tbuckley/cabot-search huggingface dataset:
Mechanisms of Action of Troglitazone in the Prevention of High Glucose–Induced Migration and Proliferation of Cultured Coronary Smooth Muscle Cells
Authors: Kenichi Yasunari, Masakazu Kohno, Hiroaki Kano, Koji Yokokawa, Mieko Minami, Junichi Yoshikawa
Journal: Circulation Research (1997)

Abstract Recent findings suggest that high glucose levels may promote atherosclerosis in coronary vascular smooth muscle cells (VSMCs). To explore the intracellular mechanisms of action by which troglitazone affects this process, we examined the effect of troglitazone on the migration and growth characteristics of cultured rabbit coronary VSMCs. Treatment with chronic high glucose medium (22.2 mmol/L) for 5 days increased VSMC migration by 92%, [ 3 H]thymidine incorporation by 135%, and cell number by 32% compared with VSMCs treated with normal glucose (5.5 mmol/L glucose+16.6 mmol/L mannose) medium. Troglitazone at 100 nmol/L and 1 μmol/L significantly suppressed high glucose–induced VSMC migration by 34% and 42%, respectively, the proliferative effect (as measured by cell number) by 17% and 27%, and [ 3 H]thymidine incorporation by 45% and 60% (n=6, P &lt;.05). The high glucose–induced impairment of insulin-mediated [ 3 H]deoxyglucose uptake was blocked by a protein kinase C (PKC) inhibitor (calphostin C, 1 μmol/L) and was also improved by troglitazone without any change in insulin receptor number and affinity. The high glucose–induced insulin-mediated increase in cell number and in [ 3 H]thymidine incorporation was suppressed by troglitazone. Troglitazone (1 μmol/L) also suppressed high glucose–induced phospholipase D activation, elevation of the cytosolic NADH/NAD + ratio (as measured by the cytosolic ratio of lactate/pyruvate), and membrane-bound PKC activation. Flow cytometric DNA histogram analysis of cell cycle stage showed that high glucose–induced increase in the percentage of cells in the S phase was suppressed by 1 μmol/L troglitazone. These findings suggest that PKC may be a link between impairment of insulin-mediated glucose uptake and the increase in migration and proliferation induced by high glucose levels and that troglitazone may be clinically useful for the treatment of high glucose–induced coronary atherosclerosis.
The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston–Leeds Osteoarthritis Knee Score)
Authors: D J Hunter, G H Lo, D Gale, A J Grainger, A Guermazi, P G Conaghan
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Aim:</h3> MRI provides unparalleled visualisation of all the anatomical structures involved in the osteoarthritis (OA) process. There is a need for reliable methods of quantifying abnormalities of these structures. The aim of this work was to assess the reliability of a novel MRI scoring system for evaluating OA of the knee and explore the validity of the bone marrow lesion (BML) scoring component of this new tool. <h3>Methods:</h3> After review of the relevant literature, a collaborative group of rheumatologists and radiologists from centres in the UK and USA established preliminary anatomical divisions, items (necessarily broadly inclusive) and scaling for a novel semi-quantitative knee score. A series of iterative reliability exercises were performed to reduce the initial items, and the reliability of the resultant Boston–Leeds Osteoarthritis Knee Score (BLOKS) was examined. A further sample had both the BLOKS and WORMS (Whole Organ MRI Score) bone marrow lesion (BML) score performed to assess the construct validity (relation to knee pain) and longitudinal validity (prediction of cartilage loss) of each scoring method. <h3>Results:</h3> The BLOKS scoring method assesses nine intra-articular regions and contains eight items, including features of bone marrow lesions, cartilage, osteophytes, synovitis, effusions and ligaments. The scaling for each feature ranges from 0–3. The inter-reader reliability for the final BLOKS items ranged from 0.51 for meniscal extrusion up to 0.79 for meniscal tear. The reliability for other key features was 0.72 for BML grade, 0.72 for cartilage morphology, and 0.62 for synovitis. Maximal BML size on the BLOKS scale had a positive linear relation with visual analogue scale (VAS) pain, however the WORMS scale did not. Baseline BML was associated with cartilage loss on both BLOKS and WORMS scale. This association was stronger for BLOKS than WORMS. <h3>Conclusion:</h3> We have designed a novel scoring system for MRI OA knee, BLOKS, that demonstrates good reliability. Preliminary inspection of the validity of one of the components of this new tool supports the validity of the BLOKS BML scoring method over an existing instrument. Further iterative development will include validation for use in both clinical trials and epidemiological studies.
Abnormal mucus in cap polyposis
Authors: M P Buisine, J F Colombel, M Lecomte-Houcke, P Gower, J P Aubert, N Porchet, A Janin
Journal: Gut (1998)

Background —Cap polyposis is a rare disease characterised by mucoid and bloody diarrhoea, with polyps covered by a cap of mucoid and fibrinopurulent exudate. The pathogenesis is not known. Aims —To pour some light on cap polyposis pathogenesis, by examining the mucus of patients and analysing the expression of five mucin genes, MUC2 , MUC3 , MUC4 , MUC5AC , and MUC5B . Patient and methods —The study was performed on biopsy specimens taken from a patient with recurrent cap polyposis. Histochemical examination, electron microscopy, and mRNA in situ hybridisation were used. Results —The mucus of cap polyposis differed in three respects from that of normal adult colon: abnormal ultrastructure of the mucus in the goblet cells, predominance of non-sulphated mucins, abnormal expression of the MUC4 , MUC3 , and MUC5AC genes. Conclusions —Most of these abnormalities have been reported for other pathological situations, suggesting that the abnormalities observed in the mucus of this patient with cap polyposis are probably secondary phenomena rather than primary. However, the mucin abnormalities detected, which reflect deregulation of the expression of three apomucin genes, abnormal glycosylation, and abnormalities of the secretion process, are also probably involved in the clinical manifestations of cap polyposis.
Circadian effects on the acute responses of salivary cortisol and IgA in well trained swimmers
Authors: L Dimitriou, N C C Sharp, M Doherty
Journal: British Journal of Sports Medicine (2002)

To examine whether time of day significantly affects salivary cortisol and IgA levels before and after submaximal swimming.Fourteen male competitive swimmers (mean (SD) age 18 (3.2) years) volunteered to participate in the study. In a fully randomised, cross over design, each subject performed 5 x 400 m front crawl at 85 (1.2)% of their seasonal best time (277 (16) seconds), with one minute rest between each 400 m, at 0600 and 1800 hours on two separate days. Timed, unstimulated saliva samples were collected before and after exercise. Saliva samples were analysed for cortisol and IgA by radioimmunoassay and single radial immunodiffusion respectively.Significant time of day effects (am and pm respectively) were observed in IgA concentration (0.396 (0.179) v 0.322 (0.105) mg/ml, p<0.05), IgA secretory rate (0.109 (0.081) v 0.144 (0.083) mg/min, p<0.01), and saliva flow rate (0.31 (0.23) v 0.46 (0.22) ml/min, p<0.001) before exercise (all values mean (SD)). Differences in cortisol levels before exercise (1.09 (0.56) v 0.67 (0.94) microg/dl) approached significance (p = 0.059). The exercise protocol did not significantly affect IgA concentration and secretory rate (p>0.05) but, in comparison with values before exercise, caused significant alterations in cortisol (p<0.01) and saliva flow rate (p<0.01). There was no significant interaction effect of time of day by exercise on any salivary variables measured (p>0.05). However, most of the values of the salivary variables before exercise were significantly inversely related to their exercise induced response (p<0.05).These results suggest a significant circadian variation in the variables measured before exercise, without showing a significant effect on their acute responses to exercise.
Glomerular Epithelial Stem Cells
Authors: Laura Lasagni, Paola Romagnani
Journal: Journal of the American Society of Nephrology (2010)

Global glomerulosclerosis with loss of podocytes in humans is typical of end-stage renal pathology. Although mature podocytes are highly differentiated and nondividing, converging evidence from experimental and clinical data suggests adult stem cells within Bowman's capsule can rescue some of this loss. Glomerular epithelial stem cells generate podocytes during kidney growth and regenerate podocytes after injury, thus explaining why various glomerular disorders undergo remission occasionally. This regenerative process, however, is often inadequate because of inefficient proliferative responses by glomerular epithelial stem cells with aging or in the setting of focal segmental glomerulosclerosis. Alternatively, an excessive proliferative response by glomerular epithelial stem cells after podocyte injury can generate new lesions such as extracapillary crescentic glomerulonephritis, collapsing glomerulopathy and tip lesions. Better understanding of the mechanisms that regulate growth and differentiation of glomerular epithelial stem cells may provide new clues for prevention and treatment of glomerulosclerosis.
Purine-Rich Foods, Dairy and Protein Intake, and the Risk of Gout in Men
Authors: Hyon K. Choi, Karen Atkinson, Elizabeth W. Karlson, Walter Willett, Gary Curhan
Journal: New England Journal of Medicine (2004)

Various purine-rich foods and high protein intake have long been thought to be risk factors for gout. Similarly, the possibility that the consumption of dairy products has a role in protecting against gout has been raised by metabolic studies. We prospectively investigated the association of these dietary factors with new cases of gout.
American Society of Clinical Oncology Technology Assessment of Pharmacologic Interventions for Breast Cancer Risk Reduction Including Tamoxifen, Raloxifene, and Aromatase Inhibition
Authors: Rowan T. Chlebowski, Nananda Col, Eric P. Winer, Deborah E. Collyar, Steven R. Cummings, Victor G. Vogel, Harold J. Burstein, Andrea Eisen, Isaac Lipkus, David G. Pfister
Journal: Journal of Clinical Oncology (2002)

OBJECTIVE: To update an evidence-based technology assessment of chemoprevention strategies for breast cancer risk reduction. POTENTIAL INTERVENTIONS: Tamoxifen, raloxifene, aromatase inhibition, and fenretinide. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer–specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO) prescribed technology assessment procedure was followed. VALUES: More weight was given to published randomized trials. BENEFITS/HARMS: A woman’s decision regarding breast cancer risk reduction strategies is complex and will depend on the importance and weight attributed to information regarding both cancer- and noncancer-related risks and benefits. CONCLUSIONS: For women with a defined 5-year projected breast cancer risk of ≥ 1.66%, tamoxifen (at 20 mg/d for 5 years) may be offered to reduce their risk. Risk/benefit models suggest that greatest clinical benefit with least side effects is derived from use of tamoxifen in younger (premenopausal) women (who are less likely to have thromboembolic sequelae and uterine cancer), women without a uterus, and women at higher breast cancer risk. Data do not as yet suggest that tamoxifen provides an overall health benefit or increases survival. In all circumstances, tamoxifen use should be discussed as part of an informed decision-making process with careful consideration of individually calculated risks and benefits. Use of tamoxifen combined with hormone replacement therapy or use of raloxifene, any aromatase inhibitor or inactivator, or fenretinide to lower the risk of developing breast cancer is not recommended outside of a clinical trial setting. This technology assessment represents an ongoing process and recommendations will be updated in a timely matter. VALIDATION: The conclusions were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors. SPONSOR: American Society of Clinical Oncology.
NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal -defensin expression
Authors: J. Wehkamp, J. Harder, M. Weichenthal, M. Schwab, E. Schäffeler, M. Schlee, K. R. Herrlinger, A. Stallmach, F. Noack, P. Fritz, J. M. Schröder, Charles L Bevins, K. Fellermann, E. F. Stange
Journal: Gut (2004)

<b>Background:</b> Mutations in NOD2, a putative intracellular receptor for bacterial peptidoglycans, are associated with a subset of Crohn's disease but the molecular mechanism linking this protein with the disease pathogenesis remains unclear. Human α defensins (HD-5 and HD-6) are antibiotic effector molecules predominantly expressed in Paneth cells of the ileum. Paneth cells also express NOD2. To address the hypothesis that the function of NOD2 may affect expression of Paneth cell defensins, we compared their expression levels with respect to NOD2 mutations in Crohn's disease. <b>Methods:</b> Forty five Crohn's disease patients (24 with NOD2 mutations, 21 with wild-type NOD2) and 12 controls were studied. Real time reverse transcription-polymerase chain reaction was performed with mucosal mRNA for HD-5, HD-6, lysozyme, secretory phospholipase A<sub>2</sub> (sPLA<sub>2</sub>), tumour necrosis factor α, interleukin 8, and human hypoxanthine phosphoribosyltransferase (housekeeping gene). Immunohistochemistry with anti-HD-5 and histological Paneth cell staining were performed in 10 patients with NOD2 mutations or wild-type genotypes. <b>Results:</b> Ileal expression of HD-5 and HD-6, but not sPLA<sub>2</sub> or lysozyme, were diminished in affected ileum, and the decrease was significantly more pronounced in patients with NOD2 mutations. In the colon, HD-5, HD-6, and sPLA<sub>2</sub> were increased during inflammation in wild-type but not in NOD2 mutated patients. In both the colon and ileum, proinflammatory cytokines and lysozyme were unaffected by NOD2 status. Immunohistochemistry identified Paneth cells as the sole source of HD-5. <b>Conclusion:</b> As alpha defensins are important in the mucosal antibacterial barrier, their diminished expression may explain, in part, the bacterial induced mucosal inflammation and ileal involvement of Crohn's disease, especially in the case of NOD2 mutations.
Polycystic Kidney Disease
Authors: Peter C. Harris, Vicente E. Torres
Journal: Annual Review of Medicine (2008)

A number of inherited disorders result in renal cyst development. The most common form, autosomal dominant polycystic kidney disease (ADPKD), is a disorder most often diagnosed in adults and caused by mutation in PKD1 or PKD2. The PKD1 protein, polycystin-1, is a large receptor-like protein, whereas polycystin-2 is a transient receptor potential channel. The polycystin complex localizes to primary cilia and may act as a mechanosensor essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract. Elucidation of defective cellular processes has highlighted potential therapies, some of which are now being tested in clinical trials. ARPKD is the neonatal form of PKD and is associated with enlarged kidneys and biliary dysgenesis. The disease phenotype is highly variable, ranging from neonatal death to later presentation with minimal kidney disease. ARPKD is caused by mutation in PKHD1, and two truncating mutations are associated with neonatal lethality. The ARPKD protein, fibrocystin, is localized to cilia/basal body and complexes with polycystin-2. Rare, syndromic forms of PKD also include defects of the eye, central nervous system, digits, and/or neural tube and highlight the role of cilia and pathways such as Wnt and Hh in their pathogenesis.
Antibodies against Pseudomonas aeruginosa in patients with bronchiectasis: helpful or harmful?
Authors: N HOIBY
Journal: Thorax (2001)

The measurement of antibodies against pathogens is mainly done for diagnostic purposes in order to detect the aetiology of infections or to confirm that protection following vaccination is present against a certain disease.

In some diseases such as chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis antibodies induced by the infection obviously do not offer any protection against the infection. On the contrary, high and rapidly increasing levels of antibodies are correlated with a poor prognosis.1 The reason for this is that immune elimination is not mediated by the antibody response because the alginate producing bacteria which are so characteristic of this disease grow as biofilms in the bronchioles.2 The biofilm mode of growth is an ancient survival strategy developed by bacteria living in the environment to exploit the micro-milieu of nutrients on surfaces and to avoid being killed by amoeba and toxic …
The IOC Centres of Excellence bring prevention to Sports Medicine
Authors: Lars Engebretsen, Roald Bahr, Jill L Cook, Wayne Derman, Carolyn A Emery, Caroline F Finch, Willem H Meeuwisse, Martin Schwellnus, Kathrin Steffen
Journal: British Journal of Sports Medicine (2014)

The protection of an athlete's health and preventing injuries and illnesses in sport are top priorities for the IOC and its Medical Commission. The IOC therefore partners with selected research centres around the world and supports research in the field of sports medicine. This has enabled the IOC to develop an international network of expert scientists and clinicians in sports injury and disease prevention research. The IOC wants to promote injury and disease prevention and the improvement of physical health of the athlete by: (1) establishing long-term research programmes on injury and disease prevention (including studies on basic epidemiology, risk factors, injury mechanisms and intervention), (2) fostering collaborative relationships with individuals, institutions and organisations to improve athletes' health, (3) implementing and collaborating with applied, ongoing and novel research and development within the framework and long-term strategy of the IOC and (4) setting up knowledge translation mechanisms to share scientific research results with the field throughout the Olympic Movement and sports community and converting these results into concrete actions to protect the health of the athletes. In 2009, the IOC also identified four research centres that had an established track record in research, educational and clinical activities to achieve these ambitions: (1) the Australian Centre for Research into Injury in Sport and its Prevention (ACRISP), Australia; (2) the Sport Injury Prevention Research Centre (SIPRC), Canada; (3) the Clinical Sport and Exercise Medicine Research (CSEM), South Africa and (4) the Oslo Sports Trauma Research Center (OSTRC), Norway. This paper highlights the work carried out by these four IOC Centres of Excellence over the past 6 years and their contribution to the world of sports medicine.
Molecular Pathogenesis and Diagnostics of Bladder Cancer
Authors: Anirban P. Mitra, Richard J. Cote
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Despite elaborate characterization of the risk factors, bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. Urothelial carcinoma is now recognized as a disease of alterations in several cellular processes. The more prevalent, less aggressive, recurrent, noninvasive tumors are characterized by constitutive activation of the Ras-MAPK pathway. The less common but more aggressive invasive tumors, which have a higher mortality rate, are characterized by alterations in the p53 and retinoblastoma pathways. Several diagnostic tests have attempted to identify these molecular alterations in tumor cells exfoliated in the urine, whereas prognostic tests have tried to identify aberrations so as to predict tumor behavior and identify therapeutic targets. The future of bladder cancer patient management will rely on the use of molecular tests to reliably diagnose the presence of disease, predict individual tumor behavior, and suggest potential targeted therapeutics.
Combination Effect of Recombinant Human Interleukin 1α with Antitumor Drugs on Syngeneic Tumors in Mice
Authors: Shinichi Nakamura, Shigeki Kashimoto, Fumie Kajikawa, Katsuhisa Nakata
Journal: Cancer Research (1991)

To investigate the combination effects of recombinant human interleukin 1α (rHu IL-1α) and antitumor drugs, groups of 7 mice bearing syngeneic tumors (Meth A sarcoma in BALB/c mice and colon 26 adenocarcinoma in BALB/c × DBA/2 F1 mice) were treated i.v. with the antitumor drugs according to the early (once daily on days 1, 4, 7, 10, and 13) and/or late (once daily on days 7, 10, 13, 16, and 19) medication schedules in combination with rHu IL-1α administered i.m. at various timings (1 day before, concurrently with, and 1 day after every drug administration). Inhibition rates of the antitumor drugs (mitomycin C, doxorubicin, cisplatin, cyclophosphamide, and 5-fluorouracil) for both the murine tumors were more or less raised by coadministration of rHu IL-1α irrespective of medication schedules and combination timings. After both early and late treatments with the optimal combinations of rHu IL-1α (0.1–3 μg/mouse) and cisplatin (2–4 mg/kg) and by the late treatment with the optimal combinations of rHu IL-1α (0.3–3 μg/mouse) and carboplatin (32 mg/kg) or thiotepa (4 mg/kg), many mice were completely cured of colon 26 adenocarcinoma and survived for more than 90 days. Combined use of rHu IL-1α and antitumor drugs seems to be beneficial in antitumor chemotherapy.
The natural environment and disease: an evolutionary perspective.
Authors: T R Southwood
Journal: BMJ (1987)

Old Testament and historical records from the ancient world all provide ample evidence of plagues-epidemics of some diseases.These were a reflection of the environment at that time.Malaria, which had probably been left behind when man initially left the tropics, could now maintain itself, for human populations were more dense and also, perhaps, man's bad land management had