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991.
Tezak Z Prandini P Boscaro M Marin A Devaney J Marino M Fanin M Trevisan CP Park J Tyson W Finkel R Garcia C Angelini C Hoffman EP Pegoraro E 《Human mutation》2003,21(2):103-111
Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients. 相似文献
992.
Jun Nakayama Kiyohiko Angata Edgar Ong Tsutomu Katsuyama Minoru Fukuda 《Pathology international》1998,48(9):665-677
Polysialic acid is a developmentally regulated carbohydrate composed of a linear homopolymer of a-2,a-linked sialic acid residues. This unique glycan is mainly attached to the neural cell adhesion molecule (N-CAM) and implicated in many morphogenic events of the neural cells by modulating the adhesive property of N-CAM. Recently, the cDNA that encodes polysialyltransferase, which is responsible for the polysialylation of N-CAM, was successfully cloned from three mammalian species. This review focuses on the molecular cloning of human polysialyltransferase, designated PST. it then describes the number of enzymes actually required for the polysialylation of N-CAM using an in vitro polysialyltransferase assay. Comparisons between PST and another polysialyltransferase, sialyltransferase X (STX), are made and it Is demonstrated that both enzymes can independently form polysiatic acid In vitro , but that during neural development they coordinately but distinctly synthesize polysialic acid on N-CAM. The role of polysialic acid in the central nervous system is also discussed. Finally, evidence that the two polysialyltransferases, PST and STX, apparently have distinct roles in the development of neural cells is provided by using a neurite outgrowth assay. 相似文献
993.
Norio Niikawa 《Journal of human genetics》1996,41(4):351-361
Summary Genomic imprinting is a biological phenomenon determined by an evolutionally acquired, underlying system that may control harmonious development and growth in mammals. It is also relevant to some genetic disorders in man. In this article, lines of biological evidence of imprinting, characteristics of the mouse and human imprinted genes, and findings and mechanisms on the occurrence of several human imprinting disorders are reviewed. 相似文献
994.
经丝裂霉素C体外处理后,将IL-6基因转染的、高分泌的IL-6的B16黑色素瘤细胞制成瘤苗。结果发现,体内注射IL-6基因转染的瘤苗后,小鼠脾脏CTL活性、NK活性及IL-2诱导的LAK活性显著升高。经IL-6基因转染瘤苗体内治疗后,荷瘤小鼠的皮下肿瘤生长显著减慢、肺转移结节数显著降低、存活期显著延长,若同时合用低剂量IL-2,则上述治疗效果更好。可见IL-6基因转染的瘤苗能有效地通过诱导机体抗肿瘤免疫功能而发挥抗肿瘤作用,与低剂量IL-2合用后,IL-6基因转染的瘤苗的抗肿瘤效果更佳。 相似文献
995.
Anca Ram Qiuhe Cao Paul E. Keck Harrison G. Pope Koichi Otani Gerard Addonizio Susan L. McElroy Sunao Kaneko Michaela Redlichova Elliot S. Gershon Pablo V. Gejman 《American journal of medical genetics. Part A》1995,60(3):228-230
Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D2 receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG→TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. © 1995 Wiley-Liss, Inc. 相似文献
996.
痢疾杆菌免疫小鼠的GALT中T淋巴细胞亚群的应答状态 总被引:1,自引:2,他引:1
以鼠伤寒杆菌G30株为对照,应用间接免疫荧光法检测了痢疾杆菌福氏2a经口服及腹腔免疫后,小鼠派伊尔氏(PP)节结、肠系膜淋巴结(MLN)及脾脏(SPt)中L3T4~+、Lyt2~+T细胞亚群的变化;并以MTT比色法测定了ConA诱导的淋巴细胞增殖反应。实验发现:无论是口服还是腹腔途径,这两种细菌都诱导出基本相似的T淋巴细胞反应,即L3T4亚群在PP及MLN中均有显著升高,而Lyt2亚群均无明显变化;口服途径仅PP淋巴细胞的增殖反应有明显升高,腹腔途径主要为MLN出现淋巴细胞显著的增殖反应。提示:在痢疾菌感染免疫中以L3T4亚群起主要作用;PP作为粘膜免疫的诱导部位;经口途径主要诱导肠道局部淋巴细胞的免疫应答,经腹腔途径虽能诱导多部位免疫应答但有否抗粘膜感染保护作用尚待研究。 相似文献
997.
Okada K Sugiura T Kuroda E Tsuji S Yamashita U 《Clinical and experimental immunology》2001,124(3):406-413
The effects of chronic administration of phenytoin, a common anticonvulsive drug, on immune responses were studied in mice. Anti-keyhole limpet haemocyanin (KLH) IgE antibody response after KLH-immunization was enhanced in phenytoin-treated mice. Proliferative responses of spleen cells induced with KLH, concanavalin A (ConA), lipopolysaccharide and anti-CD3 antibody were reduced in phenytoin-treated mice. Accessory function of spleen adherent cells on ConA-induced T cell proliferative response was reduced in phenytoin-treated mice. KLH-induced IL-4 production of spleen cells was enhanced, while IFN-gamma production was reduced in phenytoin-treated mice. In addition, production of IL-1 alpha, but not IL-6 and IL-12 by spleen adherent cells from phenytoin-treated mice was reduced. Natural killer cell activity was reduced in phenytoin-treated mice. These results suggest that phenytoin treatment preferentially induces a Th2 type response. We also observed that plasma ACTH and corticosterone levels were increased in phenytoin-treated mice, and speculated that phenytoin might act directly and indirectly, through HPA axis activation, on the immune system to modulate Th1/Th2 balance. 相似文献
998.
Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT) locus 总被引:3,自引:0,他引:3
Miyao M Hosoi T Emi M Nakajima T Inoue S Hoshino S Shiraki M Orimo H Ouchi Y 《Journal of human genetics》2000,45(6):346-350
Calcitonin (CT), a calcium-regulating hormone, lowers the calcium level in serum by inhibiting bone resorption. Because CT
may play a role in the pathogenesis of osteoporosis, genetic variations in or adjacent to the CT gene may be associated with variations in bone mineral density (BMD). The present study examined the correlation between
a dinucleotide (cytosine-adenine; CA) repeat polymorphism at the CT locus and BMD in 311 Japanese postmenopausal women (mean age, 64.1 years). Seven alleles were present in this population;
each allele contained 10, 11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated the respective genotypes A10, A11, A16,
A17, A18, A19, and A20. The A10 and A17 alleles were the predominant alleles in the population studied. Z scores (a parameter
representing deviation from the age-specific weight-adjusted average BMD) were compared between individuals that possessed
one or two alleles of each genotype and those that did not possess the allele. Subjects who possessed one or two A10 alleles
had lower BMD Z scores than those who did not (lumbar 2–4 BMD Z score; −0.148 ± 1.23 vs 0.182 ± 1.54; P = 0.04). No significant relationships were observed between allelic status and background data or biochemical parameters.
The significant association observed between BMD and genetic variations at the CT locus implies that polymorphism at this locus may be a useful marker for the genetic study of osteoporosis.
Received: August 10, 2000 / Accepted: September 6, 2000 相似文献
999.
We found a glutamine/arginine polymorphism at codon 349 of the hBUBR1 gene, encoding a protein kinase required for spindle assembly checkpoint function. The observed heterozygosity was estimated
to be 45% in the Japanese population. This polymorphism may be helpful for genetic studies of many cancer types in which chromosomal
instability is observed.
Received: October 19, 1998 / Accepted: October 24, 1998 相似文献
1000.
To investigate the age-dependent functional importance of cholinergic neocortical inputs, and to explore whether cortical cholinergic denervation in aged animals might better model the cerebral metabolic changes of Alzheimer's disease, the effects of unilateral ablation of the nucleus basalis magnocellularis (NBM) on cerebral glucose metabolism were studied in young and aged rats. Regional cerebral metabolic rates for glucose (rCMRglc) were determined, using the [14C]deoxyglucose method, in 48 brain regions of 3- and 24-month old Fischer-344 rats at 3, 7, 14 and 28 days after stereotaxic injection of ibotenate into the right NBM, and in sham-operated animals at 3 and 14 days later. For both ages the peak effect of unilateral NBM ablation occurred 3 days later: in young rats, rCMRglc was significantly reduced (compared to the contralateral side) in all 24 anterior cortical areas examined (mean decline 20%), whereas in aged animals, only 9 of 24 areas showed a significant decline in glucose utilization, and the magnitude of rCMRglc reduction (9%) was smaller. Near complete recovery of rCMRglc occurred by 7 days in young and old rats. We conclude that the basalocortical cholinergic projection plays a smaller role in neocortical function of aged rats, possibly because its tonic activity is reduced. Both young and aged rats undergo cortical metabolic normalization after unilateral NBM ablation; hence the NBM-lesioned aged rat is not a better model of the progressive decline in rCMRglc that occurs in Alzheimer's disease. 相似文献