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51.
52.
A chromosomal breakage syndrome with profound immunodeficiency 总被引:5,自引:0,他引:5
The chromosomal breakage syndromes--ataxia-telangiectasia, Fanconi's anemia, and Bloom's syndrome--are associated with growth failure, neurologic abnormalities, immunodeficiency, and an increased incidence of malignancy. The relationship between these features is unknown. We recently evaluated a 21-year-old female with more severe chromosomal breakage, immunodeficiency, and growth failure than in any of the mentioned disorders. As of November 1985, the patient remains clinically free of malignancy. At age 18, the patient's weight was 22.6 kg (50th percentile for seven years), height was 129 cm (50th percentile for eight years), and head circumference was 42 cm (50th percentile for six months). Laboratory studies demonstrated a marked decrease in both B and T cell number and function. The peripheral blood contained 400 to 900 lymphocytes/microL with 32% T11 cells, 17% T4 cells, and 21% T8 cells. The proliferative responses to phytohemagglutinin (PHA), pokeweed mitogen, and concanavalin A were less than 10% of control. There were 1% surface IgM positive cells, and serum IgG was 185 mg/dL, IgM 7 mg/dL, IgA 5 mg/dL. In lymphocyte cultures stimulated with the T cell mitogens PHA, phorbol ester, and interleukin 2, 55% of the banded metaphases demonstrated breaks or rearrangements. The majority of the breaks involved four fragile sites on chromosomes 7 and 14, 7p13, 7q35, 14q11, and 14q32. These are the sites of the genes for the T cell-antigen receptor and the immunoglobulin heavy chain and are sites of gene rearrangement in lymphocyte differentiation. Epstein-Barr virus stimulated B cells and fibroblast cultures also demonstrated a high incidence of breaks, but the sites were less selective. These findings suggest that the sites of chromosomal fragility in the chromosomal breakage syndromes may be informative and that factors other than the severity of the immunodeficiency or the high incidence of chromosomal damage may contribute to the occurrence of malignancy in the chromosomal breakage syndromes. 相似文献
53.
Jeske NA Diogenes A Ruparel NB Fehrenbacher JC Henry M Akopian AN Hargreaves KM 《Pain》2008,138(3):604-616
Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. Furthermore, siRNA-mediated knock-down of AKAP150 expression led to a significant reduction in PKA phosphorylation of TRPV1 in cultured TG neurons. In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of an AKAP antagonist significantly reduced prostaglandin E2 sensitization to thermal stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor. 相似文献
54.
Previous work examining the neurobiological substrates of social cognition in healthy individuals has reported modulation of a social cognitive network such that increased activation of the amygdala, fusiform gyrus, and superior temporal sulcus are evident when individuals judge a face to be untrustworthy as compared with trustworthy. We examined whether this pattern would be present in individuals with schizophrenia who are known to show reduced activation within these same neural regions when processing faces. Additionally, we sought to determine how modulation of this social cognitive network may relate to social functioning. Neural activation was measured using functional magnetic resonance imaging with blood oxygenation level dependent contrast in 3 groups of individuals--nonparanoid individuals with schizophrenia, paranoid individuals with schizophrenia, and healthy controls--while they rated faces as either trustworthy or untrustworthy. Analyses of mean percent signal change extracted from a priori regions of interest demonstrated that both controls and nonparanoid individuals with schizophrenia showed greater activation of this social cognitive network when they rated a face as untrustworthy relative to trustworthy. In contrast, paranoid individuals did not show a significant difference in levels of activation based on how they rated faces. Further, greater activation of this social cognitive network to untrustworthy faces was significantly and positively correlated with social functioning. These findings indicate that impaired modulation of neural activity while processing social stimuli may underlie deficits in social cognition and social dysfunction in schizophrenia. 相似文献
55.
Kohler CG Loughead J Ruparel K Indersmitten T Barrett FS Gur RE Gur RC 《Schizophrenia Research》2008,99(1-3):286-293
OBJECTIVE: Earlier studies described gaze discrimination impairment in schizophrenia. The purpose of this study was to compare gaze discrimination abilities and associated brain activation in persons with stable schizophrenia and matched controls. METHODS: 13 schizophrenia and 12 healthy participants underwent a gaze discrimination task with face stimuli rotated at 0, 4 and 8 degrees deviation. During fMRI with BOLD imaging, subjects were asked to identify whether a face was making eye contact. Subject-level parameter estimates for BOLD signal change were entered into an orientation by group mixed effect repeated measures ANOVA. RESULTS: Gaze discrimination performance did not differ between groups. Patients showed decreased activation in areas of bilateral inferior frontal and occipital areas, and select temporo-limbic regions, including amygdala. Groups differed by activation patterns according to gaze deviation. In controls, faces with 4 degrees deviation produced higher activation in frontal and temporal regions. In patients, 0 degrees deviation produced increased activation in amygdala and areas of temporal neocortex. CONCLUSIONS: Despite similar gaze discrimination abilities, schizophrenia patients exhibit decreased brain activation in areas associated with executive, emotional and visual processing. Controls exhibited increased activation associated with the more difficult task in select frontal and temporal regions. Patients exhibited increased activation associated with direct gaze in temporal regions, which may relate to common symptoms. 相似文献
56.
Children who present with unilateral or bilateral swelling of the legs are often suspected of having a deep venous thrombosis. The incidence of deep venous thrombosis in children is low and lymphoedema may be a more appropriate diagnosis. Lymphoedema can be primary or secondary. In childhood, primary lymphoedema is more common and may be seen associated with other congenital abnormalities, such as cardiac anomalies or gonadal dysgenesis. Primary hypoplastic lymphoedema is the most often encountered type. It is more common in girls, especially around puberty, and is typically painless. Atypical presentations produce diagnostic confusion and may require imaging to confirm the presence, extent, and precise anatomical nature of the lymphatic dysplasia. This article describes four patients presenting with limb pain and reviews the clinical features and imaging options in children with suspected lymphoedema. 相似文献
57.
Classifying spatial patterns of brain activity with machine learning methods: application to lie detection 总被引:1,自引:0,他引:1
Davatzikos C Ruparel K Fan Y Shen DG Acharyya M Loughead JW Gur RC Langleben DD 《NeuroImage》2005,28(3):663-668
Patterns of brain activity during deception have recently been characterized with fMRI on the multi-subject average group level. The clinical value of fMRI in lie detection will be determined by the ability to detect deception in individual subjects, rather than group averages. High-dimensional non-linear pattern classification methods applied to functional magnetic resonance (fMRI) images were used to discriminate between the spatial patterns of brain activity associated with lie and truth. In 22 participants performing a forced-choice deception task, 99% of the true and false responses were discriminated correctly. Predictive accuracy, assessed by cross-validation in participants not included in training, was 88%. The results demonstrate the potential of non-linear machine learning techniques in lie detection and other possible clinical applications of fMRI in individual subjects, and indicate that accurate clinical tests could be based on measurements of brain function with fMRI. 相似文献
58.
Shivani Ruparel Kenneth M. Hargreaves Michael Eskander Spencer Rowan Jose F.A. de Almeida Linda Roman Michael A. Henry 《Pain》2013
Endogenous TRPV1 agonists such as oxidized linoleic acid metabolites (OLAMs) and the enzymes releasing them [eg, cytochrome P450 (CYP)] are up-regulated after inflammation in the rat. However, it is not known whether such agonists are elevated in human inflammatory pain conditions. Because TRPV1 is expressed in human dental pulp nociceptors, we hypothesized that OLAM-CYP machinery is active in this tissue type and is increased under painful inflammatory conditions such as irreversible pulpitis (IP). The aim of this study was to compare CYP expression and linoleic acid (LA) metabolism in normal vs inflamed human dental pulp. Our data showed that exogenous LA metabolism was significantly increased in IP tissues compared to normal tissues and that pretreatment with a CYP inhibitor, ketoconazole, significantly inhibited LA metabolism. Additionally, extracts obtained from LA-treated inflamed tissues evoked significant inward currents in trigeminal ganglia neurons and were blocked by pretreatment with the TRPV1 antagonist IRTX. Moreover, extracts obtained from ketoconazole-pretreated inflamed tissues significantly reduced inward currents in trigeminal ganglia neurons. These data suggest that LA metabolites produced in human inflamed tissues act as TRPV1 agonists and that the metabolite production can be targeted by CYP inhibition. In addition, immunohistochemical analysis of 2 CYP isoforms, CYP2J and CYP3A1, were shown to be predominately expressed in immune cells infiltrating the inflamed dental pulp, emphasizing the paracrine role of CYP enzymes in OLAM regulation. Collectively, our data indicate that the machinery responsible for OLAM production is up-regulated during inflammation and can be targeted to develop potential analgesics for inflammatory-induced dental pain. 相似文献
59.
NB Pitts KR Ekstrand The ICDAS Foundation 《Community dentistry and oral epidemiology》2013,41(1):e41-e52
60.
James Loughead E Paul Wileyto Kosha Ruparel Mary Falcone Ryan Hopson Ruben Gur Caryn Lerman 《Neuropsychopharmacology》2015,40(6):1311-1320
Brief abstinence from smoking impairs cognition, particularly executive function, and this has a role in relapse to smoking. This study examined whether working memory-related brain activity predicts subsequent smoking relapse above and beyond standard clinical and behavioral measures. Eighty treatment-seeking smokers completed two functional magnetic resonance imaging sessions (smoking satiety vs 24 h abstinence challenge) during performance of a visual N-back task. Brief counseling and a short-term quit attempt followed. Relapse during the first 7 days was biochemically confirmed by the presence of the nicotine metabolite cotinine. Mean percent blood oxygen level-dependent (BOLD) signal change was extracted from a priori regions of interest: bilateral dorsolateral prefrontal cortex (DLPFC), medial frontal/cingulate gyrus, posterior cingulate cortex (PCC), and ventromedial prefrontal cortex. Signal from these brain regions and additional clinical measures were used to model outcome status, which was then validated with resampling techniques. Relapse to smoking was predicted by increased withdrawal symptoms, decreased left DLPFC and increased PCC BOLD percent signal change (abstinence vs smoking satiety). Receiver operating characteristic analysis demonstrated 81% area under the curve using these predictors, a significant improvement over the model with clinical variables only. The combination of abstinence-induced decreases in left DLPFC activation and reduced suppression of PCC may be a prognostic marker for poor outcome, specifically early smoking relapse. 相似文献