tbuckley/cabot-search huggingface dataset:
An association between maternal diet and colonic diverticulosis in an animal model.
Authors: L Wess, M Eastwood, A Busuttil, C Edwards, A Miller
Journal: Gut (1996)

BACKGROUND/AIMS: Maternal diet may have an effect on the health of the offspring in middle and later life. This study used the laboratory rat as an animal model to examine whether the fibre content of the maternal diet during pregnancy affected subsequent development of colonic diverticula in the offspring fed lifelong fibre deficient or higher fibre diets. METHODS: The parents of experimental animals were fed either a diet that was known to predispose to colonic diverticulosis or a control diet for one month prior to mating. The offspring were fed one of these diets for 18 months. The incidence of colonic diverticulosis, submucosal collagen content, collagen solubility in weak acid, and the composition of intestinal contents were then measured. RESULTS: Offspring of rats fed a higher fibre diet from higher fibre diet fed parents had 0% incidence of colonic diverticulosis. When offspring (regardless of parental diet) were fed a low fibre diet for life the acid solubility was lowered compared with rats fed lifelong higher fibre diet mean (SD) (0.044 (0.0007) v 0.073 (0.0015) sigmoid colon (ratio of soluble:insoluble collagen)); 21.1% had diverticulosis and there was reduced fibre fermentation. However, when the diet of the parents of the fibre deficient diet fed rats was considered, the animals whose mothers had a fibre deficient diet had lower acid solubility (0.032 (0.0007)) and an increased incidence of colonic diverticulosis (42.1%) than the animals fed a fibre deficient diet from higher fibre diet fed parents (p &lt; 0.01 in all instances). CONCLUSION: Maternal diet and the subsequent nutrition of the progeny seem to be of importance in the development of colonic diverticulosis in the rat.
Infectious disease surveillance and modelling across geographic frontiers and scientific specialties
Authors: Kamran Khan, Scott JN McNabb, Ziad A Memish, Rose Eckhardt, Wei Hu, David Kossowsky, Jennifer Sears, Julien Arino, Anders Johansson, Maurizio Barbeschi, Brian McCloskey, Bonnie Henry, Martin Cetron, John S Brownstein
Journal: The Lancet Infectious Diseases (2012)
Computer Based Guidance in the Modern Operating Room: A Historical Perspective
Authors: Frank Bova
Journal: IEEE Reviews in Biomedical Engineering (2010)

The past few decades have seen the introduction of many different and innovative approaches aimed at enhancing surgical technique. As microprocessors have decreased in size and increased in processing power, more sophisticated systems have been developed. Some systems have attempted to provide enhanced instrument control while others have attempted to provide tools for surgical guidance. These systems include robotics, image enhancements, and frame-based and frameless guidance procedures. In almost every case the system's design goals were achieved and surgical outcomes were enhanced, yet a vast majority of today's surgical procedures are conducted without the aid of these advances. As new tools are developed and existing tools refined, special attention to the systems interface and integration into the operating room environment will be required before increased utilization of these technologies can be realized.
Lipids in the Wrong Place: Visceral Fat and Nonalcoholic Steatohepatitis
Authors: Gianluca Perseghin
Journal: Diabetes Care (2011)

There is substantial evidence in both animal (1,2) and human models of lipodystrophy (3) that the accumulation of excessive fat in ectopic sites that normally lack adipose tissue, such as the skeletal muscle and the liver, may trigger whole-body insulin resistance. This article will review the evidence showing the condition of fatty liver as an independent and perhaps better indicator of disease than excessive accumulation of visceral adipose tissue.

On the basis of the hypothesis that a fatty liver may increase the risk of cardiovascular disease (CVD), this article will not only focus on the metabolic-related features, but also on the cardiovascular risk factors affecting individuals with fatty liver. The biomarkers of CVD will therefore be analyzed in patients with fatty livers. Finally, epidemiological evidence linking fatty liver to the development of type 2 diabetes and CVD will be given.

### Metabolic features of individuals with insulin impairment: what contributes more, fatty liver or visceral adipose tissue?

Nonalcoholic fatty liver disease (NAFLD) is often found together with insulin resistance syndrome (4,5) and is commonly found in those suffering from visceral adiposity (3,4). Multiple insulin-related metabolic abnormalities in both organs and tissues have been reported, including impaired insulin-mediated inhibition of hepatic glucose production in livers (4–8), impaired insulin-stimulated glucose metabolism in skeletal muscle tissue (4–9), and impaired insulin-dependent control of lipolysis in adipose tissue (4–10). These metabolic abnormalities are often present along with the increased visceral adipose tissue and a fatty liver. It is very difficult to determine the biological relevance of each anthropometric feature because they are so commonly found together in humans. Recent studies have shown that of these two indicators, i.e., intrahepatic fat content (IHF) and excess visceral adipose tissue, IHF is statistically a more relevant indicator than excess visceral adipose tissue. In insulin-treated type 2 diabetic patients, the IHF content was more …
Nylon adherent antigen-specific rosette-forming T cells.
Authors: R E Cone, R K Gershon, P W Askenase
Journal: The Journal of Experimental Medicine (1977)

Shortly after intravenous immunization of mice with heterologous erythrocytes (RBC) antigen-specific Thy 1+ cells which form rosettes with the immunizing RBC (thymic-derived lymphocytes-forming rosettes [T-RFC]) appear in the spleen. These T-RFC are much less stable than Thy 1- RFC (non-thymic-derived [B-RFC]) although most if not all of both classes of RFC adhere to nylon. T-RFC are induced with low doses of antigen (which fail to induce B-RFC) and are inhibited by higher antigen doses which are optimal for induction of B-RFC. Pretreatment of mice with cyclophosphamide prevents the high dose inhibition of T-RFC. Although there are many parallels between the production of T-RFC and delayed-type hypersensitivity (DTH) it is unlikely that the T-RFC are essential for DTH reactions since DTH can be transferred with cells which pass through nylon, and such cells are almost totally depleted of T-RFC. Thus immunization can lead to the production of large numbers of antigen-specific T-RFC whose functional role in the immune response is unknown. However, the characteristics of the T-RFC suggest that they may play an important role in amplification of suppressor cell activity.
Preclinical Evaluation of EC145, a Folate-<i>Vinca</i> Alkaloid Conjugate
Authors: Joseph A. Reddy, Ryan Dorton, Elaine Westrick, Alicia Dawson, Terri Smith, Le-Cun Xu, Marilynn Vetzel, Paul Kleindl, Iontcho R. Vlahov, Christopher P. Leamon
Journal: Cancer Research (2007)

Abstract We recently developed a new group of folate-conjugated Vinca alkaloids, one of which, EC145, emerged as a candidate for clinical development. Brief treatment of nude mice bearing ∼100 mm3 folate receptor-positive human xenografts led to complete response (CR) in 5/5 mice and cures (i.e., remission without a relapse for &amp;gt;90 days post-tumor implantation) in 4/5 mice. Multiple CRs and cures were also noted when EC145 was used to treat mice initially bearing tumors as large as 750 mm3. Likewise, complete cures (5/5) resulted following the treatment of an aggressive folate receptor–positive J6456 lymphoma model. The activity of EC145 was not accompanied by noticeable weight loss or major organ tissue degeneration. Furthermore, no significant antitumor activity (0/5 CR) was observed in EC145-treated animals that were co-dosed with an excess of a benign folate ligand, thus demonstrating the target-specific activity of EC145. The enhanced therapeutic index due to folate conjugation was also evidenced by the fact that the unconjugated drug (desacetylvinblastine monohydrazide) was found to be completely inactive when administered at nontoxic dose levels and only marginally active when given at highly toxic dose levels. Subsequent dose regimen studies confirmed that EC145 given on a more frequent, qdx5 schedule resulted in the most effective antitumor response as compared with an equivalent total dose given on thrice- or single-injection-per-week schedule. Taken together, these studies show that EC145 has significant antiproliferative activity and tolerability, thus lending support to an ongoing phase 1 trial for the treatment of advanced malignancies. [Cancer Res 2007;67(9):4434–42]
Carbapenems for the treatment of immunocompetent adult patients with nosocomial pneumonia
Authors: I. I. Siempos, K. Z. Vardakas, K. G. Manta, M. E. Falagas
Journal: European Respiratory Journal (2007)

The comparative effectiveness and safety of carbapenems with other β-lactams and fluoroquinolones for the empirical treatment of patients with hospital-acquired pneumonia remains controversial. In the present study, a meta-analysis of 12 relevant randomised controlled trials was performed. Overall, carbapenems were associated with lower mortality than fluoroquinolones or β-lactams, alone or in combination with aminoglycosides (odds ratio 0.72, 95% confidence interval 0.55–0.95). There was no difference between the compared antibiotics regarding treatment success (1.08, 0.91–1.29), microbiological success (1.04, 0.72–1.50) or development of adverse effects (0.81, 0.46–1.43). In the subset of patients with Pseudomonas aeruginosa pneumonia, carbapenems were associated with lower treatment success (0.42, 0.22–0.82) and lower eradication of P. strains (0.50, 0.24–0.89). Carbapenems are equivalent to fluoroquinolones or β-lactams, alone or in combination with aminoglycosides, for the empirical treatment of immunocompetent adult patients with hospital-acquired pneumonia. However, there is limited evidence, based predominantly on unblinded randomised controlled trials, that carbapenems are associated with lower mortality than the comparators; this association was not observed in a subset analysis of randomised controlled trials with a high methodological quality score. In patients with Pseudomonas aeruginosa pneumonia, carbapenems are associated with worse outcomes than the comparators.
Preferential nuclear compartmentalization of endogenous mink cell focus-forming-related retroviral transcripts.
Authors: M F Gourley, A M Krieg, A D Steinberg
Journal: The Journal of Experimental Medicine (1990)

Endogenous mink cell focus-forming (MCF)-like retroviral sequences in the murine genome are stable, inherited sequences analogous to other chromosomal genes. As such, it is thought that they are transcribed and translated in a manner analogous to other genes. However, when the SL12.4 CD4-, CD8- thymoma cell line was studied for nuclear/cytoplasmic distribution of endogenous MCF-related transcripts, there was a nuclear predominance. The great majority of full-length 8.4-kb endogenous MCF-related transcripts were nuclear. Even the smaller, spliced 3.0-kb transcripts were at least as prominent in the nucleus as the cytoplasm, whereas cellular RNA was 80% cytoplasmic and other cellular transcripts were represented in the cytoplasm to a much greater extent than the nucleus. Size cannot fully account for the nuclear presence of MCF-related endogenous transcripts, because the 3.0-kb MCF transcripts occurred in the nucleus to a much greater relative extent than 3.8-kb c-myb transcripts. These studies point to retroviral-like structures of these transcripts as influencing their intracellular compartmentalization.
Recurrent Horizontal Transfer of Bacterial Toxin Genes to Eukaryotes
Authors: Y. Moran, D. Fredman, P. Szczesny, M. Grynberg, U. Technau
Journal: Molecular Biology and Evolution (2012)

In this work, we report likely recurrent horizontal (lateral) gene transfer events of genes encoding pore-forming toxins of the aerolysin family between species belonging to different kingdoms of life. Clustering based on pairwise similarity and phylogenetic analysis revealed several distinct aerolysin sequence groups, each containing proteins from multiple kingdoms of life. These results strongly support at least six independent transfer events between distantly related phyla in the evolutionary history of one protein family and discount selective retention of ancestral genes as a plausible explanation for this patchy phylogenetic distribution. We discuss the possible roles of these proteins and show evidence for a convergent new function in two extant species. We hypothesize that certain gene families are more likely to be maintained following horizontal gene transfer from commensal or pathogenic organism to its host if they 1) can function alone; and 2) are immediately beneficial for the ecology of the organism, as in the case of pore-forming toxins which can be utilized in multicellular organisms for defense and predation.
The Androgen Axis in Recurrent Prostate Cancer
Authors: James L. Mohler, Christopher W. Gregory, O. Harris Ford, Desok Kim, Catharina M. Weaver, Peter Petrusz, Elizabeth M. Wilson, Frank S. French
Journal: Clinical Cancer Research (2004)

Abstract Purpose. Prostate cancer that recurs during androgen deprivation therapy is referred to as androgen-independent. High levels of expression of androgen receptor and androgen receptor-regulated genes in recurrent prostate cancer suggest a role for androgen receptor and its ligands in prostate cancer recurrence. Experimental Design. Recurrent prostate cancer specimens from 22 men whose prostate cancer recurred locally during androgen deprivation therapy and benign prostate specimens from 48 men who had received no prior treatment were studied. Androgen receptor expression was measured using monoclonal antibody and automated digital video image analysis. Tissue androgens were measured using radioimmunoassay. Results. Epithelial nuclei androgen receptor immunostaining in recurrent prostate cancer (mean optical density, 0.284 ± SD 0.115 and percentage positive nuclei, 83.7 ± 11.6) was similar to benign prostate (mean optical density, 0.315 ± 0.044 and percentage positive nuclei, 77.3 ± 13.0). Tissue levels of testosterone were similar in recurrent prostate cancer (2.78 ± 2.34 pmol/g tissue) and benign prostate (3.26 ± 2.66 pmol/g tissue). Tissue levels of dihydrotestosterone, dehydroepiandrosterone, and androstenedione were lower (Wilcoxon, P = 0.0000068, 0.00093, and 0.0089, respectively) in recurrent prostate cancer than in benign prostate, and mean dihydrotestosterone levels, although reduced, remained 1.45 nm. Androgen receptor activation in recurrent prostate cancer was suggested by the androgen-regulated gene product, prostate-specific antigen, at 8.80 ± 10.80 nmol/g tissue. Conclusions. Testosterone and dihydrotestosterone occur in recurrent prostate cancer tissue at levels sufficient to activate androgen receptor. Novel therapies for recurrent prostate cancer should target androgen receptor directly and prevent the formation of androgens within prostate cancer tissue.
MRI assessment of right atrial volume and function in pulmonary hypertension
Authors: Thomas Sproson, Andrew Swift, Smitha Rajaram, David Capener, David Kiely, Robin Condliffe, Charlie Elliot, Jim Wild
Journal: European Respiratory Journal (2012)

Background   The role of the right atrium (RA) is under-researched within pulmonary vascular disease. The aim was to investigate the use of magnetic resonance imaging (MRI) derived RA volume and function in the diagnosis and management of pulmonary hypertension (PH).   Methods   Patients attending the pulmonary vascular clinic were retrospectively analysed. Inclusion criteria were cardiac MRI and right heart catheterisation within 48 hours.  Standard cardiac-gated balanced steady state free precession sequences were used. End-systolic volume (ESV) and diastolic volume (EDV) were calculated using Simpson9s numeric integral applied to manual RA area tracings in the 4-chamber stack sequence.   Results   71 PH patients were included, mean age was 65 ± 15.5 years and 67.6% (48) were female.  RA function was shown to correlate with cardiac index (R=0.69) and mean RA pressure (R=-0.64), P   RA ejection fraction ≤ 28.3% was shown to have moderate sensitivity (80%) and specificity (71%) for identifying patients who met diagnostic criteria. RA ESV ≥48.0 ml was useful (sensitivity 96%, specificity 78%) for identifying patients with a high RA pressure, see figure 1.   Conclusion   RA pressure is a known prognostic indicator; this study suggests high RA pressure can be detected using cardiac MRI. RA function has been shown to correlate well with haemodynamic measurements and clinical data. Further research into the natural history of RA volume change in PH is needed.
Predicting Relapse in Patients With Medulloblastoma by Integrating Evidence From Clinical and Genomic Features
Authors: Pablo Tamayo, Yoon-Jae Cho, Aviad Tsherniak, Heidi Greulich, Lauren Ambrogio, Netteke Schouten-van Meeteren, Tianni Zhou, Allen Buxton, Marcel Kool, Matthew Meyerson, Scott L. Pomeroy, Jill P. Mesirov
Journal: Journal of Clinical Oncology (2011)

Purpose Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis. Patients and Methods A Bayesian cumulative log-odds model of outcome was developed from a training cohort of 96 children treated for medulloblastoma, starting with the evidence provided by clinical features of metastasis and histology (model A) and incrementally adding the evidence from gene-expression–derived features representing disease subtype–independent (model B) and disease subtype–dependent (model C) pathways, and finally high-level copy-number genomic abnormalities (model D). The models were validated on an independent test cohort (n = 78). Results On an independent multi-institutional test data set, models A to D attain an area under receiver operating characteristic (au-ROC) curve of 0.73 (95% CI, 0.60 to 0.84), 0.75 (95% CI, 0.64 to 0.86), 0.80 (95% CI, 0.70 to 0.90), and 0.78 (95% CI, 0.68 to 0.88), respectively, for predicting relapse versus no relapse. Conclusion The proposed models C and D outperform the current clinical classification schema (au-ROC, 0.68), our previously published eight-gene outcome signature (au-ROC, 0.71), and several new schemas recently proposed in the literature for medulloblastoma risk stratification.
Etretinate Blood Levels in Monitoring of Compliance and Contamination in a Chemoprevention Trial
Authors: G. P. Browman, A. Arnold, L. Booker, B. Johnstone, P. Skingley, M. N. Levine
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Etretinate Blood Levels in Monitoring of Compliance and Contamination in a Chemoprevention Trial Get access G. P. Browman, G. P. Browman * The Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Hamilton Civic and St. Joseph's Hospitals, McMaster University; and the Ontario Clinical Oncology Group *Correspondence to: Dr. G. P. Browman, Hamilton Regional Cancer Centre, 711 Concession St., Hamilton, Ontario, L8V 1C3, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Arnold, A. Arnold The Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Hamilton Civic and St. Joseph's Hospitals, McMaster University; and the Ontario Clinical Oncology Group Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Booker, L. Booker The Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Hamilton Civic and St. Joseph's Hospitals, McMaster University; and the Ontario Clinical Oncology Group Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Johnstone, B. Johnstone The Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Hamilton Civic and St. Joseph's Hospitals, McMaster University; and the Ontario Clinical Oncology Group Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Skingley, P. Skingley The Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Hamilton Civic and St. Joseph's Hospitals, McMaster University; and the Ontario Clinical Oncology Group Search for other works by this author on: Oxford Academic PubMed Google Scholar M. N. Levine M. N. Levine The Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Hamilton Civic and St. Joseph's Hospitals, McMaster University; and the Ontario Clinical Oncology Group Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 10, 22 May 1989, Pages 795–798, https://doi.org/10.1093/jnci/81.10.795 Published: 22 May 1989 Article history Received: 08 December 1988 Revision received: 21 February 1989 Accepted: 24 February 1989 Published: 22 May 1989
Voltage and Activation Mapping
Authors: Natasja M.S. de Groot, Martin J. Schalij, Katja Zeppenfeld, Nico A. Blom, Enno T. Van der Velde, Ernst E. Van der Wall
Journal: Circulation (2003)

Endocardial mapping is mandatory before radiofrequency catheter ablation (RFCA). Mapping can be performed with either unipolar or bipolar recordings. Impact of the recording technique used was studied in patients with and without structural heart disease using the 3D electroanatomic CARTO mapping system.Patients (n=44; 16 males; age 43+/-16 years) referred for RFCA of atrial flutter (AFL, n=18), focal atrial tachycardia (FAT, n=4), AV nodal reentrant tachycardia (AVNRT, n=5), or scar-related atrial reentrant tachycardia (IART, n=17) were studied. Voltage and activation maps were constructed. Unipolar and bipolar voltage distribution in the different groups was studied to establish a cutoff voltage value to facilitate delineation of scar tissue. Electrograms were recorded during tachycardia (FAT: n=246, cycle length [CL]=449+/-35 ms; AVNRT: n=182, CL=359+/-47 ms; AFL: n=1164, CL=255+/-56 ms; IART: n=2431, CL=280+/-74 ms). Unipolar voltages were greater than bipolar voltages (P<0.001). Unipolar voltages < or =1.0 mV were equally distributed in both AFL and IART patients. Bipolar voltages < or =0.1 mV were only found in patients with IART, and subsequently 0.1 mV was used as the cutoff value to delineate scar tissue. No unipolar cutoff value could be established. Timing of unipolar and bipolar local activation was correlated in all patient groups.The recording technique used has considerable impact on reconstruction of reentrant pathways and on the outcome of RFCA. In general, unipolar and bipolar recordings provide complementary information; however, only bipolar recordings allow voltage-based scar tissue delineation in patients with congenital heart disease.