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 objectives of this review are, first, to summarize results from clinical trials on patients with Parkinson's disease using grafts of either adrenal medulla or fetal substantia nigra and, second, to discuss some of the scientific issues that need to be clarified in more detail before transplantation can become a real therapeutic alternative in Parkinson's disease. Adrenal medulla autotransplantation using open microsurgery has been shown to effect a modest reduction of the duration and severity of off periods in about 30-50% of operated patients and to have a high morbidity and mortality rate. The mechanisms of improvement are unknown. It is concluded that adrenal medulla autotransplantation is an experimental approach and not a treatment for Parkinson's disease. Animal experimental data clearly favour the use of fetal dopamine (DA) neurons in patients, and clinical trials using such grafts are now going on in several countries. We have implanted human fetal mesencephalic tissue into the striatum in 6 patients. The findings indicate that fetal DA neurons can survive in the human parkinsonian brain and produce therapeutically valuable functional effects. Together with the solid animal experimental data the clinical observations support the idea that neural transplantation can be developed into an effective therapy in Parkinson's disease. However, it should be emphasized that such a treatment is presently not available and that further work is necessary to optimize the transplantation procedure, e.g. with respect to the yield of surviving DA neurons and the location and number of implantation sites to achieve the largest possible symptomatic improvement.
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PMID:Transplants in Parkinson's disease. 185 21

Schwann cells from transected peripheral nerve segments are known to produce nerve growth factor (NGF). We performed adrenal medullary grafts or cografts of adrenal medulla and sciatic nerve into the striatum of MPTP-treated young adult mice, and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host DA fibers using computerized image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers and neurochemical analysis with high performance liquid chromatography (HPLC). Adrenal medullary chromaffin cells cografted with sciatic nerve survived better than those in adrenal grafts alone; host DA fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. A large number of TH-IR surviving cells in cografted mice showed long neuronal processes which were rarely seen in the mice receiving adrenal graft alone. We conclude that cograft of adrenal medulla and sciatic nerve promotes intrinsic host DA fiber recovery better than adrenal medulla grafts alone, and that survivability of grafted chromaffin cell may promote host DA fiber recovery. Adrenal medullary autografts have been used in patients with Parkinson's disease; we suggest that if this approach is to be used in the future, methods to increase the survivability of grafted chromaffin cells, such as co-grafting with pieces of peripheral nerve, be considered to enhance the survivability of the chromaffin cells, which might be closely related to the functional recovery of the patients by this grafting procedure. Of course, such strategies as the present cografting approach must be demonstrated to work in older animals using older donor tissue before proceeding to this next step in humans.
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PMID:Cografts of adrenal medulla with peripheral nerve enhance the survivability of transplanted adrenal chromaffin cells and recovery of the host nigrostriatal dopaminergic system in MPTP-treated young adult mice. 198 43

Adrenal to striatum transplants may be effective, but many technical issues are still debated. A procedure whereby a number of grafts were stereotactically placed at the putamen and caudatum is reported. It enables grafting deep nuclei, such as the putamen, the most denervated structure in Parkinson's disease, and allows a widespread spatial distribution of multiple grafts within these huge targets, conceivably enhancing the local release of neurotransmitters at the site or in the vicinity of the denervated receptors. It also enables the use of a sizeable volume of tissue, presumably a crucial but as yet unknown factor. Although preliminary, the present data seem to warrant further clinical trials.
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PMID:Multiloci stereotactic transplantation of autologous adrenal medullary tissue to the putamen and caudatum in Parkinson's disease. Technical note. 208 Mar 42

C57BL/6 mice show decreased dopaminergic fibers and dopamine concentration in the striatum following systemic injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). We have investigated the effect of adrenal medullary grafts into the striatum of young mice treated with MPTP. Enhanced recovery of the host nigrostriatal dopaminergic system was observed in those adrenal medullary grafted mice. However, this recovery was influenced by the survivability of grafted chromaffin cells and adrenal chromaffin cells from younger donors survived better than those from older donors. Since adrenal chromaffin cells contain several kinds of neurotrophic factors such as basic fibroblast growth factor and gangliosides, survivability of those grafted chromaffin cells may play an important role concerning recovery of the host intrinsic dopaminergic fibers. Adrenal medullary grafts to the patients with Parkinson's disease are currently under way in a large number of hospitals and we suggest more consideration be given to methods which lead to enhance the grafted chromaffin cell survival, since those survivability might be closely related to the functional recovery of these patients.
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PMID:[Adrenal medullary graft induces recovery of the host nigrostriatal dopaminergic system in MPTP-induced mouse model of Parkinson's disease]. 208 33

Following unilateral dopamine (DA) denervation of the striatum in animals, there is an asymmetry in the striatal DA system. Animals with such denervations will rotate vigorously when given dopaminergic drugs. Adrenal medulla grafts placed in the lateral ventricle adjacent to a DA-denervated striatum decrease rotational behaviour induced by DA receptor agonists or DA-releasing agents. This discussion reviews research on the use of adrenal medulla grafts to reverse behavioural deficits following DA-denervation of the striatum. Results from basic animal research and from the application of the procedure to patients with Parkinson's disease suggests that at least three different fundamental processes may mediate the functional effects of adrenal medulla grafts: (a) Adrenal medulla grafts may induce changes in the blood-brain barrier; (b) adrenal medulla grafts may induce an increase in serum DA; and (c) adrenal medulla grafts may have a trophic effect on the host brain. Hypotheses are proposed to explain the behavioural effects of adrenal medulla grafts in light of the processes that are thought to mediate their effects.
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PMID:Adrenal medulla graft induced recovery of function in an animal model of Parkinson's disease: possible mechanisms of action. 220 May 96

Adrenal medullary tissue can survive transplantation to the central nervous system. Such survival has been obtained experimentally with grafts to the anterior eye chamber, to the brain and to the spinal cord, using medullary tissue from the recipient animal or unrelated animals of the same or, in some cases, different species. Appropriately placed grafts have been shown, under certain conditions, to interact with the host nervous system, exerting behavioral effects including amelioration of experimentally-induced parkinsonian symptoms. Such effects may be enhanced by administration of nerve growth factor to the grafts. On the basis of such findings, adrenal medullary tissue has been grafted to the brain of Parkinson's disease patients. Both animal and human experiments raise important questions about mechanisms of graft action and about factors that influence the outcome of these procedures.
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PMID:Transplantation of adrenal tissue into the central nervous system. 228 48

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

Adrenal medullary catecholamines were measured in tissue samples from eight patients who underwent autologous transplantation of the adrenal medulla to the caudate nucleus as a treatment for Parkinson's disease. These adrenal catecholamine levels were compared to a group of patients of similar age who underwent unilateral nephrectomy for renal cell carcinoma. The levels of each catecholamine, expressed as nanomoles per milligram wet weight tissue, were significantly lower (P less than or equal to 0.005) in the parkinsonian patients than in the nephrectomy patients. These observations support data reported previously from autopsy specimens and suggest that the adrenal medullae of parkinsonian patients may be a compromised source of dopamine-producing tissue; this may limit its effectiveness in eliciting maximum clinical improvement following transplantation.
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PMID:Decreased adrenal medullary catecholamines in adrenal transplanted parkinsonian patients compared to nephrectomy patients. 272 24

We transplanted autologous adrenal medullary cells to the caudate nucleus in 3 patients with progressive supranuclear palsy, using the method Madrazo has employed for neural transplantation in Parkinson's disease. Major and minor complications occurred post-operatively from which the patients recovered. One patient had a marked improvement in his postural stability and a decreased incidence of falling. This change was evident at 1 month after surgery and has remained for the 6 months of follow-up. Postural reflexes were not altered in the other 2 patients. There was no change in extraocular movements, speech, or the rigid-bradykinetic features of parkinsonism in any patient. Adrenal medullary transplantation has only limited efficacy in progressive supranuclear palsy.
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PMID:Autologous adrenal medullary transplant in progressive supranuclear palsy. 276 1

Epinephrine and norepinephrine-containing chromaffin cells proliferate in the adrenal glands of normal adult rats throughout life. Moreover, their rate of proliferation is markedly increased by short-term administration of reserpine, one of many agents which in long-term experiments are associated with the development of adrenal medullary tumors. Current data suggest that chromaffin cell proliferation in the adult rat adrenal is mediated by the interaction of neurogenic and hormonal signals. Reserpine is known to directly deplete catecholamine stores, and to reflexively increase the activity of the splanchnic nerve endings innervating the adrenal medulla to stimulate both secretion and synthesis of catecholamines and other secretory granule constituents. Its effect on chromaffin cell proliferation suggests that the same signals may regulate chromaffin cell number to meet physiological needs. The reserpine model might shed light on signal transduction mechanisms which normally promote or prevent proliferation of chromaffin cells and of other neuroendocrine cells during development or in adult life, and on ways in which such mechanisms are altered in the course of the development and progression of tumors. It also suggests the possibility that chromaffin cells might be propagated in vitro for use in basic biological studies or in transplants for the treatment of Parkinson's disease.
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PMID:Chromaffin cell proliferation in the adult rat adrenal medulla. 281 83


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