| 1. |
- Hagell, Peter, et al.
(författare)
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Sequential bilateral transplantation in Parkinson's disease: effects of the second graft
- 1999
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156. ; 122:6, s. 1121-1132
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Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.
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| 2. |
- Odin, Elisabeth, 1955, et al.
(författare)
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Rapid method for relative gene expression determination in human tissues using automated capillary gel electrophoresis and multicolor detection
- 1999
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Ingår i: J Chromatogr B Biomed Sci Appl. - 1387-2273. ; 734:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate a direct and automated post-polymerase chain reaction (PCR) detection system to simultaneously determine the relative gene expression levels of nine cancer-related human genes. Total RNA was prepared from flash-frozen biopsies derived from human colorectal tumors or normal mucosa and reverse-transcribed to cDNA which was PCR-amplified using primer pairs corresponding to the studied genes. In each reaction, the forward primer was labeled with a fluorescent dye. The PCR products were pooled and an internal size standard with a uniquely colored fluorescent dye was added. The samples were then subjected to automated capillary gel electrophoresis. Fragment analysis software was used to calculate the relative gene expression using beta-actin as the reference gene. We found that automated capillary gel electrophoresis with multicolor detection is a rapid, accurate and highly reproducible method for separation and quantification of PCR-amplified cDNA.
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| 3. |
- Studer, Lorenz, et al.
(författare)
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Effects of brain-derived neurotrophic factor on neuronal structure of dopaminergic neurons in dissociated cultures of human fetal mesencephalon
- 1996
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Ingår i: Experimental Brain Research. - 0014-4819. ; 108:2, s. 328-336
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Tidskriftsartikel (refereegranskat)abstract
- Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of cultured fetal mesencephalic dopaminergic neurons of rat and human origin. In the present study, BDNF was tested for its ability to influence neuronal structure of dopaminergic neurons in dissociated cultures of human fetal ventral mesencephalon after 7 days in vitro. Following immunocytochemical staining for tyrosine hydroxylase, all surviving dopaminergic neurons were counted. Computer-assisted three-dimensional reconstructions of uniform randomly selected neurons cultured with 50 ng/ml BDNF (n = 120) or without BDNF (n = 80) were made. BDNF increased the number of surviving human dopaminergic neurons by 76%. Mean soma profile area was significantly enlarged by 18% in BDNF-treated neurons as compared to controls. Analysis of parameters of neuritic size and complexity in these cultures revealed that combined neuritic length, combined neuritic volume, and neuritic field area were increased by 60%, 125% and 129%, respectively, and the mean number of segments per cell was increased by 41%. A change in neurite complexity in BDNF-treated cultures was further confirmed by the Sholl's concentric sphere analysis. These results demonstrate that BDNF promotes development and differentiation of human fetal dopaminergic neurons in vitro.
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| 4. |
- Wenning, Gregor K, et al.
(författare)
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Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease
- 1997
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 42:1, s. 95-107
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Tidskriftsartikel (refereegranskat)abstract
- Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.
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