tbuckley/cabot-search huggingface dataset:
The Swedish new variant of Chlamydia trachomatis (nvCT) remains undetected by many European laboratories as revealed in the recent PCR/NAT ring trial organised by INSTAND e.V., Germany
Authors: U Reischl, E Straube, M Unemo
Journal: Eurosurveillance (2009)

The May 2009 round of INSTAND's ring trial "Chlamydia trachomatis detection PCR/NAT" included a sample with high amount of the Swedish new variant of C. trachomatis (nvCT). A spectrum of at least 12 different commercial diagnostic nucleic acid amplification tests (NAATs) and many different in house NAATs were applied by the 128 participating laboratories which reported 152 results. Approximately 80% of the results correctly reported the presence of C. trachomatis in the nvCT specimen. The nvCT sample was mainly missed, as expected, by participants using the Roche COBAS Amplicor CT/NG (15.5% of reported results) but also by several participants using in house NAATs. The trend towards using nvCT-detecting NAATs is obvious and in addition to the new dual-target NAATs from Roche and Abbott, and BD ProbeTec ET, also a number of new CE mark-certified commercial tests from smaller diagnostic companies as well as many different in house NAATs were used. Laboratories using commercial or in house NAATs that do not detect the nvCT are encouraged to carefully monitor their C. trachomatis incidence, participate in appropriate external quality assurance and controls schemes, and consider altering their testing system. The reliable detection of low amounts of the wildtype C. trachomatis strain in other samples of the ring trial set indicates a good diagnostic performance of all applied commercial NAATs while also detecting the nvCT strain.
Protein Kinase A as Another Mediator of Ischemic Preconditioning Independent of Protein Kinase C
Authors: Shoji Sanada, Hiroshi Asanuma, Osamu Tsukamoto, Tetsuo Minamino, Koichi Node, Seiji Takashima, Tomi Fukushima, Akiko Ogai, Yoshiro Shinozaki, Masashi Fujita, Akio Hirata, Hiroko Okuda, Hiroaki Shimokawa, Hitonobu Tomoike, Masatsugu Hori, Masafumi Kitakaze
Journal: Circulation (2004)

We and others have reported that transient accumulation of cyclic AMP (cAMP) in the myocardium during ischemic preconditioning (IP) limits infarct size independent of protein kinase C (PKC). Accumulation of cAMP activates protein kinase A (PKA), which has been demonstrated to cause reversible inhibition of RhoA and Rho-kinase. We investigated the involvement of PKA and Rho-kinase in the infarct limitation by IP.Dogs were subjected to 90-minute ischemia and 6-hour reperfusion. We examined the effect on Rho-kinase activity during sustained ischemia and infarct size of (1) preischemic transient coronary occlusion (IP), (2) preischemic activation of PKA/PKC, (3) inhibition of PKA/PKC during IP, and (4) inhibition of Rho-kinase or actin cytoskeletal deactivation during myocardial ischemia. Either IP or dibutyryl-cAMP treatment activated PKA, which was dose-dependently inhibited by 2 PKA inhibitors (H89 and Rp-cAMP). IP and preischemic PKA activation substantially reduced infarct size, which was blunted by preischemic PKA inhibition. IP and preischemic PKA activation, but not PKC activation, caused a substantial decrease of Rho-kinase activation during sustained ischemia. These changes were cancelled by preischemic inhibition of PKA but not PKC. Furthermore, either Rho-kinase inhibition (hydroxyfasudil or Y27632) or actin cytoskeletal deactivation (cytochalasin-D) during sustained ischemia achieved the same infarct limitation as preischemic PKA activation without affecting systemic hemodynamic parameters, the area at risk, or collateral blood flow.Transient preischemic activation of PKA reduces infarct size through Rho-kinase inhibition and actin cytoskeletal deactivation during sustained ischemia, implicating a novel mechanism for cardioprotection by ischemic preconditioning independent of PKC and a potential new therapeutic target.
Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD
Authors: Chor Sang Chim, Albert Kwok Wai Lie, Eric Yuk Tat Chan, Herman Sung Yu Liu, Ching Wa Lau, Sze Fai Yip, Joycelyn Sim, Thomas Shek-Kong Wan, Edmond Shiu-Kwan Ma, Raymond Liang, Eric Tse, Yok-Lam Kwong
Journal: Journal of Hematology & Oncology (2012)

We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone) before autologous stem cell transplantation (ASCT). Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone) or VTD (bortezomib/thalidomide/dexamethasone) induction, and analysed prognostic factors for outcome. Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25), PAD (N = 31), VTD (N = 35)]. and received thalidomide maintenance for 2 years post-ASCT. 43 (47.3%) patients had International Staging System (ISS) III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS) and event-free (EFS) survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.
Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET)
Authors: C.R. Rossi, A. Vecchiato, G. Mastrangelo, M.C. Montesco, F. Russano, S. Mocellin, S. Pasquali, G. Scarzello, U. Basso, A. Frasson, P. Pilati, D. Nitti, A. Lurkin, I. Ray-Coquard
Journal: Annals of Oncology (2013)
Epidermal Growth Factor Receptor Activation: How Exon 19 and 21 Mutations Changed Our Understanding of the Pathway
Authors: Rafael Rosell, Miquel Taron, Noemi Reguart, Dolores Isla, Teresa Moran
Journal: Clinical Cancer Research (2006)

Abstract The discovery of epidermal growth factor receptor (EGFR) mutations in never-smokers has been the most relevant finding ever in non–small cell lung cancer. When patients whose tumors bear the sensitizing mutations are treated with the tyrosine kinase inhibitors gefitinib or erlotinib, we witness response rates and durations never before reported, including complete responses. At the same time, the presence of EGFR mutations has raised numerous new questions, tantalizing data, and new challenges for treatment. This is particularly true as we try to generalize the findings in lung cancer to other malignancies. The indiscriminate use of gefitinib or erlotinib in the general lung cancer population results in meager survival benefit for patients. Similarly, the tyrosine kinase inhibitors have limited activity in a variety of tumor types with EGFR overexpression. This has led to the question of whether EGFR remains a viable target in patients other than those whose tumors contain mutations, and whether the modest activity of cetuximab in colorectal cancer and head and neck cancer represents all that we can expect from inhibition of this pathway in the absence of mutation. Mechanisms of pathway activation other than mutation have been discovered in recent years, and include overexpression mediated by gene amplification or by amplification of a dinucleotide repeat in the EGFR promoter, mutation of an extracellular region on EGFR generating a mutant protein termed EGFRvIII, and enhanced signaling due to heterodimerization with other members of the EGFR family, particularly overexpression of HER2/HER3. The extent to which these paths to EGFR activation will confer sensitivity to the tyrosine kinase inhibitors or to EGFR monoclonal antibodies is being explored. Thus far, published clinical data suggest that there is little room for the administration of gefitinib or erlotinib in the absence of EGFR mutations. The five articles in this edition of CCR Focus will address the various mechanisms of EGFR pathway activation and provide insight into the potential for translation into clinical relevance.
Patterns of Survival in Multiple Myeloma: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2003
Authors: Sigurdur Yngvi Kristinsson, Ola Landgren, Paul W. Dickman, Åsa Rangert Derolf, Magnus Björkholm
Journal: Journal of Clinical Oncology (2007)

Purpose To define patterns of survival among all multiple myeloma (MM) patients diagnosed in Sweden during a 30-year period. Patients and Methods A total of 14,381 MM patients (7,643 males; 6,738 females) were diagnosed in Sweden from 1973 to 2003 (median age, 69.9 years; range 19 to 101 years). Patients were categorized into six age categories and four calendar periods (1973 to 1979, 1980 to 1986, 1987 to 1993, and 1994 to 2003). We computed relative survival ratios (RSRs) as measures of patient survival. Results One-year survival improved (P &lt; .001) over time in all age groups and RSRs were 0.73, 0.78, 0.80, and 0.82 for the four calendar periods; however, improvement in 5-year (P &lt; .001) and 10-year (P &lt; .001) RSR was restricted to patients younger than 70 years and younger than 60 years, respectively. For the first time, in analyses restricted to MM patients diagnosed at age younger than 60 years, we found a 29% (P &lt; .001) reduced 10-year mortality in the last calendar period (1994 to 2003) compared with the preceding calendar period (1987 to 1993). Females with MM had a 3% (P = .024) lower excess mortality than males. Conclusion One-year MM survival has increased for all age groups during the last decades; 5-year and 10-year MM survival has increased in younger patients (younger than 60 to 70 years). High-dose melphalan with subsequent autologous stem-cell transplantation, thalidomide, and a continuous improvement in supportive care measures are probably the most important factors contributing to this finding. New effective agents with a more favorable toxicity profile are needed to improve survival further, particularly in the elderly.
Early versus Delayed Invasive Intervention in Acute Coronary Syndromes
Authors: Shamir R. Mehta, Christopher B. Granger, William E. Boden, Philippe Gabriel Steg, Jean-Pierre Bassand, David P. Faxon, Rizwan Afzal, Susan Chrolavicius, Sanjit S. Jolly, Petr Widimsky, Alvaro Avezum, Hans-Jurgen Rupprecht, Jun Zhu, Jacques Col, Madhu K. Natarajan, Craig Horsman, Keith A.A. Fox, Salim Yusuf
Journal: New England Journal of Medicine (2009)

Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain.We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months.Coronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P=0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group (12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P=0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P=0.01 for heterogeneity).Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients. (ClinicalTrials.gov number, NCT00552513.)
Familial Chronic Myeloproliferative Disorders: Clinical Phenotype and Evidence of Disease Anticipation
Authors: Elisa Rumi, Francesco Passamonti, Matteo G. Della Porta, Chiara Elena, Luca Arcaini, Laura Vanelli, Cecilia Del Curto, Daniela Pietra, Emanuela Boveri, Cristiana Pascutto, Mario Cazzola, Mario Lazzarino
Journal: Journal of Clinical Oncology (2007)

Chronic myeloproliferative disorders (CMDs) have sporadic occurrence. However, familial clustering is reported. The purpose of this study was to assess the prevalence and the clinical phenotype of familial CMDs, and to study the anticipation of disease onset in successive generations.Among 458 patients with apparently sporadic CMDs, an interview-based investigation of family history was performed to identify familial cases. The clinical phenotype of familial CMDs was compared with that of sporadic CMDs. Anticipation was studied evaluating age at diagnosis and telomere length in successive generations.Among 458 patients with apparently sporadic CMDs, the prevalence of familial cases was 7.6% (35 pedigrees; 75 patients). Kolmogorov-Smirnov and two-tailed Fisher's exact tests did not demonstrate significant differences in clinical presentation between patients with familial and sporadic CMDs. Within 544 person-years of follow-up, patients with familial CMDs developed similar complications and disease evolutions as those with sporadic CMDs. The comparison of second-generation and first-generation patients showed a significantly younger age at diagnosis (Wilcoxon matched-pair test, P = .001) and a significantly higher age-dependent hazard of CMD onset (Nelson-Aalen method, P < .001) in patients of the second generation. A significant shortening of telomere length was highlighted in offspring compared with parent (P = .043).This study indicates that a thorough investigation of family history should be part of the initial work-up of patients with CMDs. Patients with familial CMDs show the same clinical features and suffer the same complications as patients with sporadic disease. Age distribution between parent and offspring and telomere length shortening provide evidence of disease anticipation.
Immunolocalization of Cystinosin, the Protein Defective in Cystinosis
Authors: Mushfequr R. Haq, Vasiliki Kalatzis, Marie-Claire Gubler, Margaret M. Town, Corinne Antignac, William G. van’t Hoff, Adrian S. Woolf
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Cystinosis is an autosomal recessive disorder associated with excessive lysosomal cystine accumulation secondary to defective lysosomal cystine efflux. <i>CTNS</i>, the gene mutated in cystinosis, codes for the lysosomal membrane protein cystinosin. Antisera were raised in rabbits to a carboxy-terminal oligopeptide sequence from cystinosin. Antisera were screened by Western blotting and immunocytochemical analyses of transfected COS-7 cells expressing either human wild-type cystinosin, a wild-type cystinosin-green fluorescent protein (GFP) fusion protein, or a fusion protein of GFP and mutant human cystinosin with a carboxy-terminal deletion. In Western blots, bands corresponding to cystinosin or cystinosin-GFP were observed in transfected cells but no signal was detected in cells expressing the carboxy-terminal mutant; preimmune sera yielded negative results in all three cases. In transfected cells expressing wild-type cystinosin, immunoreactivity appeared in subcellular vesicles. In cells expressing the wild-type cystinosin-GFP fusion protein, immunoreactivity colocalized with GFP fluorescence. Previous studies demonstrated that GFP fluorescence from this construct colocalized with immunostaining for a known lysosomal membrane protein, <i>i.e.</i>, lysosome-associated membrane protein 2. In immunohistochemical analyses, cystinosin localized to tubule epithelia in three normal human kidneys, with a pattern similar to that of lysosome-associated membrane protein 2; cystinosin immunoreactivity was absent in kidneys from patients with a <i>CTNS</i> deletion. For the first time, antisera have been raised that localize cystinosin in cells <i>in vitro</i> and <i>in vivo</i>.
Erythema gyratum repens—an immunologically mediated dermatosis?
Authors: P.J.A. HOLT, M.G. DAVIES
Journal: British Journal of Dermatology (1977)

There have been only 21 reported cases of erythema gyratum repens in the dermatological literature. Its impressive clinical appearances and constant association with malignancy pose interesting questions. We wish to present a further patient with erythema gyratum repens on whom detailed immunological investigations have been performed.
The effects of acute dynamic exercise on haemostasis in first class Scottish football referees
Authors: E E Peat, M Dawson, A McKenzie, W S Hillis
Journal: British Journal of Sports Medicine (2008)

Physical fitness may confer protection from thrombosis; however, exercise-induced platelet activation may be involved in the triggering of acute vascular events. This study aimed to assess haemostatic responses to acute exercise in trained and sedentary middle-aged subjects.21 first class Scottish football referees and 15 sedentary controls performed a treadmill exercise test. Blood sampling was performed before, immediately after and 30 minutes post-exercise. Samples were analysed for platelet count, prothrombin time, activated partial thromboplastin time (APTT) and serum fibrinogen. Platelet activation was assessed using flow cytometry with CD62 (P-selectin) and antifibrinogen antibodies at rest and in response to ADP and epinephrine.Mean maximal oxygen consumption (Vo2) (ml/kg per minute) achieved was 47.23 (5.02) in the referees and 30.1 (5.2) in sedentary controls. Total platelet count (x10(-9)/l) increased immediately post-exercise (228.2 (40.5), 278.6 (48.9) p=0.001) remaining elevated at 30 minutes in both groups. APTT (s) was reduced immediately post-exercise (32.15 (3.1), 29.7 (3.94) p=0.001) with a further reduction seen at 30 minutes (32.15 (3.1), 28.4 (3.31) p=0.001). In the referees, percentage CD62 expression increased immediately post-exercise (0.688 (0.52), 1.42 (1.3) p=0.008). Percentage antifibrinogen expression increased post-exercise (5.19 (4.31), 13.01 (14.24) p=0.017), with a further increase at 30 minutes (5.19 (4.31), 20.47 (26.8) p=0.02). Similar trends were seen in sedentary controls.This study suggests that in an older athletic population, physical fitness does not protect against the prothrombotic effects of exercise. These data suggest that during a football match when referees achieve approximately 80% of peak VO2 (23) they may be at risk of significant platelet activation. Prophylactic platelet inhibition should be considered in this group after appropriate screening and risk stratification.
Effect of Chemical Carcinogen Treatment on the Immunogenicity of Mouse Mammary Tumors Arising From Hyperplastic Alveolar Nodule Outgrowth Lines&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: B. Ruppert, W. Wei, D. Medina, G. H. Heppner
Journal: JNCI Journal of the National Cancer Institute (1978)

The experiments reported herein examined the effects of chemical carcinogen treatment of precursor hyperplastic alveolar nodules on the immunogenicity of subsequent mammary tumors in mice. The results of in vitro immunogenicity assays were compared with those of in vivo transplantation resistance tests. This comparison demonstrated that the in vitro assays predicted qualitatively and quantitatively the results from the in vivo test. In addition, the data suggested that the immunogenicity of a tumor depends on events occurring during the development of precursor hyperplastic alveolar nodules rather than during the development of subsequent mammary tumors.
Airway anatomy as a risk factor of COPD
Authors: Plamen Bokov, Christophe Delclaux
Journal: Thorax (2014)

We read with interest the study of Smith and colleagues,1 because besides their counterintuitive result of thinner airways in COPD, another important result is their smaller airway lumen areas of the whole bronchial tree. Their Table E4 shows that adjusted values of areas for confounding factors are significantly reduced from trachea to the sixth airway generation in COPD.

Based on theoretical arguments, the whole human bronchial tree anatomy can be described by only two factors: the tracheal cross-sectional area and the …
T-cell receptor Vβ CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia
Authors: A C H de Vries, A W Langerak, B Verhaaf, C M Niemeyer, J Stary, K Schmiegelow, E R van Wering, C M Zwaan, A Beishuizen, R Pieters, M M van den Heuvel-Eibrink
Journal: Leukemia (2008)
Successful treatment of recurrent rejection in renal transplant patients with photopheresis.
Authors: R Dall'Amico, L Murer, G Montini, B Andreetta, G F Zanon, G Zacchello, F Zacchello
Journal: Journal of the American Society of Nephrology (1998)

Photopheresis (ECP) is a new form of photochemotherapy that induces a selective inhibition of the host response to foreign histocompatibility antigens and reverses allograft rejection after organ transplantation. This report describes four adolescent patients with recurrent rejection episodes after renal transplantation, all uncontrolled using standard protocols of immunosuppression (intravenous steroids and OKT3), yet successfully treated with a 6-mo course of ECP. The ECP treatment was performed at weekly intervals during the first month, at 2-wk intervals during the second and third months, and then monthly for another 3 mo. Creatinine clearance improved throughout the treatment in three patients and remained unchanged in one. All patients had a pre-ECP biopsy with a grade 2 or 3 rejection (Banff) with a diffuse infiltrate CD8, CD14, LFA-1 (166 cells positive/0.048 mm2), and VLA-4 (51 cells positive/0.048 mm2) positive, as well as a tubular expression of HLA-DR (6.2 sections of tubule positive/0.048 mm2), ICAM-1, and VCAM-1 (3.1 and 2.9 sections of tubule positive/0.048 mm2). A strong reduction of cell infiltrate and expression of LFA-1 (6.6 cells positive/0.048 mm2). VLA-4 (0.7 cells positive/0.048 mm2), HLA-DR (0.2 section of tubules positive/0.048 mm2), ICAM-1 (0.3 section of tubules positive/0.048 mm2), and a disappearance of VCAM-1 staining were observed in the biopsies performed after 3 mo of ECP. All patients remained rejection-free during ECP, without infections or other complications commonly observed with increasing doses of standard immunosuppression. The clinical improvement allowed a progressive reduction of oral steroids in three of the four patients treated.