tbuckley/cabot-search huggingface dataset:
THE EFFECT OF DIET ON THE FECAL BACTERIAL FLORA OF MICE AND ON THEIR RESISTANCE TO INFECTION
Authors: René J. Dubos, Russell W. Schaedler
Journal: The Journal of Experimental Medicine (1962)

A study was made of the effect of certain dietary regimens on the lactobacillus flora in the stools of mice and on their resistance to infection. Semi-synthetic diets with purified casein or wheat gluten as sole source of protein, gave rise to much smaller numbers of viable lactobacilli in the stools than did other diets containing unidentified natural products—as present for example in mixtures of whole wheat and whole milk, or in certain commercial pellets. Furthermore, one of the lactobacillus types with rhizoid morphology disappeared completely from the stools of animals fed the semi-synthetic diet. The change in the lactobacillus flora became apparent within a very few days after the animals had been shifted from the complex to the synthetic diet Moreover, this change was not completely reversible. Whereas the total numbers of lactobacilli increased when the animals were shifted back from the synthetic to the complex diets, the rhizoid lactobacilli which had disappeared completely from the stools reappeared only slowly or not at all. In twelve consecutive experiments the three diets which gave rise to the large numbers of lactobacilli in the stools also conferred on the mice a much higher resistance to experimental infection with Staphylococcus aureus and Klebsiella pneumoniae, than did the semi-synthetic diets. However, direct evidence has not yet been obtained that the two kinds of phenomena were causally related. Following administration of endotoxin there was a rapid and very large increase in the numbers of enterococci and coliform bacilli in mice fed the semi-synthetic casein diet, but not in those fed the pellets. In two preliminary experiments carried out with another colony of mice, not pathogen-free, it was also found that the rhizoid type of lactobacilli disappeared from animals fed the semi-synthetic casein diet while enterococci and coliform bacilli progressively increased in numbers under the same conditions. The dietary effects on the lactobacillus flora, and on resistance to experimental infection, were equally pronounced whether the mice were housed in individual cages on wire grids, or grouped in larger cages with wood shavings as litter. This was true even if the bedding was changed only once weekly and became therefore grossly soiled.
Leukotriene A4 Hydrolase in Rat and Human Esophageal Adenocarcinomas and Inhibitory Effects of Bestatin
Authors: X. Chen, N. Li, S. Wang, N. Wu, J. Hong, X. Jiao, M. J. Krasna, D. G. Beer, C. S. Yang
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Esophageal adenocarcinoma (EAC) is increasing at the most rapid rate of any cancer in the United States. An esophagogastroduodenal anastomosis (EGDA) surgical model in rats mimics human gastroesophageal reflux and results in EAC. Leukotriene A4 hydrolase (LTA4H), a protein overexpressed in EAC in this model, is a rate-limiting enzyme in the biosynthesis of leukotriene B4 (LTB4), a potent inflammatory mediator. We used this model and human EAC and non-tumor tissues to elucidate the expression pattern of LTA4H and to evaluate it as a target for chemoprevention. Methods: LTA4H expression was examined by western blotting and immunohistochemistry. The functional role of LTA4H in carcinogenesis was investigated by use of an LTA4H inhibitor, bestatin, in the rat EGDA model. All statistical tests were two-sided. Results: LTA4H was overexpressed in all 10 rat EACs examined, compared with its level in normal rat tissue; it was also overexpressed in four of six human EAC tumor samples, compared with its level in adjacent non-tumor tissue. In tissue sections from 20 EGDA rats and 92 patients (86 with EAC, one with dysplasia, and five with columnar-lined esophagus), LTA4H was expressed in infiltrating inflammatory cells and overexpressed in the columnar cells of preinvasive lesions and cancers, especially in well-differentiated EACs, as compared with the basal cells of the normal esophageal squamous epithelium. Bestatin statistically significantly inhibited LTB4 biosynthesis in the esophageal tissues of EGDA rats (without bestatin = 8.28 ng/mg of protein; with bestatin = 4.68 ng/mg of protein; difference = 3.60, 95% CI = 1.59 to 5.61; P = .002) and reduced the incidence of EAC in the EGDA rats from 57.7% (15 of 26 rats) to 26.1% (6 of 23 rats) (difference = 31.6%, 95% CI = 0.3% to 56.2%; P = .042). Conclusion: LTA4H overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of EAC.
Prioritizing functional modules mediating genetic perturbations and their phenotypic effects: a global strategy
Authors: Li Wang, Fengzhu Sun, Ting Chen
Journal: Genome biology (2008)

Abstract We have developed a global strategy based on the Bayesian network framework to prioritize the functional modules mediating genetic perturbations and their phenotypic effects among a set of overlapping candidate modules. We take lethality in Saccharomyces cerevisiae and human cancer as two examples to show the effectiveness of this approach. We discovered that lethality is more conserved at the module level than at the gene level and we identified several potentially 'new' cancer-related biological processes.
Safety and immunogenicity of Staphylococcus aureus type 5 capsular polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugate vaccine in patients on hemodialysis.
Authors: P G Welch, A Fattom, J Moore, R Schneerson, J Shiloach, D A Bryla, X Li, J B Robbins
Journal: Journal of the American Society of Nephrology (1996)

Seventeen volunteers with ESRD on hemodialysis, negative for infection with HIV or hepatitis B and C and not receiving immunosuppressive therapy, were injected two times 6 wk apart with 25 micrograms of Staphylococcus aureus Type 5 capsular polysaccharide-Pseudomonas aeruginosa exoprotein A (rEPA) conjugate. Controls were healthy adults, 18 to 44 yr old, injected previously with the same vaccine. None of the patients had fever or significant elevations in their SGOT or SGPT attributable to the vaccine. Two vaccinees had transient induration > 1 cm in diameter at the injection site. The preimmunization geometric mean (GM) Type 5 antibody levels of the ESRD patients and controls were similar. Type 5 antibody levels of the three major immunoglobulin (lg) classes rose at 2 and 6 wk after immunization (P < 0.001 for lgG, P < 0.005 for lgM, and P = 0.0001 for lgA). Reimmunization at 6 wk did not elicit a booster response. At 6 months, the GM lgG level of the patients was approximately 50% of that of the healthy volunteers and 14 of 17 had a more than fourfold higher antibody level than the preimmune value. The GM lgM level, in contrast, declined to the preimmunization value. Vaccine-induced Type 5 antibodies had opsonophagocytic activity. There was a slight increase of lgG antibodies to the heterologous S. aureus Type 8 polysaccharide (P < 0.01) that was sustained at 6 months. The S. aureus Type 5-rEPA vaccine is safe and immunogenic in ESRD patients, and evaluation of its effectiveness against S. aureus bacteremia in this at-risk group is planned.
REJECTION OF TUMOR ALLOGRAFTS BY MOUSE SPLEEN CELLS SENSITIZED IN VITRO
Authors: Irun R. Cohen, Amiela Globerson, Michael Feldman
Journal: The Journal of Experimental Medicine (1971)

This paper reports a model system of cellular immunity in which allosensitization of mouse spleen cells is induced in vitro. Allosensitization was achieved by culturing spleen cells upon monolayers of allogeneic fibroblasts. The ability of the spleen cells to inhibit the growth of tumor allografts in vivo served as a functional assay of sensitization. We found that unsensitized spleen cells or spleen cells sensitized against unrelated fibroblast antigens had no inhibitory effect on the growth of allogeneic fibrosarcoma cells when they were injected together into irradiated recipients. In contrast, spleen cells which were specifically allosensitized in vitro were found to be highly effective in inhibiting the growth of an equal number of allogeneic tumor cells. Several times more spleen cells from mice sensitized in vivo were required to produce a similar immune effect. This confirms the findings of previous studies which indicate that sensitization in cell culture can promote the selection of specifically sensitized lymphocytes. Preincubating sensitizing fibroblasts with allo-antisera blocked the allosensitization of spleen cells. This suggests that antibodies binding to fibroblasts may inhibit the induction of sensitization by competing with lymphocytes for antigenic sites. Mouse spleen cells which were able to recognize and reject tumor allografts in vivo were unable to cause lysis of target fibroblasts in vitro. Such fibroblasts, however, were susceptible to lysis by rat lymphoid cells sensitized by a similar in vitro method. These findings indicate that the conditions required for lymphocyte-mediated lysis of target cells may not be directly related to the processes of antigen recognition and allograft rejection in vivo.
Functional Network Analysis Reveals Extended Gliomagenesis Pathway Maps and Three Novel MYC-Interacting Genes in Human Gliomas
Authors: Markus Bredel, Claudia Bredel, Dejan Juric, Griffith R. Harsh, Hannes Vogel, Lawrence D. Recht, Branimir I. Sikic
Journal: Cancer Research (2005)

Abstract Gene expression profiling has proven useful in subclassification and outcome prognostication for human glial brain tumors. The analysis of biological significance of the hundreds or thousands of alterations in gene expression found in genomic profiling remains a major challenge. Moreover, it is increasingly evident that genes do not act as individual units but collaborate in overlapping networks, the deregulation of which is a hallmark of cancer. Thus, we have here applied refined network knowledge to the analysis of key functions and pathways associated with gliomagenesis in a set of 50 human gliomas of various histogenesis, using cDNA microarrays, inferential and descriptive statistics, and dynamic mapping of gene expression data into a functional annotation database. Highest-significance networks were assembled around the myc oncogene in gliomagenesis and around the integrin signaling pathway in the glioblastoma subtype, which is paradigmatic for its strong migratory and invasive behavior. Three novel MYC-interacting genes (UBE2C, EMP1, and FBXW7) with cancer-related functions were identified as network constituents differentially expressed in gliomas, as was CD151 as a new component of a network that mediates glioblastoma cell invasion. Complementary, unsupervised relevance network analysis showed a conserved self-organization of modules of interconnected genes with functions in cell cycle regulation in human gliomas. This approach has extended existing knowledge about the organizational pattern of gene expression in human gliomas and identified potential novel targets for future therapeutic development.
Sagopilone Inhibits Breast Cancer Bone Metastasis and Bone Destruction Due to Simultaneous Inhibition of Both Tumor Growth and Bone Resorption
Authors: Anne Strube, Jens Hoffmann, Elizaveta Stepina, Peter Hauff, Ulrich Klar, Sanna-Maria Käkönen
Journal: Clinical Cancer Research (2009)

Bone metastases have a considerable impact on quality of life in patients with breast and other cancers. Tumors produce osteoclast-activating factors, whereas bone resorption promotes the growth of tumor cells, thus leading to a "vicious cycle" of bone metastasis. Sagopilone, a novel, fully synthetic epothilone, inhibits the growth of breast cancer cells in vitro and in vivo, and here we report its activity in the MDA-MB-231(SA) breast cancer bone metastasis mouse model.The potency of sagopilone was determined in treatment models simulating the adjuvant (preventive) and metastatic (therapeutic) settings in the clinic.We showed that sagopilone inhibited tumor burden and bone destruction, in addition to reducing tumor-induced cachexia and paraplegia. The reduction in osteolytic lesions, tumor growth in bone, and weight loss was statistically significant in the preventive model compared with the vehicle group. In the therapeutic model, sagopilone treatment significantly lowered the number of activated osteoclasts and significantly reduced the osteolytic lesion area, bone volume loss, and bone resorption compared with vehicle treatment while simultaneously inhibiting tumor burden. An in vitro assay confirmed that sagopilone inhibited osteoclast activation without cytotoxic effects, whereas paclitaxel resulted in lower inhibition and high levels of cytotoxicity.Sagopilone seems to inhibit the vicious cycle at both the tumor growth and bone resorption stages, suggesting the possibility for substantial benefit in the treatment of patients with breast cancer at risk from bone metastases or with bone lesions already present. Phase II clinical trials with sagopilone in patients with breast cancer are ongoing.
Agreement Between Clinical and Radiological Diagnosis
Authors: G. R. Sutherland
Journal: BMJ (1970)

Agreement between radiological and clinical diagnosis and the incidence of unexpected findings has been used as an indicator of the diagnostic contribution of radiology. The overall incidence of agreement was 33% - 533 out of 1,604 x-ray examinations. The wide variation in agreement in different radiological examinations is clearly related to the pathological nature of disease and the limitations of radiological techniques. If diagnostic radiology is to be effective its application rather than interpretation in the clinical situation must be emphasized in training programmes.
Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study
Authors: Pierre Fenaux, Ghulam J Mufti, Eva Hellstrom-Lindberg, Valeria Santini, Carlo Finelli, Aristoteles Giagounidis, Robert Schoch, Norbert Gattermann, Guillermo Sanz, Alan List, Steven D Gore, John F Seymour, John M Bennett, John Byrd, Jay Backstrom, Linda Zimmerman, David McKenzie, CL Beach, Lewis R Silverman
Journal: The Lancet Oncology (2009)
Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative
Authors: L Gossec, M Dougados, N Rincheval, A Balanescu, D T Boumpas, S Canadelo, L Carmona, J-P Daures, M de Wit, B A C Dijkmans, M Englbrecht, Z Gunendi, T Heiberg, J R Kirwan, E M Mola, M Matucci-Cerinic, K Otsa, G Schett, T Sokka, G A Wells, G J Aanerud, A Celano, A Dudkin, C Hernandez, K Koutsogianni, F N Akca, A-M Petre, P Richards, M Scholte-Voshaar, G Von Krause, T K Kvien
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Background:</h3> Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. <h3>Objective:</h3> To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. <h3>Methods:</h3> Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to “distribute 100 points” among the seven domains. The average ranks of importance of these domains were then computed. <h3>Results:</h3> The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. <h3>Conclusion:</h3> The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.
CT Colonography versus Colonoscopy for the Detection of Advanced Neoplasia
Authors: David H. Kim, Perry J. Pickhardt, Andrew J. Taylor, Winifred K. Leung, Thomas C. Winter, J. Louis Hinshaw, Deepak V. Gopal, Mark Reichelderfer, Richard H. Hsu, Patrick R. Pfau
Journal: New England Journal of Medicine (2007)

Advanced neoplasia represents the primary target for colorectal-cancer screening and prevention. We compared the diagnostic yield from parallel computed tomographic colonography (CTC) and optical colonoscopy (OC) screening programs.We compared primary CTC screening in 3120 consecutive adults (mean [+/-SD] age, 57.0+/-7.2 years) with primary OC screening in 3163 consecutive adults (mean age, 58.1+/-7.8 years). The main outcome measures included the detection of advanced neoplasia (advanced adenomas and carcinomas) and the total number of harvested polyps. Referral for polypectomy during OC was offered for all CTC-detected polyps of at least 6 mm in size. Patients with one or two small polyps (6 to 9 mm) also were offered the option of CTC surveillance. During primary OC, nearly all detected polyps were removed, regardless of size, according to established practice guidelines.During CTC and OC screening, 123 and 121 advanced neoplasms were found, including 14 and 4 invasive cancers, respectively. The referral rate for OC in the primary CTC screening group was 7.9% (246 of 3120 patients). Advanced neoplasia was confirmed in 100 of the 3120 patients in the CTC group (3.2%) and in 107 of the 3163 patients in the OC group (3.4%), not including 158 patients with 193 unresected CTC-detected polyps of 6 to 9 mm who were undergoing surveillance. The total numbers of polyps removed in the CTC and OC groups were 561 and 2434, respectively. There were seven colonic perforations in the OC group and none in the CTC group.Primary CTC and OC screening strategies resulted in similar detection rates for advanced neoplasia, although the numbers of polypectomies and complications were considerably smaller in the CTC group. These findings support the use of CTC as a primary screening test before therapeutic OC.
Impact of Late Treatment-Related Toxicity on Quality of Life Among Patients With Head and Neck Cancer Treated With Radiotherapy
Authors: Johannes A. Langendijk, Patricia Doornaert, Irma M. Verdonck-de Leeuw, Charles R. Leemans, Neil K. Aaronson, Ben J. Slotman
Journal: Journal of Clinical Oncology (2008)

To investigate the impact of treatment-related toxicity on health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma treated with radiotherapy either alone or in combination with chemotherapy or surgery.The study sample was composed of 425 disease-free patients. Toxicity was scored according to the European Organisation for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) late radiation-induced morbidity scoring system. HRQoL was assessed using the EORTC Quality of Life Questionnaire C30. These assessments took place at 6, 12, 18, and 24 months after completion of radiotherapy. The analysis was performed using a multivariate analysis of variance.Of the six RTOG scales investigated, two significantly affected self-reported HRQoL, salivary gland (RTOG(xerostomia)) and esophagus/pharynx (RTOG(swallowing)). Although RTOG(xerostomia) was reported most frequently, HRQoL was most affected by RTOG(swallowing), particularly in the first 18 months after completion of radiotherapy.Late radiation-induced toxicity, particularly RTOG(swallowing) and RTOG(xerostomia), has a significant impact on the more general dimensions of HRQoL. These findings suggest that the development of new radiation-induced delivery techniques should not only focus on reduction of the dose to the salivary glands, but also on anatomic structures that are involved in swallowing.
The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations
Authors: D Tripathi, G Therapondos, E Jackson, D N Redhead, P C Hayes
Journal: Gut (2002)

<b>Background:</b> The transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the management of both oesophageal and gastric variceal bleeding. Although it has been reported that gastric varices can bleed at pressures of ≤12 mm Hg, this phenomenon has been little studied in the clinical setting. <b>Aims:</b> To assess the efficacy of TIPSS on rebleeding and mortality following gastric and oesophageal variceal bleeding, and the importance of portal pressure in both groups. <b>Methods:</b> Forty eligible patients who had bled from gastric varices and 232 from oesophageal varices were studied. Patients were also subdivided into those whose portal pressure gradients (PPG) prior to TIPSS were ≤12 mm Hg (group 1) and &gt;12 mm Hg (group 2). <b>Results:</b> There was no difference in Child-Pugh score, age, sex, or alcohol related disease between patients bleeding from gastric or oesophageal varices. Patients who bled from gastric varices had a lower PPG pre-TIPSS (15.8 (0.8) <i>v</i> 21.44 (0.4) mm Hg; p&lt;0.001). There was no difference in the rebleeding rate (20.0% <i>v</i> 14.7%; NS). There was a significant difference (p&lt;0.05) in favour of the gastric varices group in the one year mortality (30.7% <i>v</i> 38.7%) and five year mortality (49.5% <i>v</i> 74.9%), particularly in those patients in group 2. Gastric variceal bleeding accounted for significantly more cases in group 1 than in group 2 (36.8% <i>v</i> 10.2%; p&lt;0.001). Most patients in group 2 who rebled had a PPG post-TIPSS of &gt;7 mm Hg. <b>Conclusions:</b> TIPSS is equally effective in the prevention of rebleeding following gastric and oesophageal variceal bleeding. A significant proportion of gastric varices bleed at a PPG ≤12 mm Hg. The improved mortality in patients with gastric variceal bleeding is seen only in those that bleed at a PPG &gt;12 mm Hg, and warrants further study.
A network-based approach to sleep apnea syndrome
Authors: Stefan Mihaicuta, Razvan Avram, Alexandru Topirceanu, Mihai Udrescu
Journal: European Respiratory Journal (2013)

Objectives. To identify patterns of developing obstructive sleep apnea (OSA), with a complex network cluster analysis.

Methods. 1367 patients, Timisoara “Victor Babes“ Hospital sleep lab, analyzed inspired by the Network Medicine approach. A patient was a node in a network where a link is inserted if there is a risk relationship between 2 corresponding patients, if two nodes have >5 of 7 parameters: sex, age, systemic hypertension, BMI>30, neck circumference, mean and desaturation index. Graphical generation with Gephi 0.8.1, to extract network attributes and reveal the compatibility clusters.

Results. AHI classifies the apnea severity.

![Figure][1] 



With network cluster analysis, 7 distinct compatibility clusters were found, each corresponding to a specific profile which leads to a certain probability of developing the disease.

![Figure][1] 



There are 3 clusters of with severe OSA (1, 2 and 5), 3 clusters with mild-moderate OSA (3, 6, and 7). Cluster 4 reflects a transitory stage that cannot be characterized by a stable AHI group.

Conclusion. Measuring simple parameters may pave a way for automatically predicting, with a high degree of accuracy, if a patient is prone to developing OSA.

 [1]: pending:yes