tbuckley/cabot-search huggingface dataset:
Presence of Type C Particles Containing Reverse Transcriptase in L1210 Leukemia2
Authors: H. S. Allaudeen, J. R. Bertino
Journal: JNCI Journal of the National Cancer Institute (1977)

A murine L1210 leukemia cell line was grown either in vitro or in vivo by ip injection of 106 cells/mouse in C57BL × DBA)F1 mice. It contained particles that resembled murine leukemia virus. Electron microscopic examination of the cells showed both intracytoplasmic and budding type C particles. Similar particles were also seen in the high-speed pellet (90,000 × g) obtained from both mouse ascitic fluid and the supernatant from cells grown in tissue culture. When the high-speed pellet was centrifuged in a sucrose density gradient, particles banding at densities 1.16–1.18 g/ml were detected. The virus appeared to be N-tropic. These type C particles contained an RNA-dependent DNA polymerase (reverse transcriptase) activity and performed endogenous DNA synthesis. The enzyme was purified from the cells and virus particles; these enzymes were indistinguishable in their properties. The molecular weight, as determined by velocity sedimentation and gel filtration, was approximately 70,000. Primer template preference studies indicated that the purified enzyme utilized synthetic ribo templates better than synthetic deoxyribo templates. It could also utilize (dG)≈15 (Cm)n, a primer template specific for reverse transcriptase. The enzyme could transcribe heteropolymeric regions of 70S RNA from Rauscher murine leukemia virus (R-MuLV) and had RNaseH activity as well. The enzyme activity was inhibited by antibody directed against the reverse transcriptase from R-MuLV. The biophysical, biochemical, and immunologic properties of the purified enzyme resembled those of the reverse transcriptase from R-MuLV.
New Clinical Subtypes of Parkinson Disease and Their Longitudinal Progression
Authors: Seyed-Mohammad Fereshtehnejad, Silvia Rios Romenets, Julius B. M. Anang, Véronique Latreille, Jean-François Gagnon, Ronald B. Postuma
Journal: JAMA Neurology (2015)

<h3>Importance</h3> There is increasing evidence that Parkinson disease (PD) is heterogeneous in its clinical presentation and prognosis. Defining subtypes of PD is needed to better understand underlying mechanisms, predict disease course, and eventually design more efficient personalized management strategies. <h3>Objectives</h3> To identify clinical subtypes of PD, compare the prognosis and progression rate between PD phenotypes, and compare the ability to predict prognosis in our subtypes and those from previously published clustering solutions. <h3>Design, Setting, and Participants</h3> Prospective cohort study. The cohorts were from 2 movement disorders clinics in Montreal, Quebec, Canada (patients were enrolled during the period from 2005 to 2013). A total of 113 patients with idiopathic PD were enrolled. A comprehensive spectrum of motor and nonmotor features (motor severity, motor complications, motor subtypes, quantitative motor tests, autonomic and psychiatric manifestations, olfaction, color vision, sleep parameters, and neurocognitive testing) were assessed at baseline. After a mean follow-up time of 4.5 years, 76 patients were reassessed. In addition to reanalysis of baseline variables, a global composite outcome was created by merging standardized scores for motor symptoms, motor signs, cognitive function, and other nonmotor manifestations. <h3>Main Outcomes and Measures</h3> Changes in the quintiles of the global composite outcome and its components were compared between different subtypes. <h3>Results</h3> The best cluster solution found was based on orthostatic hypotension, mild cognitive impairment, rapid eye movement sleep behavior disorder (RBD), depression, anxiety, and Unified Parkinson's Disease Rating Scale Part II and Part III scores at baseline. Three subtypes were defined as<i>mainly motor/slow progression</i>,<i>diffuse/malignant</i>, and<i>intermediate</i>. Despite similar age and disease duration, patients with the diffuse/malignant phenotype were more likely to have mild cognitive impairment, orthostatic hypotension, and RBD at baseline, and at prospective follow-up, they showed a more rapid progression in cognition (odds ratio [OR], 8.7 [95% CI, 4.0-18.7];<i>P</i> &lt; .001), other nonmotor symptoms (OR, 10.0 [95% CI, 4.3-23.2];<i>P</i> &lt; .001), motor signs (OR, 4.1 [95% CI, 1.8-9.1];<i>P</i> = .001), motor symptoms (OR, 2.9 [95% CI, 1.3-6.2];<i>P</i> &lt; .01), and the global composite outcome (OR, 8.0 [95% CI, 3.7-17.7];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> It is recommended to screen patients with PD for mild cognitive impairment, orthostatic hypotension, and RBD even at baseline visits. These nonmotor features identify a diffuse/malignant subgroup of patients with PD for whom the most rapid progression rate could be expected.
Effect of long-term treatment with fenspiride on clinical and functional status of patients with chronic obstructive pulmonary disease
Authors: Tetyana Pertseva, Olena Myronenko, Natalya Klimenko
Journal: European Respiratory Journal (2013)

The aim of our study was to assess the efficacy of fenspiride (F) as complementary anti-inflammatory therapy in combination with fenoteroly+ipratropium bromide (F+I) in patients COPD phenotype as chronic bronchitis.

Study population: 20 pts with COPD A-B (13 males (65%), were studied over a 6-month treatment period. Mild age 49,02+11,32 year, duration of COPD 13,03+4,76. 1st gr.(10 pts) – combined therapy with F (160 mg/day) and F+I (200+80 mcg dayly). 2nd gr. (10 pts) – only F+I (400+160 mcg/day).

Methods: the quality of life (QOL) was evaluated using the SGRQ. Functional status was accessed by pulmonary function test (PFT) and pneumotonometria, 6MWD test and Borg dyspnea scale. All studies as well as the SGRQ underwent again under the same condition in 6-months later.

Results: significant increase was observed in all of the SGRQ domains in 1st gr (p<0,01). Changes in pulmonary functions were significantly correlated with activity, impact and total SGRQ scores (p<0,001). Reduction of bronchial obstruction was less considerable and is comparable in both groups (p=0,04, p=0,038). An increase of 25,15±5,5 meters was determined in the 6 MWD. Perceived dyspnea severity and leg fatigue severity were reduced in 1st gr (p<0.05). Significant increases were obtained in the respiratory muscle strength (p=0,01).

Conclusion: the study showed greater efficacy of long-term treatment with fenspiride and fenoterol+ipratropium bromide compared with fenoterol+ipratropium bromide. This combination regimen can be recommended for the reduction of inflammation and prevention of disease progression for patients with COPD phenotype as chronic bronchitis.
Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses’ Health Study II
Authors: Holly R Harris, Karen H Costenbader, Fan Mu, Marina Kvaskoff, Susan Malspeis, Elizabeth W Karlson, Stacey A Missmer
Journal: Annals of the Rheumatic Diseases (2015)

The aetiologies of endometriosis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are all characterised by immune dysfunction. SLE and RA occur more often in women, and reproductive and hormonal factors have been shown to be related to increased risk. However, only one previous study has evaluated the temporal association between endometriosis and SLE or RA. We sought to investigate the association between laparoscopically confirmed endometriosis and subsequently diagnosed SLE and RA.We analysed data from the Nurses' Health Study II (n=114 453 women) over a 22-year follow-up period. Multivariable, time-varying Cox proportional hazards models were used to calculate HRs and 95% CIs for the association between laparoscopically confirmed endometriosis and confirmed incident SLE or RA.From 1989 to 2011, 103 incident cases of SLE and 390 cases of RA were confirmed. Laparoscopically confirmed endometriosis was significantly associated with subsequent SLE diagnosis (HR=2.03; CI 1.17 to 3.51) and RA diagnosis (HR=1.41; CI 1.05 to 1.89). These associations were robust to adjustment for SLE or RA risk factors and for potential confounders; however, adjustment for hysterectomy and oophorectomy attenuated both relations such that they were no longer significant. No significant differences by infertility status or age (<45 years) were observed.Our findings suggest an association between endometriosis and risk of SLE and RA. It remains to be understood whether and how endometriosis itself, or hysterectomy or other factors associated with endometriosis, is related to risk of SLE or RA.
Zinc Uptake in Normal and Leukemic Lymphocytes: Effect of Poly-l-ornithine2
Authors: Jerry L. Phillips, John A. Tuley, Robert P. Bowman
Journal: JNCI Journal of the National Cancer Institute (1977)

Phytohemagglutinin and poly-l-ornithine were tested for their ability to stimulate uptake of transferrin-bound zinc by lymphocytes from both normal donors and donors with chronic lymphocytic leukemia. The ratio of zinc uptake in poly-l-ornithine cultures to zinc uptake in phytohemagglutinin cultures was 0.9±0.3 for leukemic lymphocytes and 1.9±0.2 for normal lymphocytes. Results indicated that this technique may be useful in the diagnosis of chronic lymphocytic leukemia as well as in the assessment of the efficacy of chemotherapeutic regimens.
Maternal stress during pregnancy and childhood asthma: The KOALA birth cohort study
Authors: Ischa Kummeling, Monique Mommers, John Penders, Caroline Bastiaenen, Carel Thijs
Journal: European Respiratory Journal (2011)

Introduction:  Asthma is among the most common chronic diseases in children. The development of the immune system into an asthmatic makeup may begin in utero and maternal stress can drive immune responses. Increase in chronic stress of women has paralleled the rising prevalence of asthma.   Aim:  To investigate whether maternal perceived stress during pregnancy increases the risk of developing asthma in childhood.   Methods:  Within the KOALA Birth Cohort Study, The Netherlands, maternal perceived stress was ascertained by using the 10-item version of Cohen9s Perceived Stress Scale at 14 and 30 weeks of pregnancy.  Associations with parentally reported wheeze and asthma (n = 1783), total and specific IgE (n = 360) and lung function (standardized FEV1 and FVC; n =417) at age 6-7 years were analyzed using multivariable regression analyses. Asthma was defined as ever doctor-diagnosed asthma with clinical symptoms and/or the use of prophylactic asthma medication in the last 12 months.   Results:  Maternal perceived stress was not associated with asthma at age 6-7 years (stress in first trimester: adjusted OR 0.74; CI95% 0.36-1.51; third trimester: 0.82, 0.43-1.59; or both trimesters: 0.90; 0.43-1.87). Maternal stress was also not associated with allergic sensitization (first trimester: 0.50; 0.19-1.30; third trimester: 0.70; 0.28-1.72; or both trimesters: 0.39; 0.12-1.24). No statistically significant associations were found between perceived stress and FEV1 and FVC, nor between the level of stress (low, medium, high tertile) in the first or third trimesters and any outcome.   Conclusions:  This study did not find evidence for an effect of maternal stress in pregnancy on asthma development at age 6-7 years.
Fatigue in Ankylosing Spondylitis Is Associated With the Brain Networks of Sensory Salience and Attention
Authors: Qi Wu, Robert D. Inman, Karen D. Davis
Journal: Arthritis & Rheumatology (2013)

Fatigue is one of the cardinal features of ankylosing spondylitis (AS) and contributes substantially to the disability associated with this disease. The mechanisms underlying fatigue in AS remain poorly understood, and this has hampered the development of targeted, effective treatment of this disabling feature of AS. The current study was undertaken, therefore, to investigate the brain networks underlying fatigue in AS.Twenty patients with back pain secondary to AS (15 men and 5 women; mean ± SD age 34.8 ± 11.9 years) and 20 age- and sex-matched controls consented to participate in the study. Patients underwent clinical assessment of AS using the Fatigue Severity Scale, the Affect Intensity Measure, and the McGill Pain Questionnaire. Brain gray matter and white matter connectivity was assessed using 3T magnetic resonance imaging.The patients with AS had significant fatigue that correlated with measures of their emotional strength and spinal mobility. Individual fatigue scores were negatively correlated with the amount of gray matter in areas of the dorsal and ventral attention networks, the somatosensory cortices, and the caudate nucleus, but were positively correlated with gray matter within the executive control network and putamen. Moreover, in patients with high fatigue scores, white matter tracts connecting these brain structures (e.g., inferior fronto-occipital fasciculi, superior/inferior longitudinal fasciculi, and corticothalamic tracts) exhibited low fractional anisotropy (indicative of decreased white matter tract integrity).These data indicate that fatigue in AS involves sensory salience and attention brain networks.
Efficacy of pulmonary rehabilitation in patients with interstitial lung disease
Authors: Atsuhito Nakazawa, Eri Hagiwara, Ou Yamaguchi, Ryo Ogata, Takeshi Shinohara, Yusuke Matsumoto, Kaori Tsuruta, Takuma Sasaki, Takashi Ogura
Journal: European Respiratory Journal (2012)

Objectives: There are few reports describing the efficacy of pulmonary rehabilitation (PR) in patients with interstitial lung disease (ILD). We studied whether PR could improve functional status in a group of patients with ILD.

Methods: PR was carried out for 12 weeks for clinically stable outpatients of our institute. Fifteen patients with ILD were enrolled in this prospective study. Six-minute walking test (6MWT), lung function test and evaluation of health-related quality of life including SGRQ were performed before and after the program. 6MWT and lung function test were also evaluated in 18 ILD patients without PR program with an interval of 12 weeks and compared with ILD patients who completed the program.

Results: There was no significantly improved factor with the program in patients with ILD. %FVC (67.3% to 62.6%, p<0.05) and body weight (64.9 kg to 63.7 kg, p<0.05) were significantly decreased contrary to expectations. However, 6-minute walking distance (6MWD) was slightly improved after the program (369.3 m to 382.7 m) in contrast to the significant decrease in ILD patients without PR (409.4 m to 375.8 m, p<0.05). Statistically significant difference was confirmed in the amount of change in 6MWD in these two groups (13.3 m vs. -33.5 m, p<0.05). Despite that ILD patients with PR had lower lung function than those without PR at the initiation of the study, PR was effective to keep the exercise performance from deteriorating.

Conclusions: Our results show that PR prevents the deterioration of functional status in patients with ILD. PR should be considered as a standard of care for ILD patients.
Repeated lipopolysaccharide stimulation causes corticosteroid insensitive inflammation in lung via phosphoinositide-3-kinase δ signaling
Authors: Genki Kimura, Keitaro Ueda, Yuki Nishimoto, Takashi Masuko, Tadashi Kusama, Peter J. Barnes, Kazuhiro Ito, Yasuo Kizawa
Journal: European Respiratory Journal (2014)

Respiratory bacterial infections cause exacerbation of respiratory diseases such as severe asthma and COPD, which are corticosteroid refractory, and the aim is to set up corticosteroid insensitive animal model exposed to lipopolysaccharide (LPS) and evaluate the molecular signaling. Here we show that repeated intranasal LPS challenge induced corticosteroid insensitive inflammation in mice, and a phospoinositide-3-kinase (PI3K) δ inhibitor restored the corticosteroid action in that model. LPS was administrated intranasally to A/J male mice for 1-3 days, and IC87114 and/or fluticasone propionate (FP) were treated intranasally at 2 h before each LPS administration. BALF was collected at 24 h after the last LPS administration and neutrophils were quantified by FACS analysis. The level of CXCL1 in BALF was also determined using a commercially available kit. Repeated LPS exposure in contrast to single treatment showed significant increase in neutrophils and CXCL1 in BALF, which were not inhibited by FP (0.05 – 1.0 mg/ml). Phospho-Akt, a surrogate marker of PI3K activation, also increased. Although a selective PI3K δ inhibitor, IC87114 (4.0 mg/ml) alone did not a show beneficial effects, combination of IC87114 and FP elicited stronger inhibition of neutrophilia and CXCL1 production. In addition, combination of theophylline (2.0 mg/ml) and FP also showed significant inhibition on the airway inflammation induced by LPS. This profile suggests that a PI3K δ inhibitor with corticosteroid offers potential treatment of airway inflammation in patients with respiratory disease during bacterial infection.
The effect of breastfeeding on development of sensitization in preschool children
Authors: Ea Cecilie Jelding-Dannemand, Ann-Marie Malby Schoos, Klaus Bønnelykke, Hans Bisgaard
Journal: European Respiratory Journal (2013)

Background:  Mothers of children with a predisposition to atopic diseases are generally recommended extended breastfeed. However, recent studies indicate that long duration of breastfeeding increases the risk atopic dermatitis and the evidence for a protective effect on sensitization remains elusive.  Objective:  The aim of this study was to investigate the effects of the duration of exclusive and total breastfeeding on the development of sensitization in preschool children.  Method:  411 children were included from the Copenhagen Prospective Study of Asthma in Childhood (COPSAC2000) birth cohort born of mothers with a history of asthma. SPT and sIgE were simultaneously measured when the children were 6mo, 18mo, 4yrs and 6yrs old against 22 specific allergens. Allergic sensitization was defined as a SPT with a wheal size ≥ 2 mm at young age (6 and 18 months) and ≥ 3 mm at age 4 and 6 years or sIgE ≥ 0,35 IU/mL.  Information on breastfeeding was gathered by interview at the clinic when the children were 12 months old.  Results:  Neither breastfeeding exclusively for more than 4 months or 6 months showed any significant difference with regards to development of allergic sensitization in the children. Partial breastfeeding for more than 4 months compared to less than 4 months did not affect the development of sensitization either. Sub-analyses of food sensitization and sensitization to milk and egg alone was not associated with breastfeeding either.  Conclusion:  Breastfeeding does not affect the risk of sensitization in high-risk children.
Variability is not uniformly bad: The practices of psychologists generate research questions
Authors: Scott A. Huettel, Gregory Lockhead
Journal: Behavioral and Brain Sciences (2001)

The practices of economists increase experimental reproducibility relative to those of selected psychologists but should not be universally adopted. Procedures criticized by Hertwig and Ortmann as producing variable data are valuable, instead, for generating questions. The procedure of choice should depend on the theoretical goal: measure a known factor or learn what factors are important and need to be measured.
Clinical Characteristics and Molecular Profile in Patients with Non-Small Cell Lung Cancer Harboring Crkl Amplification
Authors: Hirotsugu Kenmotsu, Masaru Watanabe, Masakuni Serizawa, Haruyasu Murakami, Masahiro Endo, Takashi Nakajima, Yasuhisa Ode, Nobuyuki Yamamoto, Yasuhiro Koh, Toshiaki Takahashi
Journal: Annals of Oncology (2014)
Immunosuppression and Carcinogenesis: Contrasting Effects With 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene, Benz[&lt;italic&gt;a&lt;/italic&gt;]pyrene, and 3-Methylcholanthrene&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J K Ball
Journal: JNCI Journal of the National Cancer Institute (1970)

Neonatal injection of 30 μg of 7,12-dimethylbenz[a]anthracene (DMBA) results in a permanently suppressed humoral antibody response and a high tumor incidence (Ball et al., Science 152: 650–651, 1966). This immunosuppression has been characterized further to show that, after neonatal injection of 60 μg DMBA, both primary and secondary immunological responses to sheep erythrocytes were suppressed. In addition, the primary hemolysin response could be depressed by a dose of DMBA as low as 6 μg given to neonatal mice. This dose resulted in a thymic lymphoma incidence of 20%. The degree to which the humoral antibody response was depressed depended on the dose of DMBA injected. On the other hand, a carcinogenic dose of DMBA given to adult mice resulted in only a 1-day delay in reaching maximum antibody levels; thereafter no difference in the amount of IgG or IgM between control and treated mice could be detected. In contrast to the effect of DMBA on newborns, carcinogenic doses of benz[a]pyrene (BaP) and 3-methylcholanthrene (MCA) injected at birth did not result in any detectable immunosuppression. Although immunosuppression by a neonatal injection of DMBA correlates with a high yield of tumors of the lymphatic tissue, such a correlation was not found with BaP and MCA. The possible implications of these results are discussed.
B Cell–Specific Expression of Inducible Costimulator Ligand Is Necessary for the Induction of Arthritis in Mice
Authors: Keith M. Hamel, Yanxia Cao, Susan A. Olalekan, Alison Finnegan
Journal: Arthritis & Rheumatology (2013)

Inducible costimulator (ICOS)-ICOSL interactions are necessary for activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed on B cells, macrophages, and dendritic cells and can be induced on nonhematopoietic cells. The aim of this study was to determine whether expression of ICOSL on B cells is necessary for the development of proteoglycan (PG)-induced arthritis (PGIA).PGIA was initiated by immunizing wild-type and ICOSL-deficient (ICOSL(-/-) ) or B cell-specific ICOSL(-/-) chimeric BALB/c mice with human PG in adjuvant. The onset and severity of arthritis were monitored over time. CD4+ T cell proliferation and CD4+ T cell cytokine production were measured in vitro after the cells were restimulated with PG. Germinal center (GC) B cells, plasma cells, Tfh cells, and Treg cells were identified by staining with specific antibodies.Arthritis progression was completely inhibited in both ICOSL(-/-) mice and B cell-specific ICOSL(-/-) chimeric mice. Production of the Teff cell-produced cytokines interferon-γ and interleukin-17 (IL-17) and the antiinflammatory cytokine IL-4 was suppressed. The reduced percentages of GCs and Tfh cells and the decreased production of IL-21 correlated with a decrease in the anti-mouse PG antibody response. However, the percentage of plasma cells was not reduced despite a reduction in IgG responses.These data indicate that the signals provided by ICOSL-expressing B cells to Teff cells and Tfh cells are necessary for the development of arthritis. Thus, therapeutic blockade of ICOSL-ICOS interactions may be an effective strategy for the treatment of rheumatoid arthritis.