tbuckley/cabot-search huggingface dataset:
Airway Bacterial Concentrations and Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Sanjay Sethi, Rohin Sethi, Karen Eschberger, Phyllis Lobbins, Xueya Cai, Brydon J B Grant, Timothy F Murphy
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Increased bacterial concentration (load) in the lower airways and new bacterial strain acquisition have been posited as mechanisms for chronic obstructive pulmonary disease (COPD) exacerbations. Bacterial concentrations are higher during exacerbation than during stable disease; however, these studies are cross sectional and devoid of strain typing.Objectives: To determine if the increased bacterial concentrations function as a separate mechanism for exacerbation induction independent of new strain acquisition.Methods: In a prospective, longitudinal cohort of patients with COPD, the relationship between exacerbation occurrence, sputum bacterial concentrations, and new strain acquisition was examined.Measurements and Main Results: Clinical information, quantitative sputum cultures, and molecular typing of potential bacterial pathogen isolates. Over 81 months, 104 subjects completed 3,009 clinic visits, 560 (19.6%) during exacerbations and 2,449 (80.4%) during stable disease. Among preexisting strains, sputum concentrations of Nontypeable Haemophilus influenzae and Haemophilus haemolyticus were not different in exacerbation versus stable disease. Moraxella catarrhalis (stable, 108.38 ± 0.13 [mean ± SEM] vs. exacerbation, 107.78 ± 0.26; p = 0.02) and Streptococcus pneumoniae (stable, 108.42 ± 0.21 vs. exacerbation, 107.76 ± 0.52; p = 0.07) concentrations were lower during exacerbations compared with stable periods. Concentrations of new strains of H. influenzae (stable, 107.28 ± 0.15 vs. exacerbation, 107.76 ± 0.17; p = 0.04) and M. catarrhalis (stable, 107.85 ± 0.15 vs. exacerbation, 108.37 ± 0.14; p = 0.02), were increased during exacerbations; however, the differences were small.Conclusions: Change in bacterial load is unlikely to be an important mechanism for exacerbations. Better understanding of the host–pathogen interaction, rather than enumerating bacteria in respiratory samples, is required to provide new insights into bacterial infection in COPD.
Effect of a Haloperidol Challenge on Regional Brain Metabolism in Neuroleptic-Responsive and Nonresponsive Schizophrenic Patients
Authors: Elsa J. Bartlett, Jonathan D. Brodie, Philip Simkowitz, Ralf Schl"sser, Stephen L. Dewey, Jean-Pierre Lindenmayer, Henry Rusinek, Adam Wolkin, Robert Cancro, Wynne Schiffer
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The CNS metabolic response to a neuroleptic challenge in treatment-responsive and nonresponsive schizophrenic patients was measured in order to examine the relation between treatment outcome and the capacity to alter neurochemical function in response to acute receptor blockade. METHOD: Positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) were used to measure regional cerebral metabolism in seven schizophrenic patients judged to have been responsive to drug treatment previously and seven nonresponsive schizophrenic patients after a drug-free period of at least 3 weeks (baseline) and again 12 hours after administration of 5.0 mg of haloperidol. RESULTS: The haloperidol challenge caused widespread decreases in absolute metabolism in the nonresponsive patients but not the responsive patients. These group differences reflect the findings on the second (challenge) scans, since metabolic values at baseline were not statistically different in the two groups. The pattern of decreased metabolic activity in the nonresponders after the haloperidol challenge is similar to that previously observed in normal subjects. CONCLUSIONS: The metabolic response to drug challenge separates treatment responders from nonresponders and normal subjects. The results suggest that subtyping of schizophrenia (and other psychiatric disorders) can be achieved by measuring the physiologic response to a pharmacologic challenge in vivo with chemical brain-imaging techniques.
MEOX2 regulates nuclear factor-κB activity in vascular endothelial cells through interactions with p65 and IκBβ
Authors: Yun Chen, Arnold B. Rabson, David H. Gorski
Journal: Cardiovascular Research (2010)

AimsTumours secrete proangiogenic factors to induce the ingrowth of blood vessels, the end targets of which are vascular endothelial cells (ECs). The MEOX2 homeoprotein inhibits nuclear factor-κB (NF-κB) signalling and EC activation in response to serum and proangiogenic factors. We hypothesize that MEOX2 interacts with components of this pathway in vascular ECs to modulate NF-κB activity and EC activation and that these interactions depend upon specific domains within the MEOX2 protein.
Fatal Accidents: The Role of Psychopathology, Social Stress, and Acute Disturbance
Authors: MELVIN L. SELZER, JOSEPH E. ROGERS, SUE KERN
Journal: American Journal of Psychiatry (1968)

Significantly more psychopathology and social stress were present in 96 drivers causing fatal accidents than in a matched control group. In the fatality group, prior accidents were significantly related to psychopathology but not to social stress. Twenty percent of the fatality drivers had acutely disturbing experiences within six hours of causing a fatal accident. The authors argue that stricter controls for drivers are necessary if our highways are to be made safer.
O70 LIFETOUCH: A NOVEL REMOTE MONITORING DEVICE TO IDENTIFY PATIENTS WITH ADVANCED CIRRHOSIS MOST AT RISK OF DECOMPENSATION – A PROOF OF CONCEPT STUDY
Authors: D. Chatterjee, H. Jones, A. Gallego León, G. Privitera, R. Jalan, R. Mookerjee
Journal: Journal of Hepatology (2014)
Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin
Authors: Bart Spee, Martijn DB Jonkers, Brigitte Arends, Gerard R Rutteman, Jan Rothuizen, Louis C Penning
Journal: Molecular Cancer (2006)

Abstract Background Apoptosis resistance occurs in various tumors. The anti-apoptotic XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3 activation. Our aim is to evaluate whether RNA inhibition against XIAP increases the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and doxorubicin. We used small interfering RNA's (siRNA) directed against XIAP in three cell-lines derived from bile-duct epithelia (BDE), mammary carcinoma (P114), and osteosarcoma (D17). These cell-lines represent frequently occurring canine cancers and are highly comparable to their human counterparts. XIAP down-regulation was measured by means of quantitative PCR (Q-PCR) and Western blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or doxorubicin and compared to mock- and nonsense-treated controls. Viability was measured with a MTT assay. Results All XIAP siRNA treated cell-lines showed a mRNA down-regulation over 80 percent. Western blot analysis confirmed mRNA measurements. No compensatory effect of IAP family members was seen in XIAP depleted cells. The sensitivity of XIAP depleted cells for TRAIL was highest in BDE cells with an increase in the ED 50 of 14-fold, compared to mock- and nonsense-treated controls. The sensitivity of P114 and D17 cell-lines increased six- and five-fold, respectively. Doxorubicin treatment in XIAP depleted cells increased sensitivity in BDE cells more than eight-fold, whereas P114 and D17 cell-lines showed an increase in sensitivity of three- and five-fold, respectively. Conclusion XIAP directed siRNA's have a strong sensitizing effect on TRAIL-reduced cell-viability and a smaller but significant effect with the DNA damaging drug doxorubicin. The increase in efficacy of chemotherapeutics with XIAP depletion provides the rationale for the use of XIAP siRNA's in insensitive canine tumors.
Contribution of Body Habitus and Craniofacial Characteristics to Segmental Closing Pressures of the Passive Pharynx in Patients with Sleep-Disordered Breathing
Authors: TOSHIHIDE WATANABE, SHIROH ISONO, ATSUKO TANAKA, HIDEKI TANZAWA, TAKASHI NISHINO
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Obesity and craniofacial abnormalities may contribute to the pathogenesis of obstructive sleep apnea. The purpose of this study was to evaluate the influence of body habitus and craniofacial characteristics on types of pharyngeal closure. The types of pharyngeal closure were determined by endoscopic evaluations of closing pressures of the passive pharynx in 54 paralyzed and anesthetized patients with sleep-disordered breathing (SDB). Assessment of craniofacial characteristics of the SDB patients and 24 normal subjects were made by lateral cephalometry. As compared with normal subjects, SDB patients demonstrated receded mandibles and long lower faces with downward mandible development. SDB patients with positive closing pressures at both the velopharynx and oropharynx (VP + OP group) demonstrated smaller maxillas and mandibles than those with positive closing pressures at the velopharynx only (VP-only group). Obesity was more prominent in the VP-only group than in the VP + OP group. Our results suggest that obesity and craniofacial abnormalities contribute synergistically to increases in collapsibility of the passive pharyngeal airway in patients with SDB. Furthermore, the relative contribution of obesity and craniofacial anomaly appears to determine the type of pharyngeal closure in SDB.
Human blood monocytes, but not alveolar macrophages, reveal increased CD11b/CD18 expression and adhesion properties upon receptor-dependent activation
Authors: J Lundahl, G Hallden, CM Skold
Journal: European Respiratory Journal (1996)

The beta 2 integrin receptor CD11b/CD18 mediates adhesion to the endothelial lining as well as to extracellular matrix components. The present study was undertaken to investigate peripheral human blood monocytes (BMs) and alveolar macrophages (AMs) with respect to quantitative levels of CD11b/CD18 and adhesion properties in relation to the state of activation. BMs and AMs were recruited from healthy subjects. Quantitative analysis of the surface expression of CD11b/CD18 by flow cytometric technique and adhesion properties to albumin-coated surfaces were performed both on resting and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated cells. Receptor independent stimuli (phorbol-12-myristate-13-acetate (PMA) and ionomycin) were used in additional experiments. Intracellular stored CD11b/CD18 was evaluated by flow cytometry and immunofluorescence microscopy. The surface expression of CD11b/CD18 on resting BMs increased fivefold (p < 0.01) upon fMLP activation. On resting AMs, the surface expression of CD11b/CD18 was significantly higher (p < 0.01) compared to resting BMs but did not increase further upon activation with fMLP, PMA or ionomycin. In contrast to BMs, no evidence for an additional intracellular pool of CD11b/CD18 was found in AMs. The adherence of resting BMs did not significantly differ from the adherence of resting AMs. After fMLP activation, the adherence of BMs, but not AMs, increased significantly (p < 0.05). Our results indicate that in vivo differentiation of human blood monocytes into alveolar macrophages implies reduced responsiveness to fMLP in terms of CD11b/CD18 upregulation and adhesion properties, and that the lack of upregulation of CD11b/CD18 on alveolar macrophages presumably depends on the absence of an additional intracellular pool.
Mortality in adults aged 26-54 years related to socioeconomic conditions in childhood and adulthood: post war birth cohort study
Authors: D. Kuh
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To examine premature mortality in adults in relation to socioeconomic conditions in childhood and adulthood. <b>Design:</b> Nationally representative birth cohort study with prospective information on socioeconomic conditions. <b>Setting:</b> England, Scotland, and Wales. <b>Study members:</b> 2132 women and 2322 men born in March 1946 and followed until age 55 years. <b>Main outcome measures:</b> Deaths between 26 and 54 years of age notified by the NHS central register. <b>Results:</b> Study members whose father9s occupation was manual at age 4, or who lived in the worst housing, or who received the poorest care in childhood had double the death rate during adulthood of those living in the best socioeconomic conditions. All indicators of socioeconomic disadvantage at age 26 years, particularly lack of home ownership, were associated with a higher death rate. Manual origins and poor care in childhood remained associated with mortality even after adjusting for social class in adulthood or home ownership. The hazard ratio was 2.6 (95% confidence interval 1.5 to 4.4) for those living in manual households as children and as adults compared with those living in non-manual households at both life stages. The hazard ratio for those from manual origins who did not own their own home at age 26 years was 4.9 (2.3 to 10.5) compared with those from non-manual origins who were home owners. <b>Conclusions:</b> Socioeconomic conditions in childhood as well as early adulthood have strongly influenced the survival of British people born in the immediate post war era. <h3>What is already known on this topic</h3> Associations between socioeconomic conditions in childhood and mortality in adulthood suggest that risks to survival begin in early life Studies have been generally retrospective, been unrepresentative, used only one marker of childhood conditions, controlled inadequately for adult conditions, or not included women <h3>What this study adds</h3> The death rate for women and men between 26 and 54 years living in poor socioeconomic conditions in childhood was double that of those living in the best conditions Those for whom socioeconomic disadvantage continued into early adulthood were between three and five times more likely to die than those in the most advantageous conditions
Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP)
Authors: H. Fensterer, C. Schade-Brittinger, H.-H. Müller, S. Tebbe, J. Fass, U. Lindig, U. Settmacher, W.E. Schmidt, A. Märten, M.P. Ebert, M. Kornmann, R. Hofheinz, E. Endlicher, C. Brendel, P.J. Barth, D.K. Bartsch, P. Michl, T.M. Gress
Journal: Annals of Oncology (2013)
The contents of consciousness: From C to shining C++
Authors: Michael H. Joseph, Samuel R. H. Joseph
Journal: Behavioral and Brain Sciences (2001)

We suggest that consciousness (C) should be addressed as a multilevel concept. We can provisionally identify at least three, rather than two, levels: Gray's system should relate at least to the lowest of these three levels. Although it is unlikely to be possible to develop a behavioural test for C, it is possible to speculate as to the evolutionary advantages offered by C and how C evolved through succeeding levels. Disturbances in the relationships between the levels of C could underlie mental illness, especially schizophrenia.
Intentional schema will not do the work of a theory of mind
Authors: David Premack, Ann James Premack
Journal: Behavioral and Brain Sciences (1996)

Abstract Barresi &amp; Moore's “intentional schema” will not do the work of “theory of mind.” Their model will account neither for fundamental facts of social competence, such as the social attributions of the 10-month-old infant, nor the possibility that, though having a theory of mind, the chimpanzee's theory is “weaker” than the human's.
A REPORT ON SEVEN HUNDRED CONSECUTIVE CASES OF TINEA CAPITIS
Authors: H. M. SCOTT
Journal: British Journal of Dermatology (1911)

The following observations were made in a series of seven hundred cases of scalp ringworm seen in the Dermatological Clinic a t the London Hospital.As the ma,jority of the patients were attending the elementary schools of the districts around the hospital, the proportion of the various forms of tinea observed may be taken to represent, with some accuracy, the distribution of the ringworm parasites in the school-children of London.The hair was examined microscopically in every case and the fungus detnonstrated.. Owing t o the large amount of work in the Department it was found impossible to make cultures with any approach to regularity and the varieties of microsporon and endothrix have been grouped together.Variety offungw.-Of the 700 cases, 628 were cases of microsporon ringworm and 72 were cases of endothrix, respectively 89.8 and 10.2 per cent.&x.-405 of the 700 patients were boys and 295 girls, respectively 57.8 and 42.2 per cent.There was some difference in the sex proportion in the two varieties, the microsporon being relatively niore common in the boys.Males.Feniales.Total. Xcrosporon cases..
Efficacy and safety of meropenem–clavulanate added to linezolid-containing regimens in the treatment of MDR-/XDR-TB
Authors: Saverio De Lorenzo, Jan Wilem Alffenaar, Giovanni Sotgiu, Rosella Centis, Lia D'Ambrosio, Simon Tiberi, Mathieu S. Bolhuis, Richard van Altena, Piero Viggiani, Andrea Piana, Antonio Spanevello, Giovanni Battista Migliori
Journal: European Respiratory Journal (2012)

Clinical experience on meropenem–clavulanate to treat tuberculosis (TB) is anecdotal (according to case reports on 10 patients). The aim of our case–control study was to evaluate the contribution of meropenem–clavulanate when added to linezolid-containing regimens in terms of efficacy and safety/tolerability in treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases after 3 months of second-line treatment. 37 cases with MDR-/XDR-TB were prescribed meropenem–clavulanate (3 g daily dose) in addition to a linezolid-containing regimen (dosage range 300–1200 mg·day −1 ), designed according to international guidelines, which was prescribed to 61 controls. The clinical severity of cases was worse than that of controls (drug susceptibility profile, proportion of sputum-smear positive and of re-treatment cases). The group of cases yielded a higher proportion of sputum-smear converters (28 (87.5%) out of 32 versus nine (56.3%) out of 16; p=0.02) and culture converters (31 (83.8%) out of 37 versus 15 (62.5%) out of 24; p=0.06). Excluding XDR-TB patients (11 (11.2%) out of 98), cases scored a significantly higher proportion of culture converters than controls (p=0.03). One case had to withdraw from meropenem–clavulanate due to increased transaminase levels. The results of our study provide: 1) preliminary evidence on effectiveness and safety/tolerability of meropenem–clavulanate; 2) reference to design further trials; and 3) a guide to clinicians for its rationale use within salvage/compassionate regimens.
Interstitial lung diseases in collagen vascular diseases
Authors: C Lamblin, C Bergoin, T Saelens, B Wallaert
Journal: European Respiratory Journal (2001)

In this review, a clinical update is presented of the most important collagen vascular diseases (CVDs) and the different types of interstitial lung disease (ILD) encountered in these CVDs. These CVDs represent a heterogenous group of immunologically mediated inflammatory disorders with a large variety of affected organs besides the lungs. The frequency, clinical presentation, prognosis and response to therapy vary depending on the histological pattern (usual interstitial pneumonia, desquamative interstitial pneumonia, organising pneumonia, diffuse alveolar damage, nodular lesions, etc. ), as well as on the underlying CVD (scleroderma, rheumatoid arthritis, systemic lupus erythematosus, dermatopolymyositis, Sjögren's syndrome or mixed connective tissue disease). The diagnosis of most of these CVDs is based on a number of criteria; in several of these, however, lung involvement is not part of the diagnostic criteria. In addition, there may be overlaps between several of these CVDs. Optimal treatment varies depending on the type of collagen vascular disease and the presence of interstitial lung disease, although in many cases, a combination of corticosteroids and cytostatic drugs are given.
A Randomized Trial of High-Dose Compared with Low-Dose Omega-3 Fatty Acids in Severe IgA Nephropathy
Authors: JAMES V. DONADIO, TIMOTHY S. LARSON, ERIK J. BERGSTRALH, JOSEPH P. GRANDE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Tested was the hypothesis that high-dose omega (ω)-3 fatty acids will be more effective than low-dose ω-3 fatty acids in preserving renal function in patients with severe IgA nephropathy in a randomized, open-label, parallel-group clinical trial. Patients were assigned to receive either high-dose fatty acids (EPA 3.76 g and DHA 2.94 g) or low-dose fatty acids (EPA 1.88 g and DHA 1.47 g), both given daily in a highly purified ethyl ester concentrate (Omacor). Patients were treated for a minimum of 2 yr in the absence of a treatment failure or until study closure (January 2000). Seventy-three patients were enrolled in the trial with two ranges of elevated serum creatinine (SC): 63 patients (86%) with a range of 1.5 to 2.9 mg/dl and 10 patients (14%) with a range of 3.0 to 4.9 mg/dl. The primary end point, within-patient rates of change in SC (2-yr minimum), showed an annualized median increase in SC of 0.08 mg/dl per yr in the low-dose group and 0.10 mg/dl per yr in the high-dose group ( P = 0.51). Patients in the lower entry SC range had lower SC slopes ( P = 0.02) and less end-stage renal disease (ESRD) ( P &lt; 0.001) compared with those in the higher entry SC range. No patient died, and 18 patients developed ESRD: 10 in the low-dose group and 8 in the high-dose group ( P = 0.56). SC slopes were significantly lower, and survival free of ESRD was significantly higher (both, P = 0.04) in the 63 Omacor-treated patients compared with the 22 placebo-treated patients from our previously reported clinical trial in which both groups had a similar level of renal impairment. Patient compliance was excellent, and no serious adverse events were noted. Low-dose and high-dose ω-3 fatty acids were similar in slowing the rate of renal function loss in high-risk patients with IgA nephropathy, particularly those with moderately advanced disease.
TGF- downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients
Authors: C. A. Crane, S. J. Han, J. J. Barry, B. J. Ahn, L. L. Lanier, A. T. Parsa
Journal: Neuro-Oncology (2009)

The activating receptor NKG2D, expressed by natural killer (NK) cells and CD8+ T cells, has a role in the specific killing of transformed cells. We examined NKG2D expression in patients with glioblastoma multiforme and found that NKG2D was downregulated on NK cells and CD8+ T cells. Expression of NKG2D on lymphocytes significantly increased following tumor resection and correlated with an increased ability to kill NKG2D ligand-positive tumor targets. Despite the presence of soluble NKG2D ligands in the sera of glioblastoma patients, NKG2D downregulation was primarily caused by tumor-derived tumor growth factor-β, suggesting that blocking of this cytokine may have therapeutic benefit.