tbuckley/cabot-search huggingface dataset:
CNS involvement in systemic lupus erythematosus: a case with remarkable histopathological findings
Authors: M J Rood
Journal: Annals of the Rheumatic Diseases (2001)

Case reportA 38 year old man was admitted in a subcomatose condition.According to the accompanying family, his current state had developed the night before.The patient was known to have had systemic lupus erythematosus (SLE) for 10 years.The diagnosis was based on a history of characteristic skin lesions, pleuritis, pericarditis, arthritis, antinuclear antibody, anti-Sm antibody, and hypocomplementaemia.His spleen had been removed in his adolescence as treatment for idiopathic thrombopenic purpura, diagnosed before the onset of SLE.Currently, he was taking 10 mg prednisone daily, started a week ago because of deteriorating skin lesions.Physical examination showed a Glasgow Coma Score of 1-4-2.His body temperature and blood pressure were normal.Abdominal and thoracic examination did not disclose abnormalities.No signs of meningeal inflammation were present.The pupils were equally large and reacted adequately to light stimuli.Symmetrical retractions of the limbs occurred after inflicting pain stimuli.The right sided reflex of the quadriceps was higher than the left.A right sided Babinski's sign was noted.At the emergency ward the patient developed tonic-clonic seizures.Laboratory testing showed an erythrocyte sedimentation rate (ESR) of 32 mm/1st h and a normal haematological survey.Antinuclear antibodies and anti-dsDNA were present and no recent immune response against neurotropic viruses could be detected.Antiphospholipid antibodies were absent.Computed tomography as well as magnetic resonance imaging scanning of the brain and a chest x ray examination were normal.The cerebrospinal fluid (CSF) was clear with a normal opening pressure and contained 36 mononuclear cells/ mm 3 .Protein content of the CSF was 3.85 g/l (normal range 0.15-0.45g/l) and the IgG index was 1.3 (normal range 0.20-0.85).The albumen quotient was 36.3 (normal value <7.6).All CSF cultures were negative.Central nervous system (CNS)-SLE was diagnosed and 1000 mg methylprednisolone at three consecutive days and phenytoin was started.The clinical course of the patient was complicated after three days by an opportunistic infection with Streptococcus pneumoniae.Two days after antibiotic treatment with benzylpenicillin had resolved his pneumonia, 1200 mg of cyclophosphamide intravenously was added to the treatment because of insuYcient improvement in the patient's condition.After two days, he developed fever and because an x ray examination of the thorax showed a new
The TRPC Class of Ion Channels: A Critical Review of Their Roles in Slow, Sustained Increases in Intracellular Ca<sup>2+</sup> Concentrations
Authors: Lutz Birnbaumer
Journal: The Annual Review of Pharmacology and Toxicology (2009)

The realization that there exists a multimembered family of cation channels with structural similarity to Drosophila's Trp channel emerged during the second half of the 1990s. In mammals, depending on the species, the TRP family counts 29 or 30 members which has been subdivided into 6 subfamilies on the basis of sequence similarity. TRP channels are nonselective monovalent cation channels, most of which also allow passage of Ca 2+ . Many members of each of these families, but not all, are involved in sensory signal transduction. The C-type (for canonical or classical) subfamily, differs from the other TRP subfamilies in that it fulfills two different types of function: membrane depolarization, resembling sensory transduction TRPs, and mediation of sustained increases in intracellular Ca 2+ . The mechanism(s) by which the C-class of TRP channels—the TRPCs—are activated is poorly understood and their role in mediating intracellular Ca 2+ increases is being questioned. Both of these questions—mechanism of activation and participation in Ca 2+ entry—are the topics of this review.
SIRT3 Deacetylates Mitochondrial 3-Hydroxy-3-Methylglutaryl CoA Synthase 2 and Regulates Ketone Body Production
Authors: Tadahiro Shimazu, Matthew D. Hirschey, Lan Hua, Kristin E. Dittenhafer-Reed, Bjoern Schwer, David B. Lombard, Yu Li, Jakob Bunkenborg, Frederick W. Alt, John M. Denu, Matthew P. Jacobson, Eric Verdin
Journal: Cell Metabolism (2010)
Valproic Acid Stimulates Proliferation and Self-renewal of Hematopoietic Stem Cells
Authors: Gesine Bug, Hilal Gül, Kerstin Schwarz, Heike Pfeifer, Manuela Kampfmann, Xiaomin Zheng, Tim Beissert, Simone Boehrer, Dieter Hoelzer, Oliver Gerhard Ottmann, Martin Ruthardt
Journal: Cancer Research (2005)

Abstract Histone deacetylase inhibitors have attracted considerable attention because of their ability to overcome the differentiation block in leukemic blasts, an effect achieved either alone or in combination with differentiating agents, such as all-trans retinoic acid. We have previously reported favorable effects of the potent histone deacetylase inhibitor valproic acid in combination with all-trans retinoic acid in patients with advanced acute myeloid leukemia leading to blast cell reduction and improvement of hemoglobin. These effects were accompanied by hypergranulocytosis most likely due to an enhancement of nonleukemic myelopoiesis and the suppression of malignant hematopoiesis rather than enforced differentiation of the leukemic cells. These data prompted us to investigate the effect of valproic acid on normal hematopoietic stem cells (HSC). Here we show that valproic acid increases both proliferation and self-renewal of HSC. It accelerates cell cycle progression of HSC accompanied by a down-regulation of p21cip-1/waf-1. Furthermore, valproic acid inhibits GSK3β by phosphorylation on Ser9 accompanied by an activation of the Wnt signaling pathway as well as by an up-regulation of HoxB4, a target gene of Wnt signaling. Both are known to directly stimulate the proliferation of HSC and to expand the HSC pool. In summary, we here show that valproic acid, known to induce differentiation or apoptosis in leukemic blasts, stimulates the proliferation of normal HSC, an effect with a potential effect on its future role in the treatment of acute myeloid leukemia.
Immediate response to cigarette smoke.
Authors: P J Rees, P J Chowienczyk, T J Clark
Journal: Thorax (1982)

Using an automated method of calculating airways resistance in the body plethysmograph, we have investigated changes occurring immediately after inhalation of cigarette smoke. Decreases in specific conductance occurred by the time of the first measurement seven or eight seconds after exposure to single inhalations of cigarette smoke in 12 smokers and 12 non-smokers. Less than half of the initial change was present 40 seconds after the inhalation. Initial responses were greater in the non-smokers. Responses recurred with repeated inhalations in smokers and non-smokers. Prior administration of salbutamol and ipratropium bromide significantly inhibited the response and this inhibition appeared to be greater in non-smokers. Sodium cromoglycate inhaled as a dry powder had no effect on the response.
Mutations of the Cardiac Ryanodine Receptor (RyR2) Gene in Familial Polymorphic Ventricular Tachycardia
Authors: Päivi J. Laitinen, Kevin M. Brown, Kirsi Piippo, Heikki Swan, Joe M. Devaney, Bhoomi Brahmbhatt, Elizabeth A. Donarum, Michael Marino, Natascia Tiso, Matti Viitasalo, Lauri Toivonen, Dietrich A. Stephan, Kimmo Kontula
Journal: Circulation (2001)

Background —Familial polymorphic ventricular tachycardia is an autosomal-dominant, inherited disease with a relatively early onset and a mortality rate of ≈30% by the age of 30 years. Phenotypically, it is characterized by salvoes of bidirectional and polymorphic ventricular tachycardias in response to vigorous exercise, with no structural evidence of myocardial disease. We previously mapped the causative gene to chromosome 1q42-q43. In the present study, we demonstrate that patients with familial polymorphic ventricular tachycardia have missense mutations in the cardiac sarcoplasmic reticulum calcium release channel (ryanodine receptor type 2 [RyR2]). Methods and Results —In 3 large families studied, 3 different RyR2 mutations (P2328S, Q4201R, V4653F) were detected and shown to fully cosegregate with the characteristic arrhythmic phenotype. These mutations were absent in the nonaffected family members and in 100 healthy controls. In addition to identifying 3 causative mutations, we identified a number of single nucleotide polymorphisms that span the genomic structure of RyR2 and will be useful for candidate-based association studies for other arrhythmic disorders. Conclusions —Our data illustrate that mutations of the RyR2 gene cause at least one variety of inherited polymorphic tachycardia. These findings define a new entity of disorders of myocardial calcium signaling.
Endothelial-derived neuregulin is an important mediator of ischaemia-induced angiogenesis and arteriogenesis
Authors: N. Hedhli, L. W. Dobrucki, A. Kalinowski, Z. W. Zhuang, X. Wu, R. R. Russell, A. J. Sinusas, K. S. Russell
Journal: Cardiovascular Research (2011)

AimsNeuregulins (NRG) are growth factors that are synthesized by endothelial cells (ECs) and bind to erbB receptors. We have shown previously that NRG is proangiogenic in vitro, and that NRG/erbB signalling is important for autocrine endothelial angiogenic signalling in vitro. However, the role of NRG in the angiogenic response to ischaemia is unknown. We hypothesized that endothelial NRG is required for ischaemia-induced angiogenesis in vivo and that exogenous administration of NRG will enhance angiogenic responses after ischaemic insult.
Modulation of Baroreceptor Activity by Nitric Oxide and <i>S</i> -Nitrosocysteine
Authors: Tadashi Matsuda, James N. Bates, Stephen J. Lewis, Francois M. Abboud, Mark W. Chapleau
Journal: Circulation Research (1995)

The goal of this study was to determine whether nitric oxide (NO) and the NO donor, S-nitrosocysteine (cysNO), modulate the activity of carotid sinus baroreceptors. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in anesthetized rabbits. Baroreceptor activity decreased in a dose-dependent manner after injection of either NO or cysNO as constant pressure was maintained, and activity recovered spontaneously over time, within seconds to minutes. The baroreceptor pressure-activity relation was shifted significantly to the right by cysNO, with a profound suppression of activity at high pressure. Baroreceptor activity at 160 mm Hg averaged 76 +/- 8%, 60 +/- 6%, and 36 +/- 5% of the control maximum during exposure to 10(-4), 2 to 3 x 10(-4), and 10(-3) mol/L cysNO, respectively. The inhibition of activity by the L and D isomers of cysNO was equivalent and was blocked by reduced hemoglobin, suggesting that the effect was mediated by NO. The suppression of baroreceptor activity by cysNO was not related to vascular relaxation as measured by videomicrometer. Inhibition of soluble guanylate cyclase with methylene blue or 6-anilinoquinoline-5,8-quinone (LY83583, 10(-5) mol/L) did not attenuate and dibutyryl cGMP (10(-3) mol/L) did not mimic the suppression of baroreceptor activity by cysNO, suggesting a cGMP-independent mechanism. Activation of endogenous NO formation with thimerosal (10(-5) to 10(-4) mol/L) reduced maximum baroreceptor activity in five of eight experiments to 59 +/- 7% of the control maximum.(ABSTRACT TRUNCATED AT 250 WORDS)
Beneficial Effects of Soy Phytoestrogen Intake in Postmenopausal Women With Type 2 Diabetes
Authors: Vijay Jayagopal, Paula Albertazzi, Eric S. Kilpatrick, Elaine M. Howarth, Paul E. Jennings, David A. Hepburn, Stephen L. Atkin
Journal: Diabetes Care (2002)

Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes.A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period.Compliance with the dietary supplementation was >90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean +/- SD 8.09 +/- 21.9%, P = 0.006), insulin resistance (6.47 +/- 27.7%, P = 0.003), HbA(1c) (0.64 +/- 3.19%, P = 0.048), total cholesterol (4.07 +/- 8.13%, P = 0.004), LDL cholesterol (7.09 +/- 12.7%, P = 0.001), cholesterol/HDL cholesterol ratio (3.89 +/- 11.7%, P = 0.015), and free thyroxine (2.50 +/- 8.47%, P = 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones.These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile.
Interchange between collagenous and lymphocytic colitis in severe disease with autoimmune associations requiring colectomy: a case report.
Authors: T E Bowling, A B Price, M al-Adnani, P D Fairclough, N Menzies-Gow, D B Silk
Journal: Gut (1996)

Collagenous colitis and lymphocytic colitis present with a similar clinical picture. Whether these conditions are separate entities or whether they represent different pathological stages of the same condition is an unresolved issue.This is a case of collagenous colitis following a fulminant course in which a colectomy was necessary. In the operative specimen the thickened collagen plate, which had been present only two weeks preoperatively had been lost and the pathology was of a lymphocytic colitis. Six months postoperatively this patient developed a CREST syndrome and primary biliary cirrhosis.This case shows the lability of the collagen plate and the common ground between collagenous and lymphocytic colitis, and presents evidence that these two conditions are different manifestations of the same disease. It also describes for the first time an association between collagenous colitis and CREST syndrome and primary biliary cirrhosis.
THE ROLE OF CHEMICAL MEDIATORS IN THE INFLAMMATORY RESPONSE INDUCED BY FOREIGN BODIES: COMPARISON WITH THE SCHISTOSOME EGG GRANULOMA
Authors: R. W. Kellermeyer, K. S. Warren
Journal: The Journal of Experimental Medicine (1970)

Both divinyl benzene copolymer (plastic) beads and schistosome eggs produce inflammatory reactions after intravenous deposition into the lung of a mouse. As reported previously, the schistosome egg granuloma is an immunologic reaction of the delayed hypersensitivity type; this inflammatory process is prevented by immunosuppressive measures, and characteristically demonstrates an anamnestic response. In contradistinction, the plastic bead granuloma appears to be characteristic of a foreign body reaction; it is unaffected by immunosuppressive measures and does not demonstrate an anamnestic response with repeated exposure. The data in this report suggest that the granuloma formation around plastic beads is a nonimmunologic reaction induced by chemical mediators of inflammation. This proposal is supported by the following findings: the plastic beads activate Hageman factor in normal human and mouse plasma; the plastic beads induce vascular permeability-enhancing activity as measured in guinea pig skin and kinin-like activity in normal human and mouse plasma that is dependent on Hageman factor; ellagic acid, an agent that activates Hageman factor in vivo and is reported to diminish kininogen by consumptive depletion, markedly depresses the plastic bead granuloma. These data are consistent with the idea that the plastic bead granuloma and perhaps other foreign body inflammatory reactions are in major part dependent on kinin formation. Ellagic acid also suppressed the schistosome egg granuloma, but not to the same degree as the plastic bead granuloma. The implications of this observation are discussed in the text. Silicosis and "blue velvet disease", pathologic processes associated with the deposition of silica and magnesium trisilicate, respectively, in the lung, and the induction of a foreign body reaction may also be dependent on the activation of chemical mediators of inflammation by the silica and magnesium trisilicate particles with immunologic mechanisms participating in only a minor way, if at all. The marked suppression of experimental silicosis and blue velvet disease in mice by ellagic acid supports this idea.
Anaphylaxis after intra‐articular injection of orgotein
Authors: M. L. Díez‐Gómez, M. Hinojosa, I. Moneo, E. Losada
Journal: Allergy (1987)

Orgotein, a recently introduced anti‐inflammatory agent, is the generic name accepted in the U.S.A. for the drug version of copper‐zinc superoxide dismutase. This metallo‐enzyme is obtained from bovine liver and has a molecular weight of about 32,000. We report on a patient to whom an intra‐articular injection of orgotein caused an anaphylactic reaction. An IgE‐mediated mechanism was suggested by an immediate positive skin test to orgotein and by the finding of specific IgE against orgotein in the patient's serum.
Vascular tolerance to nitroglycerin in ascorbate deficiency
Authors: Gerald Wölkart, M. Verena Wenzl, Matteo Beretta, Heike Stessel, Kurt Schmidt, Bernd Mayer
Journal: Cardiovascular Research (2008)

Nitroglycerin (GTN) acts through release of a nitric oxide (NO)-related activator of soluble guanylate cyclase in vascular smooth muscle. Besides enzymatic GTN bioactivation catalysed by aldehyde dehydrogenase, non-enzymatic reaction of GTN with ascorbate also results in the formation of a bioactive product. Using an established guinea pig model of ascorbate deficiency, we investigated whether endogenous ascorbate contributes to GTN-induced vasodilation. Guinea pigs were fed either standard or ascorbate-free diet for 2 or 4 weeks prior to measuring the GTN response of aortic rings and isolated hearts. The effects of ascorbate on GTN metabolism were studied with purified mitochondrial aldehyde dehydrogenase (ALDH2) and isolated mitochondria. Ascorbate deprivation led to severe scorbutic symptoms and loss of body weight, but had no (2 weeks) or only slight (4 weeks) effects on aortic relaxations to a direct NO donor. The EC50 of GTN was increased from 0.058 ± 0.018 to 0.46 ± 0.066 and 5.5 ± 0.9 µM after 2 and 4 weeks of ascorbate-free diet, respectively. Similarly, coronary vasodilation to GTN was severely impaired in ascorbate deficiency. The potency of GTN was reduced to a similar extent by ALDH inhibitors in control and ascorbate-deficient blood vessels. Up to 10 mM ascorbate had no effect on GTN metabolism catalysed by purified ALDH2 or liver mitochondria isolated from ascorbate-deficient guinea pigs. Our results indicate that prolonged ascorbate deficiency causes tolerance to GTN without affecting NO/cyclic GMP-mediated vasorelaxation.
The wrong standard: Science, not politics, needed
Authors: Kenneth R. Hammond
Journal: Behavioral and Brain Sciences (2004)

Krueger &amp; Funder (K&amp;F) focus on an important problem, but they offer a political rather than a scientific remedy. “Balance” is not our problem; systematic, scientific research is. Only that sort of research will ever lead social psychology out of its current malaise that focuses on positive and negative aspects of human behavior.
Interaction of Nuclear Receptors with the Wnt/β-Catenin/Tcf Signaling Axis: Wnt You Like to Know?
Authors: David J. Mulholland, Shoukat Dedhar, Gerhard A. Coetzee, Colleen C. Nelson
Journal: Endocrine Reviews (2005)

The cross-regulation of Wnt/β-catenin/Tcf ligands, kinases, and transcription factors with members of the nuclear receptor (NR) family has emerged as a clinically and developmentally important area of endocrine cell biology. Interactions between these signaling pathways result in a diverse array of cellular effects including altered cellular adhesion, tissue morphogenesis, and oncogenesis. Analyses of NR interactions with canonical Wnt signaling reveal two broad themes: Wnt/β-catenin modulation of NRs (theme I), and ligand-dependent NR inhibition of the Wnt/β-catenin/Tcf cascade (theme II). β-Catenin, a promiscuous Wnt signaling member, has been studied intensively in relation to the androgen receptor (AR). β-Catenin acts as a coactivator of AR transcription and is also involved in cotrafficking, increasing cell proliferation, and prostate pathogenesis. T cell factor, a transcriptional mediator of β-catenin and AR, engages in a dynamic reciprocity of nuclear β-catenin, p300/CREB binding protein, and transcriptional initiation factor 2/GC receptor-interaction protein, thereby facilitating hormone-dependent coactivation and transrepression. β-Catenin responds in an equally dynamic manner with other NRs, including the retinoic acid (RA) receptor (RAR), vitamin D receptor (VDR), glucocorticoid receptor (GR), progesterone receptor, thyroid receptor (TR), estrogen receptor (ER), and peroxisome proliferator-activated receptor (PPAR). The NR ligands, vitamin D3, trans/cis RA, glucocorticoids, and thiazolidines, induce dramatic changes in the physiology of cells harboring high Wnt/β-catenin/Tcf activity. Wnt signaling regulates, directly or indirectly, developmental processes such as ductal branching and adipogenesis, two processes dependent on NR function. β-Catenin has been intensively studied in colorectal cancer; however, it is now evident that β-catenin may be important in cancers of the breast, prostate, and thyroid. This review will focus on the cross-regulation of AR and Wnt/β-catenin/Tcf but will also consider the dynamic manner in which RAR/RXR, GR, TR, VDR, ER, and PPAR modulate canonical Wnt signaling. Although many commonalities exist by which NRs interact with the Wnt/β-catenin signaling pathway, striking cell line and tissue-specific differences require deciphering and application to endocrine pathology.