tbuckley/cabot-search huggingface dataset:
Endoscopic management of gastro-oesophageal cancer-improved survival?
Authors: S. F. Neong, J. Deacon, I. R. Sargeant, D. L. Morris
Journal: Gut (2011)

<h3>Introduction</h3> Endoscopy plays an important role in the palliative management of patients diagnosed with gastro-oesophageal cancer as well as temporary alleviation of dysphagia in the curative setting. The different treatment modalities available include stent insertion, Bougie/balloon dilatation, argon beam coagulation and laser recannulation. <h3>Methods</h3> This retrospective study looked at the outcome of patients diagnosed with gastro-oesophageal cancer who had endoscopic treatment in the 5-year period from 1 January 2004 to 31 December 2008. Across the 2 district general hospitals, the authors cover a catchment population of 500 000. The medical notes, computerised notes of the multidisciplinary team (MDT) meetings and endoscopy reports of all patients diagnosed with gastro-oesophageal cancer in the 5-year period were retrospectively reviewed. The number of survivors as of 19 November 2010 were noted. Follow-up period ranged from 41 to 56 months. <h3>Results</h3> 234 and 139 patients were diagnosed with oesophageal and gastric cancer respectively over the 5-year period. Data from six patients were unavailable. 169 (38%) patients had endoscopic treatment. As of 19 November 2010, 7.4% (10) of patients traced are still alive, 8 of which received curative endoscopic therapy. The median survival in patients receiving palliative endoscopic therapy was 230 days (4–1146). In total, 88 (53%) patients had laser ablation and the median survival in this group was 267 days (21–970). The median survival in those who had no endoscopic treatment was 80 days (2–683 days). The table 1 below illustrates the different number of therapeutic endoscopic procedures performed. <h3>Conclusion</h3> Endoscopic treatment continues to play an important role especially in palliation of symptoms in patients with gastro-oesophageal cancer. There are a larger number of patients in our Trust who had endoscopic treatment in comparison with the figures recently published in the National Oesophago-Gastric Cancer Audit 2010 where about 20% of patients had endoscopic treatment, the majority in patients with oesophageal and junctional tumours. Only 1% of the cohort in the national audit received laser ablation procedures in comparison with 53% of patients in our Trust, reflecting local expertise. The survival rates in our Trust are actually higher compared to the national figures where for oesophageal cancer, median survival in the group who had palliative endoscopic therapy was 140 days and 90 days in those who had best palliative supportive care.
Insulin-like Growth Factor-1 (IGF-1) Induces WISP-2/CCN5 via Multiple Molecular Cross-talks and Is Essential for Mitogenic Switch by IGF-1 Axis in Estrogen Receptor–Positive Breast Tumor Cells
Authors: Kakali Dhar, Snigdha Banerjee, Gopal Dhar, Krishanu Sengupta, Sushanta K. Banerjee
Journal: Cancer Research (2007)

Abstract Previously, we have shown that the expression of Wnt-1–induced signaling protein-2 (WISP-2), also known as CCN5, can be regulated by multiple stimulants in estrogen receptor (ER)–positive breast tumor cells to exert their mitogenic action in these cells. Here, we show that insulin-like growth factor-1 (IGF-1), a strong mitogen, enhanced the expression of the WISP-2/CCN5 gene parallel with the induction of proliferation of ER-positive breast tumor cells. An additive effect was also seen in combination with estrogen. Perturbation of IGF-1–induced WISP-2/CCN5 expression by WISP-2–specific RNA interference impaired the mitogenic action of IGF-1 on ER-positive breast tumor cells. Furthermore, the studies have shown that the multiple molecular cross-talks and side-talks among IGF-1R, ER-α, and phosphatidylinositol 3-kinase (PI3K)/Akt signaling molecules are required to induce WISP-2/CCN5 mRNA by IGF-1 in ER-positive, noninvasive breast tumor cells. Because a pure anti-ER ICI 182,780 is not only able to suppress the up-regulation of WISP-2/CCN5 mRNA expression by IGF-1, it also suppresses the PI3K/Akt activity induced by IGF-1 in MCF-7 cells; we anticipate that the membrane ER receptor may participate in this event. Collectively, these studies propose for the first time that WISP-2/CCN5 is an integral signaling molecule in mitogenic action of IGF-1 axis in ER-positive human breast tumor cells. [Cancer Res 2007;67(4):1520–6]
Angiotensin II Type 1 Receptor Overexpression in Podocytes Induces Glomerulosclerosis in Transgenic Rats
Authors: Sigrid Hoffmann, Dirk Podlich, Brunhilde Ha[Combining Diaeresis]hnel, Wilhelm Kriz, Norbert Gretz
Journal: Journal of the American Society of Nephrology (2004)

Angiotensin II (AngII) is a critical determinant of glomerular function involving both hemodynamic and pressure-independent effects that are insufficiently understood. A novel transgenic rat (TGR) model with overexpression of the human AngII type 1 receptor (hAT1) in podocytes was developed to study the consequences of an increased AT1 signaling on the structure and function of the glomerular filter. Use of the nephrin promoter to target the podocytes resulted in an expression of the hAT1 at a level roughly two times higher than the endogenous AT1 throughout life. All male TGR developed significant albuminuria starting at 8 to 15 wk of age; systolic BP was not elevated. More or less concurrently, structural changes at the glomerulus were encountered, starting with ubiquitous formation of pseudocysts at podocytes, followed by foot process effacement and local detachments. This damage progressed to nephron loss via the well known pathway typical for classic focal segmental glomerulosclerosis. The structural changes significantly correlated with age (r(2) = 0.76) and urinary albumin excretion (r(2) = 0.70). The data provide direct evidence that increased AT1 signaling in podocytes leads to protein leakage and structural podocyte damage progressing to focal segmental glomerulosclerosis.
Priming for T helper type 2 differentiation by interleukin 2–mediated induction of interleukin 4 receptor α-chain expression
Authors: Wei Liao, Dustin E Schones, Jangsuk Oh, Yongzhi Cui, Kairong Cui, Tae-Young Roh, Keji Zhao, Warren J Leonard
Journal: Nature Immunology (2008)
Morphological findings in the liver of children with cystic fibrosis: A light and electron microscopical study
Authors: Rolf Hultcrantz, Silwa Mengarelli, Birgitta Strandvik
Journal: Hepatology (1986)

Liver tissue from five children with cystic fibrosis, obtained through percutaneous liver biopsies, have been investigated via light and electron microscopy. None of the patients had clinical evidence of liver disorder, and their blood chemistry was mainly normal. Light microscopy showed slight fibrosis in three cases, more advanced fibrosis in one case and focal cirrhotic changes in one case. All patients had fatty infiltration in the hepatocytes and glycogen in the nuclei of these cells. Electron microscopy showed an increase in the number of Ito cells around the portal tracts and also fibrosis in all patients. In the majority of hepatocytes, no evident necrosis was seen. Hypertrophy of the smooth endoplasmic reticulum and the Golgi apparatus were noted. Large lysosomes containing lipofuscin and lipids were also present. No direct evidence of cholestasis could be seen in the hepatocytes. The bile canaliculi were not dilated and did not contain bile plugs. No bile pigment was seen in the cells, and direct evidence of cholestasis was thus not found in the hepatocytes. Other organelles, such as the rough endoplasmic reticulum, peroxisomes and mitochondria, had a normal appearance. Bile ducts, even when seen in fibrotic portal tracts, were not dilated. The ultrastructural findings cannot explain the basis for the liver cell damage. Cholestasis does not seem to be a presumable etiological factor as judged from the findings in the present study.
A prospective study of anti-chromatin and anti-C1q autoantibodies in patients with proliferative lupus nephritis treated with cyclophosphamide pulses or azathioprine/methylprednisolone
Authors: C. Grootscholten, J. W C Dieker, F. D McGrath, A. Roos, R. H W M Derksen, J. van der Vlag, M. R Daha, J. H M Berden
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To study the prevalence and course of anti-chromatin (anti-nucleosome, anti-double-stranded (ds) DNA and anti-histone) and anti-C1q autoantibodies in patients with proliferative lupus nephritis (LN), treated in a randomised controlled trial with either cyclophosphamide or azathioprine plus methylprednisolone. <b>Methods:</b> Autoantibody levels were measured and analysed in 52 patients with proliferative LN, during their first year of treatment. Levels in both treatment arms were compared and associations with clinical, serological and outcome parameters were studied. <b>Results:</b> At study entry, prevalences for anti-nucleosome, anti-dsDNA, anti-histone and anti-C1q autoantibodies were 81%, 96%, 23% and 65%, respectively. Anti-chromatin autoantibodies correlated with each other, but not with anti-C1q levels. If patients were divided for their autoantibody titre at the start of treatment above or below the median, the only significant differences were higher SLE disease activity index with higher anti-nucleosome, and higher creatinine with higher anti-C1q autoantibodies. During the first year, a comparable rapid decline in the levels of anti-nucleosome, anti-dsDNA and anti-C1q autoantibodies was seen in both treatment arms. Anti-histone autoantibody levels were low and did not change. Renal flares were not preceded by rises in autoantibody titres. <b>Conclusions:</b> These results indicate that measurement of anti-chromatin and anti-C1q autoantibodies is useful for diagnosing LN, but not for monitoring disease course.
Low and High Tenascin-Expressing Tumors Are Efficiently Targeted by ST2146 Monoclonal Antibody
Authors: Rita De Santis, Claudio Albertoni, Fiorella Petronzelli, Silvia Campo, Valeria D'Alessio, Antonio Rosi, Anna Maria Anastasi, Ragnar Lindstedt, Nadia Caroni, Brunilde Arseni, Pierino Chiodi, Antonio Verdoliva, Giovanni Cassani, Marco Chinol, Giovanni Paganelli, Paolo Carminati
Journal: Clinical Cancer Research (2006)

Abstract ST2146biot is a biotinylated anti-tenascin monoclonal antibody (mAb) to be used for Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT) of solid tumors. In vivo biodistribution studies of 125I-labeled ST2146biot were done in nude mice transplanted with human HT-29 colon carcinoma and/or human U-118MG glioblastoma cells characterized for low and high tenascin expression, respectively. In vitro results show that ST2146 retains immunoreactivity upon biotinylation, in contrast to other anti-tenascin mAbs. In vivo biodistribution of ST2146 shows specific tumor accumulation up to 10 days after the i.v. injection, with no relevant differences between biotinylated and nonbiotinylated ST2146. A dose of 4 μg/mouse saturates the low tenascin-expressing human colon carcinoma HT-29, whereas the high tenascin-expressing human glioblastoma U-118MG seems to be saturated at a ST2146biot dose between 320 and 640 μg/mouse. The percentage of injected dose per gram of tumor ranges from 10% to 30%, corresponding to an amount of ST2146biot/g of tumor of ∼400 ng/g and &amp;gt;200 μg/g for HT-29 and U-118MG, respectively. Tumor to normal organs uptake ratios are between 15 and 60, confirming high tumor selectivity of ST2146biot despite its cross-reactivity with the tenascin expressed at low level in the normal mouse organs. The ST2146biot localization data are substantially confirmed even when both low and high tenascin-expressing tumors are implanted in the same animal. To our knowledge, the absolute amount of ST2146biot, specifically localized in xenotransplanted human tumors, is the highest thus far described and supports the clinical use of this mAb in PAGRIT®.
Influence of Hepatitis G Virus Infection on the Severity of Liver Disease and Response to Interferon-α in Patients with Chronic Hepatitis C
Authors: Michele Martinot
Journal: Annals of Internal Medicine (1997)

Background: Dual infection with hepatitis G virus (HGV) and hepatitis C virus (HCV) is common. The effect of HGV infection on chronic hepatitis C is not well known. Objective: To assess the prevalence of HGV infection; the effect of HGV infection on the clinical, virologic, and histologic features of patients with chronic hepatitis C treated with interferon-α; and the influence of HGV infection on response to interferon-α therapy. Design: Retrospective study. Setting: A university hospital in France. Patients: 228 patients with chronic hepatitis C treated with interferon-α (3 million U or 5 million U subcutaneously 3 times a week for 3, 6, or 12 months). Measurements: Before initiation of treatment, serum HGV RNA and serum HCV RNA were detected with branched-DNA assays and HCV genotype was determined with a line probe assay. Serum HGV RNA and serum HCV RNA were detected by polymerase chain reaction at the end of treatment and 6 months after treatment. Results: Infection with HGV was detected in 21% of patients and 32% of intravenous drug users. The median serum HGV RNA level was 33 × 106 genome equivalents/mL. Infection with HGV was more frequently found in men with a history of intravenous drug use and was associated with HCV genotype 3a (P = 0.02) independent of the source of infection. Serum HCV RNA levels, liver histologic findings, and response to interferon-α therapy did not differ between patients with and those without HGV infection. The loss of serum HGV RNA was not correlated with the biochemical response contrarily to the loss of serum HCV RNA. Conclusions: Infection with HGV occurred frequently in this sample of patients with chronic hepatitis C, especially in patients infected with HCV genotype 3a. The level of HGV viremia was high relative to the level of HCV viremia. Infection with HGV did not influence the severity of liver disease or response to interferon-α therapy.
Control of the Myocardial Contractile State by Carotid Chemo- and Baroreceptor and Pulmonary Inflation Reflexes in Conscious Dogs
Authors: Stephen F. Vatner, John D. Rutherford
Journal: Journal of Clinical Investigation (1978)

The effects of carotid chemoreceptor stimulation with intracarotid injections of either nicotine, 0.2 μg/kg, or cyanide, 2 μg/kg, were compared with the effects of bilateral carotid occlusion on left ventricular (LV) pressure, dP/dt, and diameter in conscious dogs instrumented with ultrasonic diameter gauges and miniature pressure gauges. With heart rate maintained constant, carotid chemoreceptor stimulation increased mean arterial pressure by 27±3%, LV and diastolic diameter by 4±0.9% and LV dP/dt by 21±2%. With ventilation controlled during succinylcholine infusion, carotid chemoreceptor stimulation increased mean arterial pressure by 43±2% and dP/dt by 37±5%, values significantly greater, P < 0.01, than were observed in dogs with spontaneous ventilation. Similarly, in dogs with spontaneous ventilation after vagotomy, carotid chemoreceptor stimulation also increased dP/dt by a greater amount, i.e., by 48±9%. The increases in LV end diastolic diameter were not affected significantly by either cholinergic blockade with atropine or beta adrenergic blockade with propranolol. Although cholinergic blockade did not affect the inotropic or pressor responses significantly, beta adrenergic blockade attenuated the pressor response and essentially abolished the inotropic response. Bilateral carotid occlusion increased mean arterial pressure and LV end diastolic diameter by similar amounts to those observed with chemoreceptor stimulation, but increased dP/dt significantly less, P < 0.02, i.e., by 13±2%. As was observed with chemoreceptor stimulation, inotropic responses were not affected significantly by cholinergic blockade, but were essentially abolished by beta adrenergic blockade. Thus, in the conscious dog with heart rate constant, carotid chemoreceptor stimulation induces a clear positive inotropic effect, which is greater in the absence of the attenuating influences of pulmonary inflation reflexes, and for an equal elevation in arterial pressure appears to exert a greater increase in myocardial contractility than does carotid baro-receptor unloading.
Objective assessments of port wine stains: response to temperature change
Authors: S.W. LANIGAN, J.A. COTTERILL
Journal: British Journal of Dermatology (1988)

Three objective measurements were made in 11 patients with facial port wine stains and in five controls. Laser Doppler flowmetry, reflectance spectrophotometry and skin surface temperature were all significantly elevated in the port wine stains compared with the normal contralateral cheeks and control skin (P less than 0.05). Changes in skin blood flow and temperature after local heating and cooling of the skin were similar at all sites assessed and were not associated with significant changes in reflectance spectrophotometry, the parameter which correlated most closely with skin colour.
Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings in a rabbit model of vascular injury.
Authors: S Takeshita, D Gal, G Leclerc, J G Pickering, R Riessen, L Weir, J M Isner
Journal: Journal of Clinical Investigation (1994)

Arterial gene transfer represents a novel strategy that is potentially applicable to a variety of cardiovascular disorders. Attempts to perform arterial gene transfer using nonviral vectors have been compromised by a low transfection efficiency. We investigated the hypothesis that cellular proliferation induced by arterial injury could augment gene expression after liposome-mediated gene transfer. Nondenuded and denuded rabbit arterial strips were maintained in culture for up to 21 d, after which transfection was performed with a mixture of the plasmid encoding firefly luciferase and cationic liposomes. In non-denuded arteries, the culture interval before transfection did not affect the gene expression. In contrast, denuded arteries cultured for 3-14 d before transfection yielded 7-13-fold higher expression (vs. day 0; P < 0.005). Transfection was then performed percutaneously to the iliac arteries of live rabbits with or without antecedent angioplasty. Gene expression increased when transfection was performed 3-7 d postangioplasty (P < 0.05). Proliferative activity of neointimal cells assessed in vitro by [3H]thymidine incorporation, and in vivo by immunostaining for proliferating cell nuclear antigen, increased and declined in parallel with gene expression. These findings thus indicate that the expression of liposome-mediated arterial gene transfer may be augmented in presence of ongoing cellular proliferation.
Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions
Authors: Masao Toda, Donald Y.M. Leung, Sophie Molet, Mark Boguniewicz, Rame Taha, Pota Christodoulopoulos, Takeshi Fukuda, Jack A. Elias, Qutayba A. Hamid
Journal: Journal of Allergy and Clinical Immunology (2003)
Spatial alterations of Kv channels expression and K+ currents in post-MI remodeled rat heart
Authors: B Huang
Journal: Cardiovascular Research (2001)

Objective: The hypothesis being tested in the present study is that increased anisotropic properties occurs in the remodeled post-infarction heart due to spatial alterations in Kv channels expression and K+ currents of the remodeled myocardium. Methods: Three to 4 weeks post myocardial infarction (MI) in the rat, we measured the two components of the outward K+ current, Ito-fast (f) and Ito-slow(s) in the epicardium (epi) and endocardium (endo) of noninfarcted remodeled left ventricle (LV) using patch clamp techniques. Alterations in mRNA and/or protein levels of potassium channel genes Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 were measured in epi, midmyocardium (mid), and endo regions of LV and in the right ventricle (RV). Results: In sham operated rat heart, the density of Ito-f was 2.3 times greater in epi compared to endo myocytes. In post-MI heart, the density of Ito-f and Ito-s decreased to a similar degree in LV epi and endo but the difference in Ito-f density between epi and endo persisted. The mRNA and/or protein levels of Kv1.4, Kv2.1, Kv4.2 and Kv4.3 but not Kv1.5 decreased to a varying extent in different regions of LV but not in RV of post-MI heart. Conclusions: Our results suggest that regional downregulation of Kv channels expression and density of K+ currents can be a significant determinant of increased spatial electrophysiological heterogeneity and contribute to increased electrical instability of the post-MI heart.
Brain fatty acid synthase activates PPARα to maintain energy homeostasis
Authors: Manu V. Chakravarthy, Yimin Zhu, Miguel López, Li Yin, David F. Wozniak, Trey Coleman, Zhiyuan Hu, Michael Wolfgang, Antonio Vidal-Puig, M. Daniel Lane, Clay F. Semenkovich
Journal: Journal of Clinical Investigation (2007)

Central nervous system control of energy balance affects susceptibility to obesity and diabetes, but how fatty acids, malonyl-CoA, and other metabolites act at this site to alter metabolism is poorly understood. Pharmacological inhibition of fatty acid synthase (FAS), rate limiting for de novo lipogenesis, decreases appetite independently of leptin but also promotes weight loss through activities unrelated to FAS inhibition. Here we report that the conditional genetic inactivation of FAS in pancreatic beta cells and hypothalamus produced lean, hypophagic mice with increased physical activity and impaired hypothalamic PPARalpha signaling. Administration of a PPARalpha agonist into the hypothalamus increased PPARalpha target genes and normalized food intake. Inactivation of beta cell FAS enzyme activity had no effect on islet function in culture or in vivo. These results suggest a critical role for brain FAS in the regulation of not only feeding, but also physical activity, effects that appear to be mediated through the provision of ligands generated by FAS to PPARalpha. Thus, 2 diametrically opposed proteins, FAS (induced by feeding) and PPARalpha (induced by starvation), unexpectedly form an integrative sensory module in the central nervous system to orchestrate energy balance.
Investigating the Transcriptional Control of Cardiovascular Development
Authors: Irfan S. Kathiriya, Elphège P. Nora, Benoit G. Bruneau
Journal: Circulation Research (2015)

Transcriptional regulation of thousands of genes instructs complex morphogenetic and molecular events for heart development. Cardiac transcription factors choreograph gene expression at each stage of differentiation by interacting with cofactors, including chromatin-modifying enzymes, and by binding to a constellation of regulatory DNA elements. Here, we present salient examples relevant to cardiovascular development and heart disease, and review techniques that can sharpen our understanding of cardiovascular biology. We discuss the interplay between cardiac transcription factors, cis-regulatory elements, and chromatin as dynamic regulatory networks, to orchestrate sequential deployment of the cardiac gene expression program.