Biomedical subjects

J Aoki

Publications and source records attributed to J Aoki.

At least 19 recordsLinked to original sources

PubMed2007

Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation during development and after neurotrauma.

Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling, demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries.

Animals↗

PubMed2006

Detection of pattern of myocardial fibrosis by contrast-enhanced MRI: is redefinition of uremic cardiomyopathy necessary for management of patients?

Cardiac magnetic resonance imaging (CMR) can detect cardiac tissue components for several kinds of cardiac myopathies. Mark et al. found two patterns of late gadolinium enhancement (LGE) in patients with uremic cardiomyopathy: focal LGE and diffuse LGE. The impact of these contrast-enhanced CMR findings on clinical outcomes warrants assessment in future studies.

Cardiomyopathies↗

PubMed2005

Coronary artery remodelling is related to plaque composition.

OBJECTIVE: To assess the potential relation between plaque composition and vascular remodelling by using spectral analysis of intravascular ultrasound (IVUS) radiofrequency data. METHODS AND RESULTS: 41 coronary vessels with non-significant (< 50% diameter stenosis by angiography), < or = 20 mm, non-ostial lesions located in non-culprit vessels underwent IVUS interrogation. IVUS radiofrequency data obtained with a 30 MHz catheter, were analysed with IVUS virtual histology software. A remodelling index (RI) was calculated and divided into three groups. Lesions with RI > or = 1.05 were considered to have positive remodelling and lesions with RI < or = 0.95 were considered to have negative remodelling. Lesions with RI > or = 1.05 had a significantly larger lipid core than lesions with RI 0.96-1.04 and RI < or = 0.95 (22.1 (6.3) v 15.1 (7.6) v 6.6 (6.9), p < 0.0001). A positive correlation between lipid core and RI (r = 0.83, p < 0.0001) and an inverse correlation between fibrous tissue and RI (r = -0.45, p = 0.003) were also significant. All of the positively remodelled lesions were thin cap fibroatheroma or fibroatheromatous lesions, whereas negatively remodelled lesions had a more stable phenotype, with 64% having pathological intimal thickening, 29% being fibrocalcific lesions, and only 7% fibroatheromatous lesions (p < 0.0001). CONCLUSIONS: In this study, in vivo plaque composition and morphology assessed by spectral analysis of IVUS radiofrequency data were related to coronary artery remodelling.

Coronary Stenosis↗

PubMed2005

One year clinical follow up of paclitaxel eluting stents for acute myocardial infarction compared with sirolimus eluting stents.

OBJECTIVE: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. DESIGN AND PATIENTS: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period. SETTING: Academic tertiary referral centre. RESULTS: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p = 1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p = 0.04). This was driven by stent thrombosis (n = 4), especially in the bifurcation stenting (n = 2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p = 0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p = 0.16). CONCLUSIONS: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.

Adult↗

PubMed2005

Methodological considerations and approach to cross-technique comparisons using in vivo coronary plaque characterization based on intravascular ultrasound radiofrequency data analysis: insights from the Integrated Biomarker and Imaging Study (IBIS).

Grey scale intravascular ultrasound (IVUS) is a valuable clinical tool to assess the extent and severity of coronary atheroma. However, it cannot reliably identify plaques with a high-risk of future clinical events. Serial IVUS studies to assess the progression and/or regression of atherosclerotic plaques demonstrated only modest effects, of pharmacological intervention on plaque burden, even when clinical efficacy is documented. Spectral analysis of radiofrequency ultrasound data (IVUS-virtual histology (IVUS-VH), Volcano Therapeutics, Rancho Cordova, CA) has the potential to characterize accurately plaque composition. The Integrated Biomarker and Imaging Study (IBIS) evaluated both invasive and non-invasive imaging techniques along with the assessment of novel biomarkers to characterize sub-clinical atherosclerosis. IVUS-VH was not included at the start of the IBIS protocol. The purpose of this paper is to describe the methodology we used to obtain and analyse IVUS-VH images and the approach to cross-correlations with the other techniques.

Biomarkers↗

PubMed2005

Osteoid osteoma treated with computed tomography-guided percutaneous radiofrequency ablation: a case series.

The nidi of osteoid osteoma are small and difficult to identify precisely; this can necessitate substantial resection of the surrounding normal bone. We applied percutaneous, image-guided radiofrequency ablation to treat 5 patients with osteoid osteoma. The precise location of each nidus was determined using a 3-mm-thick spiral computed tomographic scan. The most appropriate needle pathway was selected to avoid major neural and vascular structures. A 14-gauge core needle was introduced into the nidus and then exchanged for a 17-gauge straight rigid electrode with a 1-cm exposed tip to heat the lesion to 90 degrees centigrade for 5 minutes. Four of the 5 patients were discharged on the day after surgery without any external supports, and were pain-free after a few days. The remaining patient had a pes equinus contracture induced by the penetration of the calf muscles through a posterior approach but was fully recovered 6 days later. The mean follow-up period was 20.6 months. No recurrences or late complications were observed in this series. This case series shows that the computed tomography-guided percutaneous radiofrequency ablation is a simple, minimally invasive, and highly effective technique for the treatment of osteoid osteoma.

Adult↗

PubMed2005

How to accelerate the endothelialization of stents.

Coronary artery stenting is currently the most frequently performed percutaneous coronary intervention for the treatment of coronary artery disease. The endothelium is a single layer of endothelial cells lining the vascular wall and plays an integral part in maintaining vascular homeostasis. Stenting however causes significant injury to the vascular wall and endothelium, resulting in inflammation, repair and the development of neointimal hyperplasia. The ability of the endothelium to repair itself depends on both the migration of surrounding mature endothelial cells, and the attraction and adhesion of circulating endothelial progenitor cells (EPCs) to the injured region, which then differentiate into endothelial-like cells. Current therapies with drug-eluting stents interrupt the natural response to damage. Accelerating the reendothelialization of the damaged arterial segment following stent implantation is an attractive form of therapy as it is seen as hastening the natural process of repair. It potentially has the benefit of reducing the amount of neointimal hyperplasia and stent thrombosis. Studies have been performed to identify agents that augment the mobilisation and recruitment of EPCs to the injured area (statins, exercise, estrogen and cytokines). Other studies have looked at seeding stents with endothelial cells or EPCs. The most current approach is to coat anti-CD34 antibodies on a stent surface to attract circulating EPCs to the stent which then differentiate into endothelial-like cells. This approach is currently being tested in safety and feasibility clinical studies.

Animals↗

PubMed2003

The effects of frequency-encoding gradient upon detectability of the margins and height measurements of normal adult pituitary glands.

We investigated the effects of frequency-encoding gradient (FEG) upon detectability and height measurements of the normal adult pituitary gland. We obtained two sets of T1-weighted sagittal images of the pituitary gland from 70 adult subjects without known pituitary dysfunction using 1.5 tesla imagers; one with an inferior-superior FEG, and one with an anterior-posterior FEG. We classified the subjects into three types according to the distribution of fatty marrow in the clivus. Each set of images was assessed for pituitary height on midline sagittal images, and detectability of pituitary margins. Height measurements and detectability scores were evaluated for significant difference between the two FEGs. In subjects with fatty marrow in the clivus, there was significant difference between pituitary height measurements (P < 0.005) and pituitary margin detectability (P < 0.001). Care should be taken to image the pituitary gland using an anterior-posterior FEG.

Adult↗

PubMed2003

Gliomatosis cerebri evaluated by 18Falpha-methyl tyrosine positron-emission tomography.

Gliomatosis cerebri is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. CT and MRI show diffuse abnormal density or signal, without mass effect, and because these findings are nonspecific, it is difficult to make a definitive diagnosis. Our purpose was to assess the usefulness of a new tumour-detecting amino acid tracer for positron-emission tomography (PET), L-[3-(18)F] alpha-methyl tyrosine (FMT), in patients with gliomatosis cerebri. We performed FMT PET, fluorodeoxyglucose FDG PET and MRI eight patients with gliomatosis cerebri and six with non-neoplastic disease, whose MRI also showed diffuse high signal on T2-weighted images. Standardised uptake (SUV) of FMT and FDG in the area of gliomatosis was obtained and the tumour-to-normal cortex (T/N) ratio of this was compared. The tumours were shown on FMT PET as areas of increased uptake, except in one patient with severe intracranial hypertension. There were significant differences between the SUV of FMT and the T/N ratio of FMT in patients and in controls (both P<0.01), and between the T/N ratio of FMT and FDG in patients ( P<0.01). Increased uptake of FMT PET strongly suggests neoplasia. FMT PET is valuable for differentiating gliomatosis cerebri from non-neoplastic diseases showing similar diffuse high signal on T2-weighted images and little contrast enhancement.

Adult↗

PubMed2003

FDG-PET for preoperative differential diagnosis between benign and malignant soft tissue masses.

OBJECTIVE: To evaluate the standardized uptake value (SUV) of [(18)F]2-deoxy-2-fluoro- d-glucose at positron emission tomography (FDG-PET) for preoperative differential diagnosis between benign and malignant soft tissue masses. DESIGN: One hundred and fourteen soft tissue masses (80 benign, 34 malignant) were examined by FDG-PET prior to tissue diagnosis. The SUVs were calculated and compared between benign and malignant lesions and among different histologic subgroups which included three or more cases. RESULTS: There was a statistically significant difference in SUV between benign (1.80+/-1.42 [SD]) and malignant (4.20+/-3.16) soft tissue masses in total (P<0.0001). However, a considerable overlap in SUV was observed between many benign and malignant lesions. Liposarcomas (2.16+/-1.72) and synovial sarcomas (1.60+/-0.43) did not show significantly higher SUV than any benign lesions. Metastases (4.23+/-2.35) showed no statistically significant difference in SUV as compared with schwannomas (1.75+/-0.84), desmoids (2.77+/-1.32), sarcoidosis (3.62+/-1.53), or giant cell tumors of tendon sheath (GCT of TS; 5.06+/-1.63). Even malignant fibrous histiocytomas (5.37+/-1.40) could not be differentiated from sarcoidosis or GCT of TS, based on the SUV. CONCLUSIONS: A large accumulation of FDG can be observed in both benign and malignant histiocytic, fibroblastic, or neurogenic lesions. SUV at conventional FDG-PET is limited to differentiating benign from malignant soft tissue masses, when all kinds of histologic subtypes are included.

Diagnosis, Differential↗

PubMed2003

Human placental trophoblast cells express alpha-tocopherol transfer protein.

Alpha-tocopherol transfer protein (alpha-TTP), a 30 kDa cytosolic protein first described to be present in the liver and important for alpha-tocopherol trafficking, plays a major role in maintaining alpha-tocopherol levels in plasma, while alpha-tocopherol is known as the major lipid-soluble antioxidant. Expression of alpha-TTP has not only been described in animal model liver, but also in diverse other tissues such as rat brain or pregnant mouse uterus, the latter finding stressing the importance of alpha-TTP for embryogenesis and foetal development. In this study, we report the identification of alpha-TTP in human liver by anti-human alpha-TTP monoclonal antibodies made in rat and the cellular localization of alpha-TTP in term human placenta. By immunohistochemistry, intense staining of alpha-TTP was seen in syncytiotrophoblast as well as in villous and invading extravillous cytotrophoblast, while basal decidual cells showed slighter, but present staining of alpha-TTP. Foetal vessel endothelium remained unstained. It is therefore suggested that alpha-TTP may play a major role in supplying alpha-tocopherol to the foetus prior to delivery and is likely involved in maintaining adequate alpha-tocopherol levels in the foetus.

Adult↗

PubMed2003

11C-choline PET for the detection of bone and soft tissue tumours in comparison with FDG PET.

We assessed and compared the usefulness of C-choline positron emission tomography (PET) with that of 2-[ F]fluoro-2-deoxy-D-glucose (FDG) PET for the differentiation between benign and malignant bone and soft tissue tumours. A total of 43 patients with 45 lesions were included. C-choline PET and FDG PET were performed from 5 and 40 min, respectively, after injection of 275-370 MBq tracer. PET data were evaluated by using the standardized uptake value (SUV) and were analysed according to the pathological data. C-choline uptake in malignancies was 4.9+/-2.1 (n=14), which was significantly higher than that in benign lesions (2.5+/-1.7, n=31) (P <0.0001). The sensitivity, specificity and accuracy of C-choline PET were 100%, 64.5% and 75.6%, respectively, when 2.59 of the SUV was used as the cut-off value. The FDG uptake in malignancies was 5.1+/-4.2 (n=14) and was also significantly larger than that in benign lesions 2.9+/-2.9 (n=31) (P<0.003). The sensitivity, specificity and accuracy of FDG PET were 85.7%, 41.9% and 55.6%, respectively (cut-off=1.83). The C-choline uptake in the lesions correlated with FDG uptake ( r=0.61, P<0.003). In receiver operating characteristic (ROC) analysis, the area under the ROC curve for C-choline PET (area=0.847) was higher than that for FDG PET (area=0.717). This study showed that C-choline PET was superior to FDG PET in differentiation between malignant and benign lesion in bone and soft tissue tumours. C-choline PET might be useful as a screening method for malignant bone and soft tissue tumours.

Adolescent↗

PubMed2002

MR detection of microhemorrhages in neurologically healthy adults.

T2*-weighted gradient-echo (GE) magnetic resonance images frequently demonstrate small hypointense lesions in patients with systemic hypertension and spontaneous hematomas. These lesions have been suspected to represent subclinical microhemorrhages. We examined the incidence of these lesions in neurologically healthy adults, and the factors associated with them. Axial T2*-weighted GE images (TR = 1,000 ms, TE = 30 ms, flip angle = 20 degrees) were obtained in addition to conventional T1- and T2-weighted spin echo images in 450 neurologically healthy Japanese adults (289 men and 161 women; age 52.9 +/- 7.7 years, range 24-84). The overall incidence of small hypointense lesions was 3.1% (14/450), and these lesions were closely related to systemic hypertension (P < 0.0001) and heavy cigarette smoking (>20 cigarettes per day; P=0.003). Although the incidence of hypointense lesions was lower in neurologically healthy adults than in the reported incidence in patients with a hemorrhagic history, the presence of these lesions was related to the risk factors for primary intracerebral hemorrhage even in the neurologically healthy adults.

Adult↗

PubMed2002

Alpha-tocopherol transfer protein is specifically localized at the implantation site of pregnant mouse uterus.

Alpha-tocopherol transfer protein (alpha-TTP) was first described to play a major role in maintaining alpha-tocopherol levels in plasma, while alpha-tocopherol was primarily reported to be a factor relevant for reproduction. Expression of alpha-TTP is not only seen in the liver, from where it was first isolated, but also in mouse uterus, depending on its state of pregnancy, stressing the importance of alpha-TTP for embryogenesis and fetal development. The cellular localization of alpha-TTP in mouse uterus is reported here. By immunohistochemistry, alpha-TTP could be localized in the secretory columnar epithelial cells of the pregnant uterus on Days 4.5 and 6.5 postcoitum as well as in the glandular epithelial cells and the inner decidual reaction zone surrounding the implantation site. On Days 8.5 and 10.5 postcoitum (midterm of mouse pregnancy), alpha-TTP could still be detected in the uterine secretory columnar epithelial cells, while in alpha-TTP knockout mice, no immunostaining was visible. It is suggested that alpha-TTP plays a major role in supplying the placenta and consecutively the fetus with alpha-tocopherol throughout pregnancy. We conclude that alpha-tocopherol plays a role in the process of implantation and that alpha-TTP may be necessary for adequate alpha-tocopherol status of the fetus.

Animals↗

PubMed2001

Phenotypic modulation of vascular smooth muscle cells induced by unsaturated lysophosphatidic acids.

The phenotypic modulation of vascular smooth muscle cells (VSMCs) from the differentiated state to the dedifferentiated one is critically involved in the development and progression of atherosclerosis. Although many cytokines and growth factors have been reported as atherogenic factors, the critical pathogens for inducing atherosclerosis remain unknown, largely because proper examining systems of them have not been developed. We recently established primary culture systems for visceral SMCs and VSMCs in which both SMCs, when cultured on laminin with insulin-like growth factor-I, show a differentiated phenotype, as indicated by a spindle-like shape, ligand-induced contractility, and a high level of SMC differentiation marker gene expression. In this study, we searched for critical dedifferentiation factors for these SMCs using our culture system. We found that polar lipids extracted from human serum markedly induced VSMC dedifferentiation, and this activity was solely present in the lysophosphatidic acid (LPA) fraction. Among several LPA species detected in human serum lipids, unsaturated LPAs were identified as major contributors to the induction of VSMC dedifferentiation. Signaling and phenotype analyses revealed that unsaturated LPA-induced VSMC dedifferentiation is mediated through the coordinated activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. Thus, this report demonstrates the first finding that unsaturated LPAs, but not saturated LPAs, specifically induce VSMC phenotypic modulation, suggesting that these molecules could function as atherogenic factors.

Animals↗

PubMed2001

Phosphatidylserine-specific phospholipase A1 stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine.

Lysophosphatidylserine (1-acyl-2-lyso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by FcepsilonRI (high affinity receptor for IgE) cross-linking, although the precise mechanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific phospholipase A(1), PS-PLA(1), stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of FcepsilonRI cross-linker. The potency of 2-acyl-1-lyso-PS was almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA(1), in which an active serine residue (Ser(166)) was replaced with an alanine residue did not show such activity. sPLA(2)-IIA, another secretory PLA(2) that is capable of producing lyso-PS in vitro, was also a poor histamine inducer against RPMC. PS-PLA(1) significantly stimulated histamine release from crude RPMC, indicating that lyso-PS is mainly derived from cells other than mast cells. In agreement with this phenomenon, the enzyme stimulated the histamine release more efficiently when RPMC were mixed with apoptotic Jurkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA(1). Finally, heparin, which has affinity for PS-PLA(1), completely blocked the stimulatory effect of the enzyme. In conclusion, PS-PLA(1) may bind to heparan sulfate proteoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptotic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.

Animals↗

PubMed2001

Platelet-activating factor acetylhydrolases: broad substrate specificity and lipoprotein binding does not modulate the catalytic properties of the plasma enzyme.

Platelet-activating factor acetylhydrolases (PAF-AHs) are a group of enzymes that hydrolyze the sn-2 acetyl ester of PAF (phospholipase A(2) activity) but not phospholipids with two long fatty acyl groups. Our previous studies showed that membrane-bound human plasma PAF-AH (pPAF-AH) accesses its substrate only from the aqueous phase, which raises the possibility that this enzyme can hydrolyze a variety of lipid esters that are partially soluble in the aqueous phase. Here we show that pPAF-AH has broad substrate specificity in that it hydrolyzes short-chain diacylglycerols, triacylglycerols, and acetylated alkanols, and displays phospholipase A(1) activity. On the basis of all of the substrate specificity results, it appears that the minimal structural requirement for a good pPAF-AH substrate is the portion of a glyceride derivative that includes an sn-2 ester and a reasonably hydrophobic chain in the position occupied by the sn-1 chain. In vivo, pPAF-AH is bound to high and low density lipoproteins, and we show that the apparent maximal velocity for this enzyme is not influenced by lipoprotein binding and that the enzyme hydrolyzes tributyroylglycerol as well as the recombinant pPAF-AH does. Broad substrate specificity is also observed for the structurally homologous PAF-AH which occurs intracellularly [PAF-AH(II)] as well as for the PAF-AH from the lower eukaryote Physarum polycephalum although pPAF-AH and PAF-AH(II) tolerate the removal of the sn-3 headgroup better than the PAF-AH from P. polycephalum does. In contrast, the intracellular PAF-AH found in mammalian brain [PAF-AH(Ib) alpha 1/alpha 1 and alpha 2/alpha 2 homodimers] is more selectively operative on compounds with a short acetyl chain although this enzyme also displays significant phospholipase A(1) activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2001

Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a female with mental retardation, ataxia and atrophy of the brain.

We report on the molecular characterization of a translocation t(1;19)(q21.3;q13.2) in a female with mental retardation, ataxia and atrophy of the brain. Sequence analysis of the breakpoints revealed an ALU:-repeat-mediated mechanism of recombination that led to truncation of two genes: the kinase CLK2 and PAFAH1B3, the gene product of which interacts with LIS1 as part of a heterotrimeric G protein complex PAF-AH1B. In addition, two reciprocal fusion genes are present. One expressed fusion gene encodes the first 136 amino acids of PAFAH1B3 followed by the complete CLK2 protein. Truncated PAFAH1B3 protein lost its potential to interact with LIS1 whereas CLK2 activity was conserved within the fusion protein. These data emphasize the importance of PAF-AH1B in brain development and functioning and demonstrate the first fusion gene apparently not associated with cancer.

Abnormalities, Multiple↗