tbuckley/cabot-search huggingface dataset:
Rho-kinase 2 is frequently overexpressed in hepatocellular carcinoma and involved in tumor invasion #
Authors: Carmen Chak-Lui Wong, Chun-Ming Wong, Edmund Kwok-Kwan Tung, Kwan Man, Irene Oi-Lin Ng
Journal: Hepatology (2009)

Abstract Deregulation of Rho family small guanosine triphosphatases has been implicated in human carcinogenesis. Rho-kinases are downstream effectors of Rho guanosine triphosphatases in the regulation of cytoskeletal reorganization and cell motility. However, their functions in human cancers remain elusive. In this study, we aimed to investigate the role of Rho-kinases in hepatocellular carcinoma (HCC) tumor progression and invasion. We first examined the expression of the two Rho-kinases (ROCK1 and ROCK2) in human HCC, and found that ROCK2 was frequently overexpressed in primary HCCs (22/41 [53.66%]). Clinico-pathological analysis revealed that overexpression of ROCK2 was significantly associated with the presence of tumor microsatellite formation ( P = 0.005), suggesting that deregulation of ROCK2 may contribute to the intrahepatic metastasis of HCC. Consistently, we demonstrated that stable overexpression of ROCK2 significantly enhanced cell motility and invasiveness in HCC cells. Conversely, stable knockdown of ROCK2 by short hairpin RNA approach remarkably reduced HCC cell migration and invasion. Moreover, orthotopic liver xenograft models provided further support that stable knockdown of ROCK2 suppressed HCC invasion in vivo . Stable knockdown of ROCK2 in HCC cells significantly inhibited Golgi reorientation, myosin phosphatase phosphorylation, and formations of stress fibers, filopodia, and lamellipodia; these molecular and cellular events are crucial for cell motility and cancer invasion. Conclusion: Our results indicate that ROCK2 was overexpressed in human HCCs, and this overexpression was associated with a more aggressive biological behavior. Our findings also demonstrate that ROCK2 played a significant role in regulating cytoskeletal events and contributed to the invasion of HCC. (Hepatology 2009.)
DYSPHONIA: ITS SIGNIFICANCE AND MANAGEMENT
Authors: GEORGE D. WOLF
Journal: JAMA (1927)

This is unquestionably the era of the research worker. There is a demand for greater enlightenment and more accurate information on the various baffling medical questions, and modern laboratory methods bid fair to fulfil at least part of these expectations. For these reasons the medical profession has come to look to the laboratory, instead of to the clinician, for a solution of its problems. It is therefore with a certain feeling of timidity that I present this well known clinical entity for discussion. At the same time, because of this attitude, our medical literature shows a comparative paucity of topics pertaining to everyday practical problems.  Has any one a right to add to the burden of medical literature when nothing new can be contributed toward a knowledge of the subject? If the practitioner can find the desired information in almost any recent standard textbook, should he be burdened with additional
Inhaled Vasoactive Intestinal Peptide Exerts Immunoregulatory Effects in Sarcoidosis
Authors: Antje Prasse, Gernot Zissel, Niklas Lützen, Jonas Schupp, Rene Schmiedlin, Elena Gonzalez-Rey, Anne Rensing-Ehl, Gerald Bacher, Vera Cavalli, Dorian Bevec, Mario Delgado, Joachim Müller-Quernheim
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Previous studies suggest an important immunoregulatory role of vasoactive intestinal peptide (VIP) in experimental models of chronic noninfectious inflammation. Sarcoidosis is characterized by noncaseating epitheloid cell granulomas, where excessive tumor necrosis factor-α production by pulmonary macrophages plays a critical role in granuloma formation and disease progression, which may lead to fatal organ dysfunction.Objectives: To test whether inhaled VIP has an immunoregulatory role. Sarcoid alveolitis was used as a prototype of immune-mediated chronic lung inflammation.Methods: In an open clinical phase II study, we treated 20 patients with histologically proved sarcoidosis and active disease with nebulized VIP for 4 weeks.Measurements and Main Results: VIP inhalation was safe, well-tolerated, and significantly reduced the production of tumor necrosis factor-α by cells isolated from bronchoalveolar lavage fluids of these patients. VIP treatment significantly increased the numbers of bronchoalveolar lavage CD4+CD127−CD25+ T cells, which showed regulatory activities on conventional effector T cells. In vitro experiments demonstrated the capacity of VIP to convert naive CD4+CD25− T cells into CD4+CD25+FoxP3+ regulatory T cells, suggesting the generation of peripheral regulatory T cells by VIP treatment.Conclusions: This study is the first to show the immunoregulatory effect of VIP in humans, and supports the notion of inhaled VIP as an attractive future therapy to dampen exaggerated immune responses in lung disorders. Thus, the inhalation of neuropeptides may be developed into a new therapeutic principle for chronic inflammatory lung disorders in humans.
<i>Pavilion Street, Mount Adams</i>
Authors: Jeanette M. Smith
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hypothermia and Prostaglandin E<sub>1</sub> Produce Synergistic Attenuation of Ischemia-Reperfusion Lung Injury
Authors: CHI-HUE CHIANG, KERRY WU, CHENG-PING YU, HORNG-CHIN YAN, WANN-CHERNG PERNG, CHIN-PYNG WU
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Current methods of preserving lung tissue for transplantation are inadequate. In this study, we tested whether the combination of hypothermia plus prostaglandin E1 (PGE1) treatment would have synergistic attenuation on ischemia-reperfusion (I/R) lung injury. Isolated rat lung experiments with ischemia for 1 h then reperfusion for 1 h, were conducted using six different perfusates: (1) University of Wisconsin solution (UW) at 30 ° C (n = 5), (2) UW at 22 ° C (n = 5), (3) UW at 10 ° C (n = 4), (4) UW + PGE1 at 30 ° C (n = 4), (5) UW + PGE1 at 22 ° C (n = 4), and (6) UW + PGE1 at 10 ° C (n = 4). Hemodynamic changes, lung weight gain, capillary filtration coefficients, and lung pathology were analyzed to evaluate the I/R injury. Compared with 30 ° C UW, animals treated with 22 ° C UW and 10 ° C UW had less I/R lung injury, with the groups receiving 22 ° C UW showing superior results to group receiving 10 ° C UW. The addition of PGE1 to UW solution produced more attenuation of I/R injury than did UW alone. Among the six groups, 10 ° C UW + PGE1 produced the most reduction of I/R injury. This study has shown that hypothermia can attenuate I/R injury with the optimal flushing temperature being near 22 ° C. PGE1 also has a protective effect on I/R. Furthermore, hypothermia and PGE1 have synergistic attenuation of I/R lung injury. We propose that pulmonary artery flushed with cooling UW + PGE1 might improve lung preservation and improve results in lung transplantation.
A Case of Traumatic Arteriovenous Fistula Diagnosed by Radionuclide Cerebral Scan
Authors: DANIEL CHOY, I P C MURRAY
Journal: Clinical Nuclear Medicine (1982)

CHOY, DANIEL M.B., B.S., F.R.A.C.P.; MURRAY, I P C M.D., F.R.A.C.P., F.R.C.P., F.A.C.R. Author Information
A spectrum of functional effects for disease causing mutations in the Jervell and Lange-Nielsen syndrome
Authors: L Huang
Journal: Cardiovascular Research (2001)

Objective: Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited long QT syndrome (LQTS) characterised by profound sensorineural deafness and predisposition to syncope and sudden cardiac death. Mutation analysis has established the presence of mutations in affected individuals in the genes KCNQ1 and KCNE1: the potassium channel complex responsible for the cardiac IKs current involved in repolarisation of the ventricular action potential. Our objective was to determine the functional effects of disease causing mutations in JLNS. Methods: In this study we have investigated the electrophysiological effects of eight distinct JLNS mutations after expression of cRNA in Xenopus laevis oocytes. Results: KCNE1 mutant T59P/L60P showed no dominant negative effect and was a pure loss of function mutation. KCNQ1 mutant E261D showed a strong dominant-negative effect. KCNQ1 mutant R243H produced a moderate dominant-negative effect, right shifted the steady-state activation curve and led to an increased deactivation rate. The behaviour of KCNQ1 mutants 572–576del, 1008delC, R518X, Q530X, R594Q depended on the relative quantities of mutant and wild-type proteins (with a weak dominant-negative effect present at 1:3 but not 1:1 injection ratios). These data indicate the presence of an additional assembly domain before S2–S3 and the importance of the S4–S5 region in channel function and gating. Conclusions: Our data suggest a spectrum of behaviour for disease causing mutations from simple loss of function through to prominent dominant negative behaviour.
437 PATHOLOGICAL GLUCOSE LEVELS AND PRESENCE OF HYPERTENSION IDENTIFIES HCV PATIENTS WITH MINOR TREATMENT RESPONSES
Authors: E. Jaeckel, E. Zehnter, T. Lutz, I.C.H. Hey, C. John, G. Teuber, W. Schmidt, H.R. Bruch, P. Geyer, R. Heyne, M. Stern, G. Bellmann, B. Weber, C. Herold, H. Hinrichsen, S. Stoll, M.R. Manns
Journal: Journal of Hepatology (2011)
Doctor sues company over unethical marketing
Authors: F. Charatan
Journal: BMJ (2002)

Dr David Franklin, a former employee of the Warner- Lambert Pharmaceutical Company, has filed a lawsuit against the company, alleging that its sales representatives encouraged doctors to prescribe gabapentin (Neurontin) for unapproved uses.

Gabapentin was approved by the Food and Drug Administration in 1994 for the treatment of epilepsy, including elementary partial seizures and complex partial seizures …
β-Cell Dysfunction Induced by Chronic Hyperglycemia: Current Ideas on Mechanism of Impaired Glucose-Induced Insulin Secretion
Authors: John L Leahy, Susan Bonner-Weir, Gordon C Weir
Journal: Diabetes Care (1992)

Non-insulin-dependent diabetes mellitus is characterized by abnormal β-cell function. The characteristic secretory defect is a selective loss of glucose-induced insulin secretion. Substantial data have been generated in animal models to support the concept that chronic hyperglycemia causes the loss of glucorecognition (the so-called glucose toxicity hypothesis). This review summarizes the data supporting the concept of hyperglycemia-induced β-cell dysfunction and then focuses on the ideas for the mechanism of the glucose unresponsiveness. The lack of access to islet tissue in humans means that these studies have all been conducted in animal models. Another major stumbling block continues to be the lack of in vitro systems that faithfully reproduce the secretory abnormalities that occur in vivo. Despite these limitations, many hypotheses are being investigated that span most of the major intracellular steps for glucose-induced insulin secretion, including abnormalities in glucose transport, storage, metabolism/oxidation, and the second messengers. No single hypothesis stands out as being able to explain all of the characteristics of the secretory abnormalities. In the last few years major advances have occurred in our knowledge about the events that normally cause glucose-induced insulin secretion. Similarly, biochemical and molecular tools have become available to probe the different steps. As better in vitro models of the selective glucose unresponsiveness become available, rapid progress can be expected in unraveling the biochemical basis for the loss of glucose responsiveness in diabetic rat models. The long-term hope is that this information will lead to innovative new strategies for the therapy of non-insulin-dependent diabetes mellitus.
<i>IL7RA</i>Polymorphisms and Susceptibility to Multiple Sclerosis
Authors: Catherine O'Doherty, Orhun Kantarci, Koen Vandenbroeck
Journal: New England Journal of Medicine (2008)

To the Editor: Two independent, well-powered studies have recently identified the interleukin-7 receptor α (IL7RA) gene as a susceptibility gene for multiple sclerosis,1,2 thus extending and confirming earlier observations.3,4 A functional, nonsynonymous single-nucleotide polymorphism (SNP), rs6897932, located in the alternatively spliced sixth exon of the gene, was highlighted as the susceptibility-modifying polymorphism, with the C allele increasing the risk of disease (odds ratio, approximately 1.2).1,2 We genotyped nine haplotype-tagging SNPs in IL7RA in two independent case–control collections from Olmsted County, Minnesota, and Belfast, Northern Ireland, neither of which, to our knowledge, has previously been tested . . .
Temporal relationships between levels of circulating NO derivatives, vascular NO production and hyporeactivity to noradrenaline induced by endotoxin in rats
Authors: D. Paya, V. Maupoil, C. Schott, L. Rochette, J.-C. Stoclet
Journal: Cardiovascular Research (1995)

Objective: Lipopolysaccharide (LPS) induces early (within 1 h) and delayed (after several hours) impairment of vascular reactivity to catecholamines whose mechanisms are different, although they probably both involve nitric oxide (NO). Temporal and quantitative relationships between hyporeactivity to noradrenaline and NO production were investigated in a rat model of endotoxaemia allowing to clearly distinguish the two phases of hyporeactivity. Methods: Anaesthetised rats were infused with LPS (14 mg kg−1 h−1) for 1 h. Pressure responses to noradrenaline (NA) and circulating NO derivatives (nitrosyl haemoglobin, NO2−, NO3−) were monitored for 5 h after the onset of infusion. Reactivity to NA and tissue cyclic GMP level were also assessed ex vivo, in aortic rings taken at different experimental times. Results: LPS-induced early hyporeactivity to NA was associated with a moderate but significant increase in plasma NO3− level, without any significant change in concentration of the other circulating NO derivatives. Neither reactivity ex vivo nor cyclic GMP content were modified in aortae taken after 1 h of LPS infusion. By contrast, delayed hyporeactivity (5 h after the onset of LPS infusion) was associated with a large increase in all circulating NO derivatives (up to 2.5 fold), enhanced aortic cyclic GMP level and aortic hyporeactivity ex vivo. Pre-treatment of rats with NG-nitro-L-arginine methyl ester (1 mg kg−1 i.v.) entirely prevented early hyporeactivity and rise in NO3− concentration. In addition it attenuated in comparable proportion both delayed hyporeactivity to NA in vivo and circulating levels of NO derivatives. Conclusion: The results confirm the involvement of NO in the two phases of hyporeactivity to NA induced by LPS. They strongly support the view that a circulating factor is involved in triggering endothelial NO release during the early phase, whereas the delayed phase is associated with a high production of NO in vascular smooth muscle resulting from the induction of NO synthase.
The GDPAL region of the pre-s1 envelope protein is important for morphogenesis of woodchuck hepatitis virus
Authors: Minshu Yu, Suzanne U. Emerson, Paul Cote, Max Shapiro, Robert H. Purcell
Journal: Hepatology (1998)

The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV. To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region. The mutant DNA was transfected into human hepatoma cell line Huh7, and the medium was assayed for virion production by immunoprecipitation and Southern blot analysis. We found that an in-frame deletion of this small region inhibited virion formation, suggesting that the GDPAL region of the pre-S envelope protein was required for virus assembly and/or secretion of WHV. Individual replacement of alanine 204, leucine 205, or serine 206 with other amino acid residues did not affect virus production. However, substitution of either aspartic acid 202 with valine or proline 203 with leucine dramatically inhibited WHV production. Furthermore, the GDPAL mutants were individually tested for their abilities to complement a pre-S1 defective genome. The results showed that the GDPAL region functioned as part of the pre-S1 protein but was not required to function as part of the pre-S2 protein.
Iris Nevus Growth into Melanoma: Analysis of 1611 Consecutive Eyes
Authors: Carol L. Shields, Swathi Kaliki, Anne Hutchinson, Stephanie Nickerson, Jinali Patel, Swarupa Kancherla, Ani Peshtani, Shazia Nakhoda, Kristen Kocher, Emily Kolbus, Emily Jacobs, Robert Garoon, Brianna Walker, Brittany Rogers, Jerry A. Shields
Journal: Ophthalmology (2013)
Carnosinemia
Authors: Thomas L. Perry, Shirley Hansen, Bluma Tischler, Rosamund Bunting, Kenneth Berry
Journal: New England Journal of Medicine (1967)

A LARGE number of inborn errors of amino acid metabolism have now been described,1 and the list of such conditions probably is far from complete. Many of these disorders present themselves as abnormal aminoacidurias, often with associated mental deficiency and neurologic disease. We report herewith preliminary investigations on 2 patients who appear to have a new disorder of this type, involving impaired cleavage of imidazole dipeptides.A systematic program of simple chemical screening tests2 and two-dimensional paper chromatography for amino acids is being carried out on the urines of all patients newly admitted to a local hospital for mental defectives. . . .
Long Incubation Period in Kala-Azar
Authors: W. H. Jopling
Journal: BMJ (1955)

Growing evidence supports a critical role for the dorsal striatum in cognitive as well as motor control. Both lesions and <i>in vivo</i> recordings demonstrate a transition in the engaged dorsal striatal subregion, from dorsomedial to dorsolateral, as skill performance shifts from an attentive phase to a more automatic or habitual phase. What are the neural mechanisms supporting the cognitive and behavioral transitions in skill learning? To pursue this question, we used T-maze training during which rats transition from early, attentive (dorsomedial) to late habitual (dorsolateral) performance. Following early or late training, we performed the first direct comparison of bidirectional synaptic plasticity in striatal brain slices, and the first evaluation of striatal synaptic plasticity by hemisphere relative to a learned turn. Consequently, we find that long-term potentiation and long-term depression are independently modulated with learning rather than reciprocally linked as previously suggested. Our results establish that modulation of evoked synaptic plasticity with learning depends on striatal subregion, training stage, and hemisphere relative to the learned turn direction. Exclusive to the contralateral hemisphere, intrinsic excitability is enhanced in dorsomedial relative to dorsolateral medium spiny neurons early in training and population responses are dampened late in training. Neuronal reconstructions indicate dendritic remodeling after training, which may represent a novel form of pruning. In conclusion, we describe region- and hemisphere-specific changes in striatal synaptic, intrinsic, and morphological plasticity which correspond to T-maze learning stages, and which may play a role in the cognitive transition between attentive and habitual strategies. <b>SIGNIFICANCE STATEMENT</b> We investigated neural plasticity in dorsal striatum from rats that were briefly or extensively trained on a directional T-maze task. Our results demonstrate that both the extent of training and the direction a rat learns to turn control the location and type of change in synaptic plasticity. In addition, brief training produces changes in neuron excitability only within one striatal subregion, whereas all training produces widespread changes in dendritic morphology. Our results suggest that activity in dorsomedial striatum strengthens the rewarded turn after brief training, whereas activity in dorsolateral striatum suppresses unrewarded turns after extensive training. This study illuminates how plasticity mediates learning using a task recognized for transitioning subjects from attentive to automatic performance.
Adiponutrin Functions as a Nutritionally Regulated Lysophosphatidic Acid Acyltransferase
Authors: Manju Kumari, Gabriele Schoiswohl, Chandramohan Chitraju, Margret Paar, Irina Cornaciu, Ashraf Y. Rangrez, Nuttaporn Wongsiriroj, Harald M. Nagy, Pavlina T. Ivanova, Sarah A. Scott, Oskar Knittelfelder, Gerald N. Rechberger, Ruth Birner-Gruenberger, Sandra Eder, H. Alex Brown, Guenter Haemmerle, Monika Oberer, Achim Lass, Erin E. Kershaw, Robert Zimmermann, Rudolf Zechner
Journal: Cell Metabolism (2012)
More on Bacterial Antigen in the Kidney
Authors: Robert H. Heptinstall
Journal: New England Journal of Medicine (1973)

Chronic pyelonephritis remains a confused and confusing entity. One of the chief reasons is the loose way in which the term is applied to kidneys that show parenchymal scars in which there is predominantly tubular loss, interstitial fibrosis accompanied by chronic inflammatory cells, and variable changes in glomeruli, which in their extreme form are completely solidified. It is now appreciated that such scarred areas may be caused by several different processes, chief among which are ischemia, infection and obstruction. In many cases, however, the etiologic factors and pathogenetic mechanisms are unknown, and for this group, it seems advisable at present . . .
Conductive Channels Identified With Contrast-Enhanced MR Imaging Predict Ventricular Tachycardia in Systolic Heart Failure
Authors: Lian-Yu Lin, Mao-Yuan M. Su, Jien-Jiun Chen, Ling-Ping Lai, Juey-Jen Hwang, Chuen-Den Tseng, Yih-Sharng Chen, Hsi-Yu Yu, Wen-Yih I. Tseng, Jiunn-Lee Lin
Journal: JACC. Cardiovascular imaging (2013)