tbuckley/cabot-search huggingface dataset:
Cytosolic Phospholipase A2-A: A Potential TherapeuticTarget for Prostate Cancer
Authors: Manish I. Patel, Jaskirat Singh, Caroline Kurek, Sasa Lu, Fiona Maclean, Michael H. Gelb, Kieran F. Scott, Pamela J. Russell, John Boulas, Qihan Dong
Journal: Clinical Cancer Research (2008)

Purpose: Cytosolic phospholipase A2-a (cPLA2-a) provides intracellular arachidonic acid to supply both cyclooxygenase and lipoxygenase pathways. We aim to determine the expression and activation of cPLA2-a in prostate cancer cell lines and tissue and the effect of targeting cPLA2-a in vitro and in vivo. Experimental Design: The expression of cPLA2-a was determined in prostate cancer cells by reverse transcription-PCR,Western blot, and immunocytochemistry. Growth inhibition, apoptosis, and cPLA2-a activity were determined after inhibition with cPLA2-a small interfering RNA or inhibitor (Wyeth-1). Cytosolic PLA2-a inhibitor or vehicle was also administered to prostate cancer xenograft mouse models. Finally, the expression of phosphorylated cPLA2-a was deter- mined by immunohistochemistry in human normal, androgen-sensitive and androgen-insensitive prostate cancer specimens. Results: cPLA2-a is present in all prostate cancer cells lines, but increased in androgen-insensi- tive cells. Inhibition with small interfering RNA or Wyeth-1results in significant reductions in pros- tate cancer cell numbers, as a result of reduced proliferation as well as increased apoptosis, and this was also associated with a reduction in cPLA2-a activity. Expression of cyclin D1and phos- phorylation of Akt were also observed to decrease. Wyeth-1inhibited PC3 xenograft growth by f33% and again, also reduced cyclin D1. Immunohistochemistry of human prostate tissue revealed that phosphorylated cPLA2-a is increased when hormone refractory is reached. Conclusions: Expression and activation of cPLA2-a are increased in the androgen-insensitive cancer cell line and tissue. Inhibition of cPLA2-a results in cells and xenograft tumor growth inhi- bition and serves as a potentially effective therapy for hormone refractory prostate cancer.
Proadrenomedullin improves the prognostic property of the BODE index
Authors: Daiana Stolz, Wim Boersma, Branislava Milenkovic, Kostantinos Kostikas, Francesco Blasi, Joachim Aerts, Renaud Louis, Gernot Rohde, Alicia Lacoma, Lucas Boeck, Janko Rakic, Andreas Scherr, Antoni Torres, Tobias Welte, Oliver Hartmann, Sven Giersdorf, Michael Tamm
Journal: European Respiratory Journal (2012)

BACKGROUND: 

The BODE index, a multidimensional grading system assessing the respiratory and systemic expressions of COPD, proved helpful in the prognostic assessment in COPD. We hypothesize that systemic biomarkers might additionally improve categorization and outcome prediction in COPD.

METHODS: 

We prospectively evaluated 638 patients with stable COPD for ≥ 6 weeks, > 10 PY and GOLD II-IV seeking care in pulmonary tertiary hospitals in 8 European countries and included in the PROMISE cohort. The primary outcome of the study was death from any cause and from respiratory causes. Median observation time was 24 months.

RESULTS: 

There were 63 deaths among the 638 patients (9.9%). 32 (51%) of the deaths were attributed mainly to COPD. Patients with higher proadrenomedullin values were at higher risk for death (p<0.0001). In the multivariate analysis, proadrenomedullin HR (95% CI) 1.83 (1.34-2.51, p=0.0002), BMI 0.48 (0.32-0.72, p=0.0004) and 6 MWD 0.6 (0.4-0.91, p=0.0152) but not MMRC 1.31 (0.94-1.84, p=0.113) and FEV1%pred 1.17 (0.68-2, p=0.5727) were significantly associated with 2 year survival. The C-index for the prediction of mortality in the Cox-regression analysis was 0.676 for the BODE index and 0.658 for proadrenomedullin (p<0.0001 both). The addition of proadrenomedullin to the BODE index improved its performance significantly (C-index 0.743, p=0.00020). In combination with proadrenomedullin, the BMI (B), the degree of airflow obstruction (O) and dyspnea (D) domains by itself (e.g. without exercise capacity) performed similarly to the BODE index (C-index 0.772).

CONCLUSION: 

Proadrenomedullin improves the performance of the BODE index at predicting the risk of death from any cause among patients with COPD.
Diabetes and extreme altitude mountaineering
Authors: K Moore, C Thompson, R Hayes
Journal: British Journal of Sports Medicine (2001)

Increasing numbers of people with diabetes are seeking advice about participation in high altitude climbing, which has the problems of serious metabolic demands, a high likelihood of acute mountain sickness (AMS),1 and leaving the climber remote from medical care. The American Diabetes Association states that “all levels of exercise, including leisure activities, recreational sports, and competitive professional performance, can be performed by people with type 1 diabetes who do not have complications and are in good blood glucose control”.2 But, are all forms of sport suitable for people with type 1 diabetes? Lack of data on the effects of altitude on blood glucose control has led to reticence among members of the medical profession to endorse high altitude mountaineering for people with diabetes

The Diabetes Federation of Ireland Expedition to Kilimanjaro (4559 m) gave some indication of the potential hazards of extreme altitude for diabetic climbers.3 Symptoms of AMS, as measured by the well validated Lake Louise scoring system,4 occurred with similar frequency in diabetic and non-diabetic climbers, indicating that diabetes per se …
Abnormal haemostasis in small cell lung cancer.
Authors: R Milroy, J T Douglas, J Campbell, R Carter, G D Lowe, S W Banham
Journal: Thorax (1988)

Disorders of haemostasis and altered platelet activity have been documented in patients with malignant disease but their relation to response to treatment and prognosis are not known. Thrombin activity (fibrinopeptide A (FpA), plasmin mediated fibrinolysis (B beta 15-42) antigen), and platelet alpha granule release (beta thromboglobulin) were studied in 37 patients with small cell lung cancer to find out whether these indices show a relationship to chemoresponse. There was evidence of considerably increased thrombin activity, with a median fibrinopeptide A concentration of 13.2 (normal less than 4) pmol/ml, but only modestly increased fibrinolysis, with a median B beta 14-42 antigen concentration of 5.6 (normal less than 3) pmol/ml. Thus the ratio of fibrinopeptide A to B beta 15-42 concentration (FpA:B beta) was raised, with a median value of 2.2 (normal less than 1.33). In addition, 57% of patients had increased platelet alpha granule release, the median beta thromboglobulin concentration being 50 (normal less than 50) ng/ml. There was a significant association between increased thrombin generation and lack of response to chemotherapy. Furthermore, non-responders had higher FpA:B beta ratios. The same haemostatic markers were studied in nine patients who have been in complete remission for at least two years after chemotherapy for small cell lung cancer. There was a significant difference in thrombin activity and also in the ratio of thrombin activity to lysis between the pretreatment group and the group of two year survivors. Lack of response to chemotherapy appears to be related to increased thrombin activity. Such an association has not previously been reported in patients with malignant disease.
Genetic diversity of Legionella pneumophila inferred from rpoB and dotA sequences
Authors: K.S. Ko, H. Miyamoto, H.K. Lee, M.-Y. Park, K. Fukuda, B.J. Park, Y.-H. Kook
Journal: Clinical Microbiology and Infection (2006)

This study characterised the population structure of Legionella pneumophila by comparing the rpoB (300-bp) and dotA (360-bp) sequences of 267 isolates (18 reference strains, 149 Korean isolates and 100 Japanese isolates). In addition to the six clonal subgroups established previously, four subgroups, P-V to P-VIII, were identified. Subgroupings based on rpoB and dotA sequences were found to correlate with the source of the isolates, and this data may be useful for future epidemiological studies. Fourteen (five Korean and nine Japanese) isolates showed incongruent subgroupings in the rpoB and dotA trees, suggesting that genetic exchange among subgroups, and even among subspecies, may occur frequently in nature.
Random Capillary Blood Glucose Cut Points for Diabetes and Pre-Diabetes Derived From Community-Based Opportunistic Screening in India
Authors: Suresh Somannavar, Anbazhagan Ganesan, Mohan Deepa, Manjula Datta, Viswanathan Mohan
Journal: Diabetes Care (2008)

OBJECTIVE To determine random capillary blood glucose (RCBG) cut points that discriminate diabetic and pre-diabetic subjects from normal individuals. RESEARCH DESIGN AND METHODS RCBG was performed in 1,333 individuals randomly chosen from 63,305 individuals who had participated in an opportunistic screening program. An oral glucose tolerance test was also performed by venous plasma glucose on an autoanalyzer. RCBG cut points that discriminate diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) were determined using receiver operating characteristic curves. RESULTS Using 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) criterion, the RCBG cut point of 140 mg/dl (7.7 mmol/l) gave the highest sensitivity and specificity. For 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) and fasting plasma glucose (FPG) ≥126 mg/dl (7.0 mmol/l) criteria, either 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) or FPG ≥126 mg/dl (7.0 mmol/l) criterion, and the FPG ≥126 mg/dl (7.0 mmol/l) criterion, RCBG cut point was 143 mg/dl (7.9 mmol/l). RCBG cut points for IGT, IFG according to World Health Organization criterion, and IFG according to American Diabetes Association criterion were 119 mg/dl (6.6 mmol/l), 118 mg/dl (6.6 mmol/l), and 113 mg/dl (6.3 mmol/l), respectively. CONCLUSIONS Asian Indians with RCBG &amp;gt;110 mg/dl at screening can be recommended to undergo definitive testing.
Clinical and Biological Effects of Recombinant Human Interleukin-18 Administered by Intravenous Infusion to Patients with Advanced Cancer
Authors: Michael J. Robertson, James W. Mier, Theodore Logan, Michael Atkins, Henry Koon, Kevin M. Koch, Steven Kathman, Lini N. Pandite, Coreen Oei, Lyndon C. Kirby, Roxanne C. Jewell, William N. Bell, Linda M. Thurmond, Jill Weisenbach, Suzanne Roberts, Mohammed M. Dar
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Interleukin-18 (IL-18) is an immunostimulatory cytokine with antitumor activity in preclinical animal models. A phase I study of recombinant human IL-18 (rhIL-18) was done to determine the toxicity, pharmacokinetics, and biological activities of rhIL-18 in patients with advanced cancer. Experimental Design: Cohorts of patients were given escalating doses of rhIL-18, each administered as a 2-hour i.v. infusion on 5 consecutive days. Toxicities were graded using standard criteria. Serial blood samples were obtained for pharmacokinetic and pharmacodynamic measurements. Results: Twenty-eight patients (21 with renal cell cancer, 6 with melanoma, and 1 with Hodgkin's lymphoma) were given rhIL-18 in doses ranging from 3 to 1,000 μg/kg. Common side effects included chills, fever, nausea, headache, and hypotension. Common laboratory abnormalities included transient, asymptomatic grade 1 to 2 neutropenia, thrombocytopenia, anemia, hypoalbuminemia, hyponatremia, and elevations in liver transaminases. One patient in the 100 μg/kg cohort experienced transient grade 3 hypotension and grade 2 bradycardia during the first infusion of rhIL-18. No other dose-limiting toxicities were observed. Plasma concentrations of rhIL-18 increased with increasing dose, and 2.5-fold accumulation was observed with repeated dosing. Biological effects of rhIL-18 included transient lymphopenia and increased expression of activation antigens on lymphocytes and monocytes. Increases in serum concentrations of IFN-γ, granulocyte macrophage colony-stimulating factor, IL-18 binding protein, and soluble Fas ligand were observed. Two patients experienced unconfirmed partial responses after rhIL-18 treatment. Conclusions: rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. A maximum tolerated dose of rhIL-18 was not determined. Further clinical studies of rhIL-18 are warranted.
Immunostimulant therapy for rheumatoid arthritis
Authors: E. C. Huskisson, P. A. Dieppe, J. Scott, J. Trapnell, H. W. Balme, D. A. Willoughby
Journal: Annals of the Rheumatic Diseases (1976)

Heberden Society 541 tuberculous arthritis, to gout, or to a variant of the socalled seronegative peripheral arthritis as seen in Reiter's disease, arthritis associated with gastrointestinal disease, psoriasis, and ankylosing spondylitis.In all these con- ditions, however, the involvement of the proximal inter-
Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell–induced apoptosis
Authors: E. Marion Schneider, Ingrid Lorenz, Michaela Müller-Rosenberger, Gerald Steinbach, Martina Kron, Gritta E. Janka-Schaub
Journal: Blood (2002)
Compartmentalized Phosphodiesterase-2 Activity Blunts β-Adrenergic Cardiac Inotropy via an NO/cGMP-Dependent Pathway
Authors: Marco Mongillo, Carlo G. Tocchetti, Anna Terrin, Valentina Lissandron, York-Fong Cheung, Wolfgang R. Dostmann, Tullio Pozzan, David A. Kass, Nazareno Paolocci, Miles D. Houslay, Manuela Zaccolo
Journal: Circulation Research (2005)

beta-Adrenergic signaling via cAMP generation and PKA activation mediates the positive inotropic effect of catecholamines on heart cells. Given the large diversity of protein kinase A targets within cardiac cells, a precisely regulated and confined activity of such signaling pathway is essential for specificity of response. Phosphodiesterases (PDEs) are the only route for degrading cAMP and are thus poised to regulate intracellular cAMP gradients. Their spatial confinement to discrete compartments and functional coupling to individual receptors provides an efficient way to control local [cAMP]i in a stimulus-specific manner. By performing real-time imaging of cyclic nucleotides in living ventriculocytes we identify a prominent role of PDE2 in selectively shaping the cAMP response to catecholamines via a pathway involving beta3-adrenergic receptors, NO generation and cGMP production. In cardiac myocytes, PDE2, being tightly coupled to the pool of adenylyl cyclases activated by beta-adrenergic receptor stimulation, coordinates cGMP and cAMP signaling in a novel feedback control loop of the beta-adrenergic pathway. In this, activation of beta3-adrenergic receptors counteracts cAMP generation obtained via stimulation of beta1/beta2-adrenoceptors. Our study illustrates the key role of compartmentalized PDE2 in the control of catecholamine-generated cAMP and furthers our understanding of localized cAMP signaling.
Does melatonin improve sleep?: Efficacy of melatonin
Authors: Josephine Arendtw
Journal: BMJ (2006)

EDITOR—Buscemi et al in their meta-analysis report that melatonin is ineffective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction such as jet lag or shift work.1 The published reports in this domain certainly show some inconsistency, and now there is inconsistency in the meta-analyses.2 Numerous published studies, mostly with a positive result, have …
Comparison of intravenous digital subtraction angiography with radionuclide ventilation-perfusion lung scanning in patients with suspected pulmonary embolism.
Authors: K C Flint, N M Johnson, A Mannhire, P Dawson, S George, P J Ell
Journal: Thorax (1985)

Fifty one patients with suspected pulmonary embolus were studied by radionuclide ventilation-perfusion scanning and intravenous digital subtraction pulmonary angiography. In 31 patients the results of both investigations were reported as negative and in a further 11 both results were reported as positive, giving a concordance rate of 82.3%. In nine patients there was disagreement between the two investigations and an attempt to resolve this difference on the basis of clinical data was made. On this basis digital subtraction angiography would have falsely classified three patients as not having an embolus who were correctly identified by radioisotope scanning. Angiography would, however, have correctly classified four patients misclassified by ventilation-perfusion scanning. The relative merits of digital subtraction angiography and radionuclide lung scanning are discussed.
Candidate gene regions and genetic heterogeneity in gluten sensitivity
Authors: P Holopainen, K Mustalahti, P Uimari, P Collin, M Mäki, J Partanen
Journal: Gut (2001)

BACKGROUND Gluten sensitivity is a common multifactorial disorder, manifested in the small intestine or on the skin as typical coeliac disease or dermatitis herpetiformis, respectively. The only established genetic risk factor is HLA DQ2. AIMS We tested genetic linkage of previously reported chromosomal loci 5q and 11q in Finnish families with gluten sensitivity. We also tested if genetic linkage to candidate loci on 5q, 11q, 2q33, and HLA DQ differed with respect to clinical manifestations or sex. SUBJECTS We studied 102 Finnish families with affected sibpairs. For heterogeneity analysis, families were divided into subgroups according to sex and the presence of dermatitis herpetiformis, the skin manifestation of gluten sensitivity. METHODS Non-parametric linkage between microsatellite markers and disease was tested. Linkage heterogeneity between subgroups was tested using the M test. The transmission/disequilibrium test and association analysis were performed. RESULTS Evidence of linkage to 11q (MLS 1.37), but not to 5q, was found in the entire dataset of 102 families. Heterogeneity between subgroups was suggested: families with only the intestinal disease showed linkage mainly to 2q33 whereas families with dermatitis herpetiformis showed linkage to 11q and 5q, but not to 2q33. Linkage in all three non-HLA loci was strongest in families with predominantly male patients. HLA DQ2 conferred much stronger susceptibility to females than males. CONCLUSIONS Independent evidence for the suggested genetic linkage between 11q and gluten sensitivity was obtained. The possible linkage heterogeneity suggests genetic differences between intestinal and skin manifestations, and the gender dependent effect of HLA DQ2.
Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial
Authors: Bengt I Eriksson, Ola E Dahl, Nadia Rosencher, Andreas A Kurth, C Niek van Dijk, Simon P Frostick, Martin H Prins, Rohan Hettiarachchi, Stefan Hantel, Janet Schnee, Harry R Büller
Journal: The Lancet (2007)
Chronic urticaria and cancer: an epidemiological study of 1155 patients
Authors: B. LINDELÖF, B. SIGURGEIRSSON, C.F. WAHLGREN, G. EKLUND
Journal: British Journal of Dermatology (2006)

To evaluate the possible association of malignant disease with chronic urticaria 1155 consecutive cases with chronic urticaria were reviewed. The Swedish Cancer Registry, Stockholm, was searched for records reporting malignancies in the study population (1958-84), and the expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data. A malignancy was diagnosed in 36 patients with urticaria and the expected number of malignancies was 41. In 23 patients the malignancy appeared during the same year as the onset of urticaria or later. The expected number was 25.6. We conclude that chronic urticaria is not statistically associated with malignancy in general.
Extracellular purines are biomarkers of neutrophilic airway inflammation
Authors: C. R. Esther, N. E. Alexis, M. L. Clas, E. R. Lazarowski, S. H. Donaldson, C. M. Pedrosa Ribeiro, C. G. Moore, S. D. Davis, R. C. Boucher
Journal: European Respiratory Journal (2008)

Purinergic signalling regulates airway defence mechanisms, suggesting that extracellular purines could serve as airway inflammation biomarkers in cystic fibrosis (CF). The purines adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine were measured in sputum from 21 adults (spontaneously expectorated from seven CF patients, induced from 14 healthy controls) to assess normal values and CF-associated changes. Subsequently, purine levels were measured in bronchoalveolar lavage fluid (BALF) from 37 children (25 CF patients, 12 disease controls) and compared with neutrophil counts, presence of airway infection and lung function. To noninvasively assess airway purines, ATP levels were measured using luminometry in exhaled breath condensate (EBC) from 14 children with CF and 14 healthy controls, then 14 CF children during a pulmonary exacerbation. Both ATP and AMP were elevated in sputum and BALF from CF subjects compared with controls. In BALF, ATP and AMP levels were inversely related to lung function and strongly correlated with neutrophil counts. In EBC, ATP levels were increased in CF relative to controls and decreased after treatment of CF pulmonary exacerbation. The purines adenosine triphosphate and adenosine monophosphate are candidate biomarkers of neutrophilic airways inflammation. Measurement of purines in sputum or exhaled breath condensate may provide a relatively simple and noninvasive method to track this inflammation.
Physiologic corticosterone oscillations regulate murine hematopoietic stem/progenitor cell proliferation and CXCL12 expression by bone marrow stromal progenitors
Authors: O Kollet, Y Vagima, G D'Uva, K Golan, J Canaani, T Itkin, S Gur-Cohen, A Kalinkovich, G Caglio, C Medaglia, A Ludin, K Lapid, E Shezen, A Neufeld-Cohen, D Varol, A Chen, T Lapidot
Journal: Leukemia (2013)
TREATMENT OF INFLAMMATORY CONDITIONS BY RADIATIONS
Authors: J. H. D. Webster
Journal: BMJ (1932)

L MEDICAL JOUJRNAL illness.It would appear, however, that the normal immunity response of the body failed to reinforce passive immunization, since circulating antibodies were not found in a particular case tested on the seventh day of illness.These patients collapsed and died from the shock of the disease or from meningitis; their vital response was, in fact, overwhelmed at an early stage by the severity of the infection.Similarly, in a rabbit to which an excessive dose of killed pneumococcal vaccine was given experimentally, response was delayed ten days from the third, the normal day of appearance of immunity, till the thirteenth day after inoculation.7Further experience is required in the application of serum treatment to severest cases of pneumonia.
Congenital coronary artery fistula.
Authors: H Dedichen, L Skalleberg, C Cappelen
Journal: Thorax (1966)

CASE 2 R. S., a 19-year-old girl, was admitted in 1960.When she was 10 years old a congenital heart malformation was suspected but was not further investigated.She had been asymptomatic.There was no cyanosis or finger clubbing.The heart action was regular.Blood pressure was 155/80 mm.Hg.A continuous machinery murmur was heard over the apex and the left lower sternal border, and over the base of the heart a faint diastolic murmur was present.The E.C.G. was normal.Radiological examination revealed enlargement of both ventricles and the right atrium.Relative heart volume was 505 ml./m.' Right heart catheterization showed normal pressures in the right heart and pulmonary artery.There was a left-to- 121 L