tbuckley/cabot-search huggingface dataset:
RTRB-06TIME BETWEEN DIAGNOSTIC MRI AND FRAME-FIXED STEREOTACTIC RADIOSURGERY PLANNING MRI IS ASSOCIATED WITH BRAIN METASTASIS GROWTH BUT NOT WORSE LOCAL CONTROL
Authors: Michael Garcia, Sai Duriseti, Shannon Fogh, Jean Nakamura, David Larson, Philip Theodosopoulos, Michael McDermott, Penny Sneed, Steve Braunstein
Journal: Neuro-Oncology (2015)

RTRB-06. TIME BETWEEN DIAGNOSTIC MRI AND FRAME-FIXED STEREOTACTIC RADIOSURGERY PLANNING MRI IS ASSOCIATED WITH BRAIN METASTASIS GROWTH BUT NOT WORSE LOCAL CONTROL Michael Garcia, Sai Duriseti, Shannon Fogh, Jean Nakamura, David Larson, Philip Theodosopoulos, Michael McDermott, Penny Sneed, and Steve Braunstein; University of California, San Francisco, San Francisco, CA, USA BACKGROUND: Frame-fixed stereotactic radiosurgery (FFSRS) and frameless SRS precisely target brain metastases (BM). Seymour et al. recently showed patients treated with frameless SRS planned on MRI completed ≥ 14 days before treatment delivery have worse local control. An advantage of FFSRS is acquisition of planning MRI on day of SRS. We sought to describe BM growth (BMG) before SRS by comparing the preceding diagnostic MRI (dMRI) and FFSRS MRI scans. METHODS: Patients treated with FFSRS for BM at our institution from 2010 through 2013 were retrospectively reviewed. We identified 256 patients (1302 BM) without upfront surgical resection who had a dMRI for comparison of BM size on FFSRS MRI. Post-FFSRS local failure free progression (LFFP) and overall survival (OS) were compared by log-rank tests. RESULTS: Median imaging follow up was 10 months. Mean size [95%CI] of largest BM was 1.4cm [1.2-1.5]. BMG was observed on FFSRS MRI compared to dMRI for 30% patients. Mean time interval between dMRI and FFSRS was 25 days, and time interval was associated with BMG (Pearson’s r 1⁄4 0.14, p 1⁄4 0.02). The frequencies of BMG for time intervals between dMRI and FFSRS of ,7, 7-13, 14-20, 21-27, and ≥ 28 days were 11%, 12%, 32%, 36% and 38% respectively (p 1⁄4 0.02, chi square). Melanoma patients more commonly had BMG (p 1⁄4 0.03), but chemotherapy, neurologic symptoms, and dMRI slice thickness were not associated with BMG. Patients with BMG at FFSRS had similar LFFP compared to patients without growth (82% versus 88% at 6 months, p 1⁄4 0.71), and OS did notdiffer (p 1⁄4 0.47). CONCLUSION: Timebetween diagnosticMRI and SRS is associated with BMG, but LFFP is not compromised when patients receive FFSRS. Over a third of patients have clear BMG at SRS delivered 14 days afterdMRI.For framelessSRS, BMGafterplanningMRI may lead tomarginal miss. Neuro-Oncology 17:v195–v200, 2015. doi:10.1093/neuonc/nov231.6 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
Methods for inferring phylogenies from nucleic acid sequence data by using maximum likelihood and linear invariants.
Authors: W C Navidi, G A Churchill, A von Haeseler
Journal: Molecular Biology and Evolution (1991)

Likelihood methods and methods using invariants are procedures for inferring the evolutionary relationships among species through statistical analysis of nucleic acid sequences. A likelihood-ratio test may be used to determine the feasibility of any tree for which the maximum likelihood can be computed. The method of linear invariants described by Cavender, which includes Lake's method of evolutionary parsimony as a special case, is essentially a form of the likelihood-ratio method. In the case of a small number of species (four or five), these methods may be used to find a confidence set for the correct tree. An exact version of Lake's asymptotic chi 2 test has been mentioned by Holmquist et al. Under very general assumptions, a one-sided exact test is appropriate, which greatly increases power.
Linezolid penetrates in human pleural cavity: A pilot study using ultra-high pressure liquid chromatography in tandem with mass spectrometry (UPLC-MS/MS)
Authors: Dimosthenis Lykouras, Maria-Eleni Androutsou, Kiriakos Karkoulias, Olga Lagiou, Apostolos Voulgaridis, Maria Tsiamita, Panos Kitrou, Theodore Tselios, Christodoulos Flordellis, John Matsoukas, George Panayiotakopoulos, Kostas Spiropoulos
Journal: European Respiratory Journal (2014)

Introduction: Antibiotics that are used for pneumonia and pleural effusions must have a good bioavailability both in serum and pleural fluid. It is known that linezolid can enter the pleural cavity of rabbits. However, its penetration has never been documented in human pleural cavity. The aim of this study was to develop a new analytical method for the measurement of linezolid in human serum and pleural fluid so as to evaluate the penetration of linezolid in human pleura.  Materials and Methods: We developed a novel analytical method to measure linezolid in human serum and pleural fluid using Ultra Performance Liquid Chromatography (UPLC) in tandem with Mass Spectometry (MS/MS). We collected blood samples and the whole pleural fluid that was drained out of the pleural cavity of one patient that was treated with linezolid at usual doses for pneumonia with a pleural effusion. Precipitation of proteins both in serum and pleural fluid was performed using cold AcN. The samples were then analyzed in UPLC-MS/MS.  Results: The method was used to measure linezolid levels in pleural fluid of one patient with pneumonia and pleural effusion. The resulting chromatograms showed penetration of linezolid in pleural fluid, while having usual concentrations in human serum.  Conclusions: Our new chromatographic method was used for the measurement of linezolid levels in serum and pleural fluid that was collected from one patient, in order to evaluate its efficacy in pleural effusions. To the best of our knowledge, this study clearly shows for the first time that linezolid enters in human pleural cavity and reaches therapeutic concentrations.
Sulphonamide Sensitivity of H. Influenzae Strains
Authors: K. Zinnemann
Journal: BMJ (1950)

It is now a commonly acknowledged therapeutic principle, as soon as treatment is begun, to use maximal doses of sulphonamides and of antibiotics to avoid, so far as is possible, the development of drug resistance in the infecting micro-organism.Nevertheless, the incidence of resistant strains has of late been commented upon and reported more frequently.Haemophilus influenzae (Pfeiffer's bacillus) is sensitive to a comparatively wide range of sulphonamides and antibiotics, but it is also capable of developing strains resistant to the action of some of these drugs.It is therefore a suitable bacterium for the study of the anti- bacterial action of these preparations, and any theoretical and practical considerations arising from the study of its behaviour and of infections caused by it may be applicable to other pathogenic micro-organisms with a similar range of sensitivity.Effects of Combination of Antibacterial Drugs When two antibacterial drugs, each attacking bacterial populations in a different way, are allowed to act on the same bacterial culture the observed increase in the degree of sensitivity is exponential-that is, the effect of two or even more drugs is considerably greater than could be expected from the added values of the effects of each drug separately (Ungar, 1943 ; Thomas and Hayes, 1947; Mayr-Harting and Katscher, personal communication).This synergistic action is also well marked in strains resistant to penicillin when this antibiotic is combined with one of the sulphonamides (Chain and Duthie, 1945).Another principle involved, along with its bearing on clinical considerations with regard to the development of drug-resistant strains, has been stated very lucidly by Demerec (1948) as follows: "Theoretically, the most effective way of preventing the origin of resistant strains of bacteria is the use in clinical treatment of a mxture of two antibiotics, when such are available, that affect the same pathogen but are independent in their actions.The evidence of independence is that bacterial strains that have developed resistance to one antibiotic are still sensitive to the other, and vice versa.If such a mixture of two antibiotics is used, then only bacteria that are resistant to both can survive the treatment and form . . .resistant strains.Such bacteria would be exceedingly rare."It might be added that they would be rarer still if a third antibacterial drug with similar potency and mutation rate were employed.Corresponding in vivo and Clinical Observations American authors have produced in vivo experimental evidence showing that combination of the more effective sulphonamides with type-specific rabbit antiserum results not merely in an additive but in a synergistic effect (Pittman, 1942; Alexander and Leidy, 1943).TABLE I.-Clinical Results with Treatment of Various Combinations of Sulphonamides, Antiserum, and Antibiotics by Different
Comparison Between Murine Natural Antibodies and Natural Killer Cells: Recognition of Separate Target Structures as Revealed by Differential In Vitro Expression and Dependence on Glycosylation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A Grönberg, E Eriksson, F Sinangil, M Rönnholm, T Feizi, P Minden, R Kiessling
Journal: JNCI Journal of the National Cancer Institute (1985)

The specificity of complement-fixing, cytotoxic antibodies against the YAC lymphoma in sera of normal young adult (A X C57BL)F1 mice was studied. In vivo-maintained, immunoselected sublines of the YAC lymphoma expressed low amounts of the natural antibody (NAb) target structure. These cell lines were also resistant to natural killer (NK) cell-mediated lysis. After 2-3 weeks of in vitro culture the immunoselected cell lines became NK sensitive, but they remained resistant to NAb. When several independently derived variants selected for low NK sensitivity were tested for their ability to absorb NAb, the degree of absorption varied considerably among the variants. NAb could be inhibited by purified C-type virus particles and also by bacterial sonicates and various glycoprotein preparations. Treatment of target cells with tunicamycin, an inhibitor of asparagine-linked glycosylation, decreased the sensitivity to NAb lysis but had no impact on NK sensitivity. Thus the results indicated that a) NAb and NK cells recognized separate target structures and b) the target structure(s) for NAb but not for NK cells were saccharides of the N-glycosidic type.
Lack of political diversity and the framing of findings in personality and clinical psychology
Authors: Scott O Lilienfeld
Journal: Behavioral and Brain Sciences (2015)

Abstract I extend the arguments of Duarte et al. by examining the implications of political uniformity for the framing of findings in personality and clinical psychology. I argue that the one-sided framing of psychological research on political ideology has limited our understanding of the personality correlates of liberalism and conservatism.
Studies of esterase 6 in Drosophila melanogaster. XVIII. Biochemical differences between the slow and fast allozymes.
Authors: M M White, S D Mane, R C Richmond
Journal: Molecular Biology and Evolution (1988)

Most natural populations of Drosophila melanogaster are polymorphic for two major electrophoretic variants at the esterase-6 locus. The frequency of the EST 6F allozyme is greatest in populations in warmer latitudes, whereas the EST 6S allozyme is predominant in colder latitudes. Latitudinal clines in electromorph frequencies are found on three continents. Purified preparations of the allozymes have been characterized for their pH optimum, substrate specificity, organophosphate inhibition, alcohol activation, thermal stability, and kinetic parameters. These and previous analyses of the EST 6 allozymes reveal that the two variants have differences in their physical and kinetic properties that may provide a basis for the selective maintenance of the polymorphisms and an explanation of the clinal variation observed in natural populations.
Abstract 15193: Libman-Sacks Endocarditis and Cerebrovascular Disease: Role of Microparticles
Authors: Leonardo Macias, Alex Schevchuck, Paola C Roldan, Wayne L Chandler, Morayma Reyes, Clifford R Qualls, Wilmer L Sibbitt, Julia Middendorf, Carlos A Roldan
Journal: Circulation (2013)

Background: Libman-Sacks endocarditis and cerebrovascular disease (CVD) manifested as stroke/TIA or focal brain lesions on MRI are common, highly interrelated, and associated with significant morbi...
Phase II Trial of Docetaxel and Vinorelbine in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Vincent A. Miller, Lee M. Krug, Kenneth K. Ng, Barbara Pizzo, Wendy Perez, Robert T. Heelan, Mark G. Kris
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Docetaxel and vinorelbine are active agents in advanced non–small-cell lung cancer (NSCLC) and demonstrate preclinical synergism perhaps, in part, through their inactivation of the proto-oncogene bcl-2. We show that docetaxel (60 mg/m 2 ) and vinorelbine (45 mg/m 2 ) can be safely combined when given on an every 2-week schedule with filgrastim, with encouraging antitumor activity observed. PATIENTS AND METHODS: Thirty-five chemotherapy naïve patients with advanced NSCLC received vinorelbine as an intravenous push immediately followed by docetaxel as a 1-hour intravenous infusion once every 2 weeks. Prophylactic corticosteroids, ciprofloxacin, and filgrastim were used. RESULTS: We delivered median doses of 450 mg/m 2 of vinorelbine and 600 mg/m 2 of docetaxel. The major objective response rate was 51% (95% confidence interval [CI], 34% to 68%). With a median follow-up of 14 months, the predicted median survival time was 14 months, and the 1-year survival rate was 60% (95% CI, 44% to 80%). Febrile neutropenia occurred in five patients and five (1.3%) of 384 treatments. No dose-limiting neurotoxicity occurred. Symptomatic onycholysis and excessive lacrimation were observed after several months or more of therapy. CONCLUSION: Docetaxel 60 mg/m 2 and vinorelbine 45 mg/m 2 , both given every 2 weeks, is a highly active combination for the treatment of advanced NSCLC. Filgrastim largely obviates neutropenic fever and allows for the single-agent dose-intensity of both drugs to be delivered. The occurrence of certain late toxicities can limit use in some cases and suggests that the combination could also be beneficial in settings requiring briefer, fixed periods of treatment, such as in induction or postoperative therapy.
Chromosome Pulverization in Cultured Normal and Neoplastic Cells Treated With Cytochalasin B
Authors: Frank J. O'Neill
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Chromosome Pulverization in Cultured Normal and Neoplastic Cells Treated With Cytochalasin B Get access Frank J. O'Neill Frank J. O'Neill Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 6, December 1972, Pages 1733–1738, https://doi.org/10.1093/jnci/49.6.1733 Published: 01 December 1972 Article history Received: 12 July 1972 Accepted: 12 September 1972 Published: 01 December 1972
The Dual MEK/FLT3 Inhibitor E6201 Exerts Cytotoxic Activity against Acute Myeloid Leukemia Cells Harboring Resistance-Conferring FLT3 Mutations
Authors: Weiguo Zhang, Gautam Borthakur, Chen Gao, Ye Chen, Hong Mu, Vivian R. Ruvolo, Kenichi Nomoto, Nanding Zhao, Marina Konopleva, Michael Andreeff
Journal: Cancer Research (2016)

Fms-like tyrosine kinase 3 (FLT3) inhibition has elicited encouraging responses in acute myeloid leukemia (AML) therapy. Unfortunately, unless combined with a bone marrow transplant, disease relapse is frequent. In addition to the acquired point mutations in the FLT3 kinase domain that contribute to FLT3 inhibitor resistance, MEK/ERK signaling is persistently activated in AML cells even when FLT3 phosphorylation is continually suppressed. Thus, concomitant targeting of FLT3 and MAPK may potentially exert synergistic activity to counteract the resistance of AML cells to FLT3-targeted therapy. In this study, we investigated the antileukemia activity of a MEK1 and FLT3 dual inhibitor, E6201, in AML cells resistant to FLT3 inhibition. We found that E6201 exerted profound apoptogenic effects on AML cells harboring resistance-conferring FLT3 mutations. This activity appeared to be p53 dependent, and E6201-induced cytotoxicity was retained under hypoxic culture conditions and during coculture with mesenchymal stem cells that mimic the AML microenvironment. Furthermore, E6201 markedly reduced leukemia burden and improved the survival of mice in a human FLT3-mutated AML model. Collectively, our data provide a preclinical basis for the clinical evaluation of E6201 in AML patients harboring FLT3 mutations, including those who relapse following FLT3-targeted monotherapy.
Microvesicles and Vesicles of Multivesicular Bodies Versus “Virus-Like” Particles
Authors: Albert J. Dalton
Journal: JNCI Journal of the National Cancer Institute (1975)

Pellets obtained by the centrifugation of unfiltered or filtered fetal bovine serum (FBS) contained, among other things, numerous elongate and spherical microvesicles, ranging from 30 to 60 nm. They possessed a trilaminar (unit membrane) envelope and a moderately electron-dense core. Vesicles of multivesicular bodies and microvesicles associated with secretory epithelial cells and human lymphoblastoid cells in suspension culture possessed the same structure and were in the same size range as the serum microvesicles. These structures were either normal cell components or they represented the breakdown products of normal cell components and should not be confused with viruses. Though microvesicles of FBS may have been involved in the tissue culture material, at least some of the microvesicles associated with, and phagocytosed by, human lymphoblastoid cells in suspension and those in the lumen of acini of the baboon prostate were derived from the breakdown of the cristae of mitochondria in degenerating cells.
The challenge of protecting without overprotecting: The two sides of myeloid‐derived suppressor cells in hepatitis B viral infection
Authors: Maura Dandri, Jan‐Hendrik Bockmann
Journal: Hepatology (2015)

1I Department of Internal MedicineUniversity Medical Center Hamburg‐Eppendorf, Hamburg & German Center for Infection ResearchHamburg‐Lübeck‐Borstel SiteGermany †M.D. was supported by the German Research Foundation (DFG) Heisenberg Professorship DA1063/ 3‐1.
Abstract 517: The role of MYST4 in ovarian carcinoma
Authors: Tsui Lien Mao, Hsuan-Ping Lin, Jim Sheu
Journal: Cancer Research (2015)

Abstract Histone acetyltransferases (HATs) play critical roles in the process of cell growth and development. However, little is known about the relationship between MYST4, a known HAT, and human tumors. In our previous studies, we found that MYST4 was overexpressed in ovarian high-grade serous carcinomas and patients with tumors overexpressing MYST4 had significantly worse survival. To explore the role of MYST4 in ovarian carcinoma, we built up stable ovarian cancer cell lines with MYST4 knockdown by shRNA. By cell proliferation assay and flow cytometry, we found that MYST4 enhanced cancer cell growth and regulated cell cycle progression. In addition, the migration distance was significantly decreased in MYST4 knockdown cell lines, suggesting that MYST4 promotes cellular migration. Further cDNA microarray revealed several target genes that were down-regulated by MYST4 knockdown, some have been reported to be involved in tumorigenesis and aggressive tumor behavior. Together, our study suggests that MYST4 promotes cancer cell growth and migration. Overexpression of MYST4 in cancer cells may contribute to tumors toward a more aggressive behavior. Thus, MYST4 may serve as a potential target in treating ovarian carcinomas overexpressing MYST4. Citation Format: Tsui Lien Mao, Hsuan-Ping Lin, Jim Sheu. The role of MYST4 in ovarian carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 517. doi:10.1158/1538-7445.AM2015-517
Protease-activated receptor-2 protects against pancreatitis by stimulating exocrine secretion
Authors: V. P Singh, L. Bhagat, S. Navina, R. Sharif, R. K Dawra, A. K Saluja
Journal: Gut (2006)

Protease-activated receptor-2 (PAR-2) is present in the pancreas, where it has been shown to play a protective role during pancreatitis. However, the mechanism by which it protects against pancreatitis still remains to be elucidated. Acute pancreatitis is associated with premature zymogen activation and a blockage in digestive enzyme secretion.To examine the effects of PAR-2 activation on the severity of pancreatitis, and to determine whether its protective effects are mediated by affecting either premature activation or secretory blockage, or both.The results confirmed that PAR-2 -/- mice have more severe pancreatitis than wild-type mice. Interestingly, intrapancreatic trypsin levels in the PAR-2 knockouts remained high after 6 h of pancreatitis, whereas they reverted to normal in the wild types. During pancreatitis, PAR-2 mRNA levels were upregulated in wild-type mice in response to supramaximal caerulein administration. Further, after a single injection of supramaximal caerulein, PAR-2 mRNA levels were also elevated, reaching a peak at 3 h. Stimulating PAR-2 with trypsin or the PAR-2-activating peptide, serine-leucine-isoleucine-glycine-arginine-leucine (SLIGRL), induced significantly more secretion from the acini of these caerulein-sensitised mice compared with the controls. PAR-2 activation also reversed the inhibition of secretion observed in both the caerulein and arginine models.Trypsin released during the early stages of pancreatitis activates PAR-2 receptors on the acinar cells and stimulates secretion from these cells. Thus, PAR-2 activation may decrease pancreatic injury and limit the severity of pancreatitis by allowing extracellular trypsin to act as a secretagogue.
Phase II trial of cisplatin and alpha-interferon in advanced malignant melanoma.
Authors: K A Margolin, J H Doroshow, S A Akman, L A Leong, R J Morgan, G Somlo, J Raschko, C Pereira, L Yonemoto, C Ahn
Journal: Journal of Clinical Oncology (1992)

To evaluate the antitumor activity of combination cisplatin (CDDP) and alpha-interferon (alpha-IFN) in advanced, measurable metastatic melanoma.Adult patients with metastatic melanoma were required to have bidimensionally measurable lesions and a Karnofsky performance status > or = 60%. Serum creatinine < or = to 1.5 mg/dL, creatinine clearance > or = 60 mL/min, adequate organ and bone marrow function, and radiologic proof of the absence of brain metastases were required. CDDP 40 mg/m2 intravenously (IV) on day 1 and day 8, and alpha-IFN 3 million units/m2 subcutaneously on days 1 to 5 and 8 to 12 were administered every 3 to 4 weeks.Forty-two patients were entered onto this phase II trial and were assessable for response and toxicity. Three patients achieved complete responses (CRs) that lasted 31+, 5, and 8+ months. Seven patients had partial responses (PRs) and a median response duration of 4.4 months. The overall objective response rate was 24% (95% confidence interval, 12% to 39%). Toxicities were mild. Only 11% of the courses required dose reduction of alpha-IFN, and three of 128 courses required CDDP dose reduction for reversible nephrotoxicity.The combination of moderate-dose CDDP and alpha-IFN as administered in this schedule is well tolerated and possesses encouraging activity in metastatic melanoma.