Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The term 'long term neurological cripple' is an unattractive and yet an all embracing one, covering a wide spectrum of disorders from spina bifida or cerebral palsy with or without associated epilepsy and behavioural and learning problems, through muscular dystrophy, multiple sclerosis, and motor neurone disease, to the effects of head injury, cerebrovascular lesions and the degenerative disorders of later life such as Parkinson's disease and the senile and presenile dementias. Whilst many of the problems are common to several of these entities, each has its own particular aspects.
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PMID:The support of the long term neurological cripple. 10 16

In a Nigerian town with a stable population of 20,000, a door-to-door survey was conducted, using a questionnaire involving a complete census and a simple neurological evaluation which had previously showed a 95% sensitivity and an 80% specificity for detecting neurological disease. Positive responders were evaluated and categorised, using agreed criteria for diagnoses. Nearly 100% cooperation was obtained. Life prevalence ratio for at least one episode of headache was 51/1000. Crude point prevalence ratio for migrainous headache was 5.3/100, and peak age-specific ratio was in the first decade. Prevalence ratio for epilepsy was 533/100,000 and peak age-specific prevalence ratio occurred in the 5-14 years age groups. The prevalence ratio for peripheral nerve disorders was 268/100,000, and age-specific prevalence ratio for tropical neuropathy increased with age. Prevalence ratio for stroke was rather low at 58/100,000, but was probably due to the people's attitude to the disabled elderly and high mortality of stroke which showed annual mortality rate of 70/100,000 which increased with age to 1519/100,000 per year in the eighth decade. Crude prevalence ratios (cases per 100,000) for others are 112 for neurological complications (including sciatica) of spondylosis, 15 each for poliomyelitis, motor neurone disease, development speech disorders, 10 each for syncope, hereditary neuropathies. Parkinson's disease, benign essential tremor, primary cerebellar degeneration, cerebral palsy, mental retardation, organic psychosis (probable intracranial tumor) and 5 each for muscular dystrophy, pyomyositis, spina bifida occulta, alcohol dependence and cerebral malaria. The implications of the findings are important for development of community neurological services in the developing countries.
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PMID:Neurological disorders in Nigerian Africans: a community-based study. 303 73

Modern molecular biology has revealed vast numbers of large and complex proteins and genes that regulate body function. By contrast, discoveries over the past ten years indicate that crucial features of neuronal communication, blood vessel modulation and immune response are mediated by a remarkably simple chemical, nitric oxide (NO). Endogenous NO is generated from arginine by a family of three distinct calmodulin- dependent NO synthase (NOS) enzymes. NOS from endothelial cells (eNOS) and neurons (nNOS) are both constitutively expressed enzymes, whose activities are stimulated by increases in intracellular calcium. Immune functions for NO are mediated by a calcium-independent inducible NOS (iNOS). Expression of iNOS protein requires transcriptional activation, which is mediated by specific combinations of cytokines. All three NOS use NADPH as an electron donor and employ five enzyme cofactors to catalyze a five-electron oxidation of arginine to NO with stoichiometric formation of citrulline. The highest levels of NO throughout the body are found in neurons, where NO functions as a unique messenger molecule. In the autonomic nervous system NO functions NO functions as a major non-adrenergic non-cholinergic (NANC) neurotransmitter. This NANC pathway plays a particularly important role in producing relaxation of smooth muscle in the cerebral circulation and the gastrointestinal, urogenital and respiratory tracts. Dysregulation of NOS activity in autonomic nerves plays a major role in diverse pathophysiological conditions including migraine headache, hypertrophic pyloric stenosis and male impotence. In the brain, NO functions as a neuromodulator and appears to mediate aspects of learning and memory. Although endogenous NO was originally appreciated as a mediator of smooth muscle relaxation, NO also plays a major role in skeletal muscle. Physiologically muscle-derived NO regulates skeletal muscle contractility and exercise-induced glucose uptake. nNOS occurs at the plasma membrane of skeletal muscle which facilitates diffusion of NO to the vasculature to regulate muscle perfusion. nNOS protein occurs in the dystrophin complex in skeletal muscle and NO may therefore participate in the pathophysiology of muscular dystrophy. NO signalling in excitable tissues requires rapid and controlled delivery of NO to specific cellular targets. This tight control of NO signalling is largely regulated at the level of NO biosynthesis. Acute control of nNOS activity is mediated by allosteric enzyme regulation, by posttranslational modification and by subcellular targeting of the enzyme. nNOS protein levels are also dynamically regulated by changes in gene transcription, and this affords long-lasting changes in tissue NO levels. While NO normally functions as a physiological neuronal mediator, excess production of NO mediates brain injury. Overactivation of glutamate receptors associated with cerebral ischemia and other excitotoxic processes results in massive release of NO. As a free radical, NO is inherently reactive and mediates cellular toxicity by damaging critical metabolic enzymes and by reacting with superoxide to form an even more potent oxidant, peroxynitrite. Through these mechanisms, NO appears to play a major role in the pathophysiology of stroke, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.
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PMID:Endogenous nitric oxide synthesis: biological functions and pathophysiology. 1063 Jun 82

It seems plausible to hypothesize that in all forms of neurodegeneration or other forms of tissue degeneration, a common pathway exists that, when deciphered, could lead to our understanding of a variety of diseases that result in tissue necrosis, as well as offer potential for therapeutic intervention. In recent years progress toward elucidating this common pathway has been accelerated through the studies of a number of laboratories, including our own, on the role of the protease calpain in this process. Thus, in a variety of disorders, such as stroke, spinal cord injury, traumatic nerve injury, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, muscular dystrophy, cataract formation, unregulated calpain proteolysis, initiated via dysregulation of calcium ion homeostasis, participates in the pathogenesis and is a potentially unifying mechanistic event. In order to demonstrate the feasibility of the approach we have taken in using the calpain inhibitor leupeptin as a therapeutic agent, I will describe two areas of research in which we have been engaged over the past 20 years. One is our long-standing interest in muscular dystrophy. The other is of more recent vintage, and involves the use of calpain inhibitors to protect sensory hair cells and spiral ganglion neurons from damage associated with acoustic trauma, this latter in collaboration with Dr. R. Salvi at SUNY-Buffalo and Dr. A. Shulman at SUNY-Downstate.
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PMID:Calpain inhibitors as therapeutic agents in nerve and muscle degeneration. 1084 83

The acceleration signal produced by physiological tremor from four different upper limb segments (the finger, hand, forearm and upper limb) was measured by an acceleration sensor during holding posture and was analyzed by power spectrum analysis. Two prominent peaks appeared in the power spectrum, suggesting that the tremor in the four different limb segments was composed of two frequency components. The frequency of one peak at 8-12 Hz did not change between the different limb segments, while the frequency of the other peak decreased with the increase in the mass of the limb segment. A model with two reflex pathways was developed for the tremor in the four limb segments. The model includes two reflex pathways, a spinal pathway and a supraspinal pathway. The theoretical values of the frequency and the amplitude of the tremor predicted by the model were in good agreement with the experimental results. Analysis of the model revealed that one of the two frequency components of the tremor was of spinal origin and was dependent upon the mass of the limb segment, and the second was of supraspinal origin, corresponding to the frequency at 8-12 Hz. In the normal subject, it is possible that the tremor could be used to evaluate the change in neuromuscular function produced by prolonged work involving just part of a limb segments (e.g., typing). It may also be used to evaluate the neuromuscular function of patients suffering from neurological diseases such as muscular dystrophy and Parkinson's disease.
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PMID:Physiological tremor of the upper limb segments. 1156 73

Oropharyngeal dysphagia is not a single disease but a symptom complex that is recognized by difficulty in transfer of a food bolus from mouth to esophagus or by signs and symptoms of aspiration pneumonia or nasal regurgitation. Its etiologies are legion, with the most common result of underlying neuromuscular disease, including cerebrovascular accidents, Parkinson's disease, multiple sclerosis, and muscular dystrophy. There are two methods of treatment for oropharyngeal dysphagia; one is specific and directed at the underlying disease and the other is general (supportive) and designed to preserve oral intake for nutrition while preventing aspiration pneumonia. Following a general discussion of the etiology and clinical presentation of orophyarngeal dysphagia, a description of the methods for supportive care is presented as well as the approach to the treatment of cricopharyngeal dysfunction and Zenker's diverticulum.
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PMID:Oropharyngeal dysphagia. 1600 27

Charcot-Marie-Tooth disease, the most common hereditary motor and sensory neuropathy, is a slowly progressive disorder characterized by diffuse muscle weakness and prominent distal atrophy that predominantly involves the intrinsic muscles of the feet and the peroneal muscles. It results in marked reduction in functional aerobic capacity during exercise and fatigue is commonly reported. To date, no pharmacologic treatment has been shown to be effective for treating fatigue in Charcot-Marie-Tooth. Modafinil is used to treat the symptoms of fatigue and excessive daytime sleepiness in narcolepsy. However, fatigue and subsequent excessive daytime sleepiness secondary to fatigue are common symptoms in many neurologic disorders. Prior reports on patients with myotonic muscular dystrophy, multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis, have shown beneficial effects of modafinil in treating fatigue. We report 4 patients with genetically confirmed Charcot-Marie-Tooth disease who had significant fatigue that was almost completely relieved by modafinil.
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PMID:Modafinil reduces fatigue in Charcot-Marie-Tooth disease type 1A: a case series. 1706 Mar 10

Embryonic stem cells (ESCs) offer a new and remarkable potential for treating and curing a wide range of genetic diseases such as diabetes and muscular dystrophy, degenerative diseases such as Parkinson's disease, renal disease and heart disease, and traumatic injury such as spinal cord injury. Therapeutic cloning, wherein patient-specific ESCs can be derived from pre-implantation stage embryos produced by somatic cell nuclear transfer, constitutes one approach of obtaining histocompatible cells for engraftment. Recent improvements in the production of cloned embryos in non-human primate models, combined with advances in the ability to establish human ESC lines and direct their differentiation along specific pathways support the notion that therapeutic cloning may soon be feasible. This review summarizes the status and current feasibility of the approach and the technical hurdles that must be addressed, and discusses the ethical issues that have arisen as a result.
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PMID:Therapeutic cloning: status and prospects. 1769 52

Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were systematically mapped to tissues they affect from disease-relevant literature in PubMed to create a disease-tissue covariation matrix of high-confidence associations of >1,000 diseases to 73 tissues. By retrieving >2,000 known disease genes, and generating 1,500 disease-associated protein complexes, we analyzed the differential expression of a gene or complex involved in a particular disease in the tissues affected by the disease, compared with nonaffected tissues. When this analysis is scaled to all diseases in our dataset, there is a significant tendency for disease genes and complexes to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also identified complexes in Parkinson disease, cardiomyopathies, and muscular dystrophy syndromes that are similarly tissue specific. Our method represents a conceptual scaffold for organism-spanning analyses and reveals an extensive list of tissue-specific draft molecular pathways, both known and unexpected, that might be disrupted in disease.
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PMID:A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes. 1910 45

Abnormal tonic-motor activity is a key component in pathogenesis of many digestive disorders. Secondary disturbance of tonic-motor activity of digestive organs and the accompanying symptoms are known to develop in conjunction with diseases of other organs and systems, diabetes mellitus, Parkinson's disease, myotonic muscular dystrophy, amyloidosis, hyper- and hypothyroidism, hypoparathyroidism, etc. Disturbed motor activity in the gastro-duodenal region most frequently underlies functional dyspepsia, i.e. a group of symptoms unrelated to organic, systemic and metabolic diseases. Prokinetics are an important class of medicinal products for the treatment of all clinical forms of dyspepsia. One of the new ones is itopride hdrochloride having combined mechanism of action. Clinical studies of this drug revealed its high efficiency in patients with functional dyspepsia, chronic gastritis, and diabetic gastroparesis. It is well tolerated by the patients and produces no serious side effects. Inclusion of this drug in therapy improves the outcome of the treatment of disturbed motor activity of the gastrointestinal tract.
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PMID:[The use of prokinetics for the correction of motor and tonic digestive disorders]. 1946 57


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