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91.
Jihai Xu Jing Wu Xiaofeng Teng Libing Cai Huizong Yuan Xiaokun Chen Mu Hu Xin Wang Ning Jiang Hong Chen 《American journal of medical genetics. Part A》2020,182(9):2117-2123
Polydactyly and syndactyly are digital abnormalities in limb‐associated birth defects usually caused by genetic disorders. In this study, a five‐generation Chinese pedigree was found with triphalangeal thumb polysyndactyly syndrome (TPTPS), showing an autosomal dominant pattern of inheritance. We utilized linkage analysis and whole genome sequencing (WGS) for the genetic diagnosis of this pedigree. Linkage analysis was performed using a genome‐wide single nucleotide polymorphism (SNP) chip and three genomic regions were identified in chromosomes 2, 6, and 7 with significant linkage signals. WGS discovered a copy number variation (CNV) mutation caused by a large duplication region at the tail of chromosome 7 located in exons 1–5 of the LMBR1 gene, including the zone of polarizing activity regulatory sequence (ZRS), with a length of approximately 180 kb. A real‐time polymerase chain reaction (PCR) assay confirmed the duplication. The findings of our study supported the notion that large duplications including the ZRS caused TPTPS. Our study showed that linkage analysis in combination with WGS could successfully identify the disease locus and causative mutation in TPTPS, which could help elucidate the molecular mechanisms and genotype–phenotype correlations in polydactyly. 相似文献
92.
Inhibition of caspase 3 abrogates lipopolysaccharide-induced nitric oxide production by preventing activation of NF-kappaB and c-Jun NH2-terminal kinase/stress-activated protein kinase in RAW 264.7 murine macrophage cells 下载免费PDF全文
Chakravortty D Kato Y Sugiyama T Koide N Mu MM Yoshida T Yokochi T 《Infection and immunity》2001,69(3):1315-1321
The effect of caspase inhibitors on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 267.4 murine macrophage cells was investigated. Pretreatment of RAW cells with a broad caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), resulted in a striking reduction in LPS-induced NO production. Z-VAD-FMK inhibited LPS-induced NF-kappaB activation. Furthermore, it blocked phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not that of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases. Similarly, a caspase 3-specific inhibitor, Z-Asp-Glu-Val-Asp-fluoromethylketone, inhibited NO production, NF-kappaB activation, and JNK/SAPK phosphorylation in LPS-stimulated RAW cells. The attenuated NO production was due to inhibition of the expression of an inducible-type NO synthase (iNOS). The overexpression of the dominant negative mutant of JNK/SAPK and the addition of a JNK/SAPK inhibitor blocked iNOS expression but did not block LPS-induced caspase 3 activation. It was therefore suggested that the inhibition of caspase 3 might abrogate LPS-induced NO production by preventing the activation of NF-kappaB and JNK/SAPK. The caspase family, especially caspase 3, is likely to play an important role in the signal transduction for iNOS-mediated NO production in LPS-stimulated mouse macrophages. 相似文献
93.
94.
目的探讨脊肌萎缩症(SMA)的基因诊断方法.方法基于运动神经元生存基因(SMN)的两个同源拷贝碱基上的差异,应用PCR-酶切分析法对10例临床和病理诊断为Ⅰ、Ⅱ、Ⅲ型SMA的患者及其直系亲属16人、25例正常对照进行SMN基因检测.结果 10例SMA患者中9例患者缺失SMN第7、8号外显子,1例患者仅缺失第7号外显子;正常对照组及患者亲属均未发现外显子缺失.结论 PCR-酶切检测SMN基因第7号、8号外显子缺失是诊断儿童型脊肌萎缩症可靠的基因诊断方法. 相似文献
95.
鉴于热休克蛋白90β(hsp90β)基因内含子中含有维生素D3受体(VDR)结合位点,为探讨作为核受体家族成员的VDR是否对核受体特异分子伴侣的hsp90β基因的表达具有调控作用,我们开展了本项研究。分别将野生型VDR、含N端(1~133氨基酸残基)及C端(281~427氨基酸残基)片段的VDR突变体真核表达质粒与人hsp90β基因调控片段(-1039/+1531)介导的氯霉素乙酰基转移酶(CAT)报告基因质粒共转染Jurkat细胞,检测正常及经热休克(42℃,1h)处理后细胞裂解液中CAT活性。结果表明VDRN端增强、而C端抑制hsp90β的组成性表达;在热诱导条件下野生型VDR对hsp90β的表达有一定的抑制作用,而其C端片段的抑制较强。为进一步研究VDR对细胞内源性热休克基因表达的影响,我们用RTPCR方法研究了VDR的对细胞内hsp90β基因mRNA水平的影响,发现VDR过表达对hsp90β的热诱导表达明显抑制。结果提示VDR对hsp90β基因的组成性和热诱导表达的调控机制不同。 相似文献
96.
da Cunha JP Nakayasu ES Elias MC Pimenta DC Téllez-Iñón MT Rojas F Muñoz MJ Manuel M Almeida IC Schenkman S 《Molecular and biochemical parasitology》2005,140(1):75-86
Histone H1 of most eukaryotes is phosphorylated during the cell cycle progression and seems to play a role in the regulation of chromatin structure, affecting replication and chromosome condensation. In trypanosomatids, histone H1 lacks the globular domain and is shorter when compared with the histone of other eukaryotes. We have previously shown that in Trypanosoma cruzi, the agent of Chagas' disease, histone H1 is phosphorylated and this increases its dissociation from chromatin. Here, we demonstrate using mass spectrometry analysis that T. cruzi histone H1 is only phosphorylated at the serine 12 in the sequence SPKK, a typical cyclin-dependent kinase site. We also found a correlation between the phosphorylation state of histone H1 and the cell cycle. Hydroxyurea and lactacystin, which, respectively, arrest parasites at the G1/S and G2/M stages of the cell cycle, increased the level of histone H1 phosphorylation. Cyclin-dependent kinase-related enzymes TzCRK3, and less intensely the TzCRK1 were able to phosphorylate histone H1 in vitro. Histone H1 dephosphorylation was prevented by treating the parasites with okadaic acid but not with calyculin A. These findings suggest that T. cruzi histone H1 phosphorylation is promoted by cyclin dependent kinases, present during S through G2 phase of the cell cycle, and its dephosphorylation is promoted by specific phosphatases. 相似文献
97.
Su M Tokairin T Nishikawa Y Yoshioka T Takahashi O Watanabe H Doi Y Omori Y Yoshioka T Sageshima M Tanaka T Enomoto K 《Pathology international》2002,52(2):158-163
A rare case of rapidly growing osteosarcoma that developed in the uterine corpus of a 62-year-old woman is presented. The tumor occupied almost the entire pelvic cavity and extended into the abdominal cavity, with marked involvement of the intestines. Histopathologically, the tumor was composed of an osteoblastic component, accompanied by conspicuous bone formation, and a fibroblastic component. The tumor cells were positive for vimentin and osteocalcin, as well as desmin, alpha-smooth muscle actin and muscle-specific actin, but negative for h-caldesmon. The results indicated myofibroblastic differentiation in a part of the tumor. A review of 14 reported cases and our case of uterine osteosarcoma revealed that this tumor has a biologically aggressive nature, although its histopathological and immunohistochemical features are similar to those of osteosarcomas in soft tissue and bone. As the prognosis of patients with this tumor is poor, it is of importance to differentiate this tumor from other types of tumors arising from the uterine corpus. 相似文献
98.
99.
H Ishiko N Takeda K Miyamura N Kato M Tanimura K H Lin M Yin-Murphy J S Tam G F Mu S Yamazaki 《Virology》1992,187(2):748-759
Nucleotide substitutions in the viral-encoded proteinase 3C (3Cpro) region (549 nucleotides) of the RNA genome of a coxsackievirus A24 variant (CA24v), one of the agents causing acute hemorrhagic conjunctivitis (AHC), were studied using 32 isolates collected from the Eastern hemisphere in 1970-1989. Based on regression analysis of nucleotide differences among isolates, the nucleotide substitution rate of CA24v 3Cpro was estimated to be 3.7 x 10(-3)/nucleotide/year. A phylogenetic tree constructed by the modified unweighted pair group method using arithmetic averages (UPGMA) indicated that CA24v had evolved from a common ancestor which appeared in one focal place in November 1963 +/- 21 months, about 7 years before the first isolation of CA24v in Singapore. The tree also revealed that all the recent epidemic isolates in 1985-1989 including Asian and Ghanian strains diverged from each other after 1981. This finding is consistent with the evidence that AHC due to CA24v had been confined to Southeast Asia and the Indian subcontinent until 1985, then suddenly and explosively spread to other areas where no CA24v isolations had been reported. 相似文献
100.
Longitudinal study of the effects of maternal smoking on pulmonary function in children 总被引:21,自引:0,他引:21
I B Tager S T Weiss A Mu?oz B Rosner F E Speizer 《The New England journal of medicine》1983,309(12):699-703
We investigated the effects of maternal cigarette smoking on pulmonary function in a cohort of children and adolescents observed prospectively for seven years. A multivariate analysis revealed that after correction for previous forced expiratory volume in one second (FEV1), age, height, change in height, and cigarette smoking in the child, or adolescent, maternal cigarette smoking significantly lowered the expected average annual increase in FEV1 (P = 0.015). On the basis of this analysis, it is estimated that if two children have the same initial FEV1, age, height, increase in height, and personal cigarette-smoking history, but the mother of one has smoked throughout the child's life whereas the mother of the other has not, the difference in the change in FEV1 over time in the exposed child, as compared with that in the unexposed child, will be approximately 28, 51, and 101 ml after one, two, and five years, respectively, or a reduction of 10.7, 9.5, and 7.0 per cent, respectively, in the expected increase. These results suggest that passive exposure to maternal cigarette smoke may have important effects on the development of pulmonary function in children. 相似文献