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)

Metoclopramide, a dopamine antagonist, is approved in the U.S. for the treatment of various gastrointestinal disorders. Its use has been investigated in a wide variety of diseases, including those not involving the intestinal tract. Although more study is required before routine clinical use of metoclopramide can be advocated, it may be effective in the treatment of tardive dyskinesia, in decreasing the risk factors associated with anesthetic-related aspiration, and as an adjunct in the treatment of gastric bezoars. It also may be used safely in patients with Parkinson's disease. The use of metoclopramide in the treatment of neurogenic bladder, orthostatic hypotension, tumor-associated gastroparesis, nonprolactinemic amenorrhea, failure to thrive, Tourette's syndrome, anorexia nervosa, and hiccups, as well as an adjunct to migraine therapy, has been investigated, but sufficient evidence has not been accumulated to advocate the use of metoclopramide in these disorders.
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PMID:Potential uses for metoclopramide. 390 32

Malignant melanoma derives from melanocytic cells that possess the special biochemical pathway for the conversion of levodopa to melanin. Levodopa is widely employed in the treatment of Parkinson's disease, and several patients receiving levodopa have been observed to have acquired melanomas, raising concern about a possible relationship between this drug and the tumor. We encountered a 74-year-old woman in whom three distinct primary melanomas developed after she had been receiving long-term therapy with levodopa and a decarboxylase inhibitor. These lesions could be distinguished histologically from epidermotropic metastatic melanoma. Although the association between levodopa and melanoma is tenuous, careful monitoring of pigmentary changes in patients receiving levodopa is advised.
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PMID:Levodopa administration and multiple primary cutaneous melanomas. 741 57

Expression of the rate-limiting enzyme for catecholamine biosynthesis, tyrosine hydroxylase (TH), via retroviral and plasmid expression vectors improved the efficacy of conditionally immortalized nigral neural cells in ameliorating rodent and nonhuman primate models of Parkinson's disease through neural transplantation. No improvement in rotational behavior occurred when sham transplants or nondopaminergic transplants were performed. Transplantation of the temperature-sensitive immortalized parental nigral neural line with a TH expression vector resulted in improvement for at least 2 months. Improvement was accompanied by HPLC evidence of increased L-DOPA production and immunocytochemical evidence of TH in the transfected cells increased over that of the parental line. No tumor formation was detected. These results suggest that: (1) temperature-sensitive immortalized neural cells may be genetically engineered successfully to improve their efficacy for the treatment of parkinsonism; and (2) a change in L-DOPA production, as opposed to growth factor production or other factors, is likely to account for the observed improvement, since the parental and derived lines differ by a single gene.
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PMID:Neural-targeted gene therapy for rodent and primate hemiparkinsonism. 751 94

Spinal cavernous hemangioma is rare, and it is extremely rare for cavernous hemangioma to develop in the cauda equina. There has been only one report of hydrocephalus associated with cavernous hemangioma in the cauda equina. We report a case of cavernous hemangioma in the cauda equina diagnosed on the basis of the headaches due to hydrocephalus. A 67-year-old man was being treated for Parkinson's disease because of tremor of both upper extremities for several years. In December 1991 he complained of occasional headaches. On February 15, 1992 the headaches became severe and frequent, with nausea and vomiting, and his gait became unsteady. Four days later he came to our hospital. Neurological examination revealed fine finger tremor and truncal ataxia. Computerized tomography scanning and magnetic resonance imaging of the head revealed ventricular enlargement, but there were no mass lesions obstructing the cerebrospinal fluid pathway. Lumbar puncture at the L3-L4 level yielded bloody cerebrospinal fluid, and the pressure had increased to 410 mmH2O. Cerebral angiography showed no abnormal findings. Magnetic resonance imaging of the lumbar spine demonstrated an intradural tumor at the level of vertebral body L2. Spinal angiography showed no evidence of abnormal vascularity in the mass at the L2 level. On March 10, 1992, laminectomy at three levels, L1 to L3 was performed, and a well-defined blueberry-like intra-cauda equina tumor 1 cm. in diameter, was removed. One spinal nerve root passed through the tumor. The pathological diagnosis was cavernous hemangioma. After removal of the tumor, the patient's headaches improved, and a follow-up computerized tomography scan six months later showed normal ventricle size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cauda equina cavernous hemangioma associated with hydrocephalus--case report]. 754 25

Long-term survival of grafted neural cells is a major goal of neural transplantation, but typical survival rates of grafted fetal neurons are in the range of 5-10%. Whether the death of transplanted neural cells is apoptotic or necrotic is unknown. The expression of the proto-oncogene bcl-2 inhibits both apoptotic and necrotic neural cell death. In a 6-OHDA induced rat model of Parkinson's disease, Hoechst 33258 prelabelled conditionally immortalized nigral cells engineered to express bcl-2 were stereotactically transplanted into the striatum ipsilaterally to the lesioned nigrostriatal pathway. Sixteen rats received bcl-2 transfected cells, 15 received cells transfected with vector alone, and 12 received either a nondopaminergic cell line or were sham transplanted as controls. Four wk following transplantation, the rats with grafts containing bcl-2 expressing cells showed an approximately 43% decrease in apomorphine-induced rotational behavior. In contrast, 12% improvement occurred in the rats with transplanted cells transfected with vector alone (p < 0.05), and no improvement occurred in sham-operated animals (p < 0.05). Histological examination showed no tumor formation. Despite the difference in behavioral effect, no clear difference in Hoechst fluorescent staining or staining for TH, GFAP was noted; therefore, it is unknown at present whether the observed effect was due to a difference in survival or to increased efficacy per surviving transplanted neural cell, or both.
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PMID:Neural transplantation of cells expressing the anti-apoptotic gene bcl-2. 772 33

Positron emission tomography (PET) is a method for quantitative imaging of regional physiological and biochemical parameters. Positron emitting radioactive isotopes can be produced by a cyclotron, eg. the biologically important carbon (11C), oxygen (15O), and nitrogen (13N) elements. With the tomographic principle of the PET scanner the quantitative distribution of the administered isotopes can be determined and images can be provided as well as dynamic information on blood flow, metabolism and receptor function. In neurology PET has been used for investigations on numerous physiological processes in the brain: circulation, metabolism and receptor studies. In Parkinson's disease PET studies have been able to localize the pathology specifically, and in early stroke PET technique can outline focal areas with living but non-functioning cells, and this could make it possible to intervene in this early state. With positron emission tomography a quantitative evaluation of myocardial blood flow, glucose and fatty acid metabolism can be made as well as combined assessments of blood flow and metabolism. Combined studies of blood flow and metabolism can determine whether myocardial segments with abnormal motility consist of necrotic or viable tissue, thereby delineating effects of revascularisation. In the future it will probably be possible to characterize the myocardial receptor status in different cardiac diseases. The PET technique is used in oncology for clinical as well as more basic research on tumor perfusion and metabolism. Further, tumor uptake of positron labelled cytotoxic drugs might predict the clinical benefit of treatment.
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PMID:[Positron emission tomography. A new measurement method for imaging of regional and biochemical parameters]. 781 6

Brain imaging is performed using radiopharmaceuticals by single photon emission computed tomography (SPECT) and positron emission tomography (PET). SPECT and PET radiopharmaceuticals are classified according to blood-brain-barrier permeability, cerebral perfusion and metabolism receptor-binding, and antigen-antibody binding. The blood-brain-barrier (BBB) SPECT agents, such as 99mTcO4-, [99mTc]DTPA, 201TI and [67Ga]citrate are excluded by normal brain cells, but enter into tumor cells because of altered BBB. These agents were used in the earlier period for the detection of brain tumors. SPECT perfusion agents such as [123I]IMP, [99mTc]HMPAO, [99mTc]ECD are lipophilic agents and therefore, diffuse into the normal brain. These tracers have been successfully used to detect various cerebrovascular diseases such as stroke, Parkinson disease, Huntington's disease, epilepsy, dementia, and psychiatric disorders. Xenon-133 and radiolabeled microspheres have been used for the measurement of cerebral blood flow (CBF). Important receptor-binding SPECT radiopharmaceuticals include [123I]QNE, [123I]IBZM, and [123I]iomazenil. These tracers bind to specific receptors in the brain, thus displaying their distribution in various receptor-related cerebral diseases. Radioiodinated monoclonal antibodies were used for the detection of brain tumors. PET radiopharmaceuticals for brain imaging are commonly labeled with positron-emitters such as 11C, 13N, 15O, and 18F, although other radionuclides such as 82Rb, 62Cu and 68Ga also were used. The brain uptake of [13N]glutamate, [68Ga]EDTA and [82Rb]RbCl depends on the BBB permeability, but these are rarely used for brain imaging. Several cerebral perfusion agents have been introduced, of which [15O]water, [13N]ammonia, and [15O]butanol have been used more frequently. Regional CBF has been quantitated by using these tracers in normal and different cerebral disease states. Other perfusion agents include [15O]O2, [11C]CO, [11C]CO2, [18F]fluoromethane, [15O]O2, [11C]butanol, and [62Cu]PTSM. Among the PET cerebral metabolic agents, [18F]fluorodeoxyglucose (FDG) is most commonly used to detect metabolic abnormalities in the brain. Various brain tumors have been graded by [18F]FDG PET. This technique was used to detect epileptic foci by showing increased uptake in the foci during the ictal period and decreased uptake in the interictal period. Differentiation between recurrent tumors and radiation necrosis and the detection of Alzheimer's disease have been made successfully by [18F]FDG PET. Other PET metabolic agents such as [11C]deoxyglucose, and [11C]methylmethionine have drawn attention in the detection of brain tumors. [18F]fluorodopa is a cerebral neurotransmitter agent, which has been found very useful in the detection of Parkinson disease that shows reduced uptake of the tracer in the striatum of the brain.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Radiopharmaceuticals for brain imaging. 781 3

Long-term treatment of parkinsonian patients with L-DOPA leads to a loss of efficacy over time and the appearance of important side effects such as dyskinesias. Grafts of chromaffin cells of the adrenal medulla or fetal ventral mesencephalic neurons bring behavioral improvement in animal models of Parkinson's disease. These improvements are likely to be related to the secretion of dopamine by the grafted cells and/or to the reinnervation of the host tissue. In addition, a leak in the blood-brain barrier may allow peripheral catecholamines to gain access to the brain. Lack of clear effects of grafts in parkinsonian patients may be due to their poor survival in the human brain. Improvement of grafting techniques as well as the addition of neurotrophic factors to grafts may help increase their survival and improve behavioral effects. Recently, genetic techniques have allowed the creation of genetically modified cell lines which can produce L-DOPA and these cells may be grafted in the brain. Interestingly, these cell lines may be encapsulated in permselective membranes which can protect them from immunological rejection and avoid the uncontrolled cell growth of these mitotically active cells. Grafting techniques seem to be an interesting alternative to treat parkinsonian patients. Improvement of grafting procedures may help increase survival of grafts and thus enhance behavioral improvements. Moreover, genetic modification of well-known tumor cell lines or patient's own cells such as astrocytes may help avoid the low availability as well as ethical and immunological problems linked to the use of fetal human tissue.
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PMID:Grafts in the treatment of Parkinson's disease: animal models. 795 81

Over the past few years, molecular neurogenetics has developed into one of the most promising and active research fields. The new discipline applies modern molecular genetic techniques to the investigation of classical neurological disorders. In the following article, a definition of neurogenetic disease is introduced, the molecular basis of four groups of neurogenetic disorders is described and recent diagnostic developments are presented. The first group of diseases is caused by trinucleotide expansions. "Expanding" trinucleotide repeats were not known to occur in any species until about three years ago. Today, disorders such as Huntington's disease, spinocerebellar ataxia type 1, fragile X mental retardation, spinobulbar muscular atrophy and myotonic dystrophy are all known to be caused by the expansion of trinucleotides. The second group is characterized by chromosomal deletions or uniparental disomies. Lissencephaly and the Miller-Dieker syndrome, Prader-Willi and Angelman syndromes and Duchenne and Becker muscular dystrophies belong to this category. The third group includes those neurogenetic disorders that are mainly caused by point mutations such as the X-linked leukodystrophies, including Pelizaeus-Merzbacher disease and adrenoleukodystrophy, Charcot-Marie-Tooth syndrome type 1, familial forms of amyotrophic lateral sclerosis, several types of craniosynostoses and some CNS tumor syndromes. Finally, Alzheimer's and Parkinson's disease are discussed as representatives of group four, i.e. genetically heterogeneous neurological disorders.
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PMID:Molecular basis and diagnosis of neurogenetic disorders. 796 63

Parkinsonism is an uncommon movement disorder in childhood. Six unusual cases of acquired parkinsonism in hospitalized children are described. Clinical manifestations included an akinetic-rigid syndrome with and without tremor, the combination of parkinsonism and dystonia, and a parkinsonism-plus syndrome. Altered mental status, mutism, dysphagia, and sialorrhea were frequent associations. Etiologies included hypoxic-ischemic encephalopathy; haloperidol treatment with and without neuroleptic malignant syndrome; toxicity of cytosine arabinoside, cyclophosphamide, amphotericin B, and methotrexate; St. Louis encephalitis and other encephalitides; and a pineal tumor with hydrocephalus. Cranial magnetic resonance imaging results ranged from normal to profound cerebral and cerebellar atrophy with chemotherapeutic toxicity. The illnesses usually were severe enough to require pharmacotherapy. Incorrect diagnoses of depression or catatonia delayed treatment or aggravated the problem. Acute treatment included amantadine, levodopa/carbidopa with or without selegiline, diphenhydramine, or benztropine. The concentration of CSF homovanillic acid was normal in a neuroleptic-associated patient, but the level was low in an encephalitic patient. All patients demonstrated dramatic improvement, including two who were not treated; some had complete resolution of symptoms and none required continued antiparkinsonian drugs despite poor scores on the Unified Parkinson's Disease Rating Scale and the Modified Hoehn and Yahr Rating Scales. The causes of parkinsonism described are more common in a general pediatric hospital than the parkinsonism associated with the popularized Segawa syndrome.
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PMID:Clinical spectrum of secondary parkinsonism in childhood: a reversible disorder. 802 61


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