tbuckley/cabot-search huggingface dataset:
Altered expression of antioxidant enzymes and autophagic proteins in transglutaminase 2 knockout mice
Authors: Barbara D’Orio, Luana Barone, Anna Fracassi, Francesca Fanelli, Sara Sepe, Marco Segatto, Mauro Piacentini, Roberta Nardacci, Sandra Moreno
Journal: Molecular Neurodegeneration (2013)

Background Transglutaminases (TGs) are ubiquitous calcium-dependent acyl-transferases, catalysing post-translational protein modifications. Among the family members, TG2 (or “tissue” transglutaminase) acts as a multifunctional protein regulating cell processes, including autophagy [1]. TG2 is highly expressed in the nervous tissue and reportedly involved in neurodegenerative disorders. Indeed, the pathophysiology of these diseases includes insoluble aggregate formation, and covalent cross-linking of pathogenic proteins by TG2 has been suggested. Another hallmark of neurodegeneration is dysregulated autophagy, thus making the role played by TG2 in this cellular process especially relevant. Interestingly, conditions promoting TG2 activity, such as low GTP and high calcium levels, associated with oxidative stress, occur in neurodegeneration. The present study aims to clarify the role of TG2 in redox balance and autophagy. To this purpose, the expression levels of antioxidant enzymes and pro-autophagic proteins were investigated in various brain regions and liver of TG2-/mice.
Interactions among Proteins of Floral MADS-Box Genes in Basal Eudicots: Implications for Evolution of the Regulatory Network for Flower Development
Authors: C. Liu, J. Zhang, N. Zhang, H. Shan, K. Su, J. Zhang, Z. Meng, H. Kong, Z. Chen
Journal: Molecular Biology and Evolution (2010)

Floral MADS-box genes encode transcription factors that play critical roles in the development and evolution of the flower. Proteins of floral MADS-box genes regulate the expression of their downstream genes by forming various homodimers/heterodimers and quaternary complexes. Interactions among proteins of floral MADS-box genes have been documented in several model species, yet the information accumulated so far is still not sufficient to draw a general picture of the evolution of the interactions. We have characterized 28 putative floral MADS-box genes from three representative basal eudicots (i.e., Euptelea pleiospermum, Akebia trifoliata, and Pachysandra terminalis) and investigated the protein–protein interactions (PPIs) among the proteins encoded by these genes using yeast two-hybrid assays. We found that, although the PPIs in basal eudicots are largely consistent with those in core eudicots and monocots, there are lineage-specific features that have not been observed elsewhere. We also reconstructed the evolutionary histories of the PPIs among members of seven MADS-box gene lineages (i.e., AP1, AP3, PI, AG, STK, AGL2, and AGL9) in angiosperms. We revealed that the PPIs were extremely conserved in nine (or 32.1%) of the 28 possible combinations, whereas considerable variations existed in seven (25.0%) of them; in the remaining 12 (or 42.9%) combinations, however, no interaction was observed. Notably, most of the PPIs required for the formation of quaternary complexes, as suggested by the "quartet model," were highly conserved. This suggested that the evolutionarily conservative PPIs may have played critical roles in the establishment of the basic structure (or architecture) of the flower and experienced coevolution to maintain their functions. The evolutionarily variable PPIs, however, seem to have played subsidiary roles in flower development and have contributed to the variation in floral traits.
HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders
Authors: Emmanuel L. Gautier, Marit Westerterp, Neha Bhagwat, Serge Cremers, Alan Shih, Omar Abdel-Wahab, Dieter Lütjohann, Gwendalyn J. Randolph, Ross L. Levine, Alan R. Tall, Laurent Yvan-Charvet
Journal: The Journal of Experimental Medicine (2013)

A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based on expression of human leukemia disease alleles, we uncovered a mechanism by which proliferating and inflammatory myeloid cells take up and oxidize glucose during the feeding period, contributing to energy dissipation and subsequent loss of adipose mass. In vivo, lentiviral inhibition of Glut1 by shRNA prevented myeloproliferation and adipose tissue loss in mice with defective cholesterol efflux pathway in leukocytes. Thus, Glut1 was necessary to sustain proliferation and potentially divert glucose from fat storage. We also showed that overexpression of the human ApoA-I transgene to raise high-density lipoprotein (HDL) levels decreased Glut1 expression, dampened myeloproliferation, and prevented fat loss. These experiments suggest that inhibition of Glut-1 and HDL cholesterol–raising therapies could provide novel therapeutic approaches to treat the energy imbalance observed in myeloproliferative disorders.
Pilot Studies
Authors: Caroline Kistin, Michael Silverstein
Journal: JAMA (2015)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Antithrombotic Effect of Malayan Pit Viper Venom on Experimental Thrombosis of the Inferior Vena Cava Produced by a New Method
Authors: JAMES L. MARSTEN, CHAN KOK-EWE, JAY L. ANKENEY, ROBERT E. BOTTI
Journal: Circulation Research (1966)

A reliable method of producing thrombosis of the inferior vena cava in dogs is described. This consists of placing a segment of umbilical tape across the lumen of the vein and sewing it in place without interfering with blood flow. In the control animals gross thrombi were not usually present in the immediate postoperative period but were demonstrated after 24 hours. By the 7th postoperative day large red clots completely obstructing the vessel were usually found. The venom of the Malayan pit viper proved to be highly effective in preventing experimental thrombosis. The antithrombotic effect of viper venom is believed to be due primarily to induced hypofibrinogenemia. Accelerated fibrinolysis may also be a factor. The experiments suggest that Malayan pit viper venom may be effective as an antithrombotic agent.
Genes, oxidative stress, and the risk of chronic obstructive pulmonary disease
Authors: H. Koyama, D. M. Geddes
Journal: Thorax (1998)

The first-pass metabolism of foreign compounds in the lung is an important protective mechanism against oxidative stress. We investigated whether polymorphisms in the gene for microsomal epoxide hydrolase (mEPHX), an enzyme involved in this protective process, had any bearing on individual susceptibility to the development of chronic obstructive pulmonary disease (COPD) and emphysema.We designed PCR-based genotyping assays to detect variant forms of mEPHX that confer slow and fast activity. We used these assays to screen 203 blood-donor controls and groups of patients with asthma (n = 57), lung cancer (n = 50), COPD (n = 68), and emphysema (n = 94), who were attending specialised clinics in Edinburgh, UK.The proportion of individuals with innate slow mEPHX activity (homozygotes) was significantly higher in both the COPD group and the emphysema group than in the control group (COPD 13 [19%] vs control 13 [6%]; emphysema 21 [22%] vs 13 [6%]). The odds ratios for homozygous slow activity versus all other phenotypes were 4.1 (95% CI 1.8-9.7) for COPD and 5.0 (2.3-10.9) for emphysema.Genetic polymorphisms in xenobiotic enzymes may have a role in individual susceptibility to oxidant-related lung disease. Epoxide derivatives of cigarette-smoke components may be the cause of some of the lung damage characteristics of these diseases.
Dynamics of mucosal permeability and inflammation in collagenous colitis before, during, and after loop ileostomy
Authors: A Munch
Journal: Gut (2005)

Collagenous colitis has become a more frequent diagnosis but the aetiology of this disease is still unknown. We describe a female patient with intractable collagenous colitis who was treated with a temporary loop ileostomy. She was followed clinically, histopathologically, and functionally by measuring mucosal permeability before surgery, after ileostomy, and after bowel reconstruction. In our case report, active collagenous colitis was combined with increased transcellular and paracellular mucosal permeability. Diversion of the faecal stream decreased inflammation of the mucosa and normalised epithelial degeneration and mucosal permeability. After restoration of bowel continuity, mucosal permeability was altered prior to the appearance of a collagenous layer.
Curcumin prevents and reverses murine cardiac hypertrophy
Authors: Hong-Liang Li, Chen Liu, Geoffrey de Couto, Maral Ouzounian, Mei Sun, Ai-Bing Wang, Yue Huang, Cheng-Wei He, Yu Shi, Xin Chen, Mai P. Nghiem, Youan Liu, Manyin Chen, Fayez Dawood, Masahiro Fukuoka, Yuichiro Maekawa, Liyong Zhang, Andrew Leask, Asish K. Ghosh, Lorrie A. Kirshenbaum, Peter P. Liu
Journal: Journal of Clinical Investigation (2008)

Chromatin remodeling, particularly histone acetylation, plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. We hypothesized that curcumin, a natural polyphenolic compound abundant in the spice turmeric and a known suppressor of histone acetylation, would suppress cardiac hypertrophy through the disruption of p300 histone acetyltransferase-dependent (p300-HAT-dependent) transcriptional activation. We tested this hypothesis using primary cultured rat cardiac myocytes and fibroblasts as well as two well-established mouse models of cardiac hypertrophy. Curcumin blocked phenylephrin-induced (PE-induced) cardiac hypertrophy in vitro in a dose-dependent manner. Furthermore, curcumin both prevented and reversed mouse cardiac hypertrophy induced by aortic banding (AB) and PE infusion, as assessed by heart weight/BW and lung weight/BW ratios, echocardiographic parameters, and gene expression of hypertrophic markers. Further investigation demonstrated that curcumin abrogated histone acetylation, GATA4 acetylation, and DNA-binding activity through blocking p300-HAT activity. Curcumin also blocked AB-induced inflammation and fibrosis through disrupting p300-HAT-dependent signaling pathways. Our results indicate that curcumin has the potential to protect against cardiac hypertrophy, inflammation, and fibrosis through suppression of p300-HAT activity and downstream GATA4, NF-kappaB, and TGF-beta-Smad signaling pathways.
Elevated Production of Interleukin-6 Is Associated With a Lower Incidence of Disease-Related Ischemic Events in Patients With Giant-Cell Arteritis
Authors: José Hernández-Rodríguez, Marta Segarra, Carme Vilardell, Montse Sánchez, Ana García-Martínez, María-José Esteban, Josep M. Grau, Alvaro Urbano-Márquez, Dolors Colomer, Hynda K. Kleinman, Maria C. Cid
Journal: Circulation (2003)

Patients with giant-cell arteritis (GCA) who develop a strong acute-phase response are at low risk of disease-related ischemic events.To assess the potential protective role of proinflammatory cytokines in the development of ischemic events in GCA, we measured tissue expression (66 individuals) and/or circulating levels (80 individuals) of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and IL-6 in patients with biopsy-proven GCA. Tissue expression was determined by quantitative real-time polymerase chain reaction and immunohistochemistry. Circulating cytokines were determined by enzyme-linked immunoassay. We found that patients with disease-related ischemic events had lower IL-6 mRNA levels (5.9+/-2.1 versus 27.6+/-7.8 relative units, P=0.013), lower IL-6 immunohistochemical expression scores (1.5+/-0.9 versus 2.7+/-1, P=0.001), and lower circulating levels of IL-6 (13.6+/-2.1 versus 24+/-2.4 pg/mL, P=0.002) than patients without ischemic complications. No significant differences were found for either IL-1beta or TNF-alpha. We subsequently investigated direct effects of IL-6 on vessel wall components. We found that IL-6 stimulates endothelial cell proliferation and differentiation into capillary-like structures and induces full angiogenic activity in both ex vivo (aortic ring) and in vivo (chick chorioallantoic membrane) assays.GCA patients with ischemic complications have lower tissue expression and circulating levels of IL-6 than patients with no ischemic events. IL-6 has relevant direct effects on vascular wall components that might be protective: IL-6 activates a functional program related to angiogenesis that may compensate for ischemia in patients with GCA.
Should the ovaries be removed or retained at the time of hysterectomy for benign disease?
Authors: M. Hickey, M. Ambekar, I. Hammond
Journal: Human Reproduction Update (2009)

Bilateral oophorectomy is commonly performed at the time of hysterectomy for benign disease. Indications for oophorectomy vary, but in most cases relatively little high-quality information is available to inform the surgeon or patient regarding the relative risks and benefits of ovarian conservation or removal. This review will address the common clinical situations when oophorectomy may be performed and will evaluate the evidence for risk and benefit in each of these circumstances. The aim of this review is to bring together the evidence regarding oophorectomy in pre- and post-menopausal women and to highlight the areas needing further study. We searched the published literature for studies related to outcomes following surgical menopause, risk-reducing surgery for ovarian cancer, surgical treatment for endometriosis, bilateral oophorectomy for benign disease and treatment for premenstrual syndrome/premenstrual dysphoric disorder. Rates of oophorectomy at the time of hysterectomy for benign disease appear to be increasing. There is good evidence to support bilateral salpingoophorectomy (BSO) as a risk-reducing surgery for women at high risk of ovarian cancer, but relatively little evidence to support oophorectomy or BSO in other circumstances. There is growing evidence from observational studies that surgical menopause may impact negatively on future cardiovascular, psychosexual, cognitive and mental health. Clinicians and patients should fully consider the relative risks and benefits of oophorectomy on an individual basis prior to surgery.
The Cav3.1 T-type calcium channel is required for neointimal formation in response to vascular injury in mice
Authors: Bing-Hsiean Tzeng, Yen-Hui Chen, Ching-Hui Huang, Shin-Shiou Lin, Kuan-Rong Lee, Chien-Chang Chen
Journal: Cardiovascular Research (2012)

Restenosis is an undesirable consequence following percutaneous vascular interventions. However, the current strategy for preventing restenosis is inadequate. The aim of this study was to investigate the role of low-voltage gated T-type calcium channels in regulating vascular smooth muscle cell (VSMC) proliferation during neointimal formation. Wire injury of mice carotid arteries resulted in neointimal formation in the wild-type and Cav3.2−/− but not Cav3.1−/− mice, indicating a critical role of Cav3.1 in neointimal formation. In addition, we found a significant increase of Cav3.1 mRNA and protein in injured arteries. Cav3.1 knockout or knockdown (shCav3.1) reduced VSMC proliferation. Since T-channels are expressed predominantly in the G1 and S phases in VSMCs, we examined whether an abnormal G1/S transition was the cause of the reduced cell proliferation in shCav3.1 VSMCs. We found a disrupted expression of cyclin E in shCav3.1 VSMCs, and calmodulin agonist CALP1 partially rescued the defective cell proliferation. Furthermore, we demonstrated that infusion of NNC55-0396, a selective T-channel blocker, inhibited neointimal formation in wild-type mice. Cav3.1 is required for VSMC proliferation during neointimal formation, and blocking of Cav3.1 may be beneficial for preventing restenosis.
Pharmacology of Brain Na<sup>+</sup>/Ca<sup>2+</sup>Exchanger: From Molecular Biology to Therapeutic Perspectives
Authors: L. Annunziato, G. Pignataro, G. F. Di Renzo
Journal: Pharmacological Reviews (2004)

In the last two decades, there has been a growing interest in unraveling the role that the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (NCX) plays in the function and regulation of several cellular activities. Molecular biology, electrophysiology, genetically modified mice, and molecular pharmacology have helped to delve deeper and more successfully into the physiological and pathophysiological role of this exchanger. In fact, this nine-transmembrane protein, widely distributed in the brain and in the heart, works in a bidirectional way. Specifically, when it operates in the forward mode of operation, it couples the extrusion of one Ca<sup>2+</sup> ion with the influx of three Na<sup>+</sup> ions. In contrast, when it operates in the reverse mode of operation, while three Na<sup>+</sup> ions are extruded, one Ca<sup>2+</sup> enters into the cells. Different isoforms of NCX, named NCX1, NCX2, and NCX3, have been described in the brain, whereas only one, NCX1, has been found in the heart. The hypothesis that NCX can play a relevant role in several pathophysiological conditions, including hypoxia-anoxia, white matter degeneration after spinal cord injury, brain trauma and optical nerve injury, neuronal apoptosis, brain aging, and Alzheimer9s disease, stems from the observation that NCX, in parallel with selective ion channels and ATP-dependent pumps, is efficient at maintaining intracellular Ca<sup>2+</sup> and Na<sup>+</sup> homeostasis. In conclusion, although studies concerning the involvement of NCX in the pathological mechanisms underlying brain injury during neurodegenerative diseases started later than those related to heart disease, the availability of pharmacological agents able to selectively modulate each NCX subtype activity and antiporter mode of operation will provide a better understanding of its pathophysiological role and, consequently, more promising approaches to treat these neurological disorders.
A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection
Authors: Marie-Luise Berres, Sven Papen, Katrin Pauels, Petra Schmitz, Mirko Moreno Zaldivar, Claus Hellerbrand, Tobias Mueller, Thomas Berg, Ralf Weiskirchen, Christian Trautwein, Hermann E. Wasmuth
Journal: Journal of Hepatology (2008)
Endobronchial leiomyoma: a case report.
Authors: U Ozcelik, E Kotiloglu, A Gocmen, M E Senocak, N Kiper
Journal: Thorax (1995)

Abstract Leiomyoma of the lung is very rare in children. The case history is presented of an 8 year old boy with an endobronchial leiomyoma which caused total atelectasis of the left lung.
Insulin-like growth factors and insulin-like growth factor-binding proteins in relation to disease status and incidence of hypoglycaemia in patients with a gastrointestinal stromal tumour
Authors: B. Rikhof, J. van Doorn, A.J.H. Suurmeijer, M.W. Rautenberg, P.J.T.A. Groenen, M.A.J. Verdijk, P.L. Jager, S. de Jong, J.A. Gietema, W.T.A. van der Graaf
Journal: Annals of Oncology (2009)
Improving Prescribing Practices in Primary Care
Authors: Chris Del Mar
Journal: PLoS Medicine (2006)

In a new paper in PLoS Medicine, Fretheim and colleagues report the results of the Rational Prescribing in Primary Care (RaPP) trial, a cluster-randomised controlled trial of a multicomponent intervention to improve prescribing of antihypertensive and cholesterol-lowering drugs in primary care [ 1]. In a second paper, the same authors present their economic evaluation of the intervention [ 2].
A Kinetic Model of Intervertebral Stress During Lifting
Authors: G. A. Wood, K. C. Hayes
Journal: British Journal of Sports Medicine (1974)

A biomechanical model of a simple lifting motion is presented in which the forces and moments of force acting about the L4-L5 vertebral articulation were determined from kinetic and kinematic data. Derivation of the forces due to motion permitted a unique method for estimating intervertebral stress during each phase of the lift and provided a logical extension to an earlier static model of intervertebral stress presented by Troup (13). The intervertebral force was found to have a maximum value of over 400 kg during the initial phase of the lift. By partitioning this force into its shearing and compressional components, it was possible to determine quantitatively the lumbar stress involved in lifting. The values are discussed briefly in relation to the aetiology of back injuries and some of the predictions and applications of the dynamic model are also considered.