tbuckley/cabot-search huggingface dataset:
Lympho-Vascular Invasion by Detecting D2-40 Was the Potent Prognostic Predictor in Breast Cancer Patients.
Authors: S. Woo, W. Ryu, J. Lee, H. Kim, C. Kim, G. Son, E. Lee, J. Lee, J. Bae
Journal: Cancer Research (2009)

Abstract (Introduction) Distant metastasis and recurrence are the major factors of prognosis in breast cancer patients. Both of lymphovascular invasion (LVI) and blood vascular invasion (BVI) are known to be the important route for metastasis to regional lymph nodes and systemic metastasis. Despite the importance of vascular invasion as a prognostic factor, the application of vascular invasion as a histopathologic criterion is controversial. The aims of this study were to distinguish between LVI and BVI for the role of prognosis and recurrence in breast cancer patients by using an endothelial subtype specific immunohitochemical stain (podoplanin, D2-40 and CD31)Methods) Sections from 80 paraffin-embedded archival specimens of invasive breast cancer were stained for expression of podoplanin, D2-40, and CD31. The results of immunohistochemical staining were correlated with clinicopathologic features, such as tumor size, the status of lymph node metastases, estrogen receptor status, progesterone receptor status and HER2 expression, and recurrence. The patients with ductal carcinoma in situ and stage 4 breast cancer were excluded.Results) A significant correlation was found in the higher expression of D2-40, and lymph node metastasis. (P=0.02) We found a significant correlation between the expression of D2-40 and the recurrence of breast cancer. (P=0.04) However, there was no significant correlation between BVI and recurrence. A poorer disease free survival was shown in the higher expression of D2-40. (P&amp;lt;0.01) In multivariate analysis, the higher expression of D2-40 revealed a significant association with decreased disease-free survival.Conclusion) The higher expression of D2-40 was the more prognostic predictor than blood vascular invasion in breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6171.
Differential effects of carvedilol and metoprolol on isoprenaline-induced changes in β-adrenoceptor density and systolic function in rat cardiac myocytes
Authors: M Flesch
Journal: Cardiovascular Research (2001)

Objective: β-Blockers improve cardiac function and survival in heart failure patients. The underlying mechanisms are not completely elucidated. Differences between agents might be important for the development of more specific therapeutical approaches. This study investigated whether metoprolol or carvedilol alter β-adrenergic signaling differently. Methods: β-Adrenoceptor density and systolic function were determined in rat adult ventricular cardiac myocytes. Results: 12 h isoprenaline-treatment (Iso, 1 μmol/l) reduced β-adrenoceptor density by 33% (P<0.01). The effect was abolished by incubation with isoprenaline plus metoprolol (3 μmol/l), but was more pronounced after coincubation with carvedilol (0.003 μmol/l, P<0.05 Carv vs. Iso). Metoprolol alone had no effect on β-adrenoceptor density, but carvedilol induced a decrease in receptor density even in absence of isoprenaline (P<0.05 Carv vs. ctr.). The isoprenaline (0.0003–10 μmol/l) induced concentration-dependent increase in myocyte shortening was blunted after 12 h preincubation with Iso (1 μmol/l, P<0.001). This reduction was abolished or partly prevented by coincubation with metoprolol or carvedilol, respectively. Carvedilol decreased the number of receptors which had to be occupied by isoprenaline in order to obtain 50% and 90% increase in myocyte cell shortening. Comparison of guanine nucleotide-dependent binding characteristics of isoprenaline, carvedilol and metoprolol revealed β-receptor agonist like binding characteristics for carvedilol, but antagonist like binding characteristics for metoprolol. Conclusion: Metoprolol but not carvedilol prevents isoprenaline-induced downregulation of myocyte β-adrenoceptors. The difference might be due to specific binding properties of the β-blockers. Restoration of isoprenaline responsiveness by carvedilol might be due to improved coupling of β-receptors to postreceptor effects.
Adrenomedullin augments nitric oxide and tetrahydrobioptein synthesis in cytokine-stimulated vascular smooth muscle cells
Authors: Yoshiyuki Hattori, Nobuo Nakanishi, Steven S Gross, Kikuo Kasai
Journal: Cardiovascular Research (1999)

Objective: Immunostimulants increase nitric oxide (NO) and tetrahydrobiopterin (BH4) synthesis in vascular smooth muscle cells (VSMC) by coinducing expression of an isoform of NO synthase (iNOS) and GTP cyclohydrolase I (GTPCH). GTPCH is the first and rate-limiting enzyme in the synthesis of BH4, a cofactor of NO synthases. Given that adrenomedullin (AM) increases NO production, this effect of AM may involve modulation of BH4 synthesis in cytokine-stimulated VSMC. Methods: We investigated the effects of AM on the synthesis of NO and BH4, the expression of iNOS and GTPCH mRNA, and the promoter activity of iNOS and GTPCH genes in rat VSMC stimulated with interleukin-1 (IL-1). Results: IL-1 increased both NO and BH4 synthesis as well as the abundance of iNOS and GTPCH mRNA. AM significantly increased both NO and BH4 synthesis caused by IL-1 stimulation. AM also augmented the IL-1-induced increase in the abundance of iNOS and GTPCH mRNA. IL-1 activated the iNOS promoter activity as well as the GTPCH promoter activity in VSMC. AM alone had no effect on the activity of either the iNOS or the GTPCH promoter, nor did it potentiate the activation by IL-1 of either of these promoters. Conclusion: These results suggest that AM increases IL-1-induced NO and BH4 synthesis by enhancing the expression of iNOS and GTPCH genes at the post-transcriptional level. Thus, the potentiating effect of AM on NO synthesis appears to be associated with an increased expression of both genes necessary for cellular NO synthesis in VSMC.
Deaths from Asthma
Authors: G. W. Lewis
Journal: BMJ (1968)

could lower the 14 % mortality achieved in the past for immediate resection of the sig- moid colon for volvulus.At the same time I am sure that conservative management of a similar selected group could achieve a lower mortality than the 3% achieved in the past.I do not agree that the cases undergoing immediate resection included a high proportion exhibiting signs of shock and peritonitis.On the contrary, these were to some extent a selected group of good-risk patients in that resection was confined to cases which both surgeon and anaesthetist judged to be fit for further major surgery after reduction of the valvulus had been completed.This accounted for the recording of a lower mortality after untwisting and resection than after untwisting alone.I do not agree with Mr. Marcus's prog- nosis of patients refusing resection.The mortality is not greater in recurrent attacks.A mortality of 50 in 425 does not appertain to recurrences treated conservatively.A mor- tality of 3% from gangrene plus 3% from other causes would account for one death in 18 recurrences rather than the two deaths suggested by Mr. Marcus's own figures.His final prediction of four deaths is clearly an error of arithmetic.-Iam, etc.,
Pathology for the Physician
Authors: Sigmund L. Wilens
Journal: JAMA (1965)

Reviewers of bulky textbooks can only leaf through the pages, stopping periodically to scrutinize selected portions which will help give an overall evaluation. Such a technique does not work with this new edition of Boyd's<i>Pathology for the Physician.</i>The reviewer, soon trapped by one of the author's artfully turned phrases or by the collector's-item quotations from classical medical works, finds himself reading on and on in the fashion of a second-year medical student cramming for tomorrow's examination. The illustrations are also ensnaring. They represent jewels carefully selected to show the uncommon as well as the characteristic lesions of newly described conditions. If a physician, regardless of specialty, had to choose a single book with which to be shipwrecked on an island, this surely would be the best. Doctors seem to have found this out on their own, as the book has gone through seven editions and 19 printings since
Dutch health service is asked to draw up smallpox contingency plans
Authors: T. Sheldon
Journal: BMJ (2003)

The Dutch Ministry of Health has written to all local health services asking them to complete contingency plans by April for the mass vaccination against smallpox of the Dutch population of 16 million.

It has told all 39 municipal health services that although there is “no actual threat of an outbreak of smallpox” the “current political instability in the world” means that a “a high priority” should be given to preparing for an outbreak, possibly on a large scale.

The mass vaccination option is just one part of plans to counter bioterrorism being drawn up by the National Coordination Centre for …
Endothelium-Derived Hyperpolarizing Factor
Authors: Paul Coats, Fiona Johnston, John MacDonald, John J. V. McMurray, Chris Hillier
Journal: Circulation (2001)

Background —Both a vascular endothelial cytochrome P450 (CYP450) product of arachidonic acid metabolism and the potassium ion (K + ) have been identified as endothelium-derived hyperpolarizing factors (EDHFs) in animal vascular tissues. We studied the relative importance of EDHF, nitric oxide (NO), and prostacyclin (PGI 2 ) as vasodilators in human subcutaneous arteries. We also examined the mechanisms underlying the vasodilator action of EDHF to elucidate its identity. Methods and Results —Subcutaneous resistance arteries were obtained from 41 healthy volunteers. The contribution of EDHF to the vasodilation induced by acetylcholine was assessed by inhibiting production of NO, PGI 2 , and membrane hyperpolarization. The mechanisms underlying the relaxation evoked by K + and EDHF were elucidated. EDHF was found to account for ≈80% of acetylcholine-mediated vasorelaxation. Its action was insensitive to the combination of barium and ouabain, whereas barium and ouabain reversed K + -mediated vasorelaxation. EDHF-mediated vasorelaxation, however, was sensitive to the phospholipase A 2 inhibitor oleyloxyethyl phosphorylcholine and the CYP450 inhibitor ketoconazole. Conclusions —EDHF is the major contributor to endothelium-dependent vasorelaxation in human subcutaneous resistance arteries. A product of phospholipase A 2 /CYP450–dependent metabolism of arachidonic acid and not K + is the likely identity of EDHF in human subcutaneous resistance arteries.
S19 Imaging Derived Regional Lung Function Using Hyperpolarised Xenon Mri (xe-mri) And Quantitative Computed Tomography (qct) In Chronic Obstructive Pulmonary Disease (copd)
Authors: T. Matin, X. Xu, T. Doel, V. Grau, N. Rahman, A. Nickol, F. Gleeson
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> To derive quantitative regional imaging lung function parameters using hyperpolarised xenon MRI (Xe-MRI) and computed tomography (QCT), and compare these to pulmonary function tests (PFTs) in subjects with chronic pulmonary obstructive disease (COPD). <h3>Methods</h3> Twenty patients with COPD (stage II – IV GOLD criteria classification) underwent Xe-MRI at 1.5T, QCT, and PFTs. Whole lung and lobar percentage ventilated volumes were obtained using automated segmentation of multi-slice Xe-MRI ventilation images acquired at a breath hold of FRC + 1L using in-house software. Average whole lung apparent diffusion coefficients (ADCs) were calculated from multi-slice Xe-MRI diffusion-weighted images (<i>b</i>=20.855 sec/cm<sup>2</sup>). Percentage predicted PFT results were established for each participant. Whole lung and lobar QCT-derived metrics for emphysema and bronchial wall thickness were calculated from percentage of lung tissue with density of &lt;-950 HU and Pi10 (the square root of wall area for an airway with lumen perimeter of 10 mm), respectively. Pearson’s correlation coefficients were used to evaluate the relationship between whole lung and lobar imaging measures and PFTs. <h3>Results</h3> Xe-MRI whole lung average ADC showed significant correlation with: whole lung QCT percentage emphysema (<i>r = 0</i>.79, p = 0.001), whole lung Pi10 (<i>r = 0</i>.68, p &lt; 0.05), percentage predicted functional residual capacity (FRC) (<i>r = 0</i>.635, p &lt; 0.05) and demonstrated significant negative correlation with percentage predicted TLCO (<i>r</i>= -0.81, p &lt; 0.001). Whole lung QCT percentage emphysema showed a similar significant negative correlation with percentage predicted TLCO (<i>r</i>= -0.80, p &lt; 0.001). Xe-MRI lobar percentage ventilated volume showed significant correlation with lobar QCT percentage emphysema (<i>r</i>= -0.51, p &lt; &lt;0.001). The QCT-derived metrics, percentage emphysema and Pi10 demonstrated significant correlation on a whole lung (<i>r = 0</i>.75, p &lt; 0.015) and lobar basis (<i>r = 0</i>.29, p &lt; 0.015). <h3>Conclusion</h3> This study demonstrates excellent correlation between Xe-MRI, QCT-derived metrics and PFTs in COPD. New quantitative whole lung and lobar functional imaging parameters have been derived that may be of value when assessing patients with COPD for regional treatment and in trialling new therapies. Although further investigation is required, this may represent the first integrated regional lung imaging technique linked to pulmonary functional outcomes.
Bacterial Meningitis
Authors: Morton N. Swartz
Journal: New England Journal of Medicine (1984)

Fifty to 70 years ago, in the era before the introduction of the sulfonamides and antibiotic agents, relatively meager attention was given to the neurologic complications and sequelae of bacterial meningitis. The mortality from this disease was so dreadfully high that it diverted attention from the neurologic complications among the few survivors. The case-fatality rate for pneumococcal meningitis, even in the years after the introduction of specific types of antiserum for clinical use, was between 95 and 100 per cent.1 Similarly, death occurred in 92 per cent of patients with Hemophilus influenzae meningitis.2 Only in "epidemic cerebrospinal meningitis" (meningococcal meningitis) . . .
A Randomized, Placebo-Controlled, Double-Blind Trial of the Effect of Combined Therapy With Deferoxamine and Deferiprone on Myocardial Iron in Thalassemia Major Using Cardiovascular Magnetic Resonance
Authors: M.A. Tanner, R. Galanello, C. Dessi, G.C. Smith, M.A. Westwood, A. Agus, M. Roughton, R. Assomull, S.V. Nair, J.M. Walker, D.J. Pennell
Journal: Circulation (2007)

Cardiac complications secondary to iron overload are the leading cause of death in beta-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect. Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P=0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P=0.05), and absolute endothelial function (8.8% versus 3.3%; P=0.02). There was also a significantly greater improvement in serum ferritin in the combined group (-976 versus -233 microg/L; P<0.001). In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.
Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis
Authors: W. Casscells, W.K. Vaughn, H. McAllister, J.T. Willerson, W. Casscells, J.T. Willerson, W. Casscells, B. Hathorn, M. David, W. Vaughn, H.K. McAllister, J.T. Willerson, T. Krabach, G. Bearman
Journal: The Lancet (1996)
The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells
Authors: Simona Colla, Fenghuang Zhan, Wei Xiong, Xiaosong Wu, Hongwei Xu, Owen Stephens, Shmuel Yaccoby, Joshua Epstein, Bart Barlogie, John D. Shaughnessy
Journal: Blood (2007)
Induced sputum and bronchial mucosal expression of interleukin‐13 is not increased in chronic obstructive pulmonary disease
Authors: S. Saha, V. Mistry, R. Siva, D. Parker, R. May, P. Bradding, I. D. Pavord, C. E. Brightling
Journal: Allergy (2008)

Background: The Th2 cytokine interleukin‐13 (IL‐13) has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We sought to examine IL‐13 expression in COPD subjects in induced sputum and bronchus specimens. We hypothesized that inflammatory cells expressing IL‐13 localize to the airway smooth muscle bundle and bronchial glands. Methods: Interleukin‐13 was measured in sputum samples from subjects with COPD ( n = 34) across a range of severity (Global initiative for chronic Obstructive Lung Disease 2–4) and controls ( n = 14) using ELISA. IL‐13+ cells and inflammatory cells were enumerated within surgically resected proximal airway using immunohistochemical techniques from subjects with COPD ( n = 10), smoking ( n = 10) and nonsmoking controls ( n = 8). Results: Sputum IL‐13 was measurable in only 6/34 subjects with COPD and was not found in the smoking or nonsmoking control subjects. In subjects with COPD and controls there was a paucity of IL‐13+ cells. The distribution of inflammatory cells within different airway compartments was similar in COPD and controls except for an increase in CD3 + lymphocytes within bronchial glands in COPD ( P = 0.04). Conclusions: Our findings do not support a role for IL‐13 in COPD. However, the tissue localization of inflammatory cells to airway compartments, particularly the increase of T cells in glands in COPD may be important in disease.
Critical Roles for Non-pRb Targets of Human Papillomavirus Type 16 E7 in Cervical Carcinogenesis
Authors: Scott Balsitis, Fred Dick, Nicholas Dyson, Paul F. Lambert
Journal: Cancer Research (2006)

Abstract High-risk human papillomaviruses (HPV) encode two oncogenes, E6 and E7, expressed in nearly all cervical cancers. In vivo, HPV-16 E7 has been shown to induce multiple phenotypes in the context of transgenic mice, including cervical cancer. E7 is a multifunctional protein known best for its ability to inactivate the tumor suppressor pRb. To determine the importance of pRb inactivation by E7 in cervical cancer, we pursued studies with genetically engineered mice. E7 expression in estrogen-treated murine cervix induced dysplasia and invasive cancers as reported previously, but targeted Rb inactivation in cervical epithelium was not sufficient to induce any cervical dysplasia or neoplasia. Furthermore, E7 induced cervical cancer formation even when the E7-pRb interaction was disrupted by the use of a knock-in mouse carrying an E7-resistant mutant Rb allele. pRb inactivation was necessary but not sufficient for E7 to overcome differentiation-induced or DNA damage–induced cell cycle arrest, and expression patterns of the E2F-responsive genes Mcm7 and cyclin E indicate that other E2F regulators besides pRb are important targets of E7. Together, these data indicate that non-pRb targets of E7 play critical roles in cervical carcinogenesis. (Cancer Res 2006; 12(18): 9393-400)
Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma
Authors: L Chiecchio, R K M Protheroe, A H Ibrahim, K L Cheung, C Rudduck, G P Dagrada, E D Cabanas, T Parker, M Nightingale, A Wechalekar, K H Orchard, C J Harrison, N C P Cross, G J Morgan, F M Ross
Journal: Leukemia (2006)
Effects of hydrogen peroxide on action potentials and intracellular Ca2+ concentration of guinea pig heart
Authors: H. HAYASHI, H. MIYATA, H. WATANABE, A. KOBAYASHI, N. YAMAZAKI
Journal: Cardiovascular Research (1989)

Oxygen free radicals and Ca2+ overload have been implicated in the genesis of reperfusion induced arrhythmia and injury. Effects of hydrogen peroxide (H2O2) on action potentials and intracellular Ca2+ concentration ([Ca2+]i) were studied using guinea pig papillary muscles and ventricular myocytes. High concentration of H2O2 (10 mmol.litre-1) caused delayed afterdepolarisations in all six papillary muscles, and induced triggered activity in 3/6 preparations. Pretreatment with ryanodine (1 mumol.litre-1) abolished delayed afterdepolarisations and triggered activity induced by H2O2. [Ca2+]i and morphological changes in isolated ventricular myocytes of guinea pig were measured using fura-2. Quiescent and rod shaped myocytes became shortened and rounded (contracture) after the application of 0.1 and 1 mmol.litre-1 H2O2. [Ca2+]i increased from the control values of 53 (SEM 4) and 62(8) nmol.litre-1 to 110(29) and 105(24) nmol.litre-1 (p less than 0.05 v control) when cells were shortened during perfusion with 0.1 and 1 mmol.litre-1 H2O2, respectively. The values were 130(26) nmol.litre-1 (p less than 0.05 v control) and 100(18) nmol.litre-1 (p less than 0.05 v control) when the cells became rounded during perfusion with 0.1 and 1 mmol.litre-1 H2O2. We suggest that the arrhythmia caused by Ca2+ overload was induced by H2O2, possibly by lipid peroxidation of cell membrane. H2O2 was also shown to shorten cells and cause cell contracture (rounding). The mechanism of cell injury is not likely to be due to the Ca2+ overload, since the increase in [Ca2+]i during perfusion with H2O2 was not large.
Preoperative endoscopic retrograde cholangiopancreatographic treatment of complicated choledochal cysts in children: a retrospective case series
Authors: C. Houben, P. Chiu, J. Lau, K. Lee, E. Ng, Y. Tam, C. Yeung
Journal: Endoscopy (2007)

We report our experience with endoscopic retrograde cholangiopancreatography-(ERCP-)based interventions in children with complicated choledochal cysts that are refractory to conservative management. Between 1999 and 2006, 42 children (12 boys, 30 girls; median age 3 years, range 2-14.5 years) were admitted for surgical treatment of choledochal cysts. Seven of these patients (16.7%; one boy, six girls; median age 3 years, range 2-12 years) showed signs of complicated choledochal cysts, and presented with pancreatitis/cholangitis (n = 4) and obstructive jaundice (n = 3). The anatomical classification of the cysts was type Ic (n = 3), type If (n = 3), and type IV (n = 1). ERCP was successfully performed in 6/7 patients, and therapeutic interventions included removal of debris (n = 3), sphincterotomy (n = 3), and stent placement (n = 4). One patient required blood transfusion for post-sphincterotomy bleeding. The patient in whom the ERCP failed underwent ultrasound-guided percutaneous transhepatic biliary drainage. Definitive surgery was performed after a median interval of 10 days (range 7-68 days) after the ERCP intervention.