tbuckley/cabot-search huggingface dataset:
EBV covers its tracks
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

All B cells need is BAFFB cells usually conspire with T cells to break tolerance against the host and cause lupus.But Groom et al. (page 1959) now show that B cells don't always need T cells to egg them on.An activating cytokine empowers them to cause trouble all on their own.This cytokine, called BAFF (B cellactivating factor), helps B cells survive as they transit through developmental checkpoints.BAFF also enhances T cell activation.With too much BAFF, however, even B cells that should have been eliminated-such as self-reactive ones-survive.The autoreactive antibodies first secreted by these cells are relatively harmless.But presumably with help from BAFF-activated T cells, these B cells switch their antibody genes and start producing pathogenic autoantibodies.Groom et al. now find that the antibody-switching signal doesn't have to come from T cells.Mice that overexpressed BAFF but lacked T cells still developed lupus.The B cells instead derived the extra push through their Toll-like receptors (TLRs) 7 and 9, whose expression was strongly enhanced by BAFF.The authors speculate that nucleic acids released by dying cells might trigger these TLRs on self-reactive B cells.The presence of disease-inducing antibodies even when T cells are absent might explain why not all lupus patients respond to treatments that suppress T cell functions.The team is now investigating whether these patients have high levels of BAFF.
Platelet CD154 Potentiates Interferon-α Secretion by Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus
Authors: Pierre Duffau, Julien Seneschal, Carole Nicco, Christophe Richez, Estibaliz Lazaro, Isabelle Douchet, Cécile Bordes, Jean-François Viallard, Claire Goulvestre, Jean-Luc Pellegrin, Bernard Weil, Jean-François Moreau, Frédéric Batteux, Patrick Blanco
Journal: Science Translational Medicine (2010)

In the autoimmune disease lupus, platelets activated by self-antigens contribute to pathology by triggering the secretion of interferon from immune cells.
HORMONE REPLACEMENT THERAPY AND ENDOMETRIAL CARCINOMA
Authors: Richard Doll, L.J. Kinlen, D.C.G. Skegg, P.G. Smith, M.P. Vessey, J.D. Hutton, M.A.F. Murray, H.S. Jacobs, R.W. Beard, V.H.T. James, R.E. Oakey, Graham Mulley, J.R.A. Mitchell
Journal: The Lancet (1977)
Erythrocyte CR1 Determination Using Monoclonal Antibody in a Microtiter Plate ELISA; Receptors Are Not Masked by Immune Complexes
Authors: B. S. Thomsen, H. Nielsen, G. Bendixen
Journal: Allergy (1986)

The microtiter plate ELISA using monoclonal antibody is a specific, sensitive and quantitative technique for measuring CR1 on human erythrocytes. The present investigations established that receptor occupancy by immune complexes did not affect the measurements. The monoclonal anti‐CR1 antibody To5 bound unimpeded to receptors that had reacted with an excess of complement‐opsonized tetanus toxoid anti‐tetanus toxoid complexes prepared at antigen: antibody ratios between 32:1 and 1:8. The CR1 levels on erythrocytes from 11 patients with systemic lupus erythematosus (SLE) were not increased ( P &gt; 0.30) after release of CR1‐bound immune complexes by incubation with factor I. Neither did the serum from these patients contain blocking anti‐CR1 activity ( P &gt; 0.10). Additionally, the number of antigenic CR1 sites in 10 normals and in the 11 patients with SLE was well correlated with the number of functional receptor sites as assessed by binding of soluble complexes ( P &lt; 0.001). These data establish that the true CR1 levels are determined using the microtiter plate ELISA for quantitation of CR1 in patients with diseases involving immune complexes and/or autoantibodies.
Loss of Cardiac Magnesium in Experimental Heart Failure Prolongs and Destabilizes Repolarization in Dogs
Authors: Mark C.P Haigney, Shaokui Wei, Stefan Kääb, Elinor Griffiths, Ronald Berger, Richard Tunin, David Kass, Westby G Fisher, Burton Silver, Howard Silverman
Journal: Journal of the American College of Cardiology (1998)

Objectives. We sought to determine whether heart failure results in loss of cardiac magnesium sufficient to alter cellular electrophysiology. Background. Free magnesium has numerous intracellular roles affecting metabolism, excitability and RNA synthesis. Total cardiac magnesium content is reduced in heart failure, but it is unclear whether magnesium loss is primary or iatrogenic. Furthermore, it is unknown whether free magnesium levels are affected or whether a change in free magnesium would alter cellular electrophysiology. Methods. Eight mongrel dogs underwent demand ventricular pacing (VVI) at 250 beats/min for 3 weeks to induce heart failure. Sublingual epithelial magnesium was measured before pacing and at death. Left ventricular myocytes were isolated and loaded with Mag-Indo-1 to measure free magnesium ([Mg2+]i); myocytes from eight normal dogs served as controls. To test whether changes in [Mg2+]iin this range could alter cellular repolarization, current-clamped myocytes were dialyzed with 0.5 or 1.0 mmol/liter MgCl2. Results. Mean sublingual epithelial magnesium fell significantly in the paced animals, from 36.9 ± 0.5 to 33.9 ± 0.7 mEq/liter (p < 0.01). Mean cardiac [Mg2+]iwas significantly lower in the dogs with heart failure—0.49 ± 0.06 versus 1.06 ± 0.15 mmol/liter (p < 0.003). Time to 90% repolarization was significantly shorter in cells dialyzed with 1.0 mmol/liter compared with 0.5 mmol/liter MgCl2in myocytes from normal dogs or dogs with heart failure (596 ± 34 vs. 760 ± 58 ms in normal dogs and 586 ± 29 vs. 838 ± 98 ms in dogs with heart failure; p < 0.05 for each). Conclusions. Experimental heart failure results in both tissue and cardiac magnesium loss in the absence of drug therapy. Free cardiac magnesium is significantly reduced, possibly contributing to abnormal repolarization in heart failure.
Use of an ear oximeter to assess lung function.
Authors: R Al-Dulymi, R Hainsworth
Journal: Thorax (1975)

Values of arterial oxygen saturation were estimated using an ear oximeter while subjects breathed a mixture of 15% oxygen in nitrogen. Results obtained from patients with lung disease were clearly separated from results obtained from normal subjects, and the lowereing of saturation was related to the clinical severity of the disease. Patients with low oximeter readings with 15% oxygen also had low levels of arterial oxygen tension during exercise.
Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis
Authors: J Vencovsky
Journal: Annals of the Rheumatic Diseases (2003)

To evaluate a contribution of selected laboratory parameters for a prediction of progressive and erosive development in patients with early rheumatoid arthritis (RA).In a prospective study baseline levels of antibodies to cyclic citrullinated peptide (anti-CCP), IgM, IgA, and IgG rheumatoid factors (RFs) were measured by enzyme linked immunosorbent assay (ELISA) in 104 patients with RA with disease duration <2 years. Antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence. Patients were divided into two groups based either on the presence or absence of erosions or according to progression of Larsen score at the end of the 24 months' follow up.Sixty seven (64%) patients developed radiographic erosions, 49 (47%) had progression in Larsen score, and 36 (35%) progressed by more than 10 Larsen units. Significant differences in erosions and progression between the two groups were detected for anti-CCP, AKA, APF, IgM RF, IgA RF, and IgG RF. Baseline Larsen score correlated significantly with anti-CCP, IgM RF, and IgA RF levels, and all measured antibodies correlated with the progression >10 units. The combination of anti-CCP and IgM RF increased the ability to predict erosive and progressive disease.The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course. Combined analysis of anti-CCP and IgM RF provides the most accurate prediction.
Preoperative Chemoradiotherapy and Postoperative Chemotherapy with 5-Fluorouracil and Oxaliplatin Versus 5-Fluorouracil Alone in Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-04 Randomized Phase III Trial
Authors: U. Graeven, T. Liersch, R. Fietkau, W. Hohenberger, T. Hothorn, D. Arnold, H.R. Raab, C. Wittekind, C. Hess, L. Staib, H. Becker, R. Sauer, C. Rödel
Journal: Annals of Oncology (2014)
Off seasonal and pre-seasonal assessment of circulating energy sources during prolonged running at the anaerobic threshold in competitive triathletes
Authors: B Knoepfli, M C Riddell, E Ganzoni, A Burki, B Villiger, S P von Duvillard
Journal: British Journal of Sports Medicine (2004)

To compare changes in circulating energy sources during prolonged exercise in off season (OS) and pre-season (PS) training of triathletes.Nine athletes of the Swiss national triathlon team (three female, mean (SD) age 28.7 (4.9) years, height 169.8 (6.0) cm, weight 57.0 (6.2) kg, VO(2)max 66.5 (5.3) ml/min/kg; six male, mean (SD) age 24.0 (4.1) years, height 181.4 (6.9) cm, weight 73.5 (6.0) kg, VO(2)max 75.9 (4.9) ml/min/kg) were tested twice (2.5 months apart) during a 25 km aerobic capacity test run at the end of the OS and just before the season. The average training load during the OS was 9.9 h/week, and this increased to 14.4 h/week in the PS. With heart rates as reference, exercise intensity during the aerobic capacity test was 97.0 (4.9)% of the anaerobic threshold and 91.2 (4.5)% of VO(2)max. Blood samples were collected before, during, and after the aerobic capacity test. Samples were collected every 5 km during three minute rest intervals.Blood was analysed for triglyceride (TG), free fatty acids, cholesterol, high density lipoprotein cholesterol, glucose, insulin, lactate, and changes in plasma volume. A two factor (season by distance) repeated measures analysis of variance revealed an increase in capacity for prolonged exercise in the PS by a decrease in running intensity during the aerobic capacity test (% of speed at 2.0 mmol/l lactate threshold, p = 0.008), an increase in running speed at the anaerobic threshold (p = 0.003) and at 4.0 and 2.0 mmol/l (p<0.001) of the lactate threshold. A significant season by distance interaction was found for TG (p<0.001). TG concentrations peaked at 5 km and decreased logarithmically throughout the OS (1.48 (0.34) to 0.86 (0.20) mmol/l) and PS (1.90 (0.31) to 0.73 (0.18) mmol/l) tests. From the OS to the PS, there was an increase in the difference in TG at 5-15 km with a concomitant increase at 2.0 mmol/l of the lactate threshold. The peak TG concentrations at 5 km followed by a logarithmic decrease suggest that TG may also provide circulating energy. A greater logarithmic decrease in TG occurred in the PS than in the OS, indicating a higher rate of use. There was an increase in the difference in TG at 5-15 km similar to the increase in the speed at 2.0 mmol/l of the lactate threshold between the two seasons. Glucose, insulin, lactate, and free fatty acids were similar in the two seasons.Free fatty acid and TG concentrations were much higher than expected, and the two training seasons showed significantly different patterns of TG concentration during prolonged running. These responses may be related to aerobic capacity of prolonged exercise.
Pilo-sebaceous duct physiology.
Authors: W. J. CUNLIFFE, W. D. H. PERERA, P. THACKRAY, M. WILLIAMS, R. A. FORSTER, S. M. WILLIAMS
Journal: British Journal of Dermatology (1976)

We have used surface microscopy to measure the pil-sebaceous duct orifices at different sites in 150 subjects. Our data have shown that there are more pilo-sebaceous units on the face compared to the back and that these exists are smaller on the face. Despite the small exit the sebum excretion rate per gland on the forehead was not significantly different from that on the back. Thus the number of pilo-sebaceous duct units and the pilo-sebaceous canal exit size are possible factors in the localization of acne.
Trimethoprim-Sulfamethoxazole: Another Cause of Recurrent Meningitis
Authors: E. J. Haas
Journal: JAMA (1984)

To the Editor.—  Recurrent meningitis usually suggests an incompletely healed fracture of the cribriform plate of the skull. It can also be seen with Behcet's disease, Mollaret's meningitis, familial Mediterranean fever, and with various immunodeficiencies such as complement deficiency, agammaglobulinemia, and asplenia. 1 We recently encountered another cause that might be of interest to practicing physicians.  Report of a Case.—  A 52-year-old woman was referred on May 13, 1983, for evaluation of recurrent meningitis. The results of analysis at the beginning of her previous attacks are listed in the Table. All cultures were sterile. The May 6, 1983, lumbarpuncture was done soon after the onset of symptoms; the attack itself was clinically indistinguishable from her other episodes. She was receiving cefotaxime sodium at the time of referral. The patient complained that severe sinus congestion had preceded many of her attacks of meningitis. She remembered taking Septra for symptoms of
Cancer-Associated Genodermatoses
Authors: Keyoumars Soltani
Journal: JAMA (1983)

Early detection of cutaneous manifestations of systemic diseases can lead to early search for and successful management of more serious components of such disorders. This is of particular importance in the heterogenous groups of disorders called the cancer-associated genodermatoses, in which early diagnosis of skin changes can be of great aid to the physician in planning appropriate workup of the patient, identifications of affected family members and carriers, and arrangement for proper genetic counseling. The present book, edited by Drs Lynch and Fusaro, is an informative survey of the field. The ten authors have backgrounds in different disciplines of medicine, and each has contributed to the high quality of the 11 chapters in the book. The three tables listing the autosomal dominant, autosomal recessive, and sex-linked genodermatoses are comprehensive and provide the reader with a brief description of the syndromes and their related tumors. I especially enjoyed the three chapters
Does extremity-MRI improve erosion detection in severely damaged joints? A study of long-standing rheumatoid arthritis using three imaging modalities
Authors: J E Freeston, P G Conaghan, S Dass, E Vital, E M A Hensor, S Stewart, P Emery
Journal: Annals of the Rheumatic Diseases (2007)

Long-standing rheumatoid arthritis produces unique challenges when assessing damage due to joint deformity. The use of extremity magnetic resonance imaging (eMRI) offers the possibility of improved disease assessment because of greater patient tolerability.The aim of this cross-sectional study was to compare the identification of wrist erosions in a severe rheumatoid arthritis cohort by eMRI with a restricted field of view (eMRI-RV) to radiography and high field MRI, using the latter as the reference.Fifteen patients (87% female, median age 56 years) with active rheumatoid arthritis (median DAS28 7.01 and disease duration 11 years) on leflunomide were enrolled. Radiography of hands, eMRI-RV (0.2 T MagneVu MV 1000) and high field MRI of unilateral wrist joints were performed.Of 86 comparable wrist joint areas, high field MRI identified 70 erosions, eMRI-RV 32 and radiography 4. With high field MRI considered the reference, the sensitivity, specificity and accuracy of eMRI-RV for erosions were 46%, 94% and 55%, and the corresponding values for x ray were 6%, 100% and 23%, respectively.In severely damaged rheumatoid arthritis joints, sensitivity of erosion detection was markedly higher for eMRI-RV than radiography, using high field MRI as the reference. eMRI-RV was, however, less sensitive than high field MRI.
The sst1 locus controls granuloma necrosis in tuberculosis
Authors: M Almond
Journal: Thorax (2009)

There is broad variation in susceptibility to Mycobacterium tuberculosis (MTB), and mouse models play a key role in elucidating the underlying mechanisms. The authors tested the hypothesis that caseation within pulmonary lesions is a specific effect of the sst1 (supersusceptibility to tuberculosis 1) locus on chromosome 1.

Typical mouse lesions described in the literature lack central caseation. However, …
Preclinical assessment of curcumin as a potential therapy for B‐CLL
Authors: Peter C. Everett, John A. Meyers, Anthony Makkinje, Mohammed Rabbi, Adam Lerner
Journal: American Journal of Hematology (2006)

Abstract Curcumin, the principle component of the spice turmeric, has been used as an anti‐inflammatory medication in India and China for centuries. Recent studies, predominantly using actively dividing cell lines, have suggested that this compound could be used as a chemopreventative or therapeutic agent for epithelial tumors. As curcumin has been reported to inhibit the NIK/IKK complex, an activity that would be expected to induce apoptosis in B cell malignancies, we sought to determine whether curcumin induces apoptosis in vitro in primary chronic lymphocytic leukemia (B‐CLL) cells. Primary leukemic cells were incubated with varying dosages of curcumin, followed by assessment for apoptosis. The role of PPARγ or NF‐κB signaling in curcumin‐induced apoptosis was examined by cotreatment with a PPARγ antagonist or EMSA of nuclear NFκB complexes. We also examined whether a clinically achievable concentration of curcumin (1 μM) would augment the apoptotic effects of fludarabine, dexamethasone, vincristine or the PDE4 inhibitor rolipram. In B‐CLL cells from 14 patients, curcumin‐induced apoptosis with a mean EC 50 of 5.5 μM. In contrast, the EC 50 for whole mononuclear cells from a healthy donor was 21.8 μM. In a 48 hr wash‐out time course, curcumin‐induced apoptosis was time‐dependent, with a substantial reduction in apoptosis observed when curcumin was removed after 5 hr. Curcumin treatment reduced basal nuclear NF‐κB levels and 1 μM curcumin augmented both vinca alkaloid and PDE4 inhibitor‐induced apoptosis in B‐CLL cells. Our studies suggest that curcumin may augment the efficacy of established or experimental therapies for B‐CLL. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Nintendo related injuries and other problems: review
Authors: M. B. Jalink, E. Heineman, J.-P. E. N. Pierie, H. O. ten Cate Hoedemaker
Journal: BMJ (2014)

<b>Objective</b> To identify all reported cases of injury and other problems caused by using a Nintendo video gaming system. <b>Design</b> Review. <b>Data sources and review methods</b> Search of PubMed and Embase in June 2014 for reports on injuries and other problems caused by using a Nintendo gaming system. <b>Results</b> Most of the 38 articles identified were case reports or case series. Injuries and problems ranged from neurological and psychological to surgical. Traditional controllers with buttons were associated with tendinitis of the extensor of the thumb. The joystick on the Nintendo 64 controller was linked to palmar ulceration. The motion sensitive Wii remote was associated with musculoskeletal problems and various traumas. <b>Conclusions</b> Most problems are mild and prevalence is low. The described injuries were related to the way the games are controlled, which varies according to the video game console.
No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics
Authors: Alan R Sanders, Jubao Duan, Douglas F Levinson, Jianxin Shi, Deli He, Cuiping Hou, Gregory J Burrell, John P Rice, Deborah A Nertney, Ann Olincy, Pablo Rozic, Sophia Vinogradov, Nancy G Buccola, Bryan J Mowry, Robert Freedman, Farooq Amin, Donald W Black, Jeremy M Silverman, William F Byerley, Raymond R Crowe, C Robert Cloninger, Maria Martinez, Pablo V Gejman
Journal: American Journal of Psychiatry (2008)

Objective: The authors carried out a genetic association study of 14 schizophrenia candidate genes ( RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT , and ARVCF ). This study tested the hypothesis of association of schizophrenia with common single nucleotide polymorphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. Method: The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3′ untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Results: Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2 , and HTR2A did not produce nominally significant evidence to support previous evidence for association. Conclusions: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.
High Frequency of Skin-homing Melanocyte-specific Cytotoxic T Lymphocytes in Autoimmune Vitiligo
Authors: Graham S. Ogg, P. Rod Dunbar, Pedro Romero, Ji-Li Chen, Vincenzo Cerundolo
Journal: The Journal of Experimental Medicine (1998)

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. Using tetrameric complexes of human histocompatibility leukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies of circulating MelanA-specific, A*0201-restricted cytotoxic T lymphocytes (A2–MelanA tetramer+ CTLs) in seven of nine HLA-A*0201–positive individuals with vitiligo. Isolated A2–MelanA tetramer+ CTLs were able to lyse A*0201-matched melanoma cells in vitro and their frequency ex vivo correlated with extent of disease. In contrast, no A2–MelanA tetramer+ CTL could be identified ex vivo in all four A*0201-negative vitiligo patients or five of six A*0201-positive asymptomatic controls. Finally, we observed that the A2–MelanA tetramer+ CTLs isolated from vitiligo patients expressed high levels of the skin homing receptor, cutaneous lymphocyte-associated antigen, which was absent from the CTLs seen in the single A*0201-positive normal control. These data are consistent with a role of skin-homing autoreactive melanocyte-specific CTLs in causing the destruction of melanocytes seen in autoimmune vitiligo. Lack of homing receptors on the surface of autoreactive CTLs could be a mechanism to control peripheral tolerance in vivo.
Death by Voluntary Dehydration — What the Caregivers Say
Authors: Sandra Jacobs
Journal: New England Journal of Medicine (2003)

Researcher Linda Ganzini, M.D., says she was “stunned” after tallying the questionnaire results reported in this issue of the Journal (pages 359–365): Among the hospice nurses in Oregon who were surveyed, nearly twice as many had cared for patients who chose voluntary refusal of food and fluids to hasten death as had cared for patients who chose physician-assisted suicide. This study takes an initial step toward examining the experience of voluntary refusal of food and fluids for patients and their caregivers. The nurses' descriptions of the deaths resulting from voluntary refusal of food and fluids accord with the few published . . .