tbuckley/cabot-search huggingface dataset:
Low cost biological lung volume reduction therapy for advanced emphysema
Authors: Mostafa Bakeer, Taha Abd El-Gawad, Raed El-Metwaly Ali, Ahmed El-Morsi, Mohammad El-Badrawy, Solafa El-Sharawy
Journal: European Respiratory Journal (2014)

Background  : Bronchoscopic lung volume reduction (BLVR) using biological agents is one of the new alternatives to lung volume reduction surgery.    Objectives:   To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue.    Methods:   8 male patients were enrolled and divided into two groups: group A in which autologous blood was used and group B fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution CT (HRCT) volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12-week post procedure as well as for complications.    Results:   The mean (± SD) age was 57.75 ±10.62 years. In group A at 12-week post procedure there was significant improvement in the mean value of modified medical research council (mMRC) score, 6-min walk distance (6MWD), residual volume / total lung capacity (RV/TLC) ratio, forced expiratory volume in one second /forced vital capacity (FEV1/FVC) ratio, HRCT volumetry (p-value: 0.014, 0.014, 0.008, 0.008, 0.003 respectively). In group B at 12-week post procedure there was significant improvement in the mean value of FEV1/FVC ratio (p-value: 0.012).However, the improvement in the mean value of mMRC score, 6MWD, RV/TLC ratio, HRCT volumetry was not significant (p-value: 0.058, 0.075, 0.164, 0.402 respectively).All patients tolerated the procedure and were discharged 1 day later, except one in group B who developed exacerbation that was controlled by medical therapy.    Conclusion:   These Preliminary results indicate that BLVR using low cost biological agents was safe, less invasive, less costly and effective in treating advanced emphysema.
Hepatocarcinogenic Material in Urine Specimens From Humans Consuming Aflatoxin2
Authors: T. Colin Campbell, Russell O. Sinnhuber, Donald J. Lee, J. H. Wales, Lourdes Salamat
Journal: JNCI Journal of the National Cancer Institute (1974)

Extracts of urine specimens collected from human subjects known to have consumed an average of 21 µg aflatoxin B1 during a 2-day collection period were fed to rainbow trout, Salmo gairdneri. The quantity of hepatocarcinogenic aflatoxin-like material in the extracts was estimated to be equivalent to that contributed by the small quantity of aflatoxin M1 excreted. These results suggested that the major fraction of aflatoxin ingested by humans was not excreted as aflatoxins B1, M1, or P1 but rather as relatively noncarcinogenic metabolites or conjugates thereof.
Pulmonary involvement in pleural tuberculosis: How often does it mean disease activity?
Authors: Roberta Sales, Francisco Vargas, Lisete Teixeira, Marcia Seiscento, Sidney Bombarda, Sergio Alves, Leila Antonangelo
Journal: European Respiratory Journal (2011)

To evaluate in chest X-ray and high resolution computed tomography (HRCT) of patients with pleural tuberculosis (PT), the incidence of lung lesions suggestive of active disease.   Methods:  Prospective study evaluating radiological abnormalities of 88 patients with PT. The images reviewed by three independent specialists were classified according to previously established criteria:  1) Disease activity  (presence of consolidation, thick-walled cavity, centrilobular or confluent nodules, and tree-in-bud pattern);  2) Nonspecific findings  (solitary nodules, lymphadenomegaly, cylindrical bronchiectasis, and bronchial wall thickening) and,  3) Signs of residual scarring  (parenchymal fibrotic bands and traction bronchiectasis). The results were expressed as the frequency of each observed radiological finding.   Results:  All patients presented unilateral pleural effusion. Abnormal changes were observed in chest X-ray of 22 (25%) patients and in HRCT of 55 (63%). Images compatible with active pulmonary tuberculosis were detected by chest X-ray in 9 (10%) patients and by HRCT in 38 (43%). Centrilobular nodules (30.7%), confluent nodules (27.3%) and tree-in-bud pattern (10.2%) were only detected by HRCT. The presence of solitary nodules and lymphadenomegaly were more frequently detected by HRCT. Only four patients presented tomographic images suggestive of residual disease.   Conclusion:  The present study demonstrates that pulmonary involvement is quite common in pleural tuberculosis and that the lesions were mainly detected by HRCT. These findings have epidemiological implications, since patients with pleural tuberculosis should be considered as potential sources of disease infection and spread.
Adjuvant Therapy for Stage II Colon Cancer: Prognostic and Predictive Markers
Authors: Brian Vicuna, Al B. Benson
Journal: Journal of the National Comprehensive Cancer Network (2007)

The treatment of stage II colon cancer is a controversial issue that has persisted for the past decade. Clinicians must understand that accurate assessment of risk factors is the key to identifying patients who will benefit from treatment. Pathologic staging for colon cancer is based on the American Joint Committee on Cancer 6th edition staging system. In addition, distinct pathologic factors characterize a patient at high risk for stage II disease. More recent retrospective data suggest that molecular markers and gene expression microarrays may be valuable as prognostic and predictive tests. Unfortunately, previous research studies were not powered to properly assess efficacy in stage II disease. However, 2 recent clinical trials, National Surgical Adjuvant Breast and Bowel Project C-07 and MOSAIC, have provided more insight into defining the optimal treatment approach. With the development of the newer therapeutic agents, oxaliplatin and bevacizumab, ongoing trials such as Intergroup E5202 should help determine risk versus benefit of chemotherapy in the adjuvant treatment of stage II colon cancer.
Electrocardiographic Identification of Abnormal Ventricular Depolarization and Repolarization in Patients With Idiopathic Ventricular Fibrillation 11This study was supported by Grant 93.080 from The Netherlands Heart Foundation.22All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.
Authors: Heidi A.P. Peeters, Arne Sippensgroenewegen, Eric F.D. Wever, Mark Potse, Marcel C.G. Daniëls, Cornelis A. Grimbergen, Richard N.W. Hauer, Etienne O. Robles de Medina
Journal: Journal of the American College of Cardiology (1998)
Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD
Authors: Egle Kvedaraite, Magda Lourda, Maja Ideström, Puran Chen, Selma Olsson-Åkefeldt, Marianne Forkel, Désirée Gavhed, Ulrik Lindforss, Jenny Mjösberg, Jan-Inge Henter, Mattias Svensson
Journal: Gut (2015)

<h3>Objective</h3> In IBD, interleukin-23 (IL-23) and its receptor (IL-23R) are implicated in disease initiation and progression. Novel insight into which cells produce IL-23 at the site of inflammation at an early stage of IBD will promote the development of new tools for diagnosis, treatment and patient monitoring. We examined the cellular source of IL-23 in colon tissue of untreated newly diagnosed paediatric patients with IBD. <h3>Design</h3> Colon tissues from IBD and non-IBD patients were analysed by quantitative real-time PCR (qPCR), immunofluorescence confocal microscopy and flow cytometry after appropriate sample preparation. Blood samples from IBD and non-IBD patients and healthy controls were analysed using flow cytometry and qPCR. <h3>Results</h3> We discovered that tissue-infiltrating neutrophils were the main source of IL-23 in the colon of paediatric patients with IBD, while IL-23<sup>+</sup> human leucocyte antigen-DR<sup>+</sup> or IL-23<sup>+</sup>CD14<sup>+</sup> cells were scarce or non-detectable, respectively. The colonic IL-23<sup>+</sup> neutrophils expressed C-X-C motif (CXC)R1 and CXCR2, receptors for the CXC ligand 8 (CXCL8) chemokine family, and a corresponding CXCR1<sup>+</sup>CXCR2<sup>+</sup>IL-23<sup>+</sup>subpopulation of neutrophils was also identified in the blood of both patients with IBD and healthy individuals. However, CXCL8-family chemokines were only elevated in colon tissue from patients with IBD. <h3>Conclusions</h3> This study provides the first evidence of CXCR1<sup>+</sup>CXCR2<sup>+</sup>IL-23-producing neutrophils that infiltrate and accumulate in inflamed colon tissue of patients with IBD. Thus, this novel source of IL-23 may play a key role in disease progression and will be important to take into consideration in the development of future strategies to monitor, treat and prevent IBD.
Pharmacological profile of the FLT3-Tyrosine Kinase Inhibitor AST487
Authors: Johannes L. Roesel, Guido Bold, Josef Brueggen, Doriano Fabbro, Andreas Floersheimer, Michael Jensen-Rugaard, Stefan Ruetz, Ellen Weisberg, James D. Griffin, Florian Heidel, Thomas Fischer
Journal: Cancer Research (2005)

5988   The FLT3 receptor tyrosine kinase is overexpressed in 70-90% of AML patients. In addition, up to 35% of AML patients harbor mutations in the JM domain or the kinase domain of FLT3. These mutations result in ligand-independent receptor activation and hence to signal transduction and cell proliferation. Inhibition of the FLT3 mediated signalling pathway is considered to be an attractive therapeutic approach in AML. Several FLT3 tyrosine kinase inhibitors (TKI) are currently undergoing clinical evaluation including PKC412 which showed significant blast response in peripheral blood (Stone RM et al. Blood, 2004; Sep 2; Epub). Unfortunately these early clinical responses are often superseded by blast recurrence due to a yet unknown mechanisms of drug resistance. Therefore we aimed at identifying FLT3 inhibitors from a different structural class which displayed enhanced cytotoxicity against mutated FLT3 expressing leukemic cells. This strategy yielded AST487, which incorporates all features of a pharmacological useful drug candidate. AST487 is a small molecular weight inhibitor of FLT3 kinase. Besides inhibitory activity in the nanomolar range against BaF3 cells dependent on ITD (ED 50  1.8 nM) or D835Y ((ED 50  5.1 nM) mutated FLT3, this compound also inhibits related type III tyrosine kinases at cellular level. For example proliferation of BaF3 cells dependent on Tel-PDGFRβ and PCT3-RET as well as VEGF stimulated HUVEC were inhibited by AST487 in the nanomolar range (ED 50s  27-9 nM). AST487 was particularly potent against FLT3-ITD expressing human leukemic cell lines like MV4-11 and MOLM-13 (ED 50s   10%). Repeated dosing of up to 50 mg/kg were well tolerated in mice and yielded plasma levels exceeding the in vitro determined cellular ED 50  concentration for several hours. The human leukaemia cell line MV4-11 can be transplanted subcutaneously into nude mice and the antiproliferative activity of FLT3 inhibitors determined by convenient tumor measurements. Remarkably, daily oral doses of 20 and 50 mg/kg AST487 resulted in full tumor eradication. Repeated daily oral doses of 5 mg/kg AST487 resulted in sustained inhibition of MV4-11 cell proliferation with an T/C of
Real life application of basophil activation test: A real challenge for diagnosis and treatment monitoring of atopy-related diseases?
Authors: Federica Garziano, Marialuisa Bocchino, Ediva Myriam Borriello, Anna Stanziola, Claudia La Rocca, Fortunata Carbone, Francesco Flavio, Alessandro Sanduzzi, Francesco Perna
Journal: European Respiratory Journal (2012)

Skin prick test (SPT) is widely used for the diagnosis of Immunoglobulin-E (IgE)-mediated allergic diseases. Recently, a flow-cytometry based test assessing the degree of basophil de-granulation upon in vitro allergen challenge has been introduced into clinical practice. The basophil activation test (BAT) is a promising and safe tool as could obviate disadvantages of SPT also allowing testing of uncommon allergens not used in vivo. The objective of the present study was to compare BAT performance with SPT for different aeroallergens. We performed BAT and SPT in 34 adult subjects (14 males and 20 females; age range: 18-60 yrs) presenting with symptoms suggestive of rhinitis/bronchial asthma. Degranulated basophils were identified as CD123+HLA-DR-CD63+ cells. At least 3 of 9 common aeroallergens were tested, including positive and negative controls, for a total of 146 determinations. We found that BAT results were significantly correlated with SPT (r=0.834, p<0.0001). Challenge with non conventional allergens allowed the identification by means of BAT of a case of bronchial asthma and atopic dermatitis who tested positive to Brachionus, Chlorella, and Nannochloropsis. Monitoring of atopic patients undergoing immunotherapy is actually in progress. As alternative to SPT, BAT in its present form is useful for distinguishing atopic from non-atopic patients. Further successful applications may include treatment monitoring and screening/diagnosis of type I hypersensitivity to uncommon allergens.
An evaluation of the potential for inhaled xenobiotics to develop cancer in the lung using a 3D in vitro model of the human epithelial airway-wall
Authors: Martin Clift, Daniel Studer, Peter Wick, Thomas Geiser, Peter Gehr, Roel Schins, Barbara Rothen-Rutishauser
Journal: European Respiratory Journal (2011)

Nano-objects (NOs) produced by combustion processes, such as the content contained within diesel exhaust particles (DEPs), can potentiate cell mutagenesis leading to lung cancer. Little is understood however, regarding the potential for engineered NOs to cause genotoxicity. The aim of this project was to use an  in vitro  human epithelial airway-model (epithelial cell layer (16HBE14o- cells) with human monocyte derived macrophages (apical layer) and dendritic cells (basolateral layer)), with different toxicological endpoints involved in NO-induced genotoxicity. Single- and multi-walled carbon nanotubes (SWCNTs/MWCNTs), as well as crocidolite asbestos fibres (CAFs) and DEPs caused no significant ( p >0.05) cytotoxicity (lactate dehydrogenase release) up to 0.04mg/ml after 24hrs. Significant increases ( p  in vitro .  We acknowledge the support of the European Respiratory Society, Fellowship LTRF-MC1572-2010 to Dr. MJD CLIFT.
Cell Populations and Known Surface Antigens of Tumors Induced by Abelson Virus in Pristane-Primed BALB/c Mice: An Analysis by Immunoelectron Microscopy 2
Authors: Tadao Aoki, Michael Potter, Macie M. Sturm, Margaret Liu, Mary Jane Walling
Journal: JNCI Journal of the National Cancer Institute (1975)

When Abelson murine leukemia virus (MuLV-A) was inoculated into pristane-primed BALB/c mice, either plasmacytomas (PCT), lymphosarcomas, or their mixed form was induced with a shorter latent period than that for PCT induction in mice treated with pristane alone. All 3 neoplasms were designated Abelson's tumors. The morphology of the induced malignant cells and the presence of known surface antigens were analyzed by electron microscopy. The cell surface antigens (CSA) examined were PC1, X.1, Gross (GCSA), and Moloney (MCSA); viral envelope antigens (VEA) were xVEA, x1-VEA, sub-gsVEA, and MVEA. MuLV-A-pristane-induced PCT cells produced markedly fewer intracisternal type-A particles than did mineral oil-induced PCT cells. Most, if not all, mineral oil-induced PCT cells carried PC1 antigen and produced many extracellular type-C viruses carrying xVEA and x1-VEA, whereas Abelson's tumor cells had both a lower incidence and a smaller amount of PC1 and X.1 antigens and xVEA+ virus and lacked x1-VEA+ virus. In addition, most Abelson's tumors and their type-C viruses did not carry MCSA and MVEA ro GCSA and sub-gsVEA. All the macrophages in the PC1+ Abelson's tumors and many macrophages in PC1-Abelson's tumors contained various amounts of PC1 on their cell surfaces. For these reasons, Abelson's tumors were clearly distinct from pristane- or mineral oil-induced BALB/c PCT and from M-MuLV- ro G-MuLV-induced tumors.
Personal views: Should we accept all comers?
Authors: Malcolm Lewis, Glyn J Elwyn
Journal: BMJ (1999)

In the 1980s, when general practice was popular, selecting applicants to vocational training schemes was a matter of picking the best from an excess of good candidates. If competition raises standards the converse must also be true. So now that fewer doctors want a career in general practice, the overall calibre of applicants is falling, and it is essential that standards be set for accepting doctors on to vocational training schemes.
Indian medical education system is broken, Reuters investigation finds
Authors: J. Clark
Journal: BMJ (2015)

India’s medical education system is fraudulent and unprofessional, says a damning new report based on four months of investigation across the country.1

The Reuters news agency said that the ramifications of its investigation are global, noting, “India is the world’s largest exporter of doctors, with about 47 000 currently practising in the United States and about 25 000 in the United Kingdom.” In its assessment the agency used government documents, court filings, and interviews that documented widespread fraud and cheating in medical training.

The investigation found that a sixth of the country’s 398 medical schools have been accused of cheating or other transgressions such as rigging entrance exams or accepting bribes to admit students. Accreditation of schools and regulatory inspections were found to be corrupt, involving the recruitment of fake doctors to elude inspectors and paying or exploiting local villagers to pose …
Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials.
Authors: W M Gregory, M A Richards, J S Malpas
Journal: Journal of Clinical Oncology (1992)

PURPOSE A meta-analysis was performed to compare survival after treatment with melphalan and prednisolone (M + P) with that after combination chemotherapy (CCT) in patients with multiple myeloma. METHODS Meta-analysis was performed on 18 published trials comprising 3,814 patients comparing M + P with CCT. Two-year survival percentages with observed and expected deaths at 2 years were calculated for each trial, and the overview methodology was applied to these figures. RESULTS Overall results from the 18 trials suggest that there is no difference in efficacy between the two treatments. This finding, however, masks a highly significant correlation between 2-year survival rates for M + P-treated patients in individual studies and the difference between the M + P and CCT 2-year survival rates for that study (r = .69; P = .0008). In separate overviews, those studies with a high M + P 2-year survival rate showed a survival difference in favor of M + P (P = .02), whereas those with a low rate suggested a difference in favor of CCT (P V .07). Comparison of the 2-year survival rates in the M + P treatment arms of each of the studies with available data showed an inverse correlation between survival and the proportion of patients with either poor performance status (P less than .001) or immunoglobulin A (IgA) M band (P = .02). CONCLUSIONS These results imply that M + P is superior for patients with an intrinsically good prognosis and inferior for those patients with a poor prognosis. If reliable prognostic factors can be established for this disease, they could be used to select therapy for individual patients.
Biochemical Aspects of Schizophrenia
Authors: S Matthysse, J Lipinski
Journal: Annual Review of Medicine (1975)

The evidence for and against biochemical theories of schizophrenia has been the subject of several comprehensive reviews (1-3). In this article we will selectively discuss a number of lines of investigation which have attracted considerable recent interest. Research on the biochemistry of schizophrenia may, broadly speaking, be divided into two schools of thought: the inborn errors of metabolism model and the pharmacological model. The first derives from the strong evidence for genetic factors in the predisposition to schizophrenia (4--7) and the large number of genetic diseases in which a generalized metabolic disturbance or circulating toxic factor can now be identified. The pharmacological model, on the other hand, starts from the premise that understanding the mechanism of action of antipsychotic drugs may be expected to shed light on the pathophysiology of schizophrenia. The underlying assumption that phenothiazines and butyrophenones are not merely sedatives or tranquilizers, but act on the core symptoms of schizophrenia, is well supported by a number of clinical studies (8-12). On the whole, the search for metabolic abnormalities or circulating toxins has been disappointing. While many abnormalities have been reported, typically they have not been independently confirmed or appear to be artifacts of drug therapy, diet, stress, inactivity, or chronic infection (1). Several of the more intriguing hy­ potheses concerning abnormalities detectable in peripheral fluids will be discussed: the autoimmunity theory, S-protein, trans-3-methyl-2-hexenoic acid, creatine phosphokinase, histamine, and platelet monoamine oxidase.
Strontium-90 Toxicity in Mice
Authors: L. M. van Putten, M. J. de Vries
Journal: JNCI Journal of the National Cancer Institute (1962)

Journal Article Strontium-90 Toxicity in Mice Get access L. M. van Putten, L. M. van Putten Radiobiological Institute TNO, Rijswijk Z. H., Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. de Vries M. J. de Vries Radiobiological Institute TNO, Rijswijk Z. H., Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 28, Issue 3, March 1962, Pages 587–603, https://doi.org/10.1093/jnci/28.3.587 Published: 01 March 1962 Article history Received: 28 July 1961 Published: 01 March 1962
Increased intestinal sugar permeability after challenge in children with cow's milk allergy or intolerance
Authors: R. Troncone, N. Caputo, G. Florio, E. Finelli
Journal: Allergy (1994)

The diagnosis of cow's milk allergy or intolerance (CMAI) is based on clinical improvement on exclusion diet and relapse after challenge with milk. The aim of this work was to investigate the value of the cellobiose/mannitol (C/M) sugar permeability test, performed before and after cow's milk challenge, as a tool for the diagnosis of CMAI. Thirty‐two patients underwent milk challenge at a median age of 13 months (range 3–84 months). A dual sugar (C/M) permeability test with an iso‐osmolar solution was performed before and 24 h after challenge. Of the 10 patients who developed symptoms after challenge, nine showed increased postchallenge C/M ratio, whereas such an increase was observed in only one of the 22 nonrelapsed subjects. The postchallenge C/M ratio increase in relapsed subjects is to be attributed to both higher cellobiose and lower mannitol urinary excretion. These results suggest the use of the sugar permeability test, in addition to clinical observation, as an aid in the evaluation of provocation tests in infants with suspected CMAI.
Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR
Authors: Miguel Vizoso, Humberto J Ferreira, Paula Lopez-Serra, F Javier Carmona, Anna Martínez-Cardús, Maria Romina Girotti, Alberto Villanueva, Sonia Guil, Catia Moutinho, Julia Liz, Anna Portela, Holger Heyn, Sebastian Moran, August Vidal, Maria Martinez-Iniesta, Jose L Manzano, Maria Teresa Fernandez-Figueras, Elena Elez, Eva Muñoz-Couselo, Rafael Botella-Estrada, Alfonso Berrocal, Fredrik Pontén, Joost van den Oord, William M Gallagher, Dennie T Frederick, Keith T Flaherty, Ultan McDermott, Paul Lorigan, Richard Marais, Manel Esteller
Journal: Nature Medicine (2015)