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H Arai

Publications and source records attributed to H Arai.

At least 145 records · Page 8Linked to original sources
PubMed2000

Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species. Structure-activity relationship of cloned LPA receptors.

We examined the structure-activity relationship of cloned lysophosphatidic acid (LPA) receptors (endothelial cell differentiation gene (EDG) 2, EDG4, and EDG7) by measuring [Ca(2+)](i) in Sf9 insect cells expressing each receptor using LPA with various acyl chains bound at either the sn-1 or the sn-2 position of the glycerol backbone. For EDG7 the highest reactivity was observed with LPA with Delta9-unsaturated fatty acid (oleic (18:1), linoleic (18:2), and linolenic (18:3)) at sn-2 followed by 2-palmitoleoyl (16:1) and 2-arachidonoyl (20:4) LPA. In contrast, EDG2 and EDG4 showed broad ligand specificities, although EDG2 and EDG4 discriminated between 14:0 (myristoyl) and 16:0 (palmitoyl), and 12:0 (lauroyl) and 14:0 LPAs, respectively. EDG7 recognizes the cis double bond at the Delta9 position of octadecanoyl residues, since 2-elaidoyl (18:1, trans) and 2-petroselinoyl (18:1, cis-Delta12) LPA were poor ligands for EDG7. In conclusion, the present study demonstrates that each LPA receptor can be activated differentially by the LPA species.

Amino Acid Sequence↗
PubMed2000

Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I.

The scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters from high-density lipoprotein (HDL) and cholesterol secretion into bile in the liver. In this study, we identified an SR-BI-associated protein from rat liver membrane extracts by using an affinity chromatography technique. This protein of 523 amino acids contains four PDZ domains and associates with the C terminus of SR-BI by using its N-terminal first PDZ domain. Therefore, we denoted this protein as CLAMP (C-terminal linking and modulating protein). CLAMP was located mostly in the sinusoidal membranes, whereas SR-BI was detected in both sinusoidal and canalicular membranes. After the solubilization of the liver membranes with Triton X-100, SR-BI was immunoprecipitated with anti-CLAMP monoclonal antibody, suggesting the association of these proteins in vivo. By coexpressing SR-BI with CLAMP in Chinese hamster ovary cells, we observed (i) the increase in the expression level of SR-BI, (ii) the reduction in the deacylation rate of the cholesteryl esters taken up from HDL, and (iii) the change in the intracellular distribution of fluorescent lipid 1,1'-dioctadecyl-3,3, 3',3'-tetramethylindocarbocyanine percholate taken up from HDL. Taken together, these data suggest that CLAMP, a four-PDZ-domain-containing protein, is associated with SR-BI in the liver sinusoidal plasma membranes and may modulate the intracellular transport and metabolism of cholesteryl esters taken up from HDL.

Amino Acid Sequence↗
PubMed2000

Inhibition of rho-associated kinase results in suppression of neointimal formation of balloon-injured arteries.

BACKGROUND: Rho-associated kinase (ROCK), an effector of small GTPase Rho, regulates vascular tone via a calcium sensitization mechanism and plays a key role in the pathogenesis of hypertension. However, its role in vascular growth remains unclear. METHODS AND RESULTS: Y-27632, a specific ROCK inhibitor, and the overexpression of dominant-negative ROCK suppressed the mitogen-induced DNA synthesis of cultured vascular smooth muscle cells (VSMCs), which indicates the essential role of ROCK in the control of VSMC proliferation in vitro. Y-27632 also suppressed the chemotaxis of VSMCs. Male Wistar rats were systemically given Y-27632 (35 to 70 mg. kg(-1). day(-1)) through an intraperitoneal infusion. The neointimal formation of balloon-injured carotid arteries was significantly suppressed in Y-27632-treated rats (intima/media ratio, 0.22+/-0.02) compared with vehicle-treated rats (intima/media ratio, 0.92+/-0.21) or hydralazine-treated rats with a similar blood pressure decrease (intima/media ratio, 1.03+/-0.15). The phosphorylation of myosin phosphatase and myosin light chain was elevated in injured arteries in a Y-27632-sensitive manner, indicating the augmentation of ROCK activity in neointimal formation. The downregulation of the cyclin-dependent kinase inhibitor p27(kip1) in injured vessels was reversed by Y-27632 treatment, reflecting the antiproliferative effect of ROCK inhibition in vivo. CONCLUSIONS: We conclude that ROCK plays a key role in the process of neointimal formation after balloon injury. Thus, the inhibition of ROCK may be a potential therapeutic strategy for treating vascular proliferative disorders and hypertension.

Amides↗
PubMed2000

Alpha2-macroglobulin gene polymorphisms show racial diversity and are not associated with Alzheimer's disease.

Two genetic markers of the plasma protein alpha2-macroglobulin, a 5 bp deletion/insertion at the 5' splice site of exon 18 (A2MI) and the GTC/ATC (VaIIO00IIe) in exon 24 (A2M2), may have roles in the development of Alzheimer's disease (AD). Genotyping and linkage analysis of these markers in 426 Japanese sporadic AD patients, 85 autopsy-confirmed Caucasian AD cases, and, as controls, 382 Japanese and 65 Caucasians who were cognitively normal and 140 Japanese Parkinson's disease patients showed racial diversity in the frequencies and relationship of the two markers. Comparison of genotype and allele frequencies, stratification of the samples by the presence of the apolipoprotein E epsilon4 allele, and logistic regression analysis revealed no association of these markers with AD in either racial group.

Aged↗
PubMed2000

Homologs of the alpha- and beta-subunits of mammalian brain platelet-activating factor acetylhydrolase Ib in the Drosophila melanogaster genome.

The mammalian intracellular brain platelet-activating factor acetylhydrolase, implicated in the development of cerebral cortex, is a member of the phospholipase A2 superfamily. It is made up of a homodimer of the 45 kDa LIS1 protein (a product of the causative gene for type I lissencephaly) and a pair of homologous 26-kDa alpha-subunits which account for all the catalytic activity. LIS1 is hypothesized to regulate nuclear movement in migrating neurons through interactions with the cytoskeleton, while the alpha-subunits, whose structure is known, contain a trypsin-like triad within the framework of a unique tertiary fold. The physiological significance of the association of the two types of subunits is not known. In an effort to better understand the function of the complex we turned to genomic data mining in search of related proteins in lower eukaryotes. We found that the Drosophila melanogaster genome contains homologs of both alpha- and beta-subunits, and we cloned both genes. The alpha-subunit homolog has been overexpressed, purified and crystallized. It lacks two of the three active-site residues and, consequently, is catalytically inactive against PAF-AH (Ib) substrates. Our study shows that the beta-subunit homolog is highly conserved from Drosophila to mammals and is able to interact with the mammalian alpha-subunits but is unable to interact with the Drosophila alpha-subunit. Proteins 2000;39:1-8.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease.

BACKGROUND: Long-term cognitive decline in postmenopausal women is associated with aging and Alzheimer disease (AD). Estrogen replacement therapy has been reported to reduce the risk of developing AD. The distribution of estrogen receptors (ERs) in neurons overlaps that of the brain neurons known to develop AD. Estrogen increases the secretion and metabolism of amyloid precursor protein, may help synapse formation, and is reported to protect neurons from toxins. Restriction fragment length polymorphisms (RFLPs) of the ERalpha gene at intron 1 and exon 2 were associated with a low bone mineral density in postmenopausal women and also with AD in a Japanese population. OBJECTIVE: To determine whether ERalpha gene polymorphisms are associated with transcriptional activity and AD. METHODS: A luciferase reporter assay analyzed enhancer activity of the ERalpha gene at intron 1 and exon 2. This activity was evaluated according to the RFLPs. The RFLPs of the ERalpha gene were determined in Japanese patients clinically diagnosed as having AD, white patients diagnosed as having AD at autopsy, and corresponding healthy control subjects. The RFLPs were also evaluated for the contribution of the ERalpha gene RFLPs to AD. RESULTS: We found weak (about 2-fold) enhancer activity of the ERalpha gene, which differed among RFLPs. Although there were racial differences in these polymorphisms, we could not confirm the previously reported association between ERalpha gene polymorphisms and AD. CONCLUSION: Regulatory element of the ERalpha gene was found in intron 1, but we found no association between ERalpha gene polymorphisms and AD.

Aged↗
PubMed2000

Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies.

Cerebral glucose metabolism using positron emission tomography (PET) with (18)F-fluorodeoxyglucose was examined in 11 patients with probable Alzheimer's disease (AD), 6 patients with probable, and 1 patient with autopsy-confirmed dementia with Lewy bodies (DLB) as well as in 10 age-matched normal control subjects. Among widespread cortical regions showing glucose hypometabolism in the DLB group, the metabolic reduction was most pronounced in the visual association cortex compared to that in the AD group. Using a metabolic ratio of 0.92 in the visual association cortex as a cutoff (mean-2 SD of normal control subjects), DLB could be distinguished from AD with a sensitivity of 86% and a specificity of 91%. In contrast, apolipoprotein E4 allele frequency and cerebrospinal fluid tau levels did not differ significantly between the two groups. In order to further dissect out neuropathological correlates of the dysfunctional occipital lobe, postmortem brains from 19 patients with AD and 17 with DLB as well as 11 brains from normal controls were examined. A distinct and extensive spongiform change with coexisting gliosis was variably noted throughout cerebral white matter with relative sparing of gray matter in DLB. Notably, the white matter spongiform change and gliosis was most prominently and consistently found in the occipital region of DLB, and the severity of the spongiform change in each brain region generally paralleled to the regional difference in reduced glucose metabolism between the living AD and DLB patients. These findings suggest that (1) among several potential antemortem biomarkers in the diagnosis of DLB, measures of the glucose metabolism in the occipital cortex may be an informative diagnostic aid to distinguish DLB from AD; and (2) a pathological process that generates widespread spongiform change and gliosis in long projection fibers may contribute, at least in part, to the characteristic imaging features of DLB.

Aged↗
PubMed2000

CSF phosphorylated tau protein and mild cognitive impairment: a prospective study.

Cerebrospinal fluid (CSF) tau protein phosphorylated at both Thr231 and Ser235 sites (CSF/phospho-tau(231-235)) and total tau (CSF/total-tau) were quantified by sandwich ELISA in 20 patients with mild cognitive impairment (MCI) who eventually developed AD on follow-up as well as seven memory complainers with no objective memory loss. 13/20 (65%) of the MCI patients had high CSF/total-tau and detectable levels of CSF/phospho-tau(231-235), whereas these markers were low and under a detectable level in all of the memory complainers. Although either a total-tau, phospho-tau measurement or a combination of these can help in predicting if MCI will develop AD, our results suggest that the pathogenic steps of AD may be at the stage that finally leads to an accumulation of abnormally phosphorylated tau and neuron death, at least in some brain areas, when MCI patients present with the earliest detectable clinical symptoms of dementia.

Aged↗
PubMed2000

The threshold of acetazolamide vasoreactivity as an indicator of maximum cerebral blood volume.

Using xenon-enhanced computed tomographic (Xe-CT) cerebral blood flow (CBF) measurement, we attempted to determine the extent of vasoreactivity indicating reserve autoregulatory potential by comparing maximal cerebral blood volume (CBV) induced by acetazolamide activation (activated CBV) and the resting CBV. We measured the activated and resting CBVs in two different groups by the subtraction technique using contrast-enhanced CT, and measured the resting and activated CBF in both groups to calculate the percentage increase (%deltaCBF). We extracted CBF and CBV in the territory of the middle cerebral artery on both sides separately for each patient, and treated them independently. We then divided the resting CBV values in group B (25 patients, n=50) into 6 subgroups according to their %deltaCBF (below 10%, n=13; 20%, n=7; 30%, n=8; 40%, n=6; 50%, n=6; and over 50%, n=10) and examined the differences from the activated CBVs in group A (12 patients, n=24) by Dunnett's multiple comparison test. Significant differences were seen in subgroups with %deltaCBF exceeding 20% but less than 30%, and in the subgroups with higher %deltaCBF. We consider that %deltaCBF of at least 20% induced by acetazolamide indicates nonmaximal vasodilation, i.e., reserve autoregulatory potential.

Acetazolamide↗
PubMed2000

Molecular cloning and expression of a novel klotho-related protein.

Klotho protein is a novel beta-glucosidase-like protein produced predominantly in the kidney. The klotho mouse, which genetically lacks klotho gene expression, manifests various systemic phenotypes resembling aging. In the present study we succeeded in isolating a novel human protein structurally related to klotho protein. The protein possesses one beta-glucosidase-like domain and is 42% identical with klotho protein at the amino acid level. Unlike klotho protein, it possesses neither a signal sequence nor a transmembrane domain, suggesting that it is a cytosolic protein, and thus was termed cytosolic beta-glucosidase-like protein-1 (cBGL1). By Northern blot analysis cBGL1 mRNA was expressed most abundantly in the liver, followed by the small intestine, colon, spleen, and kidney. When klotho and cBGL1 gene expression was examined in renal cell carcinoma tissues, both klotho and cBGL1 mRNA levels in tumors were lower than those in nontumor regions, suggesting that renal epithelial cells may lose klotho and cBGL1 gene expression during the course of malignant transformation. In conclusion, we describe the primary structure and gene expression of a novel protein related to klotho protein.

Aged↗
PubMed2000

Association of systemic lupus erythematosus and hemolytic uremic syndrome in a child.

We describe a 10-year-old girl with systemic lupus erythematosus (SLE) who first presented with hemolytic uremic syndrome (HUS). Diagnoses were based on the classic HUS triad, including the observation of fragmented red blood cells, and on the American College of Rheumatology criteria for SLE. Plasma exchange may have been effective against both HUS and SLE in this patient, as it was associated with improvement of platelet counts, renal function, and serological findings.

Child↗
PubMed2000

A new variant of apolipoprotein E (apo E Maebashi) in lipoprotein glomerulopathy.

We have previously reported an 8-year-old girl with lipoprotein glomerulopathy. Assessment of serum apolipoprotein E (apo E) in this patient showed a discrepancy between phenotype and genotype, suggesting that she may have a variant of apo E. The present report concerns our analysis of DNA sequences of the apo E gene in the patient: nine base pairs were found to be deleted from exon 4. This mutation would appear to encode a new apo E variant lacking three amino acids. This variant may be associated with the pathogenesis of lipoprotein glomerulopathy.

Apolipoproteins E↗
PubMed2000

Early experience with poly L-lactic acid bioabsorbable fixation system for paediatric craniosynostosis surgery. Report of 3 cases.

OBJECTIVE: The authors describe early experience in the use of bioabsorbable fixation devices for cranial reconstruction of paediatric craniosynostosis patients. METHODS: Three patients, individually respectively presenting sagittal synostosis, metopic synostosis, and clover leaf skull deformity, underwent cranial reconstruction using poly L-lactic acid (PLLA) plates and screws. The patients ranged in age from 2 to 10 months at the time of surgery. The postoperative clinical follow-up ranged from 16 to 18 months. All patients showed satisfactory wound healing without signs of infection or local inflammation. The plates provided satisfactory fixation and were not palpable through the skin after 16 to 18 postoperative months. CONCLUSION: Our experience demonstrated the efficacy of PLLA bioabsorbable plates and screws for cranial reconstruction in cases of infant craniosynostosis. Prospective studies and longer follow-up of a larger number of patients is desirable for confirmation of these findings.

Absorbable Implants↗
PubMed2000

A case of subcortical meningioma.

Subcortical meningioma, which has been reported as meningioma without dural attachment, a cerebral subcortical lesion, is extremely rare. Very few findings of radiological examination of subcortical meningioma have been described. Pre-operative differentiation of this lesion is generally difficult. We characterize the peritum oural oedema adjacent to the meningioma in this region, and we suggest that radiological findings of peritum oural oedema contribute to differential diagnosis of subcortical meningiomas.

Brain Neoplasms↗
PubMed2000

Transcranial transsphenoidal approach for tuberculum sellae meningiomas.

OBJECTIVE: A series of 21 patients with tuberculum sellae meningioma who received surgical treatment is reported. PATIENTS AND METHODS: All 9 females and 12 males (mean age 49 years) presented visual disturbances of varying degrees in either one or both eyes. Eighteen of the tumours were less than 3 cm in size, and 3 were larger. Tumour resection of uniform surgical technique was performed in all cases. Following a bicoronal scalp incision, bifrontal craniotomy combined with removal of the orbital rim bilaterally was performed. The frontal dura was opened bilaterally, and the most anterior portion of the superior sagittal sinus was transected. Bifrontal retraction and arachnoid dissection along the proximal olfactory tracts brought the tumour into view. Additional dissection of the interhemispheric fissure extended the operative field to the anterior communicating artery. The anterior skull base was drilled out to resect the basal part of the tumour. In all cases, the optic canal and sphenoid sinus, and additionally in some cases the ethmoid sinus were opened. The tumour uniformly extended inferomedially to the optic nerve, and direct visualization of this portion of the tumour was possible with our approach. The opened paranasal sinuses were reconstructed with adipose tissue harvested from the patient's abdomen and the pericranial flap. RESULTS: In all patients, total or almost total resection of the tumour was accomplished. Postoperatively, visual function was improved in 11 patients, was unchanged in 8, and worsened in 2. There were no operative deaths. Cerebrospinal fluid leakage was occurred in two patients but could be conservatively managed. In a mean 3-year follow-up, tumour recurrence was observed in only one patient who presented a malignant histology. CONCLUSIONS: We are confident that our surgical approach has great clinical value in surgical resection of tuberculum sellae meningioma. The good accessibility to a tumour extending inferomedially to the optic nerve should, in particular, be stressed.

Adult↗
PubMed2000

No evidence of association between apolipoprotein E gene regulatory region polymorphism and Alzheimer's disease in Japanese.

The reported association between -491 A/T polymorphism in the regulatory region of the apolipoprotein E gene (APOE) and increased risk for Alzheimer's disease (AD) is controversial: Studies of different racial and ethnic populations have found both positive and negative associations. Examination of -491 A/T polymorphism in 216 patients with sporadic AD and 157 age- and gender-matched controls from the Japanese population revealed that, in contrast to findings for Caucasian populations, the -491 T allele, but not the A allele, was significantly more prevalent in patients with AD than in controls. This difference disappeared when the subjects were stratified by the gene dose of the APOE epsilon4 allele. Moreover, logistic regression analysis, controlling for age, sex, and the presence of the APOE epsilon4 allele, showed no association between the -491 polymorphism and AD. These results suggest that -491 polymorphism does not independently confer susceptibility to AD, but that this polymorphism is in partial linkage disequilibrium with the APOE epsilon2/3/4 polymorphism.

Aged↗
PubMed2000

External shunt for off-pump coronary artery bypass grafting: distal coronary perfusion catheter.

We invented a simple external shunt catheter for off-pump coronary artery bypass grafting. This catheter maintains coronary perfusion from femoral artery, prevents ischemia, reduces back-bleeding, and acts as a suture guide by preventing accidental missuturing of the posterior coronary wall. The insertion and withdraw technique is easier than intraluminal shunt. This catheter would be a useful tool for myocardial protection during off-pump revascularization.

Cardiac Catheterization↗