tbuckley/cabot-search huggingface dataset:
Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel
Authors: S J Langlands
Journal: Gut (2004)

<b>Background and aims:</b> The mucosa associated flora of the large intestine is important in determining mucosal function although what controls its composition is unknown. This study has determined the effect of the prebiotic carbohydrates oligofructose and inulin on the mucosal flora. <b>Methods:</b> An in vitro chemostat model of both planktonic and surface associated bacteria was used followed by an intervention study in 29 subjects undergoing colonoscopy. <b>Subjects:</b> Fourteen subjects, recruited from colonoscopy waiting lists, supplemented their diet for two weeks with a mix of 7.5 g of oligofructose and 7.5 g inulin. Fifteen subjects were recruited at the time of colonoscopy and given no supplement. Multiple endoscopic biopsies were taken from the caecum, transverse and descending colon, and rectum. The mucosal flora was characterised by culture and to species level by cellular fatty acid profiles. Cell proliferation was assessed by immunohistochemical staining for minichromosome maintenance protein 2, Ki67, and proliferating cell nuclear antigen. <b>Results:</b> In vitro prebiotics increased surface counts of bifidobacteria from 6.6 to 7.3 log<sub>10</sub> colony forming units (CFU) per slide (p&lt;0.0006) with no significant changes in planktonic bacteria. In the feeding study, prebiotics increased mucosal bifidobacteria (log CFU/g mucosa (SEM)) in both the proximal (control 5.3 (0.4) <i>v</i> prebiotic 6.3 (0.3)) (p = 0.059) and distal (control 5.2 (0.3) <i>v</i> prebiotic 6.4 (0.3)) colon (p = 0.01). Lactobacilli were also increased (3.0 (0.1) <i>v</i> 3.7 (0.2) (p = 0.02) in the proximal and 3.1 (0.1) <i>v</i> 3.6 (0.2) (p = 0.04) in the distal colon, respectively). There were significantly more eubacteria in fed subjects but no changes in total anaerobes clostridia, bacteroides, or coliforms, nor in proliferation indices. <b>Conclusion:</b> Prebiotic carbohydrates can change the composition of the mucosa associated flora significantly.
Evaluation of airway reactivity and immune characteristics as risk factors for wheezing early in life
Authors: Weiguo Yao, Florencia M. Barbé-Tuana, Conrado J. Llapur, Marcus H. Jones, Christina Tiller, Risa Kimmel, Jeffrey Kisling, Evelyn T. Nguyen, James Nguyen, Zhangsheng Yu, Mark H. Kaplan, Robert S. Tepper
Journal: Journal of Allergy and Clinical Immunology (2010)
Clinical implications. The role of selective prescribing in the increased risk of VTE associated with third-generation oral contraceptives
Authors: C Jamin
Journal: Human Reproduction Update (1999)

In the early 1960s, it became apparent that oral contraception (OC) with oestroprogestogens increased the cardiovascular, venous thromboembolic (VTE), myocardial infarction (MI) and cerebrovascular accident (CVA) risk. The change in medical prescribing patterns, the reduction in ethinyloestradiol dosage and the use of less androgenic progestogens made prescribers confident that the risks would subsequently decrease. At the end of 1995 and early 1996, four publications called into question that optimism by showing that third-generation pills induced a two-fold increase in VTE risk compared with second-generation pills. A biological rationale was due to be announced later. Since then, re-analysis of the data has shown that the thrombotic risk factors are increased in third-generation OC users but, more importantly, that those users (unlike those using second-generation pills) are the women who have not had the opportunity of revealing a latent thrombophilia and are, therefore, at a greater risk of expressing it during third-generation OC intake. When these data are considered, the difference between second- and third-generation OC users in terms of VTE risk is completely destroyed. In addition and although the risk factors (smoking in particular) are concentrated in third generation OC users, the MI risk is less in those users than in second-generation pill users. This is particularly true in the presence of a risk factor such as smoking. No difference in risk has been observed for CVA in the general population between second- and third-generation OC users, but once more among smoking women the risk is lower with third-generation OC. Key words: cerebrovascular accident/myocardial infarction/oral contraceptive/third-generation oral contraceptive/venous thromboembolism
Upregulated autocrine vascular endothelial growth factor (VEGF)/VEGF receptor-2 loop prevents apoptosis in haemangioma-derived endothelial cells
Authors: Y. Ji, S. Chen, K. Li, X. Xiao, T. Xu, S. Zheng
Journal: British Journal of Dermatology (2013)

The autocrine vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-2 loop is required to maintain the transformed phenotype of many tumours, in part, by preventing apoptotic cell death in response to many different stimuli. However, it is unclear whether constitutive VEGF/VEGFR-2 activation in haemangioma-derived endothelial cells (HaemECs) can lead to a general suppression of apoptosis.The objective of this study was to investigate whether the autocrine VEGF loop promotes HaemEC survival via its receptor, VEGFR-2.HaemECs and human umbilical vein endothelial cells (HUVECs) were serum-starved for 12-48 h. Cell apoptosis was measured. The potential mechanisms of VEGF/VEGFR-2-induced HaemEC survival were investigated, and the role of the autocrine VEGF/VEGFR-2 loop in preventing propranolol-induced apoptotic HaemEC death was also analysed.Compared with HUVECs, HaemECs showed increased resistance to apoptosis induced by serum starvation. Upregulated VEGF/VEGFR-2 signalling in HaemECs induced an autocrine signalling loop, which resulted in Akt activation. Furthermore, this activation of Akt was necessary for VEGF/VEGFR-2-induced protection against serum deprivation-induced HaemEC apoptosis. In addition, Bcl-2, which functions as an anti-apoptotic factor and direct downstream target of PI3K/Akt, was decreased by the inhibition of VEGF/VEGFR-2, which led to an increase in caspase-3 activity, caspase-9 activity and HaemEC apoptosis. Moreover, HaemECs acquired greater resistance to propranolol treatment than HUVECs, whereas inhibition of VEGF/VEGFR-2 signalling in HaemECs sensitized these cells to propranolol-induced apoptosis.Our results demonstrate that upregulation of the autocrine VEGF/VEGFR-2 loop can induce general resistance to apoptotic stimuli in HaemECs.
Breaking the Law of Valgus: the surprising and unexplained prevalence of medial patellofemoral cartilage damage
Authors: K Douglas Gross, Jingbo Niu, Joshua J Stefanik, Ali Guermazi, Frank W Roemer, Leena Sharma, Michael C Nevitt, Neil A Segal, Cora E Lewis, David T Felson
Journal: Annals of the Rheumatic Diseases (2012)

To compare the prevalence of medial and lateral patellofemoral (PF) cartilage damage in three large osteoarthritis (OA) studies and determine the relationship of this damage to varus, neutral and valgus knee alignment.In the Boston OA of the Knee, Framingham OA and Multicenter OA studies, MRIs were read for cartilage morphology at the medial and lateral patella and trochlea femoris using Whole-Organ MRI Scores (WORMS). WORMS scores ≥2 (any cartilage defect), ≥3 (areas of partial thickness loss), ≥4 (diffuse partial thickness loss) and ≥5 (extensive full thickness loss) were all variously considered as thresholds to identify damage that may indicate OA. Full-limb radiographs were measured for mechanical alignment, and varus (<-2°), neutral (-2° to 2°) and valgus (>2°) knees were identified.The prevalence of medial PF cartilage damage exceeded that of lateral damage in all three studies and according to nearly every threshold. Only among severely involved knees (WORMS ≥4 or ≥5) did the prevalence of lateral PF cartilage damage approximate that of medial damage. The high prevalence of medial PF damage persisted in all strata of knee alignment. Even among knees with valgus alignment, the prevalence of lateral PF cartilage damage equalled or surpassed that of medial PF damage only when the threshold was specific to severely involved knees.Medial PF cartilage damage is at least as prevalent within these older adult populations as lateral PF cartilage damage.
Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies
Authors: Arnaud W Thille, Andrés Esteban, Pilar Fernández-Segoviano, José-María Rodriguez, José-Antonio Aramburu, Patricio Vargas-Errázuriz, Ana Martín-Pellicer, José A Lorente, Fernando Frutos-Vivar
Journal: The Lancet Respiratory Medicine (2013)
<i>RET</i> Proto-Oncogene in the Development of Human Cancer
Authors: Charis Eng
Journal: Journal of Clinical Oncology (1999)

The RET proto-oncogene, located on chromosome subband 10q11.2, encodes a receptor tyrosine kinase expressed in tissues and tumors derived from neural crest. Germline (present in every cell of the body) mutations in RET cause multiple endocrine neoplasia type 2 (MEN 2), an inherited cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PC), and hyperparathyroidism (HPT). This knowledge has allowed molecular diagnosis and presymptomatic DNA-based testing to become possible. RET testing is considered the standard of care in MEN 2 families because clinical decisions are made based on the results of such gene testing. There appears to be a correlation between specific RET mutation type and organ-specific tumor development. Such knowledge might be useful in tailoring targeted surveillance in the near future. Somatic (in the tumor only) RET mutations have been found in a proportion of sporadic MTCs and PCs. Whether the presence of somatic RET mutation is associated with a poor prognosis is currently being investigated as another tool for molecular medicine.
The developmental expression dynamics of Drosophila melanogaster transcription factors
Authors: Boris Adryan, Sarah A Teichmann
Journal: Genome biology (2010)

Abstract Background Site-specific transcription factors (TFs) are coordinators of developmental and physiological gene expression programs. Their binding to cis -regulatory modules of target genes mediates the precise cell- and context-specific activation and repression of genes. The expression of TFs should therefore reflect the core expression program of each cell. Results We studied the expression dynamics of about 750 TFs using the available genomics resources in Drosophila melanogaster . We find that 95% of these TFs are expressed at some point during embryonic development, with a peak roughly between 10 and 12 hours after egg laying, the core stages of organogenesis. We address the differential utilization of DNA-binding domains in different developmental programs systematically in a spatio-temporal context, and show that the zinc finger class of TFs is predominantly early expressed, while Homeobox TFs exhibit later expression in embryogenesis. Conclusions Previous work, dissecting cis -regulatory modules during Drosophila development, suggests that TFs are deployed in groups acting in a cooperative manner. In contrast, we find that there is rapid exchange of co-expressed partners amongst the fly TFs, at rates similar to the genome-wide dynamics of co-expression clusters. This suggests there may also be a high level of combinatorial complexity of TFs at cis -regulatory modules.
Angiongenesis: a new theory for endometriosis
Authors: D. Healy
Journal: Human Reproduction Update (1998)

Excessive endometrial angiogenesis is proposed as an important mechanism in the pathogenesis of endometriosis. Evidence is reviewed for the hypothesis that the endometrium of women with endometriosis has an increased capacity to proliferate, implant and grow in the peritoneal cavity. Data is summarized indicating that the endometrium of patients with endometriosis shows enhanced endothelial cell proliferation. Results are also reviewed indicating that the cell adhesion molecule integrin αvβ3 is expressed in more blood vessels in the endometrium of women with endometriosis when compared with normal women. Taken together, these results provide evidence for increased endometrial angiogenesis in women with endometriosis when compared with normal subjects. Endometriosis is one of the family of angiogenic diseases. Other angiogenic diseases include solid tumours, rheumatoid arthritis, psoriasis and diabetic retinopathy. Excessive endometrial angiogenesis suggests novel new medical treatments for endometriosis aimed at the inhibition of angiogenesis. Keywords: angiogenesis/endometriosis/endothelial cell proliferation/integrins
Validation and refinement of gene-regulatory pathways on a network of physical interactions.
Authors: Chen-Hsiang Yeang, H Craig Mak, Scott McCuine, Christopher Workman, Tommi Jaakkola, Trey Ideker
Journal: Genome biology (2005)

As genome-scale measurements lead to increasingly complex models of gene regulation, systematic approaches are needed to validate and refine these models. Towards this goal, we describe an automated procedure for prioritizing genetic perturbations in order to discriminate optimally between alternative models of a gene-regulatory network. Using this procedure, we evaluate 38 candidate regulatory networks in yeast and perform four high-priority gene knockout experiments. The refined networks support previously unknown regulatory mechanisms downstream of SOK2 and SWI4.
Moving towards personalised therapy in patients with hepatocellular carcinoma: the role of the microenvironment
Authors: Gianluigi Giannelli, Bhavna Rani, Francesco Dituri, Yuan Cao, Giuseppe Palasciano
Journal: Gut (2014)

The goal of personalised therapy based on hepatocellular carcinoma (HCC) molecular characteristics is still beyond our grasp. Systemic treatments show poor efficacy, mainly because of the great heterogeneity of the tumour. Indeed, differences in aetiology, disease stage and biochemical composition of the fibrotic liver make cirrhosis itself a highly dyshomogeneous disease. Cancer cells grow in a cirrhotic microenvironment, interacting with stromal cells and engaging matrix components that differ from patient to patient, hampering the development of drugs to treat all patients. Growing evidence suggests a role for the cross-talk between HCC and the host stroma in driving disease progression and hence prognosis and survival. Many efforts have been devoted to identifying genes responsible for good or bad prognosis, but no study has yet proven helpful in guiding therapeutic choices and management over time, also taking into account the development of drug resistance. The questions of what to target and in which patient are still unsolved. In the personalised therapy scenario, the patient rather than the disease becomes the target of the therapy. However, this still requires an evidence-based medical approach. Herein, we will discuss how individual differences in terms of quality and quantity of the tissue microenvironment components affect progression of HCC. Then, we will highlight potential druggable pathways, also considering ongoing clinical trials. The development of biomarkers will be discussed in the light of new experimental research conducted with the aim of moving towards personalised therapy in patients with HCC.
Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols.
Authors: J E Freedman, B Frei, G N Welch, J Loscalzo
Journal: Journal of Clinical Investigation (1995)

GSH peroxidase (Px) catalyzes the reduction of lipid hydroperoxides (LOOH), known metabolic products of platelets and vascular cells. Because interactions between these cells are modulated by nitric oxide (NO) and LOOH inactivate NO, we investigated the effect of GSH-Px on the inhibition of platelet function by the naturally occurring S-nitrosothiol, S-nitroso-glutathione (SNO-Glu). Concentrations of SNO-Glu that alone did not inhibit platelet function (subthreshold inhibitory concentrations) were added to platelet-rich plasma together with GSH-Px (0.2-20 U/ml); this led to a dose-dependent inhibition of platelet aggregation with an IC50 of 0.6 U/ml GSH-Px. In the presence of subthreshold inhibitory concentrations of SNO-Glu, the LOOH, 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid, increased platelet aggregation, an effect reversed by GSH-Px. Glutathione and SNO-Glu were equally effective as cosubstrates for GSH-Px. Incubation of SNO-Glu with GSH-Px for 1 min led to a 48.5% decrease in the concentration of SNO-Glu. Incubation of SNO-Glu with serum albumin led to the formation of S-nitroso-albumin, an effect enhanced by GSH-Px. These observations suggest that GSH-Px has two functions: reduction of LOOH, thereby preventing inactivation of NO, and metabolism of SNO-Glu, thereby liberating NO and/or supporting further transnitrosation reactions.
Hedgehog-GLI Pathway in Medulloblastoma
Authors: Tenley C. Archer, Shyamal D. Weeraratne, Scott L. Pomeroy
Journal: Journal of Clinical Oncology (2012)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2011.41.1181 Journal of Clinical Oncology - published online before print April 16, 2012 PMID: 22508821 Hedgehog-GLI Pathway in Medulloblastoma Tenley C. ArcherxTenley C. ArcherSearch for articles by this author , Shyamal D. WeeraratnexShyamal D. WeeraratneSearch for articles by this author , Scott L. PomeroyxScott L. PomeroySearch for articles by this author Show More Children's Hospital Boston, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2011.41.1181 First Page Full Text PDF Figures and Tables © 2012 by American Society of Clinical Oncology
Fractionated working memory: Even in pebbles, it's still a soup stone
Authors: Morten H. Christiansen, Maryellen C. MacDonald
Journal: Behavioral and Brain Sciences (1999)

We agree with Caplan &amp; Waters that there are problems with the single-resource theory of sentence comprehension. However, we challenge their dual-resource alternative on theoretical and empirical grounds and point to a more coherent solution that abandons the notion of working memory resources.
My worst day
Authors: Anne M Phillips
Journal: BMJ (2006)

The day was always going to be bad. It was the middle of winter, we had too many patients, and, as the second on-call house officer, I was holding the crash bleep. Predictably, when the first crash call of the day came I was at the opposite end of the hospital. I left my senior house officer and hurried down to the radiology department as I had been directed. By the time I arrived, resuscitation was already well in progress. With horror, I realised it was one of my team's …
Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.
Authors: L M Hultén, H Lindmark, U Diczfalusy, I Björkhem, M Ottosson, Y Liu, G Bondjers, O Wiklund
Journal: Journal of Clinical Investigation (1996)

The presence of oxysterols in macrophages isolated from atherosclerotic tissue and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA were studied. Both rabbit and human macrophages, freshly isolated from atherosclerotic aorta, show about the same distribution of oxysterols, analyzed by isotope dilution mass spectrometry, except that all three preparations of human arterial-derived macrophages contained high levels of 27-hydroxycholesterol, which was not found in rabbit macrophages. To determine if oxysterols regulate LPL expression, human monocyte-derived macrophages were incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by quantitative RT-PCR. Cholesterol and other tested oxysterols showed no effect on macrophage LPL mRNA expression compared with control. LPL activity in the medium was also reduced after exposure of the macrophages to 7 beta-hydroxycholesterol and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta. There was suppression of LPL mRNA in human monocyte-derived macrophages after incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is tempting to suggest that an exposure to oxysterols may explain our earlier observation of a low level of LPL mRNA in arterial foam cells.
Increased risk of adverse pregnancy outcomes in women with rheumatoid arthritis: a nationwide population-based study
Authors: Herng-Ching Lin, Shu-Fen Chen, Hsiu-Chen Lin, Yi-Hua Chen
Journal: Annals of the Rheumatic Diseases (2009)

Using a 3-year nationwide population-based database (2001-3), this study aims to examine the relationship between rheumatoid arthritis (RA) and adverse pregnancy outcomes.The study used the Taiwan National Health Insurance Research Dataset and birth certificate registry. In total, 1912 mothers with RA and 9560 matched comparison mothers were included. Separate conditional logistic regression analyses were carried out to explore the risk of low birthweight (LBW), preterm births, small for gestational age (SGA) infants, preeclampsia and delivery mode (vaginal vs caesarean section (CS)) for the study and comparison groups.Regression analyses showed that the adjusted odds of LBW, SGA infants, preeclampsia and CS for women with RA were 1.47 (95% CI 1.22 to 1.78), 1.20 (95% CI 1.05 to 1.38), 2.22 (95% CI 1.59 to 3.11) and 1.19 (95% CI 1.07 to 1.31) times, respectively, that of comparison mothers.Women with RA had an increased risk of LBW, SGA babies, preeclampsia and CS compared with unaffected women.
Tai chi: physiological characteristics and beneficial effects on health
Authors: J X Li, Y Hong, K M Chan
Journal: British Journal of Sports Medicine (2001)

Objectives —To assess the characteristic effects of Tai Chi Chuan (TCC) exercise on metabolism and cardiorespiratory response, and to measure its effect on cardiorespiratory function, mental control, immune capacity, and the prevention of falls in elderly people. Design —A review of controlled experimental studies and clinical trials designed with one of two aims: either to assess physiological responses during the performance of TCC or to assess the impact of this exercise on general health and fitness. Main outcome measures —Metabolic rate, heart rate, blood pressure, ventilation, maximal oxygen uptake (V̇ o 2 max ), immune capacity, falls, and fall related factors. Subjects —A total of 2216 men and women. Results —Under review were 31 original studies, published in Chinese or English journals, that met the criteria for inclusion. Most of the papers written in Chinese had not been introduced into the Western literature. Nine of these studies showed that TCC can be classified as moderate exercise, as its does not demand more than 55% of maximal oxygen intake. When this form of exercise and others conducted at equal intensity were compared, TCC showed a significantly lower ventilatory equivalent (V̇ e /V̇ o 2 max ). Evidence provided by cross sectional and longitudinal studies suggests that TCC exercise has beneficial effects on cardiorespiratory and musculoskeletal function, posture control capacity, and the reduction of falls experienced by the elderly. Conclusions —TCC is a moderate intensity exercise that is beneficial to cardiorespiratory function, immune capacity, mental control, flexibility, and balance control; it improves muscle strength and reduces the risk of falls in the elderly.