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991.
Ewa Jamroz Justyna Paprocka Maria Sokół Ewa Popowska Elżbieta Ciara 《Neurologia i neurochirurgia polska》2013,47(3):283-289
Ornithine transcarbamylase (OTC) deficiency, an X-linked, semidominant disorder, is the most common inherited defect in ureagenesis, resulting in hyperammonaemia type II. The OTC gene, localised on chromosome X, has been mapped to band Xp21.1, proximate to the Duchenne muscular dystrophy (DMD) gene. More than 350 different mutations, including missense, nonsense, splice-site changes, small deletions or insertions and gross deletions, have been described so far. Almost all mutations in consensus splicing sites confer a neonatal phenotype. Most mutations in the OTC gene are ‘private’ and are distributed throughout the gene with a paucity of mutation in the sequence encoding the leader peptide (exon 1 and beginning of exon 2) and in exon 7. They have familial origin or occur de novo. Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remainder probably occur within the introns or in regulatory domains. The authors present a 4-year-old boy with the unreported missense mutation c.802A>G. The nucleotide transition leads to amino acid substitution Met to Val at codon 268 of the OTC protein. 相似文献
992.
Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors. 相似文献
993.
Tsuyoshi Yamaguchi Hui‐Ling Wang Marisela Morales 《The European journal of neuroscience》2013,38(11):3602-3610
Dopaminergic neurons of the substantia nigra compacta (SNC), ventral tegmental area (VTA) and retrorubral field (RRF) play a role in reward, motivation, learning, memory, and movement. These neurons are intermingled with GABAergic neurons. Recent evidence shows that the VTA contains glutamatergic neurons expressing vesicular glutamate transporter type 2 (VGluT2); some of them co‐express tyrosine hydroxylase (TH). Here, we used a combination of radioactive in situ hybridisation and immunohistochemistry to explore whether any of the vesicular glutamate transporters [vesicular glutamate transporter type 1 (VGluT1), VGluT2, or vesicular glutamate transporter type 3 (VGluT3)] were encoded by neurons in the SNC or RRF. We found expression of VGluT2 mRNA, but not of VGluT1 or VGluT3, in the SNC and RRF. These VGluT2 neurons rarely showed TH immunoreactivity. Within the SNC, the VGluT2 neurons were infrequently found at the rostral level, but were often seen at the medial and caudal levels intercalated in the mediolateral portion of the dorsal tier, at a ratio of one VGluT2 neuron per 4.4 TH neurons. At this level, VGluT2 neurons were also found in the adjacent substantia nigra reticulata and substantia nigra pars lateralis. Within the RRF, the VGluT2 neurons showed an increasing rostrocaudal gradient of distribution. The RRF proportion of VGluT2 neurons in relation to TH neurons was constant throughout the rostrocaudal levels, showing an average ratio of one VGluT2 neuron per 1.7 TH neurons. In summary, we provide evidence indicating that the SNC and RRF, which are traditionally considered to be dopaminergic areas, have neurons with the ability to participate in glutamate signaling. 相似文献
994.
995.
Zhenzhen Xu Hongyan Wu Hongmei Zhang Jianying Bai Zhihong Zhang 《Journal of applied toxicology : JAT》2020,40(9):1210-1218
996.
Thaís Pasqualli Pamella Eduardha E Chaves Lavínia da Veiga Pereira Élvio Adílio Serpa Luís Flávio Souza de Oliveira Michel Mansur Machado 《Clinical and experimental pharmacology & physiology》2020,47(10):1751-1757
One of the most widely used sweeteners in the world is sucralose. With sweetening power 600 times greater than sucrose, its use grows among those who seek to cut calories. Research shows that when heated, sucralose generates toxic products that attack the organism and interact with DNA. Our objective was to test this sweetener under unheated conditions and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. For this purpose, we made use of lymphocyte cultures and the analysis of their CD3+, CD4+, and CD8+ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. Our results showed that sucralose reduces non-selectively the total lymphocytes due to falls in the levels of the CD4+, CD8+, and CD4+CD8+ subpopulations. We observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that sucralose modulates the gene expression, interfering especially with the MAPK8, APTX, and EID1 genes. This article presents the results of an evidence-based approach to the safety of human health in the use of sucralose. Finally, this study points out that sucralose has cytotoxic, genotoxic, and mutagenic effects in the concentrations and conditions tested in human lymphocyte cell culture. 相似文献
997.
目的 通过研究雷替曲塞抑制裸鼠MGC-803胃癌移植瘤的生长,初步探讨其相关作用机制。方法 建立人胃癌裸鼠皮下移植瘤模型,把24只裸鼠随机分为3 组,每组8只。对照组(生理盐水),低剂量组(雷替曲塞5 mg/kg),高剂量组(雷替曲塞12 mg/kg)。每周经腹腔注射给药2次,持续2周。详细记录裸鼠精神状态、体重以及肿瘤生长情况,免疫组化法检测裸鼠肿瘤组织Ki67及PCNA蛋白表达,并通过Western blottting法检测裸鼠肿瘤组织Caspase-3及Bax蛋白表达。结果 治疗期间雷替曲塞低剂量组和高剂量组裸鼠体重均低于对照组,低剂量组、高剂量组的抑瘤率分别为27.54%、44.20%,差异有统计学意义(P<0.05);免疫组化法显示低剂量组、高剂量组Ki67阳性细胞率分别为58.95%、42.16%,PCNA阳性细胞率分别为51.36%、37.27%,均明显低于对照组(P<0.05);Western blotting法表明低剂量组、高剂量组Caspase-3和Bax蛋白表达均明显高于对照组(P<0.05)。结论 雷替曲塞可抑制人胃癌裸鼠移植瘤的生长增殖,其机制可能与提高Caspase-3和Bax蛋白表达、从而促进细胞凋亡有关。 相似文献
998.
ObjectiveRadiology is a finite health care resource in high demand at most health centers. However, anticipating fluctuations in demand is a challenge because of the inherent uncertainty in disease prognosis. The aim of this study was to explore the potential of natural language processing (NLP) to predict downstream radiology resource utilization in patients undergoing surveillance for hepatocellular carcinoma (HCC).Materials and MethodsAll HCC surveillance CT examinations performed at our institution from January 1, 2010, to October 31, 2017 were selected from our departmental radiology information system. We used open source NLP and machine learning software to parse radiology report text into bag-of-words and term frequency–inverse document frequency (TF-IDF) representations. Three machine learning models—logistic regression, support vector machine (SVM), and random forest—were used to predict future utilization of radiology department resources. A test data set was used to calculate accuracy, sensitivity, and specificity in addition to the area under the curve (AUC).ResultsAs a group, the bag-of-word models were slightly inferior to the TF-IDF feature extraction approach. The TF-IDF + SVM model outperformed all other models with an accuracy of 92%, a sensitivity of 83%, and a specificity of 96%, with an AUC of 0.971.ConclusionsNLP-based models can accurately predict downstream radiology resource utilization from narrative HCC surveillance reports and has potential for translation to health care management where it may improve decision making, reduce costs, and broaden access to care. 相似文献
999.
Patrick Kennedy Sandra Monteiro Gordon Yip Fernando Gastaldo 《Journal l'Association canadienne des radiologistes》2019,70(2):204-209
PurposeThe purpose of this study is to introduce the aortic bulge sign, a finding observed retrospectively on computed tomography prior to the acute presentation of aortoenteric fistula, and to determine its interobserver reliability.MethodsFollowing research ethics board approval, all cases of aortoenteric fistula at our institution occurring from 2011–2015 were identified retrospectively. All previous computed tomography images of patients who eventually developed aortoenteric fistula were reviewed by a single observer for the presence of a potentially predictive finding of fistulization, the aortic bulge sign. These previous images were then combined with age and sex matched controls into a case bank. Eight radiology residents and staff were instructed in observing the aortic bulge sign. These observers then reviewed the case bank in a blinded analysis to determine the interobserver reliability of this finding.ResultsFourteen cases of aortoenteric were identified. The average patient age was 70.71 years with a male-to-female ratio of 11:3. Eleven patients had previous computed tomography images available for review. With blinded analysis by multiple observers, the aortic bulge sign was identified with greater than 80% agreement in six of 11 cases (66.67%). Fleiss' kappa was calculated at k = 0.60 (95% confidence interval 0.50–0.69), corresponding to moderate-to-substantial interobserver agreement.ConclusionsThe aortic bulge sign has been retrospectively identified as a promising computed tomography finding of eventual aortoenteric fistula prior to acute presentation. Further study is required to determine the diagnostic value of this sign. 相似文献
1000.