tbuckley/cabot-search huggingface dataset:
Thymic and extrathymic origins of gut intraepithelial lymphocyte populations in mice.
Authors: B Rocha, P Vassalli, D Guy-Grand
Journal: The Journal of Experimental Medicine (1994)

We have investigated the origin of intraepithelial lymphocytes (IEL) populations in the murine gut, using reconstitution experiments in which the presence of thymus-derived cells of host or donor origin is rigorously controlled: RAG-/- mutant mice which have no T cells, were injected either with the bone marrow (BM) cells of nude mice or with selected peripheral lymph node (LN) T cells of euthymic mice. In thymectomized RAG-/- mice, injection of BM cells from nude mice led, after 2 mo, to the development of a peripheral B cell compartment and to the appearance, in the gut, of IEL bearing homodimeric CD8 alpha chains and either gamma/delta or alpha/beta TCR. In RAG-/- mice with a thymus, a similar injection led to complete lymphoid reconstitution, with the additional appearance in the gut of CD4+, CD8 alpha/beta+ or CD4+CD8 alpha/alpha+ IEL, all bearing alpha/beta TCR. In contrast, injection of LN T cells into these mice reconstituted a gut IEL population made of CD4+, CD8 alpha/beta+, or CD4+ CD8 alpha/alpha+ cells, all bearing alpha/beta TCR; CD8 alpha/alpha+ TCR-gamma/delta+ or alpha/beta+ IEL were not observed. These results demonstrate that the thymus and/or thymic-derived peripheral T cells are absolutely required for the generation of CD4+, CD8 alpha/beta+, and CD4+CD8 alpha/alpha+ IEL, which are thus thymus dependent. In contrast, TCR+ CD8 alpha/alpha+ IEL appear in the absence of the thymus, and thus are thymus independent.
Recommended Guidelines for the Management of Autologous and Allogeneic Bone Marrow Transplantation: A Report from the Eastern Cooperative Oncology Group (ECOG)
Authors: Jacob M. Rowe
Journal: Annals of Internal Medicine (1994)

Objective: To define the basic state-of-the-art medical care of the patients after bone marrow transplantation as practiced by the Eastern Cooperative Oncology Group. Data Identification: Studies examining the role of bone marrow transplantation in the care of neoplastic disorders identified using computer and bibliographic searches. Study Selection: More than 500 articles, book chapters, and abstracts from meetings, covering all therapeutic and diagnostic aspects of the patient having bone marrow transplantation were critically reviewed; information from over 200 publications is included. Results of Data Analysis: Enormous progress has been made in understanding the biology, therapy, and prophylaxis strategies of bone marrow transplantation and in extending the range of potential marrow donors to include unrelated persons. Dramatic advances have occurred in the prevention of serious infection, including cytomegalovirus infection, formerly a cause of a high rate of mortality. The advent of newer-combination, high-dose chemotherapy regimens and advances in cryopreservation and in vitro marrow purging techniques have led to increased use and greater efficacy of autologous transplantation. Recent advances using recombinant hematopoietic growth factors and autologous peripheral stem cells are likely to reduce morbidity and mortality and significantly shorten the length of hospitalization and the cost of bone marrow transplantation. Conclusions: Bone marrow transplantation now is a common procedure done throughout the world. Cooperative groups have assumed a major role in conducting clinical trials. A standardized approach defining basic standards of care will assure uniformity of management, better interpretation of data, and continued progress in the care of the patient who has had a bone marrow transplantation. Basic research and clinical trials are ongoing to define better methods for the treatment and prevention of graft-versus-host disease and hepatic veno-occlusive disease.
European Commission opts against traffic light system for food labelling
Authors: Rory Watson
Journal: BMJ (2008)

The European Commission has tabled EU-wide legislation that will require all prepacked food to display key health and nutritional information clearly on the front of the package. However, a “traffic light” system of red, amber, or green labelling will not be adopted.

The proposal, which must now be approved by European Union governments and the European parliament, is part of the commission’s antiobesity strategy. It is also designed to update rules on food labelling first introduced 30 years ago.

Presenting the initiative, Markos Kyprianou, the European commissioner for health, said that food labels could have a big influence on consumers’ purchasing decisions. …
Neurologic Abnormalities and Recovery of Human Immunodeficiency Virus from Cerebrospinal Fluid
Authors: HARRY HOLLANDER
Journal: Annals of Internal Medicine (1987)

Infectious human immunodeficiency virus (HIV) was recovered from 30 of 48 cerebrospinal fluid specimens from seropositive persons with and without neurologic symptoms or disease. Of 16 patients with only neurologic problems or other HIV-related conditions, but not the acquired immunodeficiency syndrome (AIDS), 11 had virus recovered; over half of those with AIDS also had virus isolated. Patients with headache or altered mental status had the highest recovery rate of HIV from cerebrospinal fluid. Although virus was primarily found in patients with detectable neurologic disease, it was also isolated from 5 of 8 patients with normal neurologic examinations. Two of these patients had fever alone. The presence of virus in cerebrospinal fluid did not necessarily correlate with isolation of virus from the serum. These findings suggest that HIV may at times replicate preferentially in the brain and that its presence may not immediately cause neurologic signs or symptoms.
Phosphorylation of Estrogen Receptor β at Serine 105 in Primary Breast Cancer.
Authors: W. Hamilton-Burke, A. Shaaban, M. Cummings, D. Holliday, S. Pollock, K. Horgan, V. Speirs
Journal: Cancer Research (2009)

Abstract Background: Estrogen receptor (ER) α predicts response to hormonal therapy in breast carcinoma. The role of ERβ is less well understood. ER activities can be modulated by post-translational modifications including phosphorylation and phosphorylated ERα has been correlated with patient outcome. We investigated whether ERβ phosphorylated at Serine 105 (P-S105-ERβ) is expressed in breast carcinoma and assessed its potential clinical implications.Material and Methods: Tissue microarrays comprising 427 breast tumours (23% grade 1, 43% grade 2, 34% grade 3) with median follow up 118 months and 106 endocrine resistant breast tumours (15% grade 1, 41% grade 2, 44% grade 3) with median follow up 71 months were used in this study. Expression of P-S105-ERβ was studied by immunohistochemistry and analysed against clinical data. Regulation of P-S105-ERβ in vitro was assessed by immunofluorescence and Western blotting.Results: Expression of P-S105-ERβ was mainly nuclear and could be abolished by phosphatase pre-incubation, indicating specificity. In the first cohort Allred scoring ranged from 0 to 8 (median 6). Nuclear speckling was observed in 45% of cases. P-S105-ERβ correlated with ERβ1 (Allred score ≥ 3) and was associated with better overall survival (OS) and disease free survival (DFS) (p=0.028 and p=0.027, respectively). In a multivariate Cox hazard analysis, P-S105-ERβ overexpression was a significant predictor of better survival independent of tumor grade, lymph node status, size or ERα. In the endocrine resistant cohort Allred scoring ranged from 0 to 8 (median of 4) and the overexpression of P-S105-ERβ was also associated with improved OS and DFS (p=0.044 and p=0.033, respectively). Nuclear speckling was present in only 11% of cases. The difference in expression of P-S105-ERβ and association with survival outcome between the two cohorts was statistically significant. P-S105-ERβ was expressed in MCF-7 cells and in response to 17β-estradiol (E2); levels were raised within 30 min, and sustained for 24 hours. ERβ1 expression was unaffected by this treatment. Nuclear speckling was also observed and was markedly increased at 24 hours following E2 but not Tamoxifen.Conclusion: This is the first time to our knowledge that the expression of P-S105-ERβ in breast carcinoma has been investigated. Its presence in breast carcinoma and association with improved survival suggest P-S105-ERβ might be a useful additional prognostic marker in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4141.
Does it matter that medical graduates don’t get jobs as doctors? No
Authors: Alan Maynard
Journal: BMJ (2008)

Last year’s shortfall in training places looks set to be repeated. <b>Graham Winyard</b> (doi: 10.1136/bmj.39555.457060.AD) believes this is a betrayal of students’ expectations, but <b>Alan Maynard </b>thinks it is inevitable if patients are to get the best care
AAD Wants to Convert Sun Worshipers
Authors: Marsha F. Goldsmith
Journal: JAMA (1997)

<h3>Persuade the Young People</h3> The AAD estimates that about 40 300 new cases of malignant melanoma will occur this year, a 12% increase over last year, and that about 7300 deaths in 1997 will be attributable to this most devastating form of skin cancer. That's why more than 300 PHOEBUS APOLLO is far from popular with the American Academy of Dermatology. Icarus, who soared near the blazing star but fell to death when its heat melted his wax wings, seems a mythical Greek more to the liking of AAD members—a reminder of the danger awaiting anyone who ignores the fearsome power of the sun. At its "Sun Safety: Protect Our Future" conference last month in New York, NY, the academy hammered home the message summed up in a squib in<i>Skin Savvy</i>, an 8-page supplement included in<i>USA Today</i>on "Melanoma Monday," May 2. "Sunbathing... it's a crime!" warned the
The effects of vasopressin on acute kidney injury in septic shock
Authors: Anthony C. Gordon, James A. Russell, Keith R. Walley, Joel Singer, Dieter Ayers, Michelle M. Storms, Cheryl L. Holmes, Paul C. Hébert, D. James Cooper, Sangeeta Mehta, John T. Granton, Deborah J. Cook, Jeffrey J. Presneill
Journal: Intensive Care Medicine (2009)
Radionuclide Imaging of the Thyroid Gland: Patterns, Pearls, and Pitfalls
Authors: Joel R. Smith, Elizabeth Oates
Journal: Clinical Nuclear Medicine (2004)

Optimal thyroid scintigraphy requires an understanding of 1) the embryology, anatomy, and physiology of the thyroid gland; and 2) the properties of the 2 common imaging agents, technetium-99m pertechnetate (Tc-99m) and radioiodine (I-123). The normal gland has a characteristic scintigraphic pattern with these tracers and its uptake can be quantified with I-123. Thyroid diseases often produce characteristic abnormal patterns. These abnormal patterns could be described as diffuse or focal, homogeneous or heterogeneous, increased or decreased. “Extrathyroidal” localization can be seen with esophageal activity, ectopic tissue, thyroglossal duct cyst, and substernal goiter. Thyroid scintigraphy of neonates, as a follow up to abnormal blood screening, demonstrates typical etiologic patterns. The first step in evaluating a patient with suspected thyroid disease is correlating the normal or abnormal scintigraphic pattern with available biochemical data, clinical history, and physical examination. By integrating the interpretive and technical “pearls” and “pitfalls” outlined in this article, the radiologist can be more confident in establishing a proper diagnosis.
Abnormal granulocyte morphology in patients with psoriasis
Authors: JULIE B. SEDGWICK, E.R. HURD, P.R. BERGSTRESSER
Journal: British Journal of Dermatology (1982)

Journal Article Abnormal granulocyte morphology in patients with psoriasis Get access JULIE B. SEDGWICK, JULIE B. SEDGWICK The Immunology Graduate Studies Programme and The Department of Internal Medicine, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75235, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar E.R. HURD, E.R. HURD The Immunology Graduate Studies Programme and The Department of Internal Medicine, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75235, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar P.R. BERGSTRESSER P.R. BERGSTRESSER The Immunology Graduate Studies Programme and The Department of Internal Medicine, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75235, U.S.A. Paul R. Bergstresser, M.D., Dermatology Division, 5323 Harry Hines Blvd, Dallas, Texas 75235, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue 2, 1 August 1982, Pages 165–172, https://doi.org/10.1111/j.1365-2133.1982.tb00334.x Published: 01 August 1982 Article history Accepted: 20 October 1981 Published: 01 August 1982
DURATION OF IMMUNITY FOLLOWING SMALL-POX VACCINATION
Authors: A. W. LESCOHIER
Journal: JAMA (1913)

A certain degree of reticence is felt about recording observations on the subject on which so much work has been done and with which I have had a relatively short experience. The collection of the present data, however, was prompted first, by the observation made in a larger series of cases that successful revaccination after relatively short intervals is met with surprising frequency, and, second, the variance of my results with the ideas commonly held by physicians with whom I have come in contact. In dealing with patients reporting for compulsory vaccination, and who have a certain degree of antipathy to being inoculated, not infrequently objections are offered based on statements alleged to have been made by physicians by whom they have been previously vaccinated. If the patient has an unusually sore arm not only he, but sometimes his physician as well, is inclined to believe that a permanent protection
Human migration inhibitory factor: purification and immunochemical characterization.
Authors: L H Block, H Jaksche, S Bamberger, G Ruhenstroth-Bauer
Journal: The Journal of Experimental Medicine (1978)

Using gel filtration and preparative isotachophoresis, the migration inhibitory factor (MIF) was highly purified from human lymphocytes activated with concanavalin A. MIF is an acidic protein with a mol wt of approximately equal to 25,000 daltons as determined by gel filtration and analytical polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The protein inhibits migration of macrophages in the capillary test and in addition, has a slowing effect on the electrophoretic mobility of guinea pig peritoneal macrophages. Rabbit antibodies specific for this protein, as determined by immunochemical techniques, neutralized the biological effect of MIF on migration and on the electrophoretic mobility of macrophages.
Targeting Protein Translation in Human Non–Small Cell Lung Cancer via Combined MEK and Mammalian Target of Rapamycin Suppression
Authors: Marie-Emmanuelle Legrier, Chia-Ping Huang Yang, Han-Guang Yan, Lluis Lopez-Barcons, Steven M. Keller, Roman Pérez-Soler, Susan Band Horwitz, Hayley M. McDaid
Journal: Cancer Research (2007)

Abstract Lung cancer is a genetically heterogeneous disease characterized by the acquisition of somatic mutations in numerous protein kinases, including components of the rat sarcoma viral oncogene homolog (RAS) and AKT signaling cascades. These pathways intersect at various points, rendering this network highly redundant and suggesting that combined mitogen-activated protein/extracellular signal-regulated kinase (MEK) and mammalian target of rapamycin (mTOR) inhibition may be a promising drug combination that can overcome its intrinsic plasticity. The MEK inhibitors, CI-1040 or PD0325901, in combination with the mTOR inhibitor, rapamycin, or its analogue AP23573, exhibited dose-dependent synergism in human lung cancer cell lines that was associated with suppression of proliferation rather than enhancement of cell death. Concurrent suppression of MEK and mTOR inhibited ribosomal biogenesis by 40% within 24 h and was associated with a decreased polysome/monosome ratio that is indicative of reduced protein translation efficiency. Furthermore, the combination of PD0325901 and rapamycin was significantly superior to either drug alone or PD0325901 at the maximum tolerated dose in nude mice bearing human lung tumor xenografts or heterotransplants. Except for a PTEN mutant, all tumor models had sustained tumor regressions and minimal toxicity. These data (a) provide evidence that both pathways converge on factors that regulate translation initiation and (b) support therapeutic strategies in lung cancer that simultaneously suppress the RAS and AKT signaling network. [Cancer Res 2007;67(23):11300–8]
Heterogeneity of human factor V deficiency. Evidence for the existence of antigen-positive variants
Authors: Hui Chong Chiu, Eugene Whitaker, Robert W. Colman
Journal: Journal of Clinical Investigation (1983)

Functional human Factor V has been purified using a rapid immunoaffinity method. Following barium citrate adsorption of plasma, Factor V was precipitated with polyethylene glycol at a concentration between 5 and 14%. The resulting preparation was applied to a column containing an immobilized immunoadsorbent consisting of an IgG fraction containing a naturally occurring human monoclonal (IgG4λ) antibody with inhibitory activity against human Factor V. The solid phase immunoglobulin quantitatively bound Factor V from human plasma. The bound Factor V was effectively eluted with a Tris buffer pH 7.2 containing 1.2 M NaCl and 1 M α-methyl-D-mannoside. The isolated native Factor V with high specific activity (92 U/mg) showed a single band (Mr, 350,000) on both reduced and nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Factor V was purified 5,100-fold over plasma with an overall yield of 77%. The purified Factor V when subjected to thrombin activation exhibited an 18-fold increase in coagulant activity.
Human leucocyte antigen typing in orofacial granulomatosis
Authors: J. Gibson, D. Wray
Journal: British Journal of Dermatology (2000)

Sir, Wiesenfeld et al. introduced the term orofacial granulomatosis (OFG) in 1985 to describe a constellation of oral and facial signs resembling those of Crohn’s disease (CD) clinically and histologically in patients who do not appear to have abnormalities at any other site in the gastrointestinal tract.1 Patients with OFG may be referred to a dermatologist for management, as the condition can present as persistent facial swelling which may affect the lips, cheeks, eyelids and forehead.2 Intraoral abnormalities include mucosal tags, cobblestoning and a ‘full thickness’ gingivitis; oral ulceration tends to be recurrent and of the aphthous‐type although some may be deep and persistent.1 Worsaae et al. studied 16 patients with established OFG and found none with gastrointestinal CD.3 Scully et al. reviewed 19 patients with OFG and found seven (37%) to have gastrointestinal CD.4 There remains great disparity of opinion in the literature over whether or not OFG is a discrete clinical entity, a manifestation of CD, or a manifestation of a new variant of inflammatory bowel disease. Gibson et al. have suggested an allergic basis for OFG.5 This study aimed to determine whether or not patients with OFG had human leucocyte antigen (HLA) types in common, or distinct from, those of CD, as determined in the current literature.
SETBP1 mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia: independent prognostic impact in CMML
Authors: R R Laborde, M M Patnaik, T L Lasho, C M Finke, C A Hanson, R A Knudson, R P Ketterling, A Pardanani, A Tefferi
Journal: Leukemia (2013)

SETBP1  mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia: independent prognostic impact in CMML
Germline variation in complement genes and event‐free survival in follicular and diffuse large B‐cell lymphoma
Authors: Bridget Charbonneau, Matthew J. Maurer, Zachary S. Fredericksen, Clive S. Zent, Brian K. Link, Anne J. Novak, Stephen M. Ansell, George J. Weiner, Alice H. Wang, Thomas E. Witzig, Ahmet Dogan, Susan L. Slager, Thomas M. Habermann, James R. Cerhan
Journal: American Journal of Hematology (2012)

Abstract The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event‐free survival (EFS) in follicular lymphoma (FL) and diffuse large B‐cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL ( N = 107) and DLBCL ( N = 82) patients enrolled at the Mayo Clinic from 2002 to 2005. Cox regression was used to estimate hazard ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene‐level analyses, we used a principal components based gene‐level test. In gene‐level analyses for FL EFS, CFH ( P = 0.009), CD55 ( P = 0.006), CFHR5 ( P = 0.01), C9 ( P = 0.02), CFHR1 ( P = 0.03), and CD46 ( P = 0.03) were significant at P &lt; 0.05, and these genes remained noteworthy after accounting for multiple testing ( q &lt; 0.15). SNPs in CFH , CFHR1 , and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU ( P = 0.001) and C7 ( P = 0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing ( q &gt;0.15). Genes from the regulators of complement activation ( CFH , CD55 , CFHR1 , CFHR5 , CD46 ) at 1q32–q32.1, along with C9 , were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Health Impacts of the Built Environment: Within-Urban Variability in Physical Inactivity, Air Pollution, and Ischemic Heart Disease Mortality
Authors: Steve Hankey, Julian D. Marshall, Michael Brauer
Journal: Environmental Health Perspectives (2011)

Physical inactivity and exposure to air pollution are important risk factors for death and disease globally. The built environment may influence exposures to these risk factors in different ways and thus differentially affect the health of urban populations.
Eradication of chronic <i>Helicobacter pylori</i> infection by therapeutic vaccination
Authors: J E CRABTREE
Journal: Gut (1998)

Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile exterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.