Ubiquitination of nuclear receptors

2017 ◽  
Vol 131 (10) ◽  
pp. 917-934 ◽  
Author(s):  
Jimmy El Hokayem ◽  
Celeste Amadei ◽  
Jean-Pierre Obeid ◽  
Zafar Nawaz
Keyword(s):  
Nuclear Receptors ◽  
Clinical Manifestations ◽  
Organ System ◽  
The Body ◽  
Regulatory Control ◽  
Cellular Proteins ◽  
Structural Components ◽  
Downstream Effects ◽  
External Agents ◽  
Clinical Disorders

Nuclear receptors (NRs) are cellular proteins, which upon ligand activation, act to exert regulatory control over transcription and subsequent expression. Organized via systemic classification into seven subfamilies, NRs partake in modulating a vast expanse of physiological functions essential for maintenance of life. NRs display particular characteristics towards ubiquitination, the process of addition of specific ubiquitin tags at appropriate locations. Orchestrated through groups of enzymes harboring a diverse array of specialized structural components, the ubiquitination process emphatically alters the fate or downstream effects of NRs. Such influence is especially prominent in transcriptional processes such as promoter clearing for optimization and degradation pathways eliminating or recycling targeted proteins. Ultimately, the ubiquitination of NRs carries significant implications in terms of generating pathological clinical manifestations. Increasing evidence from studies involving patients and disease models suggests a role for ubiquitinated NRs in virtually every organ system. This supports the broad repertoire of roles that NRs play in the body, including modulatory conductors, facilitators, responders to external agents, and critical constituents for pharmacological or biological interventions. This review aims to cover relevant background and mechanisms of NRs and ubiquitination, with a focus towards elucidating subsequent pathophysiology and therapeutics in clinical disorders encompassing such ubiquitinated NRs.

Fetishist disorder

2019 ◽  
Vol 1 (2) ◽  
pp. 73-77 ◽  
Author(s):  
Cristian Delcea ◽  
Dorina EUSEI
Keyword(s):  
Clinical Manifestations ◽  
The Body ◽  
Body Parts ◽  
Dsm V ◽  
Interpersonal Difficulties ◽  
Clinical Disorders ◽  
Magnus Hirschfeld ◽  
Normal Spectrum ◽  
Living Objects ◽  
Exclusive Focus

Fetishism, as a technical descriptor of atypical sexual behaviour, was noted in the writings of the well-known nineteenth century French psychologist Alfred Binet (1857–1911) (Binet, 1887) as well as prominent European sexologists Richard von Krafft-Ebing (1840–1902) (Krafft-Ebing, 1886), Havelock Ellis (1859–1939) (Ellis, 1906), and Magnus Hirschfeld (1868– 1935) (Hirschfeld, 1956). In their seminal writings, all of the afore mentioned sexologists used the terms “fetish” and “fetishism” to specifically describe an intense eroticization of either non-living objects and/or specific body parts that were symbolically associated with a person. Fetishes could be non clinical manifestations of a normal spectrum of eroticization or clinical disorders causing significant interpersonal difficulties. Ellis (1906) observed that body secretions or body products could also become fetishist expressions of “erotic symbolism”. Freud (1928) considered both body parts (e.g., the foot) or objects associated with the body (e.g., shoes) as fetish objects. For the purposes of this review, a “broader” historically based core definition for Fetishism will include intense and recurrent sexual arousal to: non-living objects, an exclusive focus on body parts or body products. Keywords: fetishism, Paraphilia, Partialism, DSM-V.

Clinical, morphological and biochemical signs of polymycotoxicosis in highly productive cows

2020 ◽  
pp. 14-17
Author(s):  
Irina A. Shkuratova ◽  
◽  
Lyudmila I. Drozdova ◽  
Aleksander I. Belousov ◽  
Keyword(s):  
Metabolic Disorders ◽  
Hepatorenal Syndrome ◽  
Morphological Changes ◽  
Clinical Manifestations ◽  
The Body ◽  
Feed Mixture ◽  
Milk Productivity ◽  
Structural Disorders ◽  
Increased Sensitivity ◽  
Penicillium Spp

Mycotoxicological monitoring of forages shows that the problem of mycotoxicosis has been relevant for several decades. Minimal doses of mycotoxins in feed lead to a decrease in milk productivity, increased sensitivity to infectious and non-infectious diseases. When several mycotoxins enter the body simultaneously, a synergistic effect develops, causing a significant increase in toxicity. Feed contaminated with several types of fungi and their toxins is dangerous for dairy cattle. It was found that the feed mixture contained the types of associations of Aspergillus spp. fungi + Fusarium; Aspergillus spp. + Penicillium spp. + Mucor spp; Fusarium + Penicillium; Mucor spp. + Fusarium + Ustilaginales. Pathogenetic features of metabolic and morphological changes in highly productive cows with polymycotoxicosis were studied. Feeding food contaminated with various metabolites of mold fungi leads to the development of signs of chronic toxemia in animals. Clinical manifestations are the development of diarrhea and dehydration, with a decrease in milk productivity. Metabolic disorders feature the development of an inflammatory process, metabolic acidosis, hyperfermentonemia, with an increase in the amount of creatinine and urea in the blood serum. Metabolic signs indicate the development of hepatorenal syndrome due to structural disorders of the liver and kidneys. Histological signs of polymicotoxicosis are intracapillary and hemorrhagic glomerulonephritis, hepatocyte micronecrosis, and proliferation of connective tissue stroma cells, which leads to the development of atrophic cirrhosis in the interstitial and circular phases.

HISTOLOGICAL CHANGES IN THE INTESTINES OF POULTRY DURING FODDER INTOXICATION

2020 ◽  
Author(s):  
E.P. Dolgov ◽  
◽  
A.A. Abramov ◽  
E.V. Kuzminova ◽  
E.V. Rogaleva ◽  
...  
Keyword(s):  
Body Weight ◽  
Histological Examination ◽  
Aflatoxin B1 ◽  
Structural Changes ◽  
Clinical Manifestations ◽  
Feed Additives ◽  
The Body ◽  
Histological Changes ◽  
Beet Pulp

The article presents the data on the study of the influence of mycotoxins combination (T-2 toxin at the concentration of 0.095 mg/kg and aflatoxin B1 in the concentration of 0.019 mg/kg) on the body of quails and the results of pharmacocorrection of toxicosis with a complex consisting of beet pulp and lecithin. Structural changes in the intestines of quais at fodder mycotoxicosis are described. The use of antitoxic feed additives in poultry led to a weakening of the action of xenobiotics, which was confirmed by an increase in the safety of poultry and increase in body weight of quails, a decrease in the clinical manifestations of intoxication, as well as in positive changes in the structure of the intestine of the poultry during histological examination.

Acute exudative paraneoplastic polymorphous vitelliform maculopathy in a patient with thymoma, myasthenia gravis, and polymyositis

2021 ◽  
pp. 112067212199404
Author(s):  
He Yu ◽  
Xinyu Ma ◽  
Nianting Tong ◽  
Zhanyu Zhou ◽  
Yu Zhang
Keyword(s):  
Myasthenia Gravis ◽  
Medical Center ◽  
Postoperative Radiotherapy ◽  
Clinical Manifestations ◽  
Subretinal Fluid ◽  
Metastatic Tumor ◽  
The Body ◽  
Pleural Thickening ◽  
History Of ◽  
Clinically Significant

Importance: This is the first reported case of acute exudative paraneoplastic polymorphous vitelliform maculopathy (AEPPVM) in a patient with thymoma, accompanied by myasthenia gravis (MG) and polymyositis. Objective: To examine the pathogenesis of ocular disease in a patient with yolk-like fundus lesions and thymoma, MG, and polymyositis throughout the body based on clinical manifestations, diagnosis, differential diagnosis, and genetic testing to determine the appropriate treatment course. Design, setting, and participants: We describe a 63-year-old woman who presented to our tertiary medical center with a 3-month history of reduced visual acuity in both eyes. Concurrent fundoscopy revealed a 2.0 × 1.7-mm, unifocal, yellow, round vitelliform lesion in the macular region, surrounded by multifocal, shallow, yellow-white pockets of subretinal fluid. The patient’s medical history included thymoma with thymectomy treatment, combined with pericardiectomy and postoperative radiotherapy (20 years prior), followed by a diagnosis of MG with suspect thymic association (15 years prior). Three years prior, the patient had been diagnosed with polymyositis related to paraneoplastic syndrome; 1 year prior, she had been examined for pleural thickening due to suspected metastatic tumor. Results: On her most recent follow-up visit at 3 months after initial diagnosis, the patient was stable with no clinically significant progression in ocular or systemic conditions.

scholarly journals Excited delirium syndrome from psychostimulant abuse can mimic a violent scene of death

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shatishraj Jothee ◽  
Mohamed Swarhib Shafie ◽  
Faridah Mohd Nor
Keyword(s):  
Clinical Manifestations ◽  
The Body ◽  
Law Enforcement Agencies ◽  
Manner Of Death ◽  
Case Presentation ◽  
Excited Delirium ◽  
The Common ◽  
Violent Scene ◽  
Naked Body ◽  
Psychostimulant Abuse

Abstract Background Previous reported cases on excited delirium syndrome studied on the common clinical manifestations of the syndrome. The usual forensics implication for the syndrome is that death commonly is associated with restraint procedures by law enforcement agencies; however, not many cases reported highlights the difficulties in attributing a violent scene of death to the syndrome. Case presentation We present a case of a partially naked body found in an apartment unit under suspicious circumstances with multiple injuries. The scene of death was violent, and the body was found with blood wiped all over the floor and walls. Investigators believed a violent crime had occurred, and a suspect was reprimanded. However, upon autopsy, it was found that all injuries were superficially inflicted and were unlikely to have been part of an act of commission or caused his death. Internal examination found no remarkable pathology. Toxicology revealed a presence of psychostimulants, that is, methamphetamine, MDMA, and ethyl alcohol. Reconstruction of events by the witness, who was initially suspected of the ‘murder’, revealed that the injuries and his death could likely be explained by an episode of excited delirium. Conclusion The case highlights the challenges faced when attributing excited delirium syndrome as a cause of death. The syndrome can present with injuries from aggressive or bizarre behaviour, coupled with the destruction of property, which may confuse investigators on the possible manner of death.

scholarly journals Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7302
Author(s):  
Bryan Latrell Holloman ◽  
Mitzi Nagarkatti ◽  
Prakash Nagarkatti
Keyword(s):  
Autoimmune Diseases ◽  
Chronic Inflammation ◽  
Cannabinoid Receptors ◽  
T Regulatory Cells ◽  
Neurological Diseases ◽  
Suppressor Cells ◽  
The Body ◽  
New Class ◽  
Wide Range ◽  
Clinical Disorders

Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative. Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.

scholarly journals Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Rebecca N. Monastero ◽  
Srinivas Pentyala
Keyword(s):  
Tumor Necrosis ◽  
Inflammatory Diseases ◽  
Low Cost ◽  
The Body ◽  
Tumor Necrosis Factors ◽  
Biochemical Pathways ◽  
Downstream Effects ◽  
Future Work ◽  
Receiver Operator Characteristics ◽  
Cutoff Levels

Cytokines, including interleukins, interferons, tumor necrosis factors, and chemokines, have a variety of pro- and anti-inflammatory effects in the body through a number of biochemical pathways and interactions. Stimuli, actions, interactions, and downstream effects of cytokines have been investigated in more depth in recent years, and clinical research has also been conducted to implicate cytokines in causal patterns in certain diseases. However, particular cutoffs of cytokines as biomarkers for disease processes have not been well studied, and this warrants future work to potentially improve diagnoses for diseases with inflammatory markers. A limited number of studies in this area are reviewed, considering diseases correlated with abnormal cytokine profiles, as well as specific cutoffs at which cytokines have been deemed clinically useful for diagnosing those diseases through Receiver Operator Characteristics modeling. In light of studies such as those discussed in this review, cytokine testing has the potential to support diagnosis due to its lack of invasiveness and low cost, compared to other common types of testing for infections and inflammatory diseases.

CHRONIC ATYPICAL NEUTROPHILIC DERMATOSIS WITH LIPODYSTROPHY AND FEVER (CANDLE SYNDROME) IN PEDIATRIC PRACTICE

2021 ◽  
Vol 100 (2) ◽  
pp. 254-261
Author(s):  
O.G. Sukhovjova ◽  
◽  
I.A. Ivanova ◽  
N.A. Kalugina ◽  
E.S. Zholobova ◽  
...  
Keyword(s):  
Clinical Observation ◽  
Clinical Manifestations ◽  
Maculopapular Rash ◽  
The Body ◽  
Neutrophilic Dermatosis ◽  
Inherited Disease ◽  
Laboratory Activity ◽  
Ubiquitinated Proteins ◽  
Systemic Inflammatory Reaction ◽  
Long Time

The purpose of this publication is to describe the CANDLE syndrome (its etiology, pathogenesis, clinical manifestations) and present a clinical observation. CANDLE syndrome is a rare genetically inherited disease caused by impaired assembly by of the protease, which leads to the accumulation of abnormal (ubiquitinated) proteins in B-lymphocytes, fibroblasts, macrophages and some other cells of the body. As a result, an excessive activation of interferon synthesis occurs and a systemic inflammatory reaction develops with symptoms such as febrile fever, skin syndrome, represented by nodules and maculopapular rash, hepatosplenomegaly, lipodystrophy, amyotrophy, delayed physical development, as well as high laboratory activity. The article describes a clinical observation of a female patient with typical symptoms of CANDLE syndrome. However, due to the rarity of the disease and lack of publications describing it, it has not been possible to diagnose the child for a long time.

Respiratory Acidosis and Alkalosis

2017 ◽  
Author(s):  
Horacio J Adrogué ◽  
Nicolaos E Madias
Keyword(s):  
Carbonic Acid ◽  
Clinical Manifestations ◽  
Respiratory Acidosis ◽  
Respiratory Alkalosis ◽  
Body Fluids ◽  
The Body ◽  
Acid Base ◽  
Acid Base Equilibrium ◽  
Therapeutic Principles ◽  
The Impact

Respiratory acid-base disorders are those disturbances in acid-base equilibrium that are expressed by a primary change in CO2 tension (Pco2) and reflect primary changes in the body’s CO2 stores (i.e., carbonic acid). A primary increase in Pco2 (and a primary increase in the body’s CO2 stores) defines respiratory acidosis or primary hypercapnia and is characterized by acidification of the body fluids. By contrast, a primary decrease in Pco2 (and a primary decrease in the body’s CO2 stores) defines respiratory alkalosis or primary hypocapnia and is characterized by alkalinization of the body fluids. Primary changes in Pco2 elicit secondary physiologic changes in plasma [HCO3ˉ] that are directional and proportional to the primary changes and tend to minimize the impact on acidity. This review presents the pathophysiology, secondary physiologic response, causes, clinical manifestations, diagnosis, and therapeutic principles of respiratory acidosis and respiratory alkalosis.  This review contains 4 figures, 3 tables, and 59 references. Key words: Respiratory acidosis, respiratory alkalosis, primary hypercapnia, primary hypocapnia, hypoxemia, pseudorespiratory alkalosis

Iron Homeostasis and Disorders in Dogs and Cats: A Review

2011 ◽  
Vol 47 (3) ◽  
pp. 151-160 ◽  
Author(s):  
Jennifer L. McCown ◽  
Andrew J. Specht
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Diagnostic Testing ◽  
Clinical Manifestations ◽  
Essential Element ◽  
The Body ◽  
Deficiency Anemia ◽  
Enzyme Systems ◽  
Living Organisms

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.

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