tbuckley/cabot-search huggingface dataset:
Hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients: The influence of virus C infection
Authors: Maria Jose Moran, Antonio Fontanellas, Eric Brudieux, Isabelle Hombrados, Victor de Ledinghen, Patrice Couzigou, Hubert de Verneuil, Rafael Enriquez De Salamanca
Journal: Hepatology (1998)

Porphyria cutanea tarda (PCT) is caused by a decreased activity of the hepatic enzyme uroporphyrinogen decarboxylase (URO-D). This deficiency causes overproduction, hepatic deposition, and increased excretion of uroporphyrin. Iron overload and hepatic viral infections are considered aggravating factors of the disease. Two forms of PCT have been described, as follows: a familial one with an inherited decrease of URO-D activity in all tissues and a sporadic one with a decreased activity of URO-D restricted to the liver. To assess whether the hepatic URO-D returns to normal during a remission of the disease, this activity was measured in liver biopsy samples in 24 sporadic PCT patients. The hepatic and urinary porphyrin concentrations were also measured. Viral status and histopathological findings were analyzed to assess their involvement in PCT. Six patients treated by phlebotomy to reduce hepatic iron and who were considered to be in clinical remission, characterized by a disappearance of cutaneous lesions, showed higher hepatic URO-D activities and lower hepatic porphyrin concentrations than did patients with overt PCT. The medians of these variables, however, did not achieve normal values. The hepatic URO-D activity showed a significant inverse relationship with both hepatic porphyrins and urinary uroporphyrin excretion. Hepatic URO-D activity was not reduced by hepatitis C virus (HCV) infection and liver damage. We conclude that the achievement of remission in PCT largely depends on the transient normalization of hepatic URO-D activity. A small increase in hepatic coproporphyrin in nonporphyric patients could reflect hepatic injury/iron/alcohol-induced oxidative stress oxidizing the accumulated heme precursors rather than a direct effect on hepatic URO-D enzyme.
Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas
Authors: J. Pallud, J.-F. Llitjos, F. Dhermain, P. Varlet, E. Dezamis, B. Devaux, R. Souillard-Scemama, N. Sanai, M. Koziak, P. Page, M. Schlienger, C. Daumas-Duport, J.-F. Meder, C. Oppenheim, F.-X. Roux
Journal: Neuro-Oncology (2012)

Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, -16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm(3)), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at -10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than -10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders.
Induced Repatterning of Type XVIII Collagen Associates with Ectopic Sonic Hedgehog and Lung Surfactant C Gene Expression and Changes in Epithelial Epigenesis in the Ureteric Bud
Authors: Seppo Vainio, Yanfeng Lin, Taina Pihlajaniemi
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. How cell and tissue interactions lead to complex organ structures and differentiated cell types during organogenesis is one of the most fundamental questions in developmental biology. The embryonic lung and kidney of the mouse are useful models for studying the molecular mechanisms of morphogenesis, and in both of these organs, the epithelial bud undergoes a characteristic branching process. This review discusses the potential role of an extracellular matrix molecule, type XVIII collagen, in the generation of the branching patterns in the lung and kidney and how its experimental respecification in tissue recombinants between the ureteric bud and lung mesenchyme correlates with changes in expression of signaling molecules such as sonic hedgehog and changes in cell fate as judged by ectopic expression of the lung surfactant C gene. E-mail: seppo.vainio@.oulu.fi
Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility
Authors: R Greaves, J Miller, L O’Donnell, A McLean, M J G Farthing
Journal: Gut (1998)

Background —Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined. Aims —To study the effect of glyceryl trinitrate, a nitric oxide donor, on gall bladder emptying in healthy subjects using a randomised, double blind, crossover, placebo controlled design. Methods —Ultrasonographic gall bladder volume was measured in the fasting state in eight healthy volunteers after randomised administration of either glyceryl trinitrate 1200 μg buccal spray or placebo spray. On two further occasions, after randomised administration of either glyceryl trinitrate 1200 μg buccal spray or placebo spray, gall bladder volumes were also measured after a liquid test meal. Results —Glyceryl trinitrate significantly increased fasting gall bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p=0.039). Glyceryl trinitrate also significantly impaired gall bladder emptying between five and 40 minutes postprandially. Gall bladder ejection fraction was also reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4 (6.5)%, p=0.016). Conclusions —This study shows that glyceryl trinitrate produces gall bladder dilatation in the fasting state and reduces postprandial gall bladder emptying, suggesting that nitric oxide mechanisms may be operative in the human gall bladder in vivo.
Reestablishment of cell polarity of rat hepatocytes in primary culture
Authors: Alexandru I. Musat, Carol A. Sattler, Gerald L. Sattler, Henry C. Pitot
Journal: Hepatology (1993)

The cell-basement membrane interaction is an important determinant of epithelial cell polarity. Although hepatocytes in situ are polarized, no morphologically identifiable basement membrane is found at their basal surface. However, several studies have demonstrated immunoreactivity to basement membrane proteins in the space of Disse, indicating the existence of an extracellular matrix, albeit of low density. Therefore we hypothesized that the interaction of hepatocytes with this matrix may determine their polarity and asked whether a basement membrane-like substrate could reestablish hepatocyte polarity in vitro. For this purpose, established monolayers of primary rat hepatocytes were cultured overlaid with a basement membrane-like matrix extracted from the Engelbreth-Holm-Swarm mouse tumor, mimicking thus the in situ tissue architecture. The hepatocytes in this culture configuration, unlike hepatocytes in classic cultures, developed distinct membrane domains, as demonstrated by the reformation of gamma-glutamyltranspeptidase, Mg(2+)-ATPase-positive bile canalicular networks and intercellular gap junctions immunolocalized to the lateral membrane with antibodies to connexin 32. The actin cytoskeleton of these cells reorganized into pericanalicular webs, and no accumulation of "stress" filaments was found beneath the membrane facing the medium. Golgi complexes appeared to be preferentially located in mitochondria-poor pericanalicular cytoplasm, indicating the polarized distribution of these organelles. Together, these data indicate that a basement membrane-like substrate present between hepatocytes and nutrient medium restores the polarity of these cells in culture. Extrapolation of these findings to the intact liver suggests that the matrix in Disse's space governs the development of hepatocyte polarity.
SERIAL CHANGES OF EVEROLIMUS–ELUTING STENT INCOMPLETE STENT APPOSITION: AN OPTICAL COHERENCE TOMOGRAPHY SUBANALYSIS FROM THE RESET TRIAL
Authors: Kunihiro Shimamura, Takashi Akasaka, Yasushi Ino, Yoshihisa Nakagawa, Keiichi Igarashi, Kengo Tanabe, Yoshihiro Morino, Masashi Iwabuchi, Kazuo Kimura, Ken Kozuma, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2013)
Electron-spin resonance study of mainstream and sidestream cigarette smoke: nature of the free radicals in gas-phase smoke and in cigarette tar.
Authors: W A Pryor, D G Prier, D F Church
Journal: Environmental Health Perspectives (1983)

Radicals in the gas phase of both mainstream and sidestream cigarette smoke have been studied using electron-spin resonance ESR spin-trapping techniques with alpha-phenyl-N-tert-butyl nitrone (PBN) as the spin trap. The principal radicals we trap appear to be alkoxyl radicals. Mainstream and sidestream gas-phase smoke each have about the same concentration of radicals, about 1 X 10(16) radicals per cigarette (or 5 X 10(14) per puff). These radicals are reactive, yet they appear to be remarkably long-lived: they are still spin trapped from gas-phase smoke after more than 5 min. We propose that a steady-state concentration of reactive radicals exists in gas phase cigarette smoke. We suggest that this steady state is produced by the slow oxidation of nitric oxide (present in high concentrations in smoke and relatively unreactive) to the more reactive nitrogen dioxide, followed by the reaction of nitrogen dioxide with reactive organic molecules in smoke (such as olefins and dienes). Preliminary experiments reported here support this hypothesis. Tar from both mainstream and sidestream smoke contains persistent free radicals that exhibit broad, single-line ESR spectra with g values of 2.003. The tar radical can be extracted into tert-butylbenzene and other organic solvents, and we have applied a variety of fractionation procedures to these solutions. Most of the radicals occur in the fractions that contain the phenolic tobacco leaf pigments. Treatment of alcoholic solutions of tar with base generates a new group of radicals that appear to be semiquinone radicals derived from the oxidation of the phenolic and polyphenolic species in tar.
Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency
Authors: I R Korponay-Szabo
Journal: Gut (2003)

<b>Background:</b> IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult. <b>Aims:</b> To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies. <b>Patients:</b> We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors. <b>Methods:</b> IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections. <b>Results:</b> The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (<i>r</i><sub>s</sub>=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p&lt;0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles. <b>Conclusions:</b> IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.
Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model
Authors: L. Castillo‐Courtade, S. Han, S. Lee, F. M. Mian, R. Buck, P. Forsythe
Journal: Allergy (2015)

Abstract Background The prebiotic nature of human milk oligosaccharides ( HMO s) and increasing evidence of direct immunomodulatory effects of these sugars suggest that they may have some therapeutic potential in allergy. Here, we assess the effect of two HMO s, 2’‐fucosyllactose and 6’‐sialyllactose, on symptomatology and immune responses in an ovalbumin‐sensitized mouse model of food allergy. Methods The effects of oral treatment with 2′‐fucosyllactose and 6′‐sialyllactose on anaphylactic symptoms induced by oral ovalbumin ( OVA ) challenge in sensitized mice were investigated. Mast cell functions in response to oral HMO treatment were also measured in the passive cutaneous anaphylaxis model, and direct effects on IgE‐mediated degranulation of mast cells were assessed. Results Daily oral treatment with 2′‐fucosyllactose or 6′‐sialyllactose attenuated food allergy symptoms including diarrhea and hypothermia. Treatment with HMO s also suppressed antigen‐induced increases in mouse mast cell protease‐1 in serum and mast cell numbers in the intestine. These effects were associated with increases in the CD 4 + CD 25 + IL ‐10 + cell populations in the Peyer's patches and mesenteric lymph nodes, while 6′‐sialyllactose also induced increased IL ‐10 and decreased TNF production in antigen‐stimulated splenocytes. Both 2′‐fucosyllactose and 6′‐sialyllactose reduced the passive cutaneous anaphylaxis response, but only 6′‐sialyllactose directly inhibited mast cell degranulation in vitro, at high concentrations. Conclusions Our results suggest that 2′‐fucosyllactose and 6′‐sialyllactose reduce the symptoms of food allergy through induction of IL ‐10 + T regulatory cells and indirect stabilization of mast cells. Thus, human milk oligosaccharides may have therapeutic potential in allergic disease.
Activation of NAD(P)H:Quinone Oxidoreductase 1 Prevents Arterial Restenosis by Suppressing Vascular Smooth Muscle Cell Proliferation
Authors: Sun-Yee Kim, Nam Ho Jeoung, Chang Joo Oh, Young-Keun Choi, Hyo-Jeong Lee, Han-Jong Kim, Joon-Young Kim, Jung Hwan Hwang, Surendar Tadi, Yong-Hyeon Yim, Ki-Up Lee, Keun-Gyu Park, Seung Huh, Ki-Nam Min, Kyeong-Hoon Jeong, Myoung Gyu Park, Tae Hwan Kwak, Gi Ryang Kweon, Kouichi Inukai, Minho Shong, In-Kyu Lee
Journal: Circulation Research (2009)

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are important pathogenic mechanisms in atherosclerosis and restenosis after vascular injury. In this study, we investigated the effects of beta-lapachone (betaL) (3,4-Dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione), which is a potent antitumor agent that stimulates NAD(P)H:quinone oxidoreductase (NQO)1 activity, on neointimal formation in animals given vascular injury and on the proliferation of VSMCs cultured in vitro. betaL significantly reduced the neointimal formation induced by balloon injury. betaL also dose-dependently inhibited the FCS- or platelet-derived growth factor-induced proliferation of VSMCs by inhibiting G(1)/S phase transition. betaL increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 in rat and human VSMCs. Chemical inhibitors of AMPK or dominant-negative AMPK blocked the betaL-induced suppression of cell proliferation and the G(1) cell cycle arrest, in vitro and in vivo. The activation of AMPK in VSMCs by betaL is mediated by LKB1 in the presence of NQO1. Taken together, these results show that betaL inhibits VSMCs proliferation via the NQO1 and LKB1-dependent activation of AMPK. These observations provide the molecular basis that pharmacological stimulation of NQO1 activity is a new therapy for the treatment of vascular restenosis and/or atherosclerosis which are caused by proliferation of VSMCs.
Predictive and Prognostic Factors for Non-Small Cell Lung Cancer--Potholes in the Road to the Promised Land
Authors: A. F. Gazdar, J. H. Schiller
Journal: JNCI Journal of the National Cancer Institute (2011)

Surgery offers the best chance of long-term cures for early-stage non–small cell lung cancer, the most common form of lung cancer. However, between one-third and one-half of early-stage tumors will relapse after curative intent resection. Adjuvant chemotherapy (ACT) offers a survival advantage for up to 15% of early-stage resected cancers and has become the standard of care. Thus, having the ability to select the minority of patients who are likely to benefit from ACT would be enormously beneficial to the majority of earlystage patients who undergo resection who could avoid experiencing the morbidity associated with ACT. This strategy would also create economic benefits in addition to the health benefits for patients. In this issue of the Journal, Chen et al. (1) present a microarray-based gene expression signature that has both prognostic and predictive values for early-stage non–small cell lung cancer. Many markers have been tested for their predictive and prognostic value in lung cancer, and some have entered clinical practice. These include pathological typing that may be used to include or exclude certain forms of therapy—for example, adenocarcinoma histology is a strong predictor of outcome of pemetrexed therapy in advanced patients, and serious hemorrhagic complications may occur after bevacizumab therapy in patients with squamous histol
Survival prediction of gastric cancer by a seven-microRNA signature
Authors: X. Li, Y. Zhang, Y. Zhang, J. Ding, K. Wu, D. Fan
Journal: Gut (2009)

<h3>Aims</h3> Several microarray studies have reported microRNA (miRNA) expression signatures that classify cancer patients into different prognostic groups. No study has evaluated the association between miRNA expression patterns and gastric cancer prognosis. In this study, we developed a seven-miRNA signature that is closely associated with survival of patients with gastric cancer. <h3>Patients and methods</h3> MiRNA expression profile was analysed by real-time RT-PCR in 100 gastric cancer patients, which were randomly assigned to either the training set or the testing set. Cox proportional hazard regression and risk-score analysis were used to identify a stage-independent set of seven-miRNA signature in the training set that could classify patients with significantly different prognosis. This miRNA signature was further validated by the testing set and an independent cohort 60 patients. <h3>Results</h3> We have identified a seven-miRNA signature (miR-10b, miR-21, miR-223, miR-338, let-7a, miR-30a-5p, miR-126) for overall survival (p=0.0009) and relapse-free survival (p=0.0005) of gastric cancer patients. Multivariate analysis shown that the risk signature was an independent predictor of overall survival (HR=3.046; 95% CI, 1.246 to 7.445, p=0.015) and relapse-free survival (HR=3.337; 95% CI, 1.298 to 8.580, p=0.012). Furthermore, the predictive value of this seven-miRNA signature was validated in the testing set of 50 patients and an independent set of 60 patients. <h3>Conclusion</h3> Our seven-miRNA signature is closely associated with relapse-free and overall survival among patients with gastric cancer. The prognostic signature could be applicable to future decisions concerning treatment.
Association between osteoarthritis of the hand and knee in a population of skeletons from London
Authors: H A Waldron
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To examine the relation between osteoarthritis of the hand and knee in a group of skeletons dating to the 18th and early 19th centuries from two sites in London. <h3>METHODS</h3> This was a case-control study of 115 cases and controls matched for age and sex. Cases were skeletons with osteoarthritis of the hands; cases and controls were assessed for the presence of osteoarthritis of any compartment of the knee. <h3>RESULTS</h3> Cases had a significant odds ratio (OR) for osteoarthritis of the knee compared with controls: OR 5.98, 95% confidence interval (CI) 1.25 to 56.37. Cases with osteoarthritis of the distal interphalangeal (DIP), proximal interphalangeal (PIP), and first carpometacarpal (CMC1) joints had increased but non-significant odds ratios for osteoarthritis of the knee in the order DIP &gt; PIP &gt; CMC1. Cases with multifocal osteoarthritis of the hands had a significantly increased odds ratio for osteoarthritis of the knee: OR 11.67, 95% CI 1.13 to 379.57. <h3>CONCLUSIONS</h3> The study confirms the association between osteoarthritis of the hand and the knee seen in contemporary populations and suggests that it is not of very recent origin.
[<sup>18</sup>F]Fluorodeoxyglucose-Avid Adrenal Masses Due to Histoplasmosis
Authors: Sneha A. Shah, Venkatesh Rangarajan, Nilendu C. Purandare, Abhishek J. Arora, Anshu R. Sharma, Seethalakshmi Viswanathan
Journal: Journal of Clinical Oncology (2008)
Clinical Lecture on One Hundred Cases of Tumours of the Urinary Bladder: Delivered at the London Hospital
Authors: E. H. Fenwick
Journal: BMJ (1893)

GENTLEMEN,-I have various reasons for selecting the subject of tumours of the urinary bladder for my clinical lecture to- day.Foremost among these is the desire to place before you some of the conclusions I have drawn from an experience of over a hundred proved cases of the disease.This material, moreover, permits me to reiterate and to emphasise the opinion I expressed in 18881 upon the diagnostic and prognostic capacity of the electric cystoscope.The subject is too wide to allow of its compression into a single lecture, so that I shall select those points which seem to me to have an important practical bearing upon the judicious and successful treatment of the disorder.Any textbook will give you the pathological varieties of vesical growth, but for my present purpose I shall ask you to consider them under their simplest clinical divisions-that is, according to their benign or malignant character.As the vesical tumours encountered in childhood are very rare, mostly of the sarcomatous type, always inoperative and in- variably fatal, my remarks will refer to adult life of both sexes.Tumours of the bladder, like similar formations of other mucous surfaces, vary greatly in their rapidity of growth and destructiveness.We are able to recognise a succulent form of epithelioma of the mucous membrane of the bladder which, in its initial symptoms and in its comparative torpor re- sembles the various forms of villous papilloma for a short period.This fact compels us to subdivide malignant growth, and to form three groups: A. Benign tumours, papillomata.B. Succulent epithelioma of the mucous membrane.c.Denser, rapidly destructive epithelioma invading the muscle wall almost as soon as the mucous membrane.