목적 : 본 연구는 뇌졸중 환자의 Hemiplegic Motor Behavior Test(HMBT)에 대한 타당도와 신뢰도를 알아보고자 하였다. 연구방법 : 본 연구를 위하여 국립재활원에 입원한 34명의 뇌졸중 환자를 대상으로 Hemiplegic Motor Behavior Tests(HMBT)가 임상적으로 뇌졸중 환자의 운동기능을 평가하기에 적합한지 알아보고자 하였다. 기준관련 타당도 분석을 이용하여 일상생활동작 수행 정도(Modified Barthel Index: MBI), 기능적 독립 수준(Modified Rankin Scale: MRS)과 상지기능 수행 평가 도구인 Brunnstrom Stage Scale(BSS), Hand Movement Scale(HMS), 자세조절(Postural Assessment Scale for Stroke: PASS-MP/CP), 체간 조절(Trunk Control Test: TCT)과의 피어슨(Pearson correlation)상관관계를 알아보았다. HMBT의 측정자내 신뢰도(Inter-rater reliability)와 측정자간 신뢰도(Intra-rater reliability)를 알아보기 위하여 Kappa계수와 Intraclass Correlation Coefficient(ICC)를 구하였으며, HMBT항목들의 내적 일치도를 알아보기 위하여 Cronbach's alpha coefficient를 구하였다. 결과 : HMBT의 U/E, H/F에 대한 측정자내 신뢰도는 각각 Kappa=.960～.950, ICC=.995～.994이었으며, 측정자간 신뢰도는 Kappa=.959～.918, ICC=.990～.986으로 신뢰도는 높은 것으로 나타났고 내적일치도는 Cronbach's alpha=.931로서 매우 높게 나타났다. HMBT는 MBI(r=.64～.66), MRS(r=-.63～.71), HMS(r=.82), BSS-Arm/Hand(r=.81～.82)와도 높은 상관관계를 보였고 PASS-MP/CP(r=.42～.52), TCT(r=.55～.64)간에 유의한 상관관계가 있는 것으로 나타나 신뢰도와 타당도가 높은 것으로 나타났다. 결론 : 본 연구 결과에서 뇌졸중 환자를 위한 HMBT는 MBI, HMS, BSS, PASS-MP/CP, TCT, MRS에서 유의한 상관관계가 있는 것으로 나타났으며, 높은 타당도와 신뢰도 및 내적 일치도를 보여 뇌졸중 환자의 실제적인 임상 평가도구로 활용이 가능할 것이다.

Human embryonic stem (hES) cells can be induced to differentiate into tyrosine hydroxylase expressing (TH+) cells that may serve as an alternative for cell replacement therapy for Parkinson's disease (PD). To examine in vitro differentiation of hES (MB03, registered in NIH) cells into TH+ cells, hES cells were induced to differentiate according to the 4-/4+ protocol using retinoic acid (RA), ascorbic acid (AA), and/or lithium chloride (LiCl) followed by culture in N2 medium for 14 days, during which time the differentiation occurs. Immunocytochemical stainings of the cells revealed that approximately 21.1% of cells treated with RA plus AA expressed TH protein that is higher than the ratio of TH+ cells seen in any other treatment groups (RA, RA+LiCl or RA+AA+LiCl). In order to see the differentiation pattern in vivo and the ability of in vitro differentiation-induced cells in easing symptomatic motor function of PD animal model, cells (2 10 cells/2) undergone 4-/4+ protocol using RA plus AA without any further treatment were transplanted into unilateral striatum of MPTP-lesioned PD animal model (C57BL/6). Following the surgery, motor behavior of the animals was examined by measuring the retention time on an accelerating rotar-rod far next 10 weeks. No significant differences in retention time of the animals were noticed until 2 weeks post-graft; however, it increased markedly at 6 weeks and 10 weeks time point after the surgery. Immunohistochemical studies confirmed that a reasonable number of TH+ cells were found at the graft site as well as other remote sites, showing the migrating nature of embryonic stem cells. These results suggest that in viかo differentiated hES cells relieve symptomatic motor behavior of PD animal model and should be considered as a promising alternative for the treatment of PD.

The purpose of this study is to evaluate an efficacy of in vitro differentiated human embryonic stem (hES, MB03) cells expressing Nurr1 in relief of symptomatic motor behavior of Parkinson's disease (PD) animal models MB03 was genetically modified to express Nurr1 protein and was induced to differentiate according to 2-/4+ protocol using retinoic acid and ascorbic acid. The differentiation-induced cells were selected for 10 to 20 days thereafter in N2 medium. Upon selection, cells expressing GFAP, TH, or NF200 were 38.8%, 11%, and 20.5%, respectively. in order to examine therapeutic effects of the differentiated cells in PD animal model, rats were unilaterally lesioned by administration of 6-kydroxydopamine HCI (6-OHDA) into medial forebrain region (MFB, AP -4.4 mm, ML 1.2 mm, DV 78 mm with incision bar set at -2.4 mm), as a reference to bregma and the surface of the skull. Confirmation of successful lesion by apomorphine-induced rotational behavior, differentiated cells were transplanted into the striatum (AP 1.0, ML 3.5, DV -5.0; AP 0.6, ML 2.5, DV -4.5). Improvements of asymmetric motor behavior by the transplantation were examined every two weeks after the surgery. In two weeks, numbers of rotation by the experimental rats were (P<0.05) of the number before transplantation, however, the ratio increased slightly to in six weeks. In contrast, the ratio of sham-grafted animals ranged from 112.3+8.5% to 139.2+28.9% during the examination. Immunohistochemical studies further confirmed the presence, survival, migration, and expression of TH of the transplanted human cells.

Main strategy for a treatment of Parkinson's disease (PD), due to a progressive degeneration of dopaminergic neurons, is a pharmaceutical supplement of dopamine derivatives or ceil replacement therapy. Both of these protocols have pros and cons; former exhibiting a dramatic relief but causing a severe side effects on long-term prescription and latter also having a proven effectiveness but having availability and ethical problems Embryonic stem (ES) cells have several characteristics suitable for this purpose. To investigate a possibility of using ES cells as a carrier of therapeutic gene(s), human ES (hES, MB03) cells were transfected with cDNAs coding for tyrosine hydroxylase (TH) in pcDNA3.1 (+) and the transfectants were selected using neomycin (250 ). Expression of TH being confirmed, two of the positive clone (MBTH2 & 8) were second transfected with GTP cyclohydrolase 1 (GTPCH 1) in pcDNA3.1 (+)-hyg followed by selection with hygromycin-B (150 ) and RT-PCR confirmation. By immune-cytochemistry, these genetically modified but undifferentiated dual drug-resistant cells were found to express few of the neuronal markers, such as NF200, -tubulin, and MAP2 as well as astroglial marker GFAP. This results suggest that over-production of BH4 by ectopically expressed GTPCH I may be involved in the induction of those markers. Transplantation of the cells into striatum of 6-OHDA- denervated PD animal model relieved symptomatic rotational behaviors of the animals. Immunohistochemical analyses showed the presence of human cells within the striatum of the recipients. These results suggest a possibility of using hES cells as a carrier of therapeutic gene(s).