tbuckley/cabot-search huggingface dataset:
High Efficacy of a <i>Listeria</i>-Based Vaccine against Metastatic Breast Cancer Reveals a Dual Mode of Action
Authors: Sun Hee Kim, Francisco Castro, Yvonne Paterson, Claudia Gravekamp
Journal: Cancer Research (2009)

Most cancer vaccines induce CTL responses to tumor-associated antigens (TAA). Killing of tumor cells occurs through TAA-specific CTL-mediated cytolysis. Here, we show that one preventive followed by two therapeutic immunizations with an attenuated Listeria monocytogenes (LM)-based vaccine eradicates all metastases and almost the entire primary tumor in the syngeneic, aggressive mouse breast tumor model 4T1. We provide strong evidence that this is due to the combined result of direct kill by Listeria infecting the tumor cells and by CTL responses against Listeria antigens. We showed by electron microscopy that LM expressing truncated listeriolysin O (LLO) and amino acid fragments 311 to 660 of TAA Mage-b (LM-LLO-Mage-b(311-660)) and the control strain LM-LLO infect tumor cells in vitro and in vivo. In vitro data indicate that tumor cell death occurs through activation of NADP(+) oxidase and increased intracellular Ca(2+) levels, both resulting in the production of high ROS levels. Because both LM-LLO and LM-LLO-Mage-b(311-660) showed equally strong efficacies in vivo, we concluded that LM-LLO was crucial and Mage-b was of less importance. We found strong CTL responses to LM-LLO in the spleen, and depletion of CD8 T cells in vivo resulted in significant tumor regrowth (52%) in LM-LLO-vaccinated mice, indicating that LM-LLO-specific CTL indeed partially contributed to tumor cell kill in vivo. This dual mode of action of a Listeria-based vaccine has not been described before and may provide new directions in the development of more effective vaccines against metastatic breast cancer.
Influence of appendectomy by maze procedure on the atrial natriuretic peptide (ANP) secretion and body fluid retention
Authors: Fumiki Yoshihara, Toshio Nishikimi, Yoshio Kosakai, Fumitaka Isobe, Yoshihiko Saito, Kenji Kangawa, Hisayuki Matsuo, Hiroaki Matsuoka, Shuichi Takishita, Yasunaru Kawashima
Journal: Journal of the American College of Cardiology (1996)
Molecular phylogeny of the volvocine flagellates.
Authors: A Larson, M M Kirk, D L Kirk
Journal: Molecular Biology and Evolution (1992)

Phylogenetic studies of approximately 2,000 bases of sequence from the large and small nuclear-encoded ribosomal RNAs are used to investigate the origins of the genus Volvox. The colonial and multicellular genera currently placed in the family Volvocaceae form a monophyletic group that is significantly closer phylogenetically to Chlamydomonas reinhardtii than it is to the other unicellular green flagellates that were tested, including Chlamydomonas eugametos, Chlorella pyrenoidosa, and Haematococcus lacustris. Statistical analysis of 251 phylogenetically informative nucleotide positions rejects the "volvocine lineage" hypothesis, which postulates a monophyletic evolutionary progression from unicellular organisms (such as Chlamydomonas), through colonial organisms (e.g., Gonium, Pandorina, Eudorina, and Pleodorina) demonstrating increasing size, cell number, and tendency toward cellular differentiation, to multicellular organisms having fully differentiated somatic and reproductive cells (in the genus Volvox). The genus Volvox appears not to be monophyletic. Volvox capensis falls outside a lineage containing other representatives of Volvox (V. aureus, V. carteri, and V. obversus), and both of these Volvox lineages are more closely related to certain colonial genera than they are to each other. This implies either a diphyletic origin of Volvox from different colonial volvocacean ancestors, a phylogenetic derivation of some of the colonial genera from a multicellular (i.e., Volvox) ancestor, or both. Considered together with previously published observations, these results suggest that the different levels of organizational and developmental complexity found in the Volvocaceae represent alternative stable states, among which evolutionary transitions have occurred several times during the phylogenetic history of this group.
Right aortic arch and Kommerell's diverticulum.
Authors: P H Wong, J W Lee
Journal: Thorax (1983)

Right aortic arch anomalies seldom produce symptoms in adult life.This report describes a patient with a right aortic arch, an aberrant left subclavian artery, and a large Kom- merell's diverticulum, which caused oesophageal compression in her third decade.We discuss the surgical approach to this uncommon anomaly. Case reportA 23-year-old woman was in good health until one year before admission, when she began to notice a sensation of obstruction behind the manubrium after having solid food and occasional choking after drinking.By the time of admission she had lost 10 kg.There were no respiratory symptoms.Examination did not show any abnormal physical signs and the blood pressure was the same in both arms.Routine haematological and biochemical investigations gave normal results, and the electrocardiogram was also normal.A chest radiograph was normal except for a right
Babesiosis in man.
Authors: W S Symmers
Journal: BMJ (1979)

<h3>Objective</h3> The difficulty in accurately assessing distance visual acuity (VA) at home limits the usefulness of remote consultation in ophthalmology. A novel web application, DigiVis, enables automated VA self-assessment using standard digital devices. This study aims to compare its accuracy and reliability in children with clinical assessment by a healthcare professional. <h3>Methods and Analysis</h3> Children aged 4–10 years were recruited from a paediatric ophthalmology service. Those with VA worse than +0.8 logMAR (Logarithm of the Minimum Angle of Resolution) or with cognitive impairment were excluded. Bland-Altman statistics were used to analyse both the accuracy and repeatability of VA self-testing. User feedback was collected by questionnaire. <h3>Results</h3> The left eyes of 89 children (median 7 years) were tested. VA self-testing showed a mean bias of 0.023 logMAR, with a limit of agreement (LOA) of ±0.195 logMAR and an intraclass correlation coefficient (ICC) of 0.816. A second test was possible in 80 (90%) children. Test–retest comparison showed a mean bias of 0.010, with an LOA of ±0.179 logMAR, an ICC of 0.815 and a repeatability coefficient of 0.012. 96% of children rated the test as good or excellent, as did 99% of their parents. <h3>Conclusion</h3> Digital self-testing gave comparable distance VA assessments with clinical testing in children and was well accepted. Since DigiVis self-testing can be performed under direct supervision using medical video consultation software, it may be a useful tool to enable a proportion of paediatric eye clinic attendances to be moved online, reducing time off school and releasing face-to-face clinical capacity for those who need it.
Lung involvement in the multisystem syndrome CHARGE association
Authors: R Sporik, R Dinwiddie, C Wallis
Journal: European Respiratory Journal (1997)

The CHARGE association is a multisystem syndrome, with a wide range of phenotypic expression, causing mortality, especially in childhood. We performed a hospital audit, in order to quantify the pulmonary implications, in 28 boys and 19 girls aged 0.02-23 yrs, with a definite diagnosis of CHARGE. A review of the records of these children with CHARGE association revealed that aspiration was common during infancy, as a result of inco-ordination of swallowing and gastro-oesophageal reflux. Aspiration was suspected in 22 of the 47 cases (47%), recurrent chest infections occurred in 22 cases (47%), and lung involvement contributed to 7 out of 17 deaths (41%). We conclude that respiratory morbidity and mortality is common in CHARGE, and decreases with age. Early diagnosis and treatment affords the best prognosis.
Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs
Authors: Andra Ivan, Marc S Halfon, Saurabh Sinha
Journal: Genome biology (2008)

We consider the problem of predicting cis-regulatory modules without knowledge of motifs. We formulate this problem in a pragmatic setting, and create over 30 new data sets, using Drosophila modules, to use as a 'benchmark'. We propose two new methods for the problem, and evaluate these, as well as two existing methods, on our benchmark. We find that the challenge of predicting cis-regulatory modules ab initio, without any input of relevant motifs, is a realizable goal.
Intelligence, hormones, sex, brain size, and biochemistry: It all needs to have equal causal standing before integration is possible
Authors: Helmuth Nyborg
Journal: Behavioral and Brain Sciences (2007)

Abstract Recent brain imaging points to differences in brain structure that relate to intelligence, but how do we model their causal relationship within a coherent framework that circumvents classic dualist traps? A bottom-level nonlinear, dynamic, multifactor, multiplicative, multidimensional, molecular (ND4M) trait-covariance time-space model may accomplish this better than traditional approaches.
Lower limb injury: improving our translation of research into clinical practice for acute injuries and long-term sequelae
Authors: Ebonie Rio, David A Opar
Journal: British Journal of Sports Medicine (2015)

Adductor-related groin pain remains the bane of the soccer medical team's existence. While MRI is commonly used to assist in diagnosis of groin pain (acute and long standing), few studies have compared symptomatic athletes with matched controls. Imaging is known to uncover pathologies that may not fit with the clinical picture and MRI is no exception. The paper by Branci et al ( see page 681 ) provides insight into the MRI findings that may be associated with soccer participation and reminds us that caution and clinical judgment must be used when interpreting the MRI of an athlete with adductor-related groin pain.

In a second paper, Branci et al try to standardise criteria to evaluate key findings in pubic and groin MRIs in athletes ( see page 692 ). It reminds us that the findings should continue to be placed in a clinical context as there is …
Limited correlation between the Health Assessment Questionnaire (HAQ) and EuroQol in rheumatoid arthritis: questionable validity of deriving quality adjusted life years from HAQ
Authors: D L Scott, B Khoshaba, E H Choy, G H Kingsley
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> There is growing emphasis on the cost-effectiveness of treating rheumatoid arthritis. Few trials directly record the health utility measures, like EuroQol, needed for economic analyses. Consequently linear regression methods have been used to transform Health Assessment Questionnaire (HAQ) scores into utility measures. The authors examined whether this is justified. <h3>Methods:</h3> The authors compared HAQ and EuroQol in cross-sectional and treatment change observational studies of rheumatoid arthritis patients; they also measured SF-36 and Nottingham Health Profiles. <h3>Results:</h3> In the cross-sectional study, HAQ and EuroQol scores were moderately inversely correlated (Spearman rank correlation, r = 0.76). HAQ showed a Gaussian distribution whereas EuroQol was bimodal. In the treatment change study, changes in HAQ and EuroQol were unrelated (r = 0.08); the changes showed similar Gaussian and bimodal distributions. <h3>Conclusions:</h3> Not all patient-based measures are analogous, and evidence of clinical equivalence, especially in treatment response, is needed before data transformation is considered. Specifically, as HAQ and EuroQol are demonstrably not equivalent, economic evaluations of treatment cost effectiveness should not be based on EuroQol data transformed from HAQ. The use of such transformed data by regulatory bodies which determine drug availability means that the issue is no longer only of academic interest but a real clinical concern.
The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome
Authors: T. K. Klooker, B. Braak, K. E. Koopman, O. Welting, M. M. Wouters, S. van der Heide, M. Schemann, S. C. Bischoff, R. M. van den Wijngaard, G. E. Boeckxstaens
Journal: Gut (2010)

<h3>Background</h3> Mast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS. <h3>Methods</h3> 60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers. <h3>Results</h3> Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen. <h3>Conclusions</h3> This study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H<sub>1</sub> receptor antagonism remains to be further investigated. <h3>Trial Registration Number</h3> NTR39, ISRCTN22504486.
Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis
Authors: Y.-W. Kim, D. Koul, S. H. Kim, A. K. Lucio-Eterovic, P. R. Freire, J. Yao, J. Wang, J. S. Almeida, K. Aldape, W. K. A. Yung
Journal: Neuro-Oncology (2013)

The Cancer Genome Atlas (TCGA) project is a large-scale effort with the goal of identifying novel molecular aberrations in glioblastoma (GBM). Here, we describe an in-depth analysis of gene expression data and copy number aberration (CNA) data to classify GBMs into prognostic groups to determine correlates of subtypes that may be biologically significant. To identify predictive survival models, we searched TCGA in 173 patients and identified 42 probe sets (P = .0005) that could be used to divide the tumor samples into 3 groups and showed a significantly (P = .0006) improved overall survival. Kaplan-Meier plots showed that the median survival of group 3 was markedly longer (127 weeks) than that of groups 1 and 2 (47 and 52 weeks, respectively). We then validated the 42 probe sets to stratify the patients according to survival in other public GBM gene expression datasets (eg, GSE4290 dataset). An overall analysis of the gene expression and copy number aberration using a multivariate Cox regression model showed that the 42 probe sets had a significant (P < .018) prognostic value independent of other variables. By integrating multidimensional genomic data from TCGA, we identified a specific survival model in a new prognostic group of GBM and suggest that molecular stratification of patients with GBM into homogeneous subgroups may provide opportunities for the development of new treatment modalities.
Molecular Evolution of Sex-Biased Genes in Drosophila
Authors: Zhi Zhang, Tina M. Hambuch, John Parsch
Journal: Molecular Biology and Evolution (2004)

Studies of morphology, interspecific hybridization, protein/DNA sequences, and levels of gene expression have suggested that sex-related characters (particularly those involved in male reproduction) evolve rapidly relative to non–sex-related characters. Here we report a general comparison of evolutionary rates of sex-biased genes using data from cDNA microarray experiments and comparative genomic studies of Drosophila. Comparisons of nonsynonymous/synonymous substitution rates (dN/dS) between species of the D. melanogaster subgroup revealed that genes with male-biased expression had significantly faster rates of evolution than genes with female-biased or unbiased expression. The difference was caused primarily by a higher dN in the male-biased genes. The same pattern was observed for comparisons among more distantly related species. In comparisons between D. melanogaster and D. pseudoobscura, genes with highly biased male expression were significantly more divergent than genes with highly biased female expression. In many cases, orthologs of D. melanogaster male-biased genes could not be identified in D. pseudoobscura through a Blast search. In contrast to the male-biased genes, there was no clear evidence for accelerated rates of evolution in female-biased genes, and most comparisons indicated a reduced rate of evolution in female-biased genes relative to unbiased genes. Male-biased genes did not show an increased ratio of nonsynonymous/synonymous polymorphism within D. melanogaster, and comparisons of polymorphism/divergence ratios suggest that the rapid evolution of male-biased genes is caused by positive selection.
Distribution of mast-cell precursors in hematopoeitic and lymphopoietic tissues of mice.
Authors: Y Kitamura, M Shimada, S Go, H Matsuda, K Hatanaka, M Seki
Journal: The Journal of Experimental Medicine (1979)

Two experimental systems were used to investigate the origin of precursor cells which differentiate into tissue mast cells in vivo. (a) Increase of mast cell number was examined in the skin, stomach, cecum, and mesentery of genetically mast cell-depleted WBB6F1 (WB X C57BL/6)-W/WV mice after the injection of various hematolymphoid cells of congenic +/+ mice. (b) Appearance of mast cells with giant granules was studied in irradiated C57BL/6-+/+ mice after the injection of lymphoid cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice. Concentrations of mast cell precursors in the thymus, lymph node and Peyer's patch were less than 0.1% of the concentration in the bone marrow. Neither treatment of donor bone marrow cells with anti-Thy-1.2 serum and complement nor thymectomy of the recipient mice affects the development of mast cells in the skin, stomach, cecum, and mesentery. Moreover, the number of mast cells increased to normal level when the skin of WBB6F1-W/WV mice was grafted on the back of nude athymic (BALB/c-nu/nu) mice. These results indicate that mast cell precursors are derived from hematopoietic tissues rather than lymphopoetic ones and that the differentiation of the precursor cells does not depend on T lymphocytes or the thymus.
High efficiency retroviral mediated gene transduction into single isolated immature and replatable CD34(3+) hematopoietic stem/progenitor cells from human umbilical cord blood.
Authors: L Lu, M Xiao, D W Clapp, Z H Li, H E Broxmeyer
Journal: The Journal of Experimental Medicine (1993)

Umbilical cord blood is rich in hematopoietic stem and progenitor cells and has recently been used successfully in the clinic as an alternative source of engrafting and marrow repopulating cells. With the likelihood that cord blood stem/progenitor cells will be used for gene therapy to correct genetic disorders, we evaluated if a TK-neo gene could be directly transduced in a stable manner into single isolated subsets of purified immature hematopoietic cells that demonstrate self-renewed ability as estimated by colony replating capacity. Sorted CD34(3+) cells from cord blood were prestimulated with erythropoietin (Epo), steel factor (SLF), interleukin (IL)-3, and granulocyte-macrophage colony stimulating factor (GM-CSF) and transduced with the gene in two ways. CD34(3+) cells were incubated with retroviral-containing supernatant from TK-neo vector-producing cells, washed, and plated directly or resorted as CD34(3+) cells into single wells containing a single cell or 10 cells. Alternatively, CD34(3+) cells were sorted as a single cell/well and then incubated with viral supernatant. These cells were cultured with Epo, SLF, IL-3, and GM-CSF +/- G418. The TK-neo gene was introduced at very high efficiency into low numbers of or isolated single purified CD34(3+) immature hematopoietic cells without stromal cells as a source of virus or accessory cells. Proviral integration was detected in primary G418-resistant(R) colonies derived from single immature hematopoietic cells, and in cells from replated colonies derived from G418R-colony forming unit-granulocyte erythroid macrophage megakaryocyte (CFU-GEMM) and -high proliferative potential colony forming cells (HPP-CFC). This demonstrates stable expression of the transduced gene into single purified stem/progenitor cells with replating capacity, results that should be applicable for future clinical studies that may utilize selected subsets of stem/progenitor cells for gene therapy.
Investigation and management of chronic cough using a probability-based algorithm
Authors: J. A. Kastelik, I. Aziz, J. C. Ojoo, R. H. Thompson, A. E. Redington, A. H. Morice
Journal: European Respiratory Journal (2005)

Chronic cough is a common and distressing symptom. A novel algorithm has been developed for the management of chronic cough, in which an assessment of clinical probability of disease determines the need to proceed to investigation. In this study, the performance of this algorithm in clinical practice was prospectively evaluated. A total of 131 consecutively referred patients (86 females) whose principal presenting symptom was a cough of duration >8 weeks were studied. Their age (median (range)) was 60 (16-88) yrs and cough duration 5.9 (0.2-65) yrs. A cause of cough was established in 93% of cases. The most frequent diagnoses were asthma (24% of cases), gastro-oesophageal disease (22%), post-viral cough (8%), bronchiectasis (8%) and interstitial lung disease (8%). Primary pulmonary disease was significantly more likely in patients with a productive cough and in patients with an abnormal chest radiograph. Only a small proportion (<8%) of patients had multiple causes of cough. The probability of treatment started on the basis of a high clinical suspicion of either asthma, gastro-oesophageal disease or rhinitis being successful was 74%. Overall, 26% of the patients were managed successfully without the need for any form of investigation other than chest radiography and spirometry. Use of the algorithm resulted in identification of the cause of cough and successful treatment in the large majority of cases. It is concluded that this protocol has the potential to improve management by providing a structured approach, reducing the number of investigations performed, and minimising unnecessary delays in treatment.