tbuckley/cabot-search huggingface dataset:
Sperm DNA Integrity in Men Treated for Childhood Cancer
Authors: Patrik Romerius, Olof Ståhl, Christian Moëll, Thomas Relander, Eva Cavallin-Ståhl, Helen Gustafsson, Kerstin Löfvander Thapper, Katarina Jepson, Marcello Spanò, Thomas Wiebe, Yvonne Lundberg Giwercman, Aleksander Giwercman
Journal: Clinical Cancer Research (2010)

It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account.In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay.In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), -0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6-10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083-5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1-4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3-18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given.DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring.
Factors associated with the requirement of ventilatory support during an acute exacerbation of COPD
Authors: Rosalind Benson, Anne Pocock, Nosheen Kazmi, Syed Huq, Sanjeev Agarwal
Journal: European Respiratory Journal (2012)

Background  Invasive or non-invasive ventilatory support is often required for patients hospitalised with acute exacerbation of COPD (AECOPD). We aimed to identify some baseline characteristics associated with subsequent requirement for ventilatory support.  Methods  A retrospective study of consecutive patients admitted with AECOPD in an acute teaching hospital.  Results  67 patients (45% male) with a mean (SD) age of 72 (12), % predicted FEV1 of 55 (20) and baseline ECOG performance status (PS) of 2 (1.2) were studied. 10 (15%) required invasive or non-invasive ventilatory support at some point during their admission.  Conclusions  Patients with AECOPD who subsequently required ventilatory support had a significantly lower SpO2, higher PaCO2 and a higher respiratory rate on admission. They also had a relatively better PS. Admission glucose and lactate levels were also important factors. Identifying high-risk patients based on these specific criteria on admission may help in managing patients with AECOPD more aggressively, thereby improving clinical outcomes.
Lung cancer detection by canine scent: will there be a lab in the lab?
Authors: M. McCulloch, K. Turner, M. Broffman
Journal: European Respiratory Journal (2012)

article in the current issue of the European Respiratory Journal reporting on a study in which trained dogs detected lung cancer with sensitivity of 90% and specificity of 72% [1].Their well-designed study involved 60 lung cancer patients and 110 healthy controls, and is novel for also including ''disease controls''; 50 patients with non-malignant lung disease.The findings of EHMANN et al. [1] corroborate the results of an earlier study of canine scent detection of lung cancer, which reported sensitivity and specificity of 99%.Together, these two papers, which achieved high accuracy while using different dogs, trainers and human subjects, beg the question of where this might all be leading.The purpose of this article is to review the evidence for canine scent detection of human cancers, and focus on how these papers may help advance knowledge in the field of lung cancer.There are very few published data on canine scent detection of cancers in general, or lung cancer in particular, and they vary widely in accuracy achieved and disease studied.However, the high accuracy of canine scent detection of lung cancer suggests dogs might, in the future, make some modest contribution to successes in lung cancer screening and detection.
THE BLOOD PRESSURE IN SPLENOMEGALIC POLYCYTHAEMIA: A SUGGESTION
Authors: F. P. Weber
Journal: BMJ (1925)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following THE BLOOD PRESSURE IN SPLENOMEGALIC POLYCYTHAEMIA: A SUGGESTION Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Ancient Gene Duplication Provided a Key Molecular Step for Anaerobic Growth of Baker's Yeast
Authors: M. Hayashi, B. Schilke, J. Marszalek, B. Williams, E. A. Craig
Journal: Molecular Biology and Evolution (2011)

Mitochondria are essential organelles required for a number of key cellular processes. As most mitochondrial proteins are nuclear encoded, their efficient translocation into the organelle is critical. Transport of proteins across the inner membrane is driven by a multicomponent, matrix-localized “import motor,” which is based on the activity of the molecular chaperone Hsp70 and a J-protein cochaperone. In Saccharomyces cerevisiae, two paralogous J-proteins, Pam18 and Mdj2, can form the import motor. Both contain transmembrane and matrix domains, with Pam18 having an additional intermembrane space (IMS) domain. Evolutionary analyses revealed that the origin of the IMS domain of S. cerevisiae Pam18 coincides with a gene duplication event that generated the PAM18/MDJ2 gene pair. The duplication event and origin of the Pam18 IMS domain occurred at the relatively ancient divergence of the fungal subphylum Saccharomycotina. The timing of the duplication event also corresponds with a number of additional functional changes related to mitochondrial function and respiration. Physiological and genetic studies revealed that the IMS domain of Pam18 is required for efficient growth under anaerobic conditions, even though it is dispensable when oxygen is present. Thus, the gene duplication was beneficial for growth capacity under particular environmental conditions as well as diversification of the import motor components.
Effectiveness of Immunosuppressive Therapy in Older Patients with Aplastic Anemia
Authors: André Tichelli
Journal: Annals of Internal Medicine (1999)

Background: Immunosuppressive therapy has been used for successful treatment of severe aplastic anemia, but little information is available on outcome in older patients. Objective: To evaluate outcome in patients older than 50 years of age who received immunosuppressive therapy for aplastic anemia. Design: Retrospective cohort study. Setting: 56 centers of the European Group for Blood and Marrow Transplantation (EBMT). Patients: 810 patients with aplastic anemia reported between 1974 and 1997. Patients were evaluated according to age group: 60 years of age or older (n = 127), 50 to 59 years of age (n = 115), and 20 to 49 years of age (n = 568; reference group). Intervention: Antilymphocyte globulin, cyclosporine, or both. Measurements: Survival, cause of death, response to treatment, relapse rate, and risk for late complications were analyzed in all patients and by age group. Results: The 5-year survival rate was 57% (95% CI, 46% to 66%) in patients 50 to 59 years of age and 50% (CI, 39% to 60%) in patients 60 years of age or older compared with 72% (CI, 68% to 76%) in patients younger than 50 years of age (P < 0.001). Response to therapy, relapse rate, and risk for clonal complications were similar in all three age groups (P > 0.2). Age was significantly associated with an increased risk for death (relative risk compared with patients 20 to 49 years of age, 1.80 [CI, 1.29 to 2.52] for patients 50 to 59 years of age and 2.57 [CI, 1.87 to 3.53] for patients ≥ 60 years of age), mainly because of bleeding or infection (P = 0.02). Response to immunosuppressive therapy in all patients at 12 months was 62% (CI, 58% to 66%); no difference was seen among the age groups in multivariate analysis (P > 0.2). Sixty-six of the 379 responding patients (17%) subsequently had relapse. The risk for clonal disorders at 10 years was 20% (CI, 15% to 27%). Conclusions: Response to immunosuppression in aplastic anemia is independent of age, but treatment is associated with increased mortality in older patients.
Pleural-fluid myeloperoxidase in complicated and noncomplicated parapneumonic pleural effusions
Authors: J. Alegre, J. Jufresa, R. Segura, A. Ferrer, L. Armadans, C. Aleman, R. Marti, E. Ruiz, T. Fernández de Sevilla
Journal: European Respiratory Journal (2002)

The diagnostic accuracy of myeloperoxidase (MPO) in pleural fluid, for differentiating between complicated and noncomplicated parapneumonic pleural effusions (PPE) evaluated prospectively. Seventy patients aged &gt;18 yrs with PPE (36 complicated and 34 noncomplicated) were studied after admission to a tertiary referral teaching hospital. MPO concentration was measured in plasma and pleural fluid using a double-antibody competitive radioimmunoassay. The concentrations of MPO in complicated and noncomplicated PPE were compared using a Mann-Whitney U-test and multiple logistic regression models were used to predict the odds that an effusion was complicated. MPO pleural-fluid concentrations were significantly higher in complicated than in noncomplicated PPE. After excluding purulent effusions, pleural-fluid MPO was the marker that best differentiated between the two types of PPE: the area under the receiver operating characteristic curve was 0.912, the sensitivity was 87.5% and the specificity was 85.1% at a cut-point limit of 3.000 µg·L −1 . The authors concluded that the concentration of pleural-fluid myeloperoxidase helps to differentiate between nonpurulent complicated and noncomplicated parapneumonic pleural effusions.
Na <sup>+</sup> -Ca <sup>2+</sup> Exchange Activity Is Localized in the T-Tubules of Rat Ventricular Myocytes
Authors: Z. Yang, C. Pascarel, D.S. Steele, K. Komukai, F. Brette, C.H. Orchard
Journal: Circulation Research (2002)

Detubulation of rat ventricular myocytes has been used to investigate the role of the t-tubules in Ca2+ cycling during excitation-contraction coupling in rat ventricular myocytes. Ca2+ was monitored using fluo-3 and confocal microscopy. In control myocytes, electrical stimulation caused a spatially uniform increase in intracellular [Ca2+] across the cell width. After detubulation, [Ca2+] rose initially at the cell periphery and then propagated into the center of the cell. Application of caffeine to control myocytes resulted in a rapid and uniform increase of intracellular [Ca2+]; the distribution and amplitude of this increase was the same in detubulated myocytes, although its decline was slower. On application of caffeine to control cells, there was a large, rapid, and transient rise in extracellular [Ca2+] as Ca2+ was extruded from the cell; this rise was significantly smaller in detubulated cells, and the remaining increase was blocked by the sarcolemmal Ca2+ ATPase inhibitor carboxyeosin. The treatment used to produce detubulation had no significant effect on Ca2+ efflux in atrial cells, which lack t-tubules. Detubulation of ventricular myocytes also resulted in loss of Na+-Ca2+ exchange current, although the density of the fast Na+ current was unaltered. It is concluded that Na+-Ca2+ exchange function, and hence Ca2+ efflux by this mechanism, is concentrated in the t-tubules, and that the concentration of Ca2+ flux pathways in the t-tubules is important in producing a uniform increase in intracellular Ca2+ on stimulation.
Increased levels of osteopontin in sputum supernatant in severe refractory asthma
Authors: V. Delimpoura, P. Bakakos, E. Tseliou, V. Bessa, G. Hillas, D. C. M. Simoes, S. Papiris, S. Loukides
Journal: Thorax (2010)

Osteopontin (OPN) is a glycoprotein that has been associated with inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an intense inflammatory and remodelling process. The aim of this study was to investigate the levels of OPN in sputum supernatants of patients with SRA, to compare them with milder forms of the disease and to investigate their possible association with mediators and cells involved in the inflammatory and remodelling process.33 patients with SRA, 29 with moderate asthma, 21 with steroid-naïve asthma and 20 healthy subjects were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of OPN, vascular endothelial growth factor, transforming growth factor beta1 (TGF-beta1), cysteinyl leukotrienes, interleukin 13 (IL-13), eosinophilic cationic protein (ECP) and IL-8 in sputum supernatants.Median (IQR) OPN levels (pg/ml) were significantly higher in patients with SRA than in those with moderate asthma, steroid-naive asthma and healthy control subjects (1840 (1125-11000) vs 130 (100-210) vs 100 (67-130) vs 50 (42-70), respectively, p<0.001). Regression analysis showed a significant association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL-13, TGF-beta1 and ECP. TGF-beta1 represented the strongest association with OPN. The above associations were not observed in milder forms of the disease or in healthy subjects.The results indicate that OPN levels are higher in SRA than in less severe forms of the disease. Moreover, OPN is associated with mediators involved in both the inflammatory and remodelling process such as TGF-beta1, IL-13 and cysteinyl leukotrienes only in SRA.
Prognostic factors of mortality and cardiovascular outcomes in the tiotropium safety and performance in respimat (TIOSPIR) trial
Authors: Ronald Dahl, Daniel Dusser, Robert Wise, Gordon Pledger, Antonio Anzueto, Achim Mueller, Andrew Fowler, Peter Calverley
Journal: European Respiratory Journal (2014)

Background: Cardiovascular (CV) comorbidities in chronic obstructive pulmonary disease (COPD) patients are frequent. We evaluated whether baseline variables can predict mortality and CV events in the TIOSPIR trial (17,116 COPD patients receiving tiotropium Respimat 5 or 2.5µg or HandiHaler 18µg for a mean of 2.3 yrs).

Methods: Exploratory pooled analysis from TIOSPIR to determine prognostic factors for mortality, major adverse CV event (MACE), fatal MACE, myocardial infarction and stroke outcomes was performed.

Results: Patients with the following characteristics had higher risk of death and/or CV event during the study period: Male, age ≥70 yrs, low FEV1, breathlessness (MMRC≥2), CV medication use and history of CV events (ischemic heart disease [IHD], cardiac arrhythmia), or exacerbation in the last year (table).

View this table:

Table: Unadjusted risk ratio (RR) by baseline characteristic for all-cause mortality/CV events





Conclusions: In TIOSPIR, prognostic factors for CV and all-cause mortality were similar, with greater risk for CV events in patients with CV medication or history (particularly IHD). High MMRC also particularly correlated with fatal CV events. Exacerbations were prognostic for both all-cause and CV death, but not for non-fatal CV events.

Funded by Boehringer Ingelheim.
THE PROPAGATION OF THE VIRUS OF EPIZOOTIC HEMORRHAGIC DISEASE OF DEER IN NEWBORN MICE AND H<scp>E</scp>LA CELLS
Authors: Norma E. Mettler, Lester G. MacNamara, Richard E. Shope
Journal: The Journal of Experimental Medicine (1962)

The New Jersey strain of EHD virus has been propagated in newborn Swiss mice by the intracerebral route and is regularly lethal beyond the first serial mouse passage. A complement-fixing antigen prepared from the brains of infected mice reacts positively with the sera of deer recovered from infection with either the New Jersey or South Dakota strain of virus, but not with the serum of normal deer. The mouse-passaged virus induced an inapparent infection in an experimental deer. The virus can also be grown serially in HeLa cell culture and induces a characteristic cytopathic effect. It is neutralizable in such cultures to high titer by the sera of deer recovered from EHD (New Jersey strain) and to lower titer by the serum of a deer recovered from EHD (South Dakota strain). Normal deer serum does not neutralize the virus in tissue culture. The HeLa cell-passaged virus induced typical lethal EHD in an experimental deer and virus could be recovered from most of the tissues of this animal in HeLa cell culture. An unexplained prozone of inhibition of cytopathogenicity at low dilutions was observed in cultures of some of the organs. The fact that EHD virus exhibited a limited sensitivity to sodium desoxycholate suggests that it may belong in the arbor virus group.
Renal Vein Renin and Juxtaglomerular Activity in Sodium-Depleted Subjects
Authors: HORACIO AJZEN, JOHN L. SIMMONS, JAMES W. WOODS
Journal: Circulation Research (1965)

Ten patients requiring surgery for renal cysts or calculi and having no evidence of secondary hyperaldosteronism were divided, as volunteers for special study, into experimental and control groups. After base line studies, the experimental group was given a diet containing 87 mEq of sodium and 1.0 g of chlorothiazide daily for ten days. Control subjects ate a normal diet. At operation, samples of peripheral and renal venous blood were obtained for measurement of renin activity and renal biopsy was taken for determination of the juxtaglomerular index. Increased renin in renal venous plasma and hypergranularity of the juxtaglomerular apparatus were found in sodium-depleted subjects but not in control subjects. These findings confirm results previously found in animals.
Tumor Necrosis Factor Antagonism With Etanercept Improves Systemic Endothelial Vasoreactivity in Patients With Advanced Heart Failure
Authors: Stephan Fichtlscherer, Lothar Rössig, Susanne Breuer, Mariuca Vasa, Stefanie Dimmeler, Andreas M. Zeiher
Journal: Circulation (2001)

Background — Anti–tumor necrosis factor (TNF)-α therapy with etanercept, a recombinant TNF receptor that binds to and functionally inactivates TNF-α, was shown to improve the functional status of patients with congestive heart failure (CHF). Because administration of TNF-α has been shown experimentally to depress endothelium-dependent relaxation, we hypothesized that TNF-α antagonism with etanercept might improve the depressed systemic endothelial vasodilator function, which importantly contributes to increased peripheral vascular resistance in patients with advanced CHF. Methods and Results — Endothelium-dependent (acetylcholine, ACH; 10 to 50 μg/min) and endothelium-independent (sodium nitroprusside, SNP; 2 to 8 μg/min) forearm blood flow (FBF) responses were measured by venous occlusion plethysmography in 13 patients with documented CHF (New York Heart Association class III) before, 6 hours after, and 7 days after subcutaneous injection of a single dose of 25 mg etanercept. Maximum ACH-induced FBF increased significantly from 6.9±1.0 to 13.0±1.6 mL/min per 100 mL of forearm tissue ( P &lt;0.05) 6 hours after administration of etanercept and returned to 7.0±1.1 mL/min per 100 mL of forearm tissue after 7 days ( P =NS), whereas SNP-induced FBF responses were not significantly affected. In contrast, FBF responses were not altered in control CHF patients, who did not receive etanercept (n=5). Etanercept-induced increases in ACH-mediated FBF were closely correlated with baseline TNF-α serum levels ( r =0.66; P &lt;0.02). Conclusions — The administration of etanercept profoundly improves systemic endothelial vasodilator capacity in patients with advanced heart failure, suggesting an important role of inflammatory mediators for impaired endothelial vasoreactivity in CHF. Improvement of systemic endothelial function might importantly contribute to the beneficial effects of etanercept on the functional status of patients with CHF.
Development of Overt Proteinuria in the Munich Wistar Fro[Combining Diaeresis]mter Rat Is Suppressed by Replacement of Chromosome 6 in a Consomic Rat Strain
Authors: Angela Schulz, Judith Weiss, Maria Schlesener, Jonna Ha[Combining Diaeresis]nsch, Markus Wehland, Norbert Wendt, Peter Kossmehl, Anika Sietmann, Daniela Grimm, Monika Stoll, Jens Randel Nyengaard, Reinhold Kreutz
Journal: Journal of the American Society of Nephrology (2006)

In a cross between the Munich Wistar Frömter (MWF) rat and spontaneously hypertensive rats (SHR), a major quantitative trait locus (QTL) was identified on rat chromosome 6 (RNO6) that demonstrated the strongest linkage to albuminuria among several QTL identified. The QTL represented the only locus that is linked to both early-onset albuminuria and increased renal interstitial fibrosis in adult animals. A consomic MWF-6(SHR) strain in which chromosome 6 from SHR was introgressed into the MWF background therefore was generated to test the relevance of this QTL. Phenotype analysis at 8 wk of age revealed that early onset of albuminuria in MWF with a 55-fold elevation of urinary albumin excretion compared with SHR (P < 0.0001) was completely abolished in MWF-6(SHR). Time-course analysis until week 24 demonstrated only a moderate increase of urinary albumin excretion in MWF-6(SHR), whereas MWF reached levels in the nephrotic range (16.6 +/- 3.5 versus 162.6 +/- 16.0 mg/24 h; P < 0.0001). At this age, analysis of glomerulosclerosis, tubulointerstitial damage, renal interstitial fibrosis, and renal collagen III mRNA expression revealed a significant improvement of all parameters in MWF-6(SHR) compared with MWF (P < 0.05). At 32 wk, MWF but not MWF-6(SHR) demonstrated overt proteinuria (354.6 +/- 37.6 versus 48.8 +/- 13.2; P < 0.0001), whereas serum urea, cholesterol, and triglyceride concentrations were lower and creatinine clearance was higher in MWF-6(SHR) compared with MWF (P < 0.05). Therefore, although albuminuria in MWF is determined by a complex interplay of several QTL, our data demonstrate that genetic exchange of one locus on RNO6 leads to marked suppression of early-onset albuminuria and renal damage in MWF.