tbuckley/cabot-search huggingface dataset:
Abstract A84: Stereotactic injections of primary medulloblastomas as a representative model of the different subgroups for preclinical drug screening
Authors: Cecilia Krona, Cecilia Dyberg, Emma Sandén, Anna Darabi, Malin Wickström, Paul Northcott, John Inge Johnsen, Peter Siesjö
Journal: Cancer Research (2014)

Abstract Established tumor cell lines are extensively used for screening of novel therapeutic compounds. However, during long-term culturing cells adjust to the conditions and acquire additional genetic aberrations, which may cause them to differ significantly from the original tumor. In vitro conditions may also fail to recapitulate aspects of the tumor microenvironment that may have an impact on cell fate, for example, drug clearance by the circulation, which would lead to renewed cell cycling and the heterogeneity of the tumor cell population versus the homogenous population of cells in culture. Predisposed genetic mouse models more closely recapitulate most aspects of human disease but they usually require complex breeding schemes and may suffer from incomplete tumor penetrance and a variable age of tumor onset. In order to establish a new medulloblastoma model for therapeutic studies, we have acquired primary cultures of medulloblastoma tumors representing the four different subtypes of medulloblastomas (Wnt, Shh, group 3 and group 4). Cells were grown as neurospheres and characterized regarding stem cell markers and immunological status. Early passages were collected and for each primary line, two NOD scid mice were orthotopically injected with 20.000 and 200.000 cells, respectively. Mice were closely monitored for symptoms of brain tumor burden (weight loss, hunched posture, uncoordinated movement, lethargy, poor balance and/or paralysis) during six months. Mice injected with cells from the SHH subgroup and group 3 medulloblastomas developed symptoms of brain tumors with a latency of 13-25 weeks. A positive correlation was observed between tumor latency and number of injected cells. Brains were collected and processed for histopathological confirmation of tumor prevalence, whole genome sequencing and gene expression analysis. Neurosphere cultures were also re-established to create a reproducible model for pre-clinical therapeutic trials on human medulloblastoma by serial orthotopic transplantation. Citation Format: Cecilia Krona, Cecilia Dyberg, Emma Sandén, Anna Darabi, Malin Wickström, Paul Northcott, John Inge Johnsen, Peter Siesjö. Stereotactic injections of primary medulloblastomas as a representative model of the different subgroups for preclinical drug screening. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A84.
Lymphotoxin-β receptor signaling regulates hepatic stellate cell function and wound healing in a murine model of chronic liver injury
Authors: Richard G. Ruddell, Belinda Knight, Janina E. E. Tirnitz‐Parker, Barbara Akhurst, Lesa Summerville, V. Nathan Subramaniam, John K. Olynyk, Grant A. Ramm
Journal: Hepatology (2008)

Lymphotoxin-beta (LTβ) is a proinflammatory cytokine and a member of the tumor necrosis factor (TNF) superfamily known for its role in mediating lymph node development and homeostasis. Our recent studies suggest a role for LTβ in mediating the pathogenesis of human chronic liver disease. We hypothesize that LTβ co-ordinates the wound healing response in liver injury via direct effects on hepatic stellate cells. This study used the choline-deficient, ethionine-supplemented (CDE) dietary model of chronic liver injury, which induces inflammation, liver progenitor cell proliferation, and portal fibrosis, to assess (1) the cellular expression of LTβ, and (2) the role of LTβ receptor (LTβR) in mediating wound healing, in LTβR−/− versus wild-type mice. In addition, primary isolates of hepatic stellate cells were treated with LTβR-ligands LTβ and LTβ-related inducible ligand competing for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT), and mediators of hepatic stellate cell function and fibrogenesis were assessed. LTβ was localized to progenitor cells immediately adjacent to activated hepatic stellate cells in the periportal region of the liver in wild-type mice fed the CDE diet. LTβR−/− mice fed the CDE diet showed significantly reduced fibrosis and a dysregulated immune response. LTβR was demonstrated on isolated hepatic stellate cells, which when stimulated by LTβ and LIGHT, activated the nuclear factor kappa B (NF-κB) signaling pathway. Neither LTβ nor LIGHT had any effect on alpha-smooth muscle actin, tissue inhibitor of metalloproteinase 1, transforming growth factor beta, or procollagen α1(I) expression; however, leukocyte recruitment-associated factors intercellular adhesion molecule 1 and regulated upon activation T cells expressed and secreted (RANTES) were markedly up-regulated. RANTES caused the chemotaxis of a liver progenitor cell line expressing CCR5. Conclusion: This study suggests that LTβR on hepatic stellate cells may be involved in paracrine signaling with nearby LTβ-expressing liver progenitor cells mediating recruitment of progenitor cells, hepatic stellate cells, and leukocytes required for wound healing and regeneration during chronic liver injury. (HEPATOLOGY 2009;49:227–239.)
PM-17 * INTRACEREBRAL IFN- DOES NOT ENHANCE THE RESPONSE TO VACCINE IMMUNOTHERAPY FOR CANINE GLIOMA
Authors: L. Pluhar, M. Olin, M. Goulart, B. Andersen, M. Hunt, J. Ohlfest
Journal: Neuro-Oncology (2014)

Due to the complexity of human tumor environment and host immune interactions, the majority of successful brain cancer therapies in rodent models fail to show the same efficacy when translated to human patients. Pet dogs with spontaneous glioma recapitulate important features of human disease and we have used this more representative model to assess the response to vaccine immunotherapy with and without interferon gamma (IFN-γ) gene therapy after surgery. Dogs with newly diagnosed glioma underwent surgical tumor debulking and were randomized to receive 1) autologous tumor lysate vaccines with CpG ODN as an adjuvant (n = 12) or 2) Ad-mediated interferon gamma (IFN-γ) gene therapy injected around the resection cavity followed by vaccine immunotherapy (n = 12). A grade IV IFN-γ dose-related toxicity (severe encephalitis and lymphocytic perivascular cuffing) resulted in death of one dog. No further adverse events were seen at a lower IFN-γ dose supporting the safety of the treatment. This immunotherapy activated a humoral response with specific tumor-reactive IgG antibodies detected after vaccination in all dogs. Addition of IFN-γ gene therapy did not affect the median overall survival time of 204 days versus 211 days with vaccine alone. As expected, there were significant differences (P = 0.036) in survival between dogs with low-grade (369 days) versus high-grade (204 days) tumors. During postmortem analysis, no dog with a low-grade tumor had recurrence, whereas all dogs with grade III/IV tumors died from progression. We hoped that forced IFN-γ expression would sensitize residual tumor cells to CTL recognition and recruit NK cells to kill MHC Ilow/- cells, thereby enhancing the effects of vaccine immunotherapy. Our data failed to support this theory, however the lack of difference could be due to the small number of dogs in each group (type II error) or to insufficient in situ expression of IFN-γ to elicit the desired effect.
Nonalcoholic steatohepatitis is frequently accompanied by metabolic diseases
Authors: Teoman Dogru, Cemal Nuri Ercin, Gokhan Erdem, Ilker Tasci, Alper Sonmez, Serkan Tapan
Journal: Hepatology (2008)

In a recent issue, van der Poorten et al.1 reported an association of nonalcoholic steatohepatitis (NASH) with liver inflammation and fibrosis independent of insulin resistance and hepatic steatosis as assessed by magnetic resonance imaging. Although this association is already present, the study is important because it provides scientific information on this clinically relevant condition. However, we think that some points should be discussed. First, as shown in Table 1, most of the patients with NASH are overweight or obese. In addition, an important portion of the study participants have other metabolic disturbances (high blood pressure, dyslipidemia, etc.) alone or in combination. It is well known that all components that constitute the metabolic syndrome (MetS) are risk factors for type 2 diabetes mellitus and also prediabetes, namely, impaired fasting glucose and/or impaired glucose intolerance.2 Although both T2DM and impaired glucose tolerance are among the components of MetS,3 plasma insulin and adipokine levels differ according to the degree of glucose dysregulation.4, 5 The same is also true for hypertension or elevated blood pressure and dyslipidemia.6, 7 Second, apart from the thiazolidinediones, no information about the drug use of the subjects could be seen in the text. We know that circulating adipokines and measures of insulin sensitivity are easily affected by medications started for the metabolic problems mentioned above.8, 9, 10 The authors state in their article that the participants were accepted as having MetS according to the Adult Treatment Panel III criteria. The diagnostic criteria can be used clinically with success; however, while designing clinical studies to display mechanistic associations, we have to give ultimate effort to exclude possible confounders that might interfere with the results. Therefore, we would like to ask the authors whether they can present some new results by categorizing the patients with NASH according to metabolic confounders such as type 2 diabetes mellitus, impaired glucose tolerance, blood pressure, and lipid profile. This may provide the readers clearer information related to the mechanism(s) of NASH. Teoman Dogru M.D.*, Cemal Nuri Ercin M.D.*, Gokhan Erdem M.D. , Ilker Tasci M.D. , Alper Sonmez M.D. , Serkan Tapan M.D.§, * Department of Gastroenterology, Gulhane School of Medicine, Etlik, Ankara, Turkey, Department of Internal Medicine, Gulhane School of Medicine, Etlik, Ankara, Turkey, Department of Endocrinology, Gulhane School of Medicine, Etlik, Ankara, Turkey, § Department of Biochemistry, Gulhane School of Medicine, Etlik, Ankara, Turkey.
Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential
Authors: S Arii
Journal: Hepatology (1996)

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP-2 and MMP-9 and the corresponding tissue inhibitor of metalloproteinase (TIMP-2 and TIMP-1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP-2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA expression. In addition, the expression of MMP-2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP-9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration in HCC.
Hydroxyurea and sodium phenylbutyrate therapy in thalassemia intermedia
Authors: Carolyn Hoppe, Elliott Vichinsky, Bradley Lewis, Dru Foote, Lori Styles
Journal: American Journal of Hematology (1999)

Hydroxyurea (HU) and sodium phenylbutyrate (SPB) have been shown to increase fetal hemoglobin (Hb F) levels in patients with thalassemia intermedia. The reported effects of these agents in increasing total Hb, however, have been inconsistent and there have been no studies on the combination of these medications. We describe the clinical response, as determined by increases in total Hb and decreased transfusion needs, in five patients with thalassemia intermedia treated with HU alone or in combination with SPB. All of the patients responded with increased levels of Hb F, but the responses in total Hb varied. Of the five patients, two had a marked response in total Hb in excess of 3 g/dl, two responded modestly with an increase in total Hb of 1–2 g/dl, and one did not respond. Prolonged responses were achieved with low doses of HU (3–10 mg/kg/day) and higher doses were associated with mild reversible hematologic or hepatic toxicity and no further increases in Hb. Sodium phenylbutyrate was added to treatment with HU in two patients, but failed to produce an increase in total Hb despite increasing Hb F levels. Of the four patients who responded to HU with an increase in total Hb, all reported symptomatic improvement and three have not required further transfusions. We conclude that low-dose HU therapy in patients with thalassemia intermedia may increase total Hb levels sufficiently to eliminate the need for transfusions. We, therefore, recommend a trial of HU for thalassemia intermedia patients in whom chronic transfusion therapy is being contemplated. Am. J. Hematol. 62:221–227, 1999. © 1999 Wiley-Liss, Inc.
A Swine Model for Teaching Endoscopic Ultrasound (EUS) Imaging and Intervention Under EUS Guidance
Authors: M. S. Bhutani, B. J. Hoffman, R. H. Hawes
Journal: Endoscopy (1998)

Endoscopic ultrasonography (EUS) has evolved into a clinically useful imaging modality. Widespread application of EUS has been hampered by the long learning curve and the paucity of training programs. We report here our efforts to develop an animal model for teaching endoscopic ultrasound.The protocol for performing endoscopic ultrasound in live pigs included general anesthesia, endotracheal intubation, and mechanical ventilatory support. An echo-endoscope was then inserted into the pig gastrointestinal tract, and attempts were made to obtain ultrasound images that were comparable to human endoscopic ultrasound images. Intervention under EUS guidance was then attempted in the swine.It was possible to image the esophageal and gastric wall, pancreas, aorta, celiac artery, superior mesenteric artery, liver, and portal vein. The images obtained were analogous to human endoscopic ultrasound images. EUS-guided interventional techniques were also carried out, including EUS-guided fine-needle aspiration and celiac plexus neurolysis.A swine model appears to be useful for hands-on teaching in endoscopic ultrasound imaging and intervention under endoscopic ultrasound guidance.
Time, Symptom Burden, Androgen Deprivation, and Self-Assessed Quality of Life after Radical Prostatectomy or Watchful Waiting: The Randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) Clinical Trial
Authors: Eva Johansson, Anna Bill-Axelson, Lars Holmberg, Erik Onelöv, Jan-Erik Johansson, Gunnar Steineck
Journal: European Urology (2008)
NHS spending in Scotland will grow by 13% in next three years compared with 33% in last three
Authors: B. Christie
Journal: BMJ (2008)

The NHS in Scotland managed to stay within its budget in the past financial year, but there are warnings that it faces challenging times ahead.

Audit Scotland says that there will be additional financial pressures from the rising cost of pay deals for staff, drugs, and fuel; meeting reduced waiting times; and delivering improvements to services. Extra staff will also be needed to achieve the full implementation of the European Working …
Treatment of mild and moderate hypertension
Authors: A. Trafford
Journal: BMJ (1981)

Evidence from the Royal College of General Practitioners cohort study points to the progestogen dosage in combined preparations as being more important in this regard.'Moreover, a lack of association with oestrogen dosage was found.In addition, a positive correlation between the risk of arterial disease and progestogen dosage has been demon-strated3 and this, in part at least, may be due to the effect on blood pressure.
Injury-Specific <i>Ex Vivo</i> Treatment of the Donor Lung: Pulmonary Thrombolysis Followed by Successful Lung Transplantation
Authors: Tiago N. Machuca, Michael K. Hsin, Harald C. Ott, Manyin Chen, David M. Hwang, Marcelo Cypel, Thomas K. Waddell, Shaf Keshavjee
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Review: Oral antiviral drugs reduce clinical recurrence in recurrent genital herpes
Authors: Andre C. Kalil, Uriel S. Sandkovsky
Journal: Annals of Internal Medicine (2015)

Source Citation Le Cleach L, Trinquart L, Do G, et al. Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients. Cochrane Database Syst Rev. 2014;8:CD009036. 25086573
Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia
Authors: Benjamin Mizukawa, Junping Wei, Mahesh Shrestha, Mark Wunderlich, Fu-Sheng Chou, Andrea Griesinger, Chad E. Harris, Ashish R. Kumar, Yi Zheng, David A. Williams, James C. Mulloy
Journal: Blood (2011)
Diabetic Complications Among American Indians of Washington, Oregon, and Idaho: Prevalence of retinopathy, end-stage renal disease, and amputations
Authors: William L Freeman, Gwendolyn M Hosey
Journal: Diabetes Care (1993)

OBJECTIVE— To estimate the prevalence of severe diabetic complications. RESEARCH DESIGN AND METHODS— We surveyed the data systems of the IHS and local care providers to identify all AI/AN people with any of three diabetic complications: retinopathy needing one or more laser treatments, ESRD needing dialysis, and one or more LEAs. We calculated prevalence rates that were sex-age adjusted to the U.S. population for total sample, each community, gender, and culture area. RESULTS–Of the population-based complete sample with diabetes, 1.7% had retinopathy, 1% ESRD, and 4% LEA. Complication rates among the culture areas were not statistically different. The LEA rate among diabetic men (5.8%) was higher than that among women (2.3%). The odds ratio was 2.2 (95% CI 1.2-4.2). One community had an extraordinarily high LEA rate of 16%. CONCLUSIONS— This study showed that IHS can use its data systems to estimate prevalence of diabetic complications and identify population groups with higher prevalence rates. The data led the IHS clinic with the high LEA rate to start a program to prevent amputations. We suggest quality assurance activities based on the methods of this study.
Incidence of influenza-associated hospitalization in rural communities in western and northern India, 2010–2012: A multi-site population-based study
Authors: Siddhivinayak Hirve, Anand Krishnan, Fatimah S. Dawood, Pallavi Lele, Siddhartha Saha, Sanjay Rai, Vivek Gupta, Kathryn E. Lafond, Sanjay Juvekar, Varsha Potdar, Shobha Broor, Renu B. Lal, Mandeep Chadha
Journal: Journal of Infection (2014)
Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid
Authors: Jin Man Kim, Sang Wook Kang, Su-Mi Shin, Duck Su Kim, Kyong-Kyu Choi, Eun-Cheol Kim, Sun-Young Kim
Journal: International Journal of Oral Science (2013)

All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and -9 in HDPCs. The productions and messenger RNA (mRNA) expressions of MMP-2 and -9 were accessed by gelatin zymography and real-time polymerase chain reaction (PCR), respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 µmol⋅L(-1) ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs, which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.
Lung Cancer and Pneumothorax
Authors: N. J. C. Snell
Journal: JAMA (1979)

<h3>To the Editor.—</h3> In their recent case report Hyde and Hyde (239:1421, 1978) stress the rarity of the association of pneumothorax with lung cancer and attempt to dissuade us from investigations to exclude malignant neoplasms. Their statement that this association is practically confined to those patients older than 40 years is simply not true, unless the authors are restricting themselves to primary bronchogenic carcinomas. If this be the case, the statement is self-evident, since primary lung cancer itself is rare in patients younger than 40 years. In fact, pneumothorax occurs more commonly with secondary malignant disease of the lungs, particularly metastases from bone sarcomas, and this is nearly always seen in those younger than 40 years. At least 68 cases of pneumothorax with primary lung cancer have been reported, and a review of the literature discloses 86 cases with metastatic disease. I am surprised that the authors have seen only
GAB2 Alleles Modify Alzheimer's Risk in APOE ɛ4 Carriers
Authors: Eric M. Reiman, Jennifer A. Webster, Amanda J. Myers, John Hardy, Travis Dunckley, Victoria L. Zismann, Keta D. Joshipura, John V. Pearson, Diane Hu-Lince, Matthew J. Huentelman, David W. Craig, Keith D. Coon, Winnie S. Liang, RiLee H. Herbert, Thomas Beach, Kristen C. Rohrer, Alice S. Zhao, Doris Leung, Leslie Bryden, Lauren Marlowe, Mona Kaleem, Diego Mastroeni, Andrew Grover, Christopher B. Heward, Rivka Ravid, Joseph Rogers, Michael L. Hutton, Stacey Melquist, Ron C. Petersen, Gene E. Alexander, Richard J. Caselli, Walter Kukull, Andreas Papassotiropoulos, Dietrich A. Stephan
Journal: Neuron (2007)
An Unusual Case of Air Embolism Precipitated by Decompression
Authors: John J. Collins
Journal: New England Journal of Medicine (1962)

THE occurrence of air embolism during submarine escape training has been very infrequent. In 67,000 ascents from depth in the Escape Training Tank at New London during the past five years, only 7 cases have occurred. One of these, which terminated fatally, has previously been reported.1 The current technic for individual escape from a submerged submarine is called "buoyant-assisted, free ascent." The person escaping enters a special isolated compartment, which is then flooded from the sea to about chest level. With compressed air the pressure within the compartment is increased to equal the outside sea pressure. The escape hatch can . . .