tbuckley/cabot-search huggingface dataset:
Different MHC class I alleles compete for presentation of overlapping viral epitopes
Authors: Lynda G. Tussey, Sarah Rowland-Jones, Timothy S. Zheng, Matthew J. Androlewicz, Peter Cresswell, Jeffrey A. Frelinger, Andrew J. McMichael
Journal: Immunity (1995)

We previously identified an HLA-B8+ donor, NW, whose lymphoblastoid cells failed to present a B8-restricted epitope from the influenza A nucleoprotein following viral infection, although added peptide could still be presented. The failure to present through HLA-B8 following viral infection appears to be specific for the NP epitope. Here, we report that donor NW makes an HLA-B2702-restricted influenza-specific CTL response to an epitope in the nucleoprotein that overlaps the B8-restricted epitope by 8 aa. Two mechanisms for the failure of this cell line to present the B8-restricted epitope following viral infection are investigated. One is that there is an antigen processing polymorphism specific to the NW cell line, so that there is either preferential generation or preferential transport of the B2702 epitope. The other is that B8 and B2702 compete for a common peptide fragment in the ER and this leads to suboptimal loading of HLA-B8.
The Eosinophil and Eosinophilia
Authors: Sheldon G. Cohen
Journal: New England Journal of Medicine (1974)

It is some 96 years since Paul Ehrlich's pioneering cytohistologic studies defined the leukocyte whose granules could be distinguished by a characteristic taking up of stains of acid quality. One such stain, eosin, has subsequently served as a standard but not unique hematologic reagent for identification. However, it is only during recent years through the almost explosive ascendency of biochemical and immunologic research that the sophisticated investigative tools for a meaningful understanding of eosinophil-related mechanisms have become available. Two articles appearing in this issue of the Journal offer examples and evidence of the progression, effectiveness and productivity of ongoing investigations. . . .
The Effect of Estrogen Use on Levels of Glucose and Insulin and the Risk of Type 2 Diabetes in American Indian Postmenopausal Women
Authors: Ying Zhang, Barbara V. Howard, Linda D. Cowan, Jeunliang Yeh, Carl F. Schaefer, Robert A. Wild, Wenyu Wang, Elisa T. Lee
Journal: Diabetes Care (2002)

OBJECTIVE—To examine the associations between estrogen use and levels of insulin and glucose as well as the effect of estrogen use on the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS—This report is based on 857 women who were both nondiabetic and postmenopausal at the baseline examination (1989–1992) and who completed a second examination (1993–1995) an average of 4 years later. The participants were divided into three groups: never, past, and current users based on their baseline estrogen use status. ANCOVA was used to compare the insulin and glucose levels among estrogen use groups. Logistic regression was used to evaluate the association between estrogen use and the incidence of type 2 diabetes. RESULTS—Postmenopausal estrogen use was associated with lower fasting glucose (0.2 mmol/l lower) but higher 2-h glucose levels (0.4 mmol/l higher) compared with never users. It was not significantly associated with the risk of type 2 diabetes compared with past and never users, based on American Diabetes Association or World Health Organization definitions of diabetes or on only a 2-h glucose level ≥11.1 mmol/l. However, the risk of type 2 diabetes increased with increasing duration of estrogen use among current users, with an odds ratio of 1.10 per year of use (95% CI: 1.01–1.19). CONCLUSIONS—The data suggest that estrogen use in American Indian postmenopausal women may relate to deterioration of glucose tolerance. Longer duration of estrogen use among current users may relate to an increased risk of type 2 diabetes.
STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS
Authors: Oswald T. Avery, James M. Neill
Journal: The Journal of Experimental Medicine (1924)

In the present work on oxidation and reduction by sterile extracts of pneumococcus, the preparations employed contain among other constituents, a hemolytic substance the properties of which have been described by Cole (1, 2) in his studies on pneumococcus hemotoxin. Pneumococcus extracts prepared by the methods described are actively hemolytic, 0.005 cc. of extract causing complete lysis of 2.5 cc. of a 1 per cent suspension of red cells from rabbit blood. This hemolytic property of pneumococcus extracts is destroyed by 10 minutes exposure to 55 degrees C. When pneumotoxin-containing extracts are protected from the action of molecular oxygen, their hemolytic activity remains unimpaired for considerable periods of time. In the presence of air, on the other hand, the stability of the hemolytic substance depends upon whether the particular type of extract contains a "complete" or "incomplete" oxidation-reduction system. Sterile broth extracts of unwashed pneumococci are reactive with molecular oxygen, and as a result of this union peroxide is formed whenever these extracts are exposed to air. The hemolytic activity of "complete" extracts of this type is rapidly decreased and finally destroyed in the presence of molecular oxygen. On the other hand, the "incomplete" type of extract prepared by saline extraction of washed pneumococci may be exposed to air with little or no loss of hemolytic power. This "incomplete" washed cell extract, unless reactivated, does not undergo autoxidation in the presence of air; under these circumstances peroxide is not formed and the hemolytic activity of this type of extract is not impaired by exposure to air. The stability of the hemolytic agent in the "incomplete" type of extract is evidence that this substance is itself not reactive with or affected by molecular oxygen, even in the presence of the cell enzymes. The destruction of the same hemolytic substance in extracts capable of undergoing autoxidation may be ascribed to the action of some peroxide formed by the union of molecular oxygen with easily oxidized or autoxidizable substances of the extract. It is now known that a peroxide, having the reactions of hydrogen peroxide, accumulates in sterile pneumococcus extracts during oxidation. It has been shown in the present study that the addition of preformed hydrogen peroxide destroys the hemolytic activity of pneumococcus extracts, although higher concentrations were required than were detected in oxidized extracts themselves. These facts and the known action of superoxides in analogous types of reaction make it seem not unlikely that the active agent in the destruction of pneumotoxin in oxidized cell extracts may be a peroxide; either hydrogen peroxide or some higher organic peroxide formed during autoxidation of the extract.
NCAA has not been given sufficient tools to identify poorly performing doctors
Authors: C. Bulstrode
Journal: BMJ (2001)

EDITOR—The government has announced a new organisation, the National Clinical Assessment Authority (NCAA), which is apparently charged with identifying poorly performing doctors. It is, however, in danger of failing to do its task because it has not been given the tools it needs to achieve this.1 There are three types of regular review needed by any professionals who are entrusted with the safety of patients.

The first meeting is for individual professionals. They may want a regular …
Factors associated with recurrence after transplantation for hepatocellular carcinoma
Authors: C. Duvoux, T. Decaens, F. Roudot-Thoraval, S. Hadni-Bresson, P. Wolf, J. Gugenheim, F. Durand, M. Neau-Cransac, O. Boillot, K. Dharancy, O. Chazoullieres, D. Dhumeaux, D. Cherqui
Journal: Journal of Hepatology (2003)
ANTI-RETROVIRAL EFFECTS OF INTERFERON-α IN AIDS-ASSOCIATED KAPOSI'S SARCOMA
Authors: H Clifford Lane, Judith Feinberg, Victoria Davey, Lawrence Deyton, Michael Baseler, Jody Manischewitz, Henry Masur, JosephA Kovacs, Betsey Herpin, Robert Walker, JuliaA Metcalf, Norman Salzman, Gerald Quinnan, AnthonyS Fauci
Journal: The Lancet (1988)
Cytotoxicity of Receptor-Mediated 16 [125I]Iodo-estradiol in Cultured MCF-7 Human Breast Cancer Cells
Authors: W. H. McLaughlin, R. A. Milius, K. M. R. Pillai, J. P. Edasery, R. D. Blumenthal, W. D. Bloomer
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Cytotoxicity of Receptor-Mediated 16α[125I]Iodo-estradiol in Cultured MCF-7 Human Breast Cancer Cells Get access W. H. McLaughlin, W. H. McLaughlin Department of Radiation Oncology, University of Pittsburgh School of Medicine, Joint Radiation Oncology Center and Pittsburgh Cancer InstitutePittsburgh, PA. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. A. Milius, R. A. Milius Department of Radiation Oncology, Mount Sinai School of MedicineNew York, NY. Search for other works by this author on: Oxford Academic PubMed Google Scholar K. M. R. Pillai, K. M. R. Pillai Department of Radiation Oncology, Mount Sinai School of MedicineNew York, NY. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. P. Edasery, J. P. Edasery Department of Radiation Oncology, Mount Sinai School of MedicineNew York, NY. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. D. Blumenthal, R. D. Blumenthal Department of Radiation Oncology, Mount Sinai School of MedicineNew York, NY. Search for other works by this author on: Oxford Academic PubMed Google Scholar W. D. Bloomer W. D. Bloomer * Department of Radiation Oncology, University of Pittsburgh School of Medicine, Joint Radiation Oncology Center and Pittsburgh Cancer InstitutePittsburgh, PA. *Correspondence to: William D. Bloomer, M.D., Department of Radiation Oncology, Joint Radiation Oncology Center, 230 Lothrop St., Pittsburgh, PA 15213. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 6, 15 March 1989, Pages 437–440, https://doi.org/10.1093/jnci/81.6.437 Published: 15 March 1989 Article history Received: 08 August 1988 Revision received: 19 December 1988 Accepted: 27 December 1988 Published: 15 March 1989
Renal Excretion of Contrast Medium after Endoscopic Retrograde Investigations
Authors: A. Weizel, U. Gelhaus-Klamant
Journal: Endoscopy (1978)

Endoscopic retrograde investigations are often performed as diagnostic procedures. The investigation of urine after such procedures in 21 patients has shown that appreciable amounts of contrast medium can be excreted renally. No such excretion could be shown when the contrast medium was injected into the gut lumen. The fact that contrast medium can be absorbed into the liver the pancreas during endoscopic retrograde procedures should influence the decision to perform these studies in patients with known allergies.
Clinical guidelines and the law
Authors: B. Hurwitz
Journal: BMJ (1995)

Fifty years ago the regius professor of physic at the University of Cambridge wrote in praise of medicine that its satisfaction lay “in the personal and individual character of its practice: the latitude with which a qualified doctor may exercise his own judgment, express his own opinions and practise his own art.”1 In the same year (1946) the BMA, sensing a threat to this latitude from proposals to establish a national health service, declared that “the medical profession should remain free to exercise the art and science of medicine according to its traditions, standards and knowledge … without interference.”2

Yet clinical practice is now governed by a vast array of regulations in the form of protocols, practice policies, clinical guidelines, and codes of practice. Their current ascendancy is not simply due to state intervention. It reflects a change in the balance of power within the framework adopted for the delivery of health care. Professional stewardship of clinical standards, health services, and the deployment …
Autophagy, p53, and Pancreatic Cancer
Authors: Christine A. Iacobuzio-Donahue, Joseph M. Herman
Journal: New England Journal of Medicine (2014)

Trials to test hydroxychloroquine, an inhibitor of autophagy, for pancreatic cancer are in progress. A recent study suggests that, in some circumstances, hydroxychloroquine may hasten the progression to invasive pancreatic ductal adenocarcinoma.
Genetic variation within the TRPM5 locus associates with prediabetic phenotypes in subjects at increased risk for type 2 diabetes
Authors: Caroline Ketterer, Karsten Müssig, Martin Heni, Katarzyna Dudziak, Elko Randrianarisoa, Robert Wagner, Fausto Machicao, Norbert Stefan, Jens J. Holst, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger
Journal: Metabolism (2011)
Clinical examination for non-cephalic presentation: External cephalic version should be a maternity service quality indicator
Authors: Stephanie Kuku, Susan Bewley
Journal: BMJ (2006)

EDITOR—The recent study by Nassar et al highlights the long known clinical failure to diagnose all breech presentations at term, especially in obese women.1 However, there is little point in improving clinical detection unless it makes a difference to mothers or babies. The point of detecting a breech is to offer external cephalic version and to discuss …
Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-β induces expression of matrix metalloproteinases 3 and 10 independently of nuclear factor-κB
Authors: K Warstat, T Pap, G Klein, S Gay, W K Aicher
Journal: Annals of the Rheumatic Diseases (2007)

We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-β induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription–polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-β induced significant increases in MMP-3 mRNA (12.35-fold, p&lt;0.001) and protein (mean 62 ng/ml, sixfold, p&lt;0.008) and in expression of MMP-10 mRNA (11.68-fold, p&lt;0.05) and protein (54 ng/ml, 20-fold, p⩾0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor-β response. No phosphorylation of nuclear factor-κB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-β suffices to induce significant expression of MMP-3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-κB phosphorylation.
Extracellular Calcium as a Candidate Mediator of Prostate Cancer Skeletal Metastasis
Authors: Jinhui Liao, Abraham Schneider, Nabanita S. Datta, Laurie K. McCauley
Journal: Cancer Research (2006)

Prostate cancer almost exclusively metastasizes to skeletal sites, indicating that the bone provides a favorable microenvironment for its localization and progression. A natural yet understudied factor in bone that could facilitate tumor localization is elevated extracellular calcium ([Ca2+]o). The present study found that elevated [Ca2+]o (2.5 mmol/L) enhanced proliferation of skeletal metastatic prostate cell lines (PC-3 and C4-2B), but not the nonskeletal metastatic, epithelial-derived prostate cell line LNCaP. The proliferative effect of elevated [Ca2+]o was associated with higher expression of the calcium-sensing receptor (CaSR), a heterotrimeric G-protein-coupled receptor that is the predominant cell-surface sensor for [Ca2+]o. Knockdown of the CaSR via RNA interference reduced cell proliferation in vitro and metastatic progression in vivo. CaSR signaling in PC-3 cells was evaluated by measuring the elevated [Ca2+]o-dependent inhibition of cyclic AMP accumulation, induced by either prostaglandin E2 or forskolin. Elevated [Ca2+]o stabilized expression of cyclin D1, a protein required for cell cycle transition. Furthermore, elevated [Ca2+]o triggered activation of the Akt signaling pathway and enhanced PC-3 cell attachment. Both pertussis toxin (a G-protein inhibitor) and LY294002 (an inhibitor of Akt signaling) reduced cell attachment. These data suggest that elevated [Ca2+]o following increased bone remodeling could facilitate metastatic localization of prostate cancer via the CaSR and the Akt signaling pathway. Taken together, [Ca2+]o is a candidate mediator of prostate cancer bone metastasis.
Alteration in Diaphragmatic Function Induced by Acute Necrotizing Pancreatitis in a Rodent Model
Authors: YVES MATUSZCZAK, NAIMA VIIRES, HALA ALLAMEDIN, MICHEL AUBIER, JEAN-MARIE DESMONTS, BERTRAND DUREUIL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Some of the common complications of acute necrotizing pancreatitis also involve pulmonary complications. These manifestations are often associated with a cephalad diaphragmatic shift. We hypothized that diaphragmatic function might be directly compromised by the acute abdominal process. This hypothesis was tested on an acute necrotizing pancreatitis (ANP) rat model. We assessed the diaphragm and peripheral (Extensor Digitorum Longus and Soleus) muscle properties in vitro using strips in control (C) and ANP animals. Contractile parameters included single twitch and a force–frequency curve (10 to 100 Hz), and an endurance capacity index (T50%) was calculated after a repetitive stimulation (30 Hz). Breathing pattern was not different between control and ANP animals, and muscular histologic examination was normal. However, ANP was associated with a marked decrease in diaphragmatic strength for all frequencies of stimulation when compared with C. Endurance capacity was also reduced in ANP animals as assessed by a lower T50% (ANP: 31 ± 10.5 s; C: 49 ± 10.3 s; p < 0.05). By contrast, no significant change in peripheral muscle function was observed in both groups. We conclude that ANP causes impairment in diaphragmatic strength and endurance capacity, whereas peripheral muscles are spared. These findings suggest that alterations in the respiratory pump may be involved in the genesis of acute respiratory failure in ANP. Matuszczak Y, Viires N, Allamedin H, Aubier M, Desmonts J-M, Dureuil B. Alteration in diaphragmatic function induced by acute necrotizing pancreatitis in a rodent model.
Furuncular myiasis: alternatives to Bacon therapy
Authors: R. J. Biggar
Journal: JAMA (1994)

To the Editor.  —As a clinician with considerable personal experience with tumbu fly myiasis while living in Africa during the 1970s, I read with interest the article by Brewer et al.1The mild lesions reported in that article were nowhere near as extensive as can occur with myiasis. In a description of my experiences with myiasis in Ghana,2I reported a Canadian child with literally dozens of developing furuncles who was also febrile and irritable. I initially mistook the condition as early chickenpox. The child had been wrapped in a still-damp blanket that had been hung outside to dry.  My family members and I have all had this condition on several occasions. I can attest to the fact that this condition is characterized by itching more than the pain described in the article (although lesions are susceptible to irritation from scratching or attempts to express the contents). Typically,
Disparities in liver transplantation in the post-model for end-stage liver disease era: Are we there yet?
Authors: Parul Dureja, Michael R. Lucey
Journal: Hepatology (2009)

In February 2002, the allocation system for liver transplantation became based on the Model for End-Stage Liver Disease (MELD) score. Before MELD, black patients were more likely to die or become too sick to undergo liver transplantation compared with white patients. Little information exists regarding sex and access to liver transplantation. OBJECTIVE: To determine the association between race, sex, and liver transplantation following introduction of the MELD system. DESIGN, SETTING, AND PATIENTS: A retrospective cohort of black and white patients (> or = 18 years) registered on the United Network for Organ Sharing liver transplantation waiting list between January 1, 1996, and December 31, 2000 (pre-MELD cohort, n = 21 895) and between February 28, 2002, and March 31, 2006 (post-MELD cohort, n = 23 793). MAIN OUTCOME MEASURES: Association between race, sex, and receipt of a liver transplant. Separate multivariable analyses evaluated cohorts within each period to identify predictors of time to death and the odds of dying or receiving liver transplantation within 3 years of listing. Patients with hepatocellular carcinoma were analyzed separately. RESULTS: Black patients were younger (mean [SD], 49.2 [10.7] vs 52.4 [9.2] years; P < .001) and sicker (MELD score at listing: median [interquartile range], 16 [12-22] vs 14 [11-19]; P < .001) than white patients on the waiting list for both periods. In the pre-MELD cohort, black patients were more likely to die or become too sick for liver transplantation than white patients (27.0% vs 21.7%) within 3 years of registering on the waiting list (odds ratio [OR], 1.51; 95% confidence interval (CI), 1.15-1.98; P = .003). In the post-MELD cohort, black race was no longer associated with increased likelihood of death or becoming too sick for liver transplantation (26.5% vs 22.0%, respectively; OR, 0.96; 95% CI, 0.74-1.26; P = .76). Black patients were also less likely to receive a liver transplant than white patients within 3 years of registering on the waiting list pre-MELD (61.6% vs 66.9%; OR, 0.75; 95% CI, 0.59-0.97; P = .03), whereas post-MELD, race was no longer significantly associated with receipt of a liver transplant (47.5% vs 45.5%, respectively; OR, 1.04; 95% CI, 0.84-1.28; P = .75). Women were more likely than men to die or become too sick for liver transplantation post-MELD (23.7% vs 21.4%; OR, 1.30; 95% CI, 1.08-1.47; P = .003) vs pre-MELD (22.4% vs 21.9%; OR, 1.08; 95% CI, 0.91-1.26; P = .37). Similarly, women were less likely than men to receive a liver transplant within 3 years both pre-MELD (64.8% vs 67.6%; OR, 0.80; 95% CI, 0.70-0.92; P = .002) and post-MELD (39.9% vs 48.7%; OR, 0.70; 95% CI, 0.62-0.79; P < .001). CONCLUSION: Following introduction of the MELD score to the liver transplantation allocation system, race was no longer associated with receipt of a liver transplant or death on the waiting list, but disparities based on sex remain.