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)

We describe a patient who developed Parkinson's disease (PD) 17 years after resection of his right cerebellum because of a Lindau tumor. He showed a classic 4.3-Hz resting tremor on the left side but a 3.1-Hz resting, postural, and intention tremor on the right side compatible with midbrain tremor (Holmes' tremor). We conclude that the generator of the tremor in PD cannot be located within the olivocerebellar loop. The cerebellum, however, seems to modulate the tremor frequency of parkinsonian rest tremor and may prevent the rest tremor from transforming into a postural and goal-directed tremor.
 ...
PMID:Function of the cerebellum in Parkinsonian rest tremor and Holmes' tremor. 1040 91

The case of a 74-year-old female patient who underwent a right hepatic lobectomy for hepatocellular carcinoma (HCC) which developed in primary biliary cirrhosis (PBC) is reported herein. During a follow-up examination for Parkinson's disease, an elevation of hepatobiliary tract-related enzymes and alpha-fetoprotein was uncovered. Diagnostic imagings showed a hypervascular, solitary, and encapsulated tumor measuring about 7 cm in diameter located mainly in the posterior segment. Positive antimitochondrial and antinuclear antibodies and a preoperative liver biopsy strongly suggested well differentiated HCC developed in PBC (Scheuer's classification stage II). Since the natural prognosis of PBC estimated by the Mayo risk score was fairly good and the liver function indicated sufficient tolerance for major hepatic resection, and preoperative computed tomography (CT) volumetry showed the atrophy of the right hepatic lobe, a right hepatic lobectomy was performed. A pathological examination revealed well encapsulated, moderately differentiated HCC with, in part, well-differentiated HCC in the tumor and stage II PBC in the noncancerous region. CT volumetry performed at postoperative day 14 showed a 146% enlargement of the remnant liver. An early detection of HCC and PBC by strict screening would prevent a limitation of surgical therapy due to a deteriorated liver function.
 ...
PMID:Right hepatic lobectomy for hepatocellular carcinoma which developed in primary biliary cirrhosis: report of a case. 1045 45

Many properties of HSV-1 are especially suitable for using this virus as a vector to treat diseases affecting the central nervous system (CNS), such as Parkinson's disease or malignant gliomas. These advantageous properties include natural neurotropism, high transduction efficiency, large transgene capacity, and the ability of entering a latent state in neurons. Selective oncolysis in combination with modulation of the immune response mediated by replication-conditional HSV-1 vectors appears to be a highly promising approach in the battle against malignant glioma. Helper virus-free HSV/AAV hybrid amplicon vectors have great promise in mediating long-term gene expression in the PNS and CNS for the treatment of various neurodegenerative disorders or chronic pain. Current research focuses on the design of HSV-1-derived vectors which are targeted to certain cell types and support transcriptionally regulatable transgene expression. Here, we review the recent developments on HSV-1-based vector systems and their applications in experimental and clinical gene therapy protocols.
Neoplasia 1999 Nov
PMID:HSV-1-based vectors for gene therapy of neurological diseases and brain tumors: part II. Vector systems and applications. 1093 55

A range of compounds in or derived from the diet modulates apoptosis in cell cultures in vitro. These observations have important implications concerning the mechanisms whereby dietary components affect health. Proapoptotic compounds could protect against cancer by enhancing elimination of initiated, precancerous cells, and antiapoptotic compounds could promote tumor formation by inhibiting apoptosis in genetically damaged cells. Proapoptotic compounds could also contribute to age-related degenerative diseases by activating cell death in postmitotic cells or shifting the normal balance of mitosis and apoptosis in tissues with regenerative capacity. Many age-related diseases, for example macular degeneration and Parkinson's disease, appear to have oxidative stress as an underlying component that interacts with genetic, dietary, and environmental factors to determine relative risk in an individual. Oxidative stress activates apoptosis, and antioxidants protect against apoptosis in vitro; thus, a central role of dietary antioxidants may be to protect against apoptosis. However, little in vivo data are available to directly link diet with altered apoptosis as an underlying determinant of disease. Moreover, the possible antagonistic effects of different dietary components and the uncertainty about whether proapoptotic compounds that may protect against cancer could contribute to degenerative diseases and vice versa indicate that there is a great need for better in vivo assessment of apoptosis and that caution should be exercised when extrapolating in vitro data on apoptosis to in vivo dietary recommendations.
 ...
PMID:Diet and apoptosis. 1094 Mar 43

Free radicals have been implicated in over a hundred disease conditions in humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinson's disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, and AIDS. Antioxidants are potent scavengers of free radicals and serve as inhibitors of neoplastic processes. A large number of synthetic and natural antioxidants have been demonstrated to induce beneficial effects on human health and disease prevention. However, the structure-activity relationship, bioavailability and therapeutic efficacy of the antioxidants differ extensively. Oligomeric proanthocyanidins, naturally occurring antioxidants widely available in fruits, vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad spectrum of biological, pharmacological and therapeutic activities against free radicals and oxidative stress. We have assessed the concentration- or dose-dependent free radical scavenging ability of a novel IH636 grape seed proanthocyanidin extract (GSPE) both in vitro and in vivo models, and compared the free radical scavenging ability of GSPE with vitamins C, E and beta-carotene. These experiments demonstrated that GSPE is highly bioavailable and provides significantly greater protection against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was also shown to demonstrate cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells. The comparative protective effects of GSPE, vitamins C and E were examined on tobacco-induced oxidative stress and apoptotic cell death in human oral keratinocytes. Oxidative tissue damage was determined by lipid peroxidation and DNA fragmentation, while apoptotic cell death was assessed by flow cytometry. GSPE provided significantly better protection as compared to vitamins C and E, singly and in combination. GSPE also demonstrated excellent protection against acetaminophen overdose-induced liver and kidney damage by regulating bcl-X(L) gene, DNA damage and presumably by reducing oxidative stress. GSPE demonstrated excellent protection against myocardial ischemia-reperfusion injury and myocardial infarction in rats. GSPE was also shown to upregulate bcl(2) gene and downregulate the oncogene c-myc. Topical application of GSPE enhances sun protection factor in human volunteers, as well as supplementation of GSPE ameliorates chronic pancreatitis in humans. These results demonstrate that GSPE provides excellent protection against oxidative stress and free radical-mediated tissue injury.
 ...
PMID:Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. 1096 38

REM sleep is the stage associated with vivid dream mentation, desynchronous cortical EEG, and atonia of antigravitary muscles. REM sleep behavior disorder (RBD) is characterized by the intermittent loss of REM sleep atonia and by the appearance of elaborate motor activity associated with dream mentation. The animal model of REM sleep without atonia indicates that lesions to the perilocus coeruleus disrupt the excitatory connection to the nucleus reticularis magnocellularis in the descending medullary reticular formation and disable the hyperpolarization of the alpha spinal motoneurons. Extensive neurologic evaluations in humans suffering from both idiopathic and symptomatic forms have not identified specific lesions; however, findings in some patients suggest that diffuse lesions of the hemispheres, bilateral thalamic abnormalities, or primary brain-stem lesions may result in the RBD. Symptomatic RBD cases are associated with several neurologic disorders such as dementia, cerebrovascular diseases, multiple sclerosis, brain-stem neoplasm. RBD has been often documented to precede or to co-occur with neurodegenerative disorders, such as dementia, Parkinson's disease and multiple system atrophy. Most importantly, RBD is readily diagnosable and treatable. Patients and their bed partners usually report immediate improvement in sleep-related motor behavior with small doses of clonazepam.
 ...
PMID:REM sleep behavior disorder. 1099 67

The development of an in vitro model for cysteine dioxygenase (CDO) expression in the brain would provide a useful model for determining the mechanisms for the regulation of CDO expression that does not involve the use of animals. Here we demonstrate the screening and characterization of a cell line that expresses CDO, the primary metabolizing enzyme of cysteine and the regulatory point of sulfate production. A panel of four commercially available tumor-derived human brain cell lines, each representing one major class of brain cell, were screened using western blotting and activity assay for cysteine dioxygenase expression. One cell line, TE 671 (human medulloblastoma) was found to express both a protein of approximately 70 kDa and CDO activity. Nuclease protection assay (NPA) of mRNA isolated from TE 671 showed the expression of a CDO mRNA. Reverse transcription-polymerase chain reaction of this mRNA and sequencing of the cDNA obtained showed that this was indeed CDO. Treatment of TE 671 cells with cysteine resulted in the upregulation of CDO mRNA, whereas treatment with tumor necrosis factor alpha resulted in the downregulation of CDO mRNA, as evidenced using NPA. The characterization of an in vitro model for CDO expression provides a useful tool for the investigation of this important enzyme, which may have an etiological role in the pathogenesis of Parkinson's disease.
 ...
PMID:Development of an in vitro model for cysteine dioxygenase expression in the brain. 1110 Oct 6

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.
 ...
PMID:Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? 1113 72

The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the primate brain in the long term and to effect functional improvement in the animals. Following polymer encapsulation, PC12 cells were transplanted into the striatum of hemiparkinsonian monkeys. The secretion of L-dopa and dopamine from the encapsulated cells, the morphology of these cells, the histology of the host striatum surrounding the capsule, and functional changes in the host animals were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the PC12 cells survived and continued to release L-dopa and dopamine even 12 months after transplantation. The histological response of the host brain surrounding the capsules was minimal and there were no signs of immunological rejection or tumor formation. The physical condition of the host animals was good for 12 months, and hematologic and cerebrospinal fluid analysis revealed that no animals suffered from infection or immunological reaction. These PC12 cell-grafted monkeys showed improvements in hand movements after transplantation, effects that lasted for at least 12 months. These results further support the potential use of this approach for the treatment of Parkinson's disease.
 ...
PMID:Grafting of encapsulated dopamine-secreting cells in Parkinson's disease: long-term primate study. 1114 70

Neoplasm is an uncommon cause of a parkinsonian syndrome. We report a woman with primary brain B-cell lymphoma presenting as Parkinson's disease. After 1 year of the illness, CT and MRI showed lesions without mass effect in the basal ganglia and corpus callosum. The patient did not respond to levodopa and right cerebellar and brain-stem signs appeared, which prompted further neuroimaging, showing an increase in size of the lesions and a right cerebellar and pontine mass. Stereotactic biopsy of the basal ganglia showed high-grade B-cell lymphoma. Despite the basal ganglia frequently being involved in lymphoma of the brain, presentation with typical or atypical parkinsonism is exceptional.
 ...
PMID:Primary brain lymphoma presenting as Parkinson's disease. 1121 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>