tbuckley/cabot-search huggingface dataset:
Efficacy of Methylprednisolone in Acute Spinal Cord Injury
Authors: Michael B. Bracken, William F. Collins, Daniel F. Freeman, Mary Jo Shepard, Franklin W. Wagner, Robert M. Silten, Karen G. Hellenbrand, Joseph Ransohoff, William E. Hunt, Phaner L. Perot, Robert G. Grossman, Barth A. Green, Howard M. Eisenberg, Nathan Rifkinson, Joseph H. Goodman, John N. Meagher, Boguslav Fischer, Guy L. Clifton, Eugene S. Flamm, Stephen E. Rawe
Journal: JAMA (1984)

A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment. Although not statistically significant, early case fatality was greater in the high-dose protocol (relative risk of 3.1 and 1.9, less than or equal to 14 and 15 to 28 days after injury, respectively) but not from 29 to 210 days after injury. Wound infections of both trauma and operative sites were more prevalent in the high-dose regimen (relative risk of 3.6).
Accumulation of 2-hydroxyglutarate is not a biomarker for malignant progression in IDH-mutated low-grade gliomas
Authors: Tareq A. Juratli, Mirko Peitzsch, Kathrin Geiger, Gabriele Schackert, Graeme Eisenhofer, Dietmar Krex
Journal: Neuro-Oncology (2013)

To determine whether accumulation of 2-hydroxyglutarate in IDH-mutated low-grade gliomas (LGG; WHO grade II) correlates with their malignant transformation and to evaluate changes in metabolite levels during malignant progression. Samples from 54 patients were screened for IDH mutations: 17 patients with LGG without malignant transformation, 18 patients with both LGG and their consecutive secondary glioblastomas (sGBM; n = 36), 2 additional patients with sGBM, 10 patients with primary glioblastomas (pGBM), and 7 patients without gliomas. The cellular tricarboxylic acid cycle metabolites, citrate, isocitrate, 2-hydroxyglutarate, α-ketoglutarate, fumarate, and succinate were profiled by liquid chromatography–tandem mass spectrometry. Ratios of 2-hydroxyglutarate/isocitrate were used to evaluate differences in 2-hydroxyglutarate accumulation in tumors from LGG and sGBM groups, compared with pGBM and nonglioma groups. IDH1 mutations were detected in 27 (77.1%) of 37 patients with LGG. In addition, in patients with LGG with malignant progression (n = 18), 17 patients were IDH1 mutated with a stable mutation status during their malignant progression. None of the patients with pGBM or nonglioma tumors had an IDH mutation. Increased 2-hydroxyglutarate/isocitrate ratios were seen in patients with IDH1-mutated LGG and sGBM, in comparison with those with IDH1-nonmutated LGG, pGBM, and nonglioma groups. However, no differences in intratumoral 2-hydroxyglutarate/isocitrate ratios were found between patients with LGG with and without malignant transformation. Furthermore, in patients with paired samples of LGG and their consecutive sGBM, the 2-hydroxyglutarate/isocitrate ratios did not differ between both tumor stages. Although intratumoral 2-hydroxyglutarate accumulation provides a marker for the presence of IDH mutations, the metabolite is not a useful biomarker for identifying malignant transformation or evaluating malignant progression.
Oral Iron Chelators
Authors: Maria Domenica Cappellini, Paolo Pattoneri
Journal: Annual Review of Medicine (2009)

Deferoxamine (DFO) was the standard of care for transfusional iron overload for &gt;40 years, requiring subcutaneous infusion for 8–12 h/day, 5–7 days/week. Oral iron chelators are an important development, offering the potential to improve compliance and patients’ quality of life. The oral, three-times-daily agent deferiprone appeared to be a promising advance; however, its use has been limited owing to serious adverse events, such as neutropenia and agranulocytosis. Therapy combining deferiprone with DFO has proved effective in the management of severe cardiac siderosis. Deferasirox is a novel, orally active agent that provides 24-h chelation with a once-daily dose. An extensive clinical trial program has demonstrated that deferasirox at appropriate doses is effective in reducing or maintaining iron burden in adult and pediatric patients. The clinical program demonstrated that deferasirox has a safety profile that is clinically manageable with regular monitoring.
In vitro and in vivo priming of T cells using dendritic cells loaded with internal cell localization signals fused cancer testis antigens
Authors: Slavoljub Milosevic
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Cancer represents a unique cell deregulation disease in patients, therefore it has become clear in recent years that successful treatment will depend on personalized cancer therapy. The immune response against cancer is activated when antigen presenting cells (APC) pick up tumor
Radioisotope scanning using a gamma camera.
Authors: H Berry, J J Barrett, A Ford-Hutchinson, E B Hamilton
Journal: Annals of the Rheumatic Diseases (1978)

Sixteen outpatients with rheumatoid arthritis took part in a placebo controlled double-blind crossover study. In addition to conventional measurements, a radioactive index was measured using a gamma camera that indicated a radioactive count over the measured joints and a comparable area of normal adjacent bone. This index showed poor correlation with other conventional measurements of change in the clinical trial.
Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage
Authors: Yeon Seok Seo, Soo Young Park, Moon Young Kim, Ju Hyun Kim, Jun Yong Park, Hyung Joon Yim, Byoung Kuk Jang, Hong Soo Kim, Taeho Hahn, Byung Ik Kim, Jeong Heo, Hyonggin An, Won Young Tak, Soon Koo Baik, Kwang Hyub Han, Jae Seok Hwang, Sang Hoon Park, Mong Cho, Soon Ho Um
Journal: Hepatology (2014)

Vasoactive drugs are recommended to be started as soon as possible in suspected variceal bleeding, even before diagnostic endoscopy. However, it is still unclear whether the therapeutic efficacies of the various vasoactive drugs used are comparable. The aim of this prospective, multicenter, randomized, noninferiority trial was to characterize the effects of terlipressin, somatostatin, and octreotide when they are initiated before endoscopic treatment in patients with acute variceal bleeding. Patients with liver cirrhosis and significant upper gastrointestinal bleeding were randomly assigned to receive early administration of terlipressin, somatostatin, or octreotide, followed by endoscopic treatment. Patients with nonvariceal bleeding were excluded after endoscopy. The primary endpoint was 5-day treatment success, defined as control of bleeding without rescue treatment, rebleeding, or mortality, with a noninferiority margin of 0.1. In total, 780 patients with variceal bleeding were enrolled: 261 in the terlipressin group; 259 in the somatostatin group; and 260 in the octreotide group. At the time of initial endoscopy, active bleeding was noted in 43.7%, 44.4%, and 43.5% of these patients, respectively ( P = 0.748), and treatment success was achieved by day 5 in 86.2%, 83.4%, and 83.8% ( P = 0.636), with similar rates of control of bleeding without rescue treatment (89.7%, 87.6%, and 88.1%; P = 0.752), rebleeding (3.4%, 4.8%, and 4.4%; P = 0.739), or mortality (8.0%, 8.9%, and 8.8%; P = 0.929). The absolute values of the lower bound of confidence intervals for terlipressin versus somatostatin, terlilpressin versus octreotide, and octreotide versus somatostatin were 0.095, 0.090, and 0.065, respectively. Conclusion : Hemostatic effects and safety did not differ significantly between terlipressin, somatostatin, and octreotide as adjuvants to endoscopic treatment in patients with acute gastroesophageal variceal bleeding. (Hepatology 2014;60:954–963)
Unique Localization of Circulating Tumor Cells in Patients With Hepatic Metastases
Authors: Long R. Jiao, Christos Apostolopoulos, Jimmy Jacob, Richard Szydlo, Natalia Johnson, Nicole Tsim, Nagy A. Habib, R. Charles Coombes, Justin Stebbing
Journal: Journal of Clinical Oncology (2009)

There are few data on the impact of immediate and differing surgical interventions on circulating tumor cells (CTCs), nor their compartmentalization or localization in different anatomic vascular sites.CTCs from consecutive patients with colorectal liver metastases were quantified before and immediately after open surgery, laparoscopic resection, open radiofrequency ablation (RFA), or percutaneous RFA. For individuals undergoing open surgery, either hepatic resections or open RFA, CTCs were examined in both systemic and portal circulation by measuring CTCs in samples derived from the peripheral vein, an artery, the hepatic portal vein, and the hepatic vein.A total of 29 consecutive patients with colorectal liver metastases with a median age of 55 years (range, 30 to 88 years) were included. CTCs were localized to the hepatic portosystemic macrocirculation with significantly greater numbers than in the systemic vasculature. Surgical procedures led to a statistically significant fall in CTCs at multiple sites measured. Conversely, RFA, either open or percutaneous, was associated with a significant increase in CTCs.Surgical resection of metastases, but not RFA, immediately decreases CTC levels. In patients with colorectal liver metastases, CTCs appear localized to the hepatic (and pulmonary) macrocirculations. This may explain why metastases in sites other than the liver and lungs are infrequently observed in cancer.
Agalsidase Benefits Renal Histology in Young Patients with Fabry Disease
Authors: Camilla Tøndel, Leif Bostad, Kristin Kampevold Larsen, Asle Hirth, Bjørn Egil Vikse, Gunnar Houge, Einar Svarstad
Journal: Journal of the American Society of Nephrology (2012)

The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7–33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.
The modulation of angiogenesis in the foreign body response by the poxviral protein M-T7
Authors: Jasper M. Boomker, Daniël T. Luttikhuizen, Henrike Veninga, Lou F.M.H. de Leij, T. Hauw The, Aalzen de Haan, Marja J.A. van Luyn, Martin C. Harmsen
Journal: Biomaterials (2005)
Sp1/NFκB/HDAC/miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia
Authors: Shujun Liu, Lai Chu Wu, Jiuxia Pang, Ramasamy Santhanam, Sebastian Schwind, Yue Zhong Wu, Christopher J. Hickey, Jianhua Yu, Heiko Becker, Kati Maharry, Michael D. Radmacher, Chenglong Li, Susan P. Whitman, Anjali Mishra, Nicole Stauffer, Anna M. Eiring, Roger Briesewitz, Robert A. Baiocchi, Kenneth K. Chan, Peter Paschka, Michael A. Caligiuri, John C. Byrd, Carlo M. Croce, Clara D. Bloomfield, Danilo Perrotti, Ramiro Garzon, Guido Marcucci
Journal: Cancer Cell (2010)
Bortezomib Inhibits PKR-Like Endoplasmic Reticulum (ER) Kinase and Induces Apoptosis via ER Stress in Human Pancreatic Cancer Cells
Authors: Steffan T. Nawrocki, Jennifer S. Carew, Kenneth Dunner, Lawrence H. Boise, Paul J. Chiao, Peng Huang, James L. Abbruzzese, David J. McConkey
Journal: Cancer Research (2005)

Abstract Bortezomib (Velcade, formerly known as PS-341) is a boronic acid dipeptide derivative that is a selective and potent inhibitor of the proteasome. We hypothesized that proteasome inhibition would lead to an accumulation of misfolded proteins in the cell resulting in endoplasmic reticulum (ER) stress. The ability of bortezomib to induce ER stress and the unfolded protein response was investigated in a human pancreatic cancer cell line, L3.6pl. Bortezomib increased expression of ER stress markers, CHOP and BiP, but inhibited PKR-like ER kinase and subsequent phosphorylation of eukaryotic initiation factor 2α (eif2α), both of which are key events in translational suppression. These effects resulted in an accumulation of ubiquitylated proteins leading to protein aggregation and proteotoxicity. Peptide inhibitor or small interfering RNA targeting ER-resident caspase-4 blocked DNA fragmentation, establishing a central role for caspase-4 in bortezomib-induced cell death. The translation inhibitor cycloheximide abrogated bortezomib-induced protein aggregation, caspase-4 processing, and all other characteristics of apoptosis. Because malignant cells have higher protein synthesis rates than normal cells, they may be more prone to protein aggregation and proteotoxicity and possess increased sensitivity to bortezomib-induced apoptosis. Taken together, the results show that bortezomib induces a unique type of ER stress compared with other ER stress agents characterized by an absence of eif2α phosphorylation, ubiquitylated protein accumulation, and proteotoxicity. (Cancer Res 2005; 65(24): 11510-9)
Recent Duplication of the Common Carp (Cyprinus carpio L.) Genome as Revealed by Analyses of Microsatellite Loci
Authors: L. David
Journal: Molecular Biology and Evolution (2003)

Genome duplications may have played a role in the early stages of vertebrate evolution, near the time of divergence of the lamprey lineage. Additional genome duplication, specifically in ray-finned fish, may have occurred before the divergence of the teleosts. The common carp (Cyprinus carpio) has been considered tetraploid because of its chromosome number (2n = 100) and its high DNA content. We studied variation using 59 microsatellite primer pairs to better understand the ploidy level of the common carp. Based on the number of PCR amplicons per individual, about 60% of these primer pairs are estimated to amplify duplicates. Segregation patterns in families suggested a partially duplicated genome structure and disomic inheritance. This could suggest that the common carp is tetraploid and that polyploidy occurred by hybridization (allotetraploidy). From sequences of microsatellite flanking regions, we estimated the difference per base between pairs of alleles and between pairs of paralogs. The distribution of differences between paralogs had two distinct modes suggesting one whole-genome duplication and a more recent wave of segmental duplications. The genome duplication was estimated to have occurred about 12 MYA, with the segmental duplications occurring between 2.3 and 6.8 MYA. At 12 MYA, this would be one of the most recent genome duplications among vertebrates. Phylogenetic analysis of several cyprinid species suggests an evolutionary model for this tetraploidization, with a role for polyploidization in speciation and diversification.
The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells
Authors: Britta Maecker, David H. Sherr, Robert H. Vonderheide, Michael S. von Bergwelt-Baildon, Naoto Hirano, Karen S. Anderson, Zhinan Xia, Marcus O. Butler, Kai W. Wucherpfennig, Carl O'Hara, Geoffrey Cole, Silvia S. Kwak, Urban Ramstedt, Andy J. Tomlinson, Roman M. Chicz, Lee M. Nadler, Joachim L. Schultze
Journal: Blood (2003)
Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity
Authors: Ton Lisman, Tamara N. Bongers, Jelle Adelmeijer, Harry L.A. Janssen, Moniek P.M. de Maat, Philip G. de Groot, Frank W.G. Leebeek
Journal: Hepatology (2006)

Cirrhosis of the liver is frequently accompanied by complex alterations in the hemostatic system, resulting in a bleeding tendency. Although many hemostatic changes in liver disease promote bleeding, compensatory mechanisms also are found, including high levels of the platelet adhesive protein von Willebrand Factor (VWF). However, conflicting reports on the functional properties of VWF in cirrhosis have appeared in literature. We have measured a panel of VWF parameters in plasma from patients with cirrhosis of varying severity and causes. Furthermore, we assessed the contribution of VWF to platelet adhesion, by measuring the ability of plasma from patients with cirrhosis to support adhesion of normal or patient platelets under flow conditions. VWF antigen levels were strongly increased in patients with cirrhosis. In contrast, the relative collagen binding activity, as well as the relative ristocetin cofactor activity, was significantly lower in patients as compared with controls, indicating loss of function. Accordingly, patients had a reduced fraction of high-molecular-weight VWF multimers. Both strongly elevated and reduced activity and antigen levels of the VWF cleaving protease ADAMTS13 were found in individual patients. Adhesion of either normal or patient platelets to a collagen surface was substantially increased when these platelets were resuspended in plasma of patients with cirrhosis, as compared with control plasma. In conclusion , highly elevated levels of VWF in patients with cirrhosis contribute to the induction of primary hemostasis despite reduced functional properties of the molecule. This phenomenon might compensate for defects in platelet number and function in patients with cirrhosis.
XELOX (Capecitabine Plus Oxaliplatin): Active First-Line Therapy for Patients With Metastatic Colorectal Cancer
Authors: Jim Cassidy, Josep Tabernero, Chris Twelves, René Brunet, Charles Butts, Thierry Conroy, Filippo Debraud, Arie Figer, Johannes Grossmann, Noriaki Sawada, Patrick Schöffski, Alberto Sobrero, Eric Van Cutsem, Eduardo Díaz-Rubio
Journal: Journal of Clinical Oncology (2004)

Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (MCRC). Oxaliplatin shows synergy with fluorouracil (FU), with little toxicity overlap. The XELOX regimen (capecitabine plus oxaliplatin), established in a previous dose-finding study, should improve on infused oxaliplatin with FU and leucovorin (FOLFOX) regimens. The present studies further characterize efficacy and safety of the XELOX regimen.The antitumor activity of XELOX was investigated in a colon cancer xenograft model. Patients with MCRC received first-line XELOX in 3-week treatment cycles: intravenous oxaliplatin 130 mg/m(2) (day 1) followed by oral capecitabine 1,000 mg/m(2) twice daily (day 1, evening, to day 15, morning).A preclinical study confirmed that capecitabine has supra-additive activity with oxaliplatin. In the clinical study, 53 of 96 patients (55%) achieved an objective response, and 30 (31%) experienced disease stabilization for >/= 3 months following treatment. After 24 months' minimum follow-up, median time to disease progression (TTP) and median overall survival were 7.7 and 19.5 months, respectively. XELOX safety was predictable and similar to the FOLFOX4 regimen, except that myelosuppression was uncommon with XELOX (grade 3 or 4 neutropenia, 7%). Most adverse events were mild to moderate, the most common being acute sensory neuropathy (85%). Sixty-day, all-cause mortality was 2%.XELOX is a highly effective first-line treatment for MCRC. Response rates, TTP, and overall survival are similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX provides a more convenient regimen, likely to be preferred by both patients and healthcare providers. Capecitabine has the potential to replace FU/LV in combination with oxaliplatin for MCRC.
Associative learning without reason or belief
Authors: James D. Miles, Robert W. Proctor, E. J. Capaldi
Journal: Behavioral and Brain Sciences (2009)

Abstract We discuss the necessity of conscious thinking in the single-system propositional model of learning. Research from honeybees to humans suggests that associative learning can take place without the need for controlled reasoning or the development of beliefs of relationships between objects or events. We conclude that a single learning system is possible, but not if it depends on complex thinking.
Identification and quantification of histochemical border zones during the evolution of myocardial infarction in the rat
Authors: M. C FISHBEIN, C. A HARE, S. A GISSEN, J. SPADARO, D. MACLEAN, P. R MAROKO
Journal: Cardiovascular Research (1980)

Journal Article Identification and quantification of histochemical border zones during the evolution of myocardial infarction in the rat Get access MICHAEL C FISHBEIN, MICHAEL C FISHBEIN * From the departments of Pathology and Medicine, Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Massachusetts 02115, and the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California 90048 *Address for reprints: Michael C Fishbein, MD, Department of Pathology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard Los Angeles, California 90048, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar CAROL A HARE, CAROL A HARE From the departments of Pathology and Medicine, Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Massachusetts 02115, and the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California 90048 Search for other works by this author on: Oxford Academic PubMed Google Scholar SALLY A GISSEN, SALLY A GISSEN From the departments of Pathology and Medicine, Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Massachusetts 02115, and the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California 90048 Search for other works by this author on: Oxford Academic PubMed Google Scholar JOEL SPADARO, JOEL SPADARO From the departments of Pathology and Medicine, Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Massachusetts 02115, and the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California 90048 Search for other works by this author on: Oxford Academic PubMed Google Scholar DEREK MACLEAN, DEREK MACLEAN From the departments of Pathology and Medicine, Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Massachusetts 02115, and the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California 90048 Search for other works by this author on: Oxford Academic PubMed Google Scholar PETER R MAROKO PETER R MAROKO From the departments of Pathology and Medicine, Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Massachusetts 02115, and the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California 90048 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 14, Issue 1, January 1980, Pages 41–49, https://doi.org/10.1093/cvr/14.1.41 Published: 01 January 1980
Bifurcated Dendritic Cell Differentiation In Vitro From Murine Lineage Phenotype-Negative c-kit+ Bone Marrow Hematopoietic Progenitor Cells
Authors: Yi Zhang, Akihisa Harada, Jian-bin Wang, Yan-yun Zhang, Shin-ichi Hashimoto, Makoto Naito, Kouji Matsushima
Journal: Blood (1998)