tbuckley/cabot-search huggingface dataset:
Final Results of a Prospective Evaluation of the Predictive Value of Interim Positron Emission Tomography in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP-14 (SAKK 38/07)
Authors: Christoph Mamot, Dirk Klingbiel, Felicitas Hitz, Christoph Renner, Thomas Pabst, Christoph Driessen, Ulrich Mey, Miklos Pless, Mario Bargetzi, Fatime Krasniqi, Federica Gigli, Thomas Hany, Andrei Samarin, Christine Biaggi, Corinne Rusterholz, Stephan Dirnhofer, Emanuele Zucca, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2015)

Our main objective was to prospectively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 14 days (R-CHOP-14) under standardized treatment and PET evaluation criteria.Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab. PET/CT examinations were performed at baseline, after two cycles (and after four cycles if the patient was PET-positive after two cycles), and at the end of treatment. PET/CT examinations were evaluated locally and by central review. The primary end point was event-free survival at 2 years (2-year EFS).Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0, 1, or 2 in 56%, 36%, or 8% of the patients, respectively. By local assessment, 83 PET/CT scans (60%) were reported as positive and 55 (40%) as negative after two cycles of R-CHOP-14. Two-year EFS was significantly shorter for PET-positive compared with PET-negative patients (48% v 74%; P = .004). Overall survival at 2 years was not significantly different, with 88% for PET-positive versus 91% for PET-negative patients (P = .46). By using central review and the Deauville criteria, 2-year EFS was 41% versus 76% (P < .001) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24% versus 72% (P < .001) for patients who had PET/CT scans at the end of treatment.Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospective trial. At this point, interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients.
HAMSTRING INJURIES IN A PREMIER LEAGUE FOOTBALL TEAM. MRI VS. CLINICAL DIAGNOSIS
Authors: D Eastwood
Journal: British Journal of Sports Medicine (2014)

Introduction Hamstring injury is the most common injury in professional football 1 MRI is often used as both a diagnostic and prognostic tool, but clinical judgment is always used to assess injury. There is little evidence in current literature to compare the two. Aims To evaluate MRI scanning for predicting time missed after hamstring injuries and compare it to clinical judgment. Methods A retrospective study was carried out, using the medical database of Sunderland AFC (SAFC): a Premier League football club. Players with a hamstring injury who had had an MRI scan were selected. Injuries occurred between 7/03/2009 and 16/02/2013. I found 'individual time-loss', 'radiological findings on MRI' and ‘clinical findings’ for each player's injury, in documentation by medical staff at SAFC. MRI findings were interpreted using a modified Peetron's classification into four grades. An established system by Jan Ekstrand 2 predicts time, in days, out of full contact training and playing football matches, based on Peetron's grades. I used this to analyse the accuracy of MRI and of clinical grading. Results In total, 27 players had hamstring injuries, all receiving an MRI scan and clinical assessment. For MRI classification, 7.4% were grade 0 injuries, 55.5% grade 1, 37.0% grade 2 and 0% grade 3. Clinical judgment assessed 3.7% at grade 0, 62.9% grade 1, 25.9% grade 2 and 7.4% grade 3. Therefore, clinical grading given by medical professionals did not always concur with grading reported from MRI. When using Erkstrand's grading system, clinical grading was more accurate in predicting time out. MRI grading appeared to underestimate injuries; injuries assessed as low grade in fact led to more days injured than predicted. Most injuries (18/27) were given the same MRI and clinical grading, illustrating that there was only some variation between methods. Conclusions MRI is helpful in verifying the diagnosis and prognosis of a hamstring injury. Clinical grading appeared more accurate than MRI grading in predicting number of days injured. However, this was not statistically significant (p value 0.25). MRI “under grading” may result in a tendency to encourage players to train too soon. Over 60% of hamstring injuries were of radiological grade 0 or 1 (no signs of fibre disruption on MRI) but, in fact, these injuries caused the majority of days out.
Clock Genes in the Heart
Authors: Martin E. Young, Peter Razeghi, Heinrich Taegtmeyer
Journal: Circulation Research (2001)

We investigated whether the heart, like other mammalian organs, possesses internal clocks, and, if so, whether pressure overload-induced hypertrophy alters the clock mechanism. Clock genes are intrinsically maintained, as shown by rhythmic changes even in single cells. Clocks are believed to confer a selective advantage by priming the cell for the expected environmental stimulus. In this way, clocks allow anticipation, thereby synchronizing responsiveness of the cell with the timing of the stimulus. We have found that in rat heart all mammalian homologues of known Drosophila clock genes (bmal1, clock, cry1, cry2, per1, per2, per3, dbp, hlf, and tef) show circadian patterns of expression and that the induction of clock output genes (the PAR [rich in proline and acidic amino acid residues] transcription factors dbp, hlf, and tef) is attenuated in the pressure-overloaded hypertrophied heart. The results expose a new dynamic regulatory system in the heart, which is partially lost with hypertrophy. Although the target genes of these PAR transcription factors are not known in the heart, the results provide evidence for a diminished ability of the hypertrophied heart to anticipate and subsequently adapt to physiological alterations during the day.
Effect of extrinsic denervation on the rate of net water transport of the feline gall bladder.
Authors: S Bjorck, H Ahlman, A Dahlstrom
Journal: Gut (1984)

The influence on the concentrating ability of the gall bladder after extrinsic denervation was studied in anaesthetised cats, previously subjected to truncal vagotomy and/or coeliacectomy , and compared with sham operated controls. Net water absorption was studied by perfusion techniques. Acute experiments were performed under basal conditions and alpha-adrenoceptor stimulation (intra-arterial infusion of noradrenaline). Gall bladder biopsies were studied by fluorescence microscopy and cytofluorimetry to visualise and quantify catecholamines. Three weeks after coeliacectomy basal absorption had decreased significantly. In the short term vagotomy group no changes were shown. In the long term vagotomy group, however, there was a four-fold increase in absorptive capacity, which decreased to control levels after alpha-adrenoceptor blockade (phentolamine). Long term vagotomy with subsequent coeliacectomy caused no significant changes. Infusion of noradrenaline increased net water absorption by 60 +/- 11% in all experimental groups except in long term vagotomised animals, where the high basal absorption was not further augmented. One hour after noradrenaline infusion controls returned to basal absorption rate, while denervated cats remained at stimulated levels. In long term vagotomised gall bladders there were morphological signs of adrenergic proliferation (increased total number of nerve terminals, sprouting and raised levels of intraneuronal noradrenaline). These results suggest that the adrenergic nervous system is important for full absorptive capacity of the gall bladder. The increased absorption after long term vagotomy, abolished after alpha-adrenoceptor blockade, might well be explained by the parallel adrenergic proliferation. This hypothesis was further corroborated in animals with long term vagotomy, where subsequent surgical adrenergic denervation restored basal absorption to control levels.
Anaylsis of ventricular activation and repolarization from intramural and epicardial potential distributions for ectopic beats in the intact dog.
Authors: M S Spach, R C Barr
Journal: Circulation Research (1975)

Ventricular activation and repolarization were examined by measuring intramural and epicardial potential distributions during ectopic sequences in intact dogs. Potential distributions were used because they provided a direct measure of all of repolarization. Ectopic sequences produced almost unidirectional excitation across the heart along with repolarization events that were different from normal. During ectopic repolarization, positive potentials occurred over a broad area surrounding the ectopic focus, and negative potentials occurred over a large area on the opposite side of the heart where excitation terminated. The potentials in the walls of both ventricles were more positive in the outer layers and more negative in the inner layers, a gradient similar to normal. A maximum initially was at the ectopic site with a magnitude greater than that of the minimum, but the maximum subsequently decreased in magnitude and shifted toward the minimum while the minimum increased in magnitude. The steepest gradients were initially around the maximum, and they then shifted toward the minimum. The results show that ventricular repolatization potential distributions during ectopic beats are predominantly influenced by gradients from one side of the heart to the other (transventricular gradients) in contrast to normal repolatization distributions which are predominantly influenced by gradients across the wall (transmural gradients).
Manifestations of Atherosclerosis
Authors: R. Chris Brown
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The report by Gordon and Kannel in the Aug 14,1972, issue ofThe Journalindicating common precursors for the three major manifestations of atherosclerosis fills an important gap in our knowledge of the relationship between peripheral vascular, cerebrovascular, and coronary atherosclerotic disease. I question whether these risk factors are really applicable in the older age groups. Gordon and Kannel note that the relationship of cigarette smoking and cholesterol to coronary heart disease does not hold in the age group 65 to 74. In a retrospective study<sup>1</sup>of elderly patients at the Veterans Administration Hospital, Dr. Ritzmann and I noted a strong association between peripheral vascular atherosclerotic disease and coronary heart disease. However, not all of the usually cited risk factors for coronary heart disease seemed to apply to these elderly war veterans. Other studies<sup>2-4</sup>have shown that the factors of obesity, serum cholesterol, and cigarette
4 THE EXTRACELLULAR MATRIX PROTEIN LAMININ ALPHA 5 REGULATES THE BEHAVIOUR OF HEPATIC PROGENITOR CELLS IN REGENERATING MOUSE LIVER
Authors: M.J. Williams, L.G. Boulter, W.-Y. Lu, T.G. Bird, H. Fujiwara, F.M. Watt, C. Ffrench-Constant, S.J. Forbes
Journal: Journal of Hepatology (2013)
Absorbed aluminium is found with two cytosolic protein fractions, other than ferritin, in the rat duodenum.
Authors: M Cochran, G Goddard, G Ramm, N Ludwigson, J Marshall, J Halliday
Journal: Gut (1993)

After in vivo perfusion of the upper intestine of the rat with a range of concentrations of aluminium chloride, entry of the metal into the portal system was only detected when the perfusate exceeded 400 mumol/l, suggesting a mucosal block. Using gel filtration of a mucosal cytosol extract, two consistently appearing aluminium peaks were identified which may represent aluminium binding proteins. Both were heat stable at 60 degrees C and had molecular sizes of about 700 (kilo daltons) (kD) and 17 kD respectively. The larger molecule was distinct from ferritin. Neither molecule associated with 59Fe nor 45Ca. It is suggested that the aluminium peaks are relatively specific aluminium binding proteins that have a scavenging role, reducing entry of the metal from the intestinal contents into the portal blood.
The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study.
Authors: Bernd Jan Sanson, Paolo Simioni, Daniela Tormene, Marco Moia, Philip W. Friederich, Menno V. Huisman, Paolo Prandoni, Alessandra Bura, László Rejtö, Philip Wells, Pier M. Mannucci, Antonio Girolami, Harry R. Büller, Martin H. Prins
Journal: Blood (1999)
Significance of the Diagnostic Q Wave of Myocardial Infarction
Authors: LEO G. HORAN, NANCY C. FLOWERS, JENNIFER C. JOHNSON
Journal: Circulation (1971)

Correlation between the QRS complex and postmortem ventricular anatomy was made in 1184 instances of normal conduction: (1) Mechanical reliance on the sheer presence or absence of a Q wave greater than 0.03 sec in duration led to "correct" diagnosis of infarction or not in 79% of the series. (2)With normal conduction, abnormal Q waves isolated to either the anteroseptal (V l -V 4 ) or inferior (II, III, a V F ) electrocardiographic zones were frequently false (46%). However, abnormal Q waves restricted to the lateral zone (V 5 -V 6 ) or in a combination of more than one electrocardiographic zone, were rarely false predictors of the presence of infarction (4%). (3) Classical localization of infarction with normal conduction was statistically relatively reliable as compared with bundle-branch block. The increased frequency of the anatomic pattern of lateral basal infarction in association with normal QRS complexes (but known infarction) suggests relative "electrical silence" of the laterobasal left ventricle in abnormal Q-wave genesis. (4) Lesions confined to a given anatomic location in the left ventricle tended to place particular emphasis and limits on the spectrum of electrocardiographic expression but did not yield a uniform single pattern of Q-wave distribution.
Double‐negative feedback loop between MicroRNA‐422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis
Authors: Jin Zhang, Yun Yang, Tian Yang, Shengxian Yuan, Ruoyu Wang, Zeya Pan, Yuan Yang, Gang Huang, Fangming Gu, Beige Jiang, Chuan Lin, Weiping Zhou
Journal: Hepatology (2014)

Growing evidence indicates that the aberrant expression of microRNAs (miRNAs) contributes to tumor development; however, the function of miRNAs in human hepatocellular carcinoma (HCC) remains largely undefined. In this study, we report that microRNA‐422a (miR‐422a) is significantly down‐regulated in HCC tumor samples and cell lines compared with normal controls, and its expression level is negatively correlated with pathological grading, recurrence, and metastasis. The restoration of miR‐422a expression in HCC tumor cells significantly inhibited cell proliferation and migration in vitro . At the same time, the overexpression of miR‐422a in HCC tumor cells significantly inhibits tumor growth and liver metastasis in xenograft tumor models. A mechanistic study identified three genes, forkhead box G1 (FOXG1), FOXQ1, and FOXE1, as miR‐422a targets in the regulation of HCC development. We also investigated the function of the three targets themselves in HCC tumorigenesis using RNAi manipulation and demonstrated that the knockdown of these targets led to significant inhibition of tumor cell proliferation and migration both in vitro and in vivo . More interestingly, a potential miR‐422a promoter region was identified. Both the promoter activity and miR‐422a expression were negatively regulated by the three targets, indicating that a double‐negative feedback loop exists between miR‐422a and its targets. Moreover, we explored the therapeutic potential of miR‐422a in HCC treatment and found that the therapeutic delivery of miR‐422a significantly inhibited tumor development in a xenograft tumor model and a diethylnitrosamine‐induced primary HCC model. Conclusion : Our findings show the critical roles of miR‐422a and its targets—FOXG1, FOXQ1, and FOXE1—in the regulation of HCC development and provide new potential candidates for HCC therapy. (H epatology 2015;61:561‐573)
Predominant antitumor effects by fully human anti-TRAIL-receptor2 (DR5) monoclonal antibodies in human glioma cells in vitro and in vivo
Authors: M. Nagane, S. Shimizu, E. Mori, S. Kataoka, Y. Shiokawa
Journal: Neuro-Oncology (2010)

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2 L) preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, thereby being investigated as a potential agent for cancer therapy. Here, we applied fully human anti-human TRAIL receptor monoclonal antibodies (mAbs) to specifically target one of death receptors for TRAIL in human glioma cells, which could also reduce potential TRAIL-induced toxicity in humans. Twelve human glioma cell lines treated with several fully human anti-human TRAIL receptor mAbs were sensitive to only anti-DR5 mAbs, whereas they were totally insensitive to anti-DR4 mAb. Treatment with anti-DR5 mAbs exerted rapid cytotoxicity and lead to apoptosis induction. The cellular sensitivity was closely associated with cell-surface expression of DR5. Expression of c-FLIPL, Akt, and Cyclin D1 significantly correlated with sensitivity to anti-DR5 mAbs. Primary cultures of glioma cells were also relatively resistant to anti-DR5 mAbs, exhibiting both lower DR5 and higher c-FLIPL expression. Downregulation of c-FLIPL expression resulted in the sensitization of human glioma cells to anti-DR5 mAbs, whereas overexpression of c-FLIPL conferred resistance to anti-DR5 mAb. Treatment of tumor-burden nude mice with the direct agonist anti-DR5 mAb KMTR2 significantly suppressed growth of subcutaneous glioma xenografts leading to complete regression. Similarly, treatment of nude mice bearing intracerebral glioma xenografts with KMTR2 significantly elongated lifespan without tumor recurrence. These results suggest that DR5 is the predominant TRAIL receptor mediating apoptotic signals in human glioma cells, and sensitivity to anti-DR5 mAbs was determined at least in part by the expression level of c-FLIPL and Akt. Specific targeting of death receptor pathway through DR5 using fully human mAbs might provide a novel therapeutic strategy for intractable malignant gliomas.
Sustained efficacy up to 4·5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial
Authors: Diane M Harper, Eduardo L Franco, Cosette M Wheeler, Anna-Barbara Moscicki, Barbara Romanowski, Cecilia M Roteli-Martins, David Jenkins, Anne Schuind, Sue Ann Costa Clemens, Gary Dubin
Journal: The Lancet (2006)
Glutathione conjugation of bromosulfophthalein in relation to hepatic glutathione content in the ratin vivo and in the perfused rat liver
Authors: Wilco C. A. Snel, Sandy K. Pang, Gerard J. MulderD
Journal: Hepatology (1995)

The relation between the rate of glutathione (GSH) conjugation and hepatic GSH content was studied in the rat in vivo and the in situ single-pass-perfused rat liver preparation with bromosulfophthalein (BSP) as the model substrate. The biliary excretion of the BSP-GSH conjugate and the hepatic GSH content were monitored simultaneously during intravenous infusions with BSP in the rat in vivo, and during liver perfusions with BSP-containing perfusion medium. Rats were pretreated with single or multiple doses of buthionine sulfoximine, an inhibitor of the de novo synthesis of GSH. Surprisingly, the excretion of the BSP-GSH conjugate was sustained at a high rate, despite a virtually complete depletion of hepatic GSH, both in the rat in vivo as well as in the perfused rat liver. The results indicate that GSH was still available for conjugation with BSP after apparent depletion of the hepatic GSH pool, presumably because of a residual de novo synthesis of GSH in the liver. Despite the multiple pretreatment with buthionine sulfoximine, the de novo GSH synthesis was sufficient to sustain a high rate of GSH conjugation of BSP. The cosubstrate-Km for GSH conjugation of BSP in the liver was estimated to be very small (approximately 0.3 mumol/g): the excretion rate of the BSP-GSH conjugate was only impaired at minimal hepatic GSH levels.
Production of Bone-resorbing Activity Corresponding to Interleukin-1α by Adult T-Cell Leukemia Cells in Humans
Authors: Fumihiko Shirakawa, Uki Yamashita, Yoshiya Tanaka, Kennichi Watanaba, Kanji Sato, Joji Haratake, Takashi Fujihira, Susumu Oda, Sumiya Eto
Journal: Cancer Research (1988)

Abstract  The physicochemical properties and relationship of bone-resorbing activity and interleukin 1 (IL-1) produced by adult T-cell leukemia (ATL) cells and cell line were studied in vitro. The culture supernatant of ATL cell line, MT2, and peripheral blood lymphocytes freshly obtained from ATL patients had both IL-1 activity detected by the stimulation of murine thymocyte-proliferative responses and bone-resorbing activity detected by the stimulation of 45Ca release from prelabeled murine fetal bones. By Sephacryl S-200 column chromatography, both activities were eluted as a single peak at approximately Mr 15,000. By the chromatofocusing technique, the isoelectric point values of both activities were estimated as pH 4.8 and 5.2. Furthermore, both activities were absorbed with rabbit anti-IL-1α antiserum, but not with anti-IL-1β antiserum. These results suggest that ATL cells and cell line produce bone-resorbing activity which corresponds to IL-1α and that this IL-1α is one of the most important causes of hypercalcemia in ATL patients.
Multi-tissue gene-expression analysis in a mouse model of thyroid hormone resistance
Authors: Lance D Miller, Peter McPhie, Hideyo Suzuki, Yasuhito Kato, Edison T Liu, Sheue-yann Cheng
Journal: Genome biology (2004)

Resistance to thyroid hormone (RTH) is caused by mutations of the thyroid hormone receptor beta (TRbeta) gene. To understand the transcriptional program underlying TRbeta mutant-induced phenotypic expression of RTH, cDNA microarrays were used to profile the expression of 11,500 genes in a mouse model of human RTH.We analyzed transcript levels in cerebellum, heart and white adipose tissue from a knock-in mouse (TRbetaPV/PV mouse) that harbors a human mutation (referred to as PV) and faithfully reproduces human RTH. Because TRbetaPV/PV mice have elevated thyroid hormone (T3), to define T3-responsive genes in the context of normal TRbeta, we also analyzed T3 effects in hyperthyroid wild-type gender-matched littermates. Microarray analysis revealed 163 genes responsive to T3 treatment and 187 genes differentially expressed between TRbetaPV/PV mice and wild-type littermates. Both the magnitude and gene make-up of the transcriptional response varied widely across tissues and conditions. We identified genes modulated in T3-dependent PV-independent, T3- and PV-dependent, and T3-independent PV-dependent pathways that illuminated the biological consequences of PV action in vivo. Most T3-responsive genes that were dysregulated in the heart and white adipose tissue of TRbetaPV/PV mice were repressed in T3-treated wild-type mice and upregulated in TRbetaPV/PV mice, suggesting the inappropriate activation of T3-suppressed genes in RTH.Comprehensive multi-tissue gene-expression analysis uncovered complex multiple signaling pathways that mediate the molecular actions of TRbeta mutants in vivo. In particular, the T3-independent mutant-dependent genomic response unveiled the contribution of a novel 'change-of-function' of TRbeta mutants to the pathogenesis of RTH. Thus, the molecular actions of TRbeta mutants are more complex than previously envisioned.