity, and the reasons why management protocols developed in the screening setting may also be useful in clinical practice are discussed. Features suggesting that a lung cancer may be slow-growing are described and appraised, areas of uncertainty are examined, modern management options for early-stage disease are evaluated and the influence that all this knowledge might have on our clinical decision-making is weighed. Further research directed at developing appropriate guidelines for these peculiar but increasingly common patients is warranted.
Managing halitosis Thorough history and examination are important
Authors: H Richardson, A J N Prichard, S G Parmar, P C Naik
Journal: BMJ (1994)

EDITOR, - Crispian Scully and colleagues' editorial describes oral and dental causes of halitosis and their treatment.1 It is important to emphasise that a thorough history and clinical examination must be undertaken. This must include examination of the nose, postnasal space, and all mucosal surfaces of the pharynx in addition to complete examination of the oral cavity and dentition.

Halitosis may be a presenting complaint of infection, inflammation, or malignancy of any part of the upper aerodigestive tract, and delay in diagnosis may …