tbuckley/cabot-search huggingface dataset:
Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma
Authors: Guohua Lou, Xiuli Song, Fan Yang, Shanshan Wu, Jing Wang, Zhi Chen, Yanning Liu
Journal: Journal of Hematology & Oncology (2015)

Hepatocellular carcinoma (HCC) displays high resistance to conventional chemotherapy. Considering that microRNA-122 (miR-122) performs an essential function to promote chemosensitivity of HCC cells, an effective vehicle-mediated miR-122 delivery may represent a promising strategy for HCC chemotherapy. An increasing interest is focused on the use of exosomes as biological vehicles for microRNAs (miRNA) transfer. Mesenchymal stem cells (MSCs) are known for their capacity to produce large amounts of exosomes. This study aimed to determine whether adipose tissue-derived MSC (AMSC) exosomes can be used for miR-122 delivery. AMSCs were transfected with a miR-122 expression plasmid. At 48 h after transfection, AMSC-derived exosomes (122-Exo) were harvested and added to recipient HCC cells. Expression levels of miR-122 in AMSCs, exosomes, and HCC cells were quantified by real-time PCR. The mRNA and protein levels of miR-122-target genes in recipient HCC cells were quantified by real-time PCR and Western blot, respectively. The effects of 122-Exo on cell viability, apoptosis, and cell cycle of HCC cells were evaluated by MTT and flow cytometry analysis. Xenograft models were used to determine whether 122-Exo can sensitize HCC cells to sorafenib in vivo. Data showed that miR-122-transfected AMSC can effectively package miR-122 into secreted exosomes, which can mediate miR-122 communication between AMSCs and HCC cells, thereby rendering cancer cells sensitive to chemotherapeutic agents through alteration of miR-122-target gene expression in HCC cells. Moreover, intra-tumor injection of 122-Exo significantly increased the antitumor efficacy of sorafenib on HCC in vivo. The findings suggest that the export of miR-122 via AMSC exosomes represents a novel strategy to enhance HCC chemosensitivity.
Separation of Cells From a Mast Cell Tumor on Density Gradients of Colloidal Silica&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Håkan Pertoft
Journal: JNCI Journal of the National Cancer Institute (1970)

A method is described for the dispersion and separation of cells from a solid mast cell tumor. Separation was carried out on density gradients of colloidal silica and polyethylene glycol and yielded 4 different cell populations in the density range 1.06–1.15 g/ml and a small amount of cells with an even lower density. Transplantation experiments indicated that most tumor-inducing cells were at densities between 1.06 and 1.08. Although the initial mechanical dispersion step destroyed some cells, the subsequent density-gradient centrifugation left the remaining cells intact. Recovery was approximately 95%. The cells did not release granular material during centrifugation and, afterward, they incorporated 14C-Ieucine into trichloroacetic acid-precipitable proteins. Their ability to induce tumors was unimpaired.
Endocrine Evaluation for Muscle Pain
Authors: Salvatore Benvenga, Antonio Toscano, Carmelo Rodolico, Giuseppe Vita, Francesco Trimarchi
Journal: Journal of the Royal Society of Medicine (2001)

In occasional patients with low adrenal cortical or thyroid function, the main symptoms are musculoskeletal1, 2. Indeed, when the features are those of a myopathy, the patient is likely to be seen first by a neurologist rather than an endocrinologist, as happened in the following two cases.
Development of Leydig Cell Tumors and Onset of Changes in the Reproductive and Endocrine Systems of Aging F344 Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Fred W. Turek, Claude Desjardins
Journal: JNCI Journal of the National Cancer Institute (1979)

The age-dependent onset of spontaneous testicular interstitial cell tumors was examined in F344 male rats. Light microscopy of testes established that nodular interstitial cell hyperplasia was evident in 3 of 5 12-month-old rats and in 5 of 5 rats at 15, 18, 21, and 24 months of age. Involution of the seminiferous epithelium was evident in all testes exhibiting extensive interstitial cell proliferation. Striking increments in serum prolactin and estradiol levels were noted with advancing age, whereas serum levels of follicle-stimulating hormone were unequivocally lower at 21 and 24 months than at 6 months of age. No measurable changes were detected in serum testosterone concentrations between 6 and 18 months of age, but marked increments in this androgen, without any measurable change in circulating luteinizing hormone titers, were apparent in 21- and 24-month-old rats. These findings point to a dynamic relationship between testicular interstitial cell tumorigenesis and age-related changes in the synthesis and/or secretion of gonadal and adenohypophyseal hormones.
Viral and Chemical Leukemia in the Rat: Comparative Study
Authors: Harry L. Ioachim, Marlene Sabbath, Barbro Andersson, Steven Keller
Journal: JNCI Journal of the National Cancer Institute (1971)

In view of the variety of clinicopathologic types of human leukemia, a comparative study of different types of experimental leukemia in the same host appeared desirable. Two types of leukemia can be induced in rats of the same strain by use of viral and chemical carcinogenic agents. Gross virus-induced leukemia is of lymphoid type and is strictly dependent on the age of the recipient and on the amount of virus administered. The thymus is a major factor in conditioning leukemogenesis and being its principal localization. 7,12-Dimethylbenz[a]anthracene (DMBA)-induced leukemia is of myeloid type and is unrelated to either the thymus or the age of the recipient. It requires repeated administration of the drug, is localized in the liver, is not prevented by splenectomy, and appears to be virus-free. These two types of leukemia were studied with the light and electron microscope, cell-free filtrates, immunofluorescence, and serial transplantation. Permanent cultures of Gross virus- and DMBA-induced leukemias, including chloromas, were also established. This comparative study provides an opportunity to consider alternate mechanisms for the process of leukemogenesis.
The first case of mycobacterium shimoidei infection in the UK
Authors: Nandini Biswas, Thomas Brown, Jonatahn Dakin
Journal: European Respiratory Journal (2011)

Case report:  We present the first case of Mycobacterium shimoidei infection in the UK. The patient is 68 years old heavy smoker with known emphysema. He was first treated for pulmonary TB in 1967 and had further 6 months of empirical therapy in 2007 for night-sweats, productive cough and new cavitating lesion. All cultures were negative at that time. He re-presented in 2009 with weight loss, night sweats, productive cough and arthralgia. His chest X-ray and CT scan showed new left upper-lobe cavitating consolidation. He was not immunocompromised and sputum specimens were smear negative. However all sputum cultures and a bronchial lavage were positive for Mycobacterium shimoidei, confirmed using a PCR reverse hybridisation technique. He was treated with ciprofloxacin, ethambutol, clarithromycin, streptomycin and rifabutin based on in-vitro sensitivities and previous case reports. After 12 months of treatment he is now well with negative sputum cultures. The CT scan changes have also resolved.   Discussion:  Mycobacterium shimoidei was first isolated by H Shimoide in 1975 and was described and named by M Tsukamura. Only a few cases have been reported worldwide. It is a distinct species of slow growing Mycobacteria which is usually identified by molecular techniques though some reported cases have been smear positive as well. The presentation is similar to other Mycobacteria and all isolates in reported cases were from pulmonary samples with radiographic evidence of cavitation, consolidation or scarring. We used in vitro sensitivity profile and previous case reports to guide choice of anti-tuberculosis therapy with good result. The patient recovered well despite late presentation and significant frailty on presentation.
Updated consensus statement on tumour necrosis factor blocking agents for the treatment of rheumatoid arthritis and other rheumatic diseases (April 2001)
Authors: D E FURST, E C KEYSTONE, F C BREEDVELD, J R KALDEN, J S SMOLEN, C E ANTONI, G R BURMESTER, L J CROFFORD, A KAVANAUGH
Journal: Annals of the Rheumatic Diseases (2001)

TNF blocking agents have proved to be effective DMARDs and they have been a major advance in the treatment of RA. Their use is expanding to other rheumatic diseases. However, rare to uncommon and unexpected toxicities have been found and others may yet be found during their use. Studies in selected areas of efficacy, toxicity, and general use of TNF blocking agents are needed to help further define the most appropriate use of these agents. Use of these drugs will require doctors experienced in the diagnosis, treatment, and assessment of RA and other rheumatic diseases. These doctors will need to make long term observations of efficacy and toxicity. Further considerations which must be made when using TNF blocking agents in this disease include the cost and a recognition that data in subgroups are still being acquired. It is hoped that this statement, which is based upon the best evidence available at the time of its creation, and modified by expert opinion, will facilitate the optimal use of these agents for our patients with RA and other rheumatic diseases.
Deletion of potentially self-reactive T cell receptor specificities in L3T4-, Lyt-2- T cells of lpr mice.
Authors: B L Kotzin, S K Babcock, L R Herron
Journal: The Journal of Experimental Medicine (1988)

The current study examines the possibility that the TCR repertoire of L3T4-, Lyt-2- cells in lpr/lpr mice is enriched for self-reactive specificities. T cells utilizing V beta 17a and V beta 8.1 gene products have been shown to be clonally eliminated in nonautoimmune mice expressing I-Ek and Mlsa/H-2k, respectively, because of their potential self reactivity. We quantitated these V beta specificities in lymph nodes and spleens of lpr/lpr mice. The results indicate that lpr-dependent L3T4-/Lyt-2- T cells, similar to normal peripheral T cells, have undergone a repertoire modification such that potential self-reactive V beta specificities have been eliminated. Evidence for tolerance in this population provides insight into the development of these aberrant cells, and may also have important implications for normal T cell development in the thymus.
Decreased ant-oxidant capacity with fiber free diet during exposure to cigarette smoke was related with changes in proportion of cecal organic acids in mice
Authors: Koichi Tomoda, Kaoru Kubo, Yoshifumi Yamamoto, Masanori Yoshikawa, Hiroshi Kimura
Journal: European Respiratory Journal (2013)

Background : Dietary fiber mitigates cough and sputum in smokers. Intake of dietary fiber is associated with a better lung function and reduced prevalence of COPD. These effects may partially come from anti-oxidant capacity by dietary fiber. However, it has not been elucidated how dietary fiber changes the anti-oxidant capacity during exposure to cigarette smoke. Dietary fibers are metabolized to organic acids in the large intestine. We hypothesized that the changes in anti-oxidant capacity by dietary fiber may be partially related with those in organic acids levels in the gut and investigated whether a fiber-free diet changes the anti-oxidant capacity and organic acid levels.  Methods: The anti-oxidant capacity as well as cecal levels of organic acids and population of micro-flora in the gut was measured after 4 months’ exposure to cigarette smoke in mice fed with a fiber-free diet.  Results:  The anti-oxidant capacity was significantly suppressed by the fiber-free diet in the non-exposed mice. The suppression in the anti-oxidant capacity further declined following exposure to cigarette smoke. In the non-smoking groups the fiber-free diet significantly increased succinic acid levels in the cecum, while in the fiber-free diet groups cigarette smoke significantly decreased acetic acid levels. The anti-oxidant capacity was correlated inversely with the ratio of succinic acid to acetic acid levels.  Conclusion: The fiber-free diet suppressed the anti-oxidant capacity in mice, and the suppression further decreased by exposure to cigarette smoke. These changes may be related with those of proportion of organic acids.
Release of Mouse Leukemia-Sarcoma Virus From Synchronized Cells2
Authors: S. Panem, W. H. Kirsten
Journal: JNCI Journal of the National Cancer Institute (1973)

The release of Kirsten mouse leukemia virus and a Kirsten mouse sarcoma-leukemia virus was studied in synchronous cell cultures. Chronically infected mouse and rat cells were synchronized by a double thymidine block. Virus release into the culture fluids was monitored at 2-hour intervals after release from thymidine inhibition by focus-forming and focus-inducing assays. Maximal virus release coincided with the time of mitosis in both cell systems.
Outcome in Patients With Myelodysplastic Syndrome After Autologous Bone Marrow Transplantation for Non-Hodgkin's Lymphoma
Authors: Jonathan W. Friedberg, Donna Neuberg, Richard M. Stone, Edwin Alyea, Haddy Jallow, Ann LaCasce, Peter M. Mauch, John G. Gribben, Jerome Ritz, Lee M. Nadler, Robert J. Soiffer, Arnold S. Freedman
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The absolute risk of myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for non–Hodgkin's lymphoma (NHL) exceeds 5% in several reported series. We report the outcome of a large cohort of patients who developed MDS after ABMT for NHL. PATIENTS AND METHODS: Between December 1982 and December 1997, 552 patients underwent ABMT for NHL, with a uniform ablative regimen of cyclophosphamide and total body irradiation followed by reinfusion of obtained marrow purged with monoclonal antibodies. MDS was strictly defined, using the French-American-British classification system, as requiring bone marrow dysplasia in at least two cell lines, with associated unexplained persistent cytopenias. RESULTS: Forty-one patients developed MDS at a median of 47 months after ABMT. The incidence of MDS was 7.4%, and actuarial incidence at 10 years is 19.8%, without evidence of a plateau. Patients who developed MDS received significantly fewer numbers of cells reinfused per kilogram at ABMT (P = .0003). Karyotypes were performed on bone marrow samples of 33 patients, and 29 patients had either del(7) or complex abnormalities. The median survival from diagnosis of MDS was 9.4 months. The International Prognostic Scoring System for MDS failed to predict outcome in these patients. Thirteen patients underwent allogeneic BMT as treatment for MDS, and all have died of BMT-related complications (11 patients) or relapse (two patients), with a median survival of only 1.8 months. CONCLUSION: Long-term follow-up demonstrates a high incidence of MDS after ABMT for NHL. The prognosis for these patients is uniformly poor, and novel treatment strategies are needed for this fatal disorder.
The effects of the morphine analogue levorphanol on leukocytes
Authors: Nancy Wurster, Peter Elsbach, Eric J. Simon, Penelope Pettis, Sharon Lebow
Journal: Journal of Clinical Investigation (1971)

Studies on bacteria have suggested that morphine-like drugs have effects on the cell membrane. To determine the effect of this class of drugs on a mammalian cell, we selected the rabbit peritoneal exudate granulocyte, which undergoes striking membrane changes during phagocytosis. We examined the effect in vitro of the morphine analogue, levorphanol on phagocytosis and metabolism by granulocytes incubated with and without polystyrene particles or live Escherichia coli. Levorphanol (1 or 2 mmoles/liter) decreased: (a) acylation of lysolecithin or lysophosphatidylethanolamine in the medium (which is stimulated about two-fold during phagocytosis) both at rest (40%) and during phagocytosis (60%); (b) uptake of latex particles and Escherichia coli, as judged by electron microscopy; (c) killing of live Escherichia coli (10-fold); (d) (14)CO(2) production from glucose-1-(14)C during phagocytosis by at least 80%; (e) K(+) content of granulocytes (35%); (f) oxidation of linoleate-1-(14)C by 50%, and its incorporation into triglyceride by more than 80%. However, levorphanol stimulated 2 to 3-fold the incorporation of linoleate-1-(14)C or palmitate-1-(14)C into several phospholipids. Glucose uptake, lactate production, and adenosine triphosphate (ATP) content are not affected by the drug. Thus, levorphanol does not appear to exert its effects through generalized metabolic suppression. Removal of levorphanol by twice resuspending the granulocytes completely reverses all inhibition. In line with observations on bacteria, it appears that the complex effects of levorphanol on granulocytes may be due at least in part to an effect on the cell membrane.
<i>TET2</i> Mutations Affect Non-CpG Island DNA Methylation at Enhancers and Transcription Factor–Binding Sites in Chronic Myelomonocytic Leukemia
Authors: Jumpei Yamazaki, Jaroslav Jelinek, Yue Lu, Matteo Cesaroni, Jozef Madzo, Frank Neumann, Rong He, Rodolphe Taby, Aparna Vasanthakumar, Trisha Macrae, Kelly R. Ostler, Hagop M. Kantarjian, Shoudan Liang, Marcos R. Estecio, Lucy A. Godley, Jean-Pierre J. Issa
Journal: Cancer Research (2015)

TET2 enzymatically converts 5-methylcytosine to 5-hydroxymethylcytosine as well as other covalently modified cytosines and its mutations are common in myeloid leukemia. However, the exact mechanism and the extent to which TET2 mutations affect DNA methylation remain in question. Here, we report on DNA methylomes in TET2 wild-type (TET2-WT) and mutant (TET2-MT) cases of chronic myelomonocytic leukemia (CMML). We analyzed 85,134 CpG sites [28,114 sites in CpG islands (CGI) and 57,020 in non-CpG islands (NCGI)]. TET2 mutations do not explain genome-wide differences in DNA methylation in CMML, and we found few and inconsistent differences at CGIs between TET2-WT and TET2-MT cases. In contrast, we identified 409 (0.71%) TET2-specific differentially methylated CpGs (tet2-DMCs) in NCGIs, 86% of which were hypermethylated in TET2-MT cases, suggesting a strikingly different biology of the effects of TET2 mutations at CGIs and NCGIs. DNA methylation of tet2-DMCs at promoters and nonpromoters repressed gene expression. Tet2-DMCs showed significant enrichment at hematopoietic-specific enhancers marked by H3K4me1 and at binding sites for the transcription factor p300. Tet2-DMCs showed significantly lower 5-hydroxymethylcytosine in TET2-MT cases. We conclude that leukemia-associated TET2 mutations affect DNA methylation at NCGI regions containing hematopoietic-specific enhancers and transcription factor-binding sites.
Impedance pneumography for assessment of a tidal breathing parameter in patients with airway obstruction
Authors: Ville-Pekka Seppä, Tiit Kööbi, Mika Kähönen, Jari Hyttinen, Jari Viik
Journal: European Respiratory Journal (2011)

Introduction:  Short-term tidal breathing analysis (TBA) parameters, like tptef:te, have indicated change in airway obstruction level in pediatric subjects, to whom conventional PFTs are inapplicable. Nocturnal TBA could provide new means for differential diagnosis and phenotyping of pediatric asthma. Recently, ambulatory impedance pneumography (IP) was reported to accurately estimate tptef:te in healthy subjects (Seppa, V.-P. et al. Chest 2010; 138(4S):816A).   Objectives:  Assess the agreement between a direct pneumotachograph (PNT) measurement and the indirect IP measurement in estimating the tptef:te parameter in patients with suspected airway obstruction.   Methods:  A simultaneous 3-minute tidal breathing recording of PNT and IP was conducted on 35 patients referred for spirometry in Tampere University Hospital. Reliable IP measurements were obtained from 27 subjects (age 18-65) having FEV1pred% mean 75% (range 26-103%) and BMI 24.8 (16.7-31.0). Agreement between methods was evaluated using the Bland-Altman analysis.   Results:  The agreement between the methods was found very good with mean difference 0.00 and 95% CI -0.10, +0.10. The agreement remained high throughout the encountered range of tptef:te values and it did not degrade in patients with more severe airway obstruction (n=6, FEV1pred% ≤60%).   Conclusion:  IP was found suitable for assessing a tidal breathing parameter regardless of presence of an airway obstruction.
Feasibility of high quality lung MRI with naturally-abundant hyperpolarised 129Xe
Authors: Neil J. Stewart, Graham Norquay, Helen Marshall, Jim M. Wild
Journal: European Respiratory Journal (2014)

Introduction: To date, imaging of pulmonary ventilation with the hyperpolarised (HP) noble gases  3 He and  129 Xe has required ∼200 mL of  3 He or ∼500 mL of enriched Xe (86%  129 Xe) to achieve sufficient image quality for clinical interpretation. However, these gases are expensive; $850 and $170 per litre of  3 He and enriched Xe, respectively. Natural abundance (NA) Xe (26%  129 Xe) presents an attractive, economical alternative ($30 per litre) for routine imaging.  Objective: To highlight the potential of NA Xe gas as a cost-effective contrast agent for imaging pulmonary ventilation.  Methods: MRI was performed at 1.5T on healthy normals and smokers.  129 Xe gas was polarised to 20-30% with an in-house, regulatory-approved polariser (Norquay et al. JAP, 2013). Subjects inhaled 1L of NA Xe for a 15s breath-hold. An optimised 3D steady-state free-precession imaging sequence (Wild et al. JMR, 2006) was implemented in order to maximise the signal-to-noise ratio (SNR) and spatial resolution achieved.  Results: All acquired image slices were of diagnostic quality, with SNRs of 23-30. The high SNR permitted identification of small ventilation defects in the lungs of healthy smokers (white arrows, Fig. 1).  Conclusions: Optimisation of MRI pulse sequences and advances in polarisation technology can facilitate acquisition of images of pulmonary ventilation of diagnostic quality, using relatively inexpensive, readily-available NA Xe gas.
The prognostic value of arterial blood gas analysis in high‐risk acute heart failure patients: an analysis of the Korean Heart Failure (<scp>KorHF</scp>) registry
Authors: Jin Joo Park, Dong‐Ju Choi, Chang‐Hwan Yoon, Il‐Young Oh, Ju Hyun Lee, Soyeon Ahn, Byung‐Su Yoo, Seok‐Min Kang, Jae‐Joong Kim, Sang‐Hong Baek, Myeong‐Chan Cho, Eun‐Seok Jeon, Shung Chull Chae, Kyu‐Hyung Ryu, Byung‐Hee Oh
Journal: European Journal of Heart Failure (2015)