tbuckley/cabot-search huggingface dataset:
Cationic Yersinia antigen-induced chronic allergic arthritis in rats. A model for reactive arthritis in humans.
Authors: A K Mertz, S R Batsford, E Curschellas, M J Kist, K B Gondolf
Journal: Journal of Clinical Investigation (1991)

Cationic antigens are known to have considerable arthritogenic potential in experimental systems. During a systematic search for suitable, naturally occurring candidates an intracellular protein was isolated from the ribosomal pellet of Yersinia enterocolitica 0:3, a bacterial strain associated with reactive arthritis in humans. The protein is highly cationic, contains two 19-kD polypeptide chains linked by a disulfide bond, and reveals a strong tendency for spontaneous aggregation. It is suggested to be a nucleic acid binding protein. We tested this antigen for its ability to induce arthritis after intra-articular challenge in preimmunized rats. An acute inflammatory phase followed by transition to chronicity was observed both by technetium-99m scintigraphy and from histology. Massive polymorphonuclear leucocyte infiltration of the synovium was seen early on and fibrosis and thickening of the joint capsule occurred in later stages. Control groups showed no evidence of inflammation. Western blot and ELISA analysis of unselected sera from Yersinia enterocolitica 0:3-infected patients revealed antibodies to the antigen in the majority of cases, whereas healthy individuals rarely reacted. This is the first report of a naturally occurring cationic antigen capable of inducing immunologic tissue injury; it justifies the speculation that cationic antigens from prokaryotic cells could trigger reactive arthritis in humans.
HUMAN ALLERGY TO MAMMALIAN SERA
Authors: Frank A. Simon
Journal: The Journal of Experimental Medicine (1942)

Four patients allergic to many mammalian sera were found to have circulating, skin-sensitizing antibodies for these sera. A study of these antibodies by in vitro neutralization and subsequent local passive transfer showed that, in the case of each patient, one particular mammalian serum neutralized antibodies for all sera whereas other mammalian sera neutralized antibodies for themselves alone or for themselves plus one or several additional sera but not for all sera. The possibility of multiple common allergenic determinants in mammalian sera is discussed.
Anti-Ro/SS-A and anti-La/SS-B antibodies associated with cardiac involvement in childhood systemic lupus erythematosus
Authors: A. C Oshiro, S. J Derbes, A. R Stopa, A. Gedalia
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> To determine the frequency and type of cardiac manifestations in children with systemic lupus erythematosus (SLE) and investigate whether cardiac involvement of SLE in children was associated with any autoantibody pattern. <h3>METHODS</h3> Retrospective analysis of the medical records of all children with SLE (31 patients) seen between January 1984 and January 1994 by the paediatric rheumatology service at Children’s Hospital in New Orleans. All patients satisfied the American College of Rheumatology criteria for the diagnosis of SLE. Paediatric SLE patients with cardiac manifestations based on echocardiogram were identified. Autoantibody tests at diagnosis were identified retrospectively by chart review, and the correlation between autoantibodies and cardiac involvement was analysed using the two tailed Fisher’s exact test. <h3>RESULTS</h3> Thirteen (42%) of 31 SLE patients had cardiac manifestations of SLE. Seven (22%) had pericarditis without myocarditis, five (16%) had pericarditis and myocarditis, and one (3%) had myocarditis without pericarditis. Two patients (6%) with pericarditis had cardiac tamponade. Cardiac manifestations of SLE usually occurred at the time of diagnosis or within six months. Anti-Ro/SS-A antibodies were present in serum samples of nine of 11 (82%) patients with cardiac involvement and in five of 15 (33%) without cardiac involvement (p=0.02). Anti-La/SS-B antibodies were present in serum samples of six of 10 (60%) patients with cardiac involvement and two of 15 (13%) without cardiac involvement (p=0.03). Anti-Sm and anti-RNP antibodies showed no correlation with the presence of cardiac disease. <h3>CONCLUSIONS</h3> Cardiac involvement in our paediatric SLE population was frequently found and correlated significantly with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies.
The Role of ATF4 Stabilization and Autophagy in Resistance of Breast Cancer Cells Treated with Bortezomib
Authors: Manuela Milani, Tomasz Rzymski, Howard R. Mellor, Luke Pike, Alberto Bottini, Daniele Generali, Adrian L. Harris
Journal: Cancer Research (2009)

The ubiquitin-proteasome system plays a key regulatory role in cellular homeostasis. The inhibition of the 26S proteasome by Bortezomib leads to the accumulation of misfolded proteins, resulting in endoplasmic reticulum stress followed by a coordinated cellular response called unfolded protein response (UPR). Endoplasmic reticulum stress is also a potent inducer of macroautophagy. Bortezomib is a selective and potent inhibitor of the 26S proteasome and is approved for the treatment of multiple myeloma. Clinical trials with Bortezomib have shown promising results for some types of cancers, but not for some others, including those of the breast. In this study, we show that Bortezomib induces the UPR and autophagy in MCF7 breast cancer cells. Surprisingly, Bortezomib did not induce phosphorylation of PERK, a key initial step of the UPR. We show that induction of autophagy by Bortezomib is dependent on the proteasomal stabilisation of ATF4 and up-regulation of LC3B by ATF4. We show that ATF4 and LC3B play a critical role in activating autophagy and protecting cells from Bortezomib-induced cell death. Our experiments also reveal that HDAC6 knockdown results in decreased LC3B protein and reduced autophagy. Our work shows that the induction of autophagy through ATF4 may be an important resistance mechanism to Bortezomib treatment in breast cancer, and targeting autophagy may represent a novel approach to sensitize breast cancers to Bortezomib.
Cancer-Related Lymphedema Risk Factors, Diagnosis, Treatment, and Impact: A Review
Authors: Electra D. Paskett, Julie A. Dean, Jill M. Oliveri, J. Phil Harrop
Journal: Journal of Clinical Oncology (2012)

Purpose Cancer-related lymphedema (LE) is an incurable condition associated with lymph-involved cancer treatments and is an increasing health, quality of life (QOL), and cost burden on a growing cancer survivor population. This review examines the evidence for causes, risk, prevention, diagnosis, treatment, and impact of this largely unexamined survivorship concern. Methods PubMed and Medline were searched for cancer-related LE literature published since 1990 in English. The resulting references (N = 726) were evaluated for strength of design, methods, sample size, and recent publication and sorted into categories (ie, causes/prevention, diagnosis, treatment, and QOL). Sixty studies were included. Results Exercise and physical activity and sentinel lymph node biopsy reduce risk, and overweight and obesity increase risk. Evidence that physiotherapy reduces risk and that lymph node status and number of malignant nodes increase risk is less strong. Perometry and bioimpedence emerged as attractive diagnostic technologies, replacing the use of water displacement in clinical practice. Swelling can also be assessed by measuring arm circumference and relying on self-report. Symptoms can be managed, not cured, with complex physical therapy, low-level laser therapy, pharmacotherapy, and surgery. Sequelae of LE negatively affect physical and mental QOL and range in severity. However, the majority of reviewed studies involved patients with breast cancer; therefore, results may not be applicable to all cancers. Conclusion Research into causes, prevention, and effect on QOL of LE and information on LE in cancers other than breast is needed. Consensus on definitions and measurement, increased patient and provider awareness of signs and symptoms, and proper and prompt treatment/access, including psychosocial support, are needed to better understand, prevent, and treat LE.
P19 Symptomatic Epstein Barr Virus (EBV) Hepatitis is uncommon, but occurs in patients of any age, including the elderly
Authors: L. Vine, K. Shephard, D. Grimes, R. Bendall, H. Dalton
Journal: Gut (2011)

<h3>Introduction</h3> Epstein Barr Virus (EBV) infection typically presents as infectious mononucleosis (IM) in young adults with the classical triad of fever, sore throat and lymphadenopathy. Mildly abnormal liver function tests (LFTs) are common but symptomatic hepatitis is rare. Symptomatic, icteric, EBV hepatitis is rarely reported in those with IM and in the elderly. <h3>Aim</h3> To review the demographics, presenting features and natural history with EBV hepatitis and to determine what factors might lead a clinician to consider a diagnosis of EBV hepatitis. <h3>Method</h3> Retrospective study of 2100 patients attending the Jaundice Hotline, a fast track referral system for patients with jaundice at The Cornwall Royal Cornwall Hospital (1998–2011). EBV hepatitis was defined as: symptomatic hepatitis with positive serology for EBV (serology included EBV nuclear antigen, EBV viral capsid antigen (VCA) IgM and VCA IgG). All patients had no evidence of biliary obstruction or parenchymal liver disease on abdominal ultrasound examination (USS), and negative serology for other hepatotropic viruses (HAV, HBV, HCV, HEV, CMV). Other causes of parenchymal liver disease were also excluded by appropriate blood tests. <h3>Results</h3> Of the total of 2100 consecutive patients with jaundice studied, 17 patients (10 males, 7 females) were diagnosed with EBV hepatitis. All patients were immunocompetent. 47% (8/17) of these patients were aged over 60 years (mean age 44 years, range 18–82). At presentation, mean (range) LFTs were: bilirubin 57 μmol/l (11–161), ALT 428 IU/l (34–1471), ALKP 339 IU/l (132–840). Only 3 patients presented as classical IM. 95% (16/17) had significant lymphocytosis and 82% (14/17) patients had splenomegaly on USS examination at initial assessment. Only 2 patients were unwell enough to be admitted to hospital. All patients fully recovered within 4–6 weeks. <h3>Conclusion</h3> Symptomatic EBV hepatitis is uncommon and causes a self-limiting illness. EBV hepatitis is not usually associated with classical symptoms of IM and occurred in patients of a wide variety of ages. The diagnosis should be considered in patients of all ages presenting with hepatitis, including those with a cholestatic picture, and especially in those with a lymphocytosis and splenomegaly.
Lung function, airway remodelling and inflammation in symptomatic infants: outcome at 3 years
Authors: K. Malmstrom, A. S. Pelkonen, L. P. Malmberg, S. Sarna, H. Lindahl, M. Kajosaari, M. Turpeinen, S. Saglani, A. Bush, T. Haahtela, P. K. Jeffery, M. J. Makela
Journal: Thorax (2011)

<h3>Background</h3> Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years. <h3>Methods</h3> 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children9s hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit. <h3>Results</h3> 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p&lt;0.001) and with the purchase of ICS (p=0.009) and β agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively). <h3>Conclusions</h3> Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children.
Importance of Myocardial Reserve in Determining Changes in Heart Rate during Levarterenol Infusion
Authors: LOUIS A. SOLOFF, FELIX CORTEZ, WILLIAM L. WINTERS
Journal: Circulation Research (1960)

Levarterenol-induced hypertension may slow, increase or produce no change in the cardiac rate of persons with cardiovascular disease. The degree of cardiac disability at least partly determines the type of response.
Abnormal Termination of Ca <sup>2+</sup> Release Is a Common Defect of RyR2 Mutations Associated With Cardiomyopathies
Authors: Yijun Tang, Xixi Tian, Ruiwu Wang, Michael Fill, S.R. Wayne Chen
Journal: Circulation Research (2012)

Rationale: Naturally occurring mutations in the cardiac ryanodine receptor (RyR2) have been associated with both cardiac arrhythmias and cardiomyopathies. It is clear that delayed afterdepolarization resulting from abnormal activation of sarcoplasmic reticulum Ca 2+ release is the primary cause of RyR2-associated cardiac arrhythmias. However, the mechanism underlying RyR2-associated cardiomyopathies is completely unknown. Objective: In the present study, we investigate the role of the NH 2 -terminal region of RyR2 in and the impact of a number of cardiomyopathy-associated RyR2 mutations on the termination of Ca 2+ release. Methods and Results: The 35-residue exon-3 region of RyR2 is associated with dilated cardiomyopathy. Single-cell luminal Ca 2+ imaging revealed that the deletion of the first 305 NH 2 -terminal residues encompassing exon-3 or the deletion of exon-3 itself markedly reduced the luminal Ca 2+ threshold at which Ca 2+ release terminates and increased the fractional Ca 2+ release. Single-cell cytosolic Ca 2+ imaging also showed that both RyR2 deletions enhanced the amplitude of store overload-induced Ca 2+ transients in HEK293 cells or HL-1 cardiac cells. Furthermore, the RyR2 NH 2 -terminal mutations, A77V, R176Q/T2504M, R420W, and L433P, which are associated with arrhythmogenic right ventricular displasia type 2, also reduced the threshold for Ca 2+ release termination and increased fractional release. The RyR2 A1107M mutation associated with hypertrophic cardiomyopathy had the opposite action (ie, increased the threshold for Ca 2+ release termination and reduced fractional release). Conclusions: These results provide the first evidence that the NH 2 -terminal region of RyR2 is an important determinant of Ca 2+ release termination, and that abnormal fractional Ca 2+ release attributable to aberrant termination of Ca 2+ release is a common defect in RyR2-associated cardiomyopathies.
Lung volume reduction surgery (LVRS) for chronic obstructive pulmonary disease (COPD) with underlying severe emphysema
Authors: J. Young, A. Fry-Smith, C. Hyde
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Lung volume reduction surgery (LVRS) has recently re-emerged as a surgical option for the treatment of end stage chronic obstructive pulmonary disease (COPD) due to underlying severe emphysema. Advocates of LVRS claim that it represents a significant breakthrough in the management of this challenging group of patients while sceptics point to uncertainty about the effectiveness of the operation. <h3>METHODS</h3> A systematic review was conducted of the evidence on the effects of LVRS in patients with end stage COPD secondary to severe emphysema. <h3>RESULTS</h3> The most rigorous evidence on the effectiveness of LVRS came from case series. Seventy five potentially relevant studies were identified and 19 individual series met the methodological criteria for inclusion. The pattern of results was consistent across individual studies despite a significant degree of clinical heterogeneity. Significant short term benefits occurred across a range of outcomes which appeared to continue into the longer term. Physiological improvements were matched by functional and subjective improvements. Early mortality rates were low and late mortality rates compared favourably with those of the general COPD population. However, the entire research base for the intervention is subject to the limitations of study designs without parallel control groups. <h3>CONCLUSIONS</h3> LVRS appears to represent a promising option in the management of patients with severe end stage emphysema. However, until the results of ongoing clinical trials are available, the considerable uncertainty that exists around the effectiveness and cost effectiveness of the procedure will remain.
Changes in oral trace gas concentrations following orthognathic surgery and intermaxillary fixation: a case study using selected ion flow tube mass spectrometry
Authors: Brian M Ross
Journal: International Journal of Oral Science (2011)

Orthognathic surgery is frequently accompanied by intermaxillary fixation. Intermaxillary fixation impedes the maintenance of effective oral hygiene and prolonged fixation can result in periodontal disease. A potential shorter term effect is the generation of oral malodour. It is unclear, however, as to how the production of malodorous compounds in the oral cavity is altered post‐surgery. Oral air concentration of sulphur containing compounds, short chain organic acids, ammonia, isoprene and acetone were measured using selected ion flow tube‐mass spectrometry in a patient who had undergone orthognathic surgery with subsequent intermaxillary fixation. Total sulphide levels rose approximately 5‐fold during fixation with metal ties, with smaller increases recorded for the other compounds measured with the exception of isoprene which remained close to baseline levels. Organic acid levels declined markedly once elastic ties had replaced metal ties, with a lesser reduction being observed in sulphide levels, with both declining further after the commencement of a chlorhexidine‐containing mouthwash. These data suggest that bacterial generation of a variety of malodorous compounds increases markedly following intermaxillary fixation. This single case also suggests that the use of elastic ties and effective oral hygiene techniques, including the use of chlorhexidine mouthwash, may help ameliorate such post‐surgical effects.
Psychiatry in Shanghai, China: Observations in 1973
Authors: DAVID N. RATNAVALE
Journal: American Journal of Psychiatry (1973)

At the invitation of the Chinese Ministry of Health, the author visited China earlier this year. He describes the structure and organization of the Shanghai Psychiatric Institute, a therapeutic community in which the staff and patients work together in a classless social organization, which is part of a medical system that blends the modern and the ancient traditional medical practices. The author presents brief general information on acupuncture and describes its use in psychiatry, but stresses the preeminence of group activities in the therapy of mental illness.
Male Sex Increases the Risk of Autoimmunity but not Type 1 Diabetes
Authors: Jeffrey P. Krischer, David D. Cuthbertson, Carla Greenbaum
Journal: Diabetes Care (2004)

OBJECTIVE—The goal of this study was to explore the role of sex on the prevalence of autoantibodies, protective genetic subtypes, β-cell function, and the incidence of type 1 diabetes in a population of first- and second-degree relatives of patients with type 1 diabetes (probands). We examined both the effect of the sex of the individual screened as well as the effect of the sex of the individual’s proband on diabetes risk variables tested. RESEARCH DESIGN AND METHODS—The Diabetes Prevention Trial-Type 1 has screened 93,188 relatives of type 1 diabetic patients from February 1994 to January 2002. After observing that more men than women were islet cell autoantibody (ICA) positive for the group as a whole, we further explored the role of sex by detailed analysis of variables in this population. RESULTS—Our data suggest only an influence of sex on the type 1 diabetes disease process. After adjustment for race, age, and relationship to proband, male sex was associated with the appearance of autoimmunity, i.e., the presence of ICA and having two or more antibodies. There was no effect of sex on the presence of other autoantibodies, insulin secretion, results of oral glucose tolerance test, or development of diabetes. CONCLUSIONS—Our finding that male sex conveys an independent increased risk for development of ICA and multiple antibodies, while at the same time finding no difference with respect to the development of diabetes, suggests that male relatives with the known risk factor of ICA are less likely than comparable female relatives to progress to overt disease, that the pathogenesis of type 1 diabetes among men is slower compared with women, or that women develop diabetes manifesting different antibody responses.
The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis
Authors: S. Vitthala, T.A. Gelbaya, D.R. Brison, C.T. Fitzgerald, L.G. Nardo
Journal: Human Reproduction Update (2008)

It is estimated that there is at least a 2-fold rise in the incidence of monozygotic twinning after assisted reproductive technology compared with natural conception. This can result in adverse pregnancy outcomes. We searched MEDLINE, EMBASE and SCISEARCH for studies that estimated the risk of monozygotic twinning and its association with any particular assisted reproductive technique. Monozygotic twinning was defined by ultrasound or Weinberg criteria. A meta-analysis of the proportion of monozygotic twins was performed using both fixed and random effects models. The search revealed 37 publications reporting on the incidence of monozygotic twins after assisted reproductive techniques. Twenty-seven studies met the inclusion criteria and were included in the meta-analysis. The summary incidence of monozygotic twins after assisted conception was 0.9% (0.8–0.9%). The incidence of monozygotic twins in natural conception is 0.4%. Blastocyst transfer and intracytoplasmic sperm injection are associated with 4.25 and 2.25 times higher risk of monozygotic twins. The risk of monozygotic twins in assisted conception is 2.25 times higher than the natural conceptions. Larger studies reporting on monozygotic twinning following single-embryo transfer or after post-natal confirmation of zygosity with DNA analysis are warranted before definitive conclusions can be drawn and guidelines produced. In order to provide adequate pre-conceptional counselling, it is important to monitor the incidence of monozygotic twins in both natural and assisted conceptions. We suggest building a national multiple pregnancy database based on accurate diagnosis of zygosity.