tbuckley/cabot-search huggingface dataset:
Pseudopalisades in Glioblastoma Are Hypoxic, Express Extracellular Matrix Proteases, and Are Formed by an Actively Migrating Cell Population
Authors: Daniel J. Brat, Amilcar A. Castellano-Sanchez, Stephen B. Hunter, Marcia Pecot, Cynthia Cohen, Elizabeth H. Hammond, Sarojini N. Devi, Balveen Kaur, Erwin G. Van Meir
Journal: Cancer Research (2004)

Necrosis and vascular proliferation are the pathologic features that distinguish the most malignant infiltrative astrocytoma, glioblastoma (GBM), from those of lower grades. In GBM, hypercellular zones called pseudopalisades typically surround necrotic foci. Although these cells are known to secrete high levels of proangiogenic factors that promote tumor growth, their origins are ill defined. We propose that pseudopalisades represent differing stages and histologic samplings of astrocytoma cells migrating away from a hypoxic/anoxic focus, often triggered by a central vaso-occlusive event. This proposition is based on our findings that pseudopalisading cells are 5-50% less proliferative and 6-20 times more apoptotic than adjacent astrocytoma, indicating that cell accumulation does not result from increased proliferation or resistance to apoptosis. Coexisting inflammatory cells account for <2% of pseudopalisading cells and cannot account for hypercellularity. Pseudopalisading cells show nuclear expression of hypoxia-inducible factor 1 alpha, consistent with their hypoxic nature, and hypoxia induces a 20-60% increase in glioma cell migration in vitro. Hypoxic cells in vitro and pseudopalisades in GBM specimens show enhanced gelatinase activity, typical of an invasive phenotype. These results suggest that pseudopalisading cells are migrating at the periphery of a hypoxic center. To uncover a potential source of hypoxia and sequence of structural events leading to pseudopalisade formation, we performed a morphometric analysis of 234 pseudopalisades from 85 pretreatment GBMs. We found distorted, degenerating, or thrombosed blood vessels within the center of more than half the pseudopalisades, suggesting that at least a subset of pseudopalisades are two-dimensional histologic representations of tumor cells migrating away from a vaso-occlusive event.
Opposing effects of prednisolone treatment on T/NKT cell- and hepatotoxin-mediated hepatitis in mice
Authors: Hyo-Jung Kwon, Young-Suk Won, Ogyi Park, Dechun Feng, Bin Gao
Journal: Hepatology (2013)

Prednisolone is a corticosteroid that has been used to treat inflammatory liver diseases such as autoimmune hepatitis and alcoholic hepatitis. However, the results have been controversial, and how prednisolone affects liver disease progression remains unknown. In the current study we examined the effect of prednisolone treatment on several models of liver injury, including T/NKT cell hepatitis induced by concanavalin A (ConA) and α-galactosylceramide (α-GalCer), and hepatotoxin-mediated hepatitis induced by carbon tetrachloride (CCl4 ) and/or ethanol. Prednisolone administration attenuated ConA- and α-GalCer-induced hepatitis and systemic inflammatory responses. Treating mice with prednisolone also suppressed inflammatory responses in a model of hepatotoxin (CCl4 )-induced hepatitis, but surprisingly exacerbated liver injury and delayed liver repair. In addition, administration of prednisolone also enhanced acetaminophen-, ethanol-, or ethanol plus CCl4 -induced liver injury. Immunohistochemical and flow cytometric analyses demonstrated that prednisolone treatment inhibited hepatic macrophage and neutrophil infiltration in CCl4 -induced hepatitis and suppressed their phagocytic activities in vivo and in vitro. Macrophage and/or neutrophil depletion aggravated CCl4 -induced liver injury and impeded liver regeneration. Finally, conditional disruption of glucocorticoid receptor in macrophages and neutrophils abolished prednisolone-mediated exacerbation of hepatotoxin-induced liver injury.Prednisolone treatment prevents T/NKT cell hepatitis but exacerbates hepatotoxin-induced liver injury by inhibiting macrophage- and neutrophil-mediated phagocytic and hepatic regenerative functions. These findings may not only increase our understanding of the steroid treatment mechanism but also help us to better manage steroid therapy in liver diseases.
Aflatoxins and Reye's disease.
Authors: D M Becroft, D R Webster
Journal: BMJ (1972)

<h3>Background</h3> Variants of <i>SCN5A</i>, encoding cardiac sodium channel, have been linked to the development of dilated cardiomyopathy (DCM). We aimed to explore novel <i>SCN5A</i> variants in patients with idiopathic DCM (iDCM) and to identify the distribute characteristics and pathological mechanisms as well as clinical phenotypes associated with the variants in patients with iDCM. <h3>Methods</h3> <i>SCN5A</i> exons sequencing was performed inpatients with iDCM (n=90) and two control cohorts (arrhythmias group, n=90, and healthy group, n=195). Clinical characteristics were compared between carriers and non-carriers. We then generated a novel heterozygous knock-in (KI) mouse by homologous recombination. Cardiac function, electrical parameters and histological characteristics were examined at basal or stimulating condition. <h3>Results</h3> We found three novel non-synonymous <i>SCN5A</i> variants associated with iDCM, including c.674G&gt;A, c.677C&gt;T, and c.4340T&gt;A. The newly defined iDCM-related variants mainly located in the S4 segment of domain I (DI-S4). Incidence of atrioventricular block was significantly higher in mutant patients with iDCM than in non-carriers. Structural injuries were absent at both basal and stress condition in KI mice carrying c.674G&gt;A (R225Q); however, this variant significantly prolonged PR intervals at baseline without affecting other ECG parameters, which was linked to decreased peak sodium current density in KI cardiomyocytes. Histological analysis of the atrioventricular node did not show any evidences of cell damages. <h3>Conclusion</h3> Our results suggest that the iDCM-related <i>SCN5A</i> variants in the DI-S4 could predispose electrical disorders by reducing peak sodium current density.
Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants
Authors: M. Louise Markert, Blythe H. Devlin, Marilyn J. Alexieff, Jie Li, Elizabeth A. McCarthy, Stephanie E. Gupton, Ivan K. Chinn, Laura P. Hale, Thomas B. Kepler, Min He, Marcella Sarzotti, Michael A. Skinner, Henry E. Rice, Jeffrey C. Hoehner
Journal: Blood (2007)
Flow‐assisted allergy diagnosis: current applications and future perspectives
Authors: D. G. Ebo, J. Sainte‐Laudy, C. H. Bridts, C. H. Mertens, M. M. Hagendorens, A. J. Schuerwegh, L. S. De Clerck, W. J. Stevens
Journal: Allergy (2006)

Physicians predominantly rely upon quantification of serum‐specific immunoglobulin E (IgE) and/or skin test to confirm clinically suspected IgE‐mediated allergy. However, for various reasons, identification of the offending allergen(s) and potentially cross‐reactive structures is not always straightforward. Flow‐assisted allergy diagnosis relies upon quantification of alterations in the expression of particular basophilic activation markers. Actually, upon challenge with a specific allergen, basophils not only secrete quantifiable bioactive mediators but also upregulate the expression of different markers which can be detected efficiently by flow cytometry using specific monoclonal antibodies. Currently, the technique has been applied in the investigation of IgE‐mediated allergy caused by classical inhalant allergens, food, Hevea latex, hymenoptera venoms and drugs. It is also appreciated; the technique proves valuable in the diagnosis of non‐IgE‐mediated (anaphylactoid) reactions such drug hypersensitivity and the detection of autoantibodies in certain forms of chronic urticaria. This review will not address immunologic features, characteristics and general pitfalls of flow‐assisted analysis of in vitro ‐activated basophils as summarized elsewhere. After a recapitulation of the principles and some specific technical issues of flow‐assisted analysis of in vitro ‐activated basophils, we principally focus on the current clinical and research applications of the basophil activation tests. Personal experience of both research groups is provided, where appropriate. Finally, a viewpoint on how the field might evolve in the following years is provided.
NSABP B-30: definitive analysis of patient outcome from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel and cyclophosphamide in women with operable, node-positive breast cancer.
Authors: SM Swain, J Jeong, CE Geyer, JP Costantino, ER Pajon, L Fehrenbacher, JN Atkins, J Polikoff, VG Vogel, JK Erban, RB Livingston, EA Perez, EP Mamounas, PA Ganz, SR Land, N Wolmark
Journal: Cancer Research (2009)

Abstract Abstract #75 Background: The primary aims of this study were to determine 1) if a concurrent regimen of therapy containing cyclophosphamide compared to a sequential regimen containing cyclophosphamide would prolong disease-free survival (DFS) and overall survival (OS) and 2) if a regimen without cyclophosphamide was at least as efficacious as the two regimens containing cyclophosphamide. The secondary aims were to compare toxicities among the three regimens and to compare differences in amenorrhea in premenopausal women in each arm and its relationship to outcome.&amp;#x2028; Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 1783 pts were randomized to Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4], 1784 pts to Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4], and 1784 to Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. The protocol specifies that 800 deaths are required for the definitive analysis. This is expected to occur by Fall 2008.&amp;#x2028; Results: Mean time on study is currently 79 months. At entry, 46% of pts were &amp;lt; 49 yrs; 54% were &amp;gt; 50 yrs. 82% were white, 10% black, 4% Hispanic. 66% had 1-3 positive nodes, 26% had 4-9, and 8% had 10+. 75% of pts were ER pos. 49% had lumpectomy, 51% mastectomy, and 24% local/regional radiotherapy. Mean tumor size was 2.5 cm. The presentation will include the first results of DFS, OS, and relevant toxicities from the trial. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 75.
Fibrinogenolysis in thrombotic thrombocytopenic purpura
Authors: Eizo Kakishita, Tetsuji Koyama, Mitsuhiro Higuchi, Osamu Kunitomi, Yoshio Oura, Kiyoyasu Nagai
Journal: American Journal of Hematology (1989)

Abstract Coagulo‐fibrinolytic factors were studied in five patients suffering from thrombotic thrombocytopenic purpura (TTP). The change in coagulation factors in the acute stage was mild compared with that found in disseminated intravascular coagulation (DIC). We observed a slight increase of fibrin‐fibrinogen degradation products (FDP) in the plasma of four patients during the acute stage of TTP, but the level of the D‐dimer remained within normal variation and was extremely low compared with that in 27 samples from patients with DIC showing the same level of FDP. At the same time, both antigen levels of tissue‐type plasminogen activator (t‐PA) and plasminogen activator inhibitor type 1 (PAI‐1) were elevated in three of the four patients tested. Although a similar change was recognized in DIC patients' plasma, the elevation of PAI‐1 in the acute stage of TTP was far higher than in overt DIC. The antigen levels of t‐PA and PAI‐1 were normal in remission, and a mild elevation of PAI‐1 was detected in one of the three patients during the early stage of TTP relapse. Enzymography revealed the appearance of free t‐PA and an increase of a substance with a 110 kD molecule, assumed to be a t‐PA and PAI‐1 complex, in TTP plasma in the acute stage, but the findings were normal for plasma from cases in remission and the early stage of relapse. Enzymography also showed a decrease of urokinase‐type plasminogen activator (u‐PA) only in the acute stage of TTP. These changes in the coagulo‐fibrinolytic factors in the acute stage of TTP suggest that fibrinogenolysis might be induced by t‐PA, released through vascular reaction at an uninvolved area of vascular lesions caused by platelet agglutinates, which would then release large amounts of PAI‐1 inhibiting t‐PA and u‐PA activities at the occlusive lesion.
Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627)
Authors: Andrew B. Lassman, Stephanie L. Pugh, Mark R. Gilbert, Kenneth D. Aldape, Sandrine Geinoz, Jan H. Beumer, Susan M. Christner, Ritsuko Komaki, Lisa M. DeAngelis, Rakesh Gaur, Emad Youssef, Henry Wagner, Minhee Won, Minesh P. Mehta
Journal: Neuro-Oncology (2015)

We conducted a phase II trial to evaluate the efficacy of dasatinib, a multitargeted tyrosine kinase inhibitor, for adults with recurrent glioblastoma (GBM). Eligibility requirements were Karnofsky performance status ≥60%; no concurrent hepatic enzyme-inducing anticonvulsants; prior treatment with surgery, radiotherapy, and temozolomide exclusively; and activation or overexpression of ≥2 putative dasatinib targets in GBM (ie, SRC, c-KIT, EPHA2, and PDGFR). Using a 2-stage design, 77 eligible participants (27 in stage 1, if favorable, and then 50 in stage 2) were needed to detect an absolute improvement in the proportion of patients either alive and progression-free patients at 6 months (6mPFS) or responding (any duration) from a historical 11% to 25%. A high rate of ineligibility (27%) to stage 1 precluded a powered assessment of efficacy, but there was also infrequent treatment-related toxicity at 100 mg twice daily. Therefore, the study was redesigned to allow intrapatient escalation by 50 mg daily every cycle as tolerated (stage 1B) before determining whether to proceed to stage 2. Escalation was tolerable in 10 of 17 (59%) participants evaluable for that endpoint; however, among all eligible patients (stages 1 and 1B, n = 50), there were no radiographic responses, median overall survival was 7.9 months, median PFS was 1.7 months, and the 6mPFS rate was 6%. The clinical benefit was insufficient to correlate tested biomarkers with efficacy. The trial was closed without proceeding to stage 2. Intraparticipant dose escalation was feasible, but dasatinib was ineffective in recurrent GBM. Clinical trials.gov identified. NCT00423735 (available at http://clinicaltrials.gov/ct2/show/NCT00423735).
Dodging cellular customs: Smuggling macromolecules into hepatocytes
Authors: Soumit K. Basu, Jayanta Roy Chowdhury
Journal: Hepatology (1994)

The potential of reconstituted Sendai viral envelopes containing only the fusion protein (F-virosomes) was evaluated for a targeted cytosolic delivery of lysozyme to human hepatoblastoma cells (HepG2) in culture. 125 I-Lysozyme loaded into F-virosomes was used to monitor its fusion-mediated transfer to the HepG2 cells. Using fusion assay based on the transfer of water soluble probe, we have demonstrated the existence of aqueous connection between F-virosomes and target cells. Target specificity of the F-virosomes was ensured by the strong interaction between terminal β-galactose moiety of F protein and the asialoglycoprotein receptor on the membrane of HepG2 cells. Incubation of the loaded F-virosomes with cells resulted in fusion-mediated injection, as inferred from the ability of cells to internalize lysozyme in the presence of azide (an inhibitor of the endocytotic process). Binding as well as fusion of the F-virosomes to HepG2 cells was solely mediated by the F protein. Introduction of 125 I-lysozyme into the HepG2 cells was confirmed by selective accumulation of acid and anti-body-precipitable radioactivity in the cytosolic compartment. The structural integrity of the internalized lysozyme was also assessed. The potential usefulness of F-virosomes with defined specificities as biological carrier for both in vitro and in vivo cytosolic delivery of macromolecules and drugs has been established.
New translocations in human lymphocytes: a mutagen monitoring system.
Authors: F Hecht, B K McCaw, D Peakman, A Robinson
Journal: Environmental Health Perspectives (1979)

The human lymphocyte is a premier cell for monitoring chromosome aneuploidy. The lymphocyte is easily obtained, can be studied before and after culture, and has been extensively investigated. Assays available for lymphocytes include the scoring of chromosome breaks (subjective and laborious), the analysis of chromosome abnormalities such as increase or decrease in number (versus normal background), dicentrics etc., and the micronucleus test (presumable end-state phenomena). We propose the monitoring of somatic chromosome translocations in human lymphocytes. Background data available from North America indicate that the frequency of de novo chromosome translocations in Halifax, Portland, Denver, and Atlanta is about 1.7 x 10(-3). The most common translocation arising in lymphocytes is between chromosomes 7 and 14 (with a frequency of 4 x 10(-4). All translocations occurring de novo in human lymphocytes tend to appear balanced with no evidence for loss or gain of chromosome material. Cytogenetic laboratories are processing lymphocytes daily. The resultant photographs and karyotypes are all scorable for de novo translocations. Suitable data on exposure to possible mutagenic agents could be collected in advance of these chromosome studies. This would provide a new method for monitoring chromosome changes in the population. The cost of monitoring lymphocyte chromosomes for somatic translocations would be small, since numerous laboratories study lymphocytes rountinely for clinical diagnostic purposes. There may be merit in availing ourselves of easily available data from a very available species: man.
Local authorities should be responsible for public health
Authors: G. Bickler, S. Ibbotson, B. McCloskey
Journal: BMJ (2011)

<h3>Objectives</h3> Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) has been proposed for patients with dementia. Here, we aim to assess the safety and effects of NBM-DBS in patients with Lewy body dementia (LBD), in a randomized, double-blind, crossover clinical trial. <h3>Methods</h3> Six patients with mild to moderate LBD (mean [SD] age, 62.2 [7.8] years) were included, operated on for bilateral NBM-DBS, and assigned to receive either active or sham NBM-DBS followed by the opposite condition for 3 months. The primary outcome was the difference in the total free recalls of the Free and Cued Selective Reminding Test (FCSRT) between active and sham NBM-DBS. Secondary outcomes were assessments of the safety and effects of NBM-DBS on cognition, motor disability, sleep, and PET imaging. <h3>Results</h3> There was no significant difference in the FCSRT score with active vs sham NBM-DBS. The surgical procedures were well tolerated in all patients, but we observed significant decreases in Stroop and Benton scores after electrode implantation. We observed no significant difference in other scales between active and sham NBM-DBS. With active NBM-DBS relative to baseline, phonemic fluency and motor disability significantly decreased. Lastly, the superior lingual gyrus metabolic activity significantly increased with active NBM-DBS. <h3>Conclusions</h3> NBM-DBS does not appear to be totally safe for patients with LBD with no evidence of cognitive benefit. <h3>ClinicalTrials.gov Identifier</h3> NCT01340001. <h3>Classification of Evidence</h3> This study provides Class II evidence that, for patients with LBD operated on for bilateral NBM-DBS, active NBM-DBS stimulation compared to sham stimulation did not significantly change selective recall scores.
Nonpathogenic SIV Infection of Sooty Mangabeys Is Characterized by Limited Bystander Immunopathology Despite Chronic High-Level Viremia
Authors: Guido Silvestri, Donald L. Sodora, Richard A. Koup, Mirko Paiardini, Shawn P. O'Neil, Harold M. McClure, Silvija I. Staprans, Mark B. Feinberg
Journal: Immunity (2003)
β2 Glycoprotein I (β2GPI) binds platelet factor 4 (PF4): implications for the pathogenesis of antiphospholipid syndrome
Authors: Marina P. Sikara, John G. Routsias, Martina Samiotaki, George Panayotou, Haralampos M. Moutsopoulos, Panayiotis G. Vlachoyiannopoulos
Journal: Blood (2009)
Liver Fibrosis in Alcoholics
Authors: Shinkichi Sato
Journal: JAMA (1986)

Radioimmunoassays were used to measure serum levels of laminin and of procollagen III peptides, both with the intact antibody and with the Fab fragments, within one week of alcohol withdrawal in 83 alcoholics admitted for detoxification and/or treatment of concomitant medical problems. All patients underwent a diagnostic liver biopsy, which revealed simple fatty liver in 22, perivenular fibrosis in 20, septal fibrosis in 21, and cirrhosis in 20. Although all three serum measurements correlated significantly with the degree of fibrosis, only the Fab radioimmunoassay of procollagen III peptides discriminated between simple fatty liver and perivenular fibrosis in a significant number of subjects. (<i>JAMA</i>1986;256:1471-1473)
Parotid Gland Swelling Due to Methimazole
Authors: Robert C. Moehlig
Journal: JAMA (1969)

<h3>To the Editor:—</h3> To the best of my knowledge, the swelling of the parotid gland due to methimazole (Tapazole) has not been reported in the literature and the manufacturer does not list this as one of the side effects. I wish, therefore, to report the following case: A 62-year-old woman with hyperthyroidism had been under the care of an allergist. On March 11, 1969, the patient was treated with methimazole, 10 mg every eight hours. Reactions to methimazole were explained to her. On April 29, the patient thought she had mumps; this involved both parotid glands. She was told to discontinue methimazole and within three days the swelling disappeared. On May 4, the patient took one methimazole tablet and the swelling of the parotids reappeared within a few hours. The relationship between the salivary glands and the thyroid is of course known. Hammett found the development of the submaxillary glands
Estimating Community Drug Abuse by Wastewater Analysis
Authors: Ettore Zuccato, Chiara Chiabrando, Sara Castiglioni, Renzo Bagnati, Roberto Fanelli
Journal: Environmental Health Perspectives (2008)

The social and medical problems of drug abuse are a matter of increasing global concern. To tackle drug abuse in changing scenarios, international drug agencies need fresh methods to monitor trends and patterns of illicit drug consumption.We tested a sewage epidemiology approach, using levels of excreted drug residues in wastewater, to monitor collective use of the major drugs of abuse in near real time.Selected drug target residues derived from use of cocaine, opiates, cannabis, and amphetamines were measured by mass spectrometry in wastewater collected at major sewage treatment plants in Milan (Italy), Lugano (Switzerland), and London (United Kingdom). The amounts of drug residues conveyed to the treatment plants, reflecting the amounts collectively excreted with urine, were used to estimate consumption of the active parent drugs.Reproducible and characteristic profiles of illicit drug use were obtained in the three cities, thus for the first time quickly revealing changes in local consumption (e.g., cocaine consumption rose significantly on weekends in Milan). Profiles of local drug consumption based on waste-water measurements are in line with national annual prevalence estimates.Patterns and trends of drug abuse in local communities can be promptly monitored by this tool, a convenient new complement to more complex, lengthy survey methods. In principle, searching the sewage for excreted compounds relevant to public health issues appears to have the potential to become a convenient source of real-time epidemiologic information.