Heart tissues of patients with PD or incidental Lewy body (LB) disease (ILBD) were examined by light and electron microscopy. LBs and alpha-synuclein-positive neurites were identified in the hearts from 9 of 11 patients with PD and from 7 of 7 patients with ILBD. LBs were present in both tyrosine hydroxylase-positive and -negative nerve processes, which are nerves of extrinsic sympathetic and intrinsic origin, respectively. These findings provide histologic evidence that the postganglionic sympathetic and intrinsic neurons in the heart are involved in the PD disease process.
Machado--Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration mapped to chromosome 14q32.1. The CAG expansions of the MJD1 gene was identified as the cause of the disease. We have analyzed 90 MJD individuals from 62 independent MJD families and found that the MJD1 repeat length is inversely correlated with the age of onset (r = -0.87). The MJD chromosomes contained 61-84 repeat units, whereas normal chromosomes displayed 14-34 repeats. In the normal chromosomes, 14 repeat units were the most common and the shortest. In association with the clinical anticipation of the disease, a parent--child analysis showed the unidirectional expansion of CAG repeats and no case of diminution in the affected family. The differences in CAG repeat length between parent and child and between siblings are greater in paternal transmission than in maternal transmission. Detailed analysis revealed that a large degree of expansion was associated with a shorter length of MJD1 gene in paternal transmission. On the other hand, the increments of increase were similar for shorter and longer expansion in maternal transmission. Among the three clinical subtypes, type I of MJD, with dystonia, showed a larger degree of expansion in CAG repeats of the gene and younger ages of onset than the other types.
Background and Purpose— Our aim was to study the efficacy of robotic therapy as an adjuvant to standard therapy during poststroke rehabilitation. Methods— Prospective, open, blinded end point, randomized, multicenter exploratory clinical trial in Japan of 60 individuals with mild to moderate hemiplegia 4 to 8 weeks post stroke randomized to receive standard therapy plus 40 minutes of either robotic or self-guided therapy for 6 weeks (7 days/week). Upper extremity impairment before and after intervention was measured using the Fugl–Meyer assessment, Wolf Motor Function Test, and Motor Activity Log. Results— Robotic therapy significantly improved Fugl–Meyer assessment flexor synergy (2.1±2.7 versus −0.1±2.4; P <0.01) and proximal upper extremity (4.8±5.0 versus 1.9±5.5; P <0.05) compared with self-guided therapy. No significant changes in Wolf Motor Function Test or Motor Activity Log were observed. Robotic therapy also significantly improved Fugl–Meyer assessment proximal upper extremity among low-functioning patients (baseline Fugl–Meyer assessment score <30) and among patients with Wolf Motor Function Test ≥120 at baseline compared with self-guided therapy ( P <0.05 for both). Conclusions— Robotic therapy as an adjuvant to standard rehabilitation may improve upper extremity recovery in moderately impaired poststroke patients. Results of this exploratory study should be interpreted with caution. Clinical Trial Registration— URL: http://www.umin.ac.jp/ . Unique identifier: UMIN000001619.
The T cell function of congenitally athymic nude mice and rats, as well as the severe immunodeficiency resulting from thymic dysplasia in humans, can be corrected by implantation of intact thymus or thymic epithelium (1-5). Either syngeneic or allogeneic thymic grafts are effective for reconstituting T cell functions in congenitally thymus-deficient rodents (6-10), although these functions are generally less effective than those of intact normal animals. Such reconstituted nude mice (grafted with allogeneic thymus or thymic epithelial cells) accept skin grafts from the syngeneic and the donor strain, whereas those derived from a third strain are vigorously rejected (4, 1 1).In the present experiments, attempts were made to reconstitute T cell functions of nude mice by transplantation of thymic rudiments obtained from embryonic rats. The results show that these grafted mice gained T cell-mediated immune function, and accepted skin grafts from the donor rat strain. These mice, however, developed severe multiple organ-localized autoimmune diseases showing features similar to the autoimmunity observed in the mice after neonatal thymectomy, as reported previously (12-16). Materials and MethodsThymic Rudiment Transplantation. The rudiments of the thymuses were aseptically dissected from 15-d-old F344/DuCcj (F344) or ACI/NMs (ACI) rat embryos or 14-d-old BALB/cAJcl (BALB/c) mouse embryos (observation of vaginal plug = day 0). Female BALB/~ nu/nu mice, 5 wk of age, (Clea Japan Inc., Tokyo, Japan) were grafted under each kidney subcapsule with two lobes of thymic rudiments. This was done with an orally controlled micropipette introduced through a dorsal incision exposing the kidney. All mice were housed in a conventional animal-care facility.Chromosome Analysis. Chromosome analysis of lymphoid cells of thymic grafts was carried out by the air-drying method (17). The cells were harvested from 5 BALB/c nu/nu mice 8 wk after grafting with F344 thymic rudiments. Colchicine (0.05 mg/g body weight) was injected subcutaneously 2 h before harvest. Cells were treated with 1% sodium citrate in water for 5 rain at 37°C, fixed in cold acetic acid/methanol (1:1), and then
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