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)

It is currently thought that genetic predisposition to imbalances in dopaminergic transmission may underlie several neurological disorders, including schizophrenia, manic depression, Tourette syndrome, Parkinson disease, Huntington disease, and alcohol abuse. Originally two receptors, D1 and D2, were thought to account for all of the pharmacological actions of dopamine. However, through homology screening three additional genes, D3, D4, and D5, and two pseudogenes closely related to D5 have been characterized. To begin our genomic and evolutionary analyses of the human D5 dopamine receptor gene and its two pseudogenes, we have mapped each of them to their respective chromosomes. By combining in situ hybridization results with sequence analysis of PCR products from microdissected chromosomes, somatic cell hybrids, and radiation hybrids, we have assigned DRD5 (the locus containing the functional human D5 receptor gene) to chromosome 4p16.1, DRD5P1 (the locus containing D5 pseudogene 1) to chromosome 2p11.1-p11.2, and DRD5P2 (the locus of D5 pseudogene 2) to chromosome 1q21.1.
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PMID:Chromosomal localization of three human D5 dopamine receptor genes. 138 8

The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism.
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PMID:DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls. 757 71

Population aging is continuously increasing in Italy and in the World. Individuals aged 60 years or more are currently 10,500,000 and will be 13,000,000 in 2015. Life quality in geriatric ages includes the maintenance of sexual power: according to recent data (Carrol et al., 1992), 80% of impotence cases are due to organic causes. In addition, the use of drugs can cause impotence. Among them tiazidic diuretics may cause an increase of sexual disturbances. Other drugs with this potential are digitalis, antihypertensive drugs (particularly beta blockers), major and minor tranquillizers, antidepressant, H2 receptor antagonists, antiparkinsonian cholinergic drugs and estrogens employed in the treatment of prostate tumors. Diseases of geriatric age that can alter sexual power are diabetes mellitus, ischemic heart disease for the accompanying depression and for the use of antidepressants; severe hypertension is complicated by impotence in 15% of cases. Among neurological diseases Parkinson's disease and multiple sclerosis can be causes of sexual dysfunctions. Patients on hemodialysis can be impotent, with recent data (Soloh et al 1992) showing that erythropoietin treatment of anemia also improve sexual dysfunctions. Prevention from a geriatric standpoint should be base on action on known risk factor as smoking, alcohol abuse and dislipidemias and with the activation of a close drug vigilance.
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PMID:[Andrologic problems and internal pathology in the elderly]. 825 79

Our current knowledge of risk factors for Alzheimer's disease is limited and primarily addresses early-onset disease. This study aimed to determine the risk factors for late-onset Alzheimer's disease using a case-control approach. Ninety-eight cases and 216 controls were gathered from an ongoing population survey on aging and dementia in Stockholm (the Kungsholmen Project). We found a high relative risk (3.2; 95% confidence interval, 1.8-5.7) with the presence of at least one first-degree relative affected by dementia. Among all the other risk factors, alcohol abuse (relative risk, 4.4; 95% confidence interval, 1.4-13.8) and manual work (relative risk for men of 5.3; 95% confidence interval, 1.1-25.5) emerged as positively associated. No clear association was found with a family history of Parkinson disease, advanced parental age at index delivery, season of birth, or previous head trauma. In conclusion, our data suggest that the main risk factor for late-onset Alzheimer's disease is a family history of dementia, as has been previously reported for early-onset disease. Moreover, alcohol abuse and occupational exposure might play a specific role for this form of the disease.
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PMID:Risk factors for late-onset Alzheimer's disease: a population-based, case-control study. 849 9

For those conditions in which loss of consciousness is the main issue, such as epilepsy, factors that contribute to risk of seizure recurrence are central to the determination of driver safety. Thus, high- and low-risk groups may be identified and factors that contribute to high risk checked. These factors also serve to develop a program to reduce such risk in the future. In the population with seizure disorders, young males under age 25 have the highest risk for traffic accidents and violations. Other factors associated with high risk are partial complex seizure type, history of drug toxicity with anticonvulsant medications, alcohol abuse or poor compliance for medications, and history of psychiatric illness. For conditions such as cerebrovascular accidents or Parkinson's disease, the recognition of the diagnosis alone is insufficient to determine driver competence. In these illnesses, the task is to recognize levels of failure of individual skills and function that specifically render a person incompetent for safe driving. Such a precise determination is currently not possible in individuals with cerebrovascular accidents or other forms of brain injury (e.g., trauma) or degenerative brain disease (e.g., Parkinson's disease). There is intuitive and general agreement that there are those so severely affected that driving has become impossible or very dangerous. Alternately, there are also those with these conditions whose driving skills and competence are virtually unaffected and pose no risk to traffic safety. Physicians vary widely in their ability and experience in judging the competence and safety of those in between these two extremes. For this reason, a standardized approach is essential both to ensure the avoidance of unnecessary bias as well as to ensure the safety of the driver and the general public. At some time in the future when all the necessary driving skills are identified and appropriate tests are developed to judge them, a battery of tests for the elderly at age 65 and at regular intervals thereafter may be used. Until then, some form of clinical judgment and legal regulation may have to be adopted. One option would be to adopt a rule similar to that in the United Kingdom where all persons with TIAs or cerebrovascular accidents would automatically suspend driving for 3 months because of the high risk for recurrence of both cerebrovascular as well as ischemic heart disease in that interval.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Seizure disorders, diabetes mellitus, and cerebrovascular disease. Considerations for older drivers. 850 82

Inconsistencies within results of case-control studies on Alzheimer's disease risk factors led to a search of the literature for a potential cofactor. Reduced cerebral blood flow was selected and literature was surveyed for evidence of a cerebral blood flow linkage with the more than 40 putative risks. Alcohol abuse, depression, head trauma, underactivity, old age, sleep disturbance, glucose utilization, Down's syndrome, and Parkinson's disease are risk factors where an association with reduced cerebral blood flow is documented. Studies were cited showing that improved cerebral blood flow is associated with factors thought to be helpful in Alzheimer's disease, such as education or occupational attainment, exercise, headache, smoking, and arthritis/anti-inflammatory drugs to the extent that aspirin is used. Sugar consumption is identified as a potential risk factor with glucose management in Alzheimer's disease also shown to involve reduced cerebral blood flow. An hypothesis is developed showing how compromised regional cerebral blood flow could fit as a cofactor for genetic, autoimmune, and neurotoxic aspects of Alzheimer's disease.
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PMID:Alzheimer's disease risk factors as related to cerebral blood flow. 873 67

In a previous report, Alzheimer's disease risk factors, including alcohol abuse, depression, Down's syndrome, cerebral glucose metabolism defect, head trauma, old age, Parkinson's disease, sleep disturbance, and underactivity, were shown to have an association with reduced cerebral blood flow. In this report an attempt is made to strengthen a hypothesis that reduced cerebral blood flow may be a required cofactor in the cause of Alzheimer's disease with examples of additional putative risks, including aluminum, ApoE 4 alleles, estrogen deficiency, family history of dementia, low education-attainment, olfactory deficit, and underactivity coupled with gender, considered to have a relationship or potential relationship with reduced cerebral blood flow. Factors, believed to ameliorate Alzheimer's disease, associated with improved or stabilized cerebral blood flow are tabulated. A tentative cerebral blood flow nomogram is shown as a potential model to possibly help predict Alzheimer's disease susceptibility.
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PMID:Alzheimer's disease risk factors as related to cerebral blood flow: additional evidence. 948 78

Bromocriptine is applied for treatment of patients with hyperprolactinaemic disorders, Parkinson's disease and acromegaly. Sometimes, this drug can be useful as adjuvant in patients with prostate hypertrophy, cocaine and alcohol abuse, or neuroleptic malignant syndrome. Recently, bromocriptine was found to improve memory. In randomized trials bromocriptine demonstrated improvement of prefrontal cortex function in traumatic brain injury patients. These informations suggest a potential possibility of this drug to therapy for patients with prefrontal damage.
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PMID:[Bromocriptine: uses until now and prospects of new therapeutic applications]. 1097 49

Different tissues display distinct sensitivities to defective mitochondrial oxidative phosphorylation (OXPHOS). Tissues highly dependent on oxygen such as the cardiac muscle, skeletal and smooth muscle, the central and peripheral nervous system, the kidney, and the insulin-producing pancreatic beta-cell are especially susceptible to defective OXPHOS. There is evidence that defective OXPHOS plays an important role in atherogenesis, in the pathogenesis of Alzheimer's disease, Parkinson's disease, diabetes, and aging. Defective OXPHOS may be caused by abnormal mitochondrial biosynthesis due to inherited or acquired mutations in the nuclear (n) or mitochondrial (mt) deoxyribonucleic acid (DNA). For instance, the presence of a mutation of the mtDNA in the pancreatic beta-cell impairs adenosine triphosphate (ATP) generation and insulin synthesis. The nuclear genome controls mitochondrial biosynthesis, but mtDNA has a much higher mutation rate than nDNA because it lacks histones and is exposed to the radical oxygen species (ROS) generated by the electron transport chain, and the mtDNA repair system is limited. Defective OXPHOS may be caused by insufficient fuel supply, by defective electron transport chain enzymes (Complexes I - IV), lack of the electron carrier coenzyme Q10, lack of oxygen due to ischemia or anemia, or excessive membrane leakage, resulting in insufficient mitochondrial inner membrane potential for ATP synthesis by the F0F1-ATPase. Human tissues can counteract OXPHOS defects by stimulating mitochondrial biosynthesis; however, above a certain threshold the lack of ATP causes cell death. Many agents affect OXPHOS. Several nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit or uncouple OXPHOS and induce the 'topical' phase of gastrointestinal ulcer formation. Uncoupled mitochondria reduce cell viability. The Helicobacter pylori induces uncoupling. The uncoupling that opens the membrane pores can activate apoptosis. Cholic acid in experimental atherogenic diets inhibits Complex IV, cocaine inhibits Complex I, the poliovirus inhibits Complex II, ceramide inhibits Complex III, azide, cyanide, chloroform, and methamphetamine inhibit Complex IV. Ethanol abuse and antiviral nucleoside analogue therapy inhibit mtDNA replication. By contrast, melatonin stimulates Complexes I and IV and Gingko biloba stimulates Complexes I and III. Oral Q10 supplementation is effective in treating cardiomyopathies and in restoring plasma levels reduced by the statin type of cholesterol-lowering drugs.
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PMID:Mitochondrial medicine--molecular pathology of defective oxidative phosphorylation. 1131 62

The prevalence of gait disorders among neurological inpatients is unknown, although disturbed gait is a common symptom. Gait disorders often lead to loss of independence with restraints for the patients and caregivers and costs for the health system. We designed a prospective study and investigated all patients admitted to a neurological hospital during a 100-day period for the presence of a gait disorder. Clinical investigation and several disease-specific rating scales were carried out for 493 patients. In 60% of the patients, a disturbance of gait was diagnosed. Most frequent diagnoses were stroke (21%), Parkinson's disease (17%), and polyneuropathy (7%). Within these diagnoses, the rate of patients with disturbed gait was high in Parkinson's disease (93%), subcortical arteriosclerotic encephalopathy (85%), and motor neuron disease (83%). Advanced age, dementia, alcohol abuse, and treatment with antiepileptics, neuroleptics, benzodiazepines, and chemotherapeutics were identified as risk factors for a gait disorder. A decline of cognitive function was accompanied by a reduction of walking speed. According to these results, gait disorders are among the most frequent symptoms in neurology.
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PMID:Prevalence of gait disorders in hospitalized neurological patients. 1539 43


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