tbuckley/cabot-search huggingface dataset:
Dysfunction of oxidized pulmonary surfactant is cholesterol-dependent
Authors: Ryan Pratt, Mustafa Al-Saiedy, Lasantha Gunasekara, Nikolay Todorov, Matthias Amrein
Journal: European Respiratory Journal (2013)

Introduction : Pulmonary surfactant dysfunction has been reported for ARDS, ALI and CF, among other inflammatory lung diseases, and associated with impaired lung function. Pulmonary surfactant coats the air-lung interface and reduces surface tension to a near zero value. Low surface tension is necessary for the lung to maintain a large gas exchange area, airway patency and high compliance. This function may become impaired during pulmonary inflammation, where reactive oxygen species (ROS) degrade surfactant lipids and proteins. Here, we show that the inhibitory mechanism is cholesterol dependent. We expose Bovine Lipid Extract Surfactant (BLES) to the Fenton-like reaction as an established model for surfactant, degraded by ROS in the inflamed lung. Function is tested  in vitro , in a captive bubble surfactometer, for the oxidized BLES in the presence and absence of cholesterol.   Methods : BLES was provided by BLES Biochemicals Inc. BLES was exposed to hydroxyl radicals generated from Fenton-like chemistry for 24 h to produce oxidized BLES. Cholesterol was added to BLES to a final concentration of 8 % wt/wt. Surface activity of surfactant was determined with a computer-controlled captive bubble surfactometer.   Conclusion : The current study shows for the first time that the inhibition of surfactant by oxidation is cholesterol-dependent. We argue that the mechanism of surfactant dysfunction demonstrated  in vitro  is relevant to inflammatory lung diseases.
Intracellular cytokine and cathelicidin secretion from monocytes and neutrophils in childhood lung tuberculosis and its relationship with vitamin D levels
Authors: Erkan Cakir, Emel Torun, Esin Cetin Aktas, Gulnur Deniz
Journal: European Respiratory Journal (2013)

Introduction: Vitamin D3 contributes to host immune responses against Mycobacterium tuberculosis through antimicrobial peptide human CAP 18+ (cathelicidin). We aim to identify the intracelluler cytocine and cathelicidine secretion from monocytes and neutrophils of active TB in children. Material- methods: Fifteen TB patients and 15 healthy children were enrolled to the study. Patients’ biochemical parametres and 25 hydroxyvitamin D were measured. The expression of human cathelicidin, TNF α, IF-γ and IL-8 from monocytes and neutrophils were analyzed by flow cytometry method in the serum. Results: The expression of IL-8 and cathelicidin from CD14 + monocytes were significantly higher in TB patients (p=0.0001).  There was no difference in IL-8 and cathelicidin expression in CD 15+ neutrophils in both groups in the appropriate concentrations of vitamin D. The expression of TNF α and IF-γ from CD14 + monocytes and CD 15+ neutrophils, in both study and control groups revealed no statistical difference.
Pseudomonas-induced neutrophil recruitment in the dog airway in vivo is mediated in part by IL-8 and inhibited by a leumedin
Authors: PG Jorens, JB Richman-Eisenstat, BP Housset, PP Massion, I Ueki, JA Nadel
Journal: European Respiratory Journal (1994)

A bacteria-free supernatant of Pseudomonas aeruginosa induces the production of neutrophil chemotactic activity in human bronchial epithelial cells in vitro that is due to the potent chemotactic factor, interleukin-8 (IL-8). Because P. aeruginosa supernatant itself is not chemotactic, we hypothesized that intratracheal P. aeruginosa induces the production of neutrophil chemotactic factors, including IL-8, in vivo. Because neutrophils play a key role in cystic fibrosis, inhibition of neutrophil recruitment might be therapeutic. We studied the effect of P. aeruginosa supernatant in the isolated tracheal segment of dogs in vivo, and we measured neutrophil chemotactic activity in vitro in the tracheal fluid. We also determined the local effect of intratracheal administration of leumedin NPC 15669, an inhibitor of neutrophil recruitment, on IL-8- and Pseudomonas-induced neutrophil accumulation. P. aeruginosa supernatant and IL-8 both caused time-dependent accumulation of neutrophils in the tracheal fluid. Tracheal fluid obtained after P. aeruginosa administration had neutrophil chemotactic activity in vitro that was significantly inhibited by the IL-8 antibody. Intratracheal NPC 15669 prevented both IL-8- and Pseudomonas-induced accumulation of neutrophils. We conclude that P. aeruginosa supernatant recruits neutrophils into the airway indirectly by inducing the production of chemotactic factors, including IL-8. Our results suggest a potential therapeutic role for leumedins in chronic airway diseases.
Activation of the Aryl Hydrocarbon Receptor by Structurally Diverse Exogenous and Endogenous Chemicals
Authors: Michael S. Denison, Scott R. Nagy
Journal: The Annual Review of Pharmacology and Toxicology (2003)

The induction of expression of genes for xenobiotic metabolizing enzymes in response to chemical insult is an adaptive response found in most organisms. In vertebrates, the AhR is one of several chemical/ligand-dependent intracellular receptors that can stimulate gene transcription in response to xenobiotics. The ability of the AhR to bind and be activated by a range of structurally divergent chemicals suggests that the AhR contains a rather promiscuous ligand binding site. In addition to synthetic and environmental chemicals, numerous naturally occurring dietary and endogenous AhR ligands have also been identified. In this review, we describe evidence for the structural promiscuity of AhR ligand binding and discuss the current state of knowledge with regards to the activation of the AhR signaling pathway by naturally occurring exogenous and endogenous ligands.
Concurrent chemotherapy/radiotherapy for limited small-cell lung carcinoma: a Southwest Oncology Group Study.
Authors: J D McCracken, L M Janaki, J J Crowley, S A Taylor, P G Giri, G B Weiss, W Gordon, L H Baker, A Mansouri, J P Kuebler
Journal: Journal of Clinical Oncology (1990)

The Southwest Oncology Group (SWOG) has conducted a phase II study to explore the efficacy and toxicity of initial, concurrent use of radiation therapy with cisplatin, etoposide (VP-16), and vincristine in limited-stage small-cell carcinoma of the lung. Two courses of cisplatin, VP-16, and vincristine chemotherapy were given with concurrent radiotherapy (XRT) to the primary tumor to a total dose of 4,500 cGy. Elective brain XRT was given to all patients concurrent with a third course of cisplatin/VP-16 therapy. Consolidation chemotherapy consisting of vincristine, methotrexate, and VP-16 alternating with Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide, was given for 12 weeks following the initial induction chemotherapy/XRT program. Patients with a complete response had all therapy discontinued. Among 154 eligible patients treated, the complete response rate was 56%, with a partial response rate of 27%. The median survival is 17.5 months with an estimated 30% survival rate at 4 years from initiation of treatment. Combined modality toxicities were acceptable with the predominant toxicity being moderate to severe leukopenia and mild radiation esophagitis. The results of this treatment program appear superior to any previously reported by our group and compare favorably to those in the literature at large.
Interferon and Prostaglandins: Effects on Human Natural and Lectin-Induced Cytotoxicity
Authors: N P Lang, J R Ortaldo, G D Bonnard, R B Herberman
Journal: JNCI Journal of the National Cancer Institute (1982)

Effects of interferons (IFN) and E-series prostaglandins (PGE) were evaluated on subpopulations of human peripheral blood mononuclear lymphocytes (PBL) that mediate natural killer (NK) activity, antibody-dependent cell-mediated cytotoxicity (ADCC), or lectin-induced cellular cytotoxicity (LICC). When PBL were separated into subpopulations depending on the presence or absence of receptors for sheep erythrocytes (E+ or E−, respectively) or for the Fcγ receptor (FcγR+ or FcγR−, respectively), LICC was mainly associated with the E+FcγR− cells and to a considerably lesser extent with E+FcγR+ cells. In contrast, NK activity and ADCC were associated with the E+ and E− subpopulations that had FcγR. IFN treatment had stronger effects on the FcγR+ subpopulations. Boosting of LICC occurred maximally in the E+FcγR+ subpopulation, and the activity of the E+FcγR− cells increased only modestly. IFN had a greater augmenting effect on the NK activity and ADCC of E+FcγR+ cells than on E−FcγR+ cells. PGE strongly inhibited all three types of cell-mediated cytotoxicity and was effective on IFN-boosted cells as well as on untreated cells.
Estimation of efficacy and safety of vaccination against pneumococcus in children with various deviations in a state of health
Authors: Tatyana Grechukha, Anna Gayvoronskaya, Marina Galytskaya
Journal: European Respiratory Journal (2012)

Actuality: The pneumococcal infection proceeds hard in children with chronic diseases, particularly in children with kidney diseases. The most effective way of prevention is vaccination.  The purpose: to estimate efficacy and safety of vaccines Prevenar and Pneumo23 in children with chronic diseases.  Materials and methods: During the period of 2009-2011 494 children were vaccinated: 230 healthy children, and 264 children with different pathologies (117 children with kidney diseases, especially with nephrotic syndrome).Two types of vaccines were used: Prevenar and Pneumo23. We analyzed the shipping of vaccination, absence of relapses of disease after immunization within a year, the decrease of acute respiratory infections within a year after vaccination.  Results: There was no statistically significant difference on frequency and expressiveness of the general and local postvaccinating reactions between group of almost healthy and group of children with various deviations in a state of health(p>0,05). The general and local reactions to vaccination were seldom observed, and the expressed reactions have been noted only at 7 (4 %) children, immunized by vaccine Prevenar and at 6 (4,5 %) children, immunized by vaccine Pneumo23. The results showed the absence of relapses of the basic disease (nephrotic syndrome) after immunization, the decrease of acute respiratory infections in ill children during the year.  The conclusion: Vaccination against pneumococcal infection is effective and safe concerning the decrease of acute respiratory infections, relapses of the basic disease as for children with deviations in a state of health, and for children with kidney diseases.
Antigenic and Oncogenic Properties of a Cell Line Derived From a Hamster Brain Tumor Induced by Simian Adenovirus 7&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Sergio Pauluzzi, Fred Rapp
Journal: JNCI Journal of the National Cancer Institute (1969)

The cells of a hamster brain tumor induced by simian adenovirus 7 (SA7) were adapted to culture in vitro after a number of passages on irradiated feeder layers of newborn hamster brain cells. Virus-specific T antigen(s) was demonstrated by complement-fixation and indirect immunofluorescence tests in the tumor cells; it was located by immunofluorcscence in the cytoplasm. The sera of hamsters carrying transplanted tumors reacted with green monkey and human embryonic kidney cells infected with SA7, but not with purified SA7 particles, and did not contain neutralizing antibodies. Infectious SA7 could not be rescued from the tumor cells, even after the cells were fused with permissive cells. SA7 brain tumor cells were more oncogenic when transplanted intracerebrally than subcutaneously. Cells from an SA7 subcutaneous tumor behaved similarly. Previous immunization with SA7 protected the hamsters somewhat against the SA7 brain tumor cells inoculated either intracerebrally or subcutaneously. The results suggest that SA7 can induce an antigen leading to rejection and that the brain cells transformed by SA7 carry the transplant rejection antigen.
Chronic extrinsic allergic alveolitis in a family with idiopathic pulmonary fibrosis: the importance of histological diagnosis
Authors: PL van Valenberg, JW Lammers, HA van den Hout, J Molema, CL van Herwaarden
Journal: European Respiratory Journal (1992)

We report a patient who presented with progressive exertional dyspnoea, chronic cough and radiographic signs of interstitial lung disease. Since several of his family members were known to have familial idiopathic pulmonary fibrosis he was also suspected to suffer from this disease. After thorough investigation, including histological examination of lung biopsies obtained by thoracoscopy, a diagnosis of chronic extrinsic allergic alveolitis was made. Current knowledge of familial idiopathic pulmonary fibrosis is discussed. This case report underlines the importance of a histological diagnosis in interstitial lung disease.
Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator.
Authors: O A Ogunbiyi, P J Goodfellow, K Herfarth, G Gagliardi, P E Swanson, E H Birnbaum, T E Read, J W Fleshman, I J Kodner, J F Moley
Journal: Journal of Clinical Oncology (1998)

PURPOSE Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer. METHODS Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated. RESULTS LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease. CONCLUSION Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.
DIFFERENTIATION OF THYMUS-DERIVED CELLS FROM PRECURSORS IN MOUSE BONE MARROW
Authors: M. O. El-Arini, D. Osoba
Journal: The Journal of Experimental Medicine (1973)

An experimental model system was developed to study the differentiation of thymus-derived (T) cells from progenitors in bone marrow. In this system transplantation of bone marrow cells depleted of T cells gave rise to T cells in the spleens of irradiated recipients within 15 days of transplantation. Thus, normal bone marrow contains a class of cells that are progeniotrs of T cells (PT cells). PT cells are different from T cells since PT cells are incapable of responding to alloantigen, are theta resistant, and band in a lighter density region than do T cells. The density profile of PT cells is different from that of hematopoietic stem cells (CFU-S); PT cells band in a denser region of the gradient than do CFU-S.
Surveillance after orchidectomy for patients with clinical stage I nonseminomatous testis tumors.
Authors: J F Sturgeon, M A Jewett, R E Alison, M K Gospodarowicz, R Blend, S Herman, H Richmond, G Thomas, W Duncan, A Munro
Journal: Journal of Clinical Oncology (1992)

PURPOSE This study was designed to determine the proportion of patients with clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) managed with surveillance after orchidectomy who have more advanced disease and, therefore, require further treatment, the time to progression, the sites of progression, and the efficacy of treatment delayed until progression was recognized. PATIENTS AND METHODS One hundred five patients were observed prospectively without further treatment after orchidectomy and full clinical staging. Treatment was given immediately upon detection of marker-positive, clinical, or radiologic evidence of disease. RESULTS Thirty-seven patients (35.2%) have required further therapy for disease progression, occurring from 2 to 21 months after diagnosis. Thirty-six patients have been successfully treated. Overall, 104 patients (99%) remain alive and free of disease at 12 to 121 months after orchidectomy. Progression occurred in the retroperitoneum in 25 of 37 patients who developed further disease on surveillance. The presence of vascular invasion in the primary tumor was predictive of an increased risk of progression. CONCLUSION Surveillance is a valid alternative to immediate retroperitoneal lymph node dissection in patients with clinical stage I NSGCTT but should be recommended only under the close supervision of physicians experienced in the diagnosis and treatment of testicular cancer.
Abstract 11625: Natural Killer T Cells are Involved in Aortic Valvular Calcification via Inhibiting Osteoclastic Differentiation in Uremic Apolipoprotein-E Deficient Mice
Authors: Atsushi Nozawa, Naoki Ishimori, Satoshi Tokuhara, Akimichi Saito, Hiroyuki Tsutsui
Journal: Circulation (2011)

Objective: Tissue calcification is actively regulated by the balance of osteoblastic and osteoclastic differentiation. Osteoclasts arise from mononuclear precursors in the presence of receptor acti...
Innovation to confront Ebola in Sierra Leone: the community-care-centre model
Authors: Susan Michaels-Strasser, Miriam Rabkin, Maria Lahuerta, Katherine Harripersaud, Roberta Sutton, Laurence Natacha Ahoua, Bibole Ngalamulume, Julie Franks, Wafaa M El-Sadr
Journal: The Lancet Global Health (2015)
Identification of a novel cell type in peripheral lymphoid organs of mice. IV. Identification and distribution in mouse spleen.
Authors: R M Steinman, J C Adams, Z A Cohn
Journal: The Journal of Experimental Medicine (1975)

White pulp nodules of mouse spleen contain a minor population of cells with morphologic features that are identical to those of dendritic cells, a cell type recently described in vitro. They have characteristic large, irregularly shaped nuclei with distinctive chromatin patterns and small nucleoli. The cytoplasm is extended in processes that contain relatively few organelles. These presumptive dendritic cells can be distinguished from other cell types that are known to exist in spleen including those that have irregular or branching cell shapes. In particular, dendritic cells do not contain the large number of lysosomes seen in phagocytes, and do not actively interiorize intravenously administered colloidal thorium dioxide particles. They also lack the well developed secretory apparatus (rough endoplasmic reticulum and Golgi zone) and microfilament bundles that are noted in connective tissue cells. These morphologic observations, combined with previous in vitro work, substantiate the existence of a novel class of cells in mouse lymphoid organs.
A phase I study of sequential vinorelbine followed by paclitaxel
Authors: D.R. Budman, L. Weiselberg, V. O'Mara, A. Buchbinder, S.M. Lichtman, L. Donahue, L.M. Adams
Journal: Annals of Oncology (1999)

Background: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cytotoxic effects.A phase I dose escalation trial of vinorelbine daily x 3 with paclitaxel on day 3 repeated every 28 days in metastatic breast cancer patients was completed.Patients and methods: Female patients, PS 0-2, without evidence of CNS disease or prior neuropathies were treated with vinorelbine at dose levels 7, 10, 13 mg/m 2 per day and paclitaxel over three hours at dose levels of 135, 175, and 200 mg/m 2 .Results: Twenty-eight patients with six dose levels were studied.At dose level 1, patients developed intolerable but reversible neutropenia.Subsequent dose levels required filgrastim.Dose limiting toxicities were myalgia and fatigue at vinorelbine 13 mg/m 2 /day and paclitaxel 200 mg/m 2 .Neuropathy was minor.Twelve of twenty-five patients with measurable disease had a rapid response which did not correlate with dose level.Conclusions: Sequential administration of these two agents demonstrates activity in breast cancer patients.Phase II dosing on this schedule should be vinorelbine 13 mg/m 2 /day x 3 and paclitaxel 175 mg/m 2 .With proper selection of patients, concern about neurologic toxicity should not impede future trials of vinorelbine with paclitaxel.
Adherence to a maintenance exercise programme 1 year after pulmonary rehabilitation: What are the predictors of drop-out?
Authors: Ankie Heerema-Poelman, Johan Wempe, Ilse Stuive
Journal: European Respiratory Journal (2012)

Objective: To study adherence to a maintenance exercise programme in patients with COPD, who had been following a pulmonary rehabilitation programme.

Methods: 70 patients with COPD were included in the study after completing the rehabilitation programme. All were referred to an community-based maintenance exercise programme. Adherence was assessed by open questionnaire after 6 and 12 months and lung function, exercise capacity, exercise self-efficacy, illness perceptions, health related quality of life, levels of anxiety and depression, duration of rehabilitation and number of exacerbations were studied as possible predictors of (non-)adherence.

Results: Ten patients died or were lost to follow-up. Of the remaining 60 patients, 73.3 and 63.3% were adherent to the exercise programme after 6 and 12 months, respectively. FEV1 ( p =0.021), HADS depression score ( p =0.025) and duration of rehabilitation ( p =0.018) were statistically significant predictors of adherence.

Conclusion: Adherence to a maintenance exercise programme, after having followed a pulmonary rehabilitation course, is quite reasonable for patients with COPD: about one third drops out during the first year. A poorer lung function, a longer rehabilitation course, and higher level of depressive symptoms are predictive for drop-out.

Practice Implications: To improve adherence to a maintenance programme, special attention should be paid to patients with lower FEV1, those with signs of depression or in need of a longer rehabilitation.
Women make up majority of trainees in seven US specialties
Authors: Michael McCarthy
Journal: BMJ (2015)

Women now account for more than half of graduate trainees in seven specialties in the United States but remain under-represented overall in graduate training programs compared with their share of the US population, as do Hispanic and black people, a study has found.1

The seven specialties in which women made up the majority of trainees were:

The specialty with the lowest percentage of women trainees was orthopedics, in which …