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

The atoll community of Fenuafala was surveyed during July-August, 1987. A disproportionate demographic structure was found: There was a large, young population with an uneven sex distribution in the adolescent cohorts. Adoption of relatives was frequent. Employment varied according to sex, with women restricted from horticulture, fisheries, and hard labour. The use of alcohol and tobacco was common. Causes of mortality included cancer, heart failure, meningitis, alcoholism, and accidents. Bacterial and fungal skin infections were prevalent. There were several cases of congenital disorders. Malaria, leprosy, and most other tropical diseases were absent. However, there was a single case of filariasis. Musculoskeletal disorders were numerous and more common among women. Falls from trees have resulted in serious sequelae including epilepsy and death. Hypertension, diabetes, and gout appear to be on the increase, but angina and myocardial infarction were not reported. There were also cases of epilepsy and Parkinson's disease.
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PMID:Fenuafala health survey: the ecology of health and disease on a coral atoll village. 280 43

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

Brain imaging has made surprisingly remarkable progress since the early, and now historic days, of invasive radiology, which has now been replaced with a number of spectacularly precise techniques: structural (CT Scan, MRI) and functional (PET, SPECT) imaging, direct imaging during neurosurgery, EEG and its computer-assisted derivatives, and transcerebral ultrasonography. We present five cases with two alleged autisms, a cerebral malaria, a panic disorder and to Parkinson disease with a depressive component. Using modern imaging methods the following respective diagnoses were arrived at: a left temporal cyst, a Sanfilippo mucopolysaccharidosis, a septum lucidum agenesis, a right temporal cyst, and a pituitary adenoma. These cases illustrate the scientific, emotional and philosophical impact, on physicians, and patients alike, of modern imaging technology. Neuroradiology, biochemistry and surgical imaging require a multi disciplinary approach and a perfect knowledge of psychiatric semeiology. In addition, they stimulate us to carefully reassess our sociocultural understanding to mental illness.
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PMID:[Clinical imaging in psychiatry]. 863 90

The spectrum of movement disorders in the tropics is different from that seen in the industrialized nations of the west. This is not surprising given the unique combination of environmental and population characteristics in the tropics. Infections seldom encountered in the west such as tuberculous meningitis, typhoid fever, Japanese encephalitis, malaria, trypanosomiasis or cysticercosis are often seen in the tropics and with global patterns of travel and immigration these conditions are becoming more common worldwide. Movement disorders associated with these infections, HIV, slow virus and prion disease are discussed. Taking into account the diverse etiologies of movement disorders in the tropics, movement disorders with a nutritional basis such as the infantile tremor syndrome, seasonal ataxia and tropical ataxic neuropathy, and manganese neurotoxicity are also reviewed. Finally, certain special characteristics of ubiquitous disorders such as Parkinson's disease, and disorders with a genetic basis such as Wilson's disease and spinocerebellar degeneration are described.
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PMID:Movement disorders in the tropics. 1247 95

A 3 year review of neurologic admissions into the adult medical wards at the UCH, Ibadan, Nigeria between January 1998 and December 2000 is presented. The study design involved the scrutiny of the records of all the neurological admissions, male and female to the medical ward. The identified cases were then classified and only cases confirmed as neurological were further analysed. Stroke, predominantly non-hemorrhagic accounted for 50.4% of cases for the period of study. Stroke is therefore the most common cause of adult neurologic admissions on medical wards of UCH. Central nervous system infections, comprising mainly of tetanus and meningitis accounted for 14.2% (111) and 12.4% (97) of case respectively. The myelopathies were the cause of neurologic admissions in 8.1% (63) of cases followed by seizure disorders. Headache was the reason for admission in 0.9% (7) of cases. Parkinsons disease, hypertensive encephalopathy, Guillian Barne syndrome, seasonal ataxic neuropathy, cavernous sinus thrombophlebitis, normal pressure hydrocephalus were rarely the cause of admission. Similarly, dystonia, and cerebral malaria recorded 0.13% (1) of cases each. A case is made for the establishment of regional stroke units in Nigeria.
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PMID:A 3-year review of neurologic admissions in University College Hospital Ibadan, Nigeria. 1452 26

Parkinson's disease (PD) is said to be less common in Africa than elsewhere in the world, but previous studies have been based on small numbers. Also, the differences may be due to the diagnostic criteria used, case finding methods and different population age structures. Developing countries have few facilities for chronic disease management and non-communicable diseases, although on the increase, tend to play second fiddle to malaria and HIV/AIDS. Previous reports suggest that, at least from anecdotal information, under-diagnosis of PD is common and long-term availability of medication, follow-up, patient education and multidisciplinary input is lacking. Published literature is scarce and there is a lack of recent information. We are currently conducting a door-to-door prevalence study in northern Tanzania in a population of 161,162. We have reviewed previous literature on PD in Africa and illustrate our personal experience of PD and its management in Africa with three cases.
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PMID:The challenge of Parkinson's disease management in Africa. 1725 91

The vitamin B(6)-derived pyridoxal 5'-phosphate (PLP) is the cofactor of enzymes catalyzing a large variety of chemical reactions mainly involved in amino acid metabolism. These enzymes have been divided in five families and fold types on the basis of evolutionary relationships and protein structural organization. Almost 1.5% of all genes in prokaryotes code for PLP-dependent enzymes, whereas the percentage is substantially lower in eukaryotes. Although about 4% of enzyme-catalyzed reactions catalogued by the Enzyme Commission are PLP-dependent, only a few enzymes are targets of approved drugs and about twenty are recognised as potential targets for drugs or herbicides. PLP-dependent enzymes for which there are already commercially available drugs are DOPA decarboxylase (involved in the Parkinson disease), GABA aminotransferase (epilepsy), serine hydroxymethyltransferase (tumors and malaria), ornithine decarboxylase (African sleeping sickness and, potentially, tumors), alanine racemase (antibacterial agents), and human cytosolic branched-chain aminotransferase (pathological states associated to the GABA/glutamate equilibrium concentrations). Within each family or metabolic pathway, the enzymes for which drugs have been already approved for clinical use are discussed first, reporting the enzyme structure, the catalytic mechanism, the mechanism of enzyme inactivation or modulation by substrate-like or transition state-like drugs, and on-going research for increasing specificity and decreasing side-effects. Then, PLP-dependent enzymes that have been recently characterized and proposed as drug targets are reported. Finally, the relevance of recent genomic analysis of PLP-dependent enzymes for the selection of drug targets is discussed.
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PMID:Pyridoxal 5'-phosphate enzymes as targets for therapeutic agents. 1750 14

Epidemiological studies suggest a link between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Although studies have been unable to clearly identify specific pesticides that contribute to PD, a few human studies have reported higher levels of the organochlorine pesticides dieldrin and DDE (a metabolite of DDT) in post-mortem PD brains. Previously, we found that exposure of mice to dieldrin caused perturbations in the nigrostriatal dopamine system consistent with those seen in PD. Given the concern over the environmental persistence and reintroduction of DDT for the control of malaria-carrying mosquitoes and other pests, we sought to determine whether DDT and its two major metabolites, DDD and DDE, could damage the dopamine system. In vitro analyses in mouse synaptosomes and vesicles demonstrated that DDT and its metabolites inhibit the plasma membrane dopamine transporter (DAT) and the vesicular monoamine transporter (VMAT2). However, exposure of mice to either DDT or DDE failed to show evidence of nigrostriatal damage or behavioral abnormalities in any of the measures examined. Thus, we report that in vitro effects of DDT and its metabolites on components of the dopamine system do not translate into neurotoxicological outcomes in orally exposed mice and DDT appears to have less dopamine toxicity when compared to dieldrin. These data suggest elevated DDE levels in PD patients may represent a measure of general pesticide exposure and that other pesticides may be responsible for the association between pesticide exposure and PD.
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PMID:Disruption of dopamine transport by DDT and its metabolites. 1853 68

We investigated epidemiologic data from 61 cases of autopsy-confirmed sporadic Creutzfeldt-Jakob disease (CJD). Dura mater-associated CJD cases and familial CJD cases were excluded. There were 34 male and 27 female cases, with an average age at onset of 66.0 +/- 10.5 years (range 27 to 89). At onset of CJD, 1 case was aged in the 20's and 1 in 30's, but there were no cases aged in the 40's. In 6 cases, age at onset was in the 80's. There was no significant difference in relation to the age at onset between males and females, averaging 66.2 +/- 12.4 years (range 27 to 89), and 65.9 7.5 years (range 53 to 82), respectively. Two cases had been employed as medical workers (a medical technologist and a nurses' aide) but neither had an apparent history of contact with CJD patients. No cases in the study had either family history of CJD or apparent contact with CJD patients. Ten cases had a history of hypertension, 5 cases had a history of diabetes mellitus, 2 cases had a history of malaria and 1 case had suffered from atomic bomb exposure. Twenty-one cases had operation history, including 2 cases of an operation involving the central nervous system. One case had a skull-base fracture operation 19 years before the onset of CJD and the other case had an atlantoaxial subluxation operation 11 years before the onset of CJD; there was no transplantation of dura mater graft in either operation. There was one case with a history of conservative treatment for cerebral hemorrhage; this case had symptomatic secondary epilepsy as a coexisting disease at the onset of CJD. Two cases had Parkinson's disease as a coexisting disease at the onset of CJD. The source hospitals enforcing medical treatment were located in the Aichi (n = 42), Gifu (n = 12) and Mie (n = 7) prefectures of the Tokai region of Japan. Regarding patients' place of residence, 22 cases resided in Nagoya-city. Nagoya University Hospital performed the autopsy in 12 cases, but 10 cases of those were transported after death from the source hospital. Departments of neurology provided clinical treatment in 54 cases. Other departments that provided treatment were Internal Medicine (n = 3), Psychiatry (n = 2), Geriatrics (n = 1), and Neurosurgery (n = 1). In 39 cases, prion protein gene analyses using peripheral blood leukocyte or cryopreserved brain tissue were performed. As for polymorphic codon 129, 36 cases (92%) showed Met/Met, 3 cases showed Met/Val (8%) and no case showed Val/Val polymorphism. Polymorphic codon 219 showed Glu/Glu homozygosity in all of the examined cases. Active autopsy performance of CJD in the Tokai region was suggested from the present study. We estimated that the CJD autopsy rate of the district was more than 50% over the past 7 years.
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PMID:[Epidemiologic study of Creutzfeldt-Jakob disease from autopsy-confirmed cases]. 1982 94

Certain cytokines, the prototype being the highly pleiotropic TNF, have many homeostatic physiological roles, are involved in innate immunity, and cause inflammation when in excess. These cytokines have long been accepted to have central roles in the pathogenesis of systemic or local non-cerebral disease states, whether acute or chronic, and whether or not caused by infectious agents. Over the last decade they have also been appreciated to be broadly important in brain physiology. As in other organs, excessive levels in brain are harmful, and its physiological complexity leads to correspondingly complex dysfunction. This review summarizes the burgeoning literature on this topic, and how the functions of these molecules, particularly TNF, are influencing the outlook of researchers on the pathophysiology of these diseases. Basic brain physiology is thus informing knowledge of the brain dysfunction that characterizes such apparently diverse states as Alzheimer's disease, trauma (mostly, but not only, to the brain), Parkinson's disease, and severe systemic infectious states, including malaria, sepsis, viral diseases and major depression. The implication is that the anti-cytokine therapies now in use, typically directed at TNF, warrant testing in these diseases in circumstances in which the therapeutic agent enters the cerebrospinal fluid. Routinely administering such drugs to patients exhibiting the neurological changes discussed in this review would simply add another organ system to what is already a very successful strategy in the treatment of inflammatory disease at other sites, such as joints, skin and gut. Clearly, the most relevant research is focussed on Alzheimer's disease, but the principles may also apply to other encephalopathies.
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PMID:The roles of TNF in brain dysfunction and disease. 2081 31


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