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1.
Jinjing Yang Xiaohu Li Renmin Yang Xuen Yu Changliang Yu Yinfeng Qian Yongqiang Yu 《PloS one》2015,10(4)
Purpose
It is well known that patients with Wilson’s disease (WD) suffer copper metabolism disorder. However, recent studies point to an additional iron metabolism disorder in WD patients. The purpose of our study was to examine susceptibility-weighted imaging (SWI) manifestations of WD in the brains of WD patients.Methods
A total of 33 patients with WD and 18 normal controls underwent conventional MRI (Magnetic resonance imaging) and SWI. The phase values were measured on SWI-filtered phase images of the bilateral head of the caudate nuclei, globus pallidus, putamen, thalamus, substantia nigra, and red nucleus. Student’s t-tests were used to compare the phase values between WD groups and normal controls.Results
The mean phase values for the bilateral head of the caudate nuclei, globus pallidus, putamen, thalamus, substantia nigra, and red nucleus were significantly lower than those in the control group (P < 0.001), and bilateral putamen was most strongly affected.Conclusions
There is paramagnetic mineralization deposition in brain gray nuclei of WD patients and SWI is an effective method to evaluate these structures. 相似文献2.
Nisreen A. Alwan Janet E. Cade Darren C. Greenwood John Deanfield Debbie A. Lawlor 《PloS one》2014,9(1)
Background
Iron deficiency is common during pregnancy. Experimental animal studies suggest that it increases cardiovascular risk in the offspring.Objective
To examine the relationship between maternal pregnancy dietary and supplement iron intake and hemoglobin, with offspring’s arterial stiffness (measured by carotid-radial pulse wave velocity), endothelial function (measured by brachial artery flow mediated dilatation), blood pressure, and adiposity (measured by body mass index), test for mediation by cord ferritin, birth weight, gestational age, and child dietary iron intake, and for effect modification by maternal vitamin C intake and offspring sex.Design
Prospective data from 2958 mothers and children pairs at 10 years of age enrolled in an English birth cohort, the Avon Longitudinal Study for Parents and Children (ALSPAC), was analysed.Results
2639 (89.2%) mothers reported dietary iron intake in pregnancy below the UK reference nutrient intake of 14.8 mg/day. 1328 (44.9%) reported taking iron supplements, and 129 (4.4%) were anemic by 18 weeks gestation. No associations were observed apart from maternal iron intake from supplements with offspring systolic blood pressure (−0.8 mmHg, 99% CI −1.7 to 0, P = 0.01 in the sample with all relevant data observed, and −0.7 mmHg, 99% CI −1.3 to 0, P = 0.008 in the sample with missing data imputed).Conclusion
There was no evidence of association between maternal pregnancy dietary iron intake, or maternal hemoglobin concentration (which is less likely to be biased by subjective reporting) with offspring outcomes. There was a modest inverse association between maternal iron supplement intake during pregnancy with offspring systolic blood pressure at 10 years. 相似文献3.
Objective
To establish a baseline of susceptibility-weighted imaging (SWI) phase value as a means of detecting iron abnormalities in cirrhotic liver and to analyze its relationship with R2*.Materials and Methods
Sixteen MnCl2 phantoms, thirty-seven healthy individuals and 87 cirrhotic patients were performed SWI and multi-echo T2*-weighted imaging, and the signal processing in NMR (SPIN) software was used to measure the radian on SWI phase images and the R2* on T2* maps. The mean minus two times standard deviation (SD) of Siemens Phase Unit (SPU) in healthy individuals was designated as a threshold to separate the regions of interest (ROIs) into high- and low-iron areas in healthy participants and cirrhotic patients. The SWI phase values of high-iron areas were calculated. The R2* values was measured in the same ROI in both healthy participants and patients.Results
SWI phase values correlated linearly with R2* values in cases of MnCl2 concentrations lower than 2.3 mM in vitro (r = −0.996, P<0.001). The mean value and SD of 37 healthy participants were 2003 and 15 (SPU), respectively. A threshold of 1973 SPU (−0.115 radians) was determined. The SWI phase value and R2* values had a negative correlation in the cirrhotic patients (r = −0.742, P<0.001). However, no similar relationship was found in the healthy individuals (r = 0.096, P = 0.576). Both SWI phase values and R2* values were found to have significant correlations with serum ferritin concentrations in 42 patients with blood samples (r = −0.512, P = 0.001 and r = 0.641, P<0.001, respectively).Conclusion
SWI phase values had significant correlations with R2* after the establishment of a baseline on the phase image. SWI phase images may be used for non-invasive quantitative measurement of mild and moderate iron deposition in hepatic cirrhosis in vivo. 相似文献4.
Background
Iron is an essential cofactor in almost all biological systems. The lactic acid bacteria (LAB), frequently employed as probiotics, are unusual in having little or no requirement for iron. Iron in the human body is sequestered by transferrins and lactoferrin, limiting bacterial growth. An increase in the availability of iron in the intestine by bleeding, surgery, or under stress leads to an increase in the growth and virulence of many pathogens. Under these high iron conditions, LAB are rapidly out-competed; for the levels of probiotic bacteria to be maintained under high iron conditions they must be able to respond by increasing growth rate to compete with the normal flora. Despite this, iron-responsive genera are poorly characterised as probiotics.Methodology/Principal Findings
Here, we show that a panel of probiotics are not able to respond to increased iron availability, and identify an isolate of Streptococcus thermophilus that can increase growth rate in response to increased iron availability. The isolate of S. thermophilus selected was able to reduce epithelial cell death as well as NF-κB signalling and IL-8 production triggered by pathogens. It was capable of crossing an epithelial cell barrier in conjunction with E. coli and downregulating Th1 and Th17 responses in primary human intestinal leukocytes.Conclusions/Significance
We propose that an inability to compete with potential pathogens under conditions of high iron availability such as stress and trauma may contribute to the lack of efficacy of many LAB-based probiotics in treating disease. Therefore, we offer an alternative paradigm which considers that probiotics should be able to be competitive during periods of intestinal bleeding, trauma or stress. 相似文献5.
Background
Iron deficiency anemia (IDA) is a global public health problem among school age children, which retards psychomotor development and impairs cognitive performance. There is limited data on prevalence and risk factors for IDA.Objective
The aim of this study was to determine the prevalence, severity, and predictors of nutritional IDA in school age children in Southwest Ethiopia.Methodology
A community based cross-sectional study was conducted in Jimma Town, Southwest Ethiopia from April to July 2013. A total of 616 school children aged 6 to 12 years were included in the study using multistage sampling technique. A structured questionnaire was used to collect sociodemographic data. Five milliliter venous blood was collected from each child for hematological examinations. Anemia was defined as a hemoglobin level lower than 11.5 g/dl and 12 g/dl for age group of 5–11 years and 12–15 years, respectively. Iron deficiency anemia was defined when serum iron and ferritin levels are below 10 µmol/l and 15 µg/dl, respectively. Moreover, fresh stool specimen was collected for diagnosis of intestinal parasitic infection. Stained thick and thin blood films were examined for detection of Plasmodium infection and study of red blood cell morphology. Dietary patterns of the study subjects were assessed using food frequency questionnaire and anthropometric measurements were done. Data were analyzed using SPSS V-20.0 for windows.Result
Overall, prevalence of anemia was 43.7%, and that of IDA was 37.4%. Not-consuming protein source foods [AOR = 2.30, 95%CI(1.04,5.14)], not-consuming dairy products [AOR = 1.83, 95%CI(1.14,5.14)], not-consuming discretionary calories [AOR = 2.77, 95%CI(1.42,5.40)], low family income [AOR = 6.14, 95%CI(2.90,12.9)] and intestinal parasitic infections [AOR = 1.45, 95%CI(1.23, 5. 27)] were predictors of IDA.Conclusion
Iron deficiency anemia is a moderate public health problem in the study site. Dietary deficiencies and intestinal parasitic infections were predictors of IDA. Therefore, emphasis should be given to the strategies for the prevention of risk factors for IDA. 相似文献6.
Background
Uric acid (UA) is an endogenous antioxidant which is known to reduce oxidative stress and also chelate iron ion. Recent studies have provided evidence that UA may play a neuroprotective role in Parkinson’s disease (PD). However, it is unknown whether UA relates to nigral iron deposition, which is a characteristic pathophysiological alteration in PD. The aim of this study was to determine the potential relationship of these two markers in patients with PD.Methods
A total of 30 patients of PD and 25 age- and gender- matched healthy controls underwent 3-Tesla MRI and laboratory tests including serum UA levels. We assessed iron levels by measuring phase shift values using susceptibility-weighted image. Mean phase shift values of the substantia nigra (SN), red nucleus, head of the caudate nucleus, globus pallidus, putamen, thalamus, and frontal white matter were calculated and correlated with serum UA levels.Results
Serum UA levels were significantly decreased in the PD patients than in the controls. Phase shift values in bilateral SN were significantly increased in the PD patients than in the controls. There was no significant correlation between serum UA levels and nigral phase shift values.Conclusions
As previous studies, low serum UA level and increased nigral iron content in the PD was reconfirmed in this study. However, we failed to find the relationship between these two markers. Our data suggest that serum UA may not be important determinant of nigral iron deposition in PD. 相似文献7.
Susceptibility-Weighted Imaging of the Anatomic Variation of Thalamostriate Vein and Its Tributaries
Background and Purpose
Thalamostriate vein (TSV) is an important tributary of the internal cerebral vein, which mainly drains the basal ganglia and deep medulla. The purpose of this study was to explore the anatomic variation and quality of TSV and its smaller tributaries using susceptibility-weighted imaging (SWI).Methods
We acquired SWI images in 40 volunteers on a 3.0T MR system using an 8-channel high-resolution phased array coil. The frequencies of the TSV and its tributaries were evaluated. We classified TSV into types I (forming a venous angle) and II (forming a false venous angle). We classified anterior caudate vein (ACV)into types 1 (1 trunk) and 2 (2 trunks) as well as into types A (joiningTSV), B (joining anterior septal vein), and C (joining the angle of both veins).Results
The TSV drains the areas of caudate nucleus, internal capsule,lentiform nucleus, external capsule, claustrum, extreme capsule and the white matter of the frontoparietal lobes,except thalamus. The frequencies of the TSV, ACV and transverse caudate vein (ACV) were 92.5%, 87.5% and 63.8%, respectively. We found TSV types I and II in 79.7%, and 20.3% with significantly different constitution ratios (P< 0.05). The most common types of ACV were type 1 (90.0%) and type A (64.3%).Conclusion
The complex three-dimensional (3D) venous architecture of TSV and its small tributaries manifests great variation, with significant and practical implications for neurosurgery. 相似文献8.
Dongqiang Song Yuanmin Li Jiatian Cao Zhihua Han Lin Gao Zuojun Xu Zhaofang Yin Guifang Wang Yuqi Fan Changqian Wang 《PloS one》2013,8(6)
Aim
Iron deficiency is a common comorbidity in chronic heart failure (CHF) which may exacerbate CHF. The c-kit+ cardiac stem cells (CSCs) play a vital role in cardiac function repair. However, much is unknown regarding the role of iron deficiency in regulating c-kit+ CSCs function. In this study, we investigated whether iron deficiency regulates c-kit+ CSCs proliferation, migration, apoptosis, and differentiation in vitro.Method
All c-kit+ CSCs were isolated from adult C57BL/6 mice. The c-kit+ CSCs were cultured with deferoxamine (DFO, an iron chelator), mimosine (MIM, another iron chelator), or a complex of DFO and iron (Fe(III)), respectively. Cell migration was assayed using a 48-well chamber system. Proliferation, cell cycle, and apoptosis of c-kit+ CSCs were analyzed with BrdU labeling, population doubling time assay, CCK-8 assay, and flow cytometry. Caspase-3 protein level and activity were examined with Western blotting and spectrophotometric detection. The changes in the expression of cardiac-specific proteins (GATA-4,TNI, and β-MHC) and cell cycle-related proteins (cyclin D1, RB, and pRB) were detected with Western blotting.Result
DFO and MIM suppressed c-kit+ CSCs proliferation and differentiation. They also modulated cell cycle and cardiac-specific protein expression. Iron chelators down-regulated the expression and phosphorylation of cell cycle-related proteins. Iron reversed those suppressive effects of DFO. DFO and MIM didn’t affect c-kit+ CSCs migration and apoptosis.Conclusion
Iron deficiency suppressed proliferation and differentiation of c-kit+ CSCs. This may partly explain how iron deficiency affects CHF prognosis. 相似文献9.
Camila Mesquita-Rodrigues Rubem F. S. Menna-Barreto Leonardo Sabóia-Vahia Silvia A. G. Da-Silva Elen M. de Souza Mariana C. Waghabi Patrícia Cuervo José B. De Jesus 《PLoS neglected tropical diseases》2013,7(10)
Background
Iron is an essential element for the survival of microorganisms in vitro and in vivo, acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships. Leishmania (Viannia) braziliensis is a parasite that is widespread in the new world and considered the major etiological agent of American tegumentary leishmaniasis. Although iron depletion leads to promastigote and amastigote growth inhibition, little is known about the role of iron in the biology of Leishmania. Furthermore, there are no reports regarding the importance of iron for L. (V.) braziliensis.Methodology/Principal Findings
In this study, the effect of iron on the growth, ultrastructure and protein expression of L. (V.) braziliensis was analyzed by the use of the chelator 2,2-dipyridyl. Treatment with 2,2-dipyridyl affected parasites'' growth in a dose- and time-dependent manner. Multiplication of the parasites was recovered after reinoculation in fresh culture medium. Ultrastructural analysis of treated promastigotes revealed marked mitochondrial swelling with loss of cristae and matrix and the presence of concentric membranar structures inside the organelle. Iron depletion also induced Golgi disruption and intense cytoplasmic vacuolization. Fluorescence-activated cell sorting analysis of tetramethylrhodamine ester-stained parasites showed that 2,2-dipyridyl collapsed the mitochondrial membrane potential. The incubation of parasites with propidium iodide demonstrated that disruption of mitochondrial membrane potential was not associated with plasma membrane permeabilization. TUNEL assays indicated no DNA fragmentation in chelator-treated promastigotes. In addition, two-dimensional electrophoresis showed that treatment with the iron chelator induced up- or down-regulation of proteins involved in metabolism of nucleic acids and coordination of post-translational modifications, without altering their mRNA levels.Conclusions
Iron chelation leads to a multifactorial response that results in cellular collapse, starting with the interruption of cell proliferation and culminating in marked mitochondrial impairment in some parasites and their subsequent cell death, whereas others may survive and resume proliferating. 相似文献10.
11.
Dong Lin Jing Ding Jian-Ying Liu Yi-Feng He Zhi Dai Cai-Zhong Chen Wei-Zhong Cheng Jian Zhou Xin Wang 《PloS one》2013,8(6)
Purpose
Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level.Methods
Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters.Results
Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients.Conclusions
Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential. 相似文献12.
Ranneberg-Nilsen T Rollag H Slettebakk R Backe PH Olsen Ø Luna L Bjørås M 《PloS one》2012,7(3):e34119
Background
Human cytomegalovirus (HCMV) uracil DNA glycosylase, UL114, is required for efficient viral DNA replication. Presumably, UL114 functions as a structural partner to other factors of the DNA-replication machinery and not as a DNA repair protein. UL114 binds UL44 (HCMV processivity factor) and UL54 (HCMV-DNA-polymerase). In the present study we have searched for cellular partners of UL114.Methodology/Principal Findings
In a yeast two-hybrid screen SMARCB1, a factor of the SWI/SNF chromatin remodeling complex, was found to be an interacting partner of UL114. This interaction was confirmed in vitro by co-immunoprecipitation and pull-down. Immunofluorescence microscopy revealed that SMARCB1 along with BRG-1, BAF170 and BAF155, which are the core SWI/SNF components required for efficient chromatin remodeling, were present in virus replication foci 24–48 hours post infection (hpi). Furthermore a direct interaction was also demonstrated for SMARCB1 and UL44.Conclusions/Significance
The core SWI/SNF factors required for efficient chromatin remodeling are present in the HCMV replication foci throughout infection. The proteins UL44 and UL114 interact with SMARCB1 and may participate in the recruitment of the SWI/SNF complex to the chromatinized virus DNA. Thus, the presence of the SWI/SNF chromatin remodeling complex in replication foci and its association with UL114 and with UL44 might imply its involvement in different DNA transactions. 相似文献13.
Mei-pian Chen Z. Ioav Cabantchik Shing Chan Godfrey Chi-fung Chan Yiu-fai Cheung 《PloS one》2014,9(11)
Background
Iron overload cardiomyopathy that prevails in some forms of hemosiderosis is caused by excessive deposition of iron into the heart tissue and ensuing damage caused by a raise in labile cell iron. The underlying mechanisms of iron uptake into cardiomyocytes in iron overload condition are still under investigation. Both L-type calcium channels (LTCC) and T-type calcium channels (TTCC) have been proposed to be the main portals of non-transferrinic iron into heart cells, but controversies remain. Here, we investigated the roles of LTCC and TTCC as mediators of cardiac iron overload and cellular damage by using specific Calcium channel blockers as potential suppressors of labile Fe(II) and Fe(III) ingress in cultured cardiomyocytes and ensuing apoptosis.Methods
Fe(II) and Fe(III) uptake was assessed by exposing HL-1 cardiomyocytes to iron sources and quantitative real-time fluorescence imaging of cytosolic labile iron with the fluorescent iron sensor calcein while iron-induced apoptosis was quantitatively measured by flow cytometry analysis with Annexin V. The role of calcium channels as routes of iron uptake was assessed by cell pretreatment with specific blockers of LTCC and TTCC.Results
Iron entered HL-1 cardiomyocytes in a time- and dose-dependent manner and induced cardiac apoptosis via mitochondria-mediated caspase-3 dependent pathways. Blockade of LTCC but not of TTCC demonstrably inhibited the uptake of ferric but not of ferrous iron. However, neither channel blocker conferred cardiomyocytes with protection from iron-induced apoptosis.Conclusion
Our study implicates LTCC as major mediators of Fe(III) uptake into cardiomyocytes exposed to ferric salts but not necessarily as contributors to ensuing apoptosis. Thus, to the extent that apoptosis can be considered a biological indicator of damage, the etiopathology of cardiosiderotic damage that accompanies some forms of hemosiderosis would seem to be unrelated to LTCC or TTCC, but rather to other routes of iron ingress present in heart cells. 相似文献14.
《PloS one》2013,8(7)
Objectives
To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson''s Disease.Methods
A retrospective study of genetic Parkinson''s diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.Results
Scans were available from 37 cases of monogenetic Parkinson''s disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson''s disease with GBA or LRRK2 mutations was greater than that for Parkinson''s disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions
The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss. 相似文献15.
Kyung-Hee Kim Fabien Maldonado Jay H Ryu Patrick W Eiken Thomas E Hartman Brian J Bartholmai Paul A Decker Eunhee S Yi 《Respiratory research》2010,11(1):37
Background
Early diagnosis of pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) has potential prognostic and therapeutic implications but can be difficult due to the lack of specific clinical manifestations or accurate non-invasive tests. Histopathologic parameters correlating with PH in IPF are also not known. Remodeling of postcapillary pulmonary vessels has been reported in the nonfibrotic areas of explanted lungs from IPF patients. We hypothesized that iron deposition and increased alveolar capillaries, the findings often seen in postcapillary PH, might predict the presence of clinical PH, independent of the severity of fibrosis or ventilatory dysfunction in IPF patients. To test this hypothesis, we examined the association between these histologic parameters and the degree of PH, with consideration of the severity of disease in IPF.Methods
Iron deposition and alveolar septal capillary density (ASCD) were evaluated on histologic sections with hematoxylin-eosin, iron, elastin and CD34 stainings. Percentage of predicted forced vital capacity (FVC%) was used for grading pulmonary function status. Fibrosis score assessed on high resolution computed tomography (HRCT) was used for evaluating overall degree of fibrosis in whole lungs. Right ventricular systolic pressure (RVSP) by transthoracic echocardiography was used for the estimation of PH. Univariate and multivariate regression analyses were performed.Results
A cohort of 154 patients was studied who had the clinicopathological diagnosis of IPF with surgical lung biopsies or explants during the period of 1997 to 2006 at Mayo Clinic Rochester. In univariate analysis, RVSP in our IPF cases was associated with both iron deposition and ASCD (p < 0.001). In multivariate analysis with FVC% and HRCT fibrosis score included, iron deposition (p = 0.02), but not ASCD (p = 0.076), maintained statistically significant association with RVSP. FVC% was associated with RVSP on univariate analysis but not on multivariate analysis, while fibrosis score lacked any association with RVSP by either univariate or multivariate analyses.Conclusions
Iron deposition and ASCD in non fibrotic lung tissue showed an association with RVSP, suggesting that these features are possible morphologic predictors of PH in IPF. 相似文献16.
17.
Jie Chen Jiule Ding Yongming Dai Wei Xing Jun Sun Zishu Zhang Yang Xuan Vasuki Pilli E. Mark Haacke Jiani Hu 《PloS one》2013,8(6)
Background
Multiple treatment options exist for the management of renal cell carcinomas. Preoperative evaluation of clear cell renal cell carcinoma (CRCC) grades is important for deciding upon the appropriate method of therapy. We hypothesize that susceptibility weighted imaging (SWI) is sensitive enough to detect intratumoral microvessles and microbleeding in renal cell carcinoma, which can be used to grade CRCC.Material and Methods
Retrospective reviews of 37 patients with pathologically proven CRCCs were evaluated. All patients underwent SWI examinations. The characteristics of intratumoral susceptibility signal intensity (ITSS) includes the likelihood of the presence of ITSS, morphology of ITSS, dominant structure of ITSS and ratio of ITSS area to tumor area, which were all assessed on SWI. The results were compared using the nonparametric Mann-Whitney test.Results
ITSS was seen in all patients except 4 patients with low-grade CRCCs. There was no significant difference between low and high-grade CRCCs when looking at the likelihood of the presence of ITSS. There was a significant difference in the mean score of dominant structures between low and high-grade CRCCs. Specifically, more dominant vascular structures and less hemorrhage were seen in low-grade tumors (2.15±1.05) compared to high-grade tumors (1.27±0.47) (P<0.005). The ratio of ITSS area to tumor area was also significantly higher for the high-grade group (1.55±0.52) than that for the low-grade group (0.88±0.43) on SWI (P<0.005).Conclusion
SWI is useful for grading CRCCs. 相似文献18.
Lucette A. Cysique Kirsten Moffat Danielle M. Moore Tammy A. Lane Nicholas W. S. Davies Andrew Carr Bruce J. Brew Caroline Rae 《PloS one》2013,8(4)
Background
Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear.Methods
92 HIV− infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV−) subjects underwent 1H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals.Results
Relative to HIV− individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (p<.04) and higher myo-inositol (mIo) (p<.04); in the caudate: lower NAA (p = .01); and in the posterior cingulate cortex: higher mIo (p<.008– also significant when Holm-Sidak corrected) and higher Choline/NAA (p<.04). Regression models showed that an HIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter.Conclusions
In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by chronic inflammation. 相似文献19.
Flück CE Pandey AV Dick B Camats N Fernández-Cancio M Clemente M Gussinyé M Carrascosa A Mullis PE Audi L 《PloS one》2011,6(5):e20178
Context
Steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH).Objective
StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported.Design
To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature.Setting
Collaboration between the University Children''s Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d''Hebron, Autonomous University, Barcelona, Spain.Patients
Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age.Results
StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol.Conclusions
StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed. 相似文献20.