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11.
Globoid cell leukodystrophy (GLD, Krabbe disease) is a severe demyelinating disease caused by a genetic defect of beta-galactocerebrosidase (GALC). To date treatment to GLD is limited to hematopoietic stem cell transplantation. Experimental approaches by means of gene therapy in twitcher mouse, an authentic murine model of human GLD, showed significant but only marginal improvements of the disease. To clarify whether the introduction of GALC could provide beneficial effects on the oligodendrocytes in GLD, we transduced twitcher oligodendrocytes by stereotactically injecting recombinant retrovirus encoding GALC-myc-tag fusion gene into the forebrain subventricular zone of neonatal twitcher mouse. In vivo effects of exogenous GALC on twitcher oligodendrocytes were studied histologically by combined immunostaining for the myc-epitope and the oligodendroglial specific marker, pi form of glutathione-S-transferase, at around 40 days of age. We show here that GALC transduction led to dramatic morphological improvement of the twitcher oligodendrocytes comparing with those in untreated twitcher controls. This study provided direct in vivo evidence that GALC transduction could prevent or correct aberrant morphology of oligodendrocytes in GLD which may be closely related to the dysfunction and/or degeneration of oligodendrocytes and the demyelination in this disease. 相似文献
12.
Tsukasa Tsunoda Toshifumi Eto Takahito Tsurifune Shigeki Tokunaga Tatsuhiro Ishii Koichi Motojima Teiji Matsumoto Tohru Segawa Kazuhide Ura Hiroshi Fukui 《Pathology international》1991,41(10):763-770
A solid and cystic tumor (SCT) was located at the head of the pancreas in a 43-year-old Japanese male, and pancreatoduodenectomy was performed on the suspicion of papillary carcinoma or cystadenocarcinoma of the pancreas. The lesion, which measured 4.5 X 4.5 X 4.0 cm, was clearly demarcated by connective tissue. The cut surface showed solid grayish-white areas with central cystic degenerative changes. The solid areas consisted of small round cells proliferating in a small solid or a pseudopapillary pattern. The tumor cells partially invaded the surrounding normal pancreatic parenchyma. Immunohistochemical studies revealed positive staining for alpha-1-antitrypsin and neuron-specific enolase, but no staining for known pancreatic hormones. Moreover, ultrastructural studies showed the absence of zymogen granules and the presence of anullate lamellae and neurosecretory granules. On the basis of these findings, a diagnosis of SCT of the pancreas was established. In order to clarify the histogenesis and biological behavior of the tumor, it is necessary to accumulate and analyze similar cases, an endeavor which in turn will contribute to the successful management of this disease. Acta Pathol Jpn 41: 763-770, 1991. 相似文献
13.
Vascular tumors of the soft tissue display a wide spectrum of histologic features and biologic behavior. Flow cytometric DNA analysis was performed on 40 vascular tumors, including nine African endemic-type Kaposi's sarcomas, nine angiosarcomas, seven hemangiopericytomas, six glomus tumors, and nine capillary hemangiomas. Six of the nine angiosarcoma cases (67%) and one of the seven hemangiopericytomas cases (14%) were aneuploid. All benign vascular tumors and Kaposi's sarcomas were diploid. Clinically, five of the six angiosarcoma patients with aneuploidy died within 2 to 28 months, while the remaining patient, who had the smallest tumor (2 x 1 cm), survived more than 4 years after the initial diagnosis was made. All three angiosarcoma patients with diploidy died within 10 to 14 months. One hemangiopericytoma patient with aneuploidy died within 1 month. No cases of benign tumor recurred. These results suggest that most vascular tumors, which generally follow a benign clinical course, were diploid and that the majority of those with a poor outcome were aneuploid. However, flow cytometrically assessed DNA ploidy has no prognostic value in angiosarcomas or hemangiopericytomas. 相似文献
14.
An inhibition enzyme-linked immunosorbent assay (inhibition-ELISA) was developed for the quantitative determination of human IgG (Gm) allotypes using rabbit anti-Gm antisera, alkaline-phosphatase-conjugated goat anti-rabbit IgG and, as the calibrant, purified human myeloma proteins possessing the relevant Gm allotype. The assay is reproducible and can detect as little as 10 ng/ml of G1m(a), G2m(n) or G3m(st), and 100 ng/ml of G1m(f) or G3m(g). Using this assay, the "gene dosage effect" and "allelic balance" in healthy Japanese were studied. 相似文献
15.
Inhibition of skin xenograft rejection by depleting T-cell receptor alpha beta-bearing cells without T-cell receptor gamma delta-bearing cells or natural killer cells by monoclonal antibody. 总被引:1,自引:0,他引:1
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Y Nishimura M Eto T Maeda K Hiromatsu N Kobayashi K Nomoto Y Y Kong K Nomoto 《Immunology》1994,83(2):196-204
We compared the effects of in vivo administration of the anti-T-cell receptor (TCR) alpha beta monoclonal antibody (mAb) (H57-597) to those of the anti-CD3 mAb (145-2C11), with or without anti-NK1.1 mAb (PK136), on xenogeneic skin graft survival in mice. In anti-TCR alpha beta mAb-treated B6 mice, F344 rat skin grafts survived for about 54 days, whereas in anti-CD3 mAb-treated B6 mice with or without anti-NK1.1 mAb treatment grafts survived about 25 days. In anti-TCR alpha beta mAb-treated B6 mice, TCR alpha beta-bearing T-lymphocyte function was completely abrogated, although TCR gamma delta-bearing T-lymphocyte function was still intact on day 9. In the anti-CD3 mAb-treated mice, the functions of both types of T lymphocytes were completely abrogated. On day 32, when most of the skin xenografts had been rejected in the anti-CD3 mAb-treated mice, the functions of both T lymphocytes had recovered considerably, and could actually respond to F344 antigens. In contrast, the function of TCR alpha beta-bearing cells had only partially recovered in the anti-TCR alpha beta mAb-treated mice. Finally, natural killer (NK) activity in the anti-TCR alpha beta mAb-treated mice was intact on day 32, when rat skin grafts still survived. In contrast, NK activity in the anti-CD3 mAb plus anti-NK1.1 mAb-treated mice did not recover on day 32, when skin xenografts had already been rejected. These results suggest that TCR gamma delta-bearing T cells and NK cells by themselves, at least in the absence of TCR alpha beta-bearing T cells, do not mediate xenogeneic skin graft rejection in mouse/rat combinations. 相似文献
16.
Suppressive effect of hyperbaric oxygenation on immune responses of normal and autoimmune mice. 总被引:4,自引:0,他引:4
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We studied the effect of hyperbaric oxygenation (HBO) on immune responses in normal and autoimmune mice. Mice were exposed to HBO in an animal chamber at a pressure of 252.5 kPa for 1 h and once a day for 5 days. The immunization of C3H/He mice with sheep erythrocytes induced marked anti-sheep erythrocyte antibody response on day 7. However, this response was markedly suppressed in HBO-treated mice. The suppression is dependent on the duration of HBO and it works on the early and the late stage of antibody responses. HBO suppresses the development of both sheep erythrocyte-specific B cells and helper T cells after the immunization. Then, we tried to expose autoimmune mice to HBO. Spontaneous immunoglobulin production of NZB and MRL/lpr spleen cells was also significantly suppressed by HBO. Furthermore, long term HBO exposure results in the suppression of the development of autoimmune symptoms such as proteinuria, facial erythema and lymphadenopathy in MRL/lpr mice. All these results suggest that HBO is applicable for the treatment of autoimmune diseases. 相似文献
17.
Direct evidence for clonal destruction of allo-reactive T cells in the mice treated with cyclophosphamide after allo-priming. 总被引:3,自引:0,他引:3
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It has previously been reported that a single i.p. injection of 200 mg/kg cyclophosphamide (CP) 2 days after priming with 10(8) donor spleen cells (SC) leads to donor-specific skin allograft tolerance in H-2 compatible, multiminor antigen incompatible murine strain combinations. It is speculated that the i.v. injection of donor cells may result in synchronized proliferation of donor-reactive host T cells and subsequently administered CP may specifically destroy these proliferating T cells in the periphery. Although this unique action of CP is considered to be a principal mechanism in this method, direct evidence has not yet been obtained. In the present article, this in vivo destructive effect of CP is clearly demonstrated by assessing detailed kinetics of host-derived blastoid T cells and donor (Mls-1a)-reactive V beta 6+ T cells in the model system of C3H mice rendered tolerant to AKR. Frequencies of the blastoid cells and V beta 6+ cells, which increased as a result of AKR priming, decreased rapidly with the administration of CP. C3H mice, which received AKR SC alone, also exhibited partial deletion of V beta 6+ T cells, but both tempo and magnitude of decrease in the frequency of V beta 6+ cells were quite different from those of the C3H mice given AKR SC and CP, which showed more rapid and profound elimination of V beta 6+ T cells. In accordance with these kinetic studies, in vitro proliferative response to Mls-1a antigens was greatly impaired in mice treated with SC and CP, whereas a low but appreciable response was detected in mice given SC alone.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
18.
Reciprocal effects of apolipoprotein E alleles (ε2 AND ε4) on plasma lipid levels in normolipidemic subjects 总被引:2,自引:0,他引:2
A significantly lower frequency of the epsilon 2 allele and a significantly higher frequency of the epsilon 3 allele were found in the normolipidemic Japanese population than those in the normolipidemic Caucasian populations. We have compared plasma lipid variables among the apolipoprotein (apo) E phenotype groups and estimated the average effects of the three common alleles (epsilon 2, epsilon 3 and epsilon 4) on plasma lipid levels in normolipidemic subjects. Plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG, VLDL-cholesterol (C) and apo E levels were high in the apo E3/2 group, intermediate in the apo E3/3 group and low in the apo E4/3 group, whereas plasma total cholesterol (TC), low density lipoprotein (LDL)-C and high density lipoprotein (HDL)-C levels were low in the apo E3/2 group, intermediate in the apo E3/3 group and high in the apo E4/3 group. Furthermore, the epsilon 2 allele had an effect to increase the TG, VLDL-TG, VLDL-C and apo E levels and decrease the TC, LDL-C and HDL-C levels, whereas the epsilon 4 allele had an effect opposite to the epsilon 2 allele. These results indicate that the epsilon 2 and epsilon 4 alleles have the reciprocal effects on plasma lipid, lipoprotein and apo E levels. 相似文献
19.
Three novel mutations of the fibrillin-1 gene and ten single nucleotide polymorphisms of the fibrillin-3 gene in Marfan syndrome patients 总被引:8,自引:0,他引:8
Uyeda T Takahashi T Eto S Sato T Xu G Kanezaki R Toki T Yonesaka S Ito E 《Journal of human genetics》2004,49(8):404-407
Marfan syndrome (MFS) is an autosomal dominant disorder of the extracellular matrix. Allelic variations in the gene for fibrillin-1 (FBN1) have been shown to cause MFS. To date, over 550 mutations have been identified in patients with MFS and related connective tissue diseases. However, about a half of MFS cases do not possess mutations in the FBN1 gene. These findings raise the possibility that variants located in other genes cause or modify MFS. To explore this possibility, firstly we analyzed FBN1 allelic variants in 12 Japanese patients with MFS, and secondly we analyzed fibrillin-3 gene (FBN3) in patients without FBN1 mutations using conformation sensitive gel electrophoresis (CSGE) and direct sequencing analysis. We identified three novel FBN1 mutations and ten FBN3 single nucleotide polymorphisms (SNPs). In this report, we could not detect a responsible mutation of the FBN3 gene for MFS. Although the number of the cases in this report is small, at least these results suggest that disease-causing mutations in exon regions of the FBN3 gene are very rare in MFS.Nucleotide sequence data reported are available in the DDBJ/EMBL/GenBank databases under the accession numbers: AB177797, AB177798, AB177799, AB177800, AB177801, AB177802, AB177803 相似文献
20.