tbuckley/cabot-search huggingface dataset:
Mechanism of impaired water excretion in acute right ventricular failure in conscious dogs.
Authors: M Yaron, C M Bennett
Journal: Circulation Research (1978)

Considerable controversy exists as to what extent left atrial receptors play a role in the physiological regulation of antidiuretic hormone (ADH) secretion.We studied conscious dogs during a stable water diuresis induced by continuous infusion of hypotonic saline, in whom acute inflation of a chronically implanted pulmonary artery balloon consistently produced antidiuresis.Following balloon inflation in nine dogs, glomerular filtration rate (GFR) (67 ± 8 to 70 ± 6 ml/min,P < 0.2) and osmolar clearance (C Osm ) (3.1 ± 0.2 to 3.3 + 0.2 ml/min,/> > 0.2) did not change.Despite a fall in plasma osmolality (287 ± 6 to 281 ± 5 mOsm/kg H 2 O,P < 0.025) and rise in mean systemic arterial pressure (100 ± 3.6 to 110 ± 3.8 mm Hg,P < 0.01), urine osmolality rose markedly (88 ± 8 to 234 ± 45 mOsm/kg H 2 O, P < 0.02), and urine flow ( 10.1 ± 0.8 to 6.3 ± 0.9 ml/min, P < 0.01) and renal free water clearance (C Hl0 ) (7.1 ± 0.8 to 2.9 ± 0.7 ml/min, P < 0.01) both fell.This acute decrease in water excretion was shown to be the consequence of a rise in plasma levels of ADH (0.72 ± 0.07 to 2.06 ± 0.20 /iU/ml) which returned toward control levels following balloon deflation (1.14 ± 0.18 /iU7ml).The changes in ADH levels were shown to be associated with reciprocal changes in left atrial pressure (10.7 ± 1.7 to 6.1 ± 1.5 mm Hg after balloon inflation, returning to 12.2 ± 1.8 mm Hg after deflation).We conclude that in conscious dogs the effects of a small fall in left atrial pressure can predominate over the combined effects of a rise in systemic arterial pressure, continued infusion of hypotonic saline, and a fall in plasma osmolality, to produce a rise in plasma levels of ADH and antidiuresis.
Passage of Leukemic Cells across the Placenta
Authors: Perry G. Rigby, Major Thomas A. Hanson, Richard S. Smith
Journal: New England Journal of Medicine (1964)

THE combination of acute leukemia and pregnancy has been recorded infrequently in a number of papers reviewing this subject.1 2 3 4 5 No cases of coincidental congenital leukemia present at birth in a child of a mother with leukemia have been cited.6 The long-term follow-up study of offspring of leukemic parents has only lately received attention.7 Yet observations on the hereditary and transmissible nature of leukemia support the indication for investigation of this situation.8 Desai and Creger,9 using quinacrine as a DNA label, have recently studied maternofetal passage of white blood cells and platelets in normal pregnant patients. The present report concerns a . . .
Preliminary clinical experience with high-definition colonoscope illuminated by light-emitting diode
Authors: H. Yanai, J. Nishikawa, T. Okamoto, K. Kikuchi, I. Sakaida
Journal: Endoscopy (2013)

The development of gastrointestinal endoscopes has been closely related to innovations in light sources and observation devices [1]. We anticipated that the light-emitting diode (LED) might be useful for innovation of the gastrointestinal endoscope system and started the development of a test scope with white LEDs on its tip [2] [3]. The LED gastrointestinal endoscope does not need a large light source apparatus or light-guiding fiber bundle. Furthermore, the LED gastrointestinal endoscope system may be manufactured simply at low cost and is relatively independent of a power supply infrastructure.
ET-07 * DOES OSMOTIC BLOOD-BRAIN BARRIER DISRUPTION ALLOWS EFFLUX PUMP SUBSTRATES DELIVERY TO THE TUMOR AND CNS?
Authors: M. Blanchette, S. Gascon, S. Tremblay, L. Tremblay, B. Guerin, M. Lepage, R. Lecomte, D. Fortin
Journal: Neuro-Oncology (2014)

Despite decades of research, the median survival of glioblastoma (GBM) patients remains 14.6 months. The presence of the blood-brain barrier (BBB) limits CNS antineoplastic drugs delivery. Many BBB characteristics are involved in the drug delivery limitation, amongst them the efflux pumps. Different delivery strategies, such as the osmotic blood-brain barrier disruption (BBBD) have been developed and used with success in GBM patients. In order to enhance BBBD efficacy, more information is needed about its dynamic process. The aim of this study was to determine if the BBBD procedure can enable the delivery of efflux pump substrates to brain parenchyma and glioma cells. Thirty-two F98-Fischer rats were randomly assigned to 6 groups: 1: control; 2: tariquidar (P-glycoprotein (PGP) inhibitor); 3: BBBD in tumor ipsilateral hemisphere; 4: tariquidar vehicle (n = 3); 5: BBBD negative control (n = 3); and 6: BBBD + tariquidar. An MRI scan was performed to allow PET-MRI images coregistration. A 1-h dynamic PET acquisition was obtained and, with 11C-Carvedilol (a PGP substrate) administered iv during the first minute of the scan. Four volumes of interest (VOI) were studied: tumor volume, distal volume to the tumor in the ipsilateral parenchyma and equivalent control VOIs in the contralateral hemisphere. 11C-Carvedilol uptake ratios of corresponding ipsilateral and contralateral VOIs were computed for every animal. 11C-Carvedilol uptake in tumors was significantly higher on average in tariquidar and BBBD + tariquidar groups compared to the control groups. When comparing 11C-Carvedilol uptake in parenchyma, there was no significant difference between the groups at study. However, only two out of six animals in the BBBD + tariquidar group did show higher 11C-Carvedilol uptake, indicating that the BBBD must be excellent for effective substrate delivery to CNS. These results demonstrate that the BBBD procedure does not allow significant delivery of efflux pump substrates to the CNS, unless excellent BBBD procedure is achieved.
Abstract 3247: Establishment of a castration-resistant prostate cancer model, JDCaP-hr: Implications for prostate cancer recurrence
Authors: Daisuke Nakata, Tsuneo Masaki, Akira Tanaka, Yuichi Kakoi, Yusuke Nakayama, Masami Kusaka, Tatsuya Watanabe
Journal: Cancer Research (2010)

Abstract There are few in vivo models of androgen-dependent prostate cancer (ADPC), and limited availability of the models makes it difficult to evaluate anticancer agents for early stage prostate cancer and to investigate the recurrence of ADPC. We previously reported JDCaP xenograft model, an ADPC model with wild type androgen receptor (AR) and TMPRSS2-ERG gene fusion, derived from skin metastatic lesions of a prostate cancer patient. JDCaP xenografts completely regressed after surgical or medical castration; however, some of them relapsed several months after castration. The relapsed JDCaP subline, designated JDCaP-hr (hormone refractory), was established by serial passage in castrated nude mice. The AR antagonist bicalutamide did not show any effect on tumor growth of JDCaP-hr, while testosterone treatment induced tumor regression of JDCaP-hr, indicating that ligand binding to AR is not necessary, rather cytotoxic, for the growth of JDCaP-hr. Direct sequencing analysis of full length AR revealed that JDCaP-hr retained wild type AR. AR mRNA expression in JDCaP-hr was approximately 7-fold higher than in JDCaP, and interestingly, truncated AR protein with molecular weight of approximately 75 kDa in addition to full length AR (110 kDa) was expressed in JDCaP-hr. Microarray analysis revealed that ubiquitin-dependent protein catabolism pathway was markedly upregulated in JDCaP-hr compared with JDCaP. JDCaP-hr cells proliferated in vitro in steroid-free medium under co-culture condition with mouse stromal cells, and secreted prostate-specific antigen into the conditioned medium. Taken together, JDCaP/JDCaP-hr is a valuable model which simulates the recurrence of ADPC to castration-resistant prostate cancer (CRPC) with common clinical features such as AR overexpression. This model provides not only useful in vivo and in vitro systems to evaluate anticancer agents for ADPC and CRPC but also intriguing implications for the recurrence of ADPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3247.
IT-32 * DIVERGENCE OF INTRATUMORAL AND SYSTEMIC T CELL REPERTOIRES REFLECTS LOCAL MONOCYTE PROFILES DURING GLIOMA PROGRESSION
Authors: J. Sims, B. Grinshpun, Y. Feng, J. Neira, J. Samanamud, B. Amendolara, P. Canoll, P. Sims, Y. Shen, J. Bruce
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma (GBM) remains prognostically dismal, with relatively modest gains in survival from conventional therapies motivating research into how its characteristic immunosuppression might be reversed with minimal damage to brain tissue. We sequenced the T cell receptor (TCR) repertoires of tumor tissue and peripheral lymphocytes from human low-grade gliomas (LGG) and GBM, and PDGF-driven murine gliomas at timepoints and with targeted signaling blockade, leveraging innovative whole-repertoire methods to elucidate the relationship between the microenvironment and systemic effector T cells. METHODS: TCR libraries were generated from cryfrozen tumor tissue and corresponding peripheral lymphocytes, using reverse transcription and PCR (iRepertoire) of the TCR-alpha and TCR-beta chains, then sequenced on an Illumina MiSeq. We developed a computational pipeline for V-J cassette mapping, in silico translation, and sequence error correction, and profiled gene expression in tumor samples by RNAseq. We calculated TCR repertoire divergence (Jensen-Shannon divergence metric) between matched brain and blood samples, and analyzed its correlation with pathway and cell type-specific gene expression in tumor tissue. RESULTS: While the blood-brain TCR divergence was characteristically low in healthy humans and mice, it was distinctively high with a strong contribution from amino acid identity, suggesting antigen-driven selection, in early-stage (D21) glioma-bearing mice which decreased and was more variable in late-stage (D42+) glioma mice. A similar trend was observed in human LGG and GBM. ComparingTCR divergence with local gene expression revealed anticorrelation with inflammation, immune response, and cytokine signaling pathways, which we attributed to microglia/monocytes. Blockade of CCL2-dependent monocyte chemoattraction/activation in mouse tumors prevented progressive decrease blood-brain TCR divergence. CONCLUSION: The divergence of the glioma TCR repertoire from the blood offers a novel, massively-parametric biomarker of tumor progression, mechanistically linked to monocyte/microglial states, both indicating a potential target for and providing a potential predictor of personalized immunotherapy for high- and low-grade glioma patients.
Delivery of a Retroviral Vector Expressing Human β-Glucuronidase to the Liver and Spleen Decreases Lysosomal Storage in Mucopolysaccharidosis VII Mice
Authors: Cuihua Gao, Mark S. Sands, Mark E. Haskins, Katherine Parker Ponder
Journal: Molecular Therapy (2000)

Mucopolysaccharidosis VII (MPS VII) is caused by β-glucuronidase (β-gluc) deficiency and results in lysosomal storage due to the inability to degrade glycosaminoglycans. Transfer of a β-gluc gene into the liver reduces hepatic pathology as well as storage in other organs via uptake of secreted protein. A Moloney murine leukemia-based retroviral vector expressing the human β-gluc cDNA was injected intravascularly into MPS VII mice during hepatocyte replication, which was induced with im injection of an adenoviral vector that transiently expressed hepatocyte growth factor (Ad.CMV.HGF). This procedure resulted in transduction of ~1% of hepatocytes, 1% of normal liver enzyme activity, and a reduction in lysosomal storage in the liver at 3.5 months. Surprisingly, controls that received retroviral vector without HGF had transduction of non-parenchymal cells in the liver, significant levels of enzyme and RNA in the liver at 2 but not 3.5 months, and reduced lysosomal storage at 3.5 months. Transduction was also achieved in the replicating cells of the spleen, where lysosomal storage was reduced. An approach using a retroviral vector without a growth factor might temporarily reduce lysosomal storage in the liver and spleen in humans. Addition of HGF might be used to augment and prolong gene transfer. Mucopolysaccharidosis VII (MPS VII) is caused by β-glucuronidase (β-gluc) deficiency and results in lysosomal storage due to the inability to degrade glycosaminoglycans. Transfer of a β-gluc gene into the liver reduces hepatic pathology as well as storage in other organs via uptake of secreted protein. A Moloney murine leukemia-based retroviral vector expressing the human β-gluc cDNA was injected intravascularly into MPS VII mice during hepatocyte replication, which was induced with im injection of an adenoviral vector that transiently expressed hepatocyte growth factor (Ad.CMV.HGF). This procedure resulted in transduction of ~1% of hepatocytes, 1% of normal liver enzyme activity, and a reduction in lysosomal storage in the liver at 3.5 months. Surprisingly, controls that received retroviral vector without HGF had transduction of non-parenchymal cells in the liver, significant levels of enzyme and RNA in the liver at 2 but not 3.5 months, and reduced lysosomal storage at 3.5 months. Transduction was also achieved in the replicating cells of the spleen, where lysosomal storage was reduced. An approach using a retroviral vector without a growth factor might temporarily reduce lysosomal storage in the liver and spleen in humans. Addition of HGF might be used to augment and prolong gene transfer.
Abstract 837: Copper efflux transporter-mediated resistance to cisplatin
Authors: Ryan A. Mathews, Roohangiz Safaei, Stephen B. Howell
Journal: Cancer Research (2012)

Abstract The copper (Cu) efflux transporters ATP7A and ATP7B individually mediate resistance to the Pt-containing chemotherapeutic agents and have been identified as a primary pathway for the sequestration and/or export of these drugs. While the structure and transport function of ATP7A and ATP7B have been well studied, the mechanism by which they mediate resistance to the Pt drugs remains unknown. The experimental system consisted of the human fibroblast cell line Me32a, which does not express either ATP7A or ATP7B, and sublines previously produced by transfection that express either ATP7A (MeMNK) or ATP7B (MeWND). The MeMNK sub-line was 2.2-fold resistant to cisplatin whereas the MeWND cells had a 1.8-fold increase in IC50. The MeMNK and MeWND cell lines also contained a small population of cells that survived lethal dosages of DDP (10 - 20%). The MeMNK and MeWND cells were also 1.6- and 1.9-fold, respectively, resistant to the specific vacuolar proton pump (V-ATPase) inhibitor bafilomycin (Baf). Further investigation revealed that cells expressing ATP7A or ATP7B also had increased expression of V-ATPase subunits A, D and H at the mRNA level that corresponded to 8.6 - 14-fold increases at the protein level indicating that ATP7A and ATP7B perturb the proton transport system that accounts for progressive acidification of vesicles in the secretory pathway. MeMNK and MeWND cells were found to be 34- and 22-fold resistant to brefeldin A (BFA) which reversibly disrupts transport of proteins in the vesicle secretory pathway and specifically targets the ADP-ribosylation factor-1 (Arf1). This led us to investigate the Arf family of proteins and we found that the levels of Arf1, Arf3 and Arf4 were markedly reduced in cells expressing ATP7A and ATP7B at the RNA level; the reduction in Arf1 appears to account for the resistance to BFA and indicates the that function of Arf1 has been taken over by some other protein. Furthermore, we found large perturbations in the level of proteins that constitute the regulatory machinery of the vesicle secretory pathway including guanine nucleotide exchange factors (GEFs) and coat protein complexes in the MeMNK and MeWND cells. These findings indicate that ATP7A and ATP7B both produce quite large perturbations in the expression of proteins whose function is essential to the formation and trafficking of vesicles in the secretory pathway. As ATP7A and ATP7B have previously been shown to be capable of sequestering cisplatin into the microvesicular fraction of the MeMNK and MeWND cells, we conclude that these changes are linked to the ability of these Cu transporters to mediate cisplatin resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 837. doi:1538-7445.AM2012-837
A NEW IMAGING METHOD FOR PERCUTANEOUS CORONARY INTERVENTION OF CHRONIC TOTAL OCCLUSIONS: REAL TIME CARDIAC COMPUTED TOMOGRAPHY AND CORONARY ANGIOGRAPHY IMAGE REGISTRATION
Authors: Futoshi Yamanaka, Tomoki Ochiai, Kazuki Tobita, Koki Shishido, Tomoyuki Tani, Kazuya Sugitatsu, Shingo Mizuno, Hidetaka Suenaga, Yutaka Tanaka, Masato Murakami, Junya Matsumi, Saeko Takahashi, Takeshi Akasaka, Shinji Tanaka, Shigeru Saito
Journal: Journal of the American College of Cardiology (2015)
SP0015 An overview of best practices in OA care
Authors: K. Dziedzic
Journal: Annals of the Rheumatic Diseases (2013)

Recommendations for the best practices in OA care can be established by a combination of consensus of expert opinion (including lay participants), high quality original studies, systematic reviews, clinical guidelines, implementation strategies and quality indicators. Recommendations can focus on diagnosis, assessment, treatment and developing measures of OA care. The European League Against Rheumatism has published a series of evidence-based guidelines for the management and the diagnosis of osteoarthritis (OA) at different joint sites. The first message that emerges from the guidelines is that there are a range of diagnostic approaches and interventions for which there is high quality evidence. The important question is, are they being adopted in clinical practice? The difficulty for the health care professional is to determine which ones should be employed. There is increasing recognition that implementation of recommendations for the better diagnosis, assessment and management of OA is very different from simply disseminating information. The good news is that a multifaceted approach may offer a potential method of changing practice and ultimately improving OA care. The complexity of evaluating the impact of such initiatives and the difficulty of getting evidence into practice cannot be underestimated. Educational programs often result in only small changes in professional behaviour but lessons can be learnt on how to improve subsequent initiatives. Our own group is studying how best to implement the NICE OA recommendations (1) and optimise the consultation for OA in UK primary care with patients, general practitioners, practice nurses and the broader multidisciplinary team. A whole systems approach is needed, which engages with practitioners and service organisations as well as the patient; the WISE model (“Whole system Informing Self-management Engagement”) (2). The WISE approach envisages informed patients receiving support and guidance from those trained practitioners who are working within a healthcare system which is geared up to be responsive to patients’ needs. To evaluate this approach we have adopted the toolkit (http://www.normalizationprocess.org/) proposed by the Normalisation Process Theory (3). This presentation will give an overview of the mechanisms by which best OA care can be implemented in the real world using UK primary care as an example. <h3>References</h3> NICES. Osteoarthritis: national clinical guideline for care and management in adults, National Institute for Health and Clinical Excellence, 2008. www.nice.org.uk/CG59 Kennedy AP, Rogers AE, Bower P, Support for self care for patients with chronic disease BMJ 2007;335:968-970 May C, Finch T. Implementing, embedding and integrating practices: an outline of Normalisation Process Theory. Sociology 2009;43:535-554. <h3>Disclosure of Interest</h3> None Declared
HIGH IMPACT, HIGH RISK: PERCUTANEOUS CORONARY INTERVENTION IN POST-CARDIAC ARREST PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION IS ASSOCIATED WITH INCREASED SURVIVAL ALONG WITH INCREASED PUBLIC REPORTING MORTALITY
Authors: David T. Kidwell, Jinesh P. Shah, Adam Farber, Kipp Slicker, Ryan Mack, Andrew M. Shakespeare, Matthew J. Crowe, Jessica E. Pruszynski, Margaret K. Strecker-McGraw, Carl Tong, Steven Costa, Timothy Mixon
Journal: Journal of the American College of Cardiology (2016)
P127 Prevalence and Incidence of Idiopathic Pulmonary Fibrosis in UK Healthcare Databases, GPRD and THIN; The Need For an IPF Registry
Authors: PL Thompson, S Chretin, F Bugnard, WC Maier, R Cameron, M Fisher, C Giot, C Hill, I Kausar
Journal: Thorax (2012)

<h3>Background</h3> Idiopathic Pulmonary Fibrosis (IPF) is a fatal respiratory illness with limited treatment options. We previously estimated the UK prevalence of IPF using The Health Improvement Network (THIN) data. We have now further investigated this using General Practise Research Database (GPRD) data. <h3>Aims</h3> Calculate the prevalence and incidence of IPF diagnoses in the GPRD in 2010. Calculate the prevalence of IPF diagnoses in the GPRD in 2007, to compare to the THIN 2007 findings. Build a matrix of epidemiological data, to better target future public health resources. <h3>Methods</h3> Descriptive cross-sectional study, using UK GPRD data to calculate the prevalence and incidence of IPF diagnoses in 2010. <h3>Patients</h3> with a Read/OXMIS code corresponding to IPF diagnosis were identified; H563.00 Idiopathic Fibrosing Alveolitis (IFA), H563z00 Idiopathic Fibrosing Alveolitis NOS (IFA NOS), H563.12 Cryptogenic Fibrosing Alveolitis (CFA), H563100 Diffuse Pulmonary Fibrosis (DPF). To investigate coding variability, IPF diagnoses were classified as broad (all codes), narrow (IFA/IFA NOS) and IFA+CFA <h3>Patients</h3> with a first record of IPF during 2010 were classed as incident. Patients with a first record of IPF prior to or during 2010 were classed as prevalent. <h3>Results</h3> In 2010 in the GPRD, IPF was most commonly diagnosed in males (56.5%) and ≥65 year olds (80.8%). Most IPF was coded as DPF (prevalence: 39.4 [37.6–41.3] per 100,000 persons; incidence: 9.6 [8.8–10.6] per 100,000 person-years). For the broad definition, IPF prevalence was 50.7 (48.6–52.8) per 100,000 persons, with an incidence of 11.0 (10.1–12.0) per 100,000 person-years. For the narrow definition, IPF prevalence was 10.1 (9.2–11.1) per 100,000 persons, with an incidence of 1.5 (1.1–1.9) per 100,000 person-years. For the IFA+CFA definition, IPF prevalence was 13.3 (12.3–14.4) per 100,000 persons, with an incidence of 1.6 (1.3–2.0) per 100,000 person-years. In 2007, compared to THIN, the GPRD IPF point prevalence was lower in both males and females, for all diagnosis definitions (Figure 1). <h3>Conclusions</h3> IPF rates differ amongst UK healthcare databases; this may be due to GP coding variability, which is an inherent limitation of database studies. A prospective IPF registry is essential to characterise this orphan disease, to better target future public health resources.