tbuckley/cabot-search huggingface dataset:
Antimetastatic Effect of Salvicine on Human Breast Cancer MDA-MB-435 Orthotopic Xenograft Is Closely Related to Rho-Dependent Pathway
Authors: Jing-Yu Lang, Hua Chen, Jin Zhou, Yi-Xiang Zhang, Xiong-Wen Zhang, Mei-Hong Li, Li-Ping Lin, Jin-Sheng Zhang, Michael P. Waalkes, Jian Ding
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Salvicine is a novel DNA topoisomerase II inhibitor with potent anticancer activity. In present study, the effect of salvicine against metastasis is evaluated using human breast carcinoma orthotopic metastasis model and its mechanism is further investigated both in animal and cellular levels. Experimental Design: The MDA-MB-435 orthotopic xenograft model was applied to detect the antimetastatic effect of salvicine. Potential target candidates were detected and analyzed by microarray technology. Candidates were verified and explored by reverse transcription-PCR and Western blot. Salvicine activities on stress fiber formation, invasion, and membrane translocation were further investigated by immunofluorescence, invasion, and ultracentrifugal assays. Results: Salvicine significantly reduced the lung metastatic foci of MDA-MB-435 orthotopic xenograft, without affecting primary tumor growth obviously. A comparison of gene expression profiles of primary tumors and lung metastatic focus between salvicine-treated and untreated groups using the CLOTECH Atlas human Cancer 1.2 cDNA microarray revealed that genes involved in tumor metastasis, particularly those closely related to cell adhesion and motility, were obviously down-regulated, including fibronectin, integrin α3, integrin β3, integrin β5, FAK, paxillin, and RhoC. Furthermore, salvicine significantly down-regulated RhoC at both mRNA and protein levels, greatly inhibited stress fiber formation and invasiveness of MDA-MB-435 cells, and markedly blocked translocation of both RhoA and RhoC from cytosol to membrane. Conclusion: The unique antimetastatic action of salvicine, particularly its specific modulation of cell motility in vivo and in vitro, is closely related to Rho-dependent signaling pathway.
Relations of Left Ventricular Mass to Fat-Free and Adipose Body Mass
Authors: Hans W. Hense, Heribert Schunkert
Journal: Circulation (1999)

We read with great interest the recent article by Bella et al, 1 which reported as its principal finding that fat-free mass (FFM) was the strongest correlate of left ventricular mass (LVM) in a large cross-sectional study of Native Americans (the Strong Heart Study).Their article agrees in many aspects with our report of a large Caucasian adult population survey (the MONICA Augsburg study), which was published earlier in 1998. 2 Body impedance analysis was used in both studies to determine the FFM.Interestingly, despite the use of different equipment for body impedance analysis, different equations, and the major differences in the anthropometric characteristics of the 2 populations, the results of these 2 investigations are impressively consistent.Our study supports the principal finding of Bella et al 1 ; we could demonstrate that substantial reductions in the association of adiposity with ventricle mass were obtained by indexing LVM to FFM.This reduction was significantly stronger than that observed by indexing for height, various exponentials of height, or body surface.However, a remarkable difference existed between the 2 studies.The sex difference in heart mass, which is traditionally reported as higher in adult men than women, was almost completely eliminated when LVM was indexed to FFM in the MONICA Augsburg study (men, 3.4 g/kg; women, 3.3 g/kg; Pϭ0.06). 2 Bella et al 1 present sex-specific criteria for LV hypertrophy based on the LVM/FFM ratio that were even lower for men (3.6 g/kg) than for women (4.4 g/kg [according to Table 6] or 4.86 g/kg [according to the text on pages 2541 and 2542]).This could indicate that in the Strong Heart Study, the whole distribution of the LVM/FFM values of women shifted to values that were higher than those in men.Alternatively, the inverted order of the partition values may be due to the comparatively few subjects in the healthy reference population and reflect the sensitivity of the 97.5th percentile partition criteria to extreme values in such a situation.A more detailed description of the Strong Heart population including, for example, mean values of LVM and LVM/FFM, would help to elucidate these associations and resolve open questions.It may help to further support the notion that fat-free body mass is the dominating anthropometric determinant of LVM in adult men and women.
Undermining the foundations: Questioning the basic notions of associationism and mental representation
Authors: Ezequiel Morsella, Travis A. Riddle, John A. Bargh
Journal: Behavioral and Brain Sciences (2009)

Abstract Perhaps the time has come to re-examine the basic notions of cognitive science. Together with previous challenges against associationism, the target article should be viewed as a call to arms to re-evaluate the empirical basis for contemporary conceptualizations of human learning and the notion of “mental representation,” a concept that has become too imprecise for describing the elements of cognition.
Effectiveness of counselling patients on physical activity in general practice: cluster randomised controlled trial
Authors: C R. Elley
Journal: BMJ (2003)

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
Augmented Expression and Activity of Extracellular Matrix-Degrading Enzymes in Regions of Low Endothelial Shear Stress Colocalize With Coronary Atheromata With Thin Fibrous Caps in Pigs
Authors: Yiannis S. Chatzizisis, Aaron B. Baker, Galina K. Sukhova, Konstantinos C. Koskinas, Michail I. Papafaklis, Roy Beigel, Michael Jonas, Ahmet U. Coskun, Benjamin V. Stone, Charles Maynard, Guo-Ping Shi, Peter Libby, Charles L. Feldman, Elazer R. Edelman, Peter H. Stone
Journal: Circulation (2011)

Background- The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata. Methods and Results- Intravascular ultrasound-based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet. Local endothelial shear stress was calculated in plaque-free subsegments of interest (n=142) with computational fluid dynamics. At week 30, the coronary arteries (n=31) were harvested and the same subsegments were identified. The messenger RNA and protein expression and elastolytic activity of selected elastases and their endogenous inhibitors were assessed. Subsegments with low preceding endothelial shear stress at week 23 showed reduced endothelial coverage, enhanced lipid accumulation, and intense infiltration of activated inflammatory cells at week 30. These lesions showed increased expression of messenger RNAs encoding matrix metalloproteinase-2, -9, and -12, and cathepsins K and S relative to their endogenous inhibitors and increased elastolytic activity. Expression of these enzymes correlated positively with the severity of internal elastic lamina fragmentation. Thin-capped atheromata developed in regions with lower preceding endothelial shear stress and had reduced endothelial coverage, intense lipid and inflammatory cell accumulation, enhanced messenger RNA expression and elastolytic activity of MMPs and cathepsins, and severe internal elastic lamina fragmentation. Conclusions- Low endothelial shear stress induces endothelial discontinuity and accumulation of activated inflammatory cells, thereby augmenting the expression and activity of elastases in the intima and shifting the balance with their inhibitors toward matrix breakdown. Our results provide new insight into the mechanisms of regional formation of plaques with thin fibrous caps.
Meningitis in infancy in England and Wales: follow up at age 5 years
Authors: H. Bedford, J. de Louvois, S. Halket, C. Peckham, R. Hurley, D. Harvey
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To describe important sequelae occurring among a cohort of children aged 5 years who had had meningitis during the first year of life and who had been identified by a prospective national study of meningitis in infancy in England and Wales between 1985 and 1987. <b>Design:</b> Follow up questionnaires asking about the children9s health and development were sent to general practitioners and parents of the children and to parents of matched controls. The organism that caused the infection and age at infection were also recorded. <b>Setting:</b> England and Wales. <b>Participants:</b> General practitioners and parents of children who had had meningitis before the age of 1 year and of matched controls. <b>Main outcome measures:</b> The prevalence of health and developmental problems and overall disability among children who had had meningitis compared with controls. <b>Results:</b> Altogether, 1584 of 1717 (92.2%) children who had had meningitis and 1391 of 1485 (93.6%) controls were successfully followed up. Among children who survived to age 5 years 247 of 1584 (15.6%) had a disability; there was a 10-fold increase in the risk of severe or moderate disability at 5 years of age among children who had had meningitis (relative risk 10.3, 95% confidence interval 6.7 to 16.0, P&lt;0.001). There was considerable variation in the rates of severe or moderate disability in children infected with different organisms. <b>Conclusion:</b> The long term consequences of having meningitis during the first year of life are significant: 32 of 1717 (1.8%) children died within five years. Not only did almost a fifth of children with meningitis have a permanent, severe or moderately severe disability, but subtle deficits were also more prevalent. <h3>What is already known on this topic</h3> Meningitis in infancy is associated with important long term consequences There is considerable variation in outcome depending on which organism caused the infection <h3>What this study adds</h3> This follow up study of 1717 children who had meningitis in infancy found that they had a 10-fold increase in risk of severe or moderate disabilities at age 5 years compared with children in the control group The outcome of having meningitis was associated with the age at infection, and children who had meningitis in the neonatal period were more likely to have health and development problems than those older than 1 month Subtle deficits, such as middle ear disease and visual and behavioural problems, were more prevalent among children who had had meningitis in infancy
Inhibition of p38 MAP kinase pathway induces apoptosis and prevents Epstein Barr virus reactivation in Raji cells exposed to lytic cycle inducing compounds
Authors: Giulia Matusali, Giuseppe Arena, Alessandra De Leo, Livia Di Renzo, Elena Mattia
Journal: Molecular Cancer (2009)

Abstract Background EBV lytic cycle activators, such as phorbol esters, anti-immunoglobulin, transforming growth factor β (TGFβ), sodium butyrate, induce apoptosis in EBV-negative but not in EBV-positive Burkitt's lymphoma (BL) cells. To investigate the molecular mechanisms allowing EBV-infected cells to be protected, we examined the expression of viral and cellular antiapoptotic proteins as well as the activation of signal transduction pathways in BL-derived Raji cells exposed to lytic cycle inducing agents. Results Our data show that, following EBV activation, the latent membrane protein 1 (LMP1) and the cellular anti-apoptotic proteins MCL-1 and BCL-2 were quickly up-regulated and that Raji cells remained viable even when exposed simultaneously to P(BU) 2 , sodium butyrate and TGFβ. We report here that inhibition of p38 pathway, during EBV activation, led to a three fold increment of apoptosis and largely prevented lytic gene expression. Conclusion These findings indicate that, during the switch from the latent to the lytic phase of EBV infection, p38 MAPK phosphorylation plays a key role both for protecting the host cells from apoptosis as well as for inducing viral reactivation. Because Raji cells are defective for late antigens expression, we hypothesize that the increment of LMP1 gene expression in the early phases of EBV lytic cycle might contribute to the survival of the EBV-positive cells.
Immunoglobulin light chain amyloidosis: 2011 update on diagnosis, risk‐stratification, and management
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2010)

Immunoglobulin (Ig) light chain amyloidosis is a clonal but nonproliferative plasma cell disorder in which fragments of an Ig light chain are deposited in tissues. The clinical features depend on the organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, and peripheral/autonomic neuropathy. Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. N-terminal pro-brain natriuretic peptide and serum troponin T values are used to classify patients into three groups of approximately equal size; median survivals are 26.4, 10.5, and 3.5 months, respectively. All patients with a visceral amyloid syndrome require therapy to prevent deposition of amyloid in other viscera and to prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is a preferred technique, but only 20% of patients are eligible. Requirements for safe SCT include mild or no cardiac involvement, troponin T value <0.06 ng/mL, age younger than 70 years, <3 organs involved, and serum creatinine value ≤1.7 mg/dL. Nontransplant candidates can be offered melphalan-dexamethasone. Pomalidomide appears to have activity, as do other combinations of chemotherapy with agents such as cyclophosphamide-thalidomide-dexamethasone, bortezomib-dexamethasone, and melphalan-prednisone-lenalidomide. Late diagnosis remains a major obstacle to initiating effective therapy when organ dysfunction is still recoverable. Recognizing the presenting syndromes is necessary for improvement in survival.
Repeated transarterial chemoembolization (TACE) in the treatment of patients with liver metastases of breast cancer: Local tumor control and survival
Authors: T. J. Vogl, R. Bauer, K. Eichler, T. Gruber
Journal: Journal of Clinical Oncology (2008)

549 Background: To evaluate the tolerability and efficacy of transarterial chemoembolization (TACE) using different drug combinations in the treatment of liver metastases in breast cancer patients concerning local tumor control and survival. Methods: 217 patients with unresectable hepatic metastases of breast cancer were repeatedly treated with TACE in 4-week intervals. In total, 1,310 chemoembolizations were performed with a mean of 6 sessions per patient. At the time of the first chemoembolization, the average age of the patients was 52.2 years (range, 29–81 years). While 62.2% of the patients showed multiple metastases, 8.8% had 1 metastasis, 9.2% had 2 metastases and 19.8% had 3 to 4 metastases. The local chemotherapy protocol consisted of mitomycin C only (8 mg/m² b.s.) (n=76), mitomycin C with gemcitabine (n=110), and gemcitabine only (1,000 mg/m2 b.s.) (n=21). Embolization was performed with lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated by magnetic resonance imaging (MRI). The change in size was calculated and the response was evaluated according to the RECIST criteria. Results: For all protocols local tumor control evaluation resulted in a partial response in 13.4% of cases, stable disease 50.2%, and progressive disease 36.4%. During the course of therapy the clinical situation changed, 142 patients (65.4%) were treated palliatively, 34 patients (15.7%) symptomatically, and 41 patients (18.9%) neoadjuvantly. The 1-year survival rate after TACE was 68%, but the 2-year survival rate had been reduced to 43%. The median survival time from the date of diagnosis was 8.2 years (according to Kaplan-Meier), and from the start of TACE treatment 19 months. Median survival time of patients after TACE therapy with mitomycin C only was 13.3 months, with gemcitabine only 11 months, and with combined mitomycin C/gemcitabine 25.4 months. The median survival time of the palliative group was 19 months, symptomatic group 6 months, and neoadjuvant group 44.3 months. Conclusions: TACE is an optional minimal-invasive therapy for treatment of liver metastases in breast cancer patients with superior results for the combination group. No significant financial relationships to disclose.
Government research will assess impact of minimum price for alcohol
Authors: A. O'Dowd
Journal: BMJ (2010)

Aim: The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. Materials and methods: We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n=3,890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Results: Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Conclusions: Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.
Predicting Macro- and Microvascular Complications in Type 2 Diabetes
Authors: Shiro Tanaka, Sachiko Tanaka, Satoshi Iimuro, Hidetoshi Yamashita, Shigehiro Katayama, Yasuo Akanuma, Nobuhiro Yamada, Atsushi Araki, Hideki Ito, Hirohito Sone, Yasuo Ohashi
Journal: Diabetes Care (2013)

OBJECTIVE To develop and validate a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years. End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for prediction. The predictive accuracy of the calculated 5-year risks was cross-validated. RESULTS Sex, age, HbA1c, years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine. The observed-to-predicted (O/P) ratios for each event were between 0.93 and 1.08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events. In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0.30 for CHD and 0.72 for stroke). C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0.725, 0.696, and 0.767) but moderate for stroke and progression of retinopathy (0.636 and 0.614). By combining macro- and microvascular risks, the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7% (P = 0.02). CONCLUSIONS The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations.
DEATH DUE TO INJECTION OF PYROGEN-CONTAINING FLUIDS DURING INSULIN SHOCK THERAPY
Authors: GEORGE G. MERRILL
Journal: American Journal of Psychiatry (1954)

A hitherto unmentioned complication of insulin shock therapy is febrile reaction from injection of pyrogen-containing glucose solutions to terminate the coma. A fatal case, with some nonfatal ones resulting from injection with the same solution, is described to call attention to the danger of such pyrogenic reactions.
1-antitrypsin deficiency: a report from the 2nd meeting of the Alpha One International Registry, Rapallo (Genoa, Italy), 2001
Authors: M. Luisetti, M. Miravitlles, R.A. Stockley
Journal: European Respiratory Journal (2002)

The Alpha One International Registry is a scientific foundation established to comply with a World Health Organization recommendation to develop a multinational registry of α 1 -antitrypsin deficiency, with the aim of creating a common database of subjects recognised in a standardised way. A commitment of the Alpha One International Registry members, belonging to 15 national registries, is to meet every 2 yrs in an open scientific conference to provide a scientific and clinical update on the deficiency. The second Alpha One International Registry meeting was held in Rapallo (Genoa, Italy) on September 27th–28th, 2001, and 26 speakers provided an exhaustive overview of all aspects of α 1 -antitrypsin deficiency, including epidemiology, genetics, biochemistry, associated conditions, established and novel therapeutic options, and markers of efficacy. In the framework of a rare and often under-recognised condition, this meeting is likely to be central to improving understanding and increasing awareness of α 1 -antitrypsin deficiency.