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 effects of insulin-induced hypoglycemia on catecholamine secretion were investigated in patients with various neurological disorders affecting the autonomic nervous system. In control subjects, insulin-induced hypoglycemia resulted in marked increases in plasma epinephrine and norepinephrine levels. Heart rates were increased within 15 minutes after the insulin injection which were associated with slight elevation and depression of systolic and diastolic blood pressure, respectively. In patients with upper level spinal cord lesions (C1-T6) of various etiology, Shy-Drager syndrome and familial amyloidosis, insulin-induced hypoglycemia failed to increase plasma epinephrine and norepinephrine levels and resulted in falls in systolic and/or diastolic blood pressure 15 minutes after the injection. Heart rates were increased at 30-45 minutes after the injection. In patients with lower spinal cord lesions (T10-L1), neurosyphilis or brain stem tumor with orthostatic hypotension, the catecholamine responses were normal and blood pressure did not fall during insulin-induced hypoglycemia. In patients with Parkinson's disease and spinocerebellar degeneration with autonomic symptoms catecholamine responses were not impaired. These findings suggest that any lesion involving the sympathetic efferent systems of baroreflex such as the spinal descending pathway, sympathetic preganglionic neuron and peripheral nervous system causes both impairment of catecholamine secretion and a fall in blood pressure during hypoglycemia, and that lesions in sympatho-afferent system may not affect the secretion of catecholamine and neural control of blood pressure.
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PMID:[Effects of insulin-induced hypoglycemia on catecholamine secretion and blood pressure in neurological disorders affecting autonomic nervous system]. 162 51

Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of amyloidosis which is related to a point mutation in the gelsolin gene localized on chromosome 9. The mutation corresponds to codon 187 of the secreted form of gelsolin, and is expressed in the amyloid fibril at residue 15. Our original FAF patient was demented, and neuropathological analysis showed Alzheimer type brain lesions associated with both classical and cortical Lewy bodies. Furthermore, antiserum against the gelsolin-derived FAF amyloid reacted strongly with both classical and cortical Lewy bodies of this FAF patient. In preliminary experiments similar results were obtained in cases of Parkinson's disease and diffuse Lewy body disease. These observations may indicate a role for gelsolin in the pathogenesis of Parkinson's disease and related conditions.
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PMID:Gelsolin variant and beta-amyloid co-occur in a case of Alzheimer's with Lewy bodies. 166 Jan 9

Gastrointestinal motility is the function of gastrointestinal smooth muscle. It is controlled by both the intrinsic and extrinsic nerves of the gastrointestinal tract and, to a lesser degree, the gastrointestinal hormones. Therefore, any abnormality of the above factors, theoretically, can cause gastrointestinal dysmotility. In a clinical situation, commonly seen is gastrointestinal dysmotility caused by either smooth muscle or intrinsic and extrinsic nerves dysfunction. Diseases that cause smooth muscle dysfunction include familial visceral myopathies, nonfamilial visceral myopathies, collagen disease, muscular dystrophies, amyloidosis, thyroid disease, and so on. Diseases that cause enteric nerve dysfunction include familial visceral neuropathies, nonfamilial visceral neuropathies, diabetes mellitus, Chagas' disease, ganglioneuromatosis of the intestine, visceral neuropathy of carcinomatosis, Parkinson's disease, and so on. The patients with neuromuscular disease of the gastrointestinal tract have a wide range of clinical manifestations regardless of the underlying cause. At one end of the spectrum, the patients may be asymptomatic, and at the other end of the spectrum, the patients may have functional obstruction of the gastrointestinal tract. Plain abdominal x-rays, upper gastrointestinal (UGI) and small bowel x-rays, enteroclysis, barium enema, and manometric studies are useful for the work-up of these patients. Enteroclysis is especially helpful in ruling out mechanical obstruction of the small intestine in patients with chronic intestinal pseudo-obstruction. Treatment is mainly symptomatic and supportive. There is no effective drug to improve gastrointestinal motility. Surgery may be helpful in selected cases of severe gastrointestinal dysmotility.
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PMID:Neuromuscular disease of the gastrointestinal tract. 200 Aug 94

Amyloid deposits of the CNS caused clinical symptoms in four members of a Hungarian family. Histological investigations revealed a systemic disease, immunohistologically the deposited material was a transthyretin variant, DNA analysis showed a new transthyretin mutation (TTRAsp 18Gly). The disease--named meningocerebrovascular amyloidosis, Hungarian type--is inherited dominantly like other already known familial amyloidoses caused by transthyretin variants, however it does not cause the usual familial polyneuropathy but symptoms similar to those of the rare oculoleptomeningeal amyloidosis. The aim of the present study is to point to differential diagnosis. Its complaints, neurological signs and clinical findings which may be suspect of atypical migraine, brain tumour, chronic leptomeningitis or herpes encephalitis, multiple sclerosis and Parkinson disease are analysed and compared with those of other known types of familial amyloidoses. Attention is drawn to symmetrical calcification on CT scans. Skin biopsy may help the diagnosis. At present, therapy is only symptomatic.
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PMID:[Clinical characteristics of Hungarian-type familial meningo-cerebrovascular amyloidosis]. 899 35

Senile dementia of Lewy body type or Lewy body dementia (SDLT or LBD) is defined as a Lewy body associated disease presenting in the elderly primarily with dementia with variable extrapyramidal disorder. Characteristic clinical symptoms include fluctuating cognitive impairment, psychotic features such as hallucinations and a particular sensitivity to neuroleptic medication. Although apolipoprotein e4 allele is increased 2-3 fold in SDLT (as in Alzheimer's disease) and beta-amyloidosis occurs in most cases, the most robust neurobiological correlate of the dementia so far identified appears to be extensive cholinergic deficits in the neocortex. This is consistent with previously reported correlations between cortical cholinergic activity and dementia in Parkinson's disease (PD) and Alzheimer's disease. There is also a significant interaction between the density of limbic cortical Lewy bodies and dementia in both SDLT and PD, although the cortical neuronal population affected remains to be identified. Cortical Lewy body density is positively correlated with the age of disease onset in PD and SDLT. This may account for the increased incidence of psychiatric syndromes, as opposed to extrapyramidal disorder in Lewy body disease with advancing age as may age-related loss of cholinergic activity in cortical areas such as the hippocampus.
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PMID:Lewy body dementia--clinical, pathological and neurochemical interconnections. 947 Jan 31

Differential expression of the amyloid precursor protein gene (APP) may be important in the development of amyloidosis in Alzheimer's disease (AD) and experimentally in the brain's response to injury. Controversial data suggests that APP isoforms containing the Kunitz protease inhibitor isoform (APP KPI+) are over expressed in the brains of patients with AD when compared to the non-Kunitz protease inhibitor containing isoforms (APP KPI-). We have investigated this hypothesis using a quantitative analysis of gene expression on brain tissue collected at post-mortem. In situ hybridization has been used with synthetic oligonucleotide probes labelled with 35S to detect the two principal splice variants of APP: APP 695 (KPI-) and APP 751 (KPI+). A prospective brain bank of frozen brain specimens has been established and includes pathologically proven AD (n=15) and other neurodegenerative disorders as controls (n=18). The controls consist of frontal lobe atrophy (n=4), Huntington's disease (n=5), Parkinson's disease (n=4), motor neuron disease (n=2), multi-infarct dementia (n=1), multisystem atrophy (n=1), and subacute sclerosing panencephalitis (n=1). We have observed no significant differences in the expression of APP 695 KPI- mRNA in frontal lobe: 17.49+/-3.26 optical density (OD) units of mRNA expression in AD vs. 16.13+/-1.76 OD units mRNA in controls (P=0.80, linear regression); or temporal lobe: 14.73+/-2.96 in AD vs. 16.49+/-2.15 in controls (P=0.55). No significant differences have been found in APP 751 KPI+ in frontal lobe: 12.86+/-2.98 in AD vs. 13.70+/-2.88 in controls (P=0.97); and temporal lobe: 13.31+/-4.93 in AD vs. 11.07+/-1.99 in controls (P=0. 65). Analysis of the ratios of APP 751 KPI+ OD units of mRNA to APP 695 KPI- mRNA revealed a trend to an increased ratio which did not reach statistical significance: frontal lobe APP 751 KPI+/APP 695 KPI- 1.92+/-1.04 in AD vs. 0.86+/-0.17 in controls (P=0.54); temporal lobe 2.54+/-1.59 in AD vs. 0.96+/-0.11 controls (P=0.34). Our data has not revealed differential expression of APP mRNA isoforms in AD and supports the hypothesis that post-translational events in APP metabolism are important in amyloidogenesis and the pathogenesis of AD.
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PMID:Amyloid precursor protein gene isoforms in Alzheimer's disease and other neurodegenerative disorders. 1067 49

Two missense mutations in the gene encoding alpha-synuclein have been linked to rare, early-onset forms of Parkinson's disease (PD). These forms of PD, as well as the common idiopathic form, are characterized by the presence of cytoplasmic neuronal deposits, called Lewy bodies, in the affected region of the brain. Lewy bodies contain alpha-synuclein in a form that resembles fibrillar Abeta derived from Alzheimer's disease (AD) amyloid plaques. One of the mutant forms of alpha-synuclein (A53T) fibrillizes more rapidly in vitro than does the wild-type protein, suggesting that a correlation may exist between the rate of in vitro fibrillization and/or oligomerization and the progression of PD, analogous to the relationship between Abeta fibrillization in vitro and familial AD. In this paper, fibrils generated in vitro from alpha-synuclein, wild-type and both mutant forms, are shown to possess very similar features that are characteristic of amyloid fibrils, including a wound and predominantly unbranched morphology (demonstrated by atomic force and electron microscopies), distinctive dye-binding properties (Congo red and thioflavin T), and antiparallel beta-sheet structure (Fourier transform infrared spectroscopy and circular dichroism spectroscopy). alpha-Synuclein fibrils are relatively resistant to proteolysis, a property shared by fibrillar Abeta and the disease-associated fibrillar form of the prion protein. These data suggest that PD, like AD, is a brain amyloid disease that, unlike AD, is characterized by cytoplasmic amyloid (Lewy bodies). In addition to amyloid fibrils, a small oligomeric form of alpha-synuclein, which may be analogous to the Abeta protofibril, was observed prior to the appearance of fibrils. This species or a related one, rather than the fibril itself, may be responsible for neuronal death.
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PMID:Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. 1070 4

Human brain ageing is associated with reductions in a variety of nicotinic receptors subtypes, whereas changes in age-related disorders including Alzheimer's disease or Parkinson's disease are more selective. In Alzheimer's disease, in the cortex there is a selective loss of the alpha4 (but not alpha3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not alpha-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Abeta1-42, but not related to plaque or tangle densities. In contrast, alpha-bungarotoxin binding is positively correlated with plaque densities in the entorhinal cortex. In human temporal cortex loss of acetylcholinesterase catalytic activity is positively correlated with decreased epibatidine binding and in a transgenic mouse model over expressing acetylcholinesterase, epibatidine binding is elevated. In Parkinson's disease, loss of striatal nicotine binding appears to occur early but is not associated with a loss of alpha4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased alpha4 immunoreactivity in the cortex and lower densities of amyloid-beta plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvement of the alpha4 subunit in beta-amyloidosis but not in nigro-striatal dopaminergic degeneration.
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PMID:Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases. 1077 Oct 16

On the basis of current literature, clinical and neuropathologic features of idiopathic autonomic neuropathy is presented. Idiopathic autonomic neuropathy is a disease characterized by acute or subacute onset, monophasic course over a period of several years, it is often preceded by an infection. The spectrum of autonomic changes ranges from cholinergic or adrenergic dysfunction to pandysautonomia, leading to heterogeneity of its clinical features. Possible sympathetic system abnormalities found in autonomic neuropathy are: poor pupillary response to light in darkness, orthostatic hypotension leading to syncope, hypotension without compensatory tachycardia, ejaculation disturbances and vasomotor instability. Possible parasympathetic dysfunctions are: salivation and lacrimation disturbances, absent pupillary constriction to light and near gaze, gastrointestinal tract immobility and impairment of gastrointestinal function, atonic bladder with large residual volume, erectile impotence. Pandysautonomia is thought to result from an immune mediated mechanism and responds well to plasmaferesis and intravenous immunoglobin therapy leading to gradual, sometimes not full, recovery. Moreover in this article we pay attention to the clinical value of many tests like cardiovascular or pharmacological studies in the diagnosis of pandysautonomia and in differentiation of pre- and postganglionic changes. In order to diagnose idiopathic autonomic neuropathy one has to rule out a large number of diseases with autonomic dysfunction e.g.: diabetes, malignant neoplasms, acute intermittent porphyria, Shy-Drager syndrome, Riley-Day's dysautonomia, Parkinson's disease, amyloidosis and others.
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PMID:[Idiopathic autonomic neuropathy (pandysautonomia)]. 1173 67

Parkinson's disease is the second most common neurodegenerative disease and results from loss of dopaminergic neurons in the substantia nigra. The aggregation and fibrillation of alpha-synuclein have been implicated as a causative factor in the disease. Glycosaminoglycans (GAGs) are routinely found associated with amyloid deposits in most amyloidosis diseases, and there is evidence to support an active role of GAGs in amyloid fibril formation in some cases. In contrast to the extracellular amyloid deposits, the alpha-synuclein deposits in Lewy body diseases are intracellular, and thus it is less clear whether GAGs may be involved. To determine whether the presence of GAGs does affect the fibrillation of alpha-synuclein, the kinetics of fibril formation were investigated in the presence of a number of GAGs and other charged polymers. Certain GAGs (heparin, heparan sulfate) and other highly sulfated polymers (dextran sulfate) were found to significantly stimulate the formation of alpha-synuclein fibrils. Interestingly, the interaction of GAGs with alpha-synuclein is quite specific, since some GAGs, e.g., keratan sulfate, had negligible effect. Heparin not only increased the rate of fibrillation but also apparently increased the yield of fibrils. The molar ratio of heparin to alpha-synuclein and the incorporation of fluorescein-labeled heparin into the fibrils demonstrate that the heparin is integrated into the fibrils and is not just a catalyst for fibrillation. The apparent dissociation constant for heparin in stimulating alpha-synuclein fibrillation was 0.19 microM, indicating a strong affinity. Similar effects of heparin were observed with the A53T and A30P mutants of alpha-synuclein. Since there is some evidence that Lewy bodies may contain GAGs, these observations may be very relevant in the context of the etiology of Parkinson's disease.
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PMID:Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro. 1181 43


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