tbuckley/cabot-search huggingface dataset:
The reactive carbonyl derivatives of proteins in neutrophils of patients with varying severity of COPD
Authors: Vilen Molotov-Luchanskiy, Larissa Muravluyova, Dmitriy Kluyev
Journal: European Respiratory Journal (2013)

Neutrophils play an appreciable role in reactions of local immunity at COPD. The aim of our study was to examine the concentration of the reactive carbonyl derivatives of proteins (RCD) in neutrophils at patients with varying severity of COPD. COPD exacerbations with development of respiratory failure had accompanied by the syndrome of bronchial obstruction at all patients. The 1 group (n = 29) included patients with COPD moderate severity, mixed form (emphysematous and bronchial). The 2 group (n = 21) consisted of patients with COPD, severe, mixed form. Group 3 (n = 35) included patients with COPD, moderate, bronchial type. Group 4 (n = 23) included patients with COPD, severe, bronchial type. In control group there were 32 healthy ones. All patients and healthy subjects had given their consent to participate. The RCD was measured in cells following the protocol of R.L. Levine et al. (1990).  RCD level in neutrophils of patients with mixed form of COPD was lower compared with controls ones (p
Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome
Authors: Silvia Vannuccini, Vicki L. Clifton, Ian S. Fraser, Hugh S. Taylor, Hilary Critchley, Linda C. Giudice, Felice Petraglia
Journal: Human Reproduction Update (2015)

Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often require assisted reproductive technologies (ART) to conceive, and advanced maternal age is a further confounding factor. The challenge is to dissect causation, correlation and confounders in determining how infertility and reproductive disorders individually or together predispose women to poor pregnancy outcomes.The published literature, to June 2015, was searched using PubMed, summarizing all evidences concerning the perinatal outcome of women with infertility and reproductive disorders and the potential mechanisms that may influence poor pregnancy outcome.Reproductive disorders (endometriosis, adenomyosis, polycystic ovary syndrome and uterine fibroids) and unexplained infertility share inflammatory pathways, hormonal aberrations, decidual senescence and vascular abnormalities that may impair pregnancy success through common mechanisms. Either in combination or alone, these disorders results in an increased risk of preterm birth, fetal growth restriction, placental pathologies and hypertensive disorders. Systemic hormonal aberrations, and inflammatory and metabolic factors acting on endometrium, myometrium, cervix and placenta are all associated with an aberrant milieu during implantation and pregnancy, thus contributing to the genesis of obstetric complications. Some of these features have been also described in placentas from ART.Reproductive disorders are common in women of childbearing age and rarely occur in isolation. Inflammatory, endocrine and metabolic mechanisms associated with these disorders are responsible for an increased incidence of obstetric complications. These patients should be recognized as 'high risk' for poor pregnancy outcomes and monitored with specialized follow-up. There is a real need for development of evidence-based recommendations about clinical management and specific obstetric care pathways for the introduction of prompt preventative care measures.
HCMV infection triggers the development of interstitial lung diseases in autoimmune disorders
Authors: Jun Xu, Wei Wang, Qun Luo, Rong-Chang Chen
Journal: European Respiratory Journal (2014)

Rationale:  Interstitial lung disease in connective tissue diseases (CTD-ILD) is a leading cause of death in these patients. However, the pathogenesis of ILD development in these patients remains unclear, although human cytomegalovirus (HCMV) microinfections have been associated with inflammatory diseases.   Objectives:  To determine the role of HCMV infection in the initiation of ILD in CTD-ILD patients.   Methods:  Herpes virus (HCMV, EBV, and HSV) DNA was tested by real-time PCR in the peripheral blood mononuclear cells (PBMCs), plasma and lung biopsies of 62 patients with CTD-ILD, 16 patients with CTD(rheumatoid arthritis RA) without ILD and 33 healthy controls. The T lymphocyte subsets and cytokine profile were analyzed by flow cytometry and liquid Chip.   Main Results:  The detection rate of HCMV was remarkably higher in patients with CTD-ILD regardless of being treated with immunosuppressors, than in either healthy controls or RA patients. HCMV infection was closely relevant to the increased frequency of CD3+CD8+T cells accompanied by the reduced regulatory T cell (Tregs) level, and to markedly increased IL-6 level with decreased TGF-β1 to IL-6 ratio, which correlated highly with the preceding parameters of disease severity. HCMV clearance contributed to significantly improved parameters of ILD severity in the patients during a 6 month follow-up after treatment. Human lung fibroblasts co-cultured with HCMV-infected PBMCs showed a remarkable increase of IL-6 expression, which is associated with an aberrant IL-6 dependent Stat3 signal that promotes myofibroblast activation.   Conclusions:  HCMV induces pulmonary fibrogenesis in autoimmunity throughout triggering an excessive IL-6 signaling.
Sustained Release of Engineered Stromal Cell–Derived Factor 1-α From Injectable Hydrogels Effectively Recruits Endothelial Progenitor Cells and Preserves Ventricular Function After Myocardial Infarction
Authors: John W. MacArthur, Brendan P. Purcell, Yasuhiro Shudo, Jeffrey E. Cohen, Alex Fairman, Alen Trubelja, Jay Patel, Philip Hsiao, Elaine Yang, Kelsey Lloyd, William Hiesinger, Pavan Atluri, Jason A. Burdick, Y. Joseph Woo
Journal: Circulation (2013)

Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell-derived factor 1-α (engineered stromal cell-derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction.Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical-initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls.We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.
Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes
Authors: Cyrille J. Cohen, Jared J. Gartner, Miryam Horovitz-Fried, Katerina Shamalov, Kasia Trebska-McGowan, Valery V. Bliskovsky, Maria R. Parkhurst, Chen Ankri, Todd. D. Prickett, Jessica S. Crystal, Yong F. Li, Mona El-Gamil, Steven A. Rosenberg, Paul F. Robbins
Journal: Journal of Clinical Investigation (2015)

Adoptively transferred tumor-infiltrating T lymphocytes (TILs) that mediate complete regression of metastatic melanoma have been shown to recognize mutated epitopes expressed by autologous tumors. Here, in an attempt to develop a strategy for facilitating the isolation, expansion, and study of mutated antigen-specific T cells, we performed whole-exome sequencing on matched tumor and normal DNA isolated from 8 patients with metastatic melanoma. Candidate mutated epitopes were identified using a peptide-MHC-binding algorithm, and these epitopes were synthesized and used to generate panels of MHC tetramers that were evaluated for binding to tumor digests and cultured TILs used for the treatment of patients. This strategy resulted in the identification of 9 mutated epitopes from 5 of the 8 patients tested. Cells reactive with 8 of the 9 epitopes could be isolated from autologous peripheral blood, where they were detected at frequencies that were estimated to range between 0.4% and 0.002%. To the best of our knowledge, this represents the first demonstration of the successful isolation of mutation-reactive T cells from patients' peripheral blood prior to immune therapy, potentially providing the basis for designing personalized immunotherapies to treat patients with advanced cancer.
Signs of oxidative stress in bronchial asthma
Authors: Helen Evsyukova
Journal: European Respiratory Journal (2013)

Oxidative modification of proteins (OMP) is the early and most reliable sign of oxidative stress which plays an important role in pathogenesis of many lung diseases. We studied the oxidative modification of proteins in 14 patients with bronchial asthma (BA) at the exacerbation of the disease and 30 healthy subjects. For the quantitative determination of products of OMP in the blood the method based on the reaction of carbonyl derivatives of oxidized amino acid residues of proteins with 2.4-dinitrofenilgidrazin was applied. As a result of this reaction 2.4-dinitrofenilgidrazons were formed, which were registered by the spectrophotometer at 270 nm (initiation stage) and 363nm (stage of elongation). The number of recovered thiols was determined by the V.V. Sokolovsky method. It was shown that BA patients at the exacerbation phase had an increased amount of carbonyl derivatives originating at the initiation of oxidation amino acid rests of proteins (0.04±0.01U/mg) than in control subjects (0.02±0.001U/mg) (p=0.01).BA patients had a decreased amount of induced by Fenton’s stimulating system carbonyl derivatives (0.11±0.02U/mg as compared with 0.16±0.01U/mg in healthy subjects, p
Effect of physiotherapy on exercise capacity in an infant with living-donor lung transplantation. -A case study-
Authors: Shuken Kobayashi, Masahiko Kimura, Atsuhiko Matsunaga, Yuko Namiki, Takashi Hentona, Tadahiro Kaneko
Journal: European Respiratory Journal (2014)

[Introduction] Lung transplantation(LT) has recently been proposed to provid a remarkable recovery of pulmonary function, but very few data are available about changes in exercise capacity, physical function and activity of daily living after LT in infant recipients.

[Subject & Methods] A 12 year-old boy was suffered from leukemia 2years ago, and stem cell transplantation was performed, finally Bronchiolitis Obliterans required LT donated from his father in another facility. According to this clinical course, his physical activity in daily living such as walking and sitting has been decreased. Stretching, resistance training and aerobic exercise under medical monitoring have been provided continuously from 12 weeks after LT. Spirometry, respiratory muscle strength, leg muscle strength, walking speed, six-minute walking distance (6MWD) was measured on 12, 18 and 24weeks after LT.

[Results] Both of spirometry and muscle strength were increased in 24 weeks compared with 12weeks after LT. However, 6MWD still remains poor until 24weeks after LT.

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[Conclusion] This case report demonstrates that exercise capacity was increased until 24weeks after LT, but further improvement of exercise capacity is needed for a LT recipient infant.
Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. Analysis of clinical results and of surrogate angiogenesis markers
Authors: F. Bertolini, W. Mingrone, A. Alietti, P.F. Ferrucci, E. Cocorocchio, F. Peccatori, S. Cineri, P. Mancuso, C. Corsini, A. Burlini, E. Zucca, G. Martinelli
Journal: Annals of Oncology (2001)
Secondary Cell-Mediated Cytotoxic Response to Challenge of Rats With Syngeneic Gross Virus-Induced Lymphoma
Authors: Moshe Glaser, Ronald Herberman
Journal: JNCI Journal of the National Cancer Institute (1976)

Secondary cell-mediated cytotoxicity generated in vivo against a syngeneic Gross virus-induced lymphoma [(C58NT)D] in WF rats was detected by the 4-hour 51Cr release assay. At 30 days or more following primary tumor cell inoculation, after the tumors had regressed, lymphoid cells had little or no detectable direct cytotoxic reactivity. At rechallenge with tumor cells, high levels of cytotoxicity were detected in the peritoneal exudate, peripheral blood, mesenteric lymph node, and spleen cells. The secondary cellular immune response after challenge developed earlier, reached higher levels, and lasted longer than the primary immune response. The secondary cytotoxic reactivity was shown to be immunologically specific by the use of various tumor cells both as target and inhibitor cells. Treatment of immune spleen cells with specific antiserum to rat T-cells and complement abolished their cytotoxic reactivity, whereas removal of complement receptor-bearing cells or phagocytic cells did not reduct the cytotoxicity. These data demonstrated that specific-memory T-cells persisted for long periods in the lymphoid organs of immune rats and could rapidly become cytotoxic from rechallenge with the tumor.
Effects of Subcutaneous Administration of Chemical Carcinogens on Leukemia in C58 Mice2
Authors: Carrie E. Whitmire
Journal: JNCI Journal of the National Cancer Institute (1979)

The effects of sc administration of 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene (DMBA), and benzo[a]pyrene (BP) on spontaneous viral leukemia and subcutaneous sarcoma induction have been studied in weanling C58/J mice. MCA produced significantly more sarcomas at the inoculation site than did DMBA or BP; moreover, it interfered with leukemia development. DMBA produced fewer sarcomas, and the incidence of leukemia was comparable to that found in the controls. BP accelerated the incidence of leukemia, although no sarcomas were produced. When the effect of the age of the mice at the time of MCA treatment on the incidence of leukemia and sarcomas was studied, newborn and weanling mice were found to develop primarily sarcomas, whereas no sarcomas were produced in the 16-week-old mice, and 52–64% of the 16-weekold mice developed leukemia. The reason no sarcomas were found in the C58 mice was apparently different from the reason no sarcomas were found in AKR mice, inasmuch as the AKR mice did not live long enough for sarcomas to develop. Immunologic surveillance may have played a part in the sarcoma suppression in the C58 mouse.
Inhibition of Carcinogenic and Toxic Effects of Polycyclic Hydrocarbons by Phenolic Anti-oxidants and Ethoxyquin&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lee W. Wattenberg
Journal: JNCI Journal of the National Cancer Institute (1972)

The antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and ethoxyquin inhibited the carcinogenicity of benzo[a]pyrene or 7,12-dimethylbenz[a]anthracene (DMBA) on the forestomach of the mouse. They also inhibited mammary tumor formation produced by oral administration of DMBA to female Sprague-Dawley rats. Alpha-tocopherol was ineffective in both the mouse and rat experiments. BHA and alpha-tocopherol did not suppress initiation of epidermal neoplasia in the mouse by DMBA. In 2 studies of the effects of antioxidants on DMBA toxicity, BHA decreased the lethality in mice of a high concentration of DMBA in the diet, and BHA, BHT, and ethoxyquin given to female rats 1 hour before oral administration of 30 mg DMBA prevented the adrenal necrosis occurring in animals not given the antioxidants.
Abstract 800: Synergistic effects of CBL0137 and gemcitabine against non-small cell lung and pancreatic cancer xenografts
Authors: Catherine Burkhart, Rachael Kohrn, Brittany Walker, David Meyer, Katerina Gurova, Andrei Gudkov
Journal: Cancer Research (2014)

Abstract CBL0137 represents a novel class of small molecules that simultaneously activate p53 and inhibit cancer-associated stress response pathways, such as NF-κB and HSF-1. The effects of CBL0137, culminating in tumor cell death, are mediated by the inhibition of FACT, a chromatin remodelling factor complex composed of SSRP1 and SPT16 subunits, that is involved in the transcription of genes with highly ordered chromatin structure, replication, and mitosis. FACT is expressed during early embryogenesis and in undifferentiated progenitors and stem cells of adult tissues while protein levels of both FACT subunits are almost undetectable in differentiated cells and tissues. FACT is expressed in several tumor types compared to equivalent normal tissues. In particular, SSRP1 is expressed in a high proportion of lung and pancreatic cancers (∼45-63%). FACT positive tumors are associated with an aggressive malignant phenotype (high grade, metastatic disease, worse overall survival). Therefore, FACT represents a potentially important target for cancer therapy. We investigated the effect of CBL0137 and its combination with gemcitabine a nucleoside analog used in treatment of non-small lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDA). We found that CBL0137 had significant antitumor activity against a H1975 NSCLC xenograft model (89.6% growth inhibition) as well as a patient-derived PDA (PDA#2) model (70.4% growth inhibition). Furthermore, CBL0137 acted synergistically with gemcitabine against both tumor types as evidenced by increased median survival time compared to each drug administered as a single agent (increase in survival time: H1975- &amp;gt;47 days combination vs 24 days CBL0137 only, 32.5 days gemcitabine only; PDA#2- &amp;gt;42 days combination vs 28 days CBL0137 only, 30.5 days gemcitabine only). Preliminary investigation into the mechanism underlying the synergy of this combination suggest that CBL0137 may enhance gemcitabine activity in part by abrogating the expression of modulators of gemcitabine response, such as cytidine deaminase and ribonucleotide reductase. Together, these data indicate that CBL0137 may provide a clinical benefit for the treatment of both NSCLC and PDA when combined with standard agent gemcitabine. Citation Format: Catherine Burkhart, Rachael Kohrn, Brittany Walker, David Meyer, Katerina Gurova, Andrei Gudkov. Synergistic effects of CBL0137 and gemcitabine against non-small cell lung and pancreatic cancer xenografts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 800. doi:10.1158/1538-7445.AM2014-800
Structure-function relationship between extracellular matrix in airway smooth muscle and dynamics of lung function in asthma
Authors: C.Y. Yick, D.S. Ferreira, R. Annoni, P.W. Kunst, E.H. Bel, R. Lutter, T. Mauad, P.J. Sterk
Journal: European Respiratory Journal (2011)

Rationale:  Asthma is characterized by an increased deposition of extracellular matrix (ECM) within the airway smooth muscle (ASM) [Panettieri 2008, Araujo 2008]. We hypothesized that ECM composition within ASM is associated with the dynamics of lung function.   Aim:  To investigate the fractional areas of collagen I and III within ASM, and their association with spirometry and respiratory resistance R rs  and reactance X rs  in asthmatics and controls.   Methods:  Atopic mild asthmatics (n=10, no ICS) and controls (n=17) were included in this cross-sectional study. Spirometry, PC 20 , R rs  and X rs  (forced oscillation technique during tidal breathing and deep inspiration) were measured. Paraffin sections from endobronchial biopsies were stained for collagen I and III by immunohistochemistry, and fractional areas were obtained by image analysis.   Results:  There was no difference in fractional areas collagen I and III within ASM between asthmatics and controls (p>0.05). However, ASM collagen III was correlated with the change in R rs  after deep inspiration in asthmatics (r=0.74, p=0.015, Fig.1). ASM collagen I and III were not associated with spirometry or PC 20 .   Conclusion:  These data show that collagen III composition within ASM is correlated with the dynamics of R rs  after deep inspiration in asthmatics  in vivo . This suggests that ECM within ASM is positively associated with impaired airway mechanics in asthma.
A Camera that Directly Measures Physical Parameters
Authors: R Ahmed, S A Vernon
Journal: Journal of the Royal Society of Medicine (1991)

Accurate measurement of physical parameters is essential for the practice of modern medicine and ophthalmology in particular. A measuring device is presented that combines a single lens reflex (SLR) camera body incorporating two aligned in-camera grids with a calibrated macrozoom attachment. The device has multiple applications wherever accurate measurements are required. The ability to measure and record physical parameters in both health and disease is essential to modern medical practice. This is particularly so in ophthalmology. Despite the relative accessibility of external structures, the clinician's measuring equipment often takes the form of a clear plastic ruler with the ever present possibility of inaccuracy from parallax and perspective 1 . Indeed, even in the hands of expert observers, the results from the commercially produced Hertel exophthalmometer are prone to significant variation 2 . Various photographic methods of measurement have been described using a fixed focal length lens system 3,4 , and recently evaluated 5 . These, however, require processing of the photographs before measurements can be taken. We present a simple, relatively inexpensive multipurpose device which can measure physical parameters directly and record photographic evidence of these measurements. In essence, the device consists of a single lens reflex (SLR) camera fitted with two carefully aligned grids, linked to a calibrated macrozoom lens.
Dietary Determinants of Gastric Cancer in South Louisiana Inhabitants&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Pelayo Correa, Elizabeth Fontham, Linda Williams Pickle, Vivien Chen, Youping Lin, William Haenszel
Journal: JNCI Journal of the National Cancer Institute (1985)

In south Louisiana, 391 recently diagnosed gastric cancer patients and an equal number of controls were interviewed. Questions asked covered residential and occupational histories, environmental exposures, tobacco use, diet, alcohol consumption, and pertinent demographic characteristics. Elevated relative risks were found for use of tobacco and alcohol products. Diet was found to be the main determinant of gastric cancer risk in south Louisiana. Both dietary patterns and dietary risk factors differed for blacks and whites, although fruits as a group and dietary vitamin C were found to exert strong protective effects for both blacks and whites. Consumption of smoked foods and homemade or home-cured meats increased risk of gastric cancer for blacks but not for whites. The findings are discussed in the light of the prevailing etiologic hypotheses.