tbuckley/cabot-search huggingface dataset:
Substantial Loss of Conserved and Gain of Novel MicroRNA Families in Flatworms
Authors: Bastian Fromm, Merete Molton Worren, Christoph Hahn, Eivind Hovig, Lutz Bachmann
Journal: Molecular Biology and Evolution (2013)

Recent studies on microRNA (miRNA) evolution focused mainly on the comparison of miRNA complements between animal clades. However, evolution of miRNAs within such groups is poorly explored despite the availability of comparable data that in some cases lack only a few key taxa. For flatworms (Platyhelminthes), miRNA complements are available for some free-living flatworms and all major parasitic lineages, except for the Monogenea. We present the miRNA complement of the monogenean flatworm Gyrodactylus salaris that facilitates a comprehensive analysis of miRNA evolution in Platyhelminthes. Using the newly designed bioinformatics pipeline miRCandRef, the miRNA complement was disentangled from next-generation sequencing of small RNAs and genomic DNA without a priori genome assembly. It consists of 39 miRNA hairpin loci of conserved miRNA families, and 22 novel miRNAs. A comparison with the miRNA complements of Schmidtea mediterranea (Turbellaria), Schistosoma japonicum (Trematoda), and Echinococcus granulosus (Cestoda) reveals a substantial loss of conserved bilaterian, protostomian, and lophotrochozoan miRNAs. Eight of the 46 expected conserved miRNAs were lost in all flatworms, 16 in Neodermata and 24 conserved miRNAs could not be detected in the cestode and the trematode. Such a gradual loss of miRNAs has not been reported before for other animal phyla. Currently, little is known about miRNAs in Platyhelminthes, and for the majority of the lost miRNAs there is no prediction of function. As suggested earlier they might be related to morphological simplifications. The presence and absence of 153 conserved miRNAs was compared for platyhelminths and 32 other metazoan taxa. Phylogenetic analyses support the monophyly of Platyhelminthes (Turbellaria + Neodermata [Monogenea {Trematoda + Cestoda}]).
Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system
Authors: Romain Cayrol, Karolina Wosik, Jennifer L Berard, Aurore Dodelet-Devillers, Igal Ifergan, Hania Kebir, Arsalan S Haqqani, Katharina Kreymborg, Sebastian Krug, Robert Moumdjian, Alain Bouthillier, Burkhard Becher, Nathalie Arbour, Samuel David, Danica Stanimirovic, Alexandre Prat
Journal: Nature Immunology (2007)
Type C RNA Viruses and Leukemogenesis: Association of Gross Strain of Murine Leukemia Virus Infection and Leukemogenesis in Rats2
Authors: Yuzuru Kawamura
Journal: JNCI Journal of the National Cancer Institute (1976)

The correlation of murine leukemia virus (MuLV) infection and leukemogenesis was examined by XC plaque assay in W/F rats neonatally infected with the rat-adapted Gross virus (RAGV). Thymic lymphomas developed in 100% of infected rats, with a mean latent period of 64 days. The virus infectivity was first detected in the thymus as early as 15 days after the virus infection; the titer steadily increased thereafter until the development of thymic lymphoma. No other tissues of virus-infected rats showed virus infectivity until the development of localized thymic lymphoma, though sera of a few rats showed low infectivity titers. In rats with generalized leukemia, however, high titers were detected in the sera and leukemic tissues. In untreated controls, all tissues tested invariably showed negative titers for MuLV infectivity at any age up to 7 months after birth. The results indicated that those tissue sites were common to both RAGV infectivity and the leukemogenic process, with the primary involvement of the thymus, and that the appearance of RAGV infectivity in various tissues represented the expression of the oncogenic genome of RAGV.
Patient-Reported Outcomes for Irritable Bowel Syndrome Are Associated With Patients' Severity Ratings of Gastrointestinal Symptoms and Psychological Factors
Authors: Jeffrey Lackner, James Jaccard, Charles Baum, Amanda Smith, Susan Krasner, Leonard Katz, Rebecca Firth, Tatayna Raby, Cathrine Powell
Journal: Clinical Gastroenterology and Hepatology (2011)
Low-Dose Growth Hormone is Cardioprotective in Uremia
Authors: Ralph Rabkin, Ibrahim Awwad, Yu Chen, Euan A. Ashley, Difei Sun, Sumita Sood, William Clusin, Paul Heidenreich, Grzegorz Piecha, Marie-Luise Gross
Journal: Journal of the American Society of Nephrology (2008)

Growth hormone (GH) is required to maintain normal cardiac structure and function and has a positive effect on cardiac remodeling in experimental and possibly human disease. Cardiac resistance to GH develops in the uremic state, perhaps predisposing to the characteristic cardiomyopathy associated with uremia. It was hypothesized that administration of low-dosage GH may have a salutary effect on the cardiac remodeling process in uremia, but because high levels of GH have adverse cardiac effects, administration of high-dosage GH may worsen uremic cardiomyopathy. In rats with chronic renal failure, quantitative cardiac morphology revealed a decrease in total capillary length and capillary length density and an increase in mean intercapillary distance and fibroblast volume density evident. Low-dosage GH prevented these changes. Collagen and TGF-beta immunostaining, increased in chronic renal failure, were also reduced by GH, suggesting a mechanism for its salutary action. Low-dosage GH also prevented thickening of the carotid artery but did not affect aortic pathology. In contrast, high-dosage GH worsened several of these variables. These results suggest that low-dosage GH may benefit the heart and possibly the carotid arteries in chronic renal failure.
Human Telomerase Reverse Transcriptase Activated by E6 Oncoprotein Is Required for Human Papillomavirus-16/18-Infected Lung Tumorigenesis
Authors: Ya-Wen Cheng, Tzu-Chin Wu, Chih-Yi Chen, Ming-Chih Chou, Jiunn-Liang Ko, Huei Lee
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Our recent report indicates that human papillomavirus (HPV)-16/18 E6 oncoprotein is expressed in lung tumors and is related to p53 inactivation. We further explored whether human telomerase reverse transcriptase (hTERT) transcription is up-regulated by E6 and contributes to lung tumor development. Experimental Design: Immunohistochemistry detected HPV-16 E6 oncoprotein in 135 lung tumors, and hTERT mRNA was evaluated by real-time reverse transcription-PCR and in situ hybridization, respectively. A small RNA interference (RNAi), Western blotting, and chromatin immunoprecipitation analysis were used to clarify whether hTERT transcription was regulated by c-Myc and Sp1. The telomerase activity and oncogenic potential of TL-1 with or without E6- or hTERT-RNAi was determined by real-time quantitative telomeric repeat amplification protocol analysis and soft-agar assay, respectively. Results: hTERT mRNA levels in E6-positive tumors, which were prevalent in females, nonsmokers, and adenocarcinomas, were significantly higher than in E6-negative tumors. In addition, hTERT mRNA levels in early tumors (stage I) were greater than levels in advanced tumors (stages II and III). Chromatin immunoprecipitation assay showed that Sp1 cooperated with c-Myc to activate hTERT transcription in TL-1 cells, which was similar to the SiHa cells. The telomerase activity of the TL-1 cells decreased concomitantly with the transfection of various doses of E6- or hTERT-RNAi. A soft-agar assay showed that the oncogenic potential of TL-1 cells was significantly reduced after being transfected with E6-RNAi. Moreover, a colony of TL-1 cells could not form after transfection with hTERT-RNAi. Conclusion: Transcriptional activation of hTERT by E6 oncoprotein is required for HPV-16/18-infected lung tumorigenesis.
Pitfalls in double‐blind, placebo‐controlled oral food challenges
Authors: B. Niggemann, K. Beyer
Journal: Allergy (2007)

Although controlled oral food challenges are considered to be the gold‐standard in the diagnosis of food related symptoms, especially if performed in a double‐blind, placebo‐controlled food challenges (DBPCFC) manner, there are still many unanswered questions and newer aspects, which may explain some pitfalls encountered during oral food challenges. For stopping an oral food challenge and declaring a challenge as positive or negative, symptoms should be objective and/or repetitive. The time interval between administering the food and observing the clinical reaction is an ambivalent factor. Possible reasons for false negative assessments include inadvertent drug use during oral challenges, and the fact that a short‐term specific oral tolerance induction (SOTI) may be induced as increasing amounts of the offended food are administered during a titrated oral food challenge. Possible reasons for false positive assessments are the difficulty to maintain an appropriate strict diet throughout the oral challenge procedure, and that the elimination diet implemented before the oral food challenge in children with atopic eczema and suspected food related symptoms may itself be responsible for immediate type clinical symptoms, which had not been reported by the parents before. Finally augmentation factors are among the most plausible explanations for the inadequate reproducibility of an oral food challenge. Although a 100% standardization of the challenge procedure does not seem realistic, efforts should be made to improve the methodology used so far. On the contrary, the possible relation of DBPCFC and SOTI may offer potential advantages for future therapeutic approaches of food allergy.
Effects of abatacept on monocytes in patients with rheumatoid arthritis
Authors: M Bonelli, E Ferner, A Savitskaya, S Bluml, C-W Steiner, E Rath, J S Smolen, C Scheinecker
Journal: Annals of the Rheumatic Diseases (2010)

Abatacept represents a soluble recombinant human fusion protein comprising the extracellular domain of human CTLA-4 and a fragment of the modified Fc domain of human IgG1 (CTLA-4Ig). Due to the interaction with CD80/CD86, abatacept inhibits the binding of CD28 and thereby effector T cell activation. In addition, inhibition of CD80/CD86 binding might also exert effects on antigen presenting cells including cells of the myelo-monocytic lineage. The authors …
Sepsis Caused by Contaminated Intravenous Fluids
Authors: STEPHEN K. FELTS
Journal: Annals of Internal Medicine (1972)

Thirty-one cases of nosocomial sepsis that occurred from July 1970 through May 1971 in a 500-bed hospital were related to bacterial contamination of intravenous fluid bottles produced by one manufacturer. The responsible microorganisms were Erwinia, Enterobacter cloacae, and Pseudomonas stutzeri. These uncommon bloodstream pathogens caused a persistent Gram-negative sepsis that was refractory to antimicrobial therapy. Discontinuation of intravenous therapy and replacement of the intravenous administration system were the only effective treatments. The organisms multiplied to concentrations of from 105 to 106 bacteria per millilitre in intravenous fluids, although the concentrations were never high enough to cause visible turbidity. Laboratory studies of these epidemic strains showed no significant differences from a control Escherichia coli in serum sensitivity, ease of phagocytosis, endotoxin production, or mouse virulence.
Ves v 5 can establish the diagnosis in patients without detectable specific IgE to wasp venom and a possible north-south difference in Api m 1 sensitization in Europe
Authors: Gunter J. Sturm, Maria Beatrice Biló, Patrizia Bonadonna, Wolfgang Hemmer, Beatrice Caruso, Danijela Bokanovic, Werner Aberer
Journal: Journal of Allergy and Clinical Immunology (2012)
Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
Authors: Nigel B. Jamieson, C. Ross Carter, Colin J. McKay, Karin A. Oien
Journal: Clinical Cancer Research (2011)

The management of pancreatic ductal adenocarcinoma (PDAC) continues to present a great challenge particularly with regard to prediction of outcome following pancreaticoduodenectomy. Molecular markers have been extensively investigated by numerous groups with the aim of enhancing prognostication; however, despite hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the clinical course following resection of PDAC, at this time, no molecular marker assay forms part of recommended clinical practice.We conducted a systematic review and meta-analysis of the published literature for immunohistochemistry-based biomarkers of PDAC outcome. A dual search strategy was applied to the PubMed database on January 6, 2010, to identify cohort studies that reported associations between immunohistochemical biomarker expression and survival outcomes in PDAC, and conformed to the REMARK (REporting recommendations for tumor MARKer prognostic studies) criteria.A total of 103 distinct proteins met all inclusion criteria. Promising markers that emerged for the prediction of overall survival included BAX (HR = 0.31, 95% CI: 0.71-0.56), Bcl-2 (HR = 0.41, 95% CI: 0.27-0.63), survivin (HR = 0.46, 95% CI: 0.29-0.73), Ki-67: (HR = 2.42, 95% CI: 1.87-3.14), COX-2 (HR = 1.39, 95% CI: 1.13-1.71), E-cadherin (HR = 1.80, 95% CI: 1.33-2.42), and S100 calcium-binding proteins, in particular S100A2 (HR = 3.23, 95% CI: 1.58-6.62).We noted that that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis. Addressing the persistent incomplete adoption of these criteria may eventually result in the incorporation of molecular marker assessment within PDAC management algorithms.
Cell-to-cell communication within intact human skin.
Authors: D Salomon, J H Saurat, P Meda
Journal: Journal of Clinical Investigation (1988)

We have characterized cell-to-cell communication (coupling) within intact human skin by microinjecting single keratinocytes with a gap junction-permeant tracer (Lucifer Yellow). 25-50 keratinocytes from different layers of the epidermis were seen to be coupled after most injections (n = 31). A few noncommunicating cells were also microinjected (n = 3) or observed within large territories of coupled keratinocytes. Microinjections of dermal fibroblasts demonstrated an extensive coupling (greater than 100 fibroblasts); however, none of the keratinocyte (n = 34) or fibroblast (n = 3) injections revealed coupling between the epidermal and dermal compartments. Cell coupling was found to be more extensive in epidermal ridges than in suprapapillary plates and, in both regions, was less extensive after injection of the basal layer of the epidermis than after that of the suprabasal layers. This study shows that junctional cell-to-cell communications take place in normal and fully differentiated human tissue. The quantitative data gathered also indicate a regional heterogeneity of keratinocyte-to-keratinocyte communication within intact adult skin and the lack of effect of retinoids on this pattern.
Intensivists are becoming gatekeepers to intensive care
Authors: M. J O'Leary
Journal: BMJ (2003)

EDITOR—Way et al present a brief overview of the major topic of end of life care in intensive care units.1 The main impact of this review might be to bring the issue to the attention of the general medical community, which may be unaware of the mode of death of most patients in intensive care.

Two interlinked issues were not covered by Way et al. The first is …
Frequent Microsatellite Instability and Mismatch Repair Gene Mutations in Young Chinese Patients With Colorectal Cancer
Authors: T. L. Chan, S. T. Yuen, L. P. Chung, J. W. C. Ho, K. Y. M. Kwan, A. S. Y. Chan, J. C. Y. Ho, S. Y. Leung, A. H. Wyllie
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: The incidence of colorectal cancer in persons under 46 years of age is substantially higher in Hong Kong than in Scotland and many other countries. Consequently, we examined whether there is a hereditary predisposition for colorectal cancer in this Southern Chinese population. METHODS: We investigated the incidence of microsatellite instability (MSI) at 10 DNA sites in 117 colorectal cancer specimens from Chinese patients of various ages. Those tumors with new alleles at 40% or more of the sites investigated were identified as highly unstable MSI (MSI-H). In young patients, we also searched for germline mutations in three mismatch repair genes (hMSH2, hMLH1, and hMSH6). RESULTS: The incidence of MSI-H varied statistically significantly with age, being observed in more than 60% of those younger than age 31 years at diagnosis and in fewer than 15% of those age 46 years or older. In 15 patients (<46 years old) whose colorectal cancers showed MSI-H, eight possessed germline mutations in either hMSH2 or hMLH1. When mutations in hMSH6 were included, more than 80% of Chinese colorectal cancer patients younger than 31 years had germline mutations in mismatch repair genes. We found a novel germline missense mutation in hMSH6 in a 29-year-old man whose tumor showed no MSI. Two patients had a 4-base-pair insertion in exon 10 causing a truncated protein; this insertion is a common polymorphism with a population allele frequency in Chinese of 5.6%. CONCLUSIONS: Our results indicate that germline mutations in mismatch repair genes contribute substantially to the pathogenesis and high incidence of colorectal cancer in young Hong Kong Chinese. However, because young Chinese and Caucasians show similar proportions of colorectal cancers with MSI-H, despite the higher incidence in the former, additional factors may underlie the high susceptibility of young Chinese to colorectal cancer.
Health literacy and sleep apnoea
Authors: R. Ghiassi, M. R. Partridge
Journal: Thorax (2010)

Determining which of our patients struggle with numeracy or literacy is difficult and clinicians overestimate the levels of patient literacy.1 In a report in this journal, we demonstrate that 33% of new patients and 16% of serial users have difficulty completing the Epworth Sleepiness Scale (ESS).2 To explore reasons for this we have assessed literacy in a further group of 122 patients attending either the Sleep Centre (Sleep group) or the Lung Function Laboratory (LF group). The level of functional literacy in medicine was assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM) questionnaire.3 A REALM score ≤60 suggests that the patient would struggle with patient education materials and …
Clinical, Molecular, and Genomic Changes in Response to a Left Ventricular Assist Device
Authors: Jennifer L. Hall, David R. Fermin, Emma J. Birks, Paul J.R. Barton, Mark Slaughter, Peter Eckman, Hideo A. Baba, Jeremias Wohlschlaeger, Leslie W. Miller
Journal: Journal of the American College of Cardiology (2011)
The effect of vasoactive agents on the left ventricular end-systolic pressure-volume relation in closed-chest dogs.
Authors: G L Freeman, W C Little, R A O'Rourke
Journal: Circulation (1986)

The left ventricular end-systolic pressure-volume relation has received intense interest as a relatively load-insensitive measure of cardiac performance. In clinical studies, pharmacologic manipulation of blood pressure has been used to determine this relation. Since previous studies have shown that acute changes in the resistance and impedance of the arterial circulation influence the left ventricular end-systolic pressure-volume relation, the use of vasoactive drugs in its determination may affect the results achieved. This study was undertaken to determine whether clinically used vasoactive drugs influence the left ventricular end-systolic pressure-volume relation. Sixteen dogs were previously instrumented with micromanometer pressure transducers and three sets of piezoelectric crystals to permit determination of left ventricular pressure and volume. The dogs were studied after autonomic blockade and sedation. End-systolic pressure-volume relations were generated by caval occlusion at control levels of blood pressure, after infusion of a vasopressor (methoxamine, n = 6; angiotensin II, n = 10), and then after infusion of nitroprusside. A composite end-systolic pressure-volume relation was also constructed with the use of control, vasopressor, and vasodilator points in each dog. Angiotensin II resulted in a leftward shift in the relation (Vo decreased from 14.32 +/- 7.3 to 8.04 +/- 10.4 ml, p less than .05) with no significant effect on slope. Methoxamine shifted the relation to the left (Vo decreased from 13.98 +/- 8.74 to -0.47 +/- 12.06 ml, p less than .05) and also reduced the slope (5.41 +/- 3.09 vs 8.28 +/- 3.94 mm Hg/ml, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of oxytetracycline administration on intestinal metabolism of oestrogens and on plasma sex hormones in healthy men.
Authors: E Hamalainen, J T Korpela, H Adlercreutz
Journal: Gut (1987)

The effect of oxytetracycline (1 g/day for five days) on the enterohepatic recycling of oestrogens and on plasma sex hormone concentrations was assessed in healthy men. Plasma oestrone (E1), oestradiol-17 beta (E2), 4-androstenedione (A), 5 alpha-dihydrotestosterone (5 alpha-DHT), total and free testosterone (T and free T), binding capacity of sex hormone binding globulin, luteinizing hormone, dehydroepiandrosterone-sulphate, urinary total E1, E2, and oestriol (E3), and oestriol-3-glucuronide (E3-3G) and faecal unconjugated and conjugated E1, E2, and E3 were measured by radioimmunoassay (RIA). Treatment with the antibiotic significantly increased the excretion of faecal conjugated oestrogens, which parallelled a decrease in urinary oestrogen excretion, especially of E3. The effect on urinary E3 could be explained almost entirely by the simultaneous decrease of urinary E3-3G concentrations. In urine and faeces the E2/E3 and E1 + E2/E3 ratios increased, probably because of the diminished reductive metabolism of oestrogens in the gut. No significant effects on plasma unconjugated oestrogen concentrations were observed. Moreover, in the present study oxytetracycline had no remarkable effect on plasma total, or free T concentrations, nor on other plasma hormones measured. Our results suggest that enterohepatic recycling and intestinal metabolism of oestrogens may be significant in men. The mechanism of action of antibiotics on oestrogen metabolism probably involves decreased hydrolysis by beta-glucuronidase of oestrogen conjugates by the intestinal contents, diminishing the reabsorption of aglycones of oestrogen conjugates and resulting in faecal loss of the steroids.
Respiration during sleep in normal man.
Authors: N J Douglas, D P White, C K Pickett, J V Weil, C W Zwillich
Journal: Thorax (1982)

Respiratory volumes and timing have been measured in 19 healthy adults during wakefulness and sleep. Minute ventilation was significantly less (p less than 0.05) in all stages of sleep than when the subject was awake (7.66 +/- 0.34(SEM) 1/min), the level in rapid-eye-movement (REM) sleep (6.46 +/- 0.29 1/min) being significantly lower than in non-REM sleep (7.18 +/- 0.39 1/min). The breathing pattern during all stages of sleep was significantly more rapid and shallow than during wakefulness, tidal volume in REM sleep being reduced to 73% of the level during wakefulness. Mean inspiratory flow rate (VT/Ti), an index of inspiratory drive, was significantly lower in REM sleep than during wakefulness or non-REM sleep. Thus ventilation falls during sleep, the greatest reduction occurring during REM sleep, when there is a parallel reduction in inspiratory drive. Similar changes in ventilation may contribute to the REM-associated hypoxaemia observed in normal subjects and in patients with chronic obstructive pulmonary disease.