tbuckley/cabot-search huggingface dataset:
Pelvic inflammatory disease
Authors: E. C. Bartlett, W. B. Levison, P. E. Munday
Journal: BMJ (2013)

A 22 year old woman in a new sexual relationship presented to her general practitioner with slightly painful intermenstrual bleeding for 10 days. She had pelvic tenderness but no cervical excitation on bimanual examination. The doctor suspected that the bleeding was a side effect of the oral contraceptive pill, started three months earlier. However, as he was unable to rule out pelvic inflammatory disease (PID), endocervical swab samples were taken to test for the sexually transmitted infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis , and broad spectrum antibiotics prescribed, after which the symptoms resolved. The swab sample confirmed the presence of C trachomatis . 

PID is due to infection of the upper female genital tract resulting in a wide range of pelvic pathology, from mild endometritis to pelvic peritonitis. Causative organisms are either sexually transmitted (such as C trachomatis , N gonorrhoeae , Mycoplasma genitalium ) or endogenous vaginal organisms (for example, Bacteroides species) that ascend into the pelvic area from the lower genital tract through the cervix.

#### How common is PID?

PID may present with classic symptoms and signs or with mild and subtle symptoms that may be easy to miss, according to a review of the evidence in national guidelines written by the British Association for Sexual Health and HIV.2

The best recent data on easily missed PID come from a retrospective audit in a walk-in centre for sexual health. This showed significantly different rates for the diagnosis of PID among 23 doctors, compared with similar rates …
Transcription-Induced DNA Double Strand Breaks: Both Oncogenic Force and Potential Therapeutic Target?
Authors: Michael C. Haffner, Angelo M. De Marzo, Alan K. Meeker, William G. Nelson, Srinivasan Yegnasubramanian
Journal: Clinical Cancer Research (2011)

Abstract An emerging model of transcriptional activation suggests that induction of transcriptional programs, for instance by stimulating prostate or breast cells with androgens or estrogens, respectively, involves the formation of DNA damage, including DNA double strand breaks (DSB), recruitment of DSB repair proteins, and movement of newly activated genes to transcription hubs. The DSB can be mediated by the class II topoisomerase TOP2B, which is recruited with the androgen receptor and estrogen receptor to regulatory sites on target genes and is apparently required for efficient transcriptional activation of these genes. These DSBs are recognized by the DNA repair machinery triggering the recruitment of repair proteins such as poly(ADP-ribose) polymerase 1 (PARP1), ATM, and DNA-dependent protein kinase (DNA-PK). If illegitimately repaired, such DSBs can seed the formation of genomic rearrangements like the TMPRSS2-ERG fusion oncogene in prostate cancer. Here, we hypothesize that these transcription-induced, TOP2B-mediated DSBs can also be exploited therapeutically and propose that, in hormone-dependent tumors like breast and prostate cancers, a hormone-cycling therapy, in combination with topoisomerase II poisons or inhibitors of the DNA repair components PARP1 and DNA-PK, could overwhelm cancer cells with transcription-associated DSBs. Such strategies may find particular utility in cancers, like prostate cancer, which show low proliferation rates, in which other chemotherapeutic strategies that target rapidly proliferating cells have had limited success. Clin Cancer Res; 17(12); 3858–64. ©2011 AACR.
Rheumatic disorders in Zimbabwe: a prospective analysis of patients attending a rheumatic diseases clinic.
Authors: M Stein, P Davis
Journal: Annals of the Rheumatic Diseases (1990)

The pattern of rheumatic disease in Africa differs from that in Europe and the United States and these differences may provide clues to its cause or pathogenesis. In a six month prospective analysis of 141 patients (83 female) attending a rheumatic diseases clinic rheumatoid arthritis was the commonest disorder, occurring in 49 patients. Twenty seven of the 49 (55%) were seropositive, 25 (51%) had erosive disease with rheumatoid nodules (13/49, 27%), and extra-articular complications (6/49, 12%), indicating a pattern of disease unlike the early reports from Africa. Systemic lupus erythematosus found in 18/141 (13%), gout in 12 (9%), ankylosing spondylitis in six (4%), and Reiter's syndrome in five (4%), in contrast with their rarity in previous reports from Africa, were not uncommon, whereas tropical polyarthritis was seldom diagnosed. The pattern of rheumatic disease in Harare, a large city, is changing to approximate more closely the pattern seen in developed countries.
Targeting p53 in Vivo: A First-in-Human Study With p53-Targeting Compound APR-246 in Refractory Hematologic Malignancies and Prostate Cancer
Authors: Sören Lehmann, Vladimir J.N. Bykov, Dina Ali, Ove Andrén, Honar Cherif, Ulf Tidefelt, Bertil Uggla, Jeffrey Yachnin, Gunnar Juliusson, Ali Moshfegh, Christer Paul, Klas G. Wiman, Per-Ola Andersson
Journal: Journal of Clinical Oncology (2012)

Purpose APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246. Patients and Methods APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg. Results MTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response. Conclusion We conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo.
Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease
Authors: M. Brodlie, M. C. McKean, G. E. Johnson, A. E. Anderson, C. M. U. Hilkens, A. J. Fisher, P. A. Corris, J. L. Lordan, C. Ward
Journal: European Respiratory Journal (2010)

Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells. Immunohistochemistry was performed on explanted CF lungs and compared with the non-suppurative condition pulmonary hypertension (PH). Airway lavages and epithelial cultures were generated from explanted CF lungs. Immunoreactivity for IL-17 was significantly increased in the lower airway epithelium in CF (median 14.1%) compared with PH (2.95%, p = 0.0001). The number of cells staining positive for IL-17 in the lower airway mucosa was also increased (64 cells·mm<sup>−1</sup> compared with 9 cells·mm<sup>−1</sup> basement membrane, p = 0.0005) and included both neutrophils in addition to mononuclear cells. IL-17 was detectable in airway lavages from explanted CF lungs. Treatment of epithelial cultures with IL-17 increased production of IL-8, IL-6 and granulocyte macrophage colony-stimulating factor. In conclusion, immunoreactive IL-17 is raised in the lower airway of people with CF and localises to both neutrophils and mononuclear cells. IL-17 increases production of pro-neutrophilic mediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.
Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma
Authors: Laura Pasqualucci, Mara Compagno, Jane Houldsworth, Stefano Monti, Adina Grunn, Subhadra V. Nandula, Jon C. Aster, Vundavally V. Murty, Margaret A. Shipp, Riccardo Dalla-Favera
Journal: The Journal of Experimental Medicine (2006)

PR domain containing 1 with zinc finger domain (PRDM1)/B lymphocyte–induced maturation protein 1 (BLIMP1) is a transcriptional repressor expressed in a subset of germinal center (GC) B cells and in all plasma cells, and required for terminal B cell differentiation. The BLIMP1 locus lies on chromosome 6q21-q22.1, a region frequently deleted in B cell lymphomas, suggesting that it may harbor a tumor suppressor gene. We report here that the BLIMP1 gene is inactivated by structural alterations in 24% (8 out of 34) activated B cell–like diffuse large cell lymphoma (ABC-DLBCL), but not in GC B cell–like (n = 0/37) or unclassified (n = 0/21) DLBCL. BLIMP1 alterations included gene truncations, nonsense mutations, frameshift deletions, and splice site mutations that generate aberrant transcripts encoding truncated BLIMP1 proteins. In all cases studied, both BLIMP1 alleles were inactivated by deletions or mutations. Furthermore, most non–GC type DLBCL cases (n = 20/26, 77%) lack BLIMP1 protein expression, despite the presence of BLIMP1 mRNA. These results indicate that a sizable fraction of ABC-DLBCL carry an inactive BLIMP1 gene, and suggest that the same gene is inactivated by epigenetic mechanisms in an additional large number of cases. These findings point to a role for BLIMP1 as a tumor suppressor gene, whose inactivation may contribute to lymphomagenesis by blocking post–GC differentiation of B cells toward plasma cells.
ASAS recommendations for variables to be collected in clinical trials/epidemiological studies of spondyloarthritis: Figure 1
Authors: Maxime Dougados, Jurgen Braun, Rubén Burgos Vargas, Laure Gossec, Walter Maksymowych, Joachim Sieper, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2012)

One of the major aims of the Assessment of SpondyloArthritis International Society (ASAS)is to facilitate/improve the conduct of clinical trials in the field of spondyloarthritis.1 Apart from the elaboration of classification and response criteria,2 3 ASAS has initiated actions in order to improve the conduct of clinical studies/trials.4 5 Based on the observation of a high interstudy variability in the collection of several data relevant to the field of spondyloarthritis, a previous initiative focused on the technique of collection of the information related …
Emerging lymphatic imaging technologies for mouse and man
Authors: Eva M. Sevick-Muraca, Sunkuk Kwon, John C. Rasmussen
Journal: Journal of Clinical Investigation (2014)

The lymphatic circulatory system has diverse functions in lipid absorption, fluid homeostasis, and immune surveillance and responds dynamically when presented with infection, inflammation, altered hemodynamics, and cancer. Visualization of these dynamic processes in human disease and animal models of disease is key to understanding the contributory role of the lymphatic circulatory system in disease and to devising effective therapeutic strategies. Longitudinal, non-destructive, and repeated imaging is necessary to expand our understanding of disease progression and regression in basic science and clinical investigations. Herein we summarize recent advances in in vivo lymphatic imaging employing magnetic resonance, computed tomography, lymphoscintigraphy, and emerging optical techniques with respect to their contributory roles in both basic science and clinical research investigations.
Can DCs forecast atherosclerosis?
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

![Graphic][1] 

Dendritic cells (green) are abundant in atherosclerosis-prone vessel regions. Atherosclerotic lesions are initiated mostly at vessel branch points and curvatures, where blood flow is irregular and inflammatory gene expression is high. Circulating blood cells—including
Newly identified loci that influence lipid concentrations and risk of coronary artery disease
Authors: Cristen J Willer, Serena Sanna, Anne U Jackson, Angelo Scuteri, Lori L Bonnycastle, Robert Clarke, Simon C Heath, Nicholas J Timpson, Samer S Najjar, Heather M Stringham, James Strait, William L Duren, Andrea Maschio, Fabio Busonero, Antonella Mulas, Giuseppe Albai, Amy J Swift, Mario A Morken, Narisu Narisu, Derrick Bennett, Sarah Parish, Haiqing Shen, Pilar Galan, Pierre Meneton, Serge Hercberg, Diana Zelenika, Wei-Min Chen, Yun Li, Laura J Scott, Paul A Scheet, Jouko Sundvall, Richard M Watanabe, Ramaiah Nagaraja, Shah Ebrahim, Debbie A Lawlor, Yoav Ben-Shlomo, George Davey-Smith, Alan R Shuldiner, Rory Collins, Richard N Bergman, Manuela Uda, Jaakko Tuomilehto, Antonio Cao, Francis S Collins, Edward Lakatta, G Mark Lathrop, Michael Boehnke, David Schlessinger, Karen L Mohlke, Gonçalo R Abecasis
Journal: Nature Genetics (2008)
A new transmyocardial degradable stent combined with growth factor, heparin, and stem cells in acute myocardial infarction
Authors: Y. Wang, X.-C. Liu, G.-W. Zhang, J. Zhao, J.-M. Zhang, R.-F. Shi, Y.-Z. Huang, C.-H. Zhao, T.-J. Liu, C.-X. Song, F. Lu, Q. Yang, G.-W. He
Journal: Cardiovascular Research (2009)

We developed a new method—transmyocardial drilling revascularization (TMDR) with absorbable stent incorporated with basic fibroblast growth factor (bFGF) and heparin. The present study tested the effect of this method with transplantation of bone marrow-derived stem cells (BMSCs) in acute myocardial infarction. Infarction was produced in mini-swine by ligating the left anterior descending (LAD) coronary artery. TMDR of 3.0 mm in diameter was made by mechanical drilling in the infarcted area. The animals that had LAD ligation were divided into six groups according to the procedures followed (n = 6 in each): control; T (TMDR); C (cell implantation); TS (TMDR+stent implantation); TC (TMDR+cell implantation); TSC (TMDR+stent implantation+cell implantation). Left ventricular (LV) function, myocardial perfusion, vascular density, and histological and morphological analyses were evaluated pre-operatively and at 30 min and 6 weeks post-operatively. Six weeks after operation, the above indices were significantly better in the TSC group than in other groups (P < 0.001 compared with the control group, and P < 0.05 or 0.01 compared with the TS and TC groups), although TS and TC also showed better results than the control group (P < 0.05). We have demonstrated in a pig model that an intramyocardial stent implanted with slow release of bFGF, heparin, and BMSC transplantation may significantly increase LV function, cardiac blood flow, and vascular density. Therefore, the present study may provide a new method for the surgical treatment of myocardial infarction.
Immunoglobulin Heavy Chain Variable Gene Usage and (Super)-antigen Drive in Chronic Lymphocytic Leukemia
Authors: Andreas Bühler, Thorsten Zenz, Stephan Stilgenbauer
Journal: Clinical Cancer Research (2010)

Increasing evidence supports the prognostic relevance of specific immunoglobulin heavy chain variable (IGHV) genes or stereotyped B-cell receptors (BCR) in chronic lymphocytic leukemia (CLL). The clonotypic BCRs differ in their specificity and affinity toward classical antigens and/or superantigens. The BCR-triggered mechanisms are distinct but could explain in part the different clinical behavior among CLL subgroups.
A Paradoxical Diurnal Movement Pattern in Obese Subjects With Type 2 Diabetes
Authors: Christian Bitz, Helle Harder, Arne Astrup
Journal: Diabetes Care (2005)

Observational studies have found an association between self-reported impaired sleep quality and subsequent risk of type 2 diabetes (1,2). In a German cohort of 4,140 men and 4,129 women (aged 25–74 years), sleeping difficulties were associated with higher risk of developing type 2 diabetes during the mean follow-up period of 7.5 years (1). In the Nurses Health Study (70,026 U.S. women aged 40–65), short sleep duration (≤5 h per day) was associated with risk of incidents of diabetes over a 10-year period (2). A few short-term trials have demonstrated that sleep restriction is associated with increased sympathoadrenal secretion of cortisol and catecholamines (3,4), decreased evening leptin, and increased ghrelin levels (5). Chronic increased sympathoadrenal activity may alter glucose homeostasis and induce insulin resistance. Thus, impaired sleep quality may act as a stress factor, stimulating appetite, promoting weight gain, and impairing glycemic control, with subsequent increased risk of type 2 diabetes.

The weakness of previous studies is the self-reporting of sleep quality and risk of confounding by associated traits. We measured movement during sleep in type 2 diabetic patients and control subjects by an objective technique and compared the sleep problems of obese subjects with type 2 diabetes with those of nondiabetic obese subjects.

Data from 24-h whole-body calorimetry measurements were used. All subjects in the type 2 diabetic group ( n = 31) were diagnosed according to …
The activities of uroporphyrinogen synthetase and cosynthetase in congenital erythropoietic porphyria (cep)
Authors: Ken Miyagi, Z. J. Petryka, Irene Bossenmaier, Ruth Cardinal, C. J. Watson
Journal: American Journal of Hematology (1976)

Abstract Normal or increased amounts of series III porphyrins with greater amounts of series I were observed on incubation of PBG in hemolysates of congenital erythropoietic porphyria vs. normal erythrocytes, human or bovine. Correlation with reticulocyte percentage was poor, in the aggregate a general trend toward increased values of both isomers I and III was noted with increasing reticulocytes. When the percent of type III was low the net amount was increased as compared with normal. Hemolysates of non‐porphyric, reticulocyte‐rich red cells (hemolytic or posthemorrhagic anemia) formed only minute amounts of type I porphyrin but at the same time no more, or even less type III than the porphyric hemolysates, although representing red cells of greater reticulocyte content. No evidence of deficient heme synthesis was observed in porphyric hemolysates incubated with [ 14 C] ‐porphobilinogen or 59 Fe. Other studies of porphyric hemolysates incubated with and without added mouse spleen synthetase failed to reveal evidence of an absolute UPG‐III cosynthetase (Co‐S) deficiency. The large increases of type I porphyrin with normal or increased formation of type III, both in the disease and in the hemolysates, are believed due to a primary increase of ALA‐S or UPG‐S activity rather than a decrease of Co‐S. Possible mutations which might be responsible for this increase are considered.
Effect of Combination Therapy With Fenofibrate and Simvastatin on Postprandial Lipemia in the ACCORD Lipid Trial
Authors: Gissette Reyes-Soffer, Colleen I. Ngai, Laura Lovato, Wahida Karmally, Rajasekhar Ramakrishnan, Stephen Holleran, Henry N. Ginsberg
Journal: Diabetes Care (2012)

The Action to Control Cardiovascular Risk in Diabetes lipid study (ACCORD Lipid), which compared the effects of simvastatin plus fenofibrate (FENO-S) versus simvastatin plus placebo (PL-S) on cardiovascular disease outcomes, measured only fasting triglyceride (TG) levels. We examined the effects of FENO-S on postprandial (PP) lipid and lipoprotein levels in a subgroup of ACCORD Lipid subjects.
A1.69 C1Q is absolutely required for disease development in experimental arthritis
Authors: Matthieu Ribon, Julie Mussard, Marina Botto, Marie-Christophe Boissier, Patrice Decker
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> The complement system is a major effector mechanism of both innate and adaptive immunity. It is activated in rheumatoid arthritis (RA) patients but the pathway involved remains unclear. RA is associated with the production of autoantibodies with some of them, anti-citrullinated peptide antibodies (ACPA), representing a diagnosis and even a prognosis marker. Antibodies are known to activate the complement system via the classical pathway in a C1q-dependent manner. But some models suggest C1q-independent pathways in arthritis. Therefore, we have investigated whether C1q is necessary for disease development in a mouse model of RA. <h3>Materials and Methods</h3> Disease development was followed in the collagen-induced arthritis (CIA) mouse model. The impact of C1q was evaluated by comparing wild-type (WT) mice and C1q-knockout (KO) true littermates. Arthritis was followed by clinical score evaluation. Inflammation and bone destruction were estimated by histology. Anti-collagen antibody, blood cytokine and C3a levels were measured by ELISA. B and T lymphocytes as well as neutrophils were analysed by flow cytometry. Osteoclastogenesis was analysed by culturing bone marrow cells with M-CSF and RANKL and then counting TRAP-positive multinucleated cells by microscopy. <h3>Results</h3> C1q is absolutely required for arthritis development in CIA as C1q-KO mice did not develop clinical signs of arthritis, although both WT and KO mice developed anti-collagen antibodies. Moreover, neither inflammation nor joint destruction were observed in C1q-KO mice. Surprisingly, no statistically significant difference was observed between WT and KO mice regarding the percentage or the activation of lymphocytes and neutrophils in the blood, spleen and lymph nodes. As a recent study suggested that C1q might influence osteoclastogenesis in vitro, we have shown that C1q deficiency does not alter osteoclast development in vivo in CIA mice. The impact of C1q on cytokine secretion and C3a production in vivo is currently being analysed. <h3>Conclusions</h3> C1q-KO mice are nearly completely protected from arthritis development and thus C1q plays a key role in the CIA model. This suggests that the classical pathway cannot be compensated by the alternative (or the lectin) pathway in this model. Our results strongly differ from those reported in the serum-transfer model where C1q is not necessary for disease development, suggesting that C1q might be involved at different steps, maybe before antibodies are produced, for example in the response to damage-associated molecular patterns (DAMP).