Biomedical subjects

T Ohmoto

Publications and source records attributed to T Ohmoto.

314 records · Page 18Linked to original sources

PubMedDate not supplied

Preliminary report of polymer-encapsulated dopamine-secreting cell grafting into the brain.

Polymer-encapsulated dopamine-secreting cell grafting is one of the most promising approaches for the treatment of Parkinson's disease. We microencapsulated dopamine secreting PC12 cells into agarose/poly(styrene sulfonic acid) complex and grafted them into the xenogeneic brain without immunosuppression. Dopamine secretion from the encapsulated cells was confirmed by high-performance liquid chromatography (HPLC) analysis before grafting. A large number of encapsulated PC12 cells survived in the brain 1 mo after transplantation and these cells were immunoreactive to tyrosine hydroxylase (TH) antibody, suggesting that these cells were secreting dopamine into the brain. There was no apparent immunological rejection or tumor formation. We concluded that microencapsulated PC12 cells survive in the xenogeneic brain without immunosuppression, and this grafting procedure is expected to be applied for the treatment of Parkinson's disease in the near future in combination with stereotaxic thalamotomy or pallidotomy.

Animals↗

PubMedDate not supplied

Accumulation of cell cycle regulatory proteins, p21 and p27, induced after hyperthermia in human glioma cells.

It was investigated whether there was a relationship between p53 p21 and p27 induction pathways in the cellular response of glioma cells to hyperthermia. Two glioma cell lines were employed. A-172 cells had the wild-type of p53, and U251 cells had the mutant-type of p53. An adenovirus harbouring wild-type p53 was also used for the overexpression. The protein induction by hyperthermia was monitored by Western blot analysis. In U251 cells, the expression of wild-type p53 and hyperthermia had an additional cytotoxic effect, but did not affect A-172 cells. Significant p21 accumulation by hyperthermia was recognized in A-172 cells, and was also recognized in p53-transduced U251 cells. On the other hand, the accumulation of p27 by hyperthermia was not seen in A-172 or U251 cells, and the exogenous expression of p53 did not affect the accumulation of p27 by hyperthermia in U251 cells. These findings suggest that the p53-p21 pathway is involved in the signal transduction after hyperthermia, rather than the p27 pathway.

Adenoviridae↗

PubMedDate not supplied

VL thalamotomy for the treatment of tremor in patients with thalamic syndrome.

A 59-year-old female who underwent successful thalamotomy for tremor in thalamic syndrome was reported. Thalamic syndrome including tremor of the left limbs and slight dysesthesia over the left side of the face was thought to be due to the vascular lesion located in the right thalamus and adjacent structure by detailed radiological and electrophysiological examination. Significant alleviation of tremor was achieved by right VL thalamotomy without any complication.

Brain Diseases↗

PubMedDate not supplied

Long-term follow-up results of bilateral thalamotomy for parkinsonism.

27 patients who underwent bilateral thalamotomy for parkinsonism over the past 10 years have been clinically evaluated. Mean follow-up period was 6.2 years after second surgery. In these cases, 8 returned to full social life without any medication, 4 were capable of social life with medical treatment, 6 were self-sufficient and 3 were semi-self-sufficient in ADL, respectively. Therapeutic drug doses were reduced in all cases. L-Dopa-induced dyskinesia was not observed after second surgery. Speech disturbance, which was not severe, was recognized in 12 cases as a complication.

Adult↗

PubMedDate not supplied

Readiness potentials recorded from the scalp and depth leads.

Readiness potentials on voluntary hand movements were recorded from the scalp (C3, C4), premotor cortex, subcortical white matter and VL nucleus of the thalamus. Subjects were healthy right-handed men and patients with involuntary movement disorders. We obtained a slow negative shift of brain electrical potentials from the scalp and cortex preceding voluntary hand movements. The mean time interval between the onset of the readiness potential and the onset of motor activity (mean T) was 0.8 sec on right hand movements and 1.0 sec on left hand movements in healthy men. In cases with parkinsonism, the mean T value was 1.4 sec in patients with akinesia, 1.1 sec in those without akinesia. The amplitude of readiness potentials was higher in the scalp contralateral to the hand movement. The readiness potentials recorded from the VL nucleus and white matter were reversed in polarity from those of scalp and cortex. Simultaneous recordings from cortex and VL nucleus showed early onset of readiness potentials from the cortex by approximately 0.1 sec compared with the VL nucleus.

Brain Mapping↗

PubMedDate not supplied

Grafting of encapsulated dopamine-secreting cells in Parkinson's disease: long-term primate study.

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.

Animals↗

PubMedDate not supplied

Evaluation of intracerebral grafting of dopamine-secreting PC12 cells into allogeneic and xenogeneic brain.

The PC12 phenochromocytoma tumor cell line is derived from a rat adrenal medullary tumor and secretes dopamine. We have previously reported that grafted microencapsulated PC12 cells using agarose and poly (styrene sulfonic acid) survived in the xenogeneic brain without immunosuppression. To investigate whether unencapsulated PC12 cells form a tumor and how they provoke immunological reaction, PC12 cell suspension was implanted into the striatum of Sprague-Dawley rat (allogeneic graft) or guinea pig (xenogeneic graft) and histological analysis using Nissl stain and immunocytochemical analysis using antityrosine hydroxylase (TH) antibody were performed 1, 2, and 4 wk after transplantation. Host animals were not immunosuppressed. PC12 cells formed a mass 1 and 2 wk after transplantation both in allogeneic and xenogeneic brain. These grafted PC12 cells were immunoreactive to anti-TH antibody. Four weeks after transplantation, however, grafted PC12 cells in the allogeneic brain were only found within the restricted area near the site of implantation. In the xenogeneic brain, only the trace of grafted PC12 cells were found around the site of implantation 4 wk after transplantation. In both allogeneic and xenogeneic animals, a number of lymphocytes were found in and around the grafts at all period investigated. These findings indicate that PC12 cells could survive in the allogeneic or xenogeneic brain for 2 wk and were ultimately rejected by immunological reaction by 4 wk after transplantation. Implantation of encapsulated PC12 cells in the allogeneic or xenogeneic brain is considered a safe and effective method for delivering dopamine into the brain because PC12 cells will not form a tumor in the long-term even if capsules are damaged in some reason.

Animals↗

PubMedDate not supplied

Evaluation of reaction of primate brain to grafted PC12 cells.

Intrastriatal implantation of polymer-encapsulated PC12 cells, which constitute a dopaminergic cell line derived from rat pheochromocytoma, has proved useful for ameliorating parkinsonian symptoms in several kinds of animals. In considering the clinical application of this technique, we should make sure that PC12 cells are rejected completely by the host immune system in case the capsule breaks. In the present study, unencapsulated PC12 cells were injected into the brain of Japanese monkeys (Macaca fuscata). Histological [hematoxylin-eosin (H&E), Nissl] and immunocytochemical [tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP)] analyses were performed 1, 2, 4, and 8 weeks after transplantation. Also, encapsulated PC12 cells were transplanted into the brain of another group of Japanese monkeys to investigate the host reaction to the capsule and to confirm that the encapsulated PC12 cells continue to survive in the host brain. H&E and GFAP staining were performed 2, 4, and 8 weeks after transplantation. L-DOPA and dopamine release from the explanted capsules was measured by high performance liquid chromatography. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell grafted groups. Although the xenografted unencapsulated cells formed a small cluster at 1 and 2 weeks after implantation, very few and no viable PC12 cells remained at 4 and 8 weeks, respectively. The reaction of the host towards the xenograft gradually decreased. Encapsulated PC12 cells retrieved from the host brain were found to release L-DOPA and dopamine continuously even 8 weeks after implantation. The host reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells, and decreased with time. These results indicate that encapsulated PC12 cell transplantation is an effective and safe strategy for the treatment of Parkinson's disease.

Animals↗