tbuckley/cabot-search huggingface dataset:
Oxidative Metabolism of Nicotine by Cigarette Smokers With Cancer of the Urinary Bladder
Authors: J. W. Gorrod, P. Jenner, G. R. Keysell, B. R. Mikhael
Journal: JNCI Journal of the National Cancer Institute (1974)

Nicotine and its major basic metabolites, cotinine and nicotine-1′-N-oxide, were measured in 24-hour urine collections from normal healthy male cigarette smokers and cigarette smokers with cancer of the urinary bladder. Analysis of replicate daily urine samples from some subjects showed the metabolite ratio cotinine/ nicotine-1′-N-oxide to be an individual index of the alternate routes of oxidative metabolism of nicotine, despite variations in urinary pH, volume, and daily nicotine intake. The ratio of cotinine to nicotine-1′-N-oxide was significantly higher in cancer patients than in the control group. The implication of this finding in relation to the etiology of the disease and the metabolism of nicotine by alternate oxidative pathways in man was discussed.
Isolation of Tumoricidal Macrophages From Lung Melanoma Metastases of Mice Treated Systemically With Liposomes Containing a Lipophilic Derivative of Muramyl Dipeptide&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: M. E. Key, J. E. Talmadge, W. E. Fogler, C. Bucana, I. J. Fidler
Journal: JNCI Journal of the National Cancer Institute (1982)

The systemic administration of multilamellar liposomes--composed of phosphatidylcholine and phosphatidylserine (7:3 mol ratio), containing the immunomodulator, muramyl tripeptide phosphatidylethanolamine (MTP-PE)--into C57BL/6N mice bearing the syngeneic B16-BL6 melanoma was associated with the eradication of spontaneous lung and lymph node metastases. Immunofluorescence and electron microscopic analyses revealed that 24 hours after the tumor-bearing mice were given iv injections of liposomes, 15% of the alveolar macrophages and 5% of the metastasis-associated macrophages contained phagocytosed liposomes. However, only macrophages isolated from lungs or metastases of mice given injections of liposomes containing MTP-PE (treatment success), but not macrophages from mice treated with empty liposomes (treatment failure), were tumoricidal against the target cells in vitro. These data provide direct evidence that the regression of established metastases, after treatment of tumor-bearing mice with liposomes containing MTP-PE, was associated with tumoricidal macrophages residing within the metastases.
Bone Tissue Engineering: Electrospun Polycaprolactone 3D Nanofibrous Scaffold with Interconnected and Hierarchically Structured Pores for Bone Tissue Engineering (Adv. Healthcare Mater. 15/2015)
Authors: Tao Xu, Jacob M. Miszuk, Yong Zhao, Hongli Sun, Hao Fong
Journal: Advanced Healthcare Materials (2015)

On page 2238, H. Sun, H. Fong, and co-workers report that electrospun PCL 3D nanofibrous scaffold with interconnected and hierarchically structured pores is morphologically/structurally similar to natural extracellular matrix (ECM), hence well-suited for cell functions and tissue formation. The in vitro results indicate that the novel scaffold supports mouse bone marrow mesenchymal stem cells' osteogenic differentiation, while the in vivo results suggest that it acts as favorable synthetic ECM for the physiological process of endochondral ossification.
Determinants of Moraxella catarrhalis colonization in healthy Dutch children during the first 14 months of life
Authors: S.J.C. Verhaegh, A. Lebon, J.A. Saarloos, H.A. Verbrugh, V.W.V. Jaddoe, A. Hofman, J.P. Hays, H.A. Moll, A. van Belkum
Journal: Clinical Microbiology and Infection (2009)
Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response
Authors: Donata Federici Canova, Anton M. Pavlov, Lucy V. Norling, Thomas Gobbetti, Sandra Brunelleschi, Pauline Le Fauder, Nicolas Cenac, Gleb B. Sukhorukov, Mauro Perretti
Journal: Journal of Controlled Release (2015)

Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with α2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of α2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble α2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of α2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of α2MG with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis.
Electron Microscopic and Bioassay Studies on a Murine Leukemia Virus (Rauscher): Preliminary Report
Authors: Robert F. Zeigel, Frank J. Rauscher
Journal: JNCI Journal of the National Cancer Institute (1963)

A technique of negative staining has been used for the study of virus particles associated with a virus-induced leukemia in mice. Up to 80 percent of particles recovered from resuspended pellets of ultracentrifuged leukemic mouse plasma showed tail-like projections extending from the “head.” The tail-like structures varied in length up to 0.5 µ and were attached to heads of approximately 120 mµ in diameter. The heads of the particles frequently were angular, with a hexagonal shape predominating. The leukemogenic po tency was highest in those fractions of plasma in which particles were observed.
Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.
Authors: L E Robertson, J R Redman, J J Butler, B M Osborne, W S Velasquez, P McLaughlin, F Swan, M A Rodriguez, F B Hagemeister, L M Fuller
Journal: Journal of Clinical Oncology (1991)

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.
Tumorigenicity of the Diastereomeric Benz[&lt;italic&gt;a&lt;/italic&gt;]anthracene 3,4-Diol-1,2-epoxides and the (+)- and (−)-Enantiomers of Benz[&lt;italic&gt;a&lt;/italic&gt;]anthracene 3,4-Dihydrodiol in Newborn Mice
Authors: Peter G. Wislocki, Mildred K. Buening, Wayne Levin, Roland E. Lehr, Dhiren R. Thakker, Donald M. Jerina, Allan H. Conney
Journal: JNCI Journal of the National Cancer Institute (1979)

The tumorigenic activity of benz[a]anthracene (BA), the (+)- and (-)-enantiomers of trans-3,4-dihydroxy-3,4-dihydrobenz[a]anthracene (BA 3,4-dihydrodiol), and the racemic diastereomers of the BA 3,4-diol-1,2-epoxides [i.e., either or both of the diastereomeric 1,2-epoxides derived from BA 3,4-dihydrodiol in which the epoxide oxygen is cis (diol epoxide-1) or trans (diol epoxide-2) to the benzylic 4-hydroxyl group) was examined in newborn Swiss-Webster mice. The mice were administered ip a total dose of 280 nmoles of compound in divided doses consisting of 40 nmoles within 24 hours of birth, 80 nmoles at 8 days of age, and 160 nmoles at 15 days of age. The experiment was terminated when the animals were 26 weeks of age. BA 3,4-diol-1,2-epoxide-2 was the most potent compound tested. All animals treated with BA 3,4-diol-1,2-epoxide-2 developed pulmonary tumors with an average of 13.3 tumors per mouse. BA 3,4-diol-1,2-epoxide-1 produced pulmonary tumors in 42% of the mice with an average of only 0.56 tumors per mouse. The (-)-enantiomer of BA 3,4-dihydrodiol with [3R,4R] absolute stereochemistry was the second most tumorigenic derivative of BA tested; it produced pulmonary tumors in 71% of the mice with an average of 1.88 tumors per mouse. BA and the (+)-enantiomer of BA 3,4-dihydrodiol had little or no tumorigenic activity at the dose tested. A comparison of the average number of pulmonary tumors per mouse revealed that BA 3,4-diol-1,2-epoxide-2 was about 30-fold more tumorigenic than was BA 3,4-diol-1,2-epoxide-1, 8-fold more tumorigenic than was (-)-BA 3,4-dihydrodiol, and greater than 85-fold more tumorigenic than was BA. These data indicate that in newborn mice BA 3,4-dihydrodiol and a BA 3,4-diol-1,2-epoxide are proximate and ultimate carcinogenic metabolites of BA, respectively.
Evaluation of Laboratory Tests in Childhood Allergy
Authors: Merja Kajosaari, Ulla M. Saarinen
Journal: Allergy (1981)

The diagnosis of atopic disease is often difficult in small children because of differences in symptoms and lack of specific and reliable laboratory tests. We evaluated the significance of four commonly used laboratory tests ‐ blood eosinophil count, total serum IgE, and eosinophil and mast cells in the nasal smear ‐ as indicators of atopy in 178 children aged 3 years. The children were followed from birth and examined at the age of 3 years. Symptoms of immediate hypersensitivity including atopic dermatitis, food allergy and pollen or animal allergy were recorded. Severe or obvious atopy correlated widi die highest levels of serum IgE. A total serum IgE level higher than 150 U/ml was found to be strongly suggestive of atopic disease. A blood eosinophil count higher than 600 × 10 9 /1 as well as an increased number of eosinophil and mast cells in die nasal smear were associated with atopy. On the other hand, normal levels of these laboratory tests did not exclude atopic disease. In other words, all of the tests were high in specificity, but low in sensitivity. Consequently, when small children's atopic disease is being diagnosed, emphasis can be laid on the elevated levels of serum total IgE, blood eosinophil count and eosinophil and mast cells in the nasal smear, all of which separately, but especially together, give valuable information on atopy.
Vascular endothelial growth factor (VEGF) as marker of pulmonary hypertension in children with asthma
Authors: Alexander Lebedenko, Olga Semernik
Journal: European Respiratory Journal (2014)

The development of pulmonary hypertension in patients with bronchial asthma is almost always associated with structural changes of the vascular bed - pulmonary vascular remodeling. VEGF is one of the most informative factors, reflecting the initial changes in the microvasculature. In this regard, the definition of VEGF in serum of patients may help identify the preconditions for the formation of pulmonary hypertension in children with asthma.  Aim: To evaluate the role of vascular endothelial growth factor in the genesis of pulmonary hypertension in children with asthma.  Methods: 30 patients with asthma were examined during the period of exacerbation. All patients underwent a comprehensive study of the cardiovascular system with the use of echocardiography. VEGF concentration in serum was determined by enzyme immunoassay.  Results: The increase of improving blood flow rate and the pulmonary artery pressure is set at 20% children with asthma. The concentration of VEGF in patients with high blood flow to the pulmonary artery (81,48 ± 12,41 pg / mmol) considerably exceeds the average children without echocardiographic evidence of pulmonary hypertension (55,71 ± 19,40 pg / mmol). Moreover, the higher pressures on the pulmonary artery, the greater the concentration of VEGF in serum of patients (r = 0,73). VEGF values was higher in patients with echocardiographic signs of diastolic dysfunction than in children with normal cardiohemodynamic indicators.  Conclusion: The determination of the concentration of VEGF in patients with asthma reveals early signs of emerging pulmonary hypertension, which determines the timeliness of appointments optimal therapy.
Maternal propensity for infections increases the risk for asthma in her child
Authors: Jakob Stokholm, Astrid Sevelsted, Klaus Bønnelykke, Hans Bisgaard
Journal: European Respiratory Journal (2014)

Objective   Maternal use of antibiotics during pregnancy has been associated with asthmatic disorders in the offspring, but it remains unknown whether this association is causal. Therefore, we have studied the temporal relation between maternal use of antibiotics and the risk of childhood asthma.   Methods   910,301 children participated in the analysis based on data from the Danish national registries 1997-2010. Asthma cases were based on hospital admissions, outpatient attendance or use of inhaled corticosteroids. The analyses included maternal antibiotic in the period 80 weeks before, during and 80 weeks after pregnancy. Results were adjusted for socioeconomic confounders and maternal asthma.   Results   Maternal use of antibiotics in pregnancy was associated with increased risk of childhood asthma: inpatient admission adjusted Incidence Rate Ratio (aIRR) [95% CI] 1.24 [1.18 - 1.30]; outpatient attendance aIRR 1.22 [1.18 - 1.27]; steroid use aIRR 1.18 [1.15-1.20]. The risk of asthma showed a dose-related association with number of maternal antibiotic treatments and was observed separately for treatment for respiratory tract infections as well as for other types of infections. However, a similar and independent association was observed for maternal antibiotic use before and after the pregnancy period.   Conclusions   Mother9s use of antibiotics exhibits a dose-related association with the risk of asthma in the child, but independent of the temporal relation. This suggests that maternal antibiotic use is a surrogate marker of mother9s general propensity for infections as the link to risk of asthma in the child.
Association of a Bundled Intervention With Surgical Site Infections Among Patients Undergoing Cardiac, Hip, or Knee Surgery
Authors: Marin L. Schweizer, Hsiu-Yin Chiang, Edward Septimus, Julia Moody, Barbara Braun, Joanne Hafner, Melissa A. Ward, Jason Hickok, Eli N. Perencevich, Daniel J. Diekema, Cheryl L. Richards, Joseph E. Cavanaugh, Jonathan B. Perlin, Loreen A. Herwaldt
Journal: JAMA (2015)

<h3>Importance</h3> Previous studies suggested that a bundled intervention was associated with lower rates of<i>Staphylococcus aureus</i>surgical site infections (SSIs) among patients having cardiac or orthopedic operations. <h3>Objective</h3> To evaluate whether the implementation of an evidence-based bundle is associated with a lower risk of<i>S aureus</i>SSIs in patients undergoing cardiac operations or hip or knee arthroplasties. <h3>Design, Setting, and Participants</h3> Twenty hospitals in 9 US states participated in this pragmatic study; rates of SSIs were collected for a median of 39 months (range, 39-43) during the preintervention period (March 1, 2009, to intervention) and a median of 21 months (range, 14-22) during the intervention period (from intervention start through March 31, 2014). <h3>Interventions</h3> Patients whose preoperative nares screens were positive for methicillin-resistant<i>S aureus</i>(MRSA) or methicillin-susceptible<i>S aureus</i>(MSSA) were asked to apply mupirocin intranasally twice daily for up to 5 days and to bathe daily with chlorhexidine-gluconate (CHG) for up to 5 days before their operations. MRSA carriers received vancomycin and cefazolin or cefuroxime for perioperative prophylaxis; all others received cefazolin or cefuroxime. Patients who were MRSA-negative and MSSA-negative bathed with CHG the night before and morning of their operations. Patients were treated as MRSA-positive if screening results were unknown. <h3>Main Outcomes and Measures</h3> The primary outcome was complex (deep incisional or organ space)<i>S aureus</i>SSIs. Monthly SSI counts were analyzed using Poisson regression analysis. <h3>Results</h3> After a 3-month phase-in period, bundle adherence was 83% (39% full adherence; 44% partial adherence). Overall, 101 complex<i>S aureus</i>SSIs occurred after 28 218 operations during the preintervention period and 29 occurred after 14 316 operations during the intervention period (mean rate per 10 000 operations, 36 for preintervention period vs 21 for intervention period, difference, −15 [95% CI, −35 to −2]; rate ratio [RR], 0.58 [95% CI, 0.37 to 0.92]). The rates of complex<i>S aureus</i>SSIs decreased for hip or knee arthroplasties (difference per 10 000 operations, −17 [95% CI, −39 to 0]; RR, 0.48 [95% CI, 0.29 to 0.80]) and for cardiac operations (difference per 10 000 operations, −6 [95% CI, −48 to 8]; RR, 0.86 [95% CI, 0.47 to 1.57]). <h3>Conclusions and Relevance</h3> In this multicenter study, a bundle comprising<i>S aureus</i>screening, decolonization, and targeted prophylaxis was associated with a modest, statistically significant decrease in complex<i>S aureus</i>SSIs.
Feasibility of eccentric exercise training (ECCt) in monocrotaline (MT) rats: Effects on survival, echocardiographic and hemodynamic parameters
Authors: Irina Enache, Stéphane Doutreleau, Fabrice Favret, Paola Di Marco, Cristina Pistea, Bernard Geny, Anne Charloux
Journal: European Respiratory Journal (2012)

ECCt may be of interest in patients with pulmonary hypertension (PH) because cardiac solicitation is much lower during ECC than during concentric exercise, performed at the same mechanical power.   Aims:  We assessed the feasibility, hemodynamic and survival effects of ECCt in MT rats with PH.   Methods:  ECCt on treadmill was initiated 2 weeks after MT injection (40mg/kg) (30 minutes at 50% of maximal speed, slope: -15°, 5 days/week for 4 weeks). Trained rats (MTecc, n=13, control ECC (CLecc), n=7) were compared with sedentary rats (MTsed, n=13, CLsed, n=7). Before and after 2 and 4 weeks training, maximal speed measurement and echocardiography were performed. At 4w, right ventricular (RV) catheterisation was performed.   Results:  The RV systolic pressure was 40±2 mmHg in MT, and 22±1mmHg in CL rats (p [figure].  Echocardiographic parameters were not significantly different in MTsed and MTecc (cardiac output (CO), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery flow acceleration time (PAAT) [figure]. RV systolic pressure was not different in MTecc (36±4mmHg) and in MTsed (42±3mmHg).   Conclusion  In this PH model, ECCt was well tolerated and not detrimental to the hemodynamic condition and survival. Whether ECCt could be an adjuvant therapy in PH deserve to be further investigated.
Airways remodeling is reversed by aerobic training in an asthma animal model
Authors: Ronaldo Aparecido Silva, Francine Maria Almeida, Clarice Rosa Olivo, Beatriz Mangueira Saraiva, Milton Arruda Martins, Celso Ricardo Fernandes Carvalho
Journal: European Respiratory Journal (2013)

Aerobic training (AT) reverses airway remodeling in murine model of asthma; however the effects triggered by AT are poorly known. Aim: Evaluate the effect of AT in airway remodeling and fibrosis mediators in an asthma model. Method: 32 Balb/c mice were divided in 4 groups (n=8): Control (CT), AT, Ovalbumin (OVA), OVA+AT. OVA groups received 4 i.p. OVA+Al(OH)-3 and OVA-inhalations (1-3%, 15 sessions, 30 min., 3xWk) that was maintained during AT. AT (50% max. exercise capacity; 60 min.) begun after chronic airway inflammation and it was performed for 4 weeks. After that, tissue lung was collected to evaluated airway smooth muscle (ASM) and epithelium thickness, collagen and elastic fibers contents and mucus expression in the airways evaluated by image analyses. It was also evaluated eosinophil and neutrophil counting and IL-5, OPN, VEGF,TGF-b, MMP-9, TIMP-1 by immnunohistochemistry in lung tissues slices. Result: Sensitized groups presented an increase of eosinophil and neutrophils, airway remodeling features and the expression of IL-5, OPN, VEGF, TGF-b, MMP-9 and TIMP-2 (*p
Cabozantinib (XL184) Inhibits Growth and Invasion of Preclinical TNBC Models
Authors: Mansoureh Sameni, Elizabeth A. Tovar, Curt J. Essenburg, Anita Chalasani, Erik S. Linklater, Andrew Borgman, David M. Cherba, Arulselvi Anbalagan, Mary E. Winn, Carrie R. Graveel, Bonnie F. Sloane
Journal: Clinical Cancer Research (2015)

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is associated with poor clinical outcome. There is a vital need for effective targeted therapeutics for TNBC patients, yet treatment strategies are challenged by the significant intertumoral heterogeneity within the TNBC subtype and its surrounding microenvironment. Receptor tyrosine kinases (RTK) are highly expressed in several TNBC subtypes and are promising therapeutic targets. In this study, we targeted the MET receptor, which is highly expressed across several TNBC subtypes.Using the small-molecule inhibitor cabozantinib (XL184), we examined the efficacy of MET inhibition in preclinical models that recapitulate human TNBC and its microenvironment. To analyze the dynamic interactions between TNBC cells and fibroblasts over time, we utilized a 3D model referred to as MAME (Mammary Architecture and Microenvironment Engineering) with quantitative image analysis. To investigate cabozantinib inhibition in vivo, we used a novel xenograft model that expresses human HGF and supports paracrine MET signaling.XL184 treatment of MAME cultures of MDA-MB-231 and HCC70 cells (± HGF-expressing fibroblasts) was cytotoxic and significantly reduced multicellular invasive outgrowths, even in cultures with HGF-expressing fibroblasts. Treatment with XL184 had no significant effects on MET(neg) breast cancer cell growth. In vivo assays demonstrated that cabozantinib treatment significantly inhibited TNBC growth and metastasis.Using preclinical TNBC models that recapitulate the breast tumor microenvironment, we demonstrate that cabozantinib inhibition is an effective therapeutic strategy in several TNBC subtypes.