tbuckley/cabot-search huggingface dataset:
ET-57 * TOPOISOMERASE II IN PRONEURAL GLIOMAS, A MODULATOR OF TRANSCRIPTION AND A THERAPEUTIC TARGET
Authors: A. M. Sonabend, A. S. Carminucci, B. Amendolara, M. Bansal, M. Praver, R. Realubit, H. Li, C. Karan, M. Banu, L. Lei, A. Califano, P. Canoll, J. Bruce
Journal: Neuro-Oncology (2014)

Topoisomerase II (TOP2) is highly expressed on proneural gliomas, but its specific function on these tumors is unknown. We found that TOP2 is expressed in gliomas from early stages, increases during progression, and is elevated in radiographically localized non-enhancing regions of human glioblastoma, an area that is challenging to target systemically, and a common source of recurrence. TOP2A is highly expressed by infiltrating tumor cells, in the tumor center and at the edges, and low on surrounding brain. TOP2 enzymatic activity was detected on proneural glioma cell lines. TOP2 poison etoposide and 3 TOP2 inhibitors showed significant cytotoxicity on a proneural glioma cells (IC50 0.3-4 mM). Moreover, intracranial etoposide convection-enhanced delivery (CED) (80 mM) was tolerated and led to a significant survival benefit in mouse proneural gliomas. In contrast, etoposide CED (4 mM) showed transient decrease in tumor growth but failed to prolong survival, consistent with ineffective tumoral concentrations in trials of systemic etoposide for recurrent gliomas. TOP2 transcriptional modulation on proneural gliomas was suggested as the activity of many key transcription factors correlates with TOP2 levels across glioblastoma patients. TOP2 pharmacological targeting is a promising treatment target for some gliomas. Refining patient selection and drug delivery is key for optimizing this therapy.
600 LONG-TERM COMMON BILE DUCT-LIGATION IN MICE INDUCES TUBULOINTERSTITIAL KIDNEY FIBROSIS AND CHRONIC RENAL FAILURE: ROLE OF BILE ACID NUCLEAR RECEPTOR FXR AND OSTEOPONTIN
Authors: P. Fickert, A. Thueringer, T. Moustafa, M. Yang, H. Jaeschke, R.G. Wells, G. Stokman, H. Denk, M. Trauner
Journal: Journal of Hepatology (2011)
Focal Asymmetric Longus Colli Uptake on FDG PET/CT
Authors: Eugene C. Lin
Journal: Clinical Nuclear Medicine (2006)

Muscular uptake on F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) examinations is commonly seen and the typical patterns are well described. Muscular uptake is usually easily differentiated from pathology by its symmetry and location or by fusion with CT. An uncommon pattern of uptake in which a focal asymmetric area of FDG uptake is seen in the longus colli muscles is described.
The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds
Authors: Alexander Hofmann, Ulrike Ritz, Sophie Verrier, David Eglin, Mauro Alini, Sabine Fuchs, C. James Kirkpatrick, Pol Maria Rommens
Journal: Biomaterials (2008)
Abstract 2628: BU32: A novel proteasome inhibitor for treatment of multiple myeloma and other types of cancer
Authors: SUDIPA SAHA ROY, NAMEER KIRMA, HAREESH NAIR, RAJESHWAR RAO TEKMAL, JOSEPH AGYIN
Journal: Cancer Research (2010)

Abstract Background: Multiple myeloma (MM) is an incurable neoplasm characterized by devastating and progressive bone destruction. Standard chemotherapeutic agents have not been effective at significantly prolonging the survival of MM patients and these agents are typically associated with often severe, dose-limiting side effects. Proteasome inhibition provides an attractive approach to cancer therapy and may have application in the treatment of MM and also other types of cancers. However, results of recent clinical trials to evaluate the effect of the proteasome inhibitor bortezomib (Velcade®, also called PS-341) in MM patients have shown limited activity when used as a single agent. This underscores the need to find new and more efficacious proteasome inhibitors for treatment of MM. We have recently synthesized a novel proteasome inhibitor BU-32 and tested its growth inhibitory effects in different MM cells including RPMI8226 (human) and 5TGM1 (mouse) and other types of cancer cells. Methods and Results: In this study, we evaluate the efficacy of the novel proteasome inhibitor BU-32 (NSC D750499) using in vitro and in vivo MM models. BU-32 exhibits strong cytotoxicity in a panel of MM cell lines - RPMI8226 and 5TGM1. Furthermore, proteasome inhibition assay reveals that BU-32 potently inhibits the chymotryptic- and caspase-like activities of the 26S proteasome. Results from our studies using real-time PCR array analyses show that BU-32 effectively down-regulates an array of angiogenesis and inflammatory markers. We show from Annexin V FITC binding studies that BU-32, like bortezomib, induces apoptosis in different MM cell lines but the effect is more prominent in case of BU-32 treated cells. Studies using an in vivo MM model show significant effect and marked reduction in osteolytic bone lesions in radiography with 0.3 mg/kg body weight dose of BU-32. Further testing of BU-32 on pancreatic cancer and various hormone regulated cancers like ovarian and prostate are currently under way. Preliminary cell viability studies on these cancer cell lines indicate BU-32 is highly effective against other cancer cells also. Annexin V FITC binding analyses show that BU-32 drug induces apoptosis to these cell lines. These studies elucidate that BU-32 is a most promising candidate drug for clinical trial as a novel treatment modality for MM and other types of cancer. Conclusion: Our results suggest that BU-32 might be a potential chemotherapeutic agent with promising antitumor activity for the treatment of MM and other types of cancer. 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 2628.
Three-Dimensional Magnetic Resonance Cardiac Imaging Shows Initial Promise
Authors: Timothy F. Kirn
Journal: JAMA (1988)

THREE-DIMENSIONAL magnetic resonance imaging (3-D MRI) of the heart is already receiving encouraging reviews from heart surgeons, says Michael Vannier, MD, an associate professor of radiology at Washington University School of Medicine, St Louis. In fact, the demand for his group's 3-D images is becoming overwhelming, Vannier says. Vannier says his group is the only one of which he is aware that is doing the 3-D MRI cardiac imaging. He credits its development to a cardiothoracic surgery fellow, John Laschinger, MD, who wondered if Washington's Mallinckrodt Institute of Radiology's 3-D imaging capabilities could be adapted to the heart. So far, the group has used 3-D MRI to evaluate congenital heart disease. The advantage of the 3-D system is that, even to an untrained eye, anomalies are apparent and the images can even be animated, Vannier says. Perhaps even more important, he says, is the fact that MRI is noninvasive.
Fluid Volume and Albumin Kinetics Occurring With Major Surgery
Authors: Robert C. Hoye
Journal: JAMA (1972)

Studies investigating fluid volume dynamics and albumin kinetics in patients undergoing major abdominal surgery indicate that during the operation, marked deficits develop in the total red blood cell volume, plasma volume, extracellular fluid volume, and the total exchangeable albumin pool. A disproportionate deficit in the plasma volume occurring in the course of the operation is believed to be secondary to a functional extracellular fluid volume deficit and abnormal losses of albumin from the intravascular compartment. Deficits in these compartments occurred during the operation in every patient studied. In some patients the plasma volume deficit immediately postoperatively amounted to close to 50% of the volume present when the patient went into the operating room. In the course of a regional node dissection in nine patients studied, a 29% deficit developed in the total body albumin pool.
Pfizer to disclose payments of $500 to healthcare prescribers
Authors: J. H. Tanne
Journal: BMJ (2009)

Pfizer, the world’s largest drug company, announced on 9 February that it would begin disclosing payments of $500 (£350; €390) or more a year to doctors and others who prescribe drugs.

The disclosures will include payments to practising US physicians, as well as principal investigators, major academic institutions, and research sites for clinical research, the company said. Pfizer said it would be the first biopharmaceutical company to disclose payments for conducting phase I-IV clinical trials as well as payments for …
Endosonographic Features of Brunner’s Gland Hamartomas Which Were Subsequently Resected Endoscopically
Authors: K. Hizawa, K. Iwai, M. Esaki, H. Suekane, S. Inuzuka, T. Matsumoto, T. Yao, M. Iida
Journal: Endoscopy (2002)

Background and Study Aims: Brunner's gland hamartomas are uncommon duodenal submucosal tumors. We aim to describe their morphological characteristics, with particular attention to the endosonographic features. Patients and Methods: We reviewed the radiological, endoscopic, endosonographic, and histological findings from six Brunner's gland hamartomas which were completely removed by endoscopic resection. Results: The lesions appeared as broad-based, sessile, or pedunculated submucosal tumors, measuring 0.7 to 2 cm in maximal diameter. Three lesions contained tiny dimple-like depressions on the surface; in one lesion these were only recognized following the use of an endoscopic dye-spraying technique. All the lesions could be safely removed by endoscopic resection after endosonographic confirmation of the layer origin within the submucosa. The internal echo structure of the tumors appeared to be solid echogenic in two, simple cystic in two, and multicystic in the remaining two lesions. In three lesions with an indistinct boundary, some stromal proliferation and solid Brunner's glands were recognized in an area extending from the mucosa to the submucosa. These endosonographic features corresponded to histological findings comprising stromal proliferation and various degrees of solid and cystic glandular Brunner's glands. Conclusions: Brunner's gland hamartoma is characterized endosonographically by a heterogeneous solid and/or cystic mass within the submucosa.
Spontaneous Subcapsular Splenic Hematoma as the Only Clinical Manifestation of Infectious Mononucleosis
Authors: Jayant M. Patel
Journal: JAMA (1982)

SPONTANEOUS rupture of the spleen due to infectious mononucleosis was first reported by King 1 in 1941. Of 107 reported cases of splenic rupture associated with infectious mononucleosis, only 18 are considered to be true spontaneous ruptures. 2 This is the report of a symptomatic, unruptured subcapsular hematoma in a patient with a high heterophil antibody titer and no other signs or symptoms. Two patients in a series of 500 consecutive cases of infectious mononucleosis probably had subcapsular splenic hematoma. 3   Report of a Case  A 20-year-old man was asymptomatic except for the sudden onset of left upper quadrant abdominal pain. When examined in the emergency room on April 25, 1979, his left upper abdomen was mildly tender, but there were no other pertinent findings except for a hematocrit reading of 38% and a hemoglobin level of 13.6 g/dL. Three days later, he was admitted because of persistent abdominal pain
Population genetic structure and ecotoxicology.
Authors: S I Guttman
Journal: Environmental Health Perspectives (1994)

Electrophoretic analyses of population genetic structure, both in the laboratory and in the field, have documented significant shifts in allozyme genotype frequencies in a variety of aquatic taxa as a result of environmental impacts. Studies are documented which indicate that contaminants may select for individuals with tolerant allozyme genotypes, causing the potential loss of individuals with sensitive genotypes. This may diminish the genetic variability and fitness of affected populations and make them more susceptible to extinction following a subsequent stress. Future research involving population genetic structure and ecotoxicology should focus on determining the mechanism of sensitivity, documenting multigenerational effects of chronic laboratory exposure on population genetic composition, investigating whether previously stressed and genetically impacted populations are more susceptible to further natural and/or anthropogenic stressors, and establishing the utility of population genetic structure as a sensitive monitor of impacts in aquatic systems and their subsequent remediation.
PD-1 and Tim-3 Regulate the Expansion of Tumor Antigen–Specific CD8+ T Cells Induced by Melanoma Vaccines
Authors: Julien Fourcade, Zhaojun Sun, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, Bratislav Janjic, Ahmad A. Tarhini, Hussein A. Tawbi, John M. Kirkwood, Stergios Moschos, Hong Wang, Philippe Guillaume, Immanuel F. Luescher, Arthur Krieg, Ana C. Anderson, Vijay K. Kuchroo, Hassane M. Zarour
Journal: Cancer Research (2013)

Although melanoma vaccines stimulate tumor antigen-specific CD8(+) T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. The vaccines included incomplete Freund's adjuvant, CpG oligodeoxynucleotide (CpG), and the HLA-A2-restricted analog peptide NY-ESO-1 157-165V, either by itself or in combination with the pan-DR epitope NY-ESO-1 119-143. Both vaccines stimulated rapid tumor antigen-specific CD8(+) T-cell responses detected ex vivo, however, tumor antigen-specific CD8(+) T cells produced more IFN-γ and exhibited higher lytic function upon immunization with MHC class I and class II epitopes. Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma.
Cost-Effectiveness of Ventricular Assist Device Therapy as a Bridge to Transplantation Compared With Nonbridged Cardiac Recipients
Authors: Ana C. Alba, Luis F. Alba, Diego H. Delgado, Vivek Rao, Heather J. Ross, Ron Goeree
Journal: Circulation (2013)

Background— Current available treatment options for advanced heart failure include heart transplantation and ventricular assist device (VAD) therapy. This project aimed to evaluate the cost-effectiveness of a bridge-to-transplantation (BTT)–VAD approach relative to direct heart transplantation in transplant-eligible patients. Methods and Results— A Markov model was used to evaluate survival benefits and costs for BTT-VAD versus nonbridged heart transplant recipients. Three different scenarios were considered according to severity of patients’ baseline hemodynamic status (high, medium, and low risk). Results are presented in terms of survival, costs, and cost-effectiveness ratio. Sensitivity analyses were used to analyze uncertainty in model estimates. Over a 20-year time horizon, BTT-VAD therapy increased survival at an increased cost relative to nonbridged heart transplant recipients: $100 841more in costs and 1.19 increased life years (LYs) in high-risk patients ($84 964/LY), $112 779 more in costs and 1.14 more LYs ($99 039/LY) in medium-risk patients, and an additional cost of $144 334 and incremental clinical benefit of 1.21 more LYs ($119 574/LY) in low-risk patients. The sensitivity analysis estimated a 59%, 54%, and 43% chance of BTT-VAD therapy being cost-effective for high-, medium-, and low-risk patients at a willingness-to-pay level of $100 000/LY. Subgroup analyses indicated that risk of post-VAD and transplantation complications, waiting time, renal dysfunction, and patient age substantially affected the cost-effectiveness ratio. Conclusions— BTT-VAD therapy is associated with improved survival and increased costs. On the basis of commonly accepted willingness-to-pay thresholds, BTT-VAD therapy is likely to be cost-effective relative to nonbridged heart transplantation in specific circumstances.
Payments are to rise sixfold for teams that deliver good diabetes care for children
Authors: Z. Kmietowicz
Journal: BMJ (2012)

Paediatric teams whose care of children and teenagers with diabetes meets 13 standards set out by the NHS in England will qualify for extra funding under a new agreement. Teams that are unable to achieve the standards by April 2013 risk having their funding withdrawn.

The best practice tariff for paediatric diabetes has been developed by leading paediatric doctors, nurses, and commissioners together with NHS Diabetes, a national organisation working to improve the quality of care for people with diabetes. It spells out 13 standards that paediatric teams need to provide to qualify for annual payments of £3189 (€3825; $5100) for each patient aged 18 years or under. Under the current Payment …
Poverty and teenage pregnancy.
Authors: B Blondel, M Kaminski, M J Saurel-Cubizolles
Journal: BMJ (1987)

With regard to the comments of Dr R Ahmad and coworkers (7 February, p 372) it is interesting that their patients undergoing carpal tunnel release did not have arthropathy affecting large joints.This suggests that the carpal tunnel syndrome, though often seen in association with the arthro- pathy that affects large joints, may have a different pathogenesis.It is therefore perhaps not surprising that synovial iron deposits were rare in their patients.Amyloid deposits may be a factor in the carpal tunnel syndromes, and some patients with amyloidosis associated with plasma cell dyscrasias are known to develop this complication.
Enhanced glomerular Toll-like receptor 4 expression and signaling in patients with type 2 diabetic nephropathy and microalbuminuria
Authors: Daniela Verzola, Laura Cappuccino, Elena D'Amato, Barbara Villaggio, Fabio Gianiorio, Mariano Mij, Alchiede Simonato, Francesca Viazzi, Gennaro Salvidio, Giacomo Garibotto
Journal: Kidney International (2014)
The effect of tobacco smoking and alcohol consumption on the prevalence of self-reported hand eczema: a cross-sectional population-based study
Authors: J.P. Thyssen, A. Linneberg, T. Menné, N.H. Nielsen, J.D. Johansen
Journal: British Journal of Dermatology (2009)

Summary Background Hand eczema is a prevalent disorder that leads to high health care costs as well as a decreased quality of life. Important risk factors include atopic dermatitis, contact allergy and wet work whereas the role of null mutations in the filaggrin gene complex remains to be clarified. It has been debated whether life-style factors such as tobacco smoking and alcohol consumption are associated with hand eczema. Objectives The current study aimed to investigate whether self-reported hand eczema was associated with smoking and alcohol consumption in the general population. Methods Between June 2006 and May 2008, a cross-sectional study was performed in the general population in Copenhagen, the capital of Denmark. A random sample of 7931 subjects aged 18–69 years old was invited to participate in a general health examination including a questionnaire; 3471 (44%) participated. Data were analysed with logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CI). Results The prevalence of hand eczema was higher among previous smokers (OR = 1·13; CI = 0·90–1·40), current light smokers (OR = 1·51; CI = 1·14–2·02) and current heavy smokers (OR = 1·38; CI = 0·99–1·92) compared with never-smokers. Conclusions Tobacco smoking was positively associated with hand eczema among adults from the general population in Denmark. Apparently, current light smokers (< 15 g daily) had a higher prevalence of hand eczema than current heavy smokers (> 15 g daily) but this needs to be reconfirmed. Alcohol consumption was not associated with hand eczema.
Poet's Corner
Authors: Sherman Silber
Journal: JAMA (1975)

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