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 mechanisms by which adrenal medulla grafts influence the function of host brains in animal models of Parkinson's disease are unclear. To explore this issue, fragments of adrenal medulla or sciatic nerve were transplanted into the lateral ventricle of bilaterally adrenalectomized (ADX) or sham-ADX rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Additional control group received sham-transplantation surgery. Behavioral effects of these procedures were tested following administration of apomorphine, amphetamine, or nicotine. Plasma catecholamines were measured before and after transplantation surgery. In both ADX and sham-ADX rats, adrenal medulla grafts produced greater decreases in apomorphine-induced rotational behavior than did sciatic nerve grafts or sham-transplanted groups. Decreases in rotation were smaller in ADX than in sham-ADX animals, regardless of graft treatment. Plasma catecholamines increased after transplantation surgery in each of the sham-ADX groups, regardless of graft type. Increases in plasma dopamine concentrations were associated with decreases in rotational behavior. Five months after transplantation, grafted chromaffin cells demonstrated catecholamine fluorescence, tyrosine hydroxylase (TH) and chromogranin A immunoreactivities, and expression of TH mRNA. It is concluded that adrenal medulla grafts produce decreases in apomorphine-induced rotation through a combination of two independent effects. One is a specific effect of adrenal medulla grafts. The second is a nonspecific effect that requires an intact adrenal gland and may be related to increases in plasma catecholamine concentrations.
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PMID:Effects of adrenal medulla grafts on plasma catecholamines and rotational behavior. 139 73

Fifteen patients with Parkinson's disease underwent open transplantation of autologous adrenal medulla to the caudate nucleus. Motor function was evaluated before and after surgery and was found to be significantly improved at 5-9 months following surgery. Cerebrospinal fluid was taken from the ventricle adjacent to the implant site at the beginning of the operation and at 1 week, 3 months, and 5-9 months following surgery. The cerebrospinal fluid was assayed for chromogranin A (CgA), the major soluble protein in chromaffin granules, and basic fibroblast growth factor (bFGF), a neurotrophic growth factor found in normal brain and adrenal medulla. CgA levels did not increase following surgery, suggesting that a significant number of chromaffin cells did not survive or that surviving chromaffin cells did not secrete a significant amount of CgA. Basic fibroblast growth factor was undetectable in the ventricular cerebrospinal fluid.
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PMID:Clinical improvement in parkinsonian patients undergoing adrenal to caudate transplantation is not reflected by chromogranin A or basic fibroblast growth factor in ventricular fluid. 199 31

Autopsy results on patients and corresponding studies in nonhuman primates have revealed that autografts of adrenal medulla into the striatum, used as a treatment for Parkinson's disease, do not survive well. Because adrenal chromaffin cell viability may be limited by the low levels of available nerve growth factor (NGF) in the striatum, the present study was conducted to determine if transected peripheral nerve segments could provide sufficient levels of NGF to enhance chromaffin cell survival in vitro and in vivo. Aged female rhesus monkeys, rendered hemiparkinsonian by the drug MPTP (n-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), received autografts into the striatum using a stereotactic approach, of either sural nerve or adrenal medulla, or cografts of adrenal medulla and sural nerve (three animals in each group). Cell cultures were established from tissue not used in the grafts. Adrenal chromaffin cells either cocultured with sural nerve segments or exposed to exogenous NGF differentiated into a neuronal phenotype. Chromaffin cell survival, when cografted with sural nerve into the striatum, was enhanced four- to eightfold from between 8000 and 18,000 surviving cells in grafts of adrenal tissue only up to 67,000 surviving chromaffin cells in cografts. In grafts of adrenal tissue only, the implant site consisted of an inflammatory focus. Surviving chromaffin cells, which could be identified by both chromogranin A and tyrosine hydroxylase staining, retained their endocrine phenotype. Cografted chromaffin cells exhibited multipolar neuritic processes and numerous chromaffin granules, and were also immunoreactive for tyrosine hydroxylase and chromogranin A. Blood vessels within the graft were fenestrated, indicating that the blood-brain barrier was not intact. Additionally, cografted chromaffin cells were observed in a postsynaptic relationship with axon terminals from an undetermined but presumably a host origin.
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PMID:NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells. 238 81

Expression of chromogranin A in various neurological diseases was examined immunohistochemically using purified anti-human chromogranin A antiserum. The antibody stained dystrophic neurites in senile plaques in Alzheimer disease brain, Pick bodies and ballooned neurons in Pick's disease brain, some Lewy bodies in the substantia nigra of Parkinson's disease, and axonal swellings in various neurological conditions including Parkinson's disease, striatonigral degeneration, Shy-Drager syndrome, amyotrophic lateral sclerosis and cerebral infarction. The present study shows that expression of chromogranin A is not an exclusive feature of Alzheimer disease or Pick's disease, and indicates that it could be a useful marker for various neurological diseases.
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PMID:Expression of chromogranin A in lesions in the central nervous system from patients with neurological diseases. 804 89

Previous investigations have demonstrated that adrenal chromaffin cells survive poorly when grafted into the striatum of rodents, nonhuman primates, and patients with Parkinson's disease. This poor survival has been attributed to the low levels of endogenous NGF within the striatum. However, chromaffin cells isolated from the nonchromaffin constituents of the adrenal medulla (fibroblasts and endothelial cells) have recently been demonstrated to survive grafting into a number of CNS sites. The present study determined whether nonchromaffin constituents of the adrenal medulla may be responsible for poor graft survival. We compared the survival of intrastriatally grafted isolated bovine chromaffin cells with that observed following implantation of either perfused adrenal medullary suspensions containing all adrenal medullary cell types or isolated chromaffin cells that were then reseeded with autologous fibroblasts and endothelial cells. Implants of perfused adrenal medullary cells survived poorly and most graft sites were infiltrated with macrophages. The chromaffin cells in this group that did survive appeared to be in the process of degeneration. In contrast, large numbers of isolated chromaffin cells survived for up to 2 months following transplantation. These cells maintained their endocrine phenotype and stained for all enzymatic markers of catecholamine synthesis as well as chromogranin A. Morphologically, these cells resembled chromaffin cells seen in situ and the perigraft region was essentially devoid of macrophages. When isolated chromaffin cells were reseeded with autologous fibroblasts and endothelial cells, the implants degenerated and few, if any, surviving chromaffin cells were observed. Interestingly, these latter grafts induced a host-derived sprouting response of tyrosine hydroxylase-immunoreactive fibers. These data demonstrate that large numbers of adrenal chromaffin cells can survive intrastriatal implantation in the absence of exposure to exogenous NGF. Rather, the nonchromaffin cells of the adrenal medulla (fibroblasts and endothelial cells) appear to compromise the viability of grafted chromaffin cells. Once they are eliminated from the graft, robust survival of chromaffin cells occurs. If clinical trials employing adrenal medullary grafts are still to be considered for the treatment of Parkinson's disease, isolation of the chromaffin cells should be considered to enhance graft viability.
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PMID:Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability. 810 42

Lewy bodies commonly observed in brains with Parkinson's disease (PD) histochemically contain both protein and lipid as chemical components. Ultrastructurally, they are composed of filamentous, vesicular and granular structures. We investigated PD brains with light and electron microscopic immunohistochemistry using antibodies against two marker proteins for neuronal secretory vesicles, synaptophysin and chromogranin A. Both antibodies immunolabeled the peripheral zones and occasionally central cores of Lewy bodies of the classical and intraneuritic types. In addition, the diffuse immunolabeling was observed in Lewy bodies of the cortical type. Furthermore, the ultrastructural immuno-decoration was found mainly in the vesicular structures, and also in the filamentous and granular structures of Lewy bodies. Immuno-blot analysis of each antibody showed no difference between PD and normal control brains. The present observations suggest that vesicular profiles of Lewy bodies represent presynaptic and dense core secretory vesicles, and therefore that the lipid elements of Lewy bodies are derived from membrane lipids of these vesicles.
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PMID:Synaptophysin and chromogranin A immunoreactivities of Lewy bodies in Parkinson's disease brains. 813 Oct 84

Chromogranin A was purified from post-mortem human brain tissue, obtained at autopsy by a three step chromatography procedure to a single band purity on SDS gel electrophoresis at 68 kDa. Purified protein was further characterized by immunoblotting using a mouse anti-chromogranin A monoclonal antibody LK2H10, which recognizes the 68 kDa chromogranin A in human brain. The results demonstrate a simple protocol of preparing CgA from the human brain. Chromogranin plays a very important role in various neurological disorder and has been examined immunohistochemically in Alzheimer's disease, Parkinson's disease, Pick's disease. The procedure of purification may be useful in further defining its biological function, biochemistry and physiological significance in the central nervous system and may be useful in delineating the molecular pathology of certain neurological disorders.
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PMID:Purification and partial characterization of chromogranin-A from human brain. 909 Apr 64

Human cerebrospinal fluid (CSF) contains chromogranin A and B and secretogranin II which represent peptides secreted from neuronal large dense core vesicles. Within these vesicles these precursor peptides are at least partly processed to smaller peptides. We analysed the CSF levels of chromogranins/secretogranin by radioimmunoassay using specific antisera. The degree of their processing was characterized by molecular sieve column chromatography followed by radioimmunoassay. As previously shown secretogranin II is fully processed to smaller peptides including the peptide secretoneurin, whereas processing of chromogranin A was more limited. For chromogranin B we found in this study a high degree of processing comparable to that of secretogranin II. An analysis of CSF from patients with multiple sclerosis, essential tremor, Alzheimer and Parkinson disease, did not reveal any differences in proteolytic processing of chromogranins/secretogranin when compared to control CSF. We conclude that in the four diseases investigated there is no change in the proteolytic processing of the chromogranins/secretogranin within the large dense core vesicles. The absolute levels of chromogranins/secretogranin varied in CSF collected in different hospitals, however their relative ratios were remarkable constant. We suggest to use this ratio as a parameter to standardise CSF levels of other peptides, e.g. neuropeptides. In Parkinson patients the chromogranin A/secretogranin II ratio was significantly increased whereas in Alzheimer patients and those with essential tremor and multiple sclerosis no change of the ratios was observed. Apparently there are only limited changes in the biosynthesis, processing, secretion and CSF clearance of these peptides in pathological conditions.
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PMID:Levels and proteolytic processing of chromogranin A and B and secretogranin II in cerebrospinal fluid in neurological diseases. 958 59

alpha-Synuclein is presynaptic nerve terminal protein and its immunoreactivity has been observed in such neurodegenerative structures as senile plaques of Alzheimer's disease or Lewy bodies of Parkinson's disease. The physiological role of alpha-synuclein is still unknown. It is speculated that alpha-synuclein may be expressed in brain tumors, especially in those showing neuronal differentiation. We examined the immunohistochemical localization of alpha-synuclein in 77 human brain tumors. alpha-Synuclein was widely distributed in the brain tumors showing neuronal differentiation. As a result, positive immunostaining for alpha-synuclein was observed in ganglioglioma, medulloblastoma, neuroblastoma, primitive neuroectodermal tumor, pineocytoma/pineoblastoma, and central neurocytoma. Compared with other neuronal markers, the positive ratio of alpha-synuclein was not as high as synaptophysin, microtubule-associated protein 2, neuron-specific enolase and tau, but it was higher than neurofilament and chromogranin A. The expression of synaptophysin was diffusely observed in the cytoplasm, cellular processes and nucleus in tumors showing neuronal differentiation; however, the expression of alpha-synuclein was predominantly observed in the cytoplasm of the tumors as well as in the cellular processes. On the other hand, non-neuronal brain tumors such as astrocytic tumors or meningiomas were totally negative for alpha-synuclein. In conclusion, the appearance of an alpha-synuclein-positive structure was not limited to neurodegenerative diseases, but could also be detected in neoplastic cells showing neuronal differentiation.
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PMID:alpha-Synuclein is expressed in a variety of brain tumors showing neuronal differentiation. 1067 22

The association with Parkinson's disease (PD) of adrenomedullary inclusions, known as 'hyaline globules' or 'adrenal bodies', has been reported for over 35 years. However, the common perception has been that adrenomedullary chromaffin cells cannot be recognized as pathological cells in PD. In the present study, we discovered that the number of adrenomedullary inclusions per unit area of the adrenal medulla was larger in PD and other Lewy body disorders (LBD) than in other neurological diseases and controls without any autonomic dysfunctions, and correlated with the duration of LBD. We also showed that the cells with adrenomedullary inclusions are all norepinephrine-secreting chromaffin cells. This was detected by PAS reaction following peroxidase immunohistochemistry of four proteins: chromogranin A, phenylethanolamine N-methyltransferase, S-100 protein and neurofilament protein. We also proved that the components of adrenomedullary inclusions are immunocytochemically different from those of Lewy bodies and Lewy-related neurites, as adrenomedullary inclusions were immunonegative to ubiquitin and alpha-synuclein as well as to the above four proteins. Therefore, contrary to current opinion, the norepinephrine-secreting adrenomedullary chromaffin cell is indeed another type of pathological cell in PD and other LBD.
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PMID:Increased norepinephrine-associated adrenomedullary inclusions in Parkinson's disease. 1574 21


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