tbuckley/cabot-search huggingface dataset:
ELECTROPHORETICALLY HOMOGENEOUS ANTIBODY SYNTHESIZED BY SPLEEN FOCI OF IRRADIATED REPOPULATED MICE
Authors: A. L. Luzzati, R. M. Tosi, A. O. Carbonara
Journal: The Journal of Experimental Medicine (1970)

10(6) splenocytes from primed donors were injected, together with sheep erythrocytes (SRBC), into X-irradiated syngeneic mice. 8 days later the spleens were excised and cut into small fragments, keeping track of their location in the organ. Each fragment was cultured individually for 24 hr in the presence of (14)C amino acids and the culture fluids were assayed for antibody activity. The antibody-producing fragments were found to be clustered in few restricted areas (foci) surrounded by negative tissue. The anti-SRBC antibody from single foci was purified by absorption on stroma followed by acid elution. Thereafter, it was subjected to electrophoresis and immunoelectrophoresis. The radioautography of the runs showed a considerable degree of homogeneity. Distinct and sharp spikes were localized in the beta and gamma region. The pattern of each focus is unique from the point of view of the number of spikes and their mobility. Eluates obtained from many pooled fragments gave a broad radioactive smear in beta-gamma region. Many foci synthesized antibody migrating as a single band. This homogeneous protein is probably the product of a clone of cells homogeneously differentiated. However, some foci producing two and probably more antibody bands were also encountered. Two interpretations of the finding can be given. Either more than one precursor may participate in the formation of a focus or a differentiation switch may occur during the clonal expansion.
ADAPTATION OF A LANSING STRAIN OF POLIOMYELITIS VIRUS TO NEWBORN MICE
Authors: Jordi Casals, Peter K. Olitsky, Ralph O. Anslow
Journal: The Journal of Experimental Medicine (1951)

By means of rapid serial passages, including 3 successive "blind" passages, the MEF1 strain, a Lansing-type poliomyelitis virus, has been adapted to new-born mice. The virus can readily be propagated in newborn mice, in which fully adapted virus induces in almost all inoculated animals the experimental disease, resulting in a much greater infectivity for the central nervous system and a uniformly short and regular incubation period.
The role of elastic restoring forces in right-ventricular filling
Authors: Candelas Pérez Del Villar, Javier Bermejo, Daniel Rodríguez-Pérez, Pablo Martínez-Legazpi, Yolanda Benito, J. Carlos Antoranz, M. Mar Desco, Juan E. Ortuño, Alicia Barrio, Teresa Mombiela, Raquel Yotti, Maria J. Ledesma-Carbayo, Juan C. Del Álamo, Francisco Fernández-Avilés
Journal: Cardiovascular Research (2015)

AimsThe physiological determinants of RV diastolic function remain poorly understood. We aimed to quantify the contribution of elastic recoil to RV filling and determine its sensitivity to interventricular interaction.
Rehospitalization rates for patients with COPD who require supplemental oxygen therapy following a hospitalization for an exacerbation
Authors: Brian Carlin, Kim Wiles, Dan Easley
Journal: European Respiratory Journal (2012)

Objective: To compare the hospital readmission rates for patients with COPD who require supplemental oxygen therapy following an exacerbation who are entered into a home-care based, respiratory therapist centered transition of care program.

Method: Patients with a diagnosis of a COPD exacerbation who required supplemental oxygen therapy on hospital discharge were entered into a post hospitalization transition of care program {Discharge, Assessment and Summary @ Home (D.A.S.H., Klingensmith HealthCare, Ford City, PA)]. The program consists of face to face visits by a respiratory therapist with the patient on days 2, 7, and 30 following hospital discharge. Education, behavior modification, skills training, oxygen titration during performance of activities of daily living, clinical assessment, and adherence data collection are components of the program. The 30 day readmission rates following discharge for all patients entered into the program over a twenty four month period (March 2010 through February 2012) were evaluated.

Results: 385 consecutive patients with COPD (mean age 71 + 12 years) from 23 different hospitals were enrolled into the program. 123 (31%) patients refused additional follow up after the first home visit. The 30 day readmission rate for those patients who chose to continue the program (209) was 2.8%.

Conclusions: The use of a multiple visit respiratory therapist based patient centered management program resulted in a significant decrease in the 30 day readmission rates for those patients who elected to continue with the DASH management program.
Correlation between magnetic resonance imaging findings and histological diagnosis of intrinsic brainstem lesions in adults
Authors: M. Dellaretti, G. Touzet, N. Reyns, F. Dubois, S. Gusmao, J. L. B. Pereira, S. Blond
Journal: Neuro-Oncology (2012)

Management of brainstem mass lesions remains a controversial issue, especially when the lesion cannot be excised and when infiltration occurs; moreover, the benefits of a stereotactic procedure are still under debate. In most studies, treatment decisions are based solely on MRI features and do not include a histopathological diagnosis. In the current study, we compared MRI characteristics with histopathological findings of intrinsic brainstem lesions and identified the characteristics associated with the diagnosis of pathologies other than diffuse glioma. From February 1988 through August 2007, 96 brainstem biopsies were performed at the Roger Salengro Hospital in Lille, France, on adult patients with intrinsic brainstem lesions not amenable to excision. Of the 96 patients, 42 were women and 54 were men, with a mean age of 41 years (range, 18-75 years). Data analysis of the MRI findings revealed focal (P < .05) and contrast enhancing lesions (P < .05), and these lesions were significant factors associated with the diagnosis of pathologies other than diffuse glioma. Focal lesions were a significant factor associated with a diagnosis of nontumor lesions (P < .05). In conclusion, the diagnostic effect of stereotactic biopsy on intrinsic brainstem lesions was greater in patients with focal or enhancing lesions shown by MRI, in whom the diagnosis of diffuse glioma was less frequent.
Suppression of cytokines and nitric oxide production, and protection against lethal endotoxemia and viral myocarditis by a new NF‐κB inhibitor
Authors: Akira Matsumori, Youichi Nunokawa, Akira Yamaki, Kanjo Yamamoto, Myung‐Woo Hwang, Tadashi Miyamoto, Masatake Hara, Ryosuke Nishio, Katsura Kitaura‐Inenaga, Koh Ono
Journal: European Journal of Heart Failure (2003)
Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study
Authors: I-H Song, F Heldmann, M Rudwaleit, H Haibel, A Weiß, J Braun, J Sieper
Journal: Annals of the Rheumatic Diseases (2011)

Objective To prospectively explore the short-term efficacy and safety of abatacept in patients with ankylosing spondylitis (AS). Methods In this prospective open-label pilot study, abatacept (10 mg/kg) was administered intravenously on days 1, 15, 29 and every 28 days thereafter up to week 24 in 15 tumour necrosis factor α (TNFα)-inhibitor naive patients (group 1) and 15 patients with inadequate response to TNFα inhibitors (group 2) with active AS. The primary end point was the proportion of patients with 40% improvement according to the Assessment of SpondyloArthritis international Society criteria (ASAS40) in both groups at week 24. Results At week 24, ASAS40 was reached by 13% of group 1 and 0% of group 2; 20% improvement (ASAS20) was reached by 27% and 20%, respectively. There was no significant change of Bath Ankylosing Spondylitis Disease Activity Index score, patient global assessment or C reactive protein. Overall, abatacept was well tolerated. Conclusions In this pilot open-label AS study a major response was not observed.
Differential Cellular Internalization of Anti-CD19 and -CD22 Immunotoxins Results in Different Cytotoxic Activity
Authors: Xing Du, Richard Beers, David J. FitzGerald, Ira Pastan
Journal: Cancer Research (2008)

Abstract B-cell malignancies routinely express surface antigens CD19 and CD22. Immunotoxins against both antigens have been evaluated, and the immunotoxins targeting CD22 are more active. To understand this disparity in cytotoxicity and guide the screening of therapeutic targets, we compared two immunotoxins, FMC63(Fv)-PE38–targeting CD19 and RFB4(Fv)-PE38 (BL22)–targeting CD22. Six lymphoma cell lines have 4- to 9-fold more binding sites per cell for CD19 than for CD22, but BL22 is 4- to 140-fold more active than FMC63(Fv)-PE38, although they have a similar cell binding affinity (Kd, ∼7 nmol/L). In 1 hour, large amounts of BL22 are internalized (2- to 3-fold more than the number of CD22 molecules on the cell surface), whereas only 5.2% to 16.6% of surface-bound FMC63(Fv)-PE38 is internalized. The intracellular reservoir of CD22 decreases greatly after immunotoxin internalization, indicating that it contributes to the uptake of BL22. Treatment of cells with cycloheximide does not reduce the internalization of BL22. Both internalized immunotoxins are located in the same vesicles. Our results show that the rapid internalization of large amounts of BL22 bound to CD22 makes CD22 a better therapeutic target than CD19 for immunotoxins and probably for other immunoconjugates that act inside cells. [Cancer Res 2008;68(15):6300–5]
Virus-induced Interferon α Production by a Dendritic Cell Subset in the Absence of Feedback Signaling In Vivo
Authors: Winfried Barchet, Marina Cella, Bernhard Odermatt, Carine Asselin-Paturel, Marco Colonna, Ulrich Kalinke
Journal: The Journal of Experimental Medicine (2002)

An effective type I interferon (IFN-α/β) response is critical for the control of many viral infections. Here we show that in vesicular stomatitis virus (VSV)-infected mouse embryonic fibroblasts (MEFs) the production of IFN-α is dependent on type I IFN receptor (IFNAR) triggering, whereas in infected mice early IFN-α production is IFNAR independent. In VSV-infected mice type I IFN is produced by few cells located in the marginal zone of the spleen. Unlike other dendritic cell (DC) subsets, FACS®-sorted CD11cintCD11b−GR-1+ DCs show high IFN-α expression, irrespective of whether they were isolated from VSV-infected IFNAR-competent or -deficient mice. Thus, VSV preferentially activates a specialized DC subset presumably located in the marginal zone to produce high-level IFN-α largely independent of IFNAR feedback signaling.
Nonstaphylococcal Infections of Cardiac Implantable Electronic Devices
Authors: George M. Viola, Leah L. Awan, Rabih O. Darouiche
Journal: Circulation (2010)

Background— Along with the rising use of cardiac implantable electronic devices (CIEDs), there has been a disproportional increase in the number of infections of such devices. Little is known about nonstaphylococcal CIED-related infections, which make up ≈10% to 30% of all CIED infections. Methods and Results— A retrospective review of hospital records of patients admitted with a CIED-related infection was conducted in 4 academic hospitals in Houston, Tex, between 2002 and 2009. Of the 504 identified patients with CIED-related infection, 80 (16%) had a nonstaphylococcal infection and were the focus of this study. The mean duration of CIED placement before infection was 109±27 weeks, whereas 44% had their device previously manipulated within a mean of 29.5±6 weeks. The mean duration of clinical symptoms before admission was 48±12.8 days. Furthermore, 13 patients (16%) presented with CIED-related endocarditis. Although not described in prior reports, we identified 3 definite and 2 suspected cases of secondary Gram-negative bacteria seeding of the CIED. Inappropriate antimicrobial coverage was provided in ≈50% of the cases with a mean period of 2.1 days. The overall mortality rate was 4%. Conclusions— Nonstaphylococcal CIED-related infections are prevalent and diverse with a relatively low virulence and mortality rate. Because nonstaphylococcal organisms are capable of secondarily seeding the CIED, a high suspicion for CIED-related infection is warranted in patients with bloodstream infection. In patients with suspected CIED infection, adequate Gram-positive and Gram-negative antibacterial coverage should be administered until microbiological data become available.
Stopping the Primal RAGE Reaction in Myocardial Infarction
Authors: Ravichandran Ramasamy, Shi Fang Yan, Ann Marie Schmidt
Journal: Circulation (2008)

2][3][4] A major cause of injury, especially in the reperfusion phase, is the influx of inflammatory cells into the stressed heart.Andrassy and colleagues show that infiltrating leukocytes express proinflammatory HMGB1 and that HMGB1 plays fundamental roles in injury responses in the I/R heart.In homeostasis, HMGB1 is largely a nuclear protein.In stress conditions, HMGB1 may be released from injured cells, particularly on necrosis.The chief receptor for HMGB1, RAGE, is expressed in multiple cell types in the I/R heart, such as inflammatory cells, and also in cardiomyocytes and vascular cells (endothelial cells and smooth muscle cells). 2Although HMGB1 may interact with distinct receptors beyond RAGE (for example, toll receptors), 5 the current study of Andrassy and colleagues reveals major roles for RAGE in transducing the effects of HMGB1 in the heart, as administration of recombinant HMGB1 or antagonists of this molecule had significant proinjury effects in the wild-type mouse heart, but no additive effects were noted in mice devoid of RAGE.The biology of RAGE, however, is complex and extends beyond HMGB1 in the injured heart.
Fumarate Is Cardioprotective via Activation of the Nrf2 Antioxidant Pathway
Authors: Houman Ashrafian, Gabor Czibik, Mohamed Bellahcene, Dunja Aksentijević, Anthony C. Smith, Sarah J. Mitchell, Michael S. Dodd, Jennifer Kirwan, Jonathan J. Byrne, Christian Ludwig, Henrik Isackson, Arash Yavari, Nicolaj B. Støttrup, Hussain Contractor, Thomas J. Cahill, Natasha Sahgal, Daniel R. Ball, Rune I.D. Birkler, Iain Hargreaves, Daniel A. Tennant, John Land, Craig A. Lygate, Mogens Johannsen, Rajesh K. Kharbanda, Stefan Neubauer, Charles Redwood, Rafael de Cabo, Ismayil Ahmet, Mark Talan, Ulrich L. Günther, Alan J. Robinson, Mark R. Viant, Patrick J. Pollard, Damian J. Tyler, Hugh Watkins
Journal: Cell Metabolism (2012)

The citric acid cycle (CAC) metabolite fumarate has been proposed to be cardioprotective; however, its mechanisms of action remain to be determined. To augment cardiac fumarate levels and to assess fumarate's cardioprotective properties, we generated fumarate hydratase (Fh1) cardiac knockout (KO) mice. These fumarate-replete hearts were robustly protected from ischemia-reperfusion injury (I/R). To compensate for the loss of Fh1 activity, KO hearts maintain ATP levels in part by channeling amino acids into the CAC. In addition, by stabilizing the transcriptional regulator Nrf2, Fh1 KO hearts upregulate protective antioxidant response element genes. Supporting the importance of the latter mechanism, clinically relevant doses of dimethylfumarate upregulated Nrf2 and its target genes, hence protecting control hearts, but failed to similarly protect Nrf2-KO hearts in an in vivo model of myocardial infarction. We propose that clinically established fumarate derivatives activate the Nrf2 pathway and are readily testable cytoprotective agents.
Risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study
Authors: Anne Kirkeby Hansen, Kirsten Wisborg, Niels Uldbjerg, Tine Brink Henriksen
Journal: BMJ (2007)

<b>Objective</b> To investigate the association between elective caesarean sections and neonatal respiratory morbidity and the importance of timing of elective caesarean sections. <b>Design</b> Cohort study with prospectively collected data from the Aarhus birth cohort, Denmark. <b>Setting</b> Obstetric department and neonatal department of a university hospital in Denmark. <b>Participants</b> All liveborn babies without malformations, with gestational ages between 37 and 41 weeks, and delivered between 1 January 1998 and 31 December 2006 (34 458 babies). <b>Main outcome measures</b> Respiratory morbidity (transitory tachypnoea of the newborn, respiratory distress syndrome, persistent pulmonary hypertension of the newborn) and serious respiratory morbidity (oxygen therapy for more than two days, nasal continuous positive airway pressure, or need for mechanical ventilation). <b>Results</b> 2687 infants were delivered by elective caesarean section. Compared with newborns intended for vaginal delivery, an increased risk of respiratory morbidity was found for infants delivered by elective caesarean section at 37 weeks’ gestation (odds ratio 3.9, 95% confidence interval 2.4 to 6.5), 38 weeks’ gestation (3.0, 2.1 to 4.3), and 39 weeks’ gestation (1.9, 1.2 to 3.0). The increased risks of serious respiratory morbidity showed the same pattern but with higher odds ratios: a fivefold increase was found at 37 weeks (5.0, 1.6 to16.0). These results remained essentially unchanged after exclusion of pregnancies complicated by diabetes, pre-eclampsia, and intrauterine growth retardation, or by breech presentation. <b>Conclusion</b> Compared with newborns delivered vaginally or by emergency caesarean sections, those delivered by elective caesarean section around term have an increased risk of overall and serious respiratory morbidity. The relative risk increased with decreasing gestational age.
Change in Visceral Adiposity Independently Predicts a Greater Risk of Developing Type 2 Diabetes Over 10 Years in Japanese Americans
Authors: Pandora L. Wander, Edward J. Boyko, Donna L. Leonetti, Marguerite J. McNeely, Steven E. Kahn, Wilfred Y. Fujimoto
Journal: Diabetes Care (2012)

Visceral adiposity is an important risk factor for cardiovascular disease and type 2 diabetes. We sought to determine whether change in intraabdominal fat area (IAF) over time predicts subsequent development of diabetes.We followed up 436 nondiabetic Japanese-American subjects (mean age 51.9 years, mean BMI 24.2 kg/m(2), 54% male) for development of diabetes. We fit a logistic regression model to examine the association over a 10-year follow-up between change in IAF at 5-year follow-up and other fat areas (measured by computed tomography) and development of incident diabetes, adjusted for age, sex, family history of diabetes in a first-degree relative, second-generation versus third-generation Japanese American (Nisei vs. Sansei), baseline IAF, BMI, weight change over time, smoking status, physical activity level, and subcutaneous fat (SCF) depot areas.Cumulative incidence of diabetes was 20.4% at 10 years. Mean change in IAF was 10.9 cm(2). An increase of 1 SD in IAF was associated with a 1.65-fold increase in the odds of diabetes over 10 years (OR = 1.65, 95% CI 1.21-2.25) after adjusting for the above covariates. This association was also independent of changes in thoracic, thigh, and abdominal SCF, as well as change in weight.We conclude that baseline IAF and accumulation of fat in this area over time are independent predictors of the development of type 2 diabetes in Japanese Americans.
Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis
Authors: William G Flight, Rowland J Bright-Thomas, Peter Tilston, Kenneth J Mutton, Malcolm Guiver, Julie Morris, A Kevin Webb, Andrew M Jones
Journal: Thorax (2013)

<h3>Background</h3> Viral respiratory infection (VRI) is a common cause of pulmonary exacerbations in children with cystic fibrosis (CF). The importance of VRI in adult CF populations is unclear. <h3>Objective</h3> To determine the incidence and clinical impact of VRI among adults with CF. <h3>Methods</h3> One hundred adults with CF were followed up prospectively for 12 months. Sputum, nose swabs and throat swabs were collected every 2 months and at onset of pulmonary exacerbation. PCR assays for adenovirus, influenza A&amp;B, human metapneumovirus, parainfluenza 1–3, respiratory syncytial virus and human rhinovirus were performed on each sample. Symptom scores, spirometry and inflammatory markers were measured at each visit. <h3>Results</h3> One or more respiratory viruses were detected in 191/626 (30.5%) visits. Human rhinovirus accounted for 72.5% of viruses. Overall incidence of VRI was 1.66 (95% CI 1.39 to 1.92) cases/patient-year. VRI was associated with increased risk of pulmonary exacerbation (OR=2.19; 95% CI 1.56 to 3.08; p&lt;0.001) and prescription of antibiotics (OR=2.26; 95% CI 1.63 to 3.13; p&lt;0.001). Virus-positive visits were associated with higher respiratory symptom scores and greater C-reactive protein levels. Virus-positive exacerbations had a lower acute fall in FEV<sub>1</sub> than virus-negative exacerbations (12.7% vs 15.6%; p=0.040). The incidence of exacerbations, but not VRI, was associated with greater lung function decline over 12 months (−1.79% per pulmonary exacerbation/year; 95% CI −3.4 to −0.23; p=0.025). <h3>Conclusion</h3> VRI is common in adults with CF and is associated with substantial morbidity. Respiratory viruses are a potential therapeutic target in CF lung disease.
Epithelial-to-Mesenchymal Transition and Resistance to Ingenol 3-Angelate, a Novel Protein Kinase C Modulator, in Colon Cancer Cells
Authors: Aïda Ghoul, Maria Serova, Lucile Astorgues-Xerri, Ivan Bieche, Guilhem Bousquet, Mariana Varna, Michel Vidaud, Edelmira Phillips, Sophie Weill, Karim A. Benhadji, François Lokiec, Esteban Cvitkovic, Sandrine Faivre, Eric Raymond
Journal: Cancer Research (2009)

Acquired resistance to protein kinase C (PKC) modulators may explain the failure of clinical trials in patients with cancer. Herein, we established a human colon cancer cell line resistant to PEP005, a drug that inhibits PKCalpha and activates PKCdelta. Colo205-R cells, selected by stepwise exposure to PEP005, were >300-fold more resistant to PEP005 than parental Colo205-S cells and were cross-resistant to phorbol 12-myristate 13-acetate, bryostatin, bistratene A, and staurosporine. No PKCalpha or PKCdelta mutation was detected in Colo205-S and Colo205-R cells. Changes in Colo205-R cells were reminiscent of the epithelial-to-mesenchymal transition (EMT) phenotype. Accordingly, Colo205-R cells were more invasive than Colo205-S in Matrigel assays and in mouse xenografts. We also found an increased mRNA expression of several EMT genes, such as those encoding for transforming growth factor-beta and vimentin, along with a decreased mRNA expression of genes involved in epithelial differentiation, such as CDH1 (E-cadherin), CLDN4 (claudin 4), S100A4, and MUC1, in Colo205-R compared with Colo205-S cells in vitro and in vivo. Interestingly, high expression of ET-1 was shown in Colo205-R cells and correlated with low sensitivity to PEP005 and staurosporine in a panel of 10 human cancer cell lines. Inhibition of the ET-1 receptor ETR-A with bosentan restored the antiproliferative effects of PEP005 in Colo205-R cells and decreased the invasive properties of this cell line. Exogenous exposure to ET-1 and silencing ET-1 expression using small interfering RNA modulated cell signaling in Colo205-S and Colo205-R. In summary, acquired resistance to PEP005 was associated with expression of EMT markers and activates the ET-1/ETR-A cell signaling.
Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial
Authors: Lars Lannfelt, Kaj Blennow, Henrik Zetterberg, Stellan Batsman, David Ames, John Harrison, Colin L Masters, Steve Targum, Ashley I Bush, Ross Murdoch, Janet Wilson, Craig W Ritchie
Journal: The Lancet Neurology (2008)