tbuckley/cabot-search huggingface dataset:
12/15-lipoxygenase–mediated enzymatic lipid oxidation regulates DC maturation and function
Authors: Tobias Rothe, Florian Gruber, Stefan Uderhardt, Natacha Ipseiz, Susanne Rössner, Olga Oskolkova, Stephan Blüml, Norbert Leitinger, Wolfgang Bicker, Valery N. Bochkov, Masayuki Yamamoto, Alexander Steinkasserer, Georg Schett, Elisabeth Zinser, Gerhard Krönke
Journal: Journal of Clinical Investigation (2015)

DCs are able to undergo rapid maturation, which subsequently allows them to initiate and orchestrate T cell-driven immune responses. DC maturation must be tightly controlled in order to avoid random T cell activation and development of autoimmunity. Here, we determined that 12/15-lipoxygenase-meditated (12/15-LO-mediated) enzymatic lipid oxidation regulates DC activation and fine-tunes consecutive T cell responses. Specifically, 12/15-LO activity determined the DC activation threshold via generation of phospholipid oxidation products that induced an antioxidative response dependent on the transcription factor NRF2. Deletion of the 12/15-LO-encoding gene or pharmacologic inhibition of 12/15-LO in murine or human DCs accelerated maturation and shifted the cytokine profile, thereby favoring the differentiation of Th17 cells. Exposure of 12/15-LO-deficient DCs to 12/15-LO-derived oxidized phospholipids attenuated both DC activation and the development of Th17 cells. Analysis of lymphatic tissues from 12/15-LO-deficient mice confirmed enhanced maturation of DCs as well as an increased differentiation of Th17 cells. Moreover, experimental autoimmune encephalomyelitis in mice lacking 12/15-LO resulted in an exacerbated Th17-driven autoimmune disease. Together, our data reveal that 12/15-LO controls maturation of DCs and implicate enzymatic lipid oxidation in shaping the adaptive immune response.
EVOLVING BIOMARKERS IMPROVE PREDICTION OF LONG-TERM MORTALITY IN PATIENTS WITH STABLE CAD: THE BIO-VILCAD SCORE
Authors: Georg Goliasch, Marcus Kleber, Tanja B. Grammer, Stefan Pilz, Andreas Tomaschitz, Günther Silbernagel, Gerald Maurer, Winfried März, Niessner Alexander
Journal: Journal of the American College of Cardiology (2014)
Cost effectiveness of primary stroke prevention in atrial fibrillation: Swedish national perspective.
Authors: C. Gustafsson, K. Asplund, M. Britton, B. Norrving, B. Olsson, L. A. Marke
Journal: BMJ (1992)

OBJECTIVE--To assess the potential effects of primary prevention with anticoagulants or aspirin in atrial fibrillation on Swedish population. DESIGN--Analysis of cost effectiveness based on the following assumptions: about 83,000 people have atrial fibrillation in Sweden, of whom 22,000 would be potential candidates for treatment with anticoagulants and 55,000 for aspirin treatment; the annual 5% stroke rate is reduced by 64% (with anticoagulants) and 25% (with aspirin); incidence of intracranial haemorrhage of 0.3%, 1.3%, or 2.0% per year; direct and indirect costs of a stroke of Kr180,000 and Kr90,000; estimated annual cost of treatment is Kr5030 for anticoagulants and Kr100 for aspirin. SETTING--Total Swedish population. MAIN OUTCOME MEASURES--Direct and indirect costs of stroke saved, number of strokes prevented, and cost of preventive treatment. RESULTS--Depending on the rate of haemorrhagic complications 34 to 83 patients would need to be treated annually with anticoagulants to prevent one stroke; 83 patients would need to be treated with aspirin. Giving anticoagulant treatment only would reduce costs by Kr60 million if the incidence of intracranial haemorrhage were 0.3% but would imply a net expense if the complication rate exceeded 1.3%. The total savings from giving anticoagulant (22,000 patients) and aspirin (55,000 patients) treatment would be Kr175 million per year corresponding to 2 million pounds per million inhabitants each year. CONCLUSIONS--Treatment with anticoagulants and, if contraindications exist, with aspirin is cost effective provided that the risk of serious haemorrhage complications due to anticoagulants is kept low.
Lipid storage myopathy: successful treatment with propranolol.
Authors: C Martyn, E H Jellinek, J N Webb
Journal: BMJ (1981)

Lipid storage myopathies are a rare but serious cause of muscle weakness characterised by the accumulation of abnormal amounts of neutral fat in type 1 fibres. A case is reported in which the patient presented with weakness of the proximal limb muscles and greatly increased activities of creatine kinase and lactate dehydrogenase. After two years lipid myopathy was diagnosed when electron microscopy confirmed the presence of large numbers of lipid particles within muscle fibres. Twelve years after the initial presentation propranolol (40 mg thrice daily) was started. Strength gradually improved and enzyme activities returned to normal. The improvement in the patient9s condition was almost certainly due to the propranolol, although the mode of action of the drug remains unknown.
All systems can be hacked
Authors: E. J. McClenaghan
Journal: BMJ (2012)

My experience with patients accessing and modifying notes has not been encouraging. 1 During my elective in sub-Saharan Africa patients had access to their notes and could modify them if they had a similar pen to do so.This allowed them to modify the more culturally unacceptable, yet clinically essential, diagnoses such as HIV.I am sure that any new system will guard against this happening, but it should be remembered that these days there is no system that cannot be hacked.
Evidence that the V kappa III gene usage is nonstochastic in both adult and newborn peripheral B cells and that peripheral CD5+ adult B cells are oligoclonal.
Authors: J C Weber, G Blaison, T Martin, A M Knapp, J L Pasquali
Journal: Journal of Clinical Investigation (1994)

There is evidence that in certain situations the expressed antibody repertoire is dominated by small subsets of V gene segments. They include fetal, CD5+, and autoantibody-forming B cells as well as low grade B cell malignancies. For instance, inside the V kappa III family of approximately 10 members, only 3 (humkv325, 328, and Vg) are used recurrently for autoantibody production. However, the significance of this recurrence is difficult to interpret without a clear vision of the actual repertoire in normal subjects. To address this, we have sequenced and compared two sets of rearranged V kappa III genes generated by cDNA PCR amplification from a normal newborn, a normal adult, and from CD5+ B cells of the same adult donor. The results show that: (a) only four V kappa III gene segments are used by neonatal and total adult B cells (humkv325, humkv328, Vg, and kv305), humkv325 being overexpressed in both repertoires; (b) there is no significant difference in terms of V kappa III gene usage between the adult and newborn repertoires; (c) regarding the junction regions, there is a favored use of the most 5' JK gene segments (Jk1-Jk2); approximately 20% of the newborn and adult junction sequences was characterized by one or two additional codons, most probably resulting from a nontemplate addition of nucleotides; (d) adult clones, in contrast to most newborn clones, show sequence divergences from prototype sequences with patterns which suggest antigen-driven diversity; (e) regarding the adult CD5+ B cell library, it is most probable that the 78 clones analyzed derived from no more than nine different VK-JK rearrangements. Humkv325 is used by at least six of them, and most of the expressed V genes were in exact or very near germline configuration. Collectively these results suggest that the expressed antibody V kappa III repertoire in the adult represents only a fraction of the potential genetic information and that it resembles the preimmune repertoire of the neonate. The data, which also suggest that the adult peripheral blood CD5+ B cell population may be dominated by a small number of B cell clones, are discussed with regards to the V kappa III usage in pathological situations.
Diversity and Stability Study on Rice Mutants Induced in Space Environment
Authors: Wei-Hong Lu, Xin-Zhu Wang, Qi Zheng, Shuang-Hong Guan, Ping Xin, Ye-Qing Sun
Journal: Genomics Proteomics & Bioinformatics (2008)

Abstract To further study the characteristics of changes on the molecular level of rice mutants induced in space environment, we analyzed proteins in leaves and seeds of four rice mutants (two high-tillering and two low-tillering) in the 8th and 9th generations after a 15-day spaceflight, and compared with their ground controls by two-dimentional polyacrylamide gel electrophoresis and reverse phase liquid chromatography (RPLC). In addition, the albumin, globulin, prolamine, glutelin, and amylose of the mutant seeds were analyzed by RPLC and ultra-violet spectrometry. The results showed that the low-abundance proteins of leaves in the peak tillering stage are more likely to be induced compared with their corresponding controls. The albumin, globulin, and prolamine of the mutant seeds revealed changes when compared with their controls, and the characteristics of changes in different mutants were stably inherited in the 8th and 9th generations, suggesting that they can be used as biomarkers to identity the mutants induced by spaceflight. Moreover, two proteins (SSP9111 and SSP6302) were found to be expressed with high intensity (two-fold change) in different mutants, which were both correlated with photosystem according to mass spectrometry and database searching.
Making friends with RITA
Authors: J. Bache
Journal: BMJ (1999)

The Calman reforms are now established. Specialist registrars have been appointed, registrars are extinct, and senior registrars have virtually disappeared. One of the features of the reforms is the record of in-training assessment (RITA), a record of the annual review of specialist registrars' progress through their training programme. RITA could easily become a purely bureaucratic exercise, generating paperwork but fulfilling no useful purpose. Alternatively, it could be extremely beneficial for all parties.

Everyone: primarily the specialist registrars, but also those responsible for the training, both directly (supervising consultants) and indirectly (directors of training programmes, postgraduate deans, etc), and the health service and thus patients.

Specialist registrars want to establish basic facts, such as the expected date of their certificate of completion of specialist training. They want to review their training to date, particularly that of the previous year, and ensure that their future training will be of maximum benefit and will rectify any deficits in their knowledge and skills. They want to ensure that all their requirements can be satisfied before the date of their certificate of completion of specialist training. As this date approaches, they want to know that their career plans are realistic.

The trainers will also need to satisfy themselves that specialist registrars' requirements are met. They will wish to ensure that the specialist registrars have received valuable and relevant training to date and that this will continue. They need to know where good training is available and, equally important, which hospitals are failing to deliver. They need to establish reasons for failure, on the part of either the trainees or the trainers. It is clearly essential that the process is confidential, mutually honest, and non-threatening. Adequate preparation is mandatory. The number of people involved should be no greater than necessary, but it is essential that the …
Adverse Effect of Hydralazine in Patients With Primary Pulmonary Hypertension
Authors: Itzhak Kronzon
Journal: JAMA (1982)

Hydralazine hydrochloride has been recommended as a treatment for primary pulmonary hypertension. Two patients who were so treated experienced further elevation of the pulmonary artery pressure and clinical deterioration. The mechanism of this adverse effect was a decrease of systemic vascular resistance attended by an increase in cardiac output without a fall in the pulmonary vascular resistance. Hemodynamic monitoring is advised in patients undergoing vasodilator therapy for primary pulmonary hypertension. (<i>JAMA</i>1982;247:3112-3114)
THE TREATMENT OF NON-TUBERCULOUS CHRONIC ARTHRITIS.
Authors: EDWIN A. LOCKE
Journal: JAMA (1907)

The past few years have marked a greater advance in the success attending the treatment of chronic arthritis than of almost any other disease. This advance, we believe, is due largely to the many important studies made as to the etiology and pathology which have resulted in the differentiation of various types, thus rendering possible more rational therapeutic indications. In the brief time allotted us we are obliged to omit entirely any account of these investigations or discussion of their bearing on treatment, and shall confine ourselves to a general outline of the treatment which, in our hands, has proved most successful. The treatment of chronic arthritis consists essentially, first, in the employment of methods influencing general metabolism, and second, local treatment of the affected joints. The first are almost universally applicable to all cases, while the second varies somewhat with the particular type. For purposes of presentation, therefore, the
Alcohol as a Primary Risk Factor in Oral Squamous Carcinoma
Authors: A. Mashberg, L. Garfinkel, S. Harris
Journal: CA A Cancer Journal for Clinicians (1981)

This case-control study investigates the role of alcohol as a primary risk factor in the development of oral cancer.A total of 181 patients diagnosed as having squa mous carcinoma of the oral cavity were interviewed, and 497 controls.The rela tive risk for drinkers adjusted for smoking was 3.3, 15.2, and 10.6 for those who drank less than six, six to nine, and 10 or more whiskey equivalents (WEs) a day, respectively.The relative risk for smokers adjusted for drinking rose only from 3.2 10 4.5 to 5.0 for smokers of 10 to 19, 20to 39, and 40 or more cigarettes a day, respectively.Beer/wine drinkers had much higher relative risks than the whiskey drinkers.The adjusted relative risk for whiskey drinkers consuming 10 or more WEs a day was 7.3; the adjusted relative risk for beer/wine drinkers consuming 10
Costal Brown Tumor Detected by Dual-phase Parathyroid Imaging and SPECT-CT in Primary Hyperparathyroidism
Authors: Giorgio Treglia, Donatella Pia Dambra, Isabella Bruno, Antonino Mulè, Alessandro Giordano
Journal: Clinical Nuclear Medicine (2008)

A 58-year-old male with primary hyperparathyroidism underwent parathyroid scintigraphy to obtain presurgical localization of a suspected parathyroid adenoma. Increased Tc-99m sestamibi uptake was seen on dual-phase imaging in a focal area corresponding to the right inferior parathyroid. An incidental finding was the intense tracer uptake in the left thorax. Immediate SPECT-CT imaging located the uptake area in the third left rib; it was subsequently demonstrated to represent a brown tumor. Brown tumors, skeletal manifestations of hyperparathyroidism, have been incidentally detected by bone scintigraphy, more rarely by Tc-99m sestamibi parathyroid scintigraphy.
Effect of selective aldosterone deficiency on acidification in nephron segments of the rat inner medulla.
Authors: T D DuBose, C R Caflisch
Journal: Journal of Clinical Investigation (1988)

Mineralocorticoid plays a role in urinary acidification and acid-base balance, but the response of the inner medulla to aldosterone has not been elucidated. A model of selective aldosterone deficiency (SAD) with hyperkalemia and hyperchloremic metabolic acidosis was employed to assess segmental acidification by measuring in situ pH, titratable acidity (TA) and total ammonia (Am). Hydrogen ion secretion was also examined as a function of the increment in in situ PCO2 in the collecting duct during bicarbonate loading. SAD rats were compared to ADX controls that received adrenalectomy and chronic replacement of gluco- and mineralocorticoid and to rats with chronic metabolic acidosis induced by oral NH4Cl (CMA). Both fractional and absolute delivery of Am to the loop of Henle was lower in SAD vs. CMA rats (1.34 to 3.63 mM, P less than 0.01). Delivery of Am to the base and tip collecting duct (BCD and TCD) was also markedly lower in SAD (1.50 vs. 0.52 and 1.77 vs. 0.47 mM, respectively, P less than 0.01). Net addition of Am and net acid between BCD and TCD, observed in CMA rats, was not observed in SAD despite equivalent degrees of systemic metabolic acidosis. Similarly, the concentration gradient favoring transfer of NH3 between loop of Henle and CD was reduced in SAD. During bicarbonate loading the increment in PCO2 at BCD, TCD and in final urine was significantly lower in SAD rats than in adrenal intact bicarbonate-loaded rats. Therefore, the acidification defect in this model of SAD appears to be a result of a decrease in ammonia production and delivery to the loop of Henle, impaired transfer from loop to collecting duct and reduction in the rate of H+ secretion by the collecting duct.
Recognition of Profilin by Toll-like Receptor 12 Is Critical for Host Resistance to Toxoplasma gondii
Authors: A. Alicia Koblansky, Dragana Jankovic, Hyunju Oh, Sara Hieny, Waradon Sungnak, Ramkumar Mathur, Matthew S. Hayden, Shizuo Akira, Alan Sher, Sankar Ghosh
Journal: Immunity (2012)
IMPACT OF ELEVATED PCSK9 LEVELS ON REGULATION OF LDL-CHOLESTEROL AFTER STATIN TREATMENT: STUDY WITH DIFFERENT TYPES OF LIPID LOWERING DRUGS
Authors: Masa-aki Kawashiri, Atsushi Nohara, Tohru Noguchi, Hayato Tada, Akihiro Inazu, Junji Kobayashi, Hiroshi Mabuchi, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2011)
Pain due to lesions of central nervous system removed by sympathetic block.
Authors: L Loh, P W Nathan, G D Schott
Journal: BMJ (1981)

Eight patients were studied in whom a lesion within the central nervous system caused constant pain and hyperpathia. Blockade of the sympathetic supply to the periphery was carried out in each patient by stellate ganglion block or intravenous infusion of guanethidine 15 mg in 30 ml saline into a limb on the affected side. On almost every occasion the pain and hypersensitivity were reduced, sometimes completely. Thus chronic pain and hyperpathia arising from a lesion in the central nervous system may be abolished by blocking the sympathetic supply to the periphery; this effect may be achieved when not all the peripheral nerves of the affected region have had their sympathetic nerve supply blocked. Such blockade may be worth repeating in the hope of achieving lasting relief of the intractable pain.
Issues in reporting epidemiological studies: Can't we all agree on confidence intervals?
Authors: Matthew W Gillman
Journal: BMJ (2005)

Users' guide to detecting misleading claims in researchMisleading claims may be symptom of even more serious flaws Editor-Montori et al justifiably draw attention to misleading claims in published clinical trials. 1 This is a serious and common problem. 2 3 However, I object to their radical proposal that only the methods and results sections should be read, while the remainder of the paper should be ignored.The proposal is inconsistent with the title of their paper, "Users' guide to detecting misleading claims in clinical research reports." 1 How are these misleading claims to be identified if the sections containing them are omitted?Furthermore, anyone capable of critically appraising a trial solely on the basis of the methods and results is unlikely to be fooled by misleading claims in the discussion.But, more importantly, the proposal would deprive the discerning reader of witnessing the conflict between the results and the unwarranted conclusions.If researchers are willing to disseminate misleading claims then their integrity is brought into question.But if so, then all aspects of the trial-including the methods and results sections-are also brought into question.Misleading claims should be identified and broadcast loudly for they signal doubts about the entire study.Large scale randomised trials create the ideal conditions for data manipulation.Yet this is merely one of a multitude of problems stemming from a flawed method. 3 The remedy?When reading a study, ignore everything except the number of patients recruited.If this is large proceed no further as there is little prospect of encountering any data of genuine benefit to patients.
Intranasal Poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population
Authors: Lis R.V. Antonelli, Antonio Gigliotti Rothfuchs, Ricardo Gonçalves, Ester Roffê, Allen W. Cheever, Andre Bafica, Andres M. Salazar, Carl G. Feng, Alan Sher
Journal: Journal of Clinical Investigation (2010)

Type I IFN has been demonstrated to have major regulatory effects on the outcome of bacterial infections. To assess the effects of exogenously induced type I IFN on the outcome of Mycobacterium tuberculosis infection, we treated pathogen-exposed mice intranasally with polyinosinic-polycytidylic acid condensed with poly-l-lysine and carboxymethylcellulose (Poly-ICLC), an agent designed to stimulate prolonged, high-level production of type I IFN. Drug-treated, M. tuberculosis-infected WT mice, but not mice lacking IFN-alphabeta receptor 1 (IFNalphabetaR; also known as IFNAR1), displayed marked elevations in lung bacillary loads, accompanied by widespread pulmonary necrosis without detectable impairment of Th1 effector function. Importantly, lungs from Poly-ICLC-treated M. tuberculosis-infected mice exhibited a striking increase in CD11b+F4/80+Gr1int cells that displayed decreased MHC II expression and enhanced bacterial levels relative to the same subset of cells purified from infected, untreated controls. Moreover, both the Poly-ICLC-triggered pulmonary recruitment of the CD11b+F4/80+Gr1int population and the accompanying exacerbation of infection correlated with type I IFN-induced upregulation of the chemokine-encoding gene Ccl2 and were dependent on host expression of the chemokine receptor CCR2. The above findings suggest that Poly-ICLC treatment can detrimentally affect the outcome of M. tuberculosis infection, by promoting the accumulation of a permissive myeloid population in the lung. In addition, these data suggest that agents that stimulate type I IFN should be used with caution in patients exposed to this pathogen.
Current and novel immunosuppressive therapy for autoimmune hepatitis
Authors: Michael A. Heneghan, Ian G. McFarlane
Journal: Hepatology (2002)

Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with autoimmune hepatitis (AIH) and results in remission induction in over 80% of patients. Sustained response to therapy may result in substantial regression of fibrosis even in advanced cases. The outcome of rapid withdrawal of immunosuppression is disease relapse in many patients. Consequently, the use of 2 mg/kg/d of azathioprine as a sole agent to maintain remission has been widely accepted in clinical practice. Persistent severe laboratory abnormalities or histologic abnormalities such as bridging necrosis or multilobular necrosis are absolute indications for treatment based on controlled clinical trials, but debate exists as to whether all patients with AIH need treatment. Examination of liver tissue remains the best method of evaluating both treatment response and need for treatment in patients who have little biochemical activity. Alternative strategies in patients who have failed to achieve remission on "standard therapy" of corticosteroids with or without azathioprine or patients with drug toxicity include the use of cyclosporine, tacrolimus, or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease. In this review we examine current management strategies of AIH, and evaluate available data pertaining to the use of novel immunosuppressive agents in this condition.