tbuckley/cabot-search huggingface dataset:
Increased Expression of Vascular Endothelial Growth Factor C in Papillary Thyroid Carcinoma Correlates with Cervical Lymph Node Metastases
Authors: Xiao-Min Yu, Chung-Yau Lo, Wai-Fan Chan, King-Yin Lam, Pauline Leung, John M. Luk
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Despite recent studies showing that vascular endothelial growth factor C (VEGF-C) mRNA is up-regulated in papillary thyroid carcinoma (PTC), the role of VEGF-C in lymph node metastasis is still unclear. The aim of this study is to investigate the expression pattern of VEGF-C immunoreactive protein in PTC and its relationship with cervical lymph node metastasis. Experimental Design: Tissue samples were obtained from 39 specimens of PTC (20 with and 19 without lymph node metastasis) as well as 20 benign thyroid nodules. Overexpression of the VEGF-C protein was evaluated by immunoblotting with specific anti-VEGF-C antibody in paired tumor and nontumor tissues from PTC. The data were compared with patients' clinicopathologic features and lymph node metastasis. Immunohistochemical staining was done on selected paraffin sections to determine cellular localization of VEGF-C and to assess flt-4 (or VEGFR-3)–positive vessel density in PTC lesions. Results: Overexpression of VEGF-C was detected in 69% of the PTC and in 5% of the benign thyroid specimens. When comparing between the metastatic and nonmetastatic groups of PTC, a higher expression level of VEGF-C was detected in both the tumor (P = 0.004) and adjacent nontumor tissues (P = 0.011). Positive immunostaining for VEGF-C was confirmed in PTC tumor tissues and metastatic lymph nodes, which correlated with flt-4-positive vessel density in tumor and peritumor tissues. The increased expression of VEGF-C protein in PTC is associated with lymph node metastasis (P = 0.004) and lymphovascular permeation (P = 0.001) but is independent of other clinicopatholgic variables. Conclusions: The VEGF-C immunoreactive protein is overexpressed in PTC lesions, which correlates with lymph node metastases. VEGF-C expression may play a role in lymphangiogenesis of PTC and further study is necessary to evaluate the clinical application of VEGF-C as a molecular marker for tumor metastases to cervical lymph nodes.
Commission will tell doctors they can raise concerns about practice even if they have signed secrecy agreements
Authors: A. O'Dowd
Journal: BMJ (2011)

Doctors are to be reassured that they are entitled to raise concerns about poor practice or patient care even if they have signed a compromise agreement when leaving a trust’s employment.

The news came at a one-off evidence session of the parliamentary health select committee on 7 December, as part of its inquiry into professional responsibility of healthcare practitioners.

A representative of the NHS regulator the Care Quality Commission told the committee’s MPs that the commission will send out a leaflet and “major communication” next week to explain clinicians’ rights in this area.

The select committee’s inquiry was prompted by an article in the Times newspaper last month, which claimed that clinicians were being …
Anatomy and radiology of the areae gastricae.
Authors: C E Mackintosh, L Kreel
Journal: Gut (1977)

The anatomy and radiology of the areae gastricae were studied in human and pig specimens and it was shown that the double contrast barium meal demonstrates a true picture of the undulating gastric mucosa, which is distinctive in appearance in the antrum body and fundus of the pig stomach. The importance of the type of barium used and the thickness of barrier mucus in the demonstration of the areae pattern is emphasised and the high incidence of duodenal ulcer in the grade 4 pattern and the low incidence in the non-coater is described. A knowledge of the anatomy and radiology of the areae gastricae pattern is central to the interpretation of the double contrast barium meal.
Comparison of Active Vitamin D Compounds and a Calcimimetic in Mineral Homeostasis
Authors: Loan Nguyen-Yamamoto, Isabel Bolivar, Stephen A. Strugnell, David Goltzman
Journal: Journal of the American Society of Nephrology (2010)

The differential effects between cinacalcet and active vitamin D compounds on parathyroid function, mineral metabolism, and skeletal function are incompletely understood. Here, we studied cinacalcet and active vitamin D compounds in mice expressing the null mutation for Cyp27b1, which encodes 25-hydroxyvitamin D-1α-hydroxylase, thereby lacking endogenous 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Vehicle-treated mice given high dietary calcium had hypocalcemia, hypophosphatemia, and marked secondary hyperparathyroidism. Doxercalciferol and 1,25(OH)(2)D(3) each normalized these parameters and corrected both the abnormal growth plate architecture and the diminished longitudinal bone growth observed in these mice. In contrast, cinacalcet suppressed serum parathyroid hormone (PTH) cyclically and did not correct the skeletal abnormalities and hypocalcemia persisted. Vehicle-treated mice given a "rescue diet" (high calcium and phosphorus, 20% lactose) had normal serum calcium and PTH levels; cinacalcet induced transient hypocalcemia and mild hypercalciuria. The active vitamin D compounds and cinacalcet normalized the increased osteoblast activity observed in mice with secondary hyperparathyroidism; cinacalcet, however, increased the number and activity of osteoclasts. In conclusion, cinacalcet reduces PTH in a cyclical manner, does not eliminate hypocalcemia, and does not correct abnormalities of the growth plate. Doxercalciferol and 1,25(OH)(2)D(3) reduce PTH in a sustained manner, normalize serum calcium, and improve skeletal abnormalities.
Regulation of Hepatocyte Growth Factor Activator Inhibitor 2 by Hypoxia in Breast Cancer
Authors: Daniele Generali, Stephen B. Fox, Alfredo Berruti, John W. Moore, Maria Pia Brizzi, Nilay Patel, Giovanni Allevi, Simone Bonardi, Sergio Aguggini, Alessandra Bersiga, Leticia Campo, Luigi Dogliotti, Alberto Bottini, Adrian L. Harris
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To examine the in vitro regulation of hepatocyte growth factor activator inhibitor type 2 (HAI-2) in breast cancer cells and the in vivo predictive role for the efficacy of chemoendocrine primary therapy in patients with breast cancer. Materials and Methods: HAI-2 regulation was studied in a panel of breast cancer cell lines comparing normoxia to hypoxia. The effect of HIF-1α RNAi on HAI-2 expression was evaluated in these cells. HAI-2 was examined in breast cancer using in situ hybridization and immunohistochemistry. The HAI-2 predictive role was assessed in T2-4 N0-1 breast cancers (n = 177) enrolled in a neoadjuvant randomized trial comparing epirubicin versus epirubicin + tamoxifen. Results: HAI-2 mRNA and protein were regulated by hypoxia in the c-erbB2–positive cell lines, SKBR3 and BT474, and controlled by HIF-1α in these cells. Immunohistochemistry confirmed this profile with high expression of HAI-2 in c-erbB2–positive breast cancer. HAI-2 was correlated with T status (P &amp;lt; 0.004), node involvement (P = 0.01), and c-erbB2 expression (P = 0.05). HAI-2 also correlated with hypoxia markers such as carbonic anhydrase IX expression (P = 0.01) and HIF-1α. Additionally, high levels of HAI-2 were a significant predictor for poor clinical complete response to preoperative epirubicin in univariate (P = 0.01) and multivariate analyses (P = 0.016). No correlation with disease-free survival and survival was observed. Conclusion: HAI-2 expression in breast cancer correlated with tumor aggressiveness in vivo. It is a HIF target in c-erbB2–positive cells and it is an independent negative predictive factor of efficacy of anthracycline therapy. The interaction of HAI-2 with the hepatocyte growth factor activation pathway may be a useful site for therapeutic intervention.
The embryonic muscle transcriptome of Caenorhabditis elegans
Authors: Rebecca M Fox, Joseph D Watson, Stephen E Von Stetina, Joan McDermott, Thomas M Brodigan, Tetsunari Fukushige, Michael Krause, David M Miller
Journal: Genome biology (2007)

Abstract Background The force generating mechanism of muscle is evolutionarily ancient; the fundamental structural and functional components of the sarcomere are common to motile animals throughout phylogeny. Recent evidence suggests that the transcription factors that regulate muscle development are also conserved. Thus, a comprehensive description of muscle gene expression in a simple model organism should define a basic muscle transcriptome that is also found in animals with more complex body plans. To this end, we applied microarray profiling of Caenorhabtidis elegans cells (MAPCeL) to muscle cell populations extracted from developing C. elegans embryos. Results We used fluorescence-activated cell sorting to isolate myo-3 ::green fluorescent protein (GFP) positive muscle cells, and their cultured derivatives, from dissociated early C. elegans embryos. Microarray analysis identified 7,070 expressed genes, 1,312 of which are enriched in the myo-3 ::GFP positive cell population relative to the average embryonic cell. The muscle enriched gene set was validated by comparisons with known muscle markers, independently derived expression data, and GFP reporters in transgenic strains. These results confirm the utility of MAPCeL for cell type specific expression profiling and reveal that 60% of these transcripts have human homologs. Conclusion This study provides a comprehensive description of gene expression in developing C. elegans embryonic muscle cells. The finding that more than half of these muscle enriched transcripts encode proteins with human homologs suggests that mutant analysis of these genes in C. elegans could reveal evolutionarily conserved models of muscle gene function, with ready application to human muscle pathologies.
Severe sepsis in cirrhosis
Authors: Thierry Gustot, François Durand, Didier Lebrec, Jean‐Louis Vincent, Richard Moreau
Journal: Hepatology (2009)

Sepsis is physiologically viewed as a proinflammatory and procoagulant response to invading pathogens. There are three recognized stages in the inflammatory response with progressively increased risk of end-organ failure and death: sepsis, severe sepsis, and septic shock. Patients with cirrhosis are prone to develop sepsis, sepsis-induced organ failure, and death. There is evidence that in cirrhosis, sepsis is accompanied by a markedly imbalanced cytokine response ("cytokine storm"), which converts responses that are normally beneficial for fighting infections into excessive, damaging inflammation. Molecular mechanisms for this excessive proinflammatory response are poorly understood. In patients with cirrhosis and severe sepsis, high production of proinflammatory cytokines seems to play a role in the worsening of liver function and the development of organ/system failures such as shock, renal failure, acute lung injury or acute respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. In addition, these patients may have sepsis-induced hyperglycemia, defective arginine-vasopressin secretion, adrenal insufficiency, or compartmental syndrome. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), early use of antibiotics and intravenous albumin administration decreases the risk for developing renal failure and improves survival. There are no randomized studies that have been specifically performed in patients with cirrhosis and severe sepsis to evaluate treatments that have been shown to improve outcome in patients without cirrhosis who have severe sepsis or septic shock. These treatments include recombinant human activated C protein and protective-ventilation strategy for respiratory failure. Other treatments should be evaluated in the cirrhotic population with severe sepsis including the early use of antibiotics in "non-SBP" infections, vasopressor therapy, hydrocortisone, renal-replacement therapy and liver support systems, and selective decontamination of the digestive tract or oropharynx. (HEPATOLOGY 2009.)
Verification of the newest reference values for spirometry in young children
Authors: Waldemar Tomalak, Jakub Radlinski, Zbigniew Doniec
Journal: European Respiratory Journal (2014)

Spirometry is a basic diagnostic tool in pulmonary medicine, also used in children. Recently new sets of reference values have been published (Stanojevic et al; AJRCCM 2009, (1)) and the so called GLI2012 (Quanjer et al. ERJ 2012 (2)) that allow interpretation of spirometry in children as young as 3 years of age.

The aim of a present study was to verify what is the distribution of calculated reference values (% predicted and z-score) in a group of children without signs of obstruction. The analysis was performed on the results obtained in 152 children aged 4-10 yrs, who before spirometry underwent oscillometric measurements (IOS) and had normal respiratory resistances, to exclude those with potential obstruction. We have analysed FEV1/FVC with both reference equations sets and also FEV0.75/FVC using equation of Stanojevic et al.

The table presents the results:

View this table:

Table 1.





The results show, that in a group of children , potentially non-obstructed, z-scores have normal distribution with mean value close to zero and SD approaching 1. The equations for reference values can be used in Polish children

Refs:

1. S. Stanojevic et al. Spirometry centile charts for young Caucasian children. AJRCCM 2009; 180:547-552.

2. Quanjer P.H.,.et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. ERJ 2012,40: 1324-1343.
12/15-Lipoxygenase Gene Disruption Attenuates Atherogenesis in LDL Receptor–Deficient Mice
Authors: Jacob George, Arnon Afek, Aviv Shaish, Hana Levkovitz, Nira Bloom, Tillmann Cyrus, Lei Zhao, Colin D. Funk, Eliott Sigal, Dror Harats
Journal: Circulation (2001)

Background Human 15-lipoxygenase (LO) and its murine analogue 12/15-LO are capable of directly oxidizing esterified fatty acids in lipoproteins and phospholipids. Because these oxidized products possess atherogenic properties, it was suggested that LOs may be involved in enhancing atherogenesis. Previous in vivo tests of the role of LOs in atherogenesis animal models, however, have yielded conflicting results. Methods and Results Aiming to study the role of the 12/15-LO in murine atherogenesis, we crossed LDL-receptor–deficient mice (LDL-R −/− ) with 12/15-LO–knockout mice and evaluated plaque formation 3 to 18 weeks after initiation of a high-fat diet. Atherosclerotic lesions were considerably reduced in the LDL-R/12/15-LO–double-knockout mice compared with LDL-R −/− mice at 3, 9, 12, and 18 weeks, at the aortic root as well as throughout the aorta. The cellular composition of plaques from mice deficient in 12/15-LO did not differ with respect to macrophage and T-lymphocyte content compared with plaques from 12/15-LO littermates. Conclusions 12/15-LO plays a dominant role in promoting atherogenesis in LDL-R −/− mice.
PWE-036 Clinical Presentation, Causes and Outcome of Ulcers in Ileo-Cecal Region: A Prospective Study from a Tropical Country
Authors: J Toshniwal, R Chawlani, A Kumar, M Kumar, A Arora
Journal: Gut (2013)

<h3>Introduction</h3> Ulcerations in the ileo-cecal (IC) region may have various causes and outcome, depending on the geographical region of the patients. Such data is scarce from tropical countries. <h3>Methods</h3> To evaluate the clinical, endoscopic and histologic characteristics of ileocecal ulcers in a tropical country. Prospective study of consecutive patients undergoing colonoscopy, and diagnosed to have ulcerations in the IC region presenting at an tertiary care centre. All patients underwent endoscopic documentation. Biopsy was obtained and their clinical presentation and outcome were recorded. <h3>Results</h3> Out of 1632 colonoscopies performed in our hospital from May 2010 to October 2011, 104 patients had ulcerations in the IC region. This population represents the study group. The median age was 44.5 years (range 18–85)and 59% were male. The predominant presentation was lower GI bleed (55.5%), pain abdomen +/-diarrhoea (36.3%), diarrhoea alone (9.9%), or miscellaneous (4.4%). Associated fever was present in 32 (31%) patients. On colonoscopy, terminal ileum could be entered in 96 (92%) cases. The distribution of ulcers was as follows: Ileum alone 40% (38/96), cecum alone 33% (32/96), and both ileum plus cecum 27% (26/96). In the 8 patients in whom ileum could not be entered ulcerations were present in the cecum and the IC valve. The ulcers were multiple in 98% and in 34% there were additional ulcers elsewhere in colon. Based on clinical presentation and investigations, the aetiology of ulcers was classified into infective causes (43%), non-infective causes (29%), and non-specific ulcers (28%) (Table). With infective cause, fever was significantly more common (47% vs 19%; p &lt; 0.01) and cecum was preferentially involved (82% vs 45%; p &lt; 0.01). Three patients (3%) died (all had presented with bleed and had non-specific ulcers), and 8 patients (8%)required surgical treatment. The remaining 93 patients (89%) had an uneventful recovery. <h3>Conclusion</h3> Unlike in Western countries the most common (&gt; 40%) cause of ulcerations of the IC region in the tropics is infections. Cecal involvement and fever are important clues to infective cause. These causes must be kept in mind while treating IC ulcers in patients from the tropics. <h3>Disclosure of Interest</h3> None Declared.
Roles of polarized neutrophils on lung tumour development in an orthotopic lung tumour mouse model
Authors: Natacha Rocks, Sandrine Bekaert, Geoff Warnock, Christelle Sepult, Raphaël Marée, J.M. Foidart, Agnes Noël, Didier Cataldo
Journal: European Respiratory Journal (2013)

Lung cancer is a highly deadly disease and results of current treatments are still deceiving. It has recently become evident that inflammation contributes to enhance tumour development by modifying the tumour microenvironment. Neutrophils represent the most abundant type of white blood cells and are an essential part of the innate immune system, suggesting their important functions in tumour biology.  The aim of this study was to understand the potential impact of neutrophilic inflammation on lung tumour development in a non invasive orthotopic mouse model. For this, Lewis Lung Carcinoma (LLC) tumour cells were intratracheally injected with or without a pro-inflammatory agent.  We report that neutrophilic inflammation induced by a polysaccharide compound is able to enhance lung tumour development while the LPS-induced inflammation only modestly increased tumour volumes. Interestingly, neutrophils isolated from lungs of mice stimulated by this inflammation-inducing polysaccharide displayed more often N2-protumoral phenotype when compared to neutrophils isolated from LPS-challenged lungs. Higher levels of β2-integrin were measured in polysaccharide-challenged lungs and an increased number of interactions of neutrophils expressing β2-integrin with ICAM-1 molecules present on epithelial pulmonary cells might be hypothesised as a mechanism for enhanced tumour development.  We propose in this study that N2-neutrophils enhance lung tumour cells anchorage on the airway epithelium by bridging the tumour cells with the epithelium. Importantly, inflammatory agents inducing N2-neutrophils mainly seem mandatory for a pro-tumour effect.
Use of lipophilic probes of membrane potential to assess human neutrophil activation. Abnormality in chronic granulomatous disease.
Authors: B E Seligmann, J I Gallin
Journal: Journal of Clinical Investigation (1980)

Previous studies using membrane potential sensitive probes have provided evidence that chemotactic factors elicit membrane potential changes in normal human neutrophils (PMN). In addition to stimulation of PMN motility, chemotactic factors also stimulate degranulation and superoxide ion (O-2) generation and it has been suggested that alteration of membrane potential activates these events (Korchak, H. M., and G. Weissmann. 1978. Proc, Natl, Acad, Sci. U. S. A. 75: 3818--3822). To further define the inter-relationship of these functions, studies were done with two indirect probes of membrane potential, 3-3'-dipentyloxacarbocyanine and triphenylmethylphosphonium ion (TPMP+) using PMN from normal subjects, from patients with abnormal O-2 production (chronic granulomatous disease [CGD]), and from patients with defective degranulation and/or chemotaxis (Cheddiak-Higashi syndrome and patients with elevated immunoglobulin (Ig)E and recurrent staphylococcal infections). The stimuli used were the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) and the secretagogues ionophore A23187 and phorbol myristate acetate (PMA). The results obtained with 3-3'-dipentyloxacarbocyanine and TPMP+ were comparable. The apparent membrane potential changes elicited by f-Met-Leu-Phe and PMA in normal PMN were reduced or entirely absent in PMN obtained from patients with CGD but normal in PMN from other patients. PMN from patients with CGD had normal calculated resting membrane potentials and normal responses elicited by the potassium ionophore valinomycin. The responses to calcium ionophore A23187 were only slightly impaired. The abnormality of the elicited response of CGD cells of f-Met-Leu-Phe and PMA could not be attributed to the absence of O-2, hydroxyl radical, singlet oxygen, or hydrogen peroxide acting on the probes. Instead this abnormality appears to be associated with a dysfunction in the normal molecular mechanism(s) stimulated upon neutrophil activation. The data suggest chemoattractant alteration of membrane potential in normal PMN is related to activation of oxidative metabolism but the relationship to chemotaxis and degranulation remains to be established.
<scp>ESC</scp> Working Group on Myocardial Function Position Paper: how to study the right ventricle in experimental models
Authors: Adelino F. Leite‐Moreira, André P. Lourenço, Jean‐Luc Balligand, Johann Bauersachs, Angela Clerk, Leon J. De Windt, Stephane Heymans, Denise Hilfiker‐Kleiner, Emilio Hirsch, Guido Iaccarino, Karol A. Kaminski, Ralph Knöll, Manuel Mayr, Guido Tarone, Thomas Thum, Carlo G. Tocchetti
Journal: European Journal of Heart Failure (2014)