tbuckley/cabot-search huggingface dataset:
New Paraoxonase 1 Polymorphism I102V and the Risk of Prostate Cancer in Finnish Men
Authors: M. Marchesani, A. Hakkarainen, T.-P. Tuomainen, J. Kaikkonen, E. Pukkala, P. Uimari, E. Seppala, M. Matikainen, O.-P. Kallioniemi, J. Schleutker, T. Lehtimaki, J. T. Salonen
Journal: JNCI Journal of the National Cancer Institute (2003)

Human serum paraoxonase eliminates carcinogenic lipid-soluble radicals. Because expression of the main human paraoxonase gene PON1 varies widely in humans, certain PON1 polymorphisms might be associated with increased risks of cancer. We sought new functional mutations in PON1 and determined whether known or new PON1 mutations were associated with the risk for prostate cancer in a prospective, random, population-based sample of Finnish men and in a case-control study.Serum paraoxonase activity was measured in 835 healthy men in the Kuopio Ischaemic Heart Disease Risk Factor Study. PON1 mutations were identified by hierarchical phenotype-targeted sequencing in DNAs from the 100 men with the lowest paraoxonase activity in this cohort, and 1595 men in the cohort were genotyped for PON1 mutations by restriction fragment length polymorphism. Multivariable analysis was used to investigate the association of known and new PON1 mutations with incident prostate cancer in 1569 cancer-free men in the cohort followed for 9-14 years. In a case-control study of Finnish men, the association of prostate cancer with the PON1 mutation identified in the cohort study was investigated in 69 case patients with familial prostate cancer and 69 unmatched healthy control subjects.We identified a new single-nucleotide PON1 polymorphism associated with decreased serum paraoxonase activity that caused an isoleucine-->valine change at codon 102 in exon 4 (I102V). Of the 1569 men cancer-free at baseline, 56 (3.6%) were carriers of the I102V mutation. After adjusting for age and cholesterol-lowering medications, the relative risk for developing prostate cancer during follow-up was 6.3 (95% confidence interval [CI] = 2.1 to 19.2) among 102V allele carriers compared with noncarriers. Other PON1 alleles were not statistically significantly associated with prostate cancer. In the case-control study, patients with familial prostate cancer were more likely to be carriers of the PON1 I102V mutation than control subjects (odds ratio = 4.3, 95% CI = 0.9 to 21.5).The PON1 102V allele appears to be associated with an increased risk for prostate cancer.
Hypoxia induces protection against etoposide-induced apoptosis: molecular profiling of changes in gene expression and transcription factor activity
Authors: Audrey Sermeus, Jean-Philippe Cosse, Marianne Crespin, Veronique Mainfroid, Francoise de Longueville, Noelle Ninane, Martine Raes, Jose Remacle, Carine Michiels
Journal: Molecular Cancer (2008)

it is now well established that hypoxia renders tumor cells resistant to radio- but also chemotherapy. However, few elements are currently available as for the mechanisms underlying this protection.in this study, physiological hypoxia was shown to inhibit apoptosis induced in HepG2 cells by etoposide. Indeed, hypoxia reduced DNA fragmentation, caspase activation and PARP cleavage. The DNA binding activity of 10 transcription factors was followed while the actual transcriptional activity was measured using specific reporter plasmids. Of note is the inhibition of the etoposide-induced activation of p53 under hypoxia. In parallel, data from low density DNA microarrays indicate that the expression of several pro- and anti-apoptotic genes was modified, among which are Bax and Bak whose expression profile paralleled p53 activity. Cluster analysis of data unravels several possible pathways involved in the hypoxia-induced protection against etoposide-induced apoptosis: one of them could be the inhibition of p53 activity under hypoxia since caspase 3 activity parallels Bax and Bak expression profile. Moreover, specific downregulation of HIF-1alpha by RNA interference significantly enhanced apoptosis under hypoxia possibly by preventing the hypoxia mediated decrease in Bak expression without altering Bax expression.these results are a clear demonstration that hypoxia has a direct protective effect on apoptotic cell death. Moreover, molecular profiling points to putative pathways responsible for tumor growth in challenging environmental conditions and cancer cell resistance to chemotherapeutic agents.
Acute effects of inhaled nitric oxide in adult respiratory distress syndrome
Authors: GA Iotti, MC Olivei, A Palo, C Galbusera, R Veronesi, A Braschi
Journal: European Respiratory Journal (1998)

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses &lt; or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.
SCREENING FOR SUDDEN CARDIAC DEATH IN ATHLETES: THE PSYCHOLOGICAL IMPACT OF BEING DIAGNOSED WITH POTENTIALLY LETHAL DISEASE
Authors: I Asif, D Price, L Fisher, R Zakrajsek, J Raabe, M Bejar, L Larsen, A Rao, K Harmon, J Drezner
Journal: British Journal of Sports Medicine (2014)

Background The purpose of cardiovascular screening in athletes is the identification of disorders at risk for sudden cardiac death. No study has assessed the experiences of athletes diagnosed with a serious cardiovascular condition. Objective To determine the psychological impact of young athletes who are diagnosed with a potentially lethal cardiac condition. Design Semi-structured interview. Setting Young competitive US Athletes. Participants 25 athletes (52% male, 80% Caucasian, median age 17.7) previously diagnosed (&gt;6 months) with potentially lethal cardiac conditions (5 HCM, 8 WPW, 4 LQTS, 3 ASD, 2 SVT, 3 other) voluntarily participated. Assessment of risk factors Athletes shared reactions and experiences regarding diagnosis, lifestyle implications, coping strategies, major concerns, and overall impact on psychosocial functioning. Main outcome measurements Audio interviews were transcribed and analyzed using consensual qualitative research (CQR) to identify themes and sub-themes. Results Athletes recalled anxiety, confusion, denial, and shock shortly after diagnosis. Disqualified collegiate athletes described prolonged emotional impact due to identity change, and had mixed emotions regarding participation in team activities in another role. Disqualified high school athletes were more accepting of their condition and chose to participate in lower intensity sports. Those undergoing simple corrective procedures depicted mentally overcoming their diagnosis quickly with little impact on daily life; however, individuals with cardiomyopathy or channelopathy had persistent reminders such as taking daily medication, monitoring HR during activity, and ensuring the presence of onsite defibrillators in case of cardiac arrest. Only a minority of athletes described emotional support mechanisms from medical programs. Diagnosis often led to new life purposes such as mentoring or coaching. Despite its impact, all athletes were appreciative and would undergo advanced cardiovascular screening again. Conclusions College athletes and those with cardiac conditions requiring disqualification from sport are at greater risk of adverse psychological consequences. Improved support mechanisms from medical programs are needed to assist athletes diagnosed with a serious cardiac disorder.
Haemodynamic and endocrinological effects of noninvasive mechanical ventilation in respiratory failure
Authors: JB Thorens, M Ritz, C Reynard, A Righetti, M Vallotton, H Favre, U Kyle, P Jolliet, JC Chevrolet
Journal: European Respiratory Journal (1997)

The aim of this study was to investigate the haemodynamic and endocrinological effects of noninvasive positive pressure ventilation (NIPPV). Eleven patients with oedema and recent hypercapnic and hypoxaemic worsening of a chronic respiratory insufficiency were included. Echocardiography, cardiac radionuclide assessment, blood catecholamines, salt and water handling hormones were measured at admission and discharge (long study (LS)). To discriminate between the action of NIPPV and other treatments, measurements were performed on the fourth day, for 4 h without NIPPV and 4 h with NIPPV (short study (SS)). NIPPV entailed a correction of P(a,CO2) and an increase of P(a,O2) in LS and SS. Oedema disappeared. Body weight decreased (from 85+/-42 to 81+/-40 kg) during LS. Systolic and mean pulmonary arterial pressure decreased in LS and SS. Right ventricular ejection fraction increased in LS. Left ventricular ejection fraction did not change. Cardiac index was normal on admission and then decreased. Natriuretic peptides and catecholamines were increased on admission, whereas plasma renin activity, aldosterone and vasopressin were normal. We suggest that in these patients, oedema can occur independently of renin-angiotensin-aldosterone-vasopressin and with a normal cardiac output. Noninvasive positive pressure ventilation allowed a correction of blood gases, associated with the resolution of oedema, a decrease in pulmonary arterial pressures and an increase in right ventricular ejection fraction.
Labeled Phosphate Distribution in Working and Nonworking Myocardium
Authors: KENNETH K. TSUBOI, NANCY M. BUCKLEY, NORMAN J. ZEIG
Journal: Circulation Research (1960)

Investigation of phosphate metabolism with the aid of labeled phosphorus has been carried out, using isolated heart preparations in which only the left ventricles perform external work. The corresponding right ventricles in such preparations perform no external work with the unique experimental advantage of a single heart, providing simultaneously both working and "resting" (nonworking) metabolic states. Comparative incorporation of labeled phosphorus into nucleotide phosphate groups, non-nucleotide soluble phosphorylated components, phospholipids and ribose nucleic acid was examined as a function of cardiac work. Incorporation of the label into the rapidly exchanged high-energy phosphate groups was found to be restricted by a prior rate--limiting entry of the externally perfused isotope into the cells, thereby precluding a measure of turnover of these groups by this technic. Differences could not be demonstrated in isotope incorporation in either the phospholipids or RNA of working as compared to nonworking myocardium. It was concluded from these results that RNA is clearly not involved in energy reactions associated with cardiac work function. Phospholipid participation, on the other hand, could be clearly excluded only insofar as the phosphate moiety of these compounds is concerned. Information relevant to a mechanism of phosphate entry into cardiac cells was obtained in which a phosphorylation of hexose appeared to be involved. The composition of cardiac tissue with respect to nucleotide and non-nucleotide soluble components was examined in working and nonworkiug myocardium. Differences in composition were not found with respect to these constituents. A major component appearing in extracts of cardiac tissue was found and subsequently identified to be α-glycerophosphate. On the basis of isotope incorporation data, it was concluded that its metabolic source was of carbohydrate rather than phospholipid origin.
Performance of a task-based questionnaire for exposure assessment of bronchial occupational carcinogens
Authors: Emmanuelle Penven, Amandine Luc, Isabelle Thaon, Christophe Paris
Journal: European Respiratory Journal (2014)

The attributable risk (AR) for lung cancer due to occupational exposures is roughly estimated at 15%. Doctors have limited knowledge of occupational exposures to bronchial carcinogens. This may explain the reason why the number of lung cancers recognized as an occupational diseases is far lower than the AR. The aim of this study is to validate a specific questionnaire in order to help doctors and patients to identify occupational exposure to bronchial carcinogens, with satisfactory performance.

Based on an earlier study (Bourgkard E, Occup Environ Med. 2013;12:884-91), a job-based (JBQ) and a task-based questionnaires (TBQ) were created, concerning the main occupational bronchial carcinogens (asbestos, silica, PAHs, exhaust fumes, paint). They were both randomly administrated to 470 lung cancer patients, in two versions (self-administered or interview). A Job Exposure and a Task-Based Matrix were also created in order to analyze data questionnaires automatically, as well as by a double independent expertise. Comparisons between algorithms and expertise were done for the 5 carcinogens agents both for the probability and the quantitative estimates of exposure.

Overall, depending of the agents, The TBQ by interview has the best results in terms of sensitivity (Se) and specificity (Sp). For instance, Se and Sp were 0.96% and 0.76% for asbestos. Conversely, the JBQ did not achieve sufficient performance, particularly for sensitivity. Quantitative comparisons also demonstrated good assessment of exposure by the TBQ.

This study demonstrates the interest of a task-based questionnaire in order to facilitate identification of the main occupational exposure of bronchial carcinogens.
Pituitary-Adrenal and Autonomic Responses to Stress in Women After Sexual and Physical Abuse in Childhood
Authors: Christine Heim
Journal: JAMA (2000)

genetic and environmental factors in the etiology of psychiatric disorders has long been a hotly debated area of investigation.Considerable evidence from a variety of studies suggests a preeminent role of early adverse experiences in the development of mood and anxiety disorders.One study 1 composed of almost 2000 women revealed that those with a history of childhood sexual or physical abuse exhibited more symptoms of depression and anxiety and had more frequently attempted suicide than women without a history of childhood abuse.4][5][6][7][8] Twin studies 9,10 have provided concordant findings.Child-
Increased levels of plasma thrombomodulin in chronic myelogenous leukemia
Authors: Eriko Morishita, Masanori Saito, Hidesaku Asakura, Hiroshi Jokaji, Chika Uotani, Ichiro Kumabashiri, Masahide Yamazaki, Tamotsu Matsuda
Journal: American Journal of Hematology (1992)

Circulating blood plasma contains proteinase-degraded forms of thrombomodulin that are soluble. We quantitatively assayed the plasma levels of thrombomodulin in 15 patients with chronic myelogenous leukemia (CML) in chronic phase by method of an enzyme-linked immunosorbent assay using a monoclonal antibody to protease-degraded products of thrombomodulin. Plasma levels of thrombomodulin in patients with CML at diagnosis were significantly increased (19.5 +/- 6.2 ng/ml: means +/- SD) compared with the levels in normal controls (8.0 +/- 1.9 ng/ml, n = 20) (P less than 0.001). Fibrin degradation products (D-dimer), thrombin-antithrombin III complex, and plasmin alpha 2-antiplasmin complex were almost normal, suggesting that intravascular coagulation or plasmin-mediated fibrinolysis little occurred in these patients. On the other hand, the plasma levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1PI) complex, which was the indicator of released leukocyte elastase, were significantly increased in CML (P less than 0.0001). The plasma levels of thrombomodulin and E-alpha 1PI complex were decreased in parallel with decline of leukocyte counts in 10 patients with CML following anti-leukemic therapy. Furthermore, a statistically significant correlation was observed between the plasma levels of thrombomodulin and E-alpha 1PI complex obtained at 39 time points in 15 patients with CML (r = 0.81, P less than 0.001). These results suggest that the increased plasma levels of thrombomodulin in CML may be partly caused by leukocyte elastase, which may split the surface thrombomodulin and release protease-degraded fragments of it into the circulation.
Asialoglycoprotein Receptor Promotes Cancer Metastasis by Activating the EGFR–ERK Pathway
Authors: Suguru Ueno, Marija Mojic, Yoshimi Ohashi, Nobuaki Higashi, Yoshihiro Hayakawa, Tatsuro Irimura
Journal: Cancer Research (2011)

Abstract Although the importance of glycans in malignant cell behavior is well documented, the potential involvement of endogenous lectins as modifiers of progression and metastasis in the tumor microenvironment has not been explored. In this study, we show that loss of the hepatic asialoglycoprotein receptor (ASGPR) in mice severely reduces the frequency of spontaneous lung metastasis after intrahepatic implantation of murine Lewis lung carcinoma (3LL) cells. Conversely, in vitro treatment with recombinant ASGPR increased the invasive and metastatic capacity of 3LL cells before intrahepatic implantation. ASGPR treatment in vitro increased the expression and production of matrix metalloproteinase-9 through activation of the epidermal growth factor receptor–extracellular signal-regulated kinase (EGFR–ERK) pathway. Our findings identify ASGPR as a novel important factor that responds to endogenous lectins in the tumor microenvironment to promote cancer metastasis by activating the EGFR–ERK pathway through interactions with counter-receptors on cancer cells. Cancer Res; 71(20); 6419–27. ©2011 AACR.
Timing Is Everything: Age of Onset Influences Long-Term Retinopathy Risk in Type 2 Diabetes, Independent of Traditional Risk Factors
Authors: Jencia Wong, Lynda Molyneaux, Maria Constantino, Stephen M. Twigg, Dennis K. Yue
Journal: Diabetes Care (2008)

OBJECTIVE—To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia. RESEARCH DESIGN AND METHODS—Retinopathy data from 624 patients with a type 2 diabetes duration of 20–30 years (group A) were analyzed by stratifying patients according to age of onset of diabetes and glycemic control. Retinopathy status was scored clinically as per a modified Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. To obviate possible bias due to a higher attrition from comorbidities in those with later-onset diabetes and retinopathy, 852 patients with type 2 diabetes of shorter duration (10–12 years, group B) were similarly studied. RESULTS—Prevalence and severity of retinopathy was significantly higher in the younger-onset, group A patients. When further stratified according to mean A1C, retinopathy risk remained increased in younger-onset patients. The greatest impact was seen in those with a mean A1C &amp;gt;9% (odds ratio [OR] for retinopathy 16.6, 7.5, and 2.7 for age of diagnosis &amp;lt;45, 45–55, and &amp;gt;55 years, respectively, P = 0.003). By logistic regression, earlier type 2 diabetes onset is associated with increased retinopathy risk, independent of traditional risk factors (OR of retinopathy 1.9, 1.1, and 1 for age of onset &amp;lt;45, 45–55, and &amp;gt;55 years, respectively). Similar results were found in group B patients. CONCLUSIONS— These data suggest an increased inherent susceptibility to diabetic retinopathy with earlier-onset type 2 diabetes. This further supports the importance of delaying development of diabetes and also implies a need for more stringent metabolic targets for younger individuals.
Safety of sublingual immunotherapy with monomeric all_ergoid in adults: multicenter post‐marketing surveillance study
Authors: C. Lombardi, S. Gargioni, A. Melchiorre, A. Tiri, P. Falagiani, G. Walter Canonica, G. Passalacqua
Journal: Allergy (2001)

Sublingual immunotherapy (SLIT) appears to be acceptably safe in clinical trials, but post-marketing data are needed to provide essential information. This study specifically evaluated the safety of commercial SLIT in adult patients in a post-marketing phase.A total of 198 patients (83 male, 115 female, mean age 24.4 years) receiving SLIT for respiratory allergy were followed up for 3 years by a specific questionnaire for side-effects. SLIT (LAIS, Lofarma SpA, Milan, Italy), a monomeric allergoid in tablets, was administered, in association with drug therapy, pre- or pre-coseasonally for pollen and continuously for mites. The average duration was 12-36 months, and the total of doses was about 32 800. Side-effects were grouped as ocular, gastrointestinal, rhinitis, asthma, urticaria, edema of tongue/lips, and anaphylaxis. The severity was graded as low (no need for treatment or dose adjusting, no interference with activities), moderate (interference with activities/need for drugs/SLIT discontinuation), and severe (life-threatening/hospitalization/emergency care).Seventeen events corresponding to 7.5% of patients and 0.52 per 1000 doses were reported. Seven episodes of rhinitis (two in two patients), three of oral itching, and one of abdominal pain were self-limiting. Two cases of urticaria and two of abdominal pain/nausea were controlled by a temporary dose-adjustment, and one case of urticaria and conjunctivitis required oral antihistamines. Medical intervention was needed in six patients only during a 3-year period.The results of this study, performed in a real situation of clinical practice, confirm the satisfactory safety profile of SLIT.
Risk of Parkinson's disease after hospital contact for head injury: population based case-control study
Authors: K. Rugbjerg, B. Ritz, L. Korbo, N. Martinussen, J. H Olsen
Journal: BMJ (2008)

To determine whether a hospital contact for a head injury increases the risk of subsequently developing Parkinson's disease.Population based case-control study.Denmark.13 695 patients with a primary diagnosis of Parkinson's disease in the Danish national hospital register during 1986-2006, each matched on age and sex to five population controls selected at random from inhabitants in Denmark alive at the date of the patient's diagnosis (n=68 445).Hospital contacts for head injuries ascertained from hospital register; frequency of history of head injury.An overall 50% increase in prevalence of hospital contacts for head injury was seen before the first registration of Parkinson's disease in this population (odds ratio 1.5, 95% confidence interval 1.4 to 1.7). The observed association was, however, due almost entirely to injuries that occurred during the three months before the first record of Parkinson's disease (odds ratio 8.0, 5.6 to 11.6), and no association was found between the two events when they occurred 10 or more years apart (1.1, 0.9 to 1.3).The steeply increased frequency of hospital contacts for a head injury during the months preceding the date at which Parkinson's disease was first recorded is a consequence of the evolving movement disorder rather than its cause.