tbuckley/cabot-search huggingface dataset:
Sugar and spice, and testosterone
Authors: D Macauley
Journal: British Journal of Sports Medicine (1999)

Warm upWomen only.This was to be an issue devoted to women in sport, with our leaders and review articles written by women and focusing on issues of particular importance to women.It was not that simple.Battle lines are no longer drawn rigidly across sport and exercise medicine and some of our authors were ambivalent.There may be some issues about which women researchers have greater understanding but, for the most part, women authors wished to be recognised as experts in their field, irrespective of sex.Our intention was to address a perceived imbalance.Women researchers do not, however, wish to be treated as special, but as equal.We publish leaders from all parts of the country and from every discipline.Clearly, there are issues of particular importance to women, such as dysmenorrhoea (p227) and bone health (p228), but thermoregulation is one that may not come immediately to mind (p225).Lindy Castell takes a common sense approach to dietary supplements (p226) and, despite editorial eVorts for segregation of the sexes, Celia Brackenridge and Rod Jaques (p229) work together on a fascinating article on child abuse.The oral contracepon July 24,
AI-19 * CHEMOKINE RECEPTOR CXCR7 IS A FUNCTIONAL RECEPTOR FOR CXCL12 IN BRAIN ENDOTHELIAL CELLS
Authors: Y. Liu, E. Carson-Walter, K. Walter
Journal: Neuro-Oncology (2014)

The chemokine CXCL12 regulates multiple cell functions through its receptor, CXCR4. However, recent studies have shown that CXCL12 also binds a second receptor, CXCR7, to potentiate signal transduction and cell activity. In contrast to CXCL12/CXCR4, few studies have focused on the role of CXCR7 in vascular biology and its role in human brain microvascular endothelial cells (HBMECs) remains unclear. In this report, we used complementary methods, including immunocytofluorescence, Western blot, and flow cytometry analyses, to demonstrate that CXCR7 was expressed on HBMECs. We then employed short hairpin RNA (shRNA) technology to knockdown CXCR7 in HBMECs. Knockdown of CXCR7 in HBMECs attenuated phosphorylation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway in response to CXCL12, and resulted in significantly reduced HBMEC proliferation, tube formation, and migration, as well as adhesion to matrigel and tumor cells. Blocking CXCR7 with a specific antibody or small molecule antagonist similarly disrupted HBMEC binding to matrigel or tumor cells. We found that tumor necrosis factor (TNF)-a, induced CXCR7 in a time and dose-response manner and that this increase preceded an increase in vascular cell adhesion molecule-1 (VCAM-1). Knockdown of CXCR7 resulted in suppression of VCAM-1, suggesting that the reduced binding of CXCR7-knockdown HBMECs may result from suppression of VCAM-1. Collectively, CXCR7 acted as a functional receptor for CXCL12 in brain endothelial cells. Targeting CXCR7 in tumor vasculature may provide novel opportunities for improving brain tumor therapy.
Activation of Virus-specific Memory B Cells in the Absence of T Cell Help
Authors: Barbara J. Hebeis, Karin Klenovsek, Peter Rohwer, Uwe Ritter, Andrea Schneider, Michael Mach, Thomas H. Winkler
Journal: The Journal of Experimental Medicine (2004)

Humoral immunity is maintained by long-lived plasma cells, constitutively secreting antibodies, and nonsecreting resting memory B cells that are rapidly reactivated upon antigen encounter. The activation requirements for resting memory B cells, particularly the role of T helper cells, are unclear. To analyze the activation of memory B cells, mice were immunized with human cytomegalovirus, a complex human herpesvirus, and tick-born encephalitis virus, and a simple flavivirus. B cell populations devoid of Ig-secreting plasma cells were adoptively transferred into T and B cell–deficient RAG-1−/− mice. Antigenic stimulation 4–6 d after transfer of B cells resulted in rapid IgG production. The response was long lasting and strictly antigen specific, excluding polyclonal B cell activation. CD4+ T cells were not involved since (a) further depletion of CD4+ T cells in the recipient mice did not alter the antibody response and (b) recipient mice contained no detectable CD4+ T cells 90 d posttransfer. Memory B cells could not be activated by a soluble viral protein without T cell help. Transfer of memory B cells into immunocompetent animals indicated that presence of helper T cells did not enhance the memory B cell response. Therefore, our results indicate that activation of virus-specific memory B cells to secrete IgG is independent of cognate or bystander T cell help.
PSITTACOSIS
Authors: T. M. Rivers, G. P. Berry
Journal: The Journal of Experimental Medicine (1931)

1. Rabbits and guinea pigs are susceptible to psittacosis virus introduced intracerebrally. By means of brain to brain passages in these animals the active agent is capable of propagation indefinitely. 2. Serial passages of the virus through rabbits and guinea pigs do not cause the active agent to lose its pathogenicity for parrots and mice. 3. The chief clinical evidences of infection in rabbits and guinea pigs following intracranial inoculation of the virus are fever and loss of weight. The pathological changes are characterized by a mild meningo-encephalitis, and fatty degeneration, focal necrosis, and infarction of the liver. 4. Rabbits upon recovery from an attack of psittacosis are actively immune. 5. Two strains of virus, human and parrot, were found to be immunologically similar. 6. No evidence was obtained to show that human convalescent serum possesses an appreciable amount of neutralizing substances.
Biomarkers of cardiovascular disease risk in 40-65-year-old men performing recommended levels of physical activity, compared with sedentary men
Authors: G M Perkins, A Owen, E M Kearney, I L Swaine
Journal: British Journal of Sports Medicine (2008)

Objective: Both the UK Department of Health and the US Centers for Disease Control and Prevention have recommended at least 30 minutes of moderate-intensity physical activity on most days for health. Specific mention is made of beneficial effects upon blood lipids. The purpose of this study was to compare biomarkers of cardiovascular disease risk in men who perform physical activity in accordance with these recommendations with those who do not. Methods: 128 healthy men, aged 40–65 years, were recruited. 61 were classified as active (performing at least the minimum recommended physical activity of ⩾4 metabolic equivalents (METs), for 6 months immediately before the study) and 67 as sedentary. Fasting blood was drawn for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoproteins (Apo) A-1 and B. Low-density lipoprotein cholesterol (LDL-C) was estimated using the Friedewald equation. Results: The median (interquartile range) physical activity level was 7.0 (5.0–10.7) versus 1.0 (0–1.8) hour/week at ⩾4 METs (active versus sedentary; p&lt;0.001). Apo A-1 was higher in the active men (p = 0.032). No significant differences were found for TC, HDL-C, LDL-C, TC:HDL-C, triglycerides, Apo B, or the Apo B:A-1 ratio. Conclusions: These findings suggest that physical activity performed according to the recommendations used in this study favourably influenced Apo A-1. The finding that cholesterol and triglycerides were not different in men achieving the recommended physical activity levels compared with sedentary men contradicts some of the claims made within the published recommendations. However, intervention studies are needed to clarify these preliminary findings.
Prospective two year follow up study comparing novel and conventional imaging procedures in patients with arthritic finger joints
Authors: M Backhaus
Journal: Annals of the Rheumatic Diseases (2002)

To carry out a prospective two year follow up study comparing conventional radiography, three-phase bone scintigraphy, ultrasonography (US), and three dimensional (3D) magnetic resonance imaging (MRI) with precontrast and dynamic postcontrast examination in detecting early arthritis. The aim of the follow up study was to monitor the course of erosions during treatment with disease modifying antirheumatic drugs by different modalities and to determine whether the radiographically occult changes like erosive bone lesions of the finger joints detected by MRI and US in the initial study would show up on conventional radiographs two years later. Additionally, to study the course of soft tissue lesions depicted in the initial study in comparison with the clinical findings.The metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints (14 joints) of the clinically more severely affected hand (soft tissue swelling and joint tenderness) as determined in the initial study of 49 patients with various forms of arthritis were examined twice. The patients had initially been divided into two groups. The follow up group I included 28 subjects (392 joints) without radiographic signs of destructive arthritis (Larsen grades 0-1) of the investigated hand and wrist, and group II (control group) included 21 patients (294 joints) with radiographs showing erosions (Larsen grade 2) of the investigated hand or wrist, or both, at the initial examination.(1) Radiography at the two year follow up detected only two erosions (two patients) in group I and 10 (nine patients) additional erosions in group II. Initial MRI had already detected both erosions in group I and seven (seven patients) of the 10 erosions in group II. Initial US had depicted one erosion in group I and four of the 10 erosions in group II. (2) In contrast with conventional radiography, 3D MRI and US demonstrated an increase in erosions in comparison with the initial investigation. (3) The abnormal findings detected by scintigraphy were decreased at the two year follow up. (4) Both groups showed a marked clinical improvement of synovitis and tenosynovitis, as also shown by MRI and US. (5) There was a striking discrepancy between the decrease in the soft tissue lesions as demonstrated by clinical findings, MRI, and US, and the significant increase in erosive bone lesions, which were primarily evident at MRI and US.Despite clinical improvement and a regression of inflammatory soft tissue lesions, erosive bone lesions were increased at the two year follow up, which were more pronounced with 3D MRI and less pronounced with US. The results of our study suggest that owing to the inadequate depiction of erosions and soft tissue lesions, conventional radiography alone has limitations in the intermediate term follow up of treatment. US has a high sensitivity for depicting inflammatory soft tissue lesions, but dynamic 3D MRI is more sensitive in differentiating minute erosions.
Sex Steroids Affect Triglyceride Handling, Glucose-Dependent Insulinotropic Polypeptide, and Insulin Sensitivity
Authors: Bruno Lapauw, Margriet Ouwens, Leen M. ′t Hart, Birgitte Wuyts, Jens J. Holst, Guy T'Sjoen, Jean-Marc Kaufman, Johannes B. Ruige
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate metabolic effects of sex steroids in nonfasting and fasting conditions, independent from changes in body composition. RESEARCH DESIGN AND METHODS A randomized clinical trial was performed to create contrasting sex steroid levels in healthy young men: by letrozole (aromatase inhibitor) to lower estradiol (E2) and increase testosterone (group T, n = 10) versus letrozole plus E2 patches to lower T and raise E2 (group E, n = 10). Mixed meals and hyperinsulinemic-euglycemic clamps were performed before and after a 1-week treatment period. RESULTS Following intervention, the postprandial triglyceride response displayed a diverging response with a decline in group T and an increase in group E; the postprandial glucose-dependent insulinotropic polypeptide (GIP) response increased in group T. Insulin sensitivity increased in group T but remained unaltered in group E. CONCLUSIONS In healthy young men, short-term changes in sex steroids affect postprandial triglyceride and GIP response and insulin sensitivity.
Telomere Length in Peripheral Blood Leukocytes and Lung Cancer Risk: A Large Case–Control Study in Caucasians
Authors: Beatriz Sanchez-Espiridion, Meng Chen, Joe Y. Chang, Charles Lu, David W. Chang, Jack A. Roth, Xifeng Wu, Jian Gu
Journal: Cancer Research (2014)

Telomere dysfunction is a crucial event in malignant transformation and tumorigenesis. Telomere length in peripheral blood leukocytes has been associated with lung cancer risk, but the relationship has remained controversial. In this study, we investigated whether the association might be confounded by study of different histological subtypes of lung cancer. We measured relative telomere lengths in patients in a large case-control study of lung cancer and performed stratified analyses according to the two major histologic subtypes [adenocarcinoma and squamous cell carcinoma (SCC)]. Notably, patients with adenocarcinoma had longer telomeres than controls, whereas patients with SCC had shorter telomeres compared with controls. Long telomeres were associated with increased risk of adenocarcinoma, with the highest risk associated with female sex, younger age (<60 years), and lighter smoking (<30 pack-years). In contrast, long telomeres were protective against SCC, particularly in male patients. Our results extend the concept that telomere length affects risk of lung cancer in a manner that differs with histologic subtype.
Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 “Gatekeeper” F691L Mutation with PLX3397
Authors: Catherine C. Smith, Chao Zhang, Kimberly C. Lin, Elisabeth A. Lasater, Ying Zhang, Evan Massi, Lauren E. Damon, Matthew Pendleton, Ali Bashir, Robert Sebra, Alexander Perl, Andrew Kasarskis, Rafe Shellooe, Garson Tsang, Heidi Carias, Ben Powell, Elizabeth A. Burton, Bernice Matusow, Jiazhong Zhang, Wayne Spevak, Prabha N. Ibrahim, Mai H. Le, Henry H. Hsu, Gaston Habets, Brian L. West, Gideon Bollag, Neil P. Shah
Journal: Cancer Discovery (2015)

Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKI) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase "gatekeeper" residues, which control access to an allosteric pocket adjacent to the ATP-binding site, has been frequently implicated in TKI resistance. The molecular underpinnings of gatekeeper mutation-mediated resistance are incompletely understood. We report the first cocrystal structure of FLT3 with the TKI quizartinib, which demonstrates that quizartinib binding relies on essential edge-to-face aromatic interactions with the gatekeeper F691 residue, and F830 within the highly conserved Asp-Phe-Gly motif in the activation loop. This reliance makes quizartinib critically vulnerable to gatekeeper and activation loop substitutions while minimizing the impact of mutations elsewhere. Moreover, we identify PLX3397, a novel FLT3 inhibitor that retains activity against the F691L mutant due to a binding mode that depends less vitally on specific interactions with the gatekeeper position.We report the first cocrystal structure of FLT3 with a kinase inhibitor, elucidating the structural mechanism of resistance due to the gatekeeper F691L mutation. PLX3397 is a novel FLT3 inhibitor with in vitro activity against this mutation but is vulnerable to kinase domain mutations in the FLT3 activation loop.
Reconstructive Surgery of the Esophagus: M K Ferguson. Futura Publishing, 2001, $105, pp 344. ISBN 0-87993-494-8
Authors: A Watson
Journal: Gut (2003)

Osteoporosis and liver disease: additional reasons for coeliac disease screeningWe read with great interest the recently published guidelines on the management of osteoporosis associated with chronic liver disease (Gut 2002;50(suppl I):i1-9).However, we would like to add a few words of comment.Associations between coeliac disease (CD) and primary biliary cirrhosis in particular and other autoimmune liver diseases in general have been reported. [1]2][3] In addition, it has been suggested that these individuals should be considered as an at risk group for whom serological testing for CD is indicated. 1Patients with CD are at high risk of developing low bone mineral density and bone turnover impairment, 1 and it has been shown that adherence to a gluten free diet has a significant positive impact on these parameters. 4 Thus we suggest that physicians caring for patients with the above mentioned liver diseases should screen them for CD in the presence of signs and symptoms suggestive of malabsorption such as osteoporosis.This seems a reasonable strategy as detection of CD will allow for a more rational therapeutic approach to the risks determined by this association.Complications due to the presence of CD, such as malnutrition, anaemia, and osteoporosis, may have a considerable impact on liver disease management and the need/success of transplantation.
Self-management Education by Group Care Reduces Cardiovascular Risk in Patients With Type 2 Diabetes: Analysis of the ROMEO Clinical Trial
Authors: Jacopo Sicuro, Lorena Charrier, Paola Berchialla, Franco Cavallo, Stefano Merlo, Aurora Mazzeo, Massimo Porta, Marina Trento
Journal: Diabetes Care (2014)

Treatment of type 2 diabetes includes lifestyle and pharmacological interventions. Drugs are marginally effective in achieving glycemic targets and reducing cardiovascular (CV) events, whereas intervention on lipids, blood pressure, and lifestyle is more effective. Rethink Organisation to iMprove Education and Outcomes (ROMEO) (ISRCTN19509463), a 4-year multicenter randomized trial, showed that patients with type 2 diabetes on group care (GC), a previously described systemic self-management education model, improved body weight, HbA1c, HDL and LDL cholesterol, blood pressure, quality of life, and health behaviors, compared with patients on usual care and similar pharmacological treatment (1). The ROMEO data set was fed into three risk engines, Framingham (2), UK Prospective Diabetes Study (UKPDS) (3), and CUORE (4), to verify if GC modifies CV risk scores.

A total of 815 non-insulin–treated patients aged <80 years were allocated to either GC or traditional care (controls). Risk calculations were performed at baseline and throughout the 4 years of the trial in 466 patients (257 on GC and 209 controls) who completed ROMEO. Reasons for dropping out were reported (5), and …
The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis
Authors: Thomas Müller, Bart van de Sluis, Alexandra Zhernakova, Ellen van Binsbergen, Andreas R. Janecke, Ashish Bavdekar, Anand Pandit, Helga Weirich-Schwaiger, Heiko Witt, Helmut Ellemunter, Johann Deutsch, Helmut Denk, Wilfried Müller, Irmin Sternlieb, M.Stuart Tanner, Cisca Wijmenga
Journal: Journal of Hepatology (2003)
Infusion of iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis.
Authors: N J McHugh, M Csuka, H Watson, G Belcher, A Amadi, E F Ring, C M Black, P J Maddison
Journal: Annals of the Rheumatic Diseases (1988)

Iloprost, a stable prostacyclin analogue, was given by intravenous infusion to 29 patients with severe Raynaud9s phenomenon, 26 of whom had systemic sclerosis (SS), and compared with placebo infusion in a double blind crossover trial. Iloprost significantly lessened the number and the severity of attacks compared with placebo. Nine patients expressed a preference for effectiveness of treatment, eight of these in favour of Iloprost. Thermography failed to show any long term effect of Iloprost. Side effects of headache, flushing, nausea, and vomiting were common, and the inconvenience of intravenous administration may limit its routine use.
Independent validation of the antiphospholipid score for the diagnosis of antiphospholipid syndrome
Authors: Savino Sciascia, Maria Laura Bertolaccini, Dario Roccatello, Munther A Khamashta
Journal: Annals of the Rheumatic Diseases (2012)

Antiphospholipid syndrome (APS) is a heterogeneous entity with a wide variation in clinical course and laboratory profile. It is accepted that the presence of antiphospholipid antibodies (aPL) confers a higher risk for both thrombosis and pregnancy morbidity, but quantifying such a risk is still a challenge. As a consequence, clinicians are unable to tailor the treatment according to the risk.

Recently, Otomo et al 1 developed and validated the so-called ‘antiphospholipid score’ (aPL-S) by testing multiple aPL and evaluating the aPL-S efficacy for the diagnosis of APS and predictive value for thrombosis. This score was shown to be a useful quantitative index for diagnosing APS and to be valuable as a predictive marker for thrombosis in autoimmune diseases.

In order to independently validate the …
Dermoscopy of cutaneous leishmaniasis
Authors: A. Llambrich, P. Zaballos, F. Terrasa, I. Torne, S. Puig, J. Malvehy
Journal: British Journal of Dermatology (2008)

Dermoscopy has been proposed as a diagnostic tool in the case of skin infections and parasitosis but no specific dermoscopic criteria have been described for cutaneous leishmaniasis (CL).To describe the dermoscopic features of CL.Dermoscopic examination (using the DermLite Foto; 3Gen, LLC, Dana Point, CA, U.S.A.) of 26 CL lesions was performed to evaluate specific dermoscopic criteria.We observed the following dermoscopic features: generalized erythema (100%), 'yellow tears' (53%), hyperkeratosis (50%), central erosion/ulceration (46%), erosion/ulceration associated with hyperkeratosis (38%) and 'white starburst-like pattern' (38%). Interestingly, at least one vascular structure described in skin neoplasms was observed in all cases: comma-shaped vessels (73%), linear irregular vessels (57%), dotted vessels (53%), polymorphous/atypical vessels (26%), hairpin vessels (19%), arborizing telangiectasia (11%), corkscrew vessels (7%) and glomerular-like vessels (7%). Combination of two or more different types of vascular structures was present in 23 of 26 CL lesions (88%), with a combination of two vascular structures in 13 cases (50%) and three or more in 10 cases (38%).Characteristic dermoscopic structures have been identified in CL. Important vascular patterns seen in melanocytic and nonmelanocytic tumours are frequently observed in this infection.