tbuckley/cabot-search huggingface dataset:
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Judith A. Kapp, Carl W. Pierce, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1973)

The cellular requirements for the development of primary IgG GAT-specific PFC responses in cultures of spleen cells from responder, C57Bl/6, mice stimulated with GAT and GAT-MBSA and in cultures of spleen cells from nonresponder, SJL and B10.S, mice stimulated with GAT-MBSA were investigated. Macrophages were required for development of responses to GAT and GAT-MBSA in cultures of spleen cells from responder mice and for responses to GAT-MBSA in cultures of spleen cells from nonresponder mice. Macrophages from nonresponder mice supported the development of responses to GAT by nonadherent responder spleen cells, indicating that the failure of nonresponder mice to respond to GAT is not due to a macrophage defect. Furthermore, responder macrophages supported the responses of nonadherent, nonresponder spleen cells to SRBC and GAT-MBSA, but not to GAT. This indicates that the capacity to respond to GAT is a function of the nonadherent population which is composed of thymus-derived (T) helper cells and precursors of antibody-producing cells. Treatment of spleen cells with anti-theta serum and complement before culture initiation abolished PFC responses to GAT and GAT-MBSA thus establishing the requirement for T cells in the development of PFC responses to these antigens. Since precursors of antibody-producing cells in nonresponder mice are capable of synthesizing antibody specific for GAT after stimulation with GAT-MBSA and since the response to GAT is thymus-dependent, it appears that nonresponder mice lack GAT-specific helper T cell function.
Empathy: Its ultimate and proximate bases
Authors: Stephanie D. Preston, Frans B. M. de Waal
Journal: Behavioral and Brain Sciences (2002)

There is disagreement in the literature about the exact nature of the phenomenon of empathy. There are emotional, cognitive, and conditioning views, applying in varying degrees across species. An adequate description of the ultimate and proximate mechanism can integrate these views. Proximately, the perception of an object's state activates the subject's corresponding representations, which in turn activate somatic and autonomic responses. This mechanism supports basic behaviors (e.g., alarm, social facilitation, vicariousness of emotions, mother-infant responsiveness, and the modeling of competitors and predators) that are crucial for the reproductive success of animals living in groups. The Perception-Action Model (PAM), together with an understanding of how representations change with experience, can explain the major empirical effects in the literature (similarity, familiarity, past experience, explicit teaching, and salience). It can also predict a variety of empathy disorders. The interaction between the PAM and prefrontal functioning can also explain different levels of empathy across species and age groups. This view can advance our evolutionary understanding of empathy beyond inclusive fitness and reciprocal altruism and can explain different levels of empathy across individuals, species, stages of development, and situations.
The Transcriptional Corepressor CtBP: A Foe of Multiple Tumor Suppressors
Authors: G. Chinnadurai
Journal: Cancer Research (2009)

CtBP1 and CtBP2 are closely related and evolutionarily conserved transcriptional corepressors. There is strong evidence linking CtBPs to tumorigenesis and tumor progression. CtBPs promote epithelial-mesenchymal transition and function as apoptosis antagonists. Also, CtBPs mediate repression of several tumor suppressor genes. Certain tumor suppressors also target CtBPs to restrain their tumor-promoting activity. Down-regulation of CtBPs mediated by some tumor suppressors results in p53-independent apoptosis and reduced tumor cell migration and invasion. The role of CtBPs in modulating the activities of different tumor suppressors is reviewed here. The results discussed here suggest that CtBPs may constitute a novel p53-independent anticancer target.
Prevalent Low-Frequency Oscillation of Heart Rate
Authors: Dan Wichterle, Jan Simek, Maria Teresa La Rovere, Peter J. Schwartz, A. John Camm, Marek Malik
Journal: Circulation (2004)

This study evaluates a novel method for postinfarction risk stratification based on frequency-domain characteristics of heart rate variability (HRV) in 24-hour Holter recordings.A new risk predictor, prevalent low-frequency oscillation (PLF), was determined in the placebo population of the European Myocardial Infarction Amiodarone Trial (EMIAT). Frequencies of peaks detected in 5-minute low-frequency HRV spectra were averaged to obtain the PLF index. PLF >or=0.1 Hz was the strongest univariate predictor of all-cause mortality associated with relative risk of 6.4 (95% CI, 3.9 to 10.6; P<10(-12)). In a multivariate Cox's regression model including clinical risk factors, mean RR interval, HRV index, low- and high-frequency HRV spectral power, and heart rate turbulence, PLF was the most powerful mortality predictor, with a relative risk of 4.6 (95% CI, 2.2 to 9.3; P=0.00003). Predictive power of PLF was blindly validated in the population of the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) trial. PLF >or=0.1 Hz was associated with univariate relative risk of 6.1 (95% CI, 2.9 to 12.9; P<10(-5)) for cardiac mortality or resuscitated cardiac arrest. In multivariate Cox's regression model including age, left ventricular ejection fraction, baroreflex sensitivity, mean RR interval, standard deviation of normal RR intervals, low- and high-frequency HRV spectral power, and heart rate turbulence, only left ventricular ejection fraction and PLF were significant predictors, with relative risks of 4.2 (95% CI, 1.5 to 11.7; P=0.007) and 3.6 (95% CI, 1.3 to 10.5; P=0.02), respectively.An innovative analysis of frequency-domain HRV, which characterizes the distribution of spectral power within the low-frequency band, is a potent and independent risk stratifier in postinfarction patients.
Increased prevalence of elevated high-sensitivity cardiac troponin T among patients with stable chronic obstructive pulmonary disease
Authors: Anke Meta Christina Neukamm, Høiseth Arne Didrik, Søyseth Vidar, Omland Torbjørn
Journal: European Respiratory Journal (2011)

Background: Previously, we have found that cardiac troponin (cTnT) elevation is frequently seen during acute exacerbations of chronic obstructive pulmonary disease (COPD) and is associated with poor survival.

Aims and objectives: To assess the prevalence of elevated high-sensitivity cTnT (hs-cTnT) in stable COPD and whether hs-cTnT is associated with pulmonary function.

Material and methods: We performed a cross-sectional case-control study. The index group consisted of 93 stable COPD patients, and the references were 113 individuals from a random sample of a general population. None of the subjects had known coronary heart disease, and the age range was 40 to 79 years in both groups. All participants underwent clinical investigation, spirometry, electrocardiography, and blood analysis including serum creatinine, NTpro-BNP, and hs-cTnT.

Results: The prevalence of hs-cTnT in the categories < 3.0, 3.0-13.9 and ≥ 14.0 ng/L was significantly different between patients and controls and is shown in the table 1. Using log-transformed hs-cTnT as the dependent variable in a linear regression model adjusting for smoking, BMI, creatinine, age, gender, NT-proBNP and hypertension we found that hs-cTnT was significantly higher (p=0.007) among the COPD patients than in the control group. In the index group we found a significant dose-response relationship between hs-cTnT and GOLD category.

View this table:

Table 1





Conclusion: Stable COPD is associated with increased levels of hs-cTnT.
Cardiovascular Reflexes from Stretch of Pulmonary Vein-Atrial Junctions in the Dog
Authors: ANTHONY J. EDIS, DAVID E. DONALD, JOHN T. SHEPHERD
Journal: Circulation Research (1970)

The reflex cardiovascular response to stretch of left pulmonary vein-atrial junctions was studied in anesthetized dogs in which both aortic nerves were cut and the carotid sinuses were isolated vascularly. After thoracotomy, the root of the left lung was tied and a small Silastic balloon (1.5-cm long), attached to a nylon catheter, was inserted into each of the three left pulmonary veins and tied so that its tip lay at the junction of the vein with the left atrium. In six dogs, heart rate response to balloon distension of 2.0 ml was studied over a range of initial heart rates (75 to 240 beats/min) achieved by varying the carotid sinus pressure. On distension of the balloons, slowing occurred if the initial heart rate was &gt; 140 to 150 beats/min and acceleration if it were less. In eight dogs, aortic blood pressure and cardiac output measured before, during, and after balloon distension (0.25 to 2.0 ml) demonstrated a hyperbolic relationship between balloon volume and decrease in calculated systemic vascular resistance. All responses were abolished by vagotomy. The reflex vasodilatation was sustained and caused by decreased adrenergic activity; the reflex bradycardia or tachycardia was due to interplay of vagal and sympathetic cardiac efferents.
Antiapoptotic Role of Growth Factors in the Myelodysplastic Syndromes: Concordance Between <i>In vitro</i> and <i>In vivo</i> Observations
Authors: Ramin Tehranchi, Bengt Fadeel, Jan Schmidt-Mende, Ann-Mari Forsblom, Emma Emanuelsson, Martin Jadersten, Birger Christensson, Robert Hast, Robert B. Howe, Jan Samuelsson, Boris Zhivotovsky, Eva Hellström-Lindberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Erythroid apoptosis in low-risk myelodysplastic syndrome (MDS) maybe mediated via mitochondrial release of cytochrome c and subsequent caspase activation. In the present study, we compared the in vitro and in vivo effects of proerythroid treatment with erythropoietin + granulocyte colony-stimulating factor (G-CSF) on myelodysplastic erythropoiesis regarding apoptosis and preferential growth of clones with cytogenetic abnormalities. Experimental Design: We enrolled 15 refractory anemia (RA) and 11 refractory anemia with ringed sideroblasts (RARS), including 5q– aberration, monosomy 7, and trisomy 8, before initiation of treatment and followed nine patients after successful treatment. The effects of G-CSF and erythropoietin were assessed. The expression of G-CSF receptor (G-CSFR) was explored during erythroid maturation. The relative growth of erythroid progenitors with cytogenetic aberrations in presence of erythropoietin was investigated. Results: Significant redistribution of cytochrome c was seen before treatment at all stages of erythroid differentiation. This release was blocked by G-CSF during the whole culture period and by erythropoietin during the latter phase. Both freshly isolated glycophorin A+ bone marrow cells and intermediate erythroblasts during cultivation retained their expression of G-CSFR. Cytochrome c release and caspase activation were significantly less pronounced in progenitors obtained from successfully treated nonanemic patients and showed no further response to G-CSF in vitro. Moreover, erythropoietin significantly promoted growth of cytogenetically normal cells from 5q– patients, whereas no such effect was observed on erythroblasts from monosomy 7 or trisomy 8 patients. Conclusion: We conclude that growth factors such as erythropoietin and G-CSF can act both via inhibition of apoptosis of myelodysplastic erythroid precursors and via selection of cytogenetically normal progenitors.
Effect of Direct-to-Consumer Genomewide Profiling to Assess Disease Risk
Authors: Cinnamon S. Bloss, Nicholas J. Schork, Eric J. Topol
Journal: New England Journal of Medicine (2011)

The use of direct-to-consumer genomewide profiling to assess disease risk is controversial, and little is known about the effect of this technology on consumers. We examined the psychological, behavioral, and clinical effects of risk scanning with the Navigenics Health Compass, a commercially available test of uncertain clinical validity and utility.
Residential Proximity to Naturally Occurring Asbestos and Mesothelioma Risk in California
Authors: Xue-lei Pan, Howard W. Day, Wei Wang, Laurel A. Beckett, Marc B. Schenker
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Little is known about environmental exposure to low levels of naturally occurring asbestos (NOA) and malignant mesothelioma (MM) risk.Objectives: To conduct a cancer registry-based case control study of residential proximity to NOA with MM in California.Methods: Incident MM cases (n = 2,908) aged 35 yr or more, diagnosed between 1988 and 1997, were selected from the California Cancer Registry and frequency matched to control subjects with pancreatic cancer (n = 2,908) by 5-yr age group and sex. Control subjects were selected by stratified random sampling from 28,123 incident pancreatic cancers in the same time period. We located 93.7% of subjects at the house or street level at initial diagnosis. Individual occupational exposure to asbestos was derived from the longest held occupation, available for 74% of MM cases and 63% of pancreatic cancers. Occupational exposure to asbestos was determined by a priori classification and confirmed by association with mesothelioma.Main Results: The adjusted odds ratios and 95% confidence interval for low, medium, and high probabilities of occupational exposures to asbestos were 1.71 (1.32–2.21), 2.51 (1.91–3.30), and 14.94 (8.37–26.67), respectively. Logistic regression analysis from a subset of 1,133 mesothelioma cases and 890 control subjects with pancreatic cancer showed that the odds of mesothelioma decreased approximately 6.3% for every 10 km farther from the nearest asbestos source, an odds ratio of 0.937 (95% confidence interval = 0.895–0.982), adjusted for age, sex, and occupational exposure to asbestos.Conclusions: These data support the hypothesis that residential proximity to NOA is significantly associated with increased risk of MM in California.
Intravital Imaging Reveals Angiotensin II–Induced Transcytosis of Albumin by Podocytes
Authors: Ina Maria Schießl, Anna Hammer, Veronika Kattler, Bernhard Gess, Franziska Theilig, Ralph Witzgall, Hayo Castrop
Journal: Journal of the American Society of Nephrology (2015)

Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and resulted in an average (±SEM) of 3.7±2.2, 72.3±18.6 (P<0.001), and 239.4±34.6 µm(3) (P<0.001) albumin-containing vesicles per glomerulus, respectively, compared with none at baseline or 10 ng/kg per minute Ang II. Immunostaining of Ang II-infused kidneys confirmed the presence of albumin-containing vesicles, which colocalized with megalin, in podocin-positive cells. Furthermore, podocyte endocytosis of albumin was markedly reduced in the presence of gentamicin, a competitive inhibitor of megalin-dependent endocytosis. Ang II infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and gentamicin further increased this concentration. Some endocytic vesicles were acidified and colocalized with LysoTracker. Most vesicles migrated from the capillary to the apical aspect of the podocyte and were eventually released into the urinary space. This transcytosis accounted for approximately 10% of total albumin filtration. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. Ang II enhances the endocytosis and transcytosis of plasma albumin by podocytes, which may eventually impair podocyte function.
Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4
Authors: S.W. Crooks, D.L. Bayley, S.L Hill, R.A Stockley
Journal: European Respiratory Journal (2000)

Neutrophils recruited to the airways in chronic obstructive pulmonary disease (COPD) are thought to mediate tissue destruction. Neutrophil recruitment is increased during bacterial exacerbations. The inflammatory process was studied in patients with an acute exacerbation of COPD in order to ascertain the role of leukotriene B4 (LTB4). The sputum of eight subjects with a bacterial exacerbation of COPD was analysed for neutrophil products (myeloperoxidase, elastase) and chemoattractants (interleukin-8 (IL-8) and LTB4). The contribution of LTB4 to the chemotactic activity of the sputum sol phase was determined using the LTB4 receptor antagonist LY293111. The concentrations of the serum acute phase proteins alpha1-proteinase inhibitor, alpha1-antichymotrypsin and C-reactive protein were measured. All patients received appropriate broad-spectrum antibiotic treatment for 7-14 days. Initially, the sputum myeloperoxidase activity was high, indicating neutrophil influx; this was associated with high levels of IL-8 and LTB4. All these concentrations fell with treatment (p<0.01). The chemotactic activity of the sputum was raised on presentation and fell with treatment (p<0.01). LTB4 contributed approximately 30% of the total chemotactic activity on presentation; this diminished with therapy. All acute phase proteins were raised on presentation and fell with therapy (p<0.01). These findings suggest that leukotriene B4 contributes to neutrophil influx into the airway in chronic obstructive pulmonary disease and may influence disease progression.
Long-term cardiac toxicity after adjuvant epirubicin-based chemotherapy in early breast cancer: French Adjuvant Study Group Results
Authors: P. Fumoleau, H. Roché, P. Kerbrat, J. Bonneterre, P. Romestaing, P. Fargeot, M. Namer, A. Monnier, P. Montcuquet, M.-J. Goudier, E. Luporsi
Journal: Annals of Oncology (2005)
A Pilot Study of the Continuous Glucose Monitoring System
Authors: Francine R. Kaufman, Leena C. Gibson, Mary Halvorson, Sue Carpenter, Lynda K. Fisher, Pisit Pitukcheewanont
Journal: Diabetes Care (2001)

OBJECTIVE—To determine whether the continuous glucose monitoring system (CGMS) (MiniMed, Sylmar, CA) could be used to make clinical decisions and whether it has an impact on glycemia in pediatric type 1 diabetic subjects. RESEARCH DESIGN AND METHODS—Pediatric subjects were recruited if they had HbA1c &amp;gt;8.0% with management problems (n = 35) or episodes of severe or nocturnal hypoglycemia or hypoglycemia unawareness associated with HbA1c ≤8.0% (n = 12). A total of 47 patients with a mean HbA1c value of 8.6 ± 1.6% (mean age 11.8 ± 4.6 years, youngest 2.7 years, and diabetes duration 5.5 ± 3.5 years) on three to four insulin injections/day (n = 24) or insulin pump therapy (n = 23) were followed with the CGMS for a mean of 69.5 ± 28 h. Comparisons were made between the number of high (&amp;gt;150 mg/dl) and low (&amp;lt;70 mg/dl) glucose patterns discerned with the sensor or the logbook, and HbA1c levels were evaluated. RESULTS—In patients on injection therapy, 30 high or low glucose patterns were discerned with the logbook records and 120 patterns with the CGMS. Specific alterations of the diabetes regimen were made. An overall significant change in HbA1c, from 3 months before wearing the sensor to 6 months after (analysis of variance 0.04), was found in the subjects. Post hoc analysis showed a significant change in HbA1c from 8.6 ± 1.5% at baseline to 8.4 ± 1.3% at 3 months (paired Student’s t test 0.03). CONCLUSIONS—The CGMS can be used by pediatric patients to detect abnormal patterns of glycemia. The information that was obtained could be used to alter the diabetes regimen and impact glycemic outcome.
Interstitial lung disease induced by antibiotics. MDCT with perfusion, MRI with DWI and MDCT guided lung biopsy
Authors: Tamara Milosavljevic, Aleksandar Ivkovic, Zoran Radovanovic
Journal: European Respiratory Journal (2013)

Purpose: main purpose is to show MDCT and MRI findings in interstitial lung disease caused by use of antibiotics and to determine role of radiology in diagnostic and proper medical care.  Material: We examined 43 patients with acute interstitial lung disease induced by non-lung therapy of antibiotics, 27 patients with pyelonephritis, 12 with bone inflammation and 4 with pan sinusitis. There were 23 female and 20 male patients. They were from 15 to 46 years old. All patients were examined on MDCT and on 1.5T MRI using standard procedure with DWI. In 16 cases we performed fine needle biopsy guided with MDCT and in 2 cases fine needle biopsy guided with Ultra sound.  Results: MDCT examination was performed in first 24 hour after arriving to hospital care. MRI was performed in first 7 days after arriving. We separate results in 3 different subgroups according to patient’s conditions and MDCT findings. First subgroup was patients with bronchiolitis. Second subgroup was patients with bronchiectasis and pneumonitis. Third subgroup was patients with hard symptoms, like cystic fibrosis and alveolar necrosis. Standard MRI examination was followed with MRI DWI. Diffuse weighted images give us answer on condition of small vessels and mediastinal condition. Lung biopsy was performed in 18 cases. In 16 patients biopsy was guided with use of 16 or 64 MDCT. In 2 patients we performed fine needle biopsy controlled by using of Ultra Sound.  Conclusion: Prolonged ILD may result in pulmonary hypertension, respiratory failure and heart failure. MDCT examinations have a great role in diagnostic and follow up of ILD. MRI with DWI is great tool for determining of small vessels and mediastinum.
Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein.
Authors: I Stamenkovic, B Seed
Journal: The Journal of Experimental Medicine (1988)

Two cDNA clones encoding the pan-B cell CD20 antigen were isolated from a COS cell expression library. The two clones bear identical coding sequences and differ only in the length of the 3' untranslated region. The predicted CD20 sequence is 297 residues long and contains three hydrophobic domains, one of which is long enough to span the membrane twice. COS cells transfected with either CD20 clone express an immunoreactive protein of 33 kD.
E Protein Function in Lymphocyte Development
Authors: Melanie W. Quong, William J. Romanow, Cornelis Murre
Journal: Annual Review of Immunology (2002)

Lymphocytes arise from hematopoietic stem cells through the coordinated action of transcription factors. The E proteins (E12, E47, HEB and E2-2) have emerged as key regulators of both B and T lymphocyte differentiation. This review summarizes the current data and examines the various functions of E proteins and their antagonists, Id2 and Id3, throughout lymphoid maturation. Beyond an established role in B and T lineage commitment, E proteins continue to be essential at subsequent stages of development. E protein activity regulates the expression of surrogate and antigen receptor genes, promotes Ig and TCR rearrangements, and coordinates cell survival and proliferation with developmental progression in response to TCR signaling. Finally, this review also discusses the role of E47 as a tumor suppressor.