Biomedical subjects

J Aoki

Publications and source records attributed to J Aoki.

At least 109 records · Page 6Linked to original sources

PubMed1998

Pentavalent technetium-99m-dimercaptosuccinic acid scintigraphy in renal osteodystrophy.

Pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy and 99mTc-hydroxymethylene diphosphonate (HMDP) bone scan were performed in one patient with renal osteodystrophy (ROD) before and after vitamin D3 pulse therapy. The bone scan showed diffusely increased tracer uptake in the whole skeleton, and no change of tracer distribution was noted before or after vitamin D3 pulse therapy. However, 99mTc(V)-DMSA scintigraphy revealed diffusely increased tracer uptake in the whole skeleton before therapy, and markedly decreased tracer uptake in the bones was seen at 5 mo after therapy. Increased uptake of 99mTc(V)-DMSA was observed at 7 mo after therapy, which reflected the laboratory findings. Technetium-99m-(V)-DMSA scintigraphy appeared to be more sensitive than the conventional 99mTc-HMDP bone scan in assessing the characteristics and therapeutic effect of bone disease in ROD.

Adult↗

PubMed1997

Protection against oxidative stress-induced cell death by intracellular platelet-activating factor-acetylhydrolase II.

Platelet-activating factor-acetylhydrolase (PAF-AH), which removes the acetyl group at the sn-2 position of PAF, is distributed widely in tissues and plasma. Tissue cytosol contains at least two types of PAF-AH, isoforms Ib and II. Isoform Ib is a tertiary G-protein complex-like heterotrimeric enzyme that is involved in brain development such as formation of the brain cortex. Isoform II (PAF-AH(II)), however, is a 40-kDa monomer and has an amino acid sequence that exhibits a 41% identity with that of plasma PAF-AH. Although PAF-AH(II) preferentialy hydrolyzes oxidized phospholipids as well as PAF in vitro, the function of this enzyme has not, as yet, been elucidated. Here, we report that PAF-AH(II) functions as an anti-oxidant phospholipase. PAF-AH(II) was found to be an N-myristoylated enzyme that has never been reported among lipases and phospholipases. In MDBK cells treated with oxidants, PAF-AH(II) translocated from cytosol to membranes within 20 min, whereas in cells treated with anti-oxidants, it translocated, conversely, from membranes to cytosol. Overexpression of PAF-AH(II) in Chinese hamster ovary-K1 cells suppressed oxidative stress-induced cell death, which occurs by apoptosis. These findings suggest that intracellular PAF-AH(II) translocates between cytosol and membranes in response to a redox state of the cell and protects the cell against oxidative stress most probably by hydrolyzing oxidized phospholipids.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

PAF analogues capable of inhibiting PAF acetylhydrolase activity suppress migration of isolated rat cerebellar granule cells.

Intracellular platelet-activating factor (PAF) acetylhydrolase in the bovine brain is a heterotrimeric enzyme composed of alpha1, alpha2 and beta subunits. The trimeric enzyme may be involved in neural cell migration, since the human homolog of the non-catalytic beta subunit is a product of the LIS-1 gene which is a causative gene for Miller-Dieker syndrome. Miller-Dieker syndrome is a form of lissencephaly that is characterized by widespread agyria of the brain and defects of neuronal cell migration. In the present study, we attempted to determine whether the catalytic activity of either the alpha1 or alpha2 subunit is required for the regulation of granule cell migration. Granule cells prepared from rat cerebellum at postnatal day 0 express all three subunit proteins (alpha1, alpha2 and beta) as determined by western blotting. Granule cell migration, which was observed in vitro on a layer coated with laminin, was effectively blocked by PAF analogs which showed PAF receptor-antagonistic activity (CV-6209 and CV-3988) and PAF receptor-agonistic activity (carbamoyl PAF). These PAF analogs also inhibited the activity of bovine brain PAF acetylhydrolase. Cell migration was restored when the inhibitors were removed by washing the treated cells with buffer, indicating that the inhibitory effect of PAF analogs is reversible. Structurally-unrelated PAF antagonists (SM-12502, TCV-309 and YM-264), none of which showed any appreciable inhibitory activity against PAF acetylhydrolase, did not block granule cell migration under the same conditions. It is suggested that the catalytic activity of PAF acetylhydrolase may play a crucial role in neural cell migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

Mouse homolog of poliovirus receptor-related gene 2 product, mPRR2, mediates homophilic cell aggregation.

Poliovirus receptor (PVR) is a cell surface glycoprotein that belongs to the immunoglobulin superfamily. Although MPH was initially reported as the mouse homolog of human PVR, recent data strongly suggest that MPH is the mouse homolog of human PRR2, a PVR-related gene 2 product, and not that of human PVR. Thus MPH is renamed mPRR2 in this study. Physiological functions of the PVR-related gene products have not been elucidated, although PVR has been well characterized as the poliovirus receptor. In this study, a possible function of mPRR2 (MPH), which is not a functional receptor for poliovirus, was investigated. Mouse L cells expressing mPRR2 were prepared. Those mouse cells showed a higher activity of cell aggregation than the parental mouse L cells. Enhancement of cell aggregation was also observed for insect Sf9 cells infected with recombinant baculovirus carrying mPRR2 cDNA. On the other hand, L cells expressing human PVR or monkey PVR (AGM alpha1 or AGM alpha2) did not show increased cell aggregation. The cell aggregation activity of L cells expressing mPRR2 was inhibited by the addition of anti-mPRR2 monoclonal antibodies or a soluble mPRR2 molecule produced by the baculovirus expression system. An immunofluorescence study revealed that mPRR2 protein was localized to the cell-cell contact sites between cells expressing mPRR2. A similar localization of mPRR2 was observed for intrinsic mPRR2 molecules of the mouse neuroblastoma cell line NS20Y. The contact site-specific localization of mPRR2 was not observed on the border between mPRR2-expressing and nonexpressing HeLa cells. Furthermore, mPRR2 proteins directly bound to each other in vitro. mPRR2 was detected on various types of cultured cells of mouse origin and in various mouse tissues. These results suggest that mPRR2 is an intercellular adhesion molecule with a homophilic binding manner.

Animals↗

PubMed1997

Efficient delivery of circulating poliovirus to the central nervous system independently of poliovirus receptor.

The transgenic (Tg) mice carrying the human gene for poliovirus receptor (PVR) are susceptible to poliovirus intravenously (i.v.) inoculated as well as intracerebrally or intraspinally inoculated. Thus, i.v.-inoculated poliovirus may invade the central nervous system (CNS) through the blood-brain barrier (BBB). To know the contribution of PVR to tissue distribution and BBB permeability of i.v.-inoculated polioviruses, these dissemination processes were investigated and compared between the Tg mice and non-Tg mice. Distribution profile of i.v.-inoculated poliovirus in various tissues of the Tg mice is similar to that in non-Tg mice. The data suggest that tissue distribution of the virus occurs independently of the transgene for PVR. The amount of poliovirus delivered to the CNS suggested the existence of a specific delivery system of the virus to the CNS. Virus accumulation in the CNS of the Tg mice was measured up to 7.5 hr after the i.v. inoculation. The viruses, regardless of whether the virulent or attenuated strain, seem to accumulate at a constant rate of approximately 0.2 microliter/min/g tissue. Similar phenomena were observed when the viruses were inoculated into non-Tg mice. The rates of the virus accumulation in the CNS are more than 100 times higher than that of albumin, which is considered not to permeate through the BBB via a specific transport system, and only three times lower than that of monoclonal antibody against transferrin receptor (OX-26), which is a potential candidate as a drug delivery vehicle specific to the CNS. These data suggest that polioviruses permeate through the BBB at a fairly high rate, independently of PVR and virus strains.

Animals↗

PubMed1997

Serine phospholipid-specific phospholipase A that is secreted from activated platelets. A new member of the lipase family.

Rat platelets secrete two types of phospholipases upon stimulation; one is type II phospholipase A2 and the other is serine-phospholipid-selective phospholipase A. In the current study we purified serine-phospholipid-selective phospholipase A and cloned its cDNA. The final preparation, purified from extracellular medium of activated rat platelets, gave a 55-kDa protein band on SDS-polyacrylamide gel electrophoresis. [3H]Diisopropyl fluorophosphate, an inhibitor of the enzyme, labeled the 55-kDa protein, suggesting that this polypeptide possesses active serine residues. The cDNA for the enzyme was cloned from a rat megakaryocyte cDNA library. The predicted 456-amino acid sequence contains a putative short N-terminal signal sequence and a GXSXG sequence, which is a motif of an active serine residue of serine esterase. Amino acid sequence homology analysis revealed that the enzyme shares about 30% homology with mammalian lipases (lipoprotein lipase, hepatic lipase, and pancreatic lipase). Regions surrounding the putative active serine, histidine, and aspartic acid, which may form a "lipase triad," were highly conserved among these enzymes. The recombinant protein, which we expressed in Sf9 insect cells using the baculovirus system, hydrolyzed a fatty acyl residue at the sn-1 position of lysophosphatidylserine and phosphatidylserine, but did not appreciably hydrolyze phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid, and triglyceride. The present enzyme, named phosphatidylserine-phospholipase A1, is the first phospholipase that exclusively hydrolyses the sn-1 position and has a strict head group specificity for the substrate.

Amino Acid Sequence↗

PubMed1997

Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer.

The platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This isoform contains a heterodimer of two homologous catalytic subunits alpha1 and alpha2, each of relative molecular mass 26K, and a non-catalytic 45K beta-subunit, a homologue of the beta-subunit of trimeric G proteins. We now report the crystal structure of the bovine alpha1 subunit of PAF-AH(Ib) at 1.7 A resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21(ras) and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like (alpha1/alpha2)beta trimer.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

Intraosseous neurilemmoma of the fibula.

We present a case of intraosseous neurilemmoma of the fibula in a 56-year-old woman. The case showed the typical radiographic appearance except for the presence of spotted calcifications that mimicked a cartilaginous tumor. Enhanced MR images revealed the heterogeneity of the tumor, which consisted of Antoni type A and B tissue.

Bone Neoplasms↗

PubMed1997

Ischiopubic insufficiency fractures: MRI appearances.

OBJECTIVE: To evaluate the MRI appearances in insufficiency fractures. DESIGN: A retrospective analysis of spin echo MR images with gadolinium-enhancement was undertaken with the emphasis on the signal change and the shape of the fracture gap and the adjacent bone marrow. PATIENTS: Five elderly women who had ischiopubic insufficiency fractures (pubis, 4; ischium 1) underwent MRI to exclude the possibility of pathologic fractures. RESULTS AND CONCLUSIONS: In no case was contrast enhancement noted at the fracture gap or the adjacent bone marrow, but a cleft-life, elongated bright signal area suggesting "fluid collection" was noted within the fracture gap. Absence of contrast enhancement and "fluid collection" at the fracture gap might suggest non-union of a fracture, which is additional information provided only by MRI.

Aged↗

PubMed1997

4-(5',6'-Dimethoxybenzothiazolyl)benzoyl fluoride and 2-(5',6'-dimethoxybenzothiazolyl)benzenesulfonyl chloride as sensitive fluorescence derivatization reagents for amines in high-performance liquid chromatography.

4-(5',6'-Dimethoxybenzothiazolyl)benzoyl fluoride (BHBT-COF) and 2-(5',6'-dimethoxybenzothiazolyl)-benzenesulfonyl chloride (BHBT-SOCI) have been developed as highly sensitive and selective fluorescence derivatization reagents for primary and secondary aliphatic amines in HPLC. These reactivities were investigated using n-propylamine, n-heptylamine and N-methylhexylamine as model compounds to optimize the derivatization conditions. Both reagents readily reacted with the amines in basic media to give the corresponding fluorescent derivatives, which were separated isocratically by reversed-phase (C18) liquid chromatography with aqueous methanol. The detection limits (signal-to-noise ratio = 3) of BHBT-COF for primary and secondary amines are approximately 3 and 30 fmol, respectively, and those of BHBT-SOCI are approximately 3 and 300 fmol, respectively, for an injection volume of 20 microliters. Both reagents gave no fluorescent derivatives for aromatic amines.

Amines↗

PubMed1997

Hemodialysis-related arthropathy. A prospective MR study with SE and GRE sequences.

PURPOSE: A prospective examination of hemodialysis-related arthropathy by MR imaging with SE and GRE sequences was undertaken to verify whether the low signal intensity on T2-weighted SE images is caused by a paramagnetic susceptibility effect derived from amyloid or from hemosiderin. MATERIAL AND METHODS: Twenty-seven joints (19 hip joints, 6 discovertebral joints of 5 lumbosacral spines and 1 cervical spine, 2 shoulder joints) in 14 patients undergoing long-term hemodialysis (duration 10-22 years, mean 17) were examined with SE T1-weighted, T2-weighted and GRE T2*-weighted sequences. RESULTS: The signal intensity of the intraarticular and periarticular masses of the involved joints was basically isointense to the muscle in all 3 pulse sequences. No significantly low signal area was found on GRE T2*-weighted images. CONCLUSION: The low signal areas in the hemodialysis-related arthropathy on SE T2-weighted images are not caused by a paramagnetic susceptibility effect, but probably by the hypocellular and fibrous nature of amyloid-containing tissues. Therefore the GRE sequence can be helpful for differentiating hemodialysis-related amyloid arthropathy from chronic hemarthrosis or juxta-articular brown tumor.

Adult↗

PubMed1997

[Allergic contact dermatitis due to eye drops. Their clinical features and the patch test results].

We studied the clinical manifestations and causative agents in cases with allergic contact dermatitis due to eye drops who consulted the Department of Dermatology, Nippon Medical School during the period of 9 years between January, 1987 and December, 1995. Among 66,165 cases who visited the department during the studied period, 3,903 were suspected as contact dermatitis or drug eruption and underwent patch test. 141 of 3,903 cases (3.6%) were patch tested with eye drops and 49 cases (34.8%) reacted positively and were diagnosed as allergic contact dermatitis. Allergic ingredients were tested in 36 cases by the patch test with every ingredient. The 49 cases diagnosed as allergic contact dermatitis by eye drops, included 17 males and 32 females. 81.6% of the patients were aged over 40 years. The most frequent ages were between 60 and 69 years. The period from onset to the first visit to us was less than two weeks in 54.1% of the cases, but 3 cases consulted us after more than six months. The determined allergens are noted in order of frequency as follows: 1) fradiomycin sulfate in 14 cases, 2) ketotifen fumarate in 6 cases, 3) dibekacin sulfate in 3 cases, 4) befunolol hydrochloride in 3 cases, 5) phenylephrine hydrochloride in 3 cases and 6) benzalkonium chloride, the preservative of eye drops in 3 cases. Fradiomycin sulfate showed cross reactions to other aminoglycosides in the present cases. Every ingredient should be tested as much as possible, because there is a possibility that a preservative or a vehicle ingredient may be the allergen, though the incidence is low.

Adolescent↗

PubMed1997

[MR spectroscopy in acute brain infarction: differentiation of infarcted and non-infarcted areas].

Two cases of brain infarction were studied using multivoxel proton MR spectroscopy (MRS). MRS of both cases clearly demonstrated an increased level of lactate and decreased N-acetylaspartate (NAA), resulting in a high lactate/NAA ratio (LNR). Case 1 without thrombolysis therapy revealed that the area where LNR was less than 1.0 did not develop to infarction. This was also confirmed by MRS of case 2, who received an interventional reperfusion 4 hours after onset. In acute stags of brain infarction, on LNR greater than 1.0 on H-MRS may predict the margin of the infarcted region. Elevation of lactate in the non-infarcted cerebral hemisphere has not been reported before, and farther evaluation is necessary.

Aspartic Acid↗

PubMed1996

cDNA cloning and expression of intracellular platelet-activating factor (PAF) acetylhydrolase II. Its homology with plasma PAF acetylhydrolase.

Platelet-activating factor (PAF) acetylhydrolase, which inactivates PAF by removing the acetyl group at the sn-2 position, is widely distributed in plasma and tissues. We previously demonstrated that tissue cytosol contains at least two types of PAF acetylhydrolase, isoforms Ib and II, and that isoform Ib is a heterotrimer comprising 45-, 30-, and 29-kDa subunits, whereas isoform II is a 40-kDa monomer. In this study, we isolated cDNA clones of bovine and human PAF acetylhydrolase isoform II. From the longest open reading frame of the cloned cDNAs, both bovine and human PAF acetylhydrolases II are predicted to contain 392 amino acid residues and to exhibit 88% identity with each other at the amino acid level. Both enzymes contain a Gly-X-Ser-X-Gly motif that is characteristic of lipases and serine esterases. Expression of isoform II cDNA in COS7 cells resulted in a marked increase in PAF acetylhydrolase activity. An immunoblot study using an established monoclonal antibody against the bovine enzyme revealed that the recombinant protein exists in the membranous fraction as well as the soluble fraction. Isoform II is expressed most abundantly in the liver and kidney in cattle, but low levels were also observed in other tissues. The amino acid sequence deduced from the cDNA of isoform II had no homology with any subunit of isoform Ib. Interestingly, however, the amino acid sequence of isoform II showed 41% identity with that of plasma PAF acetylhydrolase. Combined with previous data demonstrating that isoform II shows similar substrate specificity to plasma PAF acetylhydrolase, these results indicate that tissue type isoform II and the plasma enzyme may share a common physiologic function.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1996

Platelet-activating factor acetylhydrolase expression and activity suggest a link between neuronal migration and platelet-activating factor.

A hemizygous deletion of LIS1, the gene encoding alphaLis1 protein, causes Miller-Dieker syndrome (MDS). MDS is a developmental disorder characterized by neuronal migration defects resulting in a disorganization of the cerebral and cerebellar cortices. alphaLis1 binds to two other proteins (beta and gamma) to form a heterotrimeric cytosolic enzyme which hydrolyzes platelet-activating factor (PAF). The existence of heterotrimers is implicated from copurification and crosslinking studies carried out in vitro. To determine whether such a heterotrimeric complex could be present in tissues, we have investigated whether the alphaLis1, beta, and gamma genes are coexpressed in the developing and adult brain. We have isolated murine cDNAs and show by in situ hybridization that in developing brain tissues alphaLis1, beta, and gamma genes are coexpressed. This suggests that alphaLis1, beta, and gamma gene products form heterotrimers in developing neuronal tissues. In the adult brain, alphaLis1 and beta mRNAs continue to be coexpressed at high levels while gamma gene expression is greatly diminished. This reduction in gamma transcript levels is likely to result in a decline of the cellular concentration of alphaLis1, beta, and gamma heterotrimers. The developmental expression pattern of alphaLis1, beta, and gamma genes is consistent with the neuronal migration defects seen in MDS; regions containing migrating neurons such as the developing cerebral and cerebellar cortices express these genes at a particularly high level. Furthermore, we uncovered a correlation between gamma gene expression, granule cell migration, and PAF hydrolytic activity in the cerebellum. In this tissue gamma gene expression and PAF hydrolysis peaked at Postnatal Days P5 and P15, a period during which neuronal migration in the cerebellum is most extensive. Mechanisms by which PAF could affect neuronal migration are discussed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1996

Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders.

The dopamine D2 receptor gene is a candidate gene for schizophrenia because the potency of certain neuroleptics correlates with their affinity for this receptor. Case-control studies in 291 schizophrenics, 78 patients with affective disorders, and 579 controls on an association of a molecular variant of S311C of the dopamine D2 receptor with psychiatric disorders were conducted. The frequency of individuals with S311C was significantly higher in schizophrenics with the absence of negative symptoms (17.1%, P < 0.00001), but similar in schizophrenics with the presence of negative symptoms (5.7%, P = 0.46) when compared with the controls (4.1%). The frequency of S311C was significantly higher in familial schizophrenics from one local area but not in those from other areas. It was significant that S311C was frequently present in patients with mood-incongruent psychotic affective disorders (33.3%, P < 0.0001), but not in those with other affective disorders. These data suggest that S311C might be one of the genetic factors for symptomatic dimensions of delusions and hallucinations and might be involved in underlying clinical heterogeneity in schizophrenia and affective disorders.

Adult↗

PubMed1996

Epidural dumbbell-shaped chordoma mimicking a neurinoma.

The authors present a case of cervical chordoma which manifested in a 5-year-old boy as a dumbbell-shaped epidural tumor without bone destruction. Both CT and MRI demonstrated tumor features suggesting this diagnosis, which was confirmed by histology.

Child, Preschool↗

PubMed1996

A large thrombosed superior cerebellar artery aneurysm: a case report.

UNLABELLED: MATERIAL AND RESULT: A large thrombosed aneurysm arising from the distal superior cerebellar artery was successfully resected. DISCUSSION AND CONCLUSION: An aneurysm in this location is very rare. Accumulation of intraoperative hemodynamic data may be useful in evaluating the capacity of collateral circulation.

Adult↗