Fetal tissue transplants in animal models of Huntington's disease: the effects on damaged neuronal circuitry and behavioral deficits

Accumulating evidence indicates that grafts of embryonic neurons achieve the anatomical and functional reconstruction of damaged neuronal circuitry. The restorative capacity of grafted embryonic neural tissue is most illustrated by studies with striatal tissue transplantation in animals with striatal lesions. Striatal neurons implanted into the lesioned striatum receive some of the major striatal afferents such as the nigrostriatal dopaminergic inputs and the gluatmatergic afferents from the neocortex and thalamus. The grafted neurons also send efferents to the primary striatal targets, including the globus pallidus (GP, the rodent homologue of the external segment of the globus pallidus) and the entopeduncular nucleus (EP, the rodent homologue of the internal segment of the globus pallidus). These anatomical connections provide the reversal of the lesion-induced alterations in neuronal activities of primary and secondary striatal targets. Furthermore, intrastriatal striatal grafts improve motor and cognitive deficits seen in animals with striatal lesions. Since the grafts affect motor and cognitive behaviors that are critically dependent on the integrity of neuronal circuits of the basal ganglia, the graft-mediated recovery in these behavioral deficits is most likely attributable to the functional reconstruction of the damaged neuronal circuits. The fact that the extent of the behavioral recovery is positively correlated to the amount of grafted neurons surviving in the striatum encourages this view. Based on the animal studies, embryonic striatal tissue grafting could be a viable strategy to alleviate motor and cognitive disorders seen in patients with Huntington's disease where massive degeneration of striatal neurons occurs.     

Emotional behavior and the brain.

Basic behaviors were defined as those controlled by the hypothalamus, and emotion and instinct were defined as the drives of such behaviors. A learning method showed that fear-escape is obtained from the medial hypothalamic area except for the ventromedial nucleus. It was suggested that some neural systems responsible for threat, attack, rush and retreat are overlapped in the ventromedial nucleus. Functions of the amygdala and the septum were discussed in relation to hypothalamic activity in emotional behavior. A behavioral sequence composed of stimulation, classical conditioning, drive, reward learning and behavior was discussed, and learning, anxiety in neuroses and Morita therapy were examined from the viewpoint of the behavioral sequence.     

The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome

Tenosynovial thickening within the confined space of the carpal tunnel is thought to be the cause of the carpal tunnel syndrome (CTS). However, little is known about the pathological mechanism of tenosynovial thickening. In this study, the role of prostaglandin E(2) (PGE(2)) and vascular endothelial growth factor (VEGF) (two representative molecules that can induce oedema by increasing vascular permeability) was analysed in CTS by using immunohistochemistry and enzyme-linked immunosorptive assay (ELISA). Expression of these molecules was compared with the patients' clinical histories and a temporary increase in production of these molecules was found in cells within the vessels and synovial lining during the intermediate phase of the syndrome when the histology of the tenosynovium changes from oedematous to fibrotic. Statistical analysis clearly demonstrated that there is a close correlation between the expression of PGE(2) and VEGF. Furthermore, immunohistochemical analysis with anti-proliferating cell nuclear antigen (PCNA) revealed that the area with distinct VEGF expression closely matched the area where endothelial cells, vascular smooth muscle cells, and synovial lining cells proliferate. In contrast, despite marked alteration in the extracellular matrix (ECM) component of the tenosynovium, the fibroblasts responsible for most ECM framework production do not proliferate during any phase of CTS. Histological analysis demonstrated that angiogenesis takes place only during the intermediate phase. Since clusters of capillaries and arterioles are often surrounded by type III collagen-rich, disorganized, degenerate connective tissue, which contains fewer fibroblasts than normal, angiogenesis appears to take place as a part of a regenerative reaction that results in fibrosis. These findings strongly indicate that both PGE(2) and VEGF are expressed in the tenosynovium in CTS during the intermediate phase and induce the histological changes seen in the tenosynovium.     

Novel polymorphism in the coding region of the IL-13 receptor alpha' gene: association study with atopic asthma in the Japanese population

Interleukin (IL)-4 and IL-13 play key roles in the development of atopic asthma. The IL-13 receptor (R) alpha' chain is a component of both IL-4R and IL-13R complexes. By screening the whole coding region of the IL-13Ralpha' gene for polymorphisms, we identified a new polymorphism at nucleotide position 1050 from the ATG start codon. The allelic frequency of the C/T polymorphism in the Japanese population was found to be 0.97:0.03. Because of the low frequency of the T allele, the association study failed to indicate any significant association between this polymorphism and atopic asthma in the Japanese population. Further studies are required in other racial groups with higher frequencies of this polymorphism to elucidate the association.     

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.     

Kinetics and staining properties of mast cells proliferating in rat small intestine tunica muscularis and subserosa following infection with Nippostrongylus brasiliensis

Mucosal mast-cell hyperplasia occurs in the rat small intestine mucosa after infection with Nippostrongylus brasiliensis. In the present study, the number of mast cells was found to increase in the muscularis and subserosa as well as in the mucosa of rat small intestines 2-3 weeks after infection with this nematode. Mast cells in the muscularis were stained blue by the alcian blue/safranin sequence and did not bind berberine sulfate. The staining was blocked when tissues were fixed in neutral formalin. The increase in mast cells was transient and gradually disappeared; the half-life was 40 days. After an intravenous administration of compound 48/80, mast cells in the muscularis did not discharge granules. The results indicate that these mast cells were of the mucosal type. The mast cell phenotype in the muscularis did not change even 12 weeks after infection. Mast cells in the subserosal tissue were first of the mucosal type as were those in muscularis. After 8-12 weeks, however, many subserosal mast cells became positive for berberine sulfate and safranin. These results show that mucosal-type mast cells do not undergo phenotypic changes during the period of observation when these cells appear in the muscularis but the phenotypic expression may change as the cells arise in subserosal tissue.