Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myotonic dystrophy (m.d.) is an autosomal dominant multisystem disorder involving muscles, brain, heart, eye, endocrine system, alimentary and respiratory systems. M.d. is the most frequent cause of muscle dystrophy. Unstable CTG trinucleotide repeat at 3' untranslated end of the myotonic protein kinase gene on chromosome 19q 13.3 is the molecular basis of the disease. Normal length of CTG trinucleotide repeat is 5-40. Molecular mechanism of the myotonic dystrophy is discussed. Cataract, heart dysfunction, endocrine organs dysfunction, gallbladder stones, impotence are characteristic changes in patient with m.d. Apathy, drowsiness, sometimes dementia point to central nervous system involvement. Clinical course, correlation between CTG expansion and clinical manifestation are described. Nowadays progress in molecular genetic allows to make the diagnosis by DNA examination. Prenatal diagnosis is also possible.
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PMID:[Current problems in myotonic dystrophy]. 986 18

Dysfunction of the orexin/hypocretin neurotransmitter system leads to the sleep disorder narcolepsy. Narcolepsy is characterized by excessive daytime sleepiness and the occurrence of cataplexy--a sudden loss of muscle tone triggered by emotionally arousing events. Both symptoms can be treated with drugs that act on dopaminergic systems. Here we have investigated the effect of orexins on the firing of dopaminergic and GABAergic neurons of the substantia nigra (SN) in brain slices. Surprisingly, dopaminergic neurons in pars compacta were unaffected by orexins. In contrast, bath application of orexin A (100 nM) or orexin B (5-300 nM) greatly increased the firing rate of GABAergic neurons in pars reticulata. The orexin B-mediated excitation was unaffected by blocking synaptic transmission (using low-Ca2+/high-Mg2+ solution). However, the effect of orexin B was reduced significantly by thapsigargin (1 microM) and inhibitors of protein kinase A. The presence of orexinergic fibres in the SN pars reticulata was demonstrated by immunohistochemical methods with the fibre density increasing in the rostrocaudal direction. The orexin excitation of SN reticulata cells may help to maintain their high firing rate during waking. Furthermore, the absence of orexin effects in narcolepsy may predispose affected individuals to attacks of cataplexy.
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PMID:Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro. 1183 Feb 81

Myotonic dystrophy (MD) is a genetically determined disease with autosomal dominant mode of inheritance. Relatively recently, MD has been divided into two sub-types (MD1 and MD2). Clinical symptoms of MD1 result from the expansion of a (CTG)n trinucleotide of the gene coding for serine/threonine protein kinase and clinical symptoms in MD2 are associated with the expansion of (CCTG)n in I intron of the zinc-finger protein 9 (ZNF9). Myotonic dystrophies MD1 and MD2 are multisystem diseases with numerous symptoms and high interfamily variability, resulting from the fact that different organs are affected. Until now the mechanisms that lead to the damage of the central and peripheral nervous systems, heart muscle and endocrine system have not been fully understood. Symptoms that are characteristic of MD1 and MD2 are myotonic symptom, muscular weakness and muscular atrophy. In MD2, muscular weakness and muscular atrophy are expressed more significantly in proximal segments, which is a differentiating factor for patients with MD1 who have muscular weakness and muscular atrophy in distal segments. Apart from myotonia and symptoms of skeletal muscle damage, the disease affects smooth muscles, heart muscle and the central nervous system, causing cataract, endocrine disorders, cognitive dysfunctions, intellectual and personality disturbances as well as sleep disordered breathing with nocturnal hypoventilation, obstructive, central and mixed apneas and hypopneas. The symptoms of sleep disordered breathing is fatigue, reduced cognitive performance and excessive daytime sleepiness. The pathophysiology of the breathing disorders includes weakness of the respiratory muscles and disorder of the respiratory drive. Of some interest are the works in which authors evaluated the incidence and character of abnormalities in the peripheral and central nervous systems. It has been shown that the number of CTG-repeats in the same person with MD1 is not stable over time and may increase, which leads to disease progression and new clinical symptoms. Cardiologic disorders associated with myotonic dystrophy are common and are part of the clinical picture of the disease. The dominant pathology are conduction disturbances and cardiac arrhythmias. It is estimated that 40 to 80% of patients with MD1 have abnormalities in ECG, and rapid supra-ventricular and ventricular cardiac arrhythmias are the second common cause of death in patients with MD1. Unfortunately, most of these pathologies are asymptomatic until life-threatening conduction blocks and/or supra-ventricular tachyarrhythmias occur. Sometimes, prodromal symptoms such as collapsing, fainting or feeling of palpitation occur and they should always draw attention of the treating doctor of a patient with muscular dystrophy. This paper is aimed at characterizing some common cardiologic and sleep related respiratory disorders of patients with myotonic dystrophy which if not recognized in good time may lead to sudden death.
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PMID:[Cardiac, respiratory and sleep disorders in patients with myotonic dystrophy]. 2051 7

Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury. We conducted an observational pilot study to provide data for the potential design of a randomized study of lithium. Twenty patients with steroid refractory intestinal GVHD meeting enrollment criteria were given oral lithium carbonate. GVHD was otherwise treated per current practice, including 2 mg/kg per day of prednisone equivalent. Seventeen patients had extensive mucosal denudation (extreme endoscopic grade 3) in the duodenum or colon. We observed that 8 of 12 patients (67%) had a complete remission (CR) of GVHD and survived more than 1 year (median 5 years) when lithium administration was started promptly within 3 days of endoscopic diagnosis of denuded mucosa. When lithium was started promptly and less than 7 days from salvage therapy for refractory GVHD, 8 of 10 patients (80%) had a CR and survived more than 1 year. In perspective, a review of 1447 consecutive adult HCT patients in the preceding 6 years at our cancer center showed 0% one-year survival in 27 patients with stage 3-4 intestinal GVHD and grade 3 endoscopic appearance in the duodenum or colon. Toxicities included fatigue, somnolence, confusion or blunted affect in 50% of the patients. The favorable outcomes in patients who received prompt lithium therapy appear to support the future conduct of a randomized study of lithium for management of severe GVHD with extensive mucosal injury.
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PMID:Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease. 2881 27

Caffeine-a methylxanthine analogue of the purine bases adenine and guanine-is by far the most consumed neuro-stimulant, being the active principle of widely consumed beverages such as coffee, tea, hot chocolate, and cola. While the best-known action of caffeine is to prevent sleepiness by blocking the adenosine receptors, caffeine exerts a pleiotropic effect on cells, which lead to the activation or inhibition of various cell integrity pathways. The aim of this review is to present the main studies set to investigate the effects of caffeine on cells using the model eukaryotic microorganism Saccharomyces cerevisiae, highlighting the caffeine synergy with external cell stressors, such as irradiation or exposure to various chemical hazards, including cigarette smoke or chemical carcinogens. The review also focuses on the importance of caffeine-related yeast phenotypes used to resolve molecular mechanisms involved in cell signaling through conserved pathways, such as target of rapamycin (TOR) signaling, Pkc1-Mpk1 mitogen activated protein kinase (MAPK) cascade, or Ras/cAMP protein kinase A (PKA) pathway.
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PMID:Saccharomyces cerevisiae and Caffeine Implications on the Eukaryotic Cell. 3282 8