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81.
Graham Cocks Sarah Curran Priya Gami Dafe Uwanogho Aaron R. Jeffries Annie Kathuria Walter Lucchesi Victoria Wood Rosemary Dixon Caroline Ogilvie Thomas Steckler Jack Price 《Psychopharmacology》2014,231(6):1079-1088
Until now, models of psychiatric diseases have typically been animal models. Whether they were to be used to further understand the pathophysiology of the disorder, or as drug discovery tools, animal models have been the choice of preference in mimicking psychiatric disorders in an experimental setting. While there have been cellular models, they have generally been lacking in validity. This situation is changing with the advent of patient-specific induced pluripotent stem cells (iPSCs). In this article, we give a methodological evaluation of the current state of the iPS technology with reference to our own work in generating patient-specific iPSCs for the study of autistic spectrum disorder (ASD). In addition, we will give a broader perspective on the validity of this technology and to what extent it can be expected to complement animal models of ASD in the coming years. 相似文献
82.
Joel Jakobsson Maria Bjerke Carl Johan Ekman Carl Sellgren Anette GM Johansson Henrik Zetterberg Kaj Blennow Mikael Landén 《Neuropsychopharmacology》2014,39(10):2349-2356
Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs. 相似文献
83.
84.
Characterization of the effects of cultured vascular cells on the activation of blood coagulation 总被引:9,自引:0,他引:9
The coagulant properties of intact bovine vascular cells (aortic endothelial and smooth muscle cells) and human vascular cells (cutaneous and foreskin microvascular cells, umbilical venous endothelium) grown in vitro were studied. Compared to nonvascular cells (fibroblasts, corneal endothelial cells, fetal lung or intestinal mucosal cells), vascular cells had little procoagulant activity. Radioimmunologic measurement of thrombin in recalcified plasma demonstrated markedly lower concentrations of thrombin in the presence of vascular endothelial and smooth muscle cells compared to corneal endothelial and fetal lung cells. The low thrombin concentrations were not a consequence of thrombin binding to the vascular cells nor were they due to accelerated thrombin inactivation by antithrombin-III or alpha 2-macroglobulin. Neither vascular cells nor the nonvascular cells promoted contact activation of plasma as measured by a sensitive specific assay for kallikrein. Studies with intact cell monolayers and purified factors VIIa and X indicated that while nonvascular cells express tissue factor activity, vascular cells do not exhibit this property. These data suggest that the nonthrombogenic nature of intact vascular cells is due to their failure to initiate contact activation and to express tissue factor activity. In addition, the primary difference in coagulant potential between vascular cells and nonvascular cells is the lack of tissue factor expression by the vascular cells. 相似文献
85.
Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients. 相似文献
86.
Lindsay S. Womack William M. Sappenfield Cheryl L. Clark Washington C. Hill Robert W. Yelverton John S. Curran Linda A. Detman Vani R. Bettegowda 《Maternal and child health journal》2014,18(8):1893-1904
Non-medically indicated (NMI) deliveries prior to 39 weeks increase the risk of neonatal mortality, excess morbidity, and health care costs. The study’s purpose was to identify maternal and hospital characteristics associated with NMI deliveries prior to 39 weeks. The study included 207,775 births to women without a previous cesarean and 38,316 births to women with a previous cesarean, using data from Florida’s 2006–2007 linked birth certificate and inpatient record file. Adjusted risk ratios (ARR) and 95 % confidence intervals (CI) for characteristics were calculated using generalized estimating equation for multinomial logistic regression. Among women without a previous cesarean, NMI deliveries occurred in 18,368 births (8.8 %). Non-medically indicated inductions were more likely in women who were non-Hispanic white (ARR: 1.41, 95 % CI 1.31–1.52), privately-insured (ARR: 1.42, 95 % CI 1.26–1.59), and delivered in hospitals with <500 births per year. Non-medically indicated primary cesareans were more likely in women who were older than 35 years (ARR: 2.96, 95 % CI 2.51–3.50), non-Hispanic white (ARR: 1.44, 95 % CI 1.30–1.59), and privately-insured (ARR: 1.43, 95 % CI 1.17–1.73). Non-medically indicated primary cesareans were also more likely to occur in hospitals with <30 % nurse-midwife births, <500 births per year, and in large metro areas. Among women with previous cesarean, NMI repeat cesareans occurred in 16,746 births (43.7 %). Only weak risk factors were identified for NMI repeat cesareans. The risk factors identified varied by NMI outcome. This information can be used to inform educational campaigns and identify hospitals that may benefit from quality improvement efforts. 相似文献
87.
88.
Yoshio Okada PhD Sheraz Khan PhD Ashley Curran BS Banu Ahtam DPhil Matti S. Hämäläinen DSc Roger D. Traub MD Phillip L. Pearl MD 《Annals of neurology》2020,88(2):418-422
Neoplastic or dysplastic neuronal tissue in the brain stem and cerebellum can become epileptogenic in pediatric patients. However, it is unknown whether such tissue may transform intrinsic properties of the human cerebellum, making it capable of generating epileptic population activity. We noninvasively detected epileptiform signals unaveraged in a pediatric patient with epilepsy due to a tumor in the middle cerebellar peduncle. Analysis of generators of the signals revealed that the cerebellum ipsilateral and contralateral to the tumor was the dominant interictal spike generator and could initiate ictal activity, suggesting that human cerebellum may become capable of intrinsically generating epileptic activity. ANN NEUROL 2020;88:418–422. 相似文献
89.
Remote microphone systems for preschool-age children who are hard of hearing: access and utilization
Elizabeth A. Walker Maura Curran Meredith Spratford Patricia Roush 《International journal of audiology》2019,58(4):200-207
Objectives: Children who are hard of hearing (CHH) have restricted access to auditory-linguistic information. Remote-microphone (RM) systems reduce the negative consequences of limited auditory access. The purpose of this study was to characterise receipt and use of RM systems in young CHH in home and school settings.Design: Through a combination of parent, teacher, and audiologist report, we identified children who received RM systems for home and/or school use by 4?years of age or younger. With cross-sectional surveys, parents estimated the amount of time the child used RM systems at home and school per day.Study Sample: The participants included 217 CHH.Results: Thirty-six percent of the children had personal RMs for home use and 50% had RM systems for school. Approximately, half of the parents reported that their children used RM systems for home use for 1–2?hours per use and RM systems for school use for 2-4?hours per day.Conclusions: Results indicated that the majority of the CHH in the current study did not receive RM systems for home use in early childhood, but half had access to RM technology in the educational setting. High-quality research studies are needed to determine ways in which RM systems benefit pre-school-age CHH. 相似文献
90.
Matrix metalloproteinases in tumour invasion and metastasis. 总被引:47,自引:0,他引:47
The matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. The MMPs have been classified into different groups including collagenases, gelatinases, stromelysins, and others, particularly membrane-type MMPs, based mainly on the in vitro substrate specificity of individual MMPs. There is increasing evidence to indicate that individual MMPs have important roles in tumour invasion and metastasis. However, the current concept of the role of MMPs in tumour invasion is that they not only have a direct role in tumour invasion by facilitating extracellular matrix degradation, but as a consequence they also have an important role in maintaining the tumour micro-environment and thus promoting tumour growth. Inhibiting the action of MMPs represents a new therapeutic approach for the treatment of individual types of cancer and several broad-spectrum, low-molecular-weight MMP inhibitors are currently being assessed for clinical use. This review examines the role of MMPs in tumour invasion and metastasis, with an emphasis on studies of clinical relevance. 相似文献