tbuckley/cabot-search huggingface dataset:
Assessment for retreatment (ART) score for repeated transarterial chemoembolization in patients with hepatocellular carcinoma
Authors: Masatoshi Kudo, Tadaaki Arizumi, Kazuomi Ueshima
Journal: Hepatology (2013)

We read with great interest the article by Sieghart et al. published in Hepatology.1 The authors developed a point scoring system, the Assessment for Retreatment (ART) with Transarterial Chemoembolization (TACE), to assist in decision making whether retreating hepatocellular carcinoma (HCC) patients with TACE. Patients with HCC who received at least two TACE sessions within 90 days were the subjects of their study. The ART score differentiated patients into two groups (0-1.5 points; ≥2.5 points) with distinct prognosis (median overall survival [OS]: 23.7 versus 6.6 months; P < 0.001). These results were confirmed in an external validation cohort (median OS: 27.6 versus 8.1 months; P < 0.001). They concluded that an ART score ≥2.5 prior to second TACE can be used to identify patients with a dismal prognosis who may not benefit from further TACE sessions. Provided that this objective scoring system is universally reproducible, it will be an epoch-making development in the differentiation of patients into those who will benefit from repeated TACE and those who will not. Repeated TACE is more frequently performed in patients with HCC in Japan than in other regions. In addition, we sense that few patients in Japan receive a second TACE within 3 months. Therefore, we attempted a validation study in Japanese patients. From 2004 to 2011, 513 patients with HCC underwent >2 TACE sessions. Among them, only 49 (9.6%) had two TACE sessions within 90 days. This is a marked difference from the Sieghart et al. report1 (204 of 231 patients [88%] in Vienna and 224 of 252 patients [89%] in Innsbruck). More surprisingly, the ART score in 49 patients did not have any predictive impact on survival (Fig. 1). Several possible explanations exist for the discrepancy between the Austrian and Japanese results. First, patients with intermediate-stage HCC constitute a heterogeneous population. For example, due to the established nationwide surveillance, Japanese patients who undergo TACE usually have fewer and smaller nodules than patients in other regions of the world. Second, superselective TACE, which leads to a complete response, is routinely performed in Japan. Third, in Sieghart et al.'s study,1 the second TACE was performed 13-90 days after the first TACE. Performing a second TACE only 13 days after the first TACE suggests that the second TACE is already considered necessary after completion of the first TACE. This implies that their HCC patients had huge or bilobar advanced tumors. In Japan, such HCC cases are seldom encountered. In conclusion, the ART score could be applied to only <10% of Japanese patients and then did not have any prognostic predictive impact on survival in these patients. Therefore, the ART score should not be considered a universal point-scoring system. Masatoshi Kudo, M.D., Ph.D. Tadaaki Arizumi, M.D. Kazuomi Ueshima, M.D. Department of Gastroenterology and Hepatology Kinki University School of Medicine Osaka-Sayama, Osaka, Japan
The Comparative Physiological Disposition of ThioTEPA and TEPA in the Dog
Authors: L. B. Mellett, L. A. Woods
Journal: Cancer Research (1960)

Summary  A sensitive, specific fluorometric method for the determination of N,N′,N″-triethylenethiophosphoramide (thioTEPA) and N,N′,N″-triethylenephosphoramide (TEPA), separately and in the presence of each other, has been developed. The percentage recovery of thioTEPA or TEPA added to plasma and urine in the range of 0.05–0.2 µg/ml was 95 ± 20 per cent, and at levels of 0.2 µg-2.0 µg/ml it was 90 ± 12 per cent.  After the intravenous or oral administration of thioTEPA to dogs the presence of TEPA in the urine was demonstrated both by analytical procedures and by means of paper chromatography. After 3.0 mg/kg intravenously, the percentage excretion of TEPA was 8–13 per cent of the administered dose of thioTEPA. After 6.0 mg/kg orally, the percentage excretion of TEPA was 13–15 per cent. The plasma concentration curves of thioTEPA after 3.0 mg/kg intravenously fell rapidly to a level of 0.2 µg/ml in 2 hours. On the other hand, maximal plasma levels (1.2–1.4 µg/ml) of TEPA were not reached until 90 minutes to 2 hours. On the basis of information on plasma levels and urinary excretion of thioTEPA, at least 50 per cent of the administered dose was absorbed.  Prior administration of β-diethylaminoethyldiphenyl propyl acetate HCl (SKF 525A) delayed the conversion of thioTEPA to TEPA. This delay in conversion was accompanied by an increased toxicity in mice and dogs.  When TEPA was administered to dogs in a dose of 3.0 mg/kg intravenously, the plasma levels were 2–4 times the levels of thioTEPA after intravenous administration. The urinary recovery of TEPA was 24–34 per cent of the administered dose.  The stability of thioTEPA and TEPA in various media was investigated. There was no significant difference between the two drugs upon incubation in plasma, whole blood, or various buffers. Both drugs were stable in alkaline medium (pH 8.4) and were rapidly destroyed in acid medium (pH 4.2).  Tissue distribution of thioTEPA could not be determined, because the drug was almost completely destroyed when in contact with tissue. TEPA, on the other hand, could be determined and displayed a marked affinity for bone marrow as compared with other tissues.
A549 cell expression of ubiquitin E3 ligase RNF168 is decreased following RSV infection but increased by interferon beta treatment
Authors: Jonathan Jeyatheswaran, Louise Apperley, Paul McNamara, Brian Flanagan
Journal: European Respiratory Journal (2013)

Introduction 

Respiratory syncitial virus (RSV) is a major cause of lower respiratory tract illness in young children worldwide. We have shown previously that infection with RSV alters expression of protein linked to intrinsic antiviral defense within the epithelium, the site of initial RSV infection. SiRNA knockdown of the E3 ubiquitin ligase RNF168 in A549 cells leads to increased replication of RSV, suggesting this protein limits viral replication. RNF168 has been shown to be degraded during Herpes Simplex virus infection.

Aims 

To examine the interaction between RSV and RNF168 and determine if RSV infection leads to reduced RNF168 expression.

Method 

A549 cells were infected with RSV strain A2 at multiplicity of infection (MOI) up to 1:1. Samples were collected at 4 and 24 hours post infection and RNF168 expression measured by western blot. To examine the mechanism of down regulation, comparison was made to treatment with interferon and the TLR3 stimulant polyI:C.

Results 

Maximal change in expression was observed at 4 and 24 hours. An MOI of 1:1 resulted in a three-fold decrease in RNF168 expression compared to control at both 4 hour and 24 hours (n=3). PolyI:C and interferon both increased RNF168 expression by three-fold at 4 hours compared to control.

Conclusion 

RSV infection results in reduced expression of RNF168, suggesting this protein is important in cellular defense against RSV. This suggestion is supported by the observed increase in RNF168 expression following interferon stimulation.
Comparison of mannitol and methacholine challenge test for the diagnosis of asthma in athletes
Authors: Malika Mustafina, Alexander Cherniak, Ludmila Shogenova, Zaurbec Aisanov, Alexander Chuchalin
Journal: European Respiratory Journal (2014)

The prevalence of exercise-induced bronchoconstriction (EIB) is reported to be high among elite athletes. Diagnosis methods can generally be divided into two categories, direct and indirect tests. Methacholine acts directly on acetylcholine receptors on smooth muscle causing contraction and airway narrowing. Provocation tests that use indirect stimuli (e.g. mannitol) cause smooth muscle contraction by release of endogenous mediators. Which method is more specific and sensitive for diagnosis of bronchial hyperresponsiveness (BHR) and EIB is therefore an essential question.   Objective:  to compare specificity and sensitivity of the mannitol challenge test (MT) and methacholine challenge test (MCT) for the diagnosis of bronchial asthma in athletes.   Methods:  12 athletes (5 M/7 F, mean age 24.0±6.3 yrs) with respiratory symptoms were studied. Lung function with assessment of reversibility to salbutamol, MT and MCT were performed. The specificity and sensitivity of MT and MCT were evaluated.   Results:  Significant reversibility to salbutamol was found in 5 athletes. The fall in FEV 1  following the methacholine inhalation was more than 20% in 8 athletes. The fall in FEV 1  following the mannitol dry powder inhalation was more than 15% in 8 athletes. There was significant positive correlation between MCT-BHR and MT-BHR results. Both MCT and MT showed equally high specificity and sensitivity.   Conclusion:  Bronchial provocation tests provide objective criteria for exercise-induced bronchoconstriction and can be recommended to justify the use of inhaled beta2-agonists by athletes. Both the MCT and MT in athletes with respiratory symptoms had equally high specificity and sensitivity.
Clinical trials in allergic conjunctivits: a systematic review
Authors: F. Mantelli, A. Lambiase, S. Bonini, S. Bonini
Journal: Allergy (2011)

To cite this article: Mantelli F, Lambiase A, Bonini S, Bonini S. Clinical trials in allergic conjunctivits: a systematic review. Allergy 2011; 66: 919–924. Background: Ocular allergy represents one of the most common conditions encountered by allergists and ophthalmologists. However, there is wide variability of study designs in clinical trials of allergic conjunctivitis, which results in conflicting evidence on their optimal management. We conducted a systematic review of clinical trials to critically evaluate their quality and to highlight biases to be avoided in future clinical research in ocular allergy. Methods: Clinical trials in allergic conjunctivitis performed since 1965 were retrieved, and data on patients, interventions, comparison of interventions, and outcomes were extracted. Four authors independently assessed articles for inclusion in the systematic review and assessed trials' quality using the Jadad scale. Results: Three hundred and sixty-two trials were included in the study. Only a minority of trials fulfilled all the criteria of proper clinical trial design. In most of the studies, there was a very limited use of objective (quantifiable) parameters for both patients' selection and evaluation of drug efficacy and safety. Several outcomes of primary importance, such as disease relapses and recurrence rate, were omitted in clinical trials of allergic conjunctivitis. Conclusions: Evidence coming out of clinical trials in ocular allergy is limited, and this affects the strength of recommendations to health care providers and policy makers for optimal management. Standardized diagnostic criteria for patient selection and quantifiable primary outcomes are recommended to improve the design of future clinical trials in allergic conjunctivitis.
Emerging Infectious Diseases
Authors: Yodi Mahendradhata
Journal: JAMA (2005)

Unexplained Acute Illness -Continued Beginning in May 1993, cases of acute illness characterized by fever, myalgias, headache, and cough, followed by rapid development of respiratory failure, have been reported to the New Mexico Department of Health (NMDOH), Arizona Department of Health Services (ADHS), Colorado Department of Health (CDH), and Utah Department of Health (UDH).This report presents preliminary findings from an ongoing investigation of this problem, which suggest this illness is associated with a previously unrecognized hantavirus.On May 14, the NMDOH was notified by the Office of the Medical Investigator that two persons living in the same household had died within 5 days of each other.Their illnesses were characterized by abrupt onset of fever, myalgias, headache, and cough, followed by the rapid development of respiratory failure.Tests for Yersinia pestis and other bacterial and viral pathogens were negative.After additional persons who had recently died following a similar clinical course were reported to the the NMDOH by the Indian Health Service (IHS), the ADHS, CDH, and UDH were contacted by the NMDOH seeking other possible cases.To identify cases, public health officials established a provisional surveillance case definition of 1) radiographic evidence of unexplained bilateral pulmonary interstitial infiltrates with hypoxemia (arterial oxygen saturation of <90% while breathing room air) or 2) an autopsy finding of unexplained noncardiogenic pulmonary edema occurring during 1993.Through June 7, a total of 24 case-patients have been identified.Case-patients had onsets of illness beginning in December 1992; most (14) had onset in May (Figure 1).The most recent case-patient had onset of illness June 1.Casepatients resided in New Mexico (17), Arizona (five), Utah (one), and Colorado (one).Their median age was 34 years (range: 13-87 years; 17 were aged 18-50 years).Thirteen were male.Fourteen case-patients were American Indians, nine were white, and one was Hispanic.Twelve (50%) case-patients have died.Clinical and autopsy specimens are being processed and analyzed by CDC.Preliminary results include detection of rising titers of antibodies to hantaviruses in paired serum specimens from two of the nine case-patients; elevated single antibody titers were present in four other of the nine case-patients.The pattern of cross-reactivity to
Guidelines for Cardiopulmonary Resuscitation
Authors: John E Billi, William Montgomery, Jerry Nolan, Vinay Nadkarni
Journal: JAMA (2005)

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Abstract 15280: Comparisons of Action Potentials and Ionic Currents Between Neonatal Rat Ventricular Myocytes and Adult Zebrafish Ventricular Myocytes
Authors: Adonis Z Wu, Shien-Fong Lin, Sheng-Nan Wu
Journal: Circulation (2014)

Introduction: Zebrafish heart is established as a model to investigate cardiac electrical abnormalities. However, electrical properties of adult zebrafish cardiomyocytes are not sufficiently characterized. Hypothesis: In this study, by comparing the electrical properties between neonatal rat ventricular myocytes (NRVMs) and adult zebrafish ventricular myocytes (AZVMs), we intended to characterize the action potential (AP), action current (AC) and the properties of Na + current ( I Na ) in AZVMs. Methods: We used patch-clamp technique to characterize the electrical properties, including AP, AC and I Na , in cultured NRVMs and freshly isolated AZVMs. Results: NVRMs showed larger AP amplitude (119±6 vs. 79±4mV, p&lt;.05) but shorter AP duration (APD 90 , 136±11 vs. 213±19 ms, p&lt;.05) than those of AZVMs. The AP duration exhibited marked frequency-dependent alterations in AZVMs. Under the slow pacing rate, early after-depolarizations (EAD) emerged under slow pacing rate with 0.05 Hz. In cell-attached voltage-clamp recordings made from AZVMs, ACs could be elicited by +10 mV steps. As the depolarization step increased to +70 mV, the latency for appearance of ACs was progressively reduced from &gt;123 ms to 9.8 ms. The presence of spontaneous ACs was monitored in spontaneously beating NRVMs and AZVMs. The AC amplitude in NRVMs was larger compared to that in AZVMs (17.3±2.1 vs. 11.6±1.1 pA, p&lt;.05), although firing frequency of AC in NRVMs is higher than in AZVMs (1.13±0.09 vs. 0.38±0.03 Hz, p&lt;.05). The lowering effect of ranolazine, a I Na antagonist, on firing frequency was significantly larger in NRVMs (1.13±0.09 to 0.31±0.02 Hz, p&lt;.05) than in AZVMs (0.38±0.03 to 0.27±0.02 Hz). There was a hyperpolarizing shift of peak I Na in AZVM compared to NRVM. Conclusions: Our results demonstrated major differences in the cellular electrical behavior between AZVMs and NRVMs.
3,3′-diindolylmethane, a major acid condensation product of indole-3-carbinol, induce expression of NAG-1 and ATF3 in colorectal cancer cells.
Authors: Seong-Ho Lee, Jong-Sik Kim, Kiyoshi Yamaguchi, Thomas E. Eling, Seung Joon Baek
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5589 

Epidemiological studies have suggested that nutrition plays an important role in carcinogenesis and dietary factors have been estimated to account for up to 80% of cancers of the gastrointestinal tract and approximately 30% of cancer morbidity and mortality might be prevented with proper adjustment of diets. Indole-3-carbinol (I3C), present in cruciferous vegetables, and its major in vivo product 3,3′-diindolylmethane (DIM), have been reported to suppress cancer development. The present study was performed to investigate whether I3C and DIM influence the expression of the TGF-β superfamily gene NAG-1 (nonsteroidal anti-inflammatory drug-activated gene-1) and ATF3 (activating transcription factor 3), that are associated with pro-apoptotic and anti-tumorigenic activities. I3C repressed cell proliferation and induced NAG-1 expression in a concentration-dependent manner. DIM increased the expression of NAG-1 as well as the promoter activity of NAG-1 in a p53 independent manner. The induction of ATF3 was earlier than that of NAG-1 and up-regulated NAG-1 expression, suggesting a possible mechanism of ATF3-mediated NAG-1 expression. The DIM treatment increased the levels of ATF3 mRNA and protein via transcriptional regulation through a PKC-dependent pathway. Our results suggest that I3C repress cell proliferation through up-regulation of NAG-1, and ATF3 may play a pivotal role in DIM-induced NAG-1 expression in human colorectal cancer cells.
Liver regeneration by stem/progenitor cells
Authors: Tohru Itoh, Atsushi Miyajima
Journal: Hepatology (2013)

The liver is renowned for its strong, robust regenerative capacity, employing different modes of regeneration according to type and extent of injury. The process of compensatory hypertrophy of the liver upon partial hepatectomy has been standing as a classical model for studying organ regeneration in mammals and a subject of exhaustive analyses. Meanwhile, in view of the physiological relevance for many of the human liver pathologies induced upon toxic insults or hepatitis, other injury models have recently drawn increasing attention. In those damaged livers where hepatocyte proliferation is compromised, adult liver stem/progenitor cells (LPCs) are activated and differentiate to hepatocytes and cholangiocytes, leading to functional recovery of the organ. Here, we summarize and discuss recent findings on the mechanisms underlying the regeneration process of the liver. Whereas the primary focus of this article is on those related to LPC-mediated regeneration, we also introduce topics on compensatory hypertrophy, where application of new technologies and molecular genetics approaches in mice has gained a paradigm shift. Identification of various markers for LPC populations has expedited their characterization and enabled us to examine their differentiation potential in vivo using genetic lineage-tracing approaches. Comprehensive studies regarding intercellular signaling pathways and their modes of action have succeeded in elucidating novel frameworks for the LPC-niche interaction functioning in the regenerating liver. Conclusion : Advancing our understanding of the cellular and molecular mechanisms for liver regeneration should provide a basis for developing therapeutic strategies to treat patients with liver disease. (HEPATOLOGY 2014;59:1617-1626)
Predictive Value of Brachial Flow-Mediated Dilation for Incident Cardiovascular Events in Population Based Adults Free of Cardiovascular Disease at Baseline: The Multi-Ethnic Study of Atherosclerosis
Authors: Joseph Yeboah
Journal: Circulation (2008)

Abstract 1255 Joseph Yeboah, Gregory L Burke, John R Crouse, Wake Forest Univ Sch of Med, Winston Salem, NC; Joao A Lima, John Hopkins Univ, Baltimore, MD; Craig Johnson, Univ of Washington, Seattle, WA; Joseph F Polak, Tufts-New England Medical Ctr, Boston, MA; Aaron Folsom, Univ of Minnesota, Minneapolis, MN; Wendy Post, John Hopkins Univ, Baltimore, MD; David M Herrington, Wake Forest Univ Sch of Med, Winston Salem, NC Joseph Yeboah, 2008 Finalist and Presenting Author
Absence of regional hemispheric volume asymmetries in first-episode schizophrenia
Authors: R M Bilder, H Wu, B Bogerts, G Degreef, M Ashtari, J M Alvir, P J Snyder, J A Lieberman
Journal: American Journal of Psychiatry (1994)

The goal of this study was to determine whether patients experiencing their first episode of schizophrenia differ from healthy subjects in regional cerebral hemispheric volumes or asymmetries.Regional volumes corresponding to prefrontal, premotor, sensorimotor, occipitoparietal, and temporal lobes in each hemisphere were measured on contiguous coronal magnetic resonance images in 70 patients experiencing their first episode of schizophrenia and in 51 healthy comparison subjects.Patients did not differ from the comparison subjects in regional or total hemispheric volumes, but they had abnormal hemispheric asymmetries. Subjects in the comparison group had significant lateral asymmetries in each region: their occipitoparietal and sensorimotor regions were larger on the left, and their premotor, prefrontal, and temporal regions were larger on the right. Patients lacked lateral asymmetries and showed significantly less asymmetry than healthy subjects in occipitoparietal, premotor, and prefrontal regions. Absence of the normal asymmetry was more common among patients initially diagnosed with the undifferentiated than with the paranoid subtype of schizophrenia and was associated with more severe negative symptoms among men. Asymmetries were related to sex and handedness regardless of diagnosis; specifically, dextral men showed more asymmetry than nondextral men or dextral women.The absence of normal hemispheric asymmetries suggests an anomaly in the development of laterally specialized cerebral systems in schizophrenia, and this may be associated with an initial presentation of nonparanoid psychosis.
Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I
Authors: Parastoo Momeni, Gernot Glöckner, Olaf Schmidt, Diane von Holtum, Beate Albrecht, Gabriele Gillessen-Kaesbach, Raoul Hennekam, Peter Meinecke, Bernhard Zabel, André Rosenthal, Bernhard Horsthemke, Hermann-Josef Lüdecke
Journal: Nature Genetics (2000)