tbuckley/cabot-search huggingface dataset:
Phenotype in murine offspring is altered by maternal smoke exposure
Authors: Petra Nathan, Stefan Dehmel, Katrin Milger, Nora Krahl, A. Önder Yildirim, Gerrit John-Schuster, Rabea Imker, Raphael Prungnaud, Oliver Eickelberg, Susanne Krauss-Etschmann
Journal: European Respiratory Journal (2014)

Background  In utero  exposure to cigarette smoke is a major risk factor for impaired lung function development and asthma risk in the offspring. To understand the mechanisms underlying this phenomenon animal models are required. Therefore, we aimed to establish a murine model of prenatal cigarette smoke exposure that replicates human findings.   Methods  Female mice were exposed daily to mainstream cigarette smoke during pregnancy starting from embryonic day (E) 2.5 until E17.5. Offspring were delivered by caesarean section at E18.5 or spontaneously. Lung and body weights were documented at birth and body weights were further monitored until postnatal day (PND) 20. Inspiratory capacity (Ic) and airway hyperresponsiveness (AHR) were measured at PND21 and 56. Histology (MLI, alveolar area), protein and mRNA quantification (Sec14L3) were done for all time points.   Results  Maternal weight gain during pregnancy was not affected by smoke after normalization for litter weight (E18.5). In the offspring, smoke exposure was associated with significantly impaired body and lung weight development. In smoke exposed males lung function tests revealed significantly decreased Ic at PND21 (p   Conclusions  Our model of prenatal smoke exposure is in agreement with findings in humans where maternal smoking during pregnancy is associated intrauterine and postnatal growth retardation and impaired lung function. Therefore, our smoke model is currently used to study gene regulatory networks and epigenetic mechanisms.
Persistence of DNA Single-Strand Breaks and Other Tests as Indicators of the Liver Carcinogenicity of 1-Nitroso-5,6-dihydrouracil and the Noncarcinogenicity of 1-Nitroso-5,6-dihydrothymine2
Authors: Terence A. Lawson, Sidney S. Mirvish, Parviz Pour, Gary Williams
Journal: JNCI Journal of the National Cancer Institute (1984)

The cyclic nitrosourea 1-nitroso-5,6-dihydrothymine [(NDHT) 1-nitrosodihydrothymine] was not significantly carcinogenic when it was administered for 1 year in drinking water (206 mg/liter) to MRC-Wistar rats. In acute toxicity tests, ip injection of saline solutions of 1-nitroso-5,6-dihydrouracil [(NDHU) CAS: 16813-36-8; 1-nitrosohydrouracil], a strong liver carcinogen in rats, produced only mild liver toxicity but marked focal degeneration of myocardial fibers. NDHU injected ip in water solution produced subcapsular liver damage. NDHU, but not NDHT, induced unscheduled DNA synthesis in hepatocyte primary cultures. NDHU, NDHT, and methylnitrosourea [(MNU) CAS: 684-93-5; N-methyl-N-nitrosourea], a liver carcinogen only under special conditions, were tested for their ability, when injected ip into rats, to produce liver DNA damage measured as strand breaks by alkaline sucrose gradient centrifugation. The three nitrosoureas produced similar maximum DNA damage of 2.2–3.2 strand breaks/108 daltons. Eighty percent of the damage due to NDHU persisted for 7 days, and the damage at that time was significantly greater than that produced by NDHT and MNU. The varying persistence of liver DNA damage may explain why NDHU, but not NDHT, is a liver carcinogen.
Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party.
Authors: J P Sculier, M Paesmans, G Bureau, G Dabouis, P Libert, G Vandermoten, O Van Cutsem, M C Berchier, F Ries, J Michel
Journal: Journal of Clinical Oncology (1993)

PURPOSE A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs. PATIENTS AND METHODS Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [i.v.] on day 1; etoposide [VP16] 120 mg/m2 i.v. on day 1; cyclophosphamide [CPA] 500 mg/m2 i.v. on day 1; cisplatin 60 mg/m2 i.v. on day 8; vindesine [VDS] 3 mg/m2 i.v. on day 8; vincristine [VCR] 2 mg i.v. on day 15; methotrexate [MTX] 100 mg/m2 i.v. on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 i.v. on day 1; CPA 1 g/m2 i.v. on day 1; VP16 80 mg/m2 i.v. on days 1 to 3). RESULTS In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm. CONCLUSION Weekly MDC failed to improve survival rates in patients with SCLC.
Acute hepatitis C virus infection induces anti‐host cell receptor antibodies with virus‐neutralizing properties
Authors: Rajiv G. Tawar, Che C. Colpitts, Jörg Timm, Tanja Fehm, Michael Roggendorf, Helga Meisel, Nicolas Meyer, François Habersetzer, François‐Loïc Cosset, Thomas Berg, Mirjam B. Zeisel, Thomas F. Baumert
Journal: Hepatology (2015)

Hepatitis C virus (HCV) causes persistent infection in the majority of infected individuals. The mechanisms of persistence and clearance are only partially understood. Antibodies (Abs) against host cell entry receptors have been shown to inhibit HCV infection in cell culture and animal models. In this study, we aimed to investigate whether anti‐receptor Abs are induced during infection in humans in vivo and whether their presence is associated with outcome of infection. We established an enzyme‐linked immunosorbant assay using a recombinant CD81‐claudin‐1 (CLDN1) fusion protein to detect and quantify Abs directed against extracellular epitopes of the HCV CD81‐CLDN1 coreceptor complex. The presence of anti‐receptor Abs was studied in serum of patients from a well‐defined cohort of a single‐source HCV outbreak of pregnant women and several control groups, including uninfected pregnant women, patients with chronic hepatitis B and D virus (HBV/HDV) infection, and healthy individuals. Virus‐neutralizing activity of Abs was determined using recombinant cell culture–derived HCV (HCVcc). Our results demonstrate that HCV‐infected patients have statistically significantly higher anti‐CD81/CLDN1 Ab titers during the early phase of infection than controls. The titers were significantly higher in resolvers compared to persisters. Functional studies using immunoadsorption and HCV cell culture models demonstrate that HCV‐neutralizing anti‐receptor Abs are induced in the early phase of HCV infection, but not in control groups. Conclusion : The virus‐neutralizing properties of these Abs suggest a role for control of viral infection in conjunction with antiviral responses. Characterization of these anti‐receptor Abs opens new avenues to prevent and treat HCV infection. (H epatology 2015;62:726–736)
Factors associated with the risk of to continue smoking after one year of treatment for cessation in specialized service
Authors: Ilda Godoy, Angélica T. Biral, Raíssa J. Almeida, André L. Bertani, Thais Garcia, Suzana E. Tanni, Irma Godoy
Journal: European Respiratory Journal (2014)

Objective: To evaluate factors associated with the risk of continuing to smoke after one year of treatment. Methods:  we retrospectively analyzed data collected during the evaluation for admission in smoking cessation program in the smoking cessation program of the School of Medicine in Botucatu, Brazil, between January and December2012.The independent variables were gender, age, educational level, age started smoking, degree of nicotine dependence, previous attempts to cessation, prior use resource to quit smoking, anxiety and depression scores and use of additional resource during treatment were evaluated in 245 smokers.One year following treatment interviews was carried out by telephone call to assess whether patients were still smoking. Multiple logistic regression was used to analyze risk to continue smoking.Results: 61% were female, with a median age of 52 (16-82) years and the onset of smoking of 14 (3-47) years. 13.5% were illiterate and 51.8% had not completed high school. The degree of dependence was high / very high in 62%, moderate in 15% and low / very low 23%. The majority (76%) had made at least one attempt smoking cessation. The median score was 8 of anxiety and depression 5 points. More than half (55%) of respondents did not quit smoking. Variables associated with risk to continue smoking were age, previous use of some resource to quit smoking, the association of tobacco use with moments of sadness and use additional resources during treatment.Conclusion: The results of this study are in agreement with the literature and emphasize the difficulty in smoking cessation in youth groups and the need for tailored programs for this group.
Combined Procedure of Surgical Repair and Cell Transplantation for Left Ventricular Aneurysm: An Experimental Study
Authors: Yutaka Sakakibara, Keiichi Tambara, Fanglin Lu, Takeshi Nishina, Genichi Sakaguchi, Noritoshi Nagaya, Kazunobu Nishimura, Ren-Ke Li, Richard D. Weisel, Masashi Komeda
Journal: Circulation (2002)

This study was designed to investigate the efficacy of the combined procedure of left ventricular (LV) repair and fetal cardiomyocyte transplantation (CM-TX) in a rat myocardial infarction model.A moderate-sized LV aneurysm was created by proximal ligation of the left coronary artery in 47 Lewis rats. Four weeks later, they were underwent another operation and received culture medium injection (n=10; group I), fetal CM-TX (n=10; group II), purse-string LV repair with culture medium injection (n=14; group III), or LV repair with fetal CM-TX (n=13; group IV). They were echocardiographically followed-up during the subsequent 4 weeks, and cardiac catheterization was performed in the final week. In the late period, LV dimension in group IV was smaller than that in group III (end-diastolic dimension, 0.92+/-0.02 versus 1.01+/-0.03 cm, P=0.0090; end-systolic dimension, 0.62+/-0.02 versus 0.74+/-0.04 cm, P=0.0093; at the fourth week), although they initially showed similar decreases in both groups. At the final week, end-systolic elastance was higher in group IV than in groups I, II, or III (0.61+/-0.10 versus 0.19+/-0.03, 0.30+/-0.09, 0.33+/-0.07 mm Hg/ micro L, P=0.0002, 0.0037, and 0.0042, respectively).Fetal CM-TX exerted preventive effects against late LV dilation and dysfunction after LV repair in the rat model. The results suggest that repair surgery combined with fetal CM-TX may enhance the surgical benefits for patients with LV aneurysm in the long term.
A Case of Metastatic Sarcomatoid Renal Cell Carcinoma Which Obtained Long-Term Survival by Multidisciplinary Treatment
Authors: Hiroshi Yaegashi, Kouji Izumi, Satoru Ueno, Yuji Maeda, Yoshifumi Kadono, Yasuhide Kitagawa, Hiroyuki Konaka, Atsushi Mizokami, Mikio Namiki
Journal: Annals of Oncology (2014)
Detection of previously undiagnosed COPD: A role for bronchodilator reversibility testing?
Authors: Peter Kjeldgaard, Jens Dollerup, Ronald Dahl, Anders Løkke, Charlotte Suppli Ulrik
Journal: European Respiratory Journal (2014)

Background and objective: Under-diagnosis of COPD is a widespread problem, and early detection of COPD is likely to improve the outcome. The study objective was to evaluate the role of bronchodilator reversibility testing [BD test] in early COPD case finding.  Method: A high-risk population was identified as the participating GPs (n=241) recruited subjects≥ 35 yrs, relevant exposure and at least one respiratory symptom. Age, smoking status, BMI, Dyspnoea score (MRC), and spirometry data was obtained. Individuals with airway obstruction (FEV 1 /FVC l 0.70) at screening spirometry underwent a BD test (salbutamol); a positive BD test was defined as ΔFEV 1 g 0.2 L and 12%.  Results: A total of 4.049 (49% females) subjects were included; mean age 58 years, BMI 27, and 32 pack-years, of which 23 % (n=937) had airway obstruction at screening spirometry. A positive BD test was found in 143 of the 937 subjects (15.3%); of these subjects, a diagnosis of COPD and asthma was confirmed in 58 and 60 subjects, respectively. In subjects with a confirmed diagnosis of COPD, the mean increase in FEV 1 following BD was 0.113 L (SD 0.100 L), and 70% of the subjects had an increase in FEV 1 l 0.200 L. The subjects with COPD and a positive BD test were characterised by a higher prevalence of dyspnoea (72% vs. 57%, p=0.02), but less cough (55% vs. 75%, p=0.001) compared to COPD subjects without BD reversibility.  Conclusion: A substantial proportion of previously undiagnosed subjects with COPD have a positive BD reversibility test, but systematic testing for BD reversibility in the setting of early COPD case finding seems to be of little diagnostic value.
Changes Caused in the Homing Patterns of Chromium 51-Labeled Lymphoid Cells by Moloney Sarcoma Virus Infection 2
Authors: Ronald W. Gillette, Adrienne Fox
Journal: JNCI Journal of the National Cancer Institute (1977)

The homing properties of murine lymphoid cells changed significantly during the course of Moloney murine sarcoma virus (MuSV-M) tumor induction, growth, and regression. When 51Cr-labeled spleen cells from BALB/c donors with progressing MuSV-M-induced tumors were injected into normal syngeneic recipients, a reduced content of spleen-seeking cells was observed, whereas similar preparations from animals with regressing tumors exhibited elevated percentages of spleen-seeking cells. The percentage of spleen-seeking cells contained in the lymph nodes of donors bearing MuSV-M-induced tumors increased in both instances. The homing of thymus or bone marrow cells was unchanged by MuSV-M infection. When the migration of spleen cells from MuSV-M-inoculated donors was studied as a function of time, the spleen-seeking populations returned to normal levels by day 15 after an initial increase from day 3 to 8. If the tumor progressed further, an additional decrease ensued, whereas the spleen-seeking population of donors with regressing tumors returned to above-normal levels. The lymph node-seeking population of the spleen and lymph nodes also declined when MuSV-M-induced tumors grew progressively. When MuSV-M-immune spleen cells were injected iv into MuSV-M-challenged recipients, significant early migration of such cells to recipient spleens was observed. Trapping of labeled splenocytes from normal donors was generally delayed. Increased sequestration of both immune spleen and lymph node cells in the lymph nodes of MuSV-M-infected recipients also occurred. The migration of both immune and normal lymph node cells to the spleens of MuSV-M-inoculated recipients was about equivalent, which suggested both specific and nonspecific elements in the response to MuSV-M. Athymic mice were also responsive to MuSV-M. When 51Cr-labeled spleen cells from MuSV-M-inoculated nu/nu donors were injected into normal mice, a sustained and significant increase in the percentages of spleen-seeking cells was observed. The data suggested that the response to MuSV-M involved both T- and B-lymphocyte recognition.
Spirometry and measurement of airway resistance by the interrupter technique (rint) in preschool children: Influence of atopy
Authors: Lucia Leonardi, Anna Rugiano, Gabriella Giancane, Annalisa di Coste, Paola Panza, Giancarlo Tancredi, Luciana Indinnimeo, Marzia Duse
Journal: European Respiratory Journal (2011)

Background:  Pulmonary function tests play an important role in the diagnosis, and management of respiratory diseases in children. The aim of our study was to evaluate the lung function by performing spirometry and airway resistance by the interrupter technique (Rint) in pre-school children in relation to their atopic status.   Materials and methods:  We studied 83 asymptomatic children (Males: 51 and Females: 32, mean age 5.15 years ± 0.72 SD). For each child has been collected the family history concerning: atopy, respiratory diseases, history of gestational and neonatal period. In all children, Skin Prick Test (SPT) to inhalant and food allergens were performed. Rint, by requiring minimal cooperation to be carried out, were performed in all subjects. Spirometry was also well tolerated by 56 subjects and was used to determine FEV 1  and FEV 0,5.    Results:  Twenty-two subjects (26.5%) had positive SPT. The following table shows the values of the main spirometric and Rint parameters of atopic (A) and not atopic subjects (NA).   Conclusions:  Despite our study assess the feasibility and repeatibility of both tests in preschool children, spirometric parameters were not statistically different between atopic and not atopic children, while mean values of Rint E were significant lower in non atopic compared to atopic children.
Effects of a home-based early pulmonary rehabilitation program on health resources use after a severe exacerbation of COPD
Authors: Roser Coll-Fernández, Natàlia Martínez, Montserrat Baré, Francisco Daniel Epelde, Estela Júlia, Fernanda María Caballero, Eduard Monsó
Journal: European Respiratory Journal (2013)

Introduction: Exacerbations and hospitalizations in COPD patients represent a major health burden and the impact of early pulmonary rehabilitation programs(PRP) on hospital readmissions after an exacerbation is controversial.  Objectives:To assess the effect of a home-based PRP just after an exacerbation of COPD,on future hospitalization and emergency visits.  Methods: Following a cohort design, COPD patients who undergone inhospital treatment for an acute exacerbation were enrolled on a home PRP within 48-72 hours of discharge (I group) including education and exercise training for 8 weeks; and were compared with a non-intervention group which received usual care(UC group).Primary outcome was the rate of hospital readmission for acute exacerbations and secondary outcome emergency visits during one-year follow-up period.Mann-Whitney test was used to compare differences between groups, p  Results: 20 patients underwent the intervention program, but 3 patients were withdrawn because they failed to meet the whole program.46 patients were included in UC group (I group mean [SD] age 75[8] years and FEV1 47[11]% predicted; UC group 72[7] years, 44[15]% predicted, ns).Difference in number of hospital readmissions was significant (I group 0 [interquartile range (IQR) 0-0 ]; UC group 0 [IQR 0-2], p  Conclusions: A post-exacerbation home multidisciplinary PRP in COPD reduce postexacerbation events that require admission without an effect on visits at emergency departments over a one-year period.
A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain
Authors: Deepitha Selvaraj, Vijayan Gangadharan, Christoph W. Michalski, Martina Kurejova, Sebastian Stösser, Kshitij Srivastava, Matthias Schweizerhof, Johannes Waltenberger, Napoleone Ferrara, Paul Heppenstall, Masabumi Shibuya, Hellmut G. Augustin, Rohini Kuner
Journal: Cancer Cell (2015)

Highlights•VEGF induces nociceptive sensitization via VEGFR1 in peripheral sensory neurons•VEGFR1 is upregulated in sensory nerves in human cancer and mouse cancer models•Sensory-neuron-specific loss of VEGFR1 attenuates tumor-induced nerve remodeling•Local/systemic blockade of VEGFR1 or VEGF family ligands attenuates cancer painSummaryCancer pain is a debilitating disorder and a primary determinant of the poor quality of life. Here, we report a non-vascular role for ligands of the Vascular Endothelial Growth Factor (VEGF) family in cancer pain. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented tumor-induced nerve remodeling and attenuated cancer pain in diverse mouse models in vivo. These findings identify a therapeutic potential for VEGFR1-modifying drugs in cancer pain and suggest a palliative effect for VEGF/VEGFR1-targeting anti-angiogenic tumor therapies.Graphical abstract
The Cell Membrane and Cell Signals as Targets in Cancer Chemotherapy AACR, EORTC, and BACR Special Conference in Cancer Research
Authors: Garth Powis, John Hickman, Paul Workman, Thomas R. Tritton, Jean-Pierre Abita, Wolfgang E. Berdel, Andreas Gescher, Harold L. Moses, Garth L. Nicolson
Journal: Cancer Research (1990)

Summary  The final session of the meeting was an open and frank discussion of ways in which it might be possible to use the targets that had been discussed at the meeting for new anticancer drug development and of what the potential problems of this approach were. A consensus was reached that, while most work to date had focused on mechanisms of growth control in normal cells, future efforts should be made simultaneously on two fronts. First, and perhaps self-evidently, we need to increase the sophistication of our understanding of the differences in membrane biology and signalling mechanisms that exist between normal and tumor cells. The second stage is expected to follow naturally from the first, namely the development of agents that could successfully exploit these differences for the purposes of chemotherapy. Many of the drugs discussed at the meeting were discovered by random screening or by molecular modification of existing agents, and this work predated attempts to use membrane and signalling targets for cancer drug development. The actions of such drugs on the cell membrane had been discovered serendipitously and only following some understanding of the basic biology of membrane signal translation. The next period of drug development will focus on agents specifically directed to cell membrane and signalling targets. This promises to be an exciting phase of cancer chemotherapy, with some attention focused away from the traditional sites for anticancer drug action. Naturally, this effort will require the concerted interdisciplinary collaboration of basic molecular biologists and cell physiologists with innovative chemists, cancer pharmacologists, experimental chemotherapists, and clinicians. This first international meeting showed how specialists in these different areas can be brought together successfully to assess progress, define problems, and indicate avenues in which real advances are to be made. The ultimate success of this approach will be judged by future advances made in new drug development, but most of the meeting participants left with a sense of high anticipation and returned to their laboratories with new ideas. In anticipation of these advances, a second international meeting is planned in 3 years time.