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1.
《Brain & development》2021,43(10):1023-1028
BackgroundAromatic L-amino acid decarboxylase (AADC) deficiency, caused by a pathogenic variant in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disorder in which catecholamine and serotonin are not synthesized. From a large number of reports, it has been recognized that most affected patients show severe developmental delay in a bedridden state and are unable to speak. On the other hand, patients with a mild phenotype with AADC deficiency have been reported, but they number only a few cases. Therefore, the variation of phenotypes of the disease appears to be broad, and it may be challenging to diagnose an atypical phenotype as AADC deficiency.Case reportWe report novel compound heterozygous variants in DDC (c.202G > A and c.254C > T) in two sisters, whose main complaint was mild developmental delay, by whole-exome sequencing (WES). Additionally, we describe their clinical features and provide an image that shows the variants located at different sites responsible for the catalysis of AADC in a three-dimensional structure. The patients were prescribed a Monoamine oxidase (MAO) inhibitor after diagnosis.InterpretationOur cases indicate that a comprehensive genomic approach helps to diagnose AADC deficiency with atypical features, and underscore the significance of understanding the variations of this disorder for diagnosis and appropriate treatment. 相似文献
2.
《Saudi Dental Journal》2022,34(7):565-571
PurposeThis study aimed to evaluate the neuroprotective ability of the conditioned medium of stem cells from human exfoliated deciduous teeth (CM-SHED) to prevent glutamate-induced apoptosis of neural progenitors.Materials and methodsNeural progenitors were isolated from two-day-old rat brains, and the conditioned medium was obtained from a mesenchymal stem cell SHED. Four groups were examined: neural progenitor cells cultured in neurobasal medium with (N + ) and without (N-) glutamate and glycine, and neural progenitor cells cultured in CM-SHED with (K + ) and without (K-) glutamate and glycine.ResultsThe expression of GABA A1 receptor (GABAAR1) messenger RNA (mRNA) in neural progenitor measured by real-time quantitative PCR. GABA contents were measured by enzyme-linked immunosorbent assay, whereas the apoptosis markers caspase-3 and 7-aminoactinomycin D were analysed with a Muse® cell analyzer. The viability of neural progenitor cells in the K + group (78.05 %) was higher than the control group N- (73.22 %) and lower in the N + group (68.90 %) than in the control group. The K + group showed the highest GABA content, which significantly differed from that in the other groups, whereas the lowest content was observed in the N + group. The expression level of GABAAR1 mRNA in the K + group was the highest compared to that in the other groups. CM-SHED potently protected the neural progenitors from apoptosis.ConclusionsCM-SHED may effectively prevent glutamate-induced apoptosis of neural progenitors. 相似文献
3.
目的分析抗胰岛素抗体(IAA)、抗胰岛细胞抗体(ICA)和抗谷氨酸脱羧酶抗体(GADA)在患者中的分布情况及实验室指标的变化,探讨三种糖尿病相关抗体对疾病发生、发展变化的预示价值,为疾病治疗提供依据。方法分析2008-2018年在四川大学华西医院联合检测了IAA、ICA和GADA三种抗体患者的相关信息。将抗体阳性患者分为3个不同的年龄组(<40岁、40~59岁、>59岁),比较抗体检测结果组合在各年龄组间分布差异,分析抗体阳性患者疾病分布情况。以抗体阳性分组,分析三种抗体单项阳性组(单阳组)患者实验室指标检测结果的差异。结果三种抗体在不同年龄组间的分布差异无统计学意义(P>0.05);糖尿病患者人群IAA抗体单项阳性占65.08%;三种抗体主要存在于糖尿病患者中(占92.03%),其他疾病(如癌症、低血糖、系统性红斑狼疮)患者也可出现。碱性磷酸酶在IAA单阳组中的水平显著低于ICA单阳组(P<0.05);尿酸和肌酐在IAA单阳组中的水平显著高于GADA单阳组(P<0.05);球蛋白和肾小球滤过率在IAA单阳组水平显著低于GADA单阳组(P<0.05);空腹胰岛素在IAA单阳组水平显著高于ICA和GADA单阳组(P<0.05)。结论IAA、ICA和GADA三种抗体在各年龄组分布相近。IAA可作为糖尿病抗体检测的首选指标,IAA阳性糖尿病患者更应该注意其并发肾功能损害的风险。 相似文献
4.
目的:检测胰岛素自身抗体(IAA)、胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GADA)和血清C肽,筛选出成年隐匿型自身免疫性糖尿病(LADA)对其进行早诊断、早治疗。方法:采用ELISA法检测188例初诊糖尿病患者血清IAA、ICA和GADA,化学发光法检测空腹和餐后C肽。结果:阳性组50例患者中,GADA阳性率(16.0%)高于ICA阳性率(12.2%)和IAA阳性率(7.4%)。双抗体阳性率为6.9%,三抗体阳性率为1.1%。抗体阳性患者的空腹和餐后C肽明显低于抗体阴性患者,双抗体和三抗体阳性患者的空腹和餐后C肽低于单抗体阳性患者。结论:自身抗体阳性患者的胰岛功能明显低于阴性患者。双抗体或三抗体的阳性患者,其胰岛功能丧失的更多。通过三抗体联合检测在初诊糖尿病患者中筛选LADA,对其早诊断早治疗具重要意义。 相似文献
5.
K. Rinsho K. Uchida S. Samma R. Ovasu 《Journal of cancer research and clinical oncology》1988,114(3):231-234
Summary We previously demonstrated that repeated intravesical instillation of DFMO, an irreversible inhibitor of ornithine decarboxylase, inhibits (or retards) urinary bladder carcinogenesis in rats. The present investigation was conducted to determine if high intraluminal concentration of DFMO alters initiation by MNU and to determine if DFMO inhibition is due to arrest of tumor progression or simply retardation of the tumor development. Results showed that the inhibitory effects demonstrated by DFMO treatment during the early phase of study disappeared as the observation period was extended. Failure to suppress tumor development might be due to failure to control intracellular polyamine levels below the critical level and this failure in turn might be due to the rapid fall of intravesical DFMO concentration following instillation.Abbreviations DFMO
-difluoromethylornithine
- HTB
heterotopically transplanted rat urinary bladder
- MNU
N-methyl-N-nitrosourea
- ODC
ornithine decarboxylase
Supported by NIH grant CA 33511 相似文献
6.
7.
Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens. 总被引:2,自引:0,他引:2
S Bo G Menato S Pinach A Signorile C Bardelli A Lezo B Marchisio L Gentile M Cassader M Massobrio G Pagano 《Diabetic medicine》2003,20(1):64-68
AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful. 相似文献
8.
Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies 总被引:7,自引:0,他引:7
Helicobacter pylori infects the stomach of half of the human population worldwide and causes chronic active gastritis, which can lead to peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The host immune response to the infection is ineffective, because the bacterium persists and the inflammation continues for decades. Bacterial activation of epithelial cells, dendritic cells, monocytes, macrophages, and neutrophils leads to a T helper cell 1 type of adaptive response, but this remains inadequate. The host inflammatory response has a key functional role in disrupting acid homeostasis, which impacts directly on the colonization patterns of H pylori and thus the extent of gastritis. Many potential mechanisms for the failure of the host response have been postulated, and these include apoptosis of epithelial cells and macrophages, inadequate effector functions of macrophages and dendritic cells, VacA inhibition of T-cell function, and suppressive effects of regulatory T cells. Because of the extent of the disease burden, many strategies for prophylactic or therapeutic vaccines have been investigated. The goal of enhancing the host's ability to generate protective immunity has met with some success in animal models, but the efficacy of potential vaccines in humans remains to be demonstrated. Aspects of H pylori immunopathogenesis are reviewed and perspectives on the failure of the host immune response are discussed. Understanding the mechanisms of immune evasion could lead to new opportunities for enhancing eradication and prevention of infection and associated disease. 相似文献
9.
11C‐PE2I and 18F‐Dopa PET for assessing progression rate in Parkinson's: A longitudinal study 下载免费PDF全文
10.
Dimitrios Stagos Gregorios D. Amoutzias Antonios Matakos Argyris Spyrou Aristides M. Tsatsakis Dimitrios Kouretas 《Food and chemical toxicology》2012
Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity. 相似文献